bluuebunny/crossref_metadata_2025 huggingface dataset:
Follow-up clinical results in patients undergoing percutaneous transluminal coronary angioplasty.
Authors: Mabin T A , Holmes D R , Smith H C , Vlietstra R E , Reeder G S , Bresnahan J F , Bove A A , Hammes L N , Elveback L R , Orszulak T A
Published: June 2011

Complete follow-up data were obtained from 229 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1979 and 1982 (mean follow-up 14 months, range 6 to 37). Single-vessel disease was present in 143 and multivessel disease in 86. PTCA was successful in 153 patients (67%). Failure was followed initially by bypass surgery in 59 and by continued medical therapy in 17. After successful PTCA, 90% of patients were improved subjectively and 74% were asymptomatic at follow-up. After unsuccessful PTCA but prompt bypass, 90% were improved subjectively and 85% were asymptomatic. Among the 229 patients, 39 (17%) required an additional intervention because of angina during follow-up; 15 of these had repeat PTCA and 18 had bypass surgery. Among patients with successful PTCA, revascularization was complete in 77% and partial in 23%. The completeness of revascularization with PTCA had a significant impact on follow-up. The follow-up data of patients with successful single-vessel PTCA and of those with multivessel disease with complete revascularization were similar. When the patients with complete revascularization were compared with those with multivessel disease but incomplete revascularization, the follow-up data were characterized by a higher incidence of angina or need for bypass surgery in the latter group (63%) than in the former group (29%); those with incomplete revascularization also had a significantly reduced event-free survival.
Hemodynamic changes mimicking a vasodilator drug response in the absence of drug therapy after right heart catheterization in patients with chronic heart failure.
Authors: Packer M , Medina N , Yushak M
Published: June 2011

We suspected that patients with severe chronic heart failure may show hemodynamic changes after cardiac catheterization in the absence of drug therapy that could complicate assessment of the hemodynamic effects of new vasodilator and inotropic agents. To evaluate this phenomenon prospectively, hemodynamic variables were measured in 21 patients with heart failure 30 min and 2, 6, 24, and (in 12 patients) 48 hr after right heart catheterization, during which time therapy was not altered. During the first 2 hr we noted a significant increase in cardiac index and decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure, and systemic vascular resistance (p less than .01); a further decline in left ventricular filling pressure was noted over the next 24 hr, after which all hemodynamic variables remained stable. The magnitude of these hemodynamic changes resembled the effects of many established vasodilator drugs and was further enhanced after meals. These data indicate that hemodynamic improvement may be observed without any therapeutic intervention during the course of invasive studies in patients with severe chronic heart failure; such changes may lead investigators to attribute efficacy to ineffective drug therapy. To minimize the occurrence of such responses, we recommend that intravascular catheters be inserted the day before drug evaluation and that hemodynamic measurements be made with patients in a postprandial state.
Impaired thickening of nonischemic myocardium during acute regional ischemia in the dog.
Authors: Lima J A , Becker L C , Melin J A , Lima S , Kallman C A , Weisfeldt M L , Weiss J L
Published: June 2011

To study the regional function of nonischemic myocardium after the onset of regional ischemia, graded circumflex coronary arterial stenosis was induced in 18 open-chest anesthetized dogs. Two-dimensional echocardiographic views were obtained at each degree of occlusion in a cross-sectional plane marked by two to three metal beads sewn to the left ventricular epicardium. Percent systolic thickening was measured at 16 equally spaced points around the left ventricle and correlated with microsphere-determined regional myocardial blood flow. Baseline thickening averaged 44.9 +/- 6.4%. During transmural ischemia percent systolic thickening decreased to -16.1 +/- 4.0% in the ischemic region and also decreased in adjacent nonischemic regions (to 2.4 +/- 2.4% in segments closest to the ischemic region [adjacent 1] and to 15.5 +/- 3.9 in segments further away [adjacent 2]), but was unchanged in segments directly opposite the ischemic region (remote region). During subendocardial ischemia, percent systolic thickening fell only in the ischemic and adjacent 1 regions (1.4 +/- 5.2% and 24.9 +/- 5.0%, respectively). Dipyridamole, 0.21 to 0.42 mg/min iv, given to seven dogs during transmural ischemia, caused a three- to fivefold increase in flow to the nonischemic and no change in flow to the ischemic region; function was not altered in any region. Propranolol, 0.1 mg/kg iv, was given to five dogs during transmural ischemia to depress contractility in the remote region. Percent systolic thickening fell in the remote (from 50.0 +/- 7.7% to 34.6 +/- 5.6%), but increased in adjacent 1 (from -0.25 +/- 3.7% to 15.2 +/- 3.9%) and in adjacent 2 (from 17.4 +/- 2.8% to 33.4 +/- 3.9%) regions, and remained unchanged in the ischemic region. We conclude the following: During transmural ischemia percent systolic thickening is markedly impaired in nonischemic myocardium immediately adjacent to the ischemic region, and is impaired to a lesser degree in regions located relatively far from the ischemic border. Dysfunction therefore overestimates the extent of regional ischemia after total coronary occlusion. During subendocardial ischemia function ceases in the ischemic region and functional impairment of nonischemic myocardium is restricted to immediately adjacent regions. Dysfunction of adjacent regions is not caused by "relative ischemia" related to increased local oxygen demands or to a steal phenomenon. Mechanical tethering of nonischemic myocardium adjacent to ischemic regions, secondary to changes in left ventricular shape during contraction, may contribute to the impairment of systolic thickening in adjacent regions during transmural ischemia.
Lipoprotein predictors of the severity of coronary artery disease in men and women.
Authors: Reardon M F , Nestel P J , Craig I H , Harper R W
Published: June 2011

In this study we examined the relationships between levels of several components of plasma lipoproteins and severity of coronary artery disease in 65 men and 42 women who underwent coronary arteriography for suspected coronary disease. Severity of coronary atherosclerosis was scored as the extent of disease seen at arteriography. Univariate analyses of the relationships between the plasma lipoprotein parameters and score for severity of atherosclerosis revealed a marked difference between men and women. In men, the score for severity of atherosclerosis was strongly related to the low-density lipoprotein (LDL) cholesterol and apolipoprotein B concentrations, whereas in women it was related to the triglyceride concentrations in plasma intermediate-density lipoprotein (IDL) and LDL and to the cholesterol and apolipoprotein B concentrations in IDL. The significance of these correlations was not negated by possible confounding factors such as alcohol intake, diabetes, and treatment with thiazides and beta-adrenergic blockers. Stepwise regression analyses of data adjusted for weight and age indicated that 22% of the variation in the score for severity of atherosclerosis could be accounted for by levels of LDL cholesterol in men. No other lipoprotein parameter could account for any further variation. In contrast, cholesterol did not account for any variation in the score for severity of atherosclerosis in women, whereas plasma triglyceride accounted for 16% of the observed variation in this group. No relationships were found between score for severity of atherosclerosis and high-density lipoprotein cholesterol or plasma apolipoprotein A-I concentrations in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Superiority of combined diltiazem and propranolol therapy for angina pectoris.
Authors: Strauss W E , Parisi A F
Published: June 2011

Twenty-four patients with stable angina were evaluated in a 14 week crossover trial. A single-blind placebo period (baseline 1) was followed by two double-blind periods evaluating maximum tolerated doses of diltiazem (up to 360 mg daily) vs placebo. Over the next 1 to 4 weeks, propranolol was started and increased until clinically documented beta-blockade was achieved (baseline 2). The final phase consisted of a pair of evaluation periods comparing propranolol plus the maximum tolerated dose of diltiazem to propranolol and placebo. The daily rate of angina attack was 1.6 during baseline, was unchanged during placebo therapy, but fell during treatment with diltiazem to 0.6 (p less than .005). With the addition of diltiazem to propranolol, the angina rate was improved (0.3) compared with that with either propranolol alone (0.6) or propranolol and placebo (0.5) (p less than .01). Total exercise duration during baseline 1 was 360 sec and increased to 497 sec with diltiazem, 481 sec with propranolol, and 527 sec with the combination of diltiazem and propranolol. Two patients with reduced ejection fractions developed congestive heart failure with propranolol. The combination of diltiazem and propranolol similarly resulted in congestive heart failure in one patient who had tolerated both drugs alone.
Left ventricular systolic and diastolic function in coronary artery disease: effects of revascularization on exercise-induced ischemia.
Authors: Carroll J D , Hess O M , Hirzel H O , Turina M , Krayenbuehl H P
Published: June 2011

Left ventricular systolic and diastolic function were studied before and after surgical revascularization in a group of 24 patients with stable angina who all had an excellent clinical response to surgery. With use of micromanometer left ventricular pressure measurements and ventricular volumes, calculated from biplane cineangiograms, left ventricular function at rest and during exercise before and after surgery was compared. Before surgery all patients had exercise-induced ischemia with new asynergy, a fall in ejection fraction from 57% to 49% (p less than .001), and a rise in left ventricular end-diastolic pressure from 23 to 37 mm Hg (p less than .001). Postoperative exercise resulted in no new asynergy and ejection fraction rose from 59% to 61% (p less than .05). Left ventricular end-diastolic pressure still rose from 17 to 25 mm Hg (p less than .01). Left ventricular pressure decay during exercise was greatly improved after revascularization and allowed maintenance of reduced early diastolic pressures. The early diastolic pressure nadir before surgery rose from 9 to 21 mm Hg (p less than .001); the postoperative nadir was 5 mm Hg at rest and 6 mm Hg during exercise. All patients had an upward shift in the diastolic pressure-volume relationship during preoperative exercise. After revascularization there was no upward shift in some patients and a much smaller shift in others. The postoperative increase in left ventricular end-diastolic pressure was due to increased end-diastolic volume, not altered compliance. There was an increase in mean right atrial pressure during exercise either before (6 to 11 mm Hg) or after surgery (4 to 10 mm Hg). These increases were quite variable, suggesting no consistent role of pericardial restraint during exercise. Early diastolic peak filling rate during exercise was greater after surgery (1260 vs 950 ml/sec, p less than .001). In fact, during postoperative exercise early diastolic filling rates were greater than normal, reflecting the persistence of abnormally high atrial pressures for filling. As at preoperative study, late diastolic filling during exercise was restricted after revascularization when compared with that in a control group. Postoperatively patients undergoing bypass procedures with a good clinical result showed significantly improved left ventricular diastolic and systolic function. Persistent elevation of end-diastolic and atrial pressures and other abnormalities of diastolic function may reflect chronic structural changes and need to be taken into account when evaluating patients after bypass surgery.
Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery.
Authors: Brown B G , Cukingnan R A , DeRouen T , Goede L V , Wong M , Fee H J , Roth J A , Carey J S
Published: June 2011

One hundred forty-seven consecutive coronary bypass patients were enrolled in a randomized, double-blind, risk-stratified, placebo-controlled prospective trial evaluating the effect on graft patency of 325 mg tid aspirin (ASA) plus 75 mg tid dipyridamole (DP) or ASA alone. One hundred twenty-seven patients (399 total grafts) underwent surgery, initiation of drug therapy 67 +/- 27 (SD) hr postoperatively, five clinic visits, and repeat angiography at 1 year. A logistic regression statistical model was used to determine the effects of 28 different measured variables on graft patency and to adjust for these effects in determining the relationship between antiplatelet therapy and graft occlusion. No patient-specific variable contributed significantly to the prediction of occlusion in either the placebo or the treated group. Six graft-specific variables (arterial diameter, severity of stenosis, graft flow, reactive hyperemia, presence or absence of collaterals, and graft type) did contribute and were included in the model. Twenty-one percent of placebo-treated grafts became occluded. Compared with placebo, the relative risk of graft occlusion with ASA was 0.47 (p = .04); with ASA + DP, it was 0.50 (p = .04). This benefit was principally due to reduction of occlusion in the most common and presumably most important groups of grafts, those in which flow exceeded 40 ml/min, or supplying arteries having luminal diameters greater than 1.5 mm. Grafts lacking reactive hyperemia had a 32% occlusion frequency in placebo-treated patients; relative risk of their occlusion averaged 0.26 (p less than .01) with platelet-inhibiting therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of the sympathetic nervous system on limb circulation and metabolism during exercise in patients with heart failure.
Authors: Wilson J R , Ferraro N , Wiener D H
Published: June 2011

During exercise in patients with heart failure, activation of sympathetic vasoconstrictor nerves may impair vasodilation in active skeletal muscle and thereby interfere with skeletal muscle blood flow. To investigate this hypothesis, we examined the effect of acute alpha-adrenergic blockade with systemic administration of prazosin (10 patients) or regional administration of phentolamine (eight patients) on blood flow, vascular resistance, oxygen consumption (VO2), and lactate release in the leg during maximal bicycle exercise in patients with heart failure. During control exercise, systemic VO2 increased to 12.6 +/- 4.3 ml/min/kg (normal greater than 20 to 25 ml/min/kg), leg blood flow to 2.8 +/- 1.8 liters/min, and leg lactate release to 362 +/- 256 mg/min. Prazosin decreased systemic vascular resistance (12.5 +/- 3.2 to 9.7 +/- 2.5 units; p less than .003) and mean arterial pressure (101 +/- 20 to 87 +/- 22 mm Hg; p less than .002) at maximal exercise, supporting the presence of substantial sympathetic vasoconstrictor nerve activity. Prazosin also decreased leg resistance during exercise. However, the magnitude of leg blood flow, leg oxygen extraction, and leg VO2 during exercise were unchanged, suggesting that vasodilation in the leg was produced by an autoregulatory response to the drop in blood pressure rather than by blockade of sympathetic vasoconstriction. Maximal systemic VO2 and leg lactate release were also not improved. Regional blockade with phentolamine did not substantially drop the arterial blood pressure and had no effect on vasodilation, blood flow, VO2, and lactate release in the leg during exercise. These data suggest that during exercise in patients with heart failure, the sympathetic nervous system helps to sustain arterial blood pressure and that this beneficial effect is not associated with adverse effects on blood flow to working skeletal muscle.
Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man.
Authors: Wilson R F , Laughlin D E , Ackell P H , Chilian W M , Holida M D , Hartley C J , Armstrong M L , Marcus M L , White C W
Published: June 2011

Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was varied from 0.1 to 5.7 times control CBFV. Changes in mean CBFV measured intraluminally by catheter in the left anterior descending and left circumflex arteries were similar to those measured simultaneously with an epicardial Doppler probe on the surface of the same vessel (n = 85, r = .95, slope = 1.04) and to changes in coronary sinus flow (n = 69, r = .97, slope = 1.06) measured with timed venous collections. Identical maximal coronary reactive hyperemic responses with the catheter present and absent in the artery being studied demonstrated that coronary obstruction by the catheter was minimal. Safety studies in six additional calves demonstrated that the catheter caused small changes in coronary endothelial permeability. Histologic studies revealed no endothelial denudation or thrombus formation. Stable phasic recordings of coronary blood flow velocity have been obtained in 58 of 70 patients studied. One of the 70 patients studied had abrupt coronary occlusion probably related to catheter-induced vasospasm. In 10 normal patients, intracoronary meglumine diatrizoate increased CBFV to 3.5 times that at rest (range 2.8 to 5.0). CBFV rose 5.0-fold after an intravenous infusion of dipyridamole (range 3.8 to 7.0). In each patient, dipyridamole produced greater vasodilation than meglumine diatrizoate. The time- and dose-response characteristics to dipyridamole infusion were heterogeneous, underscoring the advantage of continuous on-line measurement of CBFV in the measurement of vasodilator reserve. This method of measuring CBFV and assessing vasodilator reserve in the catheterization laboratory should facilitate studies of the coronary circulation in man.
Coronary anatomy and left ventricular function in the first 12 hours of acute myocardial infarction: the Western Washington Randomized Intracoronary Streptokinase Trial.
Authors: Stadius M L , Maynard C , Fritz J K , Davis K , Ritchie J L , Sheehan F , Kennedy J W
Published: June 2011

The relationships among clinical variables, coronary anatomy, and left ventricular function during the early hours of acute myocardial infarction (AMI) were evaluated from data acquired in the Western Washington Intracoronary Streptokinase Trial. All patients had symptoms and electrocardiographic changes typical of AMI. All data were obtained before treatment with streptokinase. Mean time to catheterization was 4.1 hr after onset of symptoms. Coronary angiograms (n = 245) were analyzed for location of infarct-related occlusion and collateral flow to the infarct bed. Left ventricular ejection fraction and regional left ventricular function were quantitated in 227. Sixty-two percent of occlusions were in the most proximal segment of the involved coronary artery. Collateral circulation was seen in 42% overall, in 31% with left anterior descending artery (LAD) occlusion, and in 52% with right coronary artery (RCA) occlusion (p less than .005). Left ventricular ejection fraction was lowest and regional function was most abnormal in the group with proximal LAD occlusion. Hyperkinesis was present in 32%; in those with hyperkinesis, hyperkinetic segment length was longest in those with RCA or circumflex occlusion. Multivariate analysis identified proximal LAD occlusion as the factor most closely associated with left ventricular ejection fraction and with measures of left ventricular regional hypofunction. We conclude that (1) AMI is usually caused by occlusion or subtotal occlusion in the most proximal portion of the involved coronary artery, (2) collateral circulation is more frequent with RCA than with LAD occlusion, and (3) location of the infarct-related occlusion is the most important determinant of global and regional left ventricular function in the early hours of AMI.
Diastolic abnormalities in patients with hypertrophic cardiomyopathy: relation to magnitude of left ventricular hypertrophy.
Authors: Spirito P , Maron B J , Chiarella F , Bellotti P , Tramarin R , Pozzoli M , Vecchio C
Published: June 2011

To investigate the relationship between diastolic abnormalities and left ventricular hypertrophy, 52 patients with hypertrophic cardiomyopathy (HCM) and 22 normal subjects were studied with digitized M mode echocardiography and two-dimensional echocardiography. Echocardiographic indexes of diastolic function were compared in patients with different extent of left ventricular hypertrophy. Time interval from minimum left ventricular internal dimension to mitral valve opening and time to peak rate of increase in left ventricular internal dimension were significantly prolonged (80 +/- 31 and 100 +/- 37 msec, respectively) in patients with HCM and the most extensive left ventricular hypertrophy compared with those in patients with mild left ventricular hypertrophy (59 +/- 25 and 74 +/- 34 msec, respectively; p less than .01). Furthermore, peak rate of posterior wall diastolic excursion was significantly reduced in those patients with HCM and posterior wall hypertrophy (8.3 +/- 4.0 cm/sec) compared with that in patients with HCM but normal posterior wall thickness (11.2 +/- 3.4 cm/sec; p less than .002). However, abnormal M mode echocardiographic indexes of diastolic function were also identified in a substantial proportion of patients (i.e., 73%) with HCM and only mild left ventricular hypertrophy. In these patients, time interval from minimum left ventricular internal dimension to mitral valve opening (59 +/- 25 msec), peak rate (12 +/- 4 cm/sec), and time to peak rate of increase in left ventricular internal dimension (74 +/- 34 msec) were significantly different from normal (25 +/- 12 msec, 21 +/- 3 cm/sec, and 49 +/- 12 msec, respectively; p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of beta-adrenoreceptor-blocking drugs in patients with Raynaud's phenomenon.
Authors: Coffman J D , Rasmussen H M
Published: June 2011

Digital vasospastic phenomena have been reported to result from use of nonselective and cardioselective beta-adrenoreceptor-blocking drugs. The effects of 80 mg/day propranolol and 100 mg/day metoprolol on finger hemodynamics and clinical responses were compared with those of placebo in 16 patients with Raynaud's phenomenon. A double-blind, 2 week crossover study design was used with a 2 week washout placebo period between drugs. Total fingertip blood flow (FBF) as determined by venous occlusion plethysmography, fingertip capillary flow (FCF) as determined by radioisotope disappearance rate, and finger systolic blood pressure (FSP) were measured in a 28.3 degrees and a 20 degrees C room at the end of each period. Subjects kept diaries to record vasospastic attacks. There were no significant changes in FBF, FCF, or FSP in the warm or cool environment during drug treatment as compared with during the placebo period. A decrease in pulse rate occurred with both drugs and there was a decrease in blood pressure with metoprolol. There were no significant changes in the number of vasospastic attacks or in the patients' overall evaluation of their conditions while they were receiving the drugs. It is concluded that the presence of Raynaud's phenomenon is not a contraindication to the use of beta-adrenoreceptor-blocking drugs in the normotensive population.
The effects of overdrive pacing and lidocaine on atrioventricular junctional rhythm in man: the role of abnormal automaticity.
Authors: Tenczer J , Littmann L , Rohla M , Fenyvesi T
Published: June 2011

The effects of overdrive pacing and lidocaine were studied in 22 patients with atrioventricular (AV) junctional rhythms. Based on the responses to cardiac pacing and lidocaine, patients were divided into two groups. AV junctional rhythms in group I (17 patients) were suppressed by overdrive pacing, and their rates were decreased by lidocaine. Lidocaine also prolonged the junctional recovery time in these patients. AV junctional rhythms in group II (five patients) were not suppressed by overdrive pacing. In contrast, the rate increased after overdrive pacing. Lidocaine did not alter the basic cycle lengths or the recovery times of the AV junctional rhythms in this group of patients. The data suggest that AV junctional rhythms in group I were caused by normal automaticity, while those in group II were probably due to abnormal automaticity.
Catheter-mediated electrical ablation of the posterior septum via the coronary sinus: electrophysiologic and histologic observations in dogs.
Authors: Coltorti F , Bardy G H , Reichenbach D , Greene H L , Thomas R , Breazeale D G , Alferness C , Ivey T D
Published: June 2011

In a series of 12 dogs, the electrophysiologic and histologic effects of a single damped sine-wave shock delivered via standard electrocatheters to the region of the coronary sinus orifice were investigated. Six dogs received 200 J and six received 360 J of stored energy. The shock was delivered to two consecutive proximal poles of a standard quadripolar catheter positioned at the coronary sinus orifice and connected to the positive output (anode) of a defibrillator. A disc electrode positioned on the anterior chest wall served as the cathode (negative pole). During the shock, voltage and current were recorded. Electrophysiologic testing was done before and 4 weeks after the shock. At 4 weeks, animals were killed and serial sections of the atrioventricular groove and conduction system were performed. No significant long-term change in atrioventricular conduction, spontaneous or induced atrial or ventricular arrhythmias was observed. However, transient atrioventricular block was seen in five and idioventricular rhythms in six animals in the short term. No persistent electrocardiographic changes were observed, and no sudden deaths occurred. Microscopically, transmural injury at the anulus proper or basilar ventricular epicardium was inconstant and infrequent. However, transmural atrial injury at the level of the coronary sinus was produced over a 10 +/- 5 mm length with the 200 J shock and a 21 +/- 6 mm length with the 360 J shock. Neither coronary artery injury nor damage to the conduction system was seen and cardiac tamponade did not occur. However, localized intramural atrial rupture of the coronary sinus wall (on the endocardial aspect only) was observed in each dog, consistent with barotrauma. With the present technique, atrial injury potentially capable of blocking the effects of accessory pathway conduction could be produced without other electrophysiologic alterations or complications. Injury to the anulus proper (and therefore to any accessory pathway per se) is probably unlikely. Barotrauma may play a significant role in the type of injury observed in this study.
A role for PAF-acether (platelet-activating factor) in platelet-dependent vascular diseases?
Authors: Benveniste J , Chignard M
Published: June 2011

Platelets-isolated or in conjunction with leukocytes-interact with vessel walls in many experimental and human diseases. Several mediators are held responsible for platelet activation and interaction with leukocytes, among which PAF-acether (platelet-activating factor) is a prime candidate. This phospholipid mediator is released by most inflammatory cells, including neutrophils, by isolated organs such as kidney and heart, is a potent platelet and neutrophil agonist, and exerts major vasoactive properties. Its biosynthesis involves a two-step enzymatic process yielding the active molecule from the membrane alkyl-ether choline-containing phospholipids. The first step implicates a phospholipase A2 that hydrolyzes a long-chain fatty acid (which can be arachidonic acid) from membrane phospholipids, leaving the intermediate compound lyso PAF-acether, a PAF-acether precursor that is acetylated by an acetyltransferase in a second step. It can also result from deacetylation of PAF-acether by an acetylhydrolase. PAF-acether release might explain the intervention of platelets in diseases such as glomerulonephritis and allergic vasculitis, in which the involvement of neutrophils and platelets is frequently noted. The end result of these complex sets of cell-to-cell interactions is the release of most known inflammatory mediators, influencing vascular permeability, cell infiltration, and smooth muscle contraction. Nevertheless, direct evidence for the implication of these rather well-defined cellular and molecular interactions in human pathologic states remains to be obtained.
Locally acting growth factors for vascular smooth muscle cells: endogenous synthesis and release from platelets.
Authors: Bowen-Pope D F , Ross R , Seifert R A
Published: June 2011

Release of platelet-derived growth factor (PDGF) from platelets has been postulated to stimulate at least some of the cell proliferation seen at sites of tissue damage, both beneficially (wound healing) and perniciously (during formation of atherosclerotic lesions). Two other growth factors have been localized to the platelet: epidermal growth factor and transforming growth factor. These factors may function synergistically with PDGF in promoting smooth muscle cell proliferation in the injured vessel wall. PDGF-like molecules (PDGF-c) that bind to the PDGF receptor and are at least partially recognized by antiserum against PDGF may also be synthesized by vessel wall cells themselves under certain circumstances. Arterial endothelial cells secrete several mitogens, one of which is a PDGF-c. Release is greatly stimulated by exposure of the cells to physiologic concentrations of thrombin. Also, aortic smooth muscle cells from 2-week-old rats secrete mitogenic levels of PDGF-c. In this case, PDGF-c accounts for all the mitogenic activity in conditioned medium (when assayed on 3T3 cells). Smooth muscle cells obtained from adult rat aortae secrete 150-fold less PDGF-c. In a third example, when adult rat carotid arteries are damaged with a balloon catheter, smooth muscle cells migrate into the intima of the artery and proliferate. By 2 weeks, the number of smooth muscle cells in the artery has doubled. When these intimal smooth muscle cells are cultured, they are found to secrete PDGF-c. These findings suggest that activation of endogenous synthesis of PDGF-c may contribute to the smooth muscle cell proliferation seen in response to vascular injury.
Death and other time-related events after valve replacement.
Authors: Blackstone E H , Kirklin J W
Published: June 2011

A total of 1533 patients received primary aortic and/or mitral valve replacement, with or without tricuspid valve surgery or other associated cardiac procedures, from January 1, 1975, to July 1, 1979. Actuarial survival at 5 years was 74%. The hazard function (instantaneous risk) of death was highest immediately after operation. Among the incremental risk factors for premature death from any cause were preoperative NYHA class, any valve lesion other than aortic stenosis, aortic cross-clamp time, and combined aortic and mitral valve replacement. Ten modes of death were identified, each with its unique hazard function and risk factors. The commonest mode was cardiac failure. Sudden death was the next commonest, and the early phase of its hazard function peaked about 3 weeks after operation. Seventy-five patients (6.7% of the 1533) had 103 valve reoperations in the follow-up period. Actuarial survival after reoperation was less than that after the primary operation; whether the reoperation was the first, second, or third was a risk factor. Actuarial freedom from prosthetic valve endocarditis (PVE) was 97% at 1 year, and that of periprosthetic leakage without evident infection was 98.8%; the hazard function for the event PVE had an early phase peaking at about 6 weeks and a constant low phase throughout, whereas that of periprosthetic leakage had a single early peaking phase. After reoperations, the actuarial freedom from PVE and periprosthetic leakage was less than that after the original operation. The risk factors for the development of periprosthetic leakage without evident infection were similar but not identical to those for PVE. Among patients receiving a bioprosthesis, 91% were free of bioprosthetic degeneration 5 years after operation. The hazard function was single and continuously rising, and young age and female gender were risk factors. Actuarial freedom from acute prosthetic thrombosis was 97.9% at 5 years. The single hazard function for this event peaked at 10 months. The risk of thrombosis was higher in female patients. The uses of this integrated study, and the inferences from it, are described.
Non-Q wave perioperative myocardial infarction: assessment of the incidence and severity of regional dysfunction with quantitative two-dimensional echocardiography.
Authors: Force T , Kemper A J , Bloomfield P , Tow D E , Khuri S F , Josa M , Parisi A F
Published: June 2011

Since the widespread use of hypothermic potassium cardioplegia began, marked reductions in perioperative mortality and the rate of Q wave-associated myocardial infarctions have been noted. No study to date has evaluated whether there has been an equally dramatic improvement in the incidence of postoperative myocardial infarctions unassociated with Q wave development. We used a previously validated quantitative two-dimensional echocardiographic analytic algorithm to determine the incidence and severity of regional wall motion abnormalities (RWMAs) and first-pass radionuclide ventriculography to assess deterioration in global left ventricular function in the four following groups of patients (total n = 65): (1) those with peak postoperative creatine kinase (CK)-MB levels equal to or less than the mean value for patients undergoing coronary artery bypass surgery at our institution (n = 10), (2) those with CK-MB levels between the mean and 1 SD above the mean (n = 10), (3) those with peak CK-MB levels higher than 1 SD above the mean (n = 25), and (4) those with new pathologic Q waves on the postoperative electrocardiogram (n = 20). All patients had electrocardiograms without pathologic Q waves and normal wall motion and ejection fraction by contrast ventriculography before surgery. The incidence of postoperative RWMA by two-dimensional echocardiography for groups 1 through 4 was 0%, 20%, 55%, and 89%, respectively. Percent of abnormal left ventricular segments, wall motion scores, and the deterioration in left ventricular ejection fraction as assessed by radionuclide ventriculography were similar for patients with new RWMAs whether or not new Q waves developed (p = NS for all).(ABSTRACT TRUNCATED AT 250 WORDS)
Noninvasive estimation of valve area in patients with aortic stenosis by Doppler ultrasound and two-dimensional echocardiography.
Authors: Skjaerpe T , Hegrenaes L , Hatle L
Published: June 2011

In 30 patients with aortic stenosis, 14 of whom also had significant aortic regurgitation, the velocities in the stenotic jet (V') and below the valve (V) were recorded by Doppler ultrasound. With two-dimensional echocardiography, two subvalvular areas (A) were calculated from leading-to-leading edge ("large") and trailing-to-leading edge ("inner") diameter measurements. The aortic valve area was calculated by the equation of continuity (A' = A X peak V/peak V') and by calculating stroke volume below the valve [A X integral of V (t) and dividing by the integral of V' (t) (= A"). Based on cardiac output estimations from single-plane angiographic images, Gorlin's formula was used to calculate invasive valve areas. In patients with no or mild aortic regurgitation a second invasive estimate was based on cardiac output measured by the Fick method. The best correlation was found when A' (with "large" diameter) was compared with invasive results based on cardiac output measured by the Fick method (r = .89, SEE +/- 0.12, n = 16); the worst was found when A" (with "large" diameter) was compared with invasive results based on cardiac output measurements by single-plane angiography (r = .80, SEE +/- 0.20, n = 30). The results indicate that valve area in patients with aortic stenosis can be reliably estimated noninvasively, even in those with significant aortic regurgitation.
Comparative systemic and renal effects of dopamine and angiotensin-converting enzyme inhibition with enalaprilat in patients with heart failure.
Authors: Maskin C S , Ocken S , Chadwick B , LeJemtel T H
Published: June 2011

Renal and systemic hemodynamics were measured during titration of dopamine and serially after intravenous administration of enalaprilat in nine patients with chronic severe congestive heart failure. During titration of dopamine, renal blood flow increased by 99%, from 304 +/- 120 to 604 +/- 234 ml/min (p less than .01) at a dose of dopamine of 2.1 micrograms/kg/min, which produced only a 21% increase in cardiac index, from 1.96 +/- 0.36 to 2.38 +/- 0.35 liters/min/m2 (p less than .05). Cardiac index was increased maximally at a dose of 4.0 micrograms/kg/min dopamine; however, renal blood flow was not further augmented. In contrast, after intravenous administration of enalaprilat, peak improvement of renal blood flow and cardiac index occurred concomitantly. Renal blood flow increased by 35%, from 316 +/- 97 to 427 +/- 107 ml/min (p less than .05), and cardiac index increased by 18%, from 1.99 +/- 0.40 to 2.35 +/- 0.40 liters/min/m2 (p less than .05). At similar increases in cardiac index, dopamine produced a greater increase in renal blood flow than enalaprilat: 604 +/- 234 vs 427 +/- 107 ml/min (p less than .05). Mean systemic arterial pressure, however, was greater with dopamine than with enalaprilat (78.1 +/- 16.7 vs 70.2 +/- 17.2 mm Hg; p less than .05) at peak effect. Thus, although both drugs appear to be potent renal vasodilators in patients with severe congestive heart failure, dopamine may be more effective in augmenting renal blood flow.
Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects.
Authors: Bonow R O , Dilsizian V , Rosing D R , Maron B J , Bacharach S L , Green M V
Published: June 2011

Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 +/- 1.3 to 3.7 +/- 1.3 end-diastolic volumes/sec; p less than .001) was associated with an increase in exercise tolerance (from 5.9 +/- 3.6 to 8.7 +/- 4.7 min; p less than .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p less than .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11%) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p less than .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p less than .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil.
Frequency-dependent effects of amitriptyline on ventricular conduction and cardiac rhythm in dogs.
Authors: Nattel S
Published: June 2011

Although overdoses of tricyclic antidepressant are known to produce both sinus tachycardia and ventricular tachyarrhythmias in man, these have been assumed to occur by independent mechanisms. This study was designed to evaluate the relationship of ventricular activation frequency to the cardiotoxic effects of amitriptyline. When amitriptyline was infused into dogs with formalin-induced atrioventricular (AV) block to evaluate a broad range of pacing frequencies, the drug produced dose-related QRS prolongation that was markedly frequency dependent. Similar frequency-dependent depression of the maximum rate of depolarization (Vmax) was noted for canine Purkinje fibers superfused with amitriptyline in vitro. The time constant of recovery from amitriptyline-induced block was dose independent and averaged 228 msec in vivo and 216 msec in vitro. When amitriptyline was infused into dogs with intact AV conduction, sinus tachycardia occurred within 15 min, followed by progressive QRS prolongation and ventricular tachyarrhythmias after an average 29 min. Slowing of sinus rate by vagal stimulation (seven dogs) or intravenous metoprolol (five dogs) reproducibly reversed the QRS prolongation and ventricular tachyarrhythmias caused by amitriptyline. These studies show that amitriptyline produces frequency-related depression of ventricular conduction in vivo, with a time dependence similar to effects on the maximum rate of depolarization in vitro. Interventions that slow heart rate reverse the adverse effects of amitriptyline on ventricular conduction and cardiac rhythm.
Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia.
Authors: Myers M L , Bolli R , Lekich R F , Hartley C J , Roberts R
Published: June 2011

Reperfusion after reversible regional ischemia has been shown to result in delayed recovery of myocardial function, but the mechanism responsible for this phenomenon remains unknown. We explored the potential role of oxygen-free radicals as mediators of postischemic dysfunction in open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 hr of reperfusion. Treated animals (n = 19) received an infusion of the oxygen free-radical scavengers superoxide dismutase (SOD; 15,000 U/kg) and catalase (CAT; 55,000 U/kg) for 1 hr starting 15 min before LAD occlusion, while control animals (n = 20) received an equal volume of saline. SOD and CAT produced no discernible effect on heart rate, aortic pressure, or left atrial pressure. Collateral flow to the ischemic zone (radioactive microspheres) was 0.07 +/- 0.01 ml/min/g in both groups. The size of the occluded bed as determined by postmortem perfusion was 26.1 +/- 1.2% of the left ventricle in the control group and 26.5 +/- 0.9% in the treated group. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed-Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs, both at 1 hr (43.8 +/- 14.3 vs 12.8 +/- 11.6) and 2 hr of reperfusion (74.2 +/- 8.4 vs 31.6 +/- 9.8, p less than .005). This improved recovery of function obtained with SOD and CAT suggests that oxygen-free radicals play an important role in the genesis of myocardial dysfunction after a brief episode of regional ischemia.
Effect of serial brief ischemic episodes on extracellular K+, pH, and activation in the pig.
Authors: Fleet W F , Johnson T A , Graebner C A , Gettes L S
Published: June 2011

This study was performed to determine the reproducibility of the ionic and electrical changes associated with serial ischemic episodes. We used ion-selective and bipolar plunge electrodes to determine the changes in left ventricular extracellular potassium ([K+]e), extracellular pH (pHe), and local activation during sequential 10 min occlusions of the left anterior descending coronary artery separated by 50 min of reperfusion in open-chest anesthetized pigs. We found that uniformly during the initial occlusion, and in approximately 50% of animals during the second occlusion, [K+]e rose more rapidly but to a lower level than in subsequent occlusions. By the third occlusion the changes in [K+]e were reproducible. Extracellular acidosis was greatest in the first occlusion and decreased progressively with each subsequent occlusion. Local activation was characterized by a decrease in spontaneous improvement and increase in block with each successive occlusion. The occurrence of ventricular fibrillation could not be directly attributed to the magnitude of the change in [K+]e or pHe. Moreover, the occurrence of ventricular fibrillation in one occlusion did not necessarily predict its occurrence thereafter. Our results indicate that serial episodes of ischemia are associated with different but predictable changes in ionic and electrical events that may be clinically relevant and that must be appreciated before the results from similar protocols with serial ischemic episodes can be interpreted meaningfully.
Mechanisms of improving regional and global ventricular function by preload alterations during acute ischemia in the canine left ventricle.
Authors: Lew W Y , Ban-Hayashi E
Published: June 2011

We examined the influence of left ventricular end-diastolic pressure (LVEDP) on the mechanical interaction between ischemic and nonischemic areas during acute myocardial ischemia. Circumferentially oriented ultrasonic segment gauges were implanted in the midwall of the anterior apex and posterior apex of the left ventricle in seven anesthetized dogs. Stroke volume was measured with a flow probe around the ascending aorta in five of these animals. We varied LVEDP with vena caval occlusion and dextran infusions to three matched levels (7, 12, and 19 mm Hg) before and 30 min after complete occlusion of the mid left anterior descending coronary artery. With acute ischemia, the anterior apex or ischemic zone demonstrated marked segmental lengthening during isovolumetric systole (end-diastole to aortic valve opening) and akinesis during the ejection phase (aortic valve opening to closure). In the posterior apex or nonischemic area, isovolumetric shortening increased and ejection phase shortening decreased during acute ischemia when compared with those under control conditions at the same LVEDP. Thus, a portion of the shortening generated by the nonischemic area was expended in stretching the ischemic zone during isovolumetric systole, thereby reducing the amount of ejection phase shortening. As LVEDP was increased, there was a parallel decrease in both the amount of isovolumetric lengthening in the ischemic zone and the isovolumetric shortening in the nonischemic area. As a result, acute ischemia produced less of a reduction in ejection phase shortening in the nonischemic area and in stroke volume at high as compared with low LVEDP. We conclude that the ischemic zone imposes a mechanical disadvantage on the nonischemic area, the magnitude of which is directly proportional to the amount of isovolumetric lengthening or bulge in the ischemic zone. An increase in LVEDP during acute ischemia improves regional and global ventricular function by both the Frank-Starling mechanism in the nonischemic (but not the ischemic) area and by reducing the mechanical disadvantage that the ischemic zone imposes on the nonischemic area.