bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal exercise hemodynamics in patients with normal systolic function late after aortic valve replacement.
Authors: Monrad E S , Hess O M , Murakami T , Nonogi H , Corin W J , Krayenbuehl H P
Published: June 2011

We studied the hemodynamic response to supine bicycle exercise in 20 patients late (10 +/- 2 years) after aortic valve replacement (for aortic stenosis in 12 patients, aortic insufficiency in six patients, and for combined stenosis and insufficiency in two patients). The pulmonary artery wedge pressure was obtained with a pulmonary artery balloon catheter, and left ventriculography was performed by digital-subtraction angiography after injection of radiographic contrast into the pulmonary artery. These patients were compared with 11 control subjects with no or minimal cardiac disease studied routinely for evaluation of chest pain in whom left ventricular end-diastolic pressure and a direct contrast ventriculogram were obtained. Compared with the control population, the study population had similar left heart filling pressures (7 +/- 3 vs 9 +/- 3 mm Hg, NS), but higher left ventricular ejection fractions (75 +/- 7% vs 67 +/- 7%, p less than .02) and higher left ventricular muscle mass indexes (106 +/- 28 vs 85 +/- 9 g/m2, p less than .01). Elevated myocardial muscle mass led to lower systolic wall stress in the study population than in the control subjects (254 +/- 65 vs 320 +/- 49 10(3).dynes/cm2, p less than .01) and might explain the higher ejection fraction observed. Fourteen patients had a normal response to exercise (with left heart filling pressures of 16 +/- 4 vs 18 +/- 2 mm Hg for control subjects, NS; and left ventricular ejection fraction of 77 +/- 8% vs 73 +/- 5% for control subjects, NS). However, while the remaining six patients had a normal exercise left ventricular ejection fraction (72 +/- 9%, NS), they had an abnormal rise in left heart filling pressure (33 +/- 8 mm Hg, p less than .01). Preoperatively these patients also had higher left ventricular mid- and end-diastolic pressures at similar diastolic volumes, suggesting a decrease in chamber compliance. Thus, late after aortic valve replacement there is a subgroup of patients who, despite normal hemodynamics and normal left ventricular systolic function as assessed by the left ventricular ejection fraction at rest, have an abnormal response to exercise characterized primarily by a substantial rise in left heart filling pressures. Preoperatively this group also has a decrease in diastolic chamber compliance despite nearly normal left ventricular ejection fractions. This abnormality appears to result from a primary derangement of diastolic function that is not evident at rest.
Interactions of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications.
Authors: Lucore C L , Sobel B E
Published: June 2011

To delineate interactions of infused tissue-type plasminogen activator (t-PA) with inhibitors in plasma and their impact on fibrinolytic activity, serial plasma samples from patients with acute myocardial infarction and from normal rabbits given infusions of t-PA were assayed for t-PA antigen, activity of "fast acting" plasminogen activator inhibitor (PAI-1), and the presence and nature of t-PA-inhibitor complexes. In patients, endogenous t-PA circulated predominantly as a 100 kilodalton (kDa) complex with PAI-1, as verified by immunoprecipitation. During infusions, t-PA circulated not only as free t-PA (55 kDa) but also in complexes with PAI-1 (100 kDa), alpha 2-antiplasmin (110 kDa), and C1-esterase inhibitor (170 kDa). After termination of infusions, levels of free t-PA declined, while inhibitor complexes remained prominent. Free PAI-1 activity, assayed spectrophotometrically, was markedly elevated in the 24 hr interval after infusion of t-PA in 47% of patients with infarction. The specific activity of t-PA during infusions was 0.4 IU/ng or greater. However, during the 3 hr interval after infusions in patients, specific activity declined in association with prominence of t-PA complexes, predominantly with PAI-1. Infusions of t-PA in normal rabbits did not result in reactive increases in PAI-1 activity or in the t-PA-PAI-1 complex. After infusions, t-PA was associated predominantly with alpha 2-antiplasmin and C1-esterase inhibitor rather than PAI-1. t-PA inhibitor complexes were seen despite immediate acidification of whole blood, indicating that they were present in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative effects of nitroprusside and pinacidil on myocardial blood flow and infarct size in awake dogs with acute myocardial infarction.
Authors: Imai N , Liang C S , Stone C K , Sakamoto S , Hood W B
Published: June 2011

The effect of nitroprusside in limiting myocardial infarct was compared with that of pinacidil, a new antihypertensive agent with potent coronary vasodilator properties, in instrumented awake dogs subjected to 4 hr of left anterior descending coronary artery occlusion and 20 hr of reperfusion. Dogs were randomly assigned to receive intravenous normal saline, nitroprusside, or pinacidil beginning 40 min after the onset of coronary artery occlusion and continuing throughout the occlusion and the first hour of reperfusion. Nitroprusside and pinacidil were titrated to decrease mean aortic pressure by 25 mm Hg; normal saline had no effect on mean aortic pressure. Other systemic hemodynamic variables were not significantly altered by normal saline or nitroprusside, and myocardial blood flow did not change during normal saline infusion in normal and ischemic myocardium. In contrast, nitroprusside increased the blood flow and the endocardial/epicardial flow ratio in ischemic myocardium. This increase in ischemic myocardial blood flow was accompanied by a significant reduction in infarct size (40 +/- 3% of region at risk vs 58 +/- 4% in the normal saline group; p less than .05). Pinacidil increased heart rate, cardiac output, and the peak rate of rise of left ventricular pressure. Furthermore, despite causing a threefold to fourfold increase in normal myocardial blood flow, pinacidil had no effect on either blood flow to ischemic myocardium or infarct size (57 +/- 5%). The data indicate that the marked coronary vasodilator effect of pinacidil does not cause an increase in ischemic blood flow or a reduction in infarct size.(ABSTRACT TRUNCATED AT 250 WORDS)
Improvement in myocardial performance without a decrease in high-energy phosphate metabolites after isoproterenol in Syrian cardiomyopathic hamsters.
Authors: Camacho S A , Wikman-Coffelt J , Wu S T , Watters T A , Botvinick E H , Sievers R , James T L , Jasmin G , Parmley W W
Published: June 2011

To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi]) and intracellular pH (pHi) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10(-6)M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p less than .005 compared with control; n = 5), O2 consumption eightfold (p less than .0005), and PCr by 40% (p less than .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p less than .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p less than .05 for both), during isoproterenol infusion. pHi decreased in normal animals (p less than .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 +/- 0.002 to 0.144 +/- 0.030 mumol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 +/- 5.85 mumol/ml heart water due to the presence of dystrophic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)
Immediate enhancement of left ventricular relaxation by coronary artery bypass grafting: intraoperative assessment.
Authors: Humphrey L S , Topol E J , Rosenfeld G I , Borkon A M , Baumgartner W A , Gardner T J , Maruschak G , Weiss J L
Published: June 2011

We investigated the effect of coronary artery bypass grafting on the rate of left ventricular relaxation as defined by the time constant for isovolumetric relaxation, T, measured in milliseconds. Completeness of relaxation at rapid heart rates was determined by comparison of the relationship between left ventricular pressure and echocardiographic left ventricular cross-sectional cavity area during rapid ventricular pacing with that obtained after a prolonged diastole when the ventricle was maximally relaxed. Twelve patients with coronary artery disease had significantly higher T values (94.5 +/- 6.2) than six patients without coronary artery disease who were undergoing other open heart procedures (39.5 +/- 5.0, p less than .001). T was significantly reduced after coronary artery bypass grafting (68.2 +/- 5.1, p = .007), but was unchanged in the six control patients after cardiopulmonary bypass (37.8 +/- 4.5, p = .54). Similar changes were found during rapid pacing to 100, 120, and 140/min. Incomplete relaxation was detected in three of 10 (heart rate 120 beats/min) and nine of 11 (heart rate 140 beats/min) patients with coronary artery disease and this decreased to 0 of 10 (heart rate 120 beats/min) and six of 11 (heart rate 140 beats/min) patients after coronary artery bypass. Incomplete relaxation before bypass at a heart rate of 120 beats/min averaged 0.9 +/- 0.3 mm Hg. At a heart rate of 140 beats/min, incomplete relaxation averaged 5.6 +/- 1.6 mm Hg before and 1.4 +/- 0.5 mm Hg after bypass. Intake of beta-blockers or calcium-channel blockers, body temperature, and systolic blood pressure were not found to be related to these changes. We conclude that immediately after coronary artery bypass relaxation of left ventricular muscle is enhanced and incomplete relaxation at rapid heart rates is less likely. The most probable cause of this improvement in ventricular relaxation after coronary artery bypass grafting is relief of ischemia.
Assessment of thallium-201 redistribution versus glucose uptake as predictors of viability after coronary occlusion and reperfusion.
Authors: Melin J A , Wijns W , Keyeux A , Gurné O , Cogneau M , Michel C , Bol A , Robert A , Charlier A , Pouleur H
Published: June 2011

Both 201Tl redistribution and persistent glucose uptake have been proposed as markers of viability after reperfusion. In the present study, they have been compared in the same open-chest canine preparation of occlusion and reperfusion. Ten fasting dogs were subjected to 2 hr of left anterior descending coronary artery occlusion and 4 hr of reperfusion. Myocardial blood flow was determined by a microsphere technique 100 min after occlusion and 3 hr after reperfusion. 201Tl was injected intravenously 20 min before reperfusion. Serial biopsy samples were obtained from ischemic and normal areas. 18F-2-deoxyglucose, a tracer of exogenous glucose uptake, was injected 3 hr after reperfusion. Thirty minutes before the animals were killed, simultaneous blood samples were taken from the femoral artery and the regional coronary veins draining the reperfused and the remote areas. Dogs were killed 4 hr after reperfusion was established. Area at risk was assessed by dye injection in vivo and area of necrosis by triphenyl tetrazolium chloride (TTC) staining, with confirmation by electron microscopy. Immediately after death, endocardial and epicardial samples were taken from regions characterized as risk regions, areas of necrosis, areas of patchy necrosis, and normal areas. These samples were counted in a scintillation well counter. Four hours after reperfusion, in ischemic myocardium (TTC positive) the relative 201Tl gradient between ischemic and normal regions was 26 +/- 13%, whereas in necrotic samples, this gradient was 71 +/- 26%.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs.
Authors: Puddu P E , Jouve R , Langlet F , Guillen J C , Lanti M , Reale A
Published: June 2011

To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Cox's regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study.
Effects of procainamide on intra-atrial [corrected] electrograms during atrial fibrillation: implications [corrected] for detection algorithms.
Authors: Ropella K M , Sahakian A V , Baerman J M , Swiryn S
Published: June 2011

The effects of antiarrhythmic drugs on electrograms have implications for arrhythmia-detection algorithms in implantable antitachycardia devices. Filtered and unfiltered intra-atrial electrograms were analyzed in eight patients who received procainamide (50 mg/min iv, up to 1000 mg) during 11 episodes of atrial fibrillation. Continuous recordings were made before, during, and after the infusion. The recordings were digitized, divided into 4.27 sec segments, and analyzed for atrial rate, median frequency and amplitude probability density function. Significant differences were noted before and after infusion of procainamide for atrial rate (498 +/- 97 vs 356 +/- 146 beats/min; p less than .005), median frequency (5.50 +/- 1.22 vs 4.24 +/- 0.99 Hz; p less than .0005), and density (58.3 +/- 13.9% vs 69.1 +/- 15.0%; p less than .005). Pre- and postprocainamide values were compared with published criteria for detection of atrial fibrillation. Before procainamide, only 2.3%, 5.7%, and 3.4% of the data segments failed to meet criteria for atrial fibrillation by rate, frequency content, and density, respectively. In contrast, after procainamide, 50%, 36.4%, and 28.4% of the data segments failed to meet these same criteria, despite electrograms still meeting morphologic criteria for atrial fibrillation. Thus procainamide resulted in changes sufficient to cause failure of published criteria for detection of atrial fibrillation. These findings have broad implications for the function of antitachycardia devices in patients receiving antiarrhythmic drug therapy.
Late results in patients with tetralogy of Fallot repaired during infancy.
Authors: Walsh E P , Rockenmacher S , Keane J F , Hougen T J , Lock J E , Castaneda A R
Published: June 2011

Between 1973 and 1985, 220 infants (age 1 day to 18 months, mean = 7 months) underwent repair of tetralogy of Fallot (TOF) or TOF/pulmonary atresia with 17 early deaths. Follow-up status was ascertained for 184 of 203 survivors (91%) at a postoperative interval of 2 to 185 months (mean = 60 months). Significant residual hemodynamic lesions included ventricular septal defect in three, and right ventricular outflow gradient in excess of 40 mm Hg in 24. Reoperation or interventional catheter procedures were performed in 31 of 184 (17%) patients. All postoperative electrocardiograms were reviewed; only two of 184 patients had ventricular ectopy on any tracing. Holter data from 41 patients revealed one with sinus node dysfunction, 12 with Lown grade 1 ectopy, and one with Lown grade 2 or greater. Conduction defects, evaluated by electrocardiographic and electrophysiologic measurements, were not different from those reported for TOF patients undergoing repair at later ages. No study patient received antiarrhythmic medication, although one required a pacemaker for sinus node dysfunction. There were three late deaths, all unrelated to arrhythmia. TOF repair in infancy appears to be associated with an acceptable hemodynamic outcome, and a low incidence of ventricular ectopy and sudden death at 5 year follow-up.
Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: possible role for a novel class of vasodilator metabolites.
Authors: Proctor K G , Shatkin S , Kaminski P M , Falck J R , Capdevila J H
Published: June 2011

To examine the contribution of arachidonic acid (AA) metabolites to the maintenance of cutaneous vasomotor tone after thermal injury, enzyme inhibitors were topically applied to the hamster cheek pouch before and after a spot burn. By use of video microscopy, blood flow was measured in adjacent arterioles that supplied the injured site. Ringer's solutions containing no drug (vehicle), indomethacin (cyclooxygenase inhibitor), BW755c (cyclooxygenase/lipoxygenase inhibitor), or ketoconazole (lipoxygenase/cytochrome P450 inhibitor) continuously suffused the entire tissue. There were no effects of these drugs on preburn blood flow at concentrations that blocked the vascular effects evoked by topical AA. In all groups, blood flow transiently increased after burn and thereafter decreased to levels that were altered by treatment. These results could not be attributed to alterations in vascular reactivity because neither the burn nor the drugs altered the vasodilation evoked by adenosine or prostacyclin. Relative to Ringer's, indomethacin had no effect, BW755c caused vasodilation, and ketoconazole caused vasoconstriction, which suggests that cytochrome P450 products might be vasoactive mediators in injured tissue. Therefore, purified synthetic compounds were compared with known vasodilators. The potency was prostacyclin greater than 12R-hydroxyeicostetraenoic acid greater than adenosine = 5,6 epoxyeicosatrienoic acid greater than AA, which supports the hypothesis that AA can be the source of a novel class of nonprostaglandin vasodilator compounds. In addition, at least one of the vasodilator responses was stereospecific. Nevertheless, the exact explanation for the differential effects of AA inhibitors on postburn blood flow is unknown.
Right ventricular diastolic pressure-volume relations and regional dimensions during acute alterations in loading conditions.
Authors: Dell'Italia L J , Walsh R A
Published: June 2011

Acute pharmacologically mediated parallel shifts in the left ventricular diastolic pressure-volume relation may be due to the restraining effect of the pericardium and/or leftward displacement of the interventricular septum. The existence and cause of this phenomenon in the right ventricle has not been studied in animals or in man. Accordingly, we altered right ventricular pressure with intravenous phenylephrine (0.2 to 0.3 mg) and nitroprusside (0.5 to 1.5 micrograms/kg/min) to achieve three disparate peak right ventricular pressures in nine normal subjects after partial autonomic blockade with atropine (1 mg) and propranolol (0.15 mg/kg). Simultaneous high-fidelity right ventricular pressures and biplane cineventriculographic volumes were acquired during the three resultant loading conditions. Right atrial pacing maintained heart rate constant at each pressure level. Peak right ventricular systolic pressure (23 +/- 3 vs 31 +/- 9 vs 45 +/- 6 mm Hg, all p less than .01) and right ventricular end-diastolic pressure (4 +/- 2 vs 8 +/- 4 vs 11 +/- 3 mm Hg, all p less than .01) were significantly different at low, medium, and high loading conditions, respectively. Right ventricular diastolic pressure-volume relations were, in parallel, shifted upward with altered loading in each patient. This was manifest by an unchanged dynamic chamber stiffness constant and a significant increase in the diastolic pressure volume y intercept at each load (1.98 +/- 2.21 vs 5.33 +/- 5.39 vs 8.51 +/- 3.99 mm Hg, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of ventricular tachycardia with use of the morphology of the endocardial electrogram.
Authors: Langberg J J , Gibb W J , Auslander D M , Griffin J C
Published: June 2011

Currently available antitachycardia devices rely primarily on timing information to define abnormal rhythms. It would be useful to have more specific means of automatically identifying pathologic tachycardias. Using unfiltered (0.04 to 500 Hz bandpass) recordings made during electrophysiologic testing in 10 patients with ventricular tachycardia (VT), we studied the differences in electrogram morphology during sinus rhythm and VT. Signals were digitized at 1 kHz. A template of a normal sinus rhythm electrogram was created for each patient by averaging five sinus complexes from the beginning of each study. Ten sinus electrograms just before the onset of VT and 10 electrograms during stable monomorphic VT were compared with this template. The difference in morphology between a given electrogram and its template was quantitated by superimposing the two signals and measuring the area between the curves. There was no overlap in the ranges of these "area of the difference" measurements between sinus and VT electrograms from any of the 10 patients studied, including four with intraventricular conduction disturbances. In contrast, discrete features of the signal, including peak amplitude and maximum dV/dt, did not reliably differentiate sinus from VT electrograms. Bandpass filtering, sample window size, and digitizing rate were manipulated to determine the minimal signal content necessary for the area of difference method to reliably identify VT. These interventions suggest that the low-frequency far-field portion of the signal is primarily responsible for the morphologic differences between sinus and VT electrograms. In conclusion, the morphology of VT electrograms in man is consistently and distinctly different from the morphology of sinus electrograms.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of coronary occlusion on cardiac and body surface PQRST isoarea maps of dogs with abnormal activation simulating left bundle branch block.
Authors: Hirai M , Burgess M J , Haws C W
Published: June 2011

The possibility of detecting myocardial infarction in the presence of left bundle branch block by analysis of cardiac and body surface PQRST isoarea maps was studied in nine open-chest and six closed-chest dogs. Recordings were taken during supraventricular drive or right atrial plus right ventricular pacing in control periods and at intervals for up to 10 hr after left anterior descending coronary artery occlusion. Right ventricular pacing was used to simulate left bundle branch block. Myocardial infarction was documented with triphenyl tetrazolium staining. The PQRST areas during supraventricular drive and right atrial plus right ventricular pacing were highly correlated to each other both before and after coronary occlusion. The PQRST isoarea maps after coronary occlusion showed a strong pole overlying the ischemic area on the cardiac surface in open-chest animals and over the left anterior thorax in closed-chest animals. The PQRST pole was positive during the first 1 to 2 hr of occlusion and became negative after several hours. The findings demonstrate that localized abnormalities due to ischemia and infarction are manifest in body and cardiac surface PQRST isoarea maps of both supraventricular complexes and right ventricular paced complexes. The findings suggest that PQRST isoarea maps may aid in identification and localization of ischemic or infarcted myocardium in the setting of abnormal activation such as left bundle branch block.
Assessment of immediate and long-term functional results of percutaneous transluminal coronary angioplasty.
Authors: Zijlstra F , den Boer A , Reiber J H , van Es G A , Lubsen J , Serruys P W
Published: June 2011

Assessment of the functional significance of coronary artery lesions during cardiac catheterization has recently become possible by calculating coronary flow reserve from both myocardial contrast appearance time and density in the resting and hyperemic states determined from digitized coronary cineangiograms. However, the interobserver and intraobserver variabilities, as well as the short-, medium-, and long-term variabilities of the coronary flow reserve measurements, have to be established before this technique becomes an acceptable means of assessing the immediate and long-term functional results of revascularization procedures such as percutaneous transluminal coronary angioplasty (PTCA). Variability was defined as the mean difference and standard deviation of the difference between duplicate determinations of coronary flow reserve. The intraobserver variability (mean difference +/- SD) in the measurement of coronary flow reserve was -0.01 +/- 0.07. Interobserver variability by two observers was +0.08 +/- 0.52. Short-term variability based on the analysis of two coronary cineangiograms taken 5 minutes apart was -0.02 +/- 0.26. Medium-term variability (coronary cineangiographies repeated 1-3 hours apart) was found to be -0.06 +/- 0.52. Long-term variability (coronary cineangiographies repeated 3-5 months apart) was 0.11 +/- 0.63. Having established the reproducibility of this radiographic method, we studied the prospective changes in coronary flow reserve in 25 patients undergoing PTCA for single vessel coronary artery disease. Coronary flow reserve measurements and quantitative coronary cineangiography were performed before, immediately after, and 3-5 months after PTCA. PTCA resulted in an immediate increase in coronary flow reserve from 1 +/- 0.3 to 2.3 +/- 0.6 with a concomitant increase in obstruction area from 0.9 +/- 0.3 to 3.3 +/- 0.7 mm2. Nine of the 25 patients developed restenosis defined as a diameter stenosis greater than 50% at follow-up. The other 16 patients had a coronary flow reserve of 3.3 +/- 0.6, which was measured 3-5 months after PTCA. Coronary flow reserve measurement from digitized coronary cineangiograms is a reproducible method for the assessment of the physiological importance of coronary artery obstructions. Short-, medium-, and long-term investigations of the functional results of interventions such as pharmacological therapy or revascularization can be performed reliably with this technique.
Modest changes in high-density lipoprotein concentration and metabolism with prolonged exercise training.
Authors: Thompson P D , Cullinane E M , Sady S P , Flynn M M , Bernier D N , Kantor M A , Saritelli A L , Herbert P N
Published: June 2011

High-density lipoprotein (HDL) metabolism was studied in eight sedentary men before and after 14 and 32-48 weeks of exercise training. Subjects rode stationary bicycles 1 hour daily, 5 days each week for 14 weeks (n = 8), and 4 days each week thereafter for a total of 32-48 weeks (n = 7) of training. HDL metabolism was assessed with 125I-radiolabeled autologous HDL while subjects consumed defined diets. Maximal oxygen uptake increased 26 +/- 7% (p less than 0.001) after 14 weeks but did not increase further with more prolonged training. Body weight and estimated body fat did not change. HDL cholesterol increased 5 +/- 3 mg/dl, and triglycerides decreased 19 +/- 23 mg/dl after 14 weeks (p less than 0.025 for both), but there were no additional changes with continued training. Postheparin plasma lipoprotein lipase activity was 22% higher than baseline activity after both 14 (p less than 0.025) and 32 or more weeks of exercise. In contrast, hepatic triglyceride lipase activity was 16 +/- 8% and 15 +/- 8% lower than baseline at each measurement (p less than 0.005 for both). The disappearance rate of triglycerides after an intravenously administered fat solution was 24 +/- 24% higher at 14 weeks and 49 +/- 18% (p less than 0.005) higher after more prolonged training. Total and low-density lipoprotein cholesterol and apolipoprotein A-I and A-II concentrations at the end of study were not different from initial values. Plasma volume was 8% above initial values at both post-training measurements. The biological half-life of apolipoprotein A-I was unchanged at 14 weeks but was 10 +/- 13% longer (p = 0.07) and increased in all but one subject at the end of the study. Half-life for apolipoprotein A-II was 8 +/- 8% (p = 0.031) and 11 +/- 14% (p = 0.06) above baseline at 14 and 32 or more weeks, respectively. The synthetic rates for apolipoproteins A-I and A-II were not different from baseline values at 32-48 weeks. We conclude that 8-11 months of exercise training in previously sedentary men enhances fat tolerance and increases HDL cholesterol concentrations by prolonging HDL survival. The changes in HDL apolipoprotein survival, however, do not approximate the differences previously noted between elite endurance athletes and sedentary men. Changes in HDL cholesterol concentration were not large and suggest that the potential for exercise-related changes in HDL may be modest in many subjects.
Variability of transient myocardial ischemia in ambulatory patients with coronary artery disease.
Authors: Nabel E G , Barry J , Rocco M B , Campbell S , Mead K , Fenton T , Orav E J , Selwyn A P
Published: June 2011

Ambulatory electrocardiographic (ECG) monitoring of patients with chronic stable angina has demonstrated frequent and prolonged episodes of ischemic ST segment depression, but its clinical use requires an understanding of the components and extent of variability. Therefore, variations in the frequency and duration of episodes of ST segment depression were evaluated with ambulatory ECG recording at daily, weekly, and monthly intervals in 42 patients with chronic stable angina and known coronary artery disease. Data were analyzed with a nested analysis of variance design that yields estimates of variance components. From the estimates of variance components, power calculations and minimum significant percent reductions in frequency and duration of ischemia were derived. During 4,656 hours of ambulatory ECG monitoring, 1,262 episodes of ischemic ST segment depression were detected. The frequency of episodes was 6.3 +/- 0.45/24 hr (mean +/- SEM), and the duration of episodes was 18.3 +/- 2.8/24 hr. Because of variability over time, the ability to detect significant changes was dependent upon the number of subjects, length of monitoring period, and intervals between monitoring periods. In a clinical trial, for example, a sample size of 25 patients monitored for 48 hours with 1 week between control and test conditions would require a 65% reduction in frequency, whereas a sample size of 50 patients monitored under similar conditions would require a 46% reduction in frequency, to attribute the change with 90% power to a therapeutic intervention rather than to a spontaneous variation. When monitoring a single patient for 48 hours with 1 week or 1 month between control and repeat monitoring sessions, episodes of ischemic ST depression must be eliminated to detect significant therapeutic changes in ischemic activity at the 95% confidence level.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial.
Authors: Greenberg B , Massie B , Bristow J D , Cheitlin M , Siemienczuk D , Topic N , Wilson R A , Szlachcic J , Thomas D
Published: June 2011

Although vasodilator drugs acutely reduce regurgitation and improve cardiac performance in aortic insufficiency, their long-term effects on left ventricular size and function are uncertain. Consequently, we performed a double-blinded, placebo-controlled trial using hydralazine in 80 minimally symptomatic patients who had clinically stable, moderate-to-severe aortic insufficiency. Patients randomized to hydralazine displayed a progressive reduction in left ventricular end-diastolic volume index (LVEDVI) measured by radionuclide angiography, the predetermined end point of the study. At 24 months, mean LVEDVI had been reduced by 30 +/- 38 ml/m2, an 18% reduction from baseline. In contrast, LVEDVI changed minimally in patients randomized to placebo, and the intergroup differences over time were statistically significant (p less than 0.03). The hydralazine group also experienced reductions in left ventricular end-systolic volume index and increases in ejection fraction that were significantly different (both p less than 0.01) from changes in placebo-treated patients. These findings show that long-term treatment with hydralazine reduces the volume overload in aortic insufficiency and suggest that such therapy may have a beneficial effect on the natural history of the disease.
Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function.
Authors: Martin G V , Sheehan F H , Stadius M , Maynard C , Davis K B , Ritchie J L , Kennedy J W
Published: June 2011

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had significantly better wall motion of noninfarct areas (SD, 0.36 vs. -0.08, p = 0.02). Treatment effects on function of noninfarct regions were most apparent in the subset of patients with multivessel disease. Thus, intravenous streptokinase preserves left ventricular function in patients with acute myocardial infarction. This benefit includes favorable effects on the function of regions remote from the site of infarction.
Pathological features of coronary arteries in children with Kawasaki disease in which coronary arterial aneurysm was absent at autopsy. Quantitative analysis.
Authors: Fujiwara T , Fujiwara H , Nakano H
Published: June 2011

Coronary arteries in six children who had Kawasaki disease but lacked coronary arterial aneurysms were examined. Four children died of myocarditis at the acute stage, and two children died of bacterial sepsis or as a result of an occurrence during cineangiography at the healed stage. Twenty-one children without Kawasaki disease were examined as controls. The six children with Kawasaki disease had no thrombi, recanalization, or stenosis greater than 50% in the major coronary arteries. Three patients had dilatation of the major coronary arteries at the acute stage. Two of the three patients died during the acute stage, and autopsy showed slight dilatation of coronary arteries and abnormal intimal thickening due to panvasculitis. In the third child, who died at the healed stage, dilatation of the coronary arteries detected by two-dimensional echocardiography at the acute stage had disappeared at the healed stage. No dilatation of the major coronary arteries was seen at autopsy. However, abnormal fibrous intimal thickening of the major coronary arteries without inflammatory changes was found. The other three patients had no dilatation of the major coronary arteries at the acute stage. Two patients died at the acute stage, and slight inflammation without abnormal intimal thickening was seen in the intima and the adventitial area. In the third patient, who died during the healed stage, two-dimensional echocardiography revealed no dilatation during the clinical course, and there was no inflammatory changes or abnormal intimal thickening at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
Early diastolic filling dynamics during experimental mitral regurgitation in the conscious dog.
Authors: Katayama K , Tajimi T , Guth B D , Matsuzaki M , Lee J D , Seitelberger R , Peterson K L
Published: June 2011

Diastolic flow into the left ventricle during mitral regurgitation must increase as total stroke volume increases in response to the volume overload. The mechanisms that allow augmented diastolic filling are not fully defined. Accordingly, the left ventricle of five dogs was instrumented with a micromanometer and sonomicrometers and studied during the conscious state before (control) and after the creation of significant mitral regurgitation. Serial measurements were made at control and up to 4 weeks after the creation of the volume overload. Heart rate, peak systolic wall stress, and peak positive dP/dt showed no significant changes between control and subsequent observations. End-diastolic volume and total stroke volume progressively and significantly increased during the 4-week course. When compared with the control state (51 +/- 4, mean +/- SD), the filling fraction during the first 40% of diastolic time was increased at 4 days (67 +/- 10%, p less than 0.001), 2 weeks (72 +/- 6%, p less than 0.001), and 4 weeks (76 +/- 10%, p less than 0.001). During the period of adaptation to the volume overload, filling fraction correlated with end-diastolic volume (r = 0.52, p less than 0.02) and total stroke volume (r = 0.80, p less than 0.001). Compared with the control state (0.81 +/- 0.04), eccentricity of the left ventricle at end systole decreased at 4 weeks (0.79 +/- 0.06, p less than 0.05); the absolute change in this ratio during the first 40% of diastolic time was significantly augmented at 2 weeks (0.09 +/- 0.02, p less than 0.05) and 4 weeks (0.11 +/- 0.04, p less than 0.005) compared with control (0.05 +/- 0.02). Ventricular elastance (pressure/volume) at end systole (minimum volume) was 1.70 +/- 0.50 mm Hg/ml at control, 1.09 +/- 0.46 at 4 days (p less than 0.05), 0.96 +/- 0.42 at 2 weeks (p less than 0.01), and 0.99 +/- 0.22 at 4 weeks (p less than 0.01). Moreover, the elastance change during the rapid-filling phase was significantly diminished after creation of mitral regurgitation. Thus, during the volume overload of mitral regurgitation, the left ventricle accommodates a higher percentage of its total stroke volume during early diastole; this adaptation can be correlated with augmented systolic shortening, and thereby with increased restorative forces or elastic recoil, and with reduced chamber elastance and eccentricity during the early part of diastole. Other potential mechanisms include altered systolic and relaxation loading, augmented elastic recoil of the left atrium, left atrium and left ventricular pressure gradient, accelerated myocardial inactivation, and increased adrenergic stimulation.
Cellular electrophysiological changes during ischemia in isolated, coronary-perfused cat ventricle with healed myocardial infarction.
Authors: Kimura S , Bassett A L , Cameron J S , Huikuri H , Kozlovskis P L , Myerburg R J
Published: June 2011

Cellular electrophysiological consequences of acute ischemia superimposed on healed myocardial infarction were studied in isolated, coronary-perfused cat left ventricles 2-4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, and the preparations were superfused with Tyrode's solution gassed with 95% N2-5% CO2. Transmembrane action potentials were recorded from the endocardial cells in normal and infarcted zones. There were no significant differences in measured action potential variables and refractory periods between cells in the normal and infarcted zones before acute ischemia. When coronary perfusion was discontinued ("ischemia"), resting potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened progressively in cells of the normal zone. However, the action potential changes were less prominent, and the refractory period was unchanged in cells in the infarcted zone. As a result, there were significant differences in resting membrane potential, action potential amplitude, action potential duration, and refractory period between cells in the normal and infarcted zones at 10 minutes of ischemia. These differences became larger as the ischemic period was prolonged. Spontaneous rapid ventricular activity was observed during the last 20-30 minutes of ischemia in four of eight preparations with healed myocardial infarction, whereas no spontaneous rapid ventricular activity was recorded in any of six normal heart preparations. Our data suggest that superimposition of acute ischemia on healed myocardial infarction produces electrophysiological inhomogeneities that may enhance arrhythmogenesis.
Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine.
Authors: van der Kraaij A M , Mostert L J , van Eijk H G , Koster J F
Published: June 2011

To investigate whether iron is involved in the reperfusion syndrome by aggravating free radical injury, the hearts from iron-loaded and control rats were perfused under normoxic, anoxic, and reperfusion conditions. Normoxic perfusion revealed no change in coronary flow, contractility, or lactate dehydrogenase (LDH) release between these two groups. Under anoxic and reperfusion conditions, however, we found a significant increase of ventricle fibrillation (56% vs. 0%, p less than 0.01, n = 9), a significantly lower recovery of contractility (21 +/- 7.4% vs. 81 +/- 6.6%, mean +/- SEM; p less than 0.001), and a significant increase of LDH release (667 +/- 142 vs. 268 +/- 37 mU LDH/min/g wet wt, mean +/- SEM; p less than 0.05). Administration of either 20 microM of the antioxidant (+)-cyanidanol-3 or 50 microM of the iron-chelator deferoxamine totally prevented the generation of ventricle fibrillation and normalized contractility to control levels in the iron-loaded group. Moreover, 20 microM (+)-cyanidanol-3 significantly lowered LDH release in this period (312 +/- 67 mU), whereas deferoxamine had no protective effect on this LDH release (1,494 +/- 288 mU). Normal hearts appeared to be protected by 20 microM (+)-cyanidanol-3 as well. In this group (n = 6), a significantly higher recovery of contractility (97.1 +/- 3.2% vs. 81 +/- 6.6%, p less than 0.05) and a significantly lower release of LDH (110 +/- 27 vs. 268 +/- 37 mU, p less than 0.05) was found compared with the control group (n = 9). No difference in superoxide dismutase or glutathione peroxidase activity was found between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Detection, localization, and quantitation of bioprosthetic mitral valve regurgitation. An in vitro two-dimensional color-Doppler flow-mapping study.
Authors: Vandenberg B F , Dellsperger K C , Chandran K B , Kerber R E
Published: June 2011

The usefulness of two-dimensional color-Doppler flow-imaging (2D Doppler) in the detection, localization, and quantitation of bioprosthetic mitral valve regurgitation is uncertain. Mitral bioprostheses, before and after the creation of transvalvular (n = 33), paravalvular (n = 17), or combined (n = 23) defects, were mounted in a pulsed duplication system (flow rates, 2.5-6.5 l/min; pulse rate, 70 beats/min). An Aloka 880 2D Doppler system (Japan) was used to image the regurgitant jets in the simulated left atrial chamber, analogous to images obtained with transesophageal echocardiography. Jet area was corrected to an estimate of stroke volume: 2D Doppler measurements were divided by [(valve effective orifice area) X (continuous-wave Doppler-determined mean diastolic filling velocity)]/pulse rate. Regurgitant fraction and regurgitant volume were measured by an electromagnetic flow probe. 2D Doppler correctly identified the presence and location of paravalvular regurgitation. In transvalvular and combined transvalvular-paravalvular defects, there were six incorrect interpretations, all having transvalvular regurgitant volumes less than 4 ml/beat. In the presence of transvalvular regurgitation, jet area, length, and width correlated linearly with regurgitant volume (r = 0.82, 0.80, and 0.68, respectively; p less than 0.0001) and regurgitant fraction (r = 0.62, 0.61, and 0.45, respectively; p less than 0.001). Correlations with regurgitant fraction were improved when 2D Doppler measurements were corrected for stroke volume (r = 0.78, 0.79, and 0.67, respectively; p less than 0.0001). Mitral bioprostheses with transvalvular defects were also studied at varying flow rates (3.2-7.5 l/min) and pulse rates (70, 90, and 110 beats/min). The correlation between jet area and regurgitant volume was improved with a second-order polynomial regression (r = 0.93, p less than 0.0001). Our conclusions are that 1) in this in vitro model analogous to transesophageal imaging, 2D Doppler accurately detects and localizes bioprosthetic mitral valve regurgitation; 2) in transvalvular bioprosthetic mitral valve regurgitation, 2D Doppler measurement of jet area has a curvilinear relation with regurgitant volume, and correlation with regurgitant fraction is improved with correction for stroke volume; and 3) in paravalvular bioprosthetic mitral valve regurgitation, correlations between 2D Doppler measurements and regurgitant volumes are weaker, possibly because of jet eccentricity.