bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary artery imaging with intravascular high-frequency ultrasound.
Authors: Potkin B N , Bartorelli A L , Gessert J M , Neville R F , Almagor Y , Roberts W C , Leon M B
Published: June 2011

Safe and effective clinical application of new interventional therapies may require more precise imaging of atherosclerotic coronary arteries. To determine the reliability of catheter-based intravascular ultrasound as an imaging modality, a miniaturized prototype ultrasound system (1-mm transducer; center frequency, 25 MHz) was used to acquire two-dimensional, cross-sectional images in 21 human coronary arteries from 13 patients studied at necropsy who had moderate-to-severe atherosclerosis. Fifty-four atherosclerotic sites imagined by ultrasound were compared with formalin-fixed and fresh histological sections of the coronary arteries with a digital video planimetry system. Ultrasound and histological measurements correlated significantly (all p less than 0.0001) for coronary artery cross-sectional area (r = 0.94), residual lumen cross-sectional area (r = 0.85), percent cross-sectional area (r = 0.84), and linear wall thickness (plaque and media) measured at 0 degrees, 90 degrees, 180 degrees, and 270 degrees (r = 0.92). Moreover, ultrasound accurately predicted histological plaque composition in 96% of cases. Anatomic features of the coronary arteries that were easily discernible were the lumen-plaque and media-adventitia interfaces, very bright echoes casting acoustic shadows in calcified plaques, bright and homogeneous echoes in fibrous plaques, and relatively echo-lucent images in lipid-filled lesions. These data indicate that intravascular ultrasound provides accurate image characterization of the artery lumen and wall geometry as well as the presence, distribution, and histological type of atherosclerotic plaque. Thus, ultrasound imaging appears to have great potential application for enhanced diagnosis of coronary atherosclerosis and may serve to guide new catheter-based techniques in the treatment of coronary artery disease.
Tolerance of the hypertrophic heart to ischemia. Studies in compensated and failing dog hearts with pressure overload hypertrophy.
Authors: Gaasch W H , Zile M R , Hoshino P K , Weinberg E O , Rhodes D R , Apstein C S
Published: June 2011

Tolerance of the canine heart to prolonged ischemic arrest was studied in 10 hearts from normal control dogs and 15 hearts from dogs with left ventricular hypertrophy (LVH); experiments were performed 1 year after banding the aorta in 8-week-old puppies. At 1 year, hemodynamic studies revealed decreased left ventricular (LV) fiber shortening and elevated end-diastolic pressure (EDP) in five dogs (group with LVH failure); 10 dogs exhibited normal shortening and normal EDP (group with LVH compensation). The left ventricle-to-body weight ratio (g/kg) was 4.4 +/- 0.8 in the control group of dogs, 7.7 +/- 1.0 in the group with LVH compensation, and 10 +/- 2.5 in the group with LVH failure. The tolerance to 60 minutes of global ischemia (37 degrees C) followed by 90 minutes of reperfusion was studied in an isolated blood-perfused heart apparatus (isovolumic left ventricle, coronary perfusion pressure of 100 mm Hg). In the baseline (preischemic) state, coronary blood flow, myocardial oxygen consumption, lactate extraction, and myocardial high-energy phosphate content were essentially equal in the three groups; with LV volume adjusted to produce a systolic pressure of 100 mm Hg, there were no significant differences in LVEDP among the three groups. During ischemia, the diastolic (asystolic) pressure increased from 11 +/- 3 to 28 +/- 16 mm Hg (p less than 0.05) in the group with LVH failure; however, it did not increase in the control or the LVH compensation groups. Myocardial ATP levels declined equally in all three groups. During early reperfusion, lactate washout was lowest in the group with LVH failure. By 90 minutes of reperfusion, there were no significant differences in coronary blood flow, myocardial oxygen consumption, lactate extraction, or high-energy phosphate levels. High diastolic pressure persisted at 90 minutes of reperfusion in the LVH failure group (EDP was 34 +/- 19 mm Hg); however, there was no significant change in EDP during reperfusion in the control or with LVH compensation groups. After 90 minutes of reperfusion, developed pressures in the control (54 +/- 9 mm Hg), the LVH compensation (49 +/- 18 mm Hg), and the LVH failure (67 +/- 17 mm Hg) groups were not significantly different. These data indicate that hearts with compensated LVH do not exhibit an impaired tolerance to ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension.
Authors: Linder L , Kiowski W , Bühler F R , Lüscher T F
Published: June 2011

In isolated blood vessels, acetylcholine releases endothelium-derived relaxing factor (EDRF). In vivo, the vasodilator action of acetylcholine may be mediated by EDRF, but prostacyclin or prejunctional inhibition of adrenergic neurotransmission may also be involved. Therefore, we investigated whether acetylcholine releases EDRF in humans in vivo and, if so, whether the response altered in essential hypertension. Acetylcholine was infused into the brachial artery, and forearm blood flow measured by venous occlusion plethysmography. In control subjects, acetylcholine (0.02-16 micrograms/min/100 ml tissue) increased flow from 2.4 +/- 5.0 to 20.6 +/- 5.2 ml/min/100 ml tissue (n = 14; p less than 0.05) and decreased forearm vascular resistance from 42.0 +/- 4.1 to 6.0 +/- 1.4 units (p less than 0.03), a response comparable to that of sodium nitroprusside (0.6 micrograms/min ml tissue). Acetylsalicylic acid (500 mg i.v.) given to block vascular prostacyclin production did not alter the response (n = 14). alpha-Adrenoceptor blockade by phentolamine (12 micrograms/min/100 ml tissue) did not prevent the increase in flow evoked by acetylcholine. In hypertensive patients, the decrease in forearm vascular resistance induced by acetylcholine but not evoked by sodium nitroprusside was reduced as compared with controls (14.5 +/- 3.1 and 6.1 +/- 1.6 units, respectively; n = 8; p less than 0.05). Thus, the vascular effects of acetylcholine in the human forearm circulation are independent of prostaglandins and adrenergic neurotransmission and therefore are most likely to be mediated by EDRF; the acetylcholine-induced release of EDRF is blunted in patients with essential hypertension.
Assessment of renin dependency of hypertension with a dipeptide renin inhibitor.
Authors: Weber M A , Neutel J M , Essinger I , Glassman H N , Boger R S , Luther R
Published: June 2011

To evaluate the participation of the renin-angiotensin system in sustaining hypertension, we administered the specific dipeptide renin inhibitor enalkiren (A-64662) to 18 patients with essential hypertension. Ascending intravenous bolus doses (0.03, 0.1, 0.3, and 1.0 mg/kg) of the inhibitor were each given at 45-minute intervals to patients maintained on an ad libitum sodium diet who were studied while in bed in the semirecumbent posture. Enalkiren produced marked decreases in plasma renin activity (PRA) that were still evident 8 hours after completion of dosing. Systolic and diastolic blood pressures were decreased in a dose-dependent fashion without an effect on heart rate. Repetition of this procedure after patients were subjected to sodium depletion by 1 week of thiazide treatment produced amplified decreases in blood pressure. Despite the short plasma half-life of the inhibitor, these blood pressure-lowering effects were sustained for 4-8 hours when compared with parallel placebo administration in the same patients. Both the baseline PRA and the inhibitor-induced changes in PRA correlated significantly with blood pressure changes during the unstimulated and the sodium-depleted studies. However, effects of the inhibitor on diastolic blood pressure in the latter study correlated most closely with actual increases in renin produced by diuretic pretreatment. Thus, this specific renin inhibitor has demonstrated the dependency of blood pressure on the renin-angiotensin system even during basal conditions in hypertensive patients. Moreover, renin response to sodium depletion appears to be an attribute that additionally characterizes individual hypertensive patients.
Spectral characteristics of heart rate variability before and during postural tilt. Relations to aging and risk of syncope.
Authors: Lipsitz L A , Mietus J , Moody G B , Goldberger A L
Published: June 2011

Fourier analysis of heart rate (HR) may be used to characterize overall HR variability as well as low- and high-frequency components attributable to sympathetic and vagal influences, respectively. We analyzed HR spectral characteristics of 12 healthy young (18-35 years) and 10 healthy old (71-94 years) subjects before and during 60 degrees head-up tilt. Total spectral power in the 0.01-0.40-Hz frequency range and low-frequency (0.06-0.10 Hz) and high-frequency (0.15-0.40 Hz) components of the HR power spectrum were significantly lower in old than in young subjects in supine and upright positions. To characterize and compare overall HR variability in young and old subjects, we computed the regression lines relating the log amplitude to the log frequency of the supine HR spectra (l/fx plots). The regression lines for old subjects were lower and steeper (mean slope, -0.78 [5%, 95% confidence limits (CL), -0.73, -0.83]) than in young (mean slope, -0.67 [CL, -0.62, -0.72]), indicating not only reduced overall spectral amplitude but also relatively greater attenuation of high-frequency HR components in the old subjects. This finding illustrates a novel way to quantify the loss of autonomic influences on HR regulation as a function of age. During postural tilt, HR variability was unchanged in the old subjects. For the entire group of young subjects, total HR variability increased during tilt. Six young subjects developed vasovagal syncope during tilt, enabling us to examine differences in the HR spectra of these subjects while they were asymptomatic before syncope.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitation of venous clot lysis with the D-dimer immunoassay during fibrinolytic therapy requires correction for soluble fibrin degradation.
Authors: Brenner B , Francis C W , Totterman S , Kessler C M , Rao A K , Rubin R , Kwaan H C , Gabriel K R , Marder V J
Published: June 2011

Plasma cross-linked fibrin-degradation products were analyzed using a D-dimer (DD) immunoassay in patients with deep vein thrombosis (DVT) or acute myocardial infarction (MI) treated with fibrinolytic therapy, and the results were correlated with clot lysis documented angiographically. In 13 patients with DVT, the mean DD concentration increased 10-fold (1,074 +/- 252 to 10,333 +/- 1,004 ng/ml) during therapy, but neither the peak level nor the DD concentration integrated over the course of therapy correlated with clot lysis. Since plasma DD can derive from degradation of soluble plasma fibrin as well as from thrombi, the contribution of the former was estimated by in vitro incubation of the pretreatment plasma with plasminogen activator. Subtraction of this value from the measured posttreatment DD concentration provided a "corrected" level that represented DD originating from lysis of thrombi. This modification resulted in improved correlation of DD levels with clot lysis. The mean corrected peak DD was higher in patients with successful thrombolysis (8,780 +/- 1,352 ng/ml) compared with patients without lysis (3,075 +/- 589 ng/ml, p less than 0.001). There was a moderate correlation between the volume of clot lysed and the corrected peak DD (r = 0.62) and a higher correlation with the corrected DD integrated over the course of treatment (r = 0.97). By contrast, the corrected DD concentrations were near zero in patients treated for MI with or without thrombolytic reperfusion, suggesting that fibrin in small coronary thrombi did not contribute significantly to total plasma DD during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of flecainide and quinidine on human atrial action potentials. Role of rate-dependence and comparison with guinea pig, rabbit, and dog tissues.
Authors: Wang Z G , Pelletier L C , Talajic M , Nattel S
Published: June 2011

Flecainide and other class IC antiarrhythmic drugs are effective in the prevention and termination of atrial fibrillation, but the mechanism of this action is unknown. To gain insights into potential cellular mechanisms, we evaluated the response of human atrial action potentials to equimolar therapeutic concentrations of flecainide and quinidine and compared this response to that of guinea pig, rabbit, and dog atria. Both compounds reduced Vmax more as activation rate increased, but flecainide was more potent than quinidine and had slower kinetics. The rate-dependence of Vmax reduction was similar for all species, but human tissue was more sensitive to the drugs tested. In contrast to changes in Vmax, drug-induced alterations in action potential duration showed opposite rate-dependence for the two drugs. Quinidine increased action potential duration to 95% repolarization (APD95) in human atria by 33 +/- 7% (mean +/- SD) at a cycle length of 1,000 msec, but this effect was reduced as cycle length decreased, to 12 +/- 4% (p less than 0.001) at a cycle length of 300 msec. Flecainide increased APD95 (by 6 +/- 3%) much less than quinidine at a cycle length of 1,000 msec, but its effect was increased by faster pacing, to 27 +/- 12% at a cycle length of 300 msec and 35 +/- 8% (p less than 0.001) at the shortest 1:1 cycle length. The rate-dependent response of APD to drugs was qualitatively similar but quantitatively different among species. Human tissue showed the greatest frequency-dependent drug effects on repolarization, followed by tissue from dogs and rabbits. Guinea pig atria showed the least (and statistically nonsignificant) rate-dependence of drug effect on APD. Drug-induced changes in refractoriness paralleled those in APD. We conclude that: 1) flecainide and quinidine both increase APD in human atrial tissue but with opposite rate-dependence, 2) the effects of flecainide to increase atrial APD and refractoriness are enhanced by the rapid rates typical of atrial fibrillation, and 3) animal tissues may differ importantly from human in both their sensitivity and rate-dependent response to antiarrhythmic drugs. The salutary response of atrial fibrillation to flecainide may be due to enhancement of drug action by the rapid atrial activation rates characteristic of this arrhythmia.
Comparison of ST segment/heart rate index to standard ST criteria for analysis of exercise electrocardiogram.
Authors: Lachterman B , Lehmann K G , Detrano R , Neutel J , Froelicher V F
Published: June 2011

The objective of our study was to compare the discriminating power of a proposed ST segment/heart rate index with that of a standard method of assessing exercise-induced ST segment depression for diagnosing coronary artery disease. We used a cross-sectional retrospective analysis of exercise test and coronary angiographic data. The study took place in a 1,200-bed Veterans Affairs Medical Center; participants were 328 male patients who had undergone both a sign and symptom-limited treadmill test and coronary angiography. The sensitivity of the ST segment/heart rate index was 54% at a cut point of 0.021 mm/(beats/min), corresponding to a specificity of 73%. The standard visual ST segment analysis had a sensitivity of 58% at this same specificity, which corresponded to an ST segment cut point of 1-mm depression relative to rest (p = NS). Similarly, for diagnosing three-vessel or left main coronary disease, no significant difference was found between the sensitivities or the two measurements at cut points of equivalent specificity. In this consecutive series of patients presenting for routine clinical testing, the ST segment/heart rate index did not improve the diagnostic accuracy of the exercise test for identifying the presence or severity of coronary artery disease relative to standard visual criteria.
Sites of conduction block in accessory atrioventricular pathways. Basis for concealed accessory pathways.
Authors: Kuck K H , Friday K J , Kunze K P , Schlüter M , Lazzara R , Jackman W M
Published: June 2011

Catheter recordings of accessory pathway (AP) activation were used to identify the site of antegrade and retrograde AP conduction block in 126 consecutive patients undergoing electrophysiological testing. Activation was recorded from 89 of 121 left free-wall and posteroseptal pathways (left APs) and from 12 of 24 right free-wall, midseptal, and anteroseptal pathways (right APs). The recorded APs were further subdivided into those exhibiting consistent antegrade conduction during sinus rhythm (overt APs: 50 left APs, eight right APs), those exhibiting intermittent antegrade conduction (intermittent APs: six left APs, two right APs), and those exhibiting only retrograde conduction (concealed APs: 33 left APs, two right APs). The sites of block were recorded during decremental atrial and ventricular stimulation. The sites of both antegrade and retrograde block were determined in 40 of 50 overt left APs and six of eight overt right APs. Antegrade and retrograde block occurred at or near the AP-ventricular (AP-V) interface in 37 of 40 overt left APs and two of six overt right APs and at the atrial-AP (A-AP) interface in one of 40 overt left APs and four of six overt right APs. In three of three overt left APs with no retrograde conduction, retrograde block occurred at or near the AP-V interface. The site of antegrade and retrograde block differed in only two of 58 overt pathways. There was no difference between overt APs limited at the A-AP or the AP-V interface in the shortest atrial or ventricular pacing cycle length maintaining 1:1 antegrade or retrograde AP conduction, respectively. Both antegrade and retrograde block occurred near the AP-V interface in four of six intermittent left APs and zero of two intermittent right APs and near the A-AP interface in two of six intermittent left APs and one of two intermittent right APs. The sites of both antegrade and retrograde block were determined in 28 of 33 concealed left APs, and both occurred at or near the AP-V interface in 26 and A-AP interface in two APs. In two of two concealed right APs, antegrade block occurred at the AP-V interface. These findings suggest that both antegrade and retrograde conduction are limited by factors operating near the AP-V interface in overt left APs and at the A-AP or AP-V interface in overt right APs. Factors limiting antegrade conduction in concealed APs appear to be located almost always near the AP-V interface.
Catheter ablation of Mahaim fibers with preservation of atrioventricular nodal conduction.
Authors: Haissaguerre M , Warin J F , Le Metayer P , Maraud L , De Roy L , Montserrat P , Massiere J P
Published: June 2011

Three patients with refractory preexcited tachycardia implicating Mahaim fibers underwent attempted catheter ablation of the accessory pathway. In the absence of demonstrable retrograde conduction in Mahaim fibers, we located the accessory pathway ventricular insertion site using the criteria of concordance between paced and spontaneous QRS morphologies during pace-mapping and earliest onset of local electrogram relative to surface preexcited QRS. At this site, a QS-like pattern of unfiltered unipolar electrograms with steep downstroke was recorded. The optimal site appeared radiologically at the right ventricular anterior wall or the adjacent septum, 2-4 cm from the tricuspid anulus. Three to six 160-J shocks were delivered at this site using an anterior chest wall plate as anode. After fulguration, conduction through the Mahaim tract was absent. A right bundle branch block persisted in two patients. All patients remained free of preexcited tachycardia during 12-16 months of follow-up. Postablation electrophysiological assessment showed no preexcitation in any patient. No reciprocating tachycardia was inducible, even during isoproterenol infusion. Atrioventricular nodal conduction parameters were unchanged from baseline study. Catheter ablation of Mahaim fibers is an effective alternative method for the treatment of tachycardias that include the accessory pathway in the circuit.
Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.
Authors: Austin M A , King M C , Vranizan K M , Krauss R M
Published: June 2011

In a community-based study of 301 subjects from 61 nuclear families, two distinct phenotypes (denoted A and B) were identified by nondenaturing gradient gel electrophoretic analysis of low density lipoprotein (LDL) subclasses. Phenotype A was characterized by predominance of large, buoyant LDL particles, and phenotype B consisted of a major peak of small, dense LDL particles. Previous analysis of the family data by complex segregation analysis demonstrated that these phenotypes appear to be inherited as a single-gene trait. In the present study, the phenotypes were found to be closely associated with variations in plasma levels of other lipid, lipoprotein, and apolipoprotein measurements. Specifically, phenotype B was associated with increases in plasma levels of triglyceride and apolipoprotein B, with mass of very low and intermediate density lipoproteins, and with decreases in high density lipoprotein (HDL) cholesterol, HDL2 mass, and plasma levels of apolipoprotein A-I. Thus, the proposed genetic locus responsible for LDL subclass phenotypes also results in an atherogenic lipoprotein phenotype.
Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group.
Authors: Uretsky B F , Jessup M , Konstam M A , Dec G W , Leier C V , Benotti J , Murali S , Herrmann H C , Sandberg J A
Published: June 2011

A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p less than 0.05) in anaerobic threshold at 1 month with enoximone. (2.7 +/- 0.8 ml O2/kg/min) compared with placebo (-0.8 +/- 1.2 ml O2/kg/min). This improvement was not sustained at 4 months (0.5 +/- 1.7 ml O2/kg/min with enoximone and 0.2 +/- 1.5 ml O2/kg/min with placebo). The dropout rate was significantly higher (p less than 0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p less than 0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Elastase-induced experimental aneurysms in rats.
Authors: Anidjar S , Salzmann J L , Gentric D , Lagneau P , Camilleri J P , Michel J B
Published: June 2011

An experimental in vivo model of aortic aneurysm was established by perfusing an isolated segment of rat abdominal aorta with pancreatic elastase. Ten rats were used in each protocol. Saline-perfused aortas developed no aneurysmal dilations. Elastase-perfused aortas contained aneurysms in the perfused area and a total loss of elastic tissue. Control aortas contained no elastic tissue lesions. There was a quantitative relation between the amount of elastase perfused and aneurysm formation: 1-2 units induced neither macroscopic nor microscopic lesions; 3-6 units induced microscopic elastic tissue damage without macroscopic aneurysm; and more than 6 units produced aneurysmal dilation in all cases. In situ elastase secretion by macrophages was induced by perfusing rat aortas with thioglycollate-activated macrophages or with thioglycollate alone. There was aortitis without true aneurysm and a total loss of elastic tissue in the vicinity of activated macrophages within the aortic media. Perfusion of infra-aneurysmal amount of elastase (1 or 2 units) or thioglycollate plus plasmin (2 units) always induced a large aneurysm, whereas plasmin alone induced neither macroscopic nor microscopic lesions. These morphological results were supported by the significantly elevated elastolytic activity within the aortic wall of animals perfused with thioglycollate plus plasmin 9 days, after perfusion (207.6 +/- 54.8 micrograms elastin-rhodamine lysed/18 hr; control rats, 25.43 +/- 11.13). The results suggest that the presence of elastase within the aortic media leads to aneurysm formation. Activated macrophages within the aortic media may be responsible for elastase secretion and elastic tissue destruction. Plasmin may enhance elastase activity and aggravate the aneurysmal lesion.
Immunosuppression with high doses of cyclophosphamide reduces the severity of myocarditis but increases the mortality in murine Coxsackievirus B3 myocarditis.
Authors: Kishimoto C , Thorp K A , Abelmann W H
Published: June 2011

To test the therapeutic efficacy of immunosuppression with cyclophosphamide (CYP) on coxsackievirus B3 (CB3) myocarditis, 2-week-old DBA/2 mice were inoculated with 3 X 10(2) plaque-forming units of CB3 virus. CYP (100 mg/kg/day s.c.) was administered daily on days 0-8 (experiment 1; group 2), days 8-21 (experiment 2; group 4), and days 21-34 (experiment 3; group 6). Groups 1, 3, and 5 were infected control groups for each experiment. Spleen, thymus, and body weights were measured. In experiment 1, survival rate in group 2 on day 8 was low compared with group 1 (nine of 51 versus eight of 28; p = NS), and myocardial virus titers in group 2 on day 8 were higher (p less than 0.05) compared with group 1; however, cellular infiltration and myocardial necrosis in group 2 were less severe (p less than 0.05), and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 2, survival rate in group 4 on day 21 was significantly lower (six of 24 versus 12 of 16; p less than 0.01), but cellular infiltration, myocardial necrosis, and calcification in group 4 were significantly less severe, and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 3, survival rate, cardiac histopathology, and serum neutralizing antibody titers did not differ between groups 5 and 6. In experiments 1, 2, and 3, the treated groups were characterized by lower spleen-to-body-weight and thymus-to-body-weight ratios and by marked cellular depletion in spleen and thymus.(ABSTRACT TRUNCATED AT 250 WORDS)
Minimum left ventricular pressure during beta-adrenergic stimulation in human subjects. Evidence for elastic recoil and diastolic "suction" in the normal heart.
Authors: Udelson J E , Bacharach S L , Cannon R O , Bonow R O
Published: June 2011

The influence of elastic recoil and restoring forces on diastolic left ventricular pressure decay and minimum left ventricular pressures has been demonstrated in animal models but has not been studied in the human heart. To investigate this issue in the normal human left ventricle, we studied eight patients with chest pain and normal coronary arteries with simultaneous measurement of left ventricular volume (by radionuclide angiography) and pressure (by micromanometer catheter) and coronary sinus blood flow. Electrocardiographic-gated data were obtained in the basal state, during rapid atrial pacing, and during isoproterenol infusion to a similar heart rate. Compared with pacing, isoproterenol increased ejection fraction and reduced end-systolic volume (p less than 0.005), end-systolic pressure (p less than 0.005), and the half-time of pressure decline after peak negative dP/dt (T1/2) (p less than 0.001). Negative diastolic pressure developed in seven of eight patients during isoproterenol (range, -0.5 to -2.4 mm Hg) but in only one of eight during pacing (-0.2 mm Hg). These reduced diastolic pressures during isoproterenol were accompanied by increased stroke volume (reflecting increased transmitral flow) and diminished pulmonary wedge pressure (reflecting left atrial pressure). The magnitude of reduction in minimum diastolic pressure during pacing and isoproterenol was related to the change in end-systolic volume (r = 0.79, p less than 0.001), ejection fraction (r = -0.74, p less than 0.001), T1/2 (r = -0.57, p less than 0.02), and coronary sinus flow (r = 0.73, p less than 0.005). Stronger correlations were observed in analyzing changes during isoproterenol alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppression of repolarization-related arrhythmias in vitro and in vivo by low-dose potassium channel activators.
Authors: Fish F A , Prakash C , Roden D M
Published: June 2011

Marked prolongation of cardiac action potentials and of QT intervals has been associated with early afterdepolarizations and triggered activity in vitro and with ventricular tachycardia in vivo. Because the antihypertensive potassium channel activators pinacidil and cromakalim are known to accelerate repolarization in cardiac tissues, we performed in vitro and in vivo experiments to test the hypothesis that these agents would block the arrhythmogenic effects of delayed repolarization. Early afterdepolarizations and triggered activity were elicited in canine cardiac Purkinje fibers driven at cycle lengths of 4 seconds or more (K0, 2.7 mM) during superfusion with quinidine, cesium, or sematilide, a methylsulfonylamino parasubstituted analogue of procainamide with class III antiarrhythmic activity. The potassium channel activators invariably (17 of 17) abolished this form of abnormal automaticity. This effect was observed at low concentrations that did not alter action potential characteristics at shorter cycle lengths. Intravenous Cs+ (total dose, 4.5 mM/kg) was used to produce ventricular arrhythmias in anesthetized rabbits randomly pretreated in a double-blind fashion with either low-dose pinacidil (0.2 mg/kg) or vehicle. Pinacidil pretreatment resulted in significantly fewer total ventricular ectopic beats (168 +/- 157 versus 582 +/- 448, p less than 0.005) and episodes of ventricular tachycardia (four of nine versus nine of nine, p = 0.057). At this dose, pinacidil did not alter mean blood pressure before Cs+ and maximal hypertensive response after Cs+. In summary, the potassium channel activators pinacidil and cromakalim suppressed triggered activity related to prolonged repolarization at concentrations that did not affect action potential characteristics at normal rates in vitro; pinacidil blunted arrhythmias produced by cesium administration in vivo without lowering blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables.
Authors: Lee K L , Pryor D B , Pieper K S , Harrell F E , Califf R M , Mark D B , Hlatky M A , Coleman R E , Cobb F R , Jones R H
Published: June 2011

To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available.
Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs.
Authors: Roth D M , White F C , Nichols M L , Dobbs S L , Longhurst J C , Bloor C M
Published: June 2011

The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise.
Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials.
Authors: Califf R M , Harrelson-Woodlief L , Topol E J
Published: June 2011

In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment.
An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence.
Authors: Holme I
Published: June 2011

The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For every 1% reduction in cholesterol, an estimated 2.5% reduction in CHD incidence is indicated (95% CL: 1.1, 3.9). With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials. With regard to total mortality, this efficiency was higher in secondary than in primary preventive trials. The efficiency was also somewhat dependent on the baseline cholesterol level. This study shows that cholesterol reduction is effective in lowering CHD incidence, but cholesterol reduction must be at least 8-9% to be effective in lowering total mortality.
Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy.
Authors: Frenneaux M P , Counihan P J , Caforio A L , Chikamori T , McKenna W J
Published: June 2011

To investigate the incidence of abnormal exercise blood pressure responses in hypertrophic cardiomyopathy (HCM) and the potential role of hemodynamic instability as a mechanism of sudden death, 129 consecutive patients with HCM underwent maximal symptom-limited treadmill exercise testing with blood pressure recording. Four patterns of blood pressure response were observed. Forty-three patients had significant exercise hypotension, with either a continuous fall in systolic blood pressure (n = 5) from the start of exercise or a sudden fall in systolic blood pressure (20-100 mm Hg; mean, 40 mm Hg) from the peak value (n = 38), 23 patients had a normal response during exercise but an abnormal blood pressure response in the recovery period, and the remaining 62 patients demonstrated a normal blood pressure response. Patients with exercise hypotension were younger (33 +/- 14 versus 46 +/- 14 years) and more of them had a family history of HCM and sudden death compared with those with a normal blood pressure response (15 of 43 versus 6 of 62 patients). Similarly, the 23 patients with abnormal recovery blood pressure responses were younger (43 +/- 16 versus 46 +/- 14 years) and had a higher incidence of a family history of sudden death (10 of 24 versus 6 of 62 patients). Left ventricular cavity dimensions were smaller in those with exercise hypotension, but 11 other clinical, echocardiographic, and arrhythmic variables were similar. To assess the mechanism of exercise hypotension, 14 patients who demonstrated exercise hypotension and 14 symptomatic patients with a normal exercise blood pressure response underwent invasive hemodynamic exercise testing.(ABSTRACT TRUNCATED AT 250 WORDS)
Prostacyclin and acetylcholine as screening agents for acute pulmonary vasodilator responsiveness in primary pulmonary hypertension.
Authors: Palevsky H I , Long W , Crow J , Fishman A P
Published: June 2011

Epoprostenol sodium (prostacyclin) administered intravenously is considered the standard for assessing the ability of the pulmonary circulation to vasodilate. At present, epoprostenol sodium is an investigational drug that has limited availability. In contrast, acetylcholine, also a pulmonary vasodilator, is readily available. Therefore, we assessed the feasibility of using acetylcholine as an alternative to prostacyclin in testing for the capacity of the pulmonary vasculature to vasodilate. Twenty-three patients with primary pulmonary hypertension (mean pulmonary arterial pressure, 58.5 +/- 13.4 mm Hg) received incremental infusions of prostacyclin and acetylcholine to predetermined maximal infusion rates as part of a battery of vasodilator agents administered according to standard protocols (mean, 5.4 +/- 1.2 agents/patient; range, 3-8 agents/patient); the administration of the different agents was timed to avoid synergistic effects. Of all the agents tested, prostacyclin and acetylcholine were most consistently effective in evoking acute pulmonary vasodilation, and both seemed to distinguish patients capable of manifesting acute pulmonary vasodilation from those who were not. However, at maximal doses set by protocol, prostacyclin generally elicited a greater vasodilator response than acetylcholine. The difference in magnitude of response may have been due to use of prescribed dosages of acetylcholine that were submaximal. In other respects, the two agents were similar; both were equally well-tolerated, and side effects were mild and resolved rapidly when the vasodilator infusions were stopped. We conclude that in the majority of patients with primary pulmonary hypertension, acetylcholine appears to be an effective and available substitute for prostacyclin in screening for pulmonary vasodilator responsiveness.
Left ventricular regional wall stress in dilated cardiomyopathy.
Authors: Hayashida W , Kumada T , Nohara R , Tanio H , Kambayashi M , Ishikawa N , Nakamura Y , Himura Y , Kawai C
Published: June 2011

Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janz's method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p less than 0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22 +/- 14% versus 54 +/- 9%, respectively, p less than 0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32 +/- 17% versus 15 +/- 4%, respectively, p less than 0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r = -0.60 to -0.86, p less than 0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM.
Long-term results of catheter ablation of idiopathic right ventricular tachycardia.
Authors: Morady F , Kadish A H , DiCarlo L , Kou W H , Winston S , deBuitlier M , Calkins H , Rosenheck S , Sousa J
Published: June 2011

Ten consecutive patients with recurrent episodes of symptomatic, idiopathic, sustained monomorphic ventricular tachycardia (VT) originating in the right ventricle underwent an attempt at catheter ablation of the ventricular tachycardia. There were seven women and three men, with a mean age of 39 +/- 14 years (+/- SD). None of the patients had any evidence of structural heart disease. The VT had a left bundle branch block configuration and an inferior axis in each patient, and the mean cycle length was 313 +/- 75 msec. Based on the methods of induction of the VT and the response of the VT to verapamil, the VT mechanism was presumed to be reentry in six patients, triggered activity in three patients, and catecholamine-sensitive automaticity in one patient. Sites for ablation were guided by pace mapping, and an appropriate target site was identified in the right ventricular outflow tract in each patient. From one to three shocks of 100-360 J (mean total, 336 +/- 195 J) were delivered from a defibrillator between the tip of the ablation catheter (cathode) and a patch electrode on the anterior chest (anode). An electrophysiology test 7-9 days after ablation demonstrated that VT was still inducible in only one patient, who was treated with amiodarone. One other patient had a recurrence of VT 3 weeks after ablation and was treated with verapamil. Eight of 10 patients were not treated with antiarrhythmic medications and have had no episodes of symptomatic VT during 15-68 months of follow-up (mean follow-up, 33 +/- 18 months). There were no acute or long-term complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional wall motion abnormalities after prolonged exercise in the normal left ventricle.
Authors: Douglas P S , O'Toole M L , Woolard J
Published: June 2011

To determine whether regional wall motion abnormalities exist or contribute to left ventricular dysfunction, we obtained two-dimensional echocardiograms in 12 athletes before (baseline), immediately after (race finish), and 1 day after (recovery) the Hawaii Ironman Triathlon (a 3.9-km swimming, 180.2-km bicycling, and 42.2-km running event). Left ventricular short-axis and apical four-chamber views were computer digitized and divided into six segments, and radial chord shortening and area ejection fraction were calculated. Global ejection fraction fell at race finish (51% versus 46%, p less than 0.05) but recovered by 1 day (54%, p less than 0.01 by repeated-measures analysis of variance). With the apical four-chamber view, midseptal and apical-septal motion were reduced at race finish but returned to baseline during recovery (midseptal radial chord shortening: 21%, 8%, 22%; apical-septal radial chord shortening: 27%, 12%, 25%; midseptal area ejection fraction: 39%, 30%, 40%; apical-septal area ejection fraction: 44% baseline, 33% race finish, 43% recovery; all p less than 0.01). In contrast, with the parasternal short-axis view, wall motion did not change at race finish but tended to be elevated during recovery and became significant for anteroseptal motion (radial chord shortening: 29%, 30%, 36%; area ejection fraction: 49% baseline, 51% race finish, 58% recovery; both p less than 0.05). Lateral wall motion was unchanged. In addition, an index of septal curvature was calculated using the ratio of the septal-lateral wall minor axis to the perpendicular anteroposterior minor axis. At all three data collections, this ratio remained close to 1.0 at end systole and end diastole.(ABSTRACT TRUNCATED AT 250 WORDS)