Search PubMed⌕ Search

Biomedical subjects

W Grossman

Publications and source records attributed to W Grossman.

At least 163 records · Page 9Linked to original sources
PubMed1981

Improved right ventricular function and reduced pulmonary vascular resistance during prazosin therapy of congestive heart failure.

Although the effect of systemic vasodilator therapy on left ventricular function in congestive heart failure has been extensively evaluated, little is known about its effect on pulmonary vascular resistance and right ventricular function. Since pulmonary vascular resistance is mediated in part by alpha-adrenergic receptors, we studied the effects of the alpha-adrenergic antagonist prazosin on right ventricular function as determined by a radionuclide ventriculographic technique which assessed right and left ventricular ejection fractions simultaneously. In 11 patients treated for two months with prazosin, right ventricular ejection fraction increased from 0.28 +/- 0.04 to 0.44 +/- 0.07 (p less than 0.01). In 10 patients who received a single dose of prazosin 48 hours after withdrawal of prior prazosin therapy, right ventricular ejection fraction increased from 0.29 to 0.05 to 0.38 +/- 0.06 (p less than 0.02). In nine patients who received a single dose of prazosin during right sided heart catheterization, pulmonary vascular resistance decreased from 358 +/- 70 to 236 +/- 60 dyne-sec-cm -5 (p less than 0.01). These studies suggest that prazosin has beneficial effects on right ventricular function both immediately and long-term in patients with severe congestive heart failure. Although the mechanism of this effect is not known, possibilities include a direct effect of prazosin on the pulmonary vasculature, a secondary reduction in right ventricular afterload due to improved left ventricular performance and a withdrawal of reflex-mediated pulmonary vasoconstriction due to improved left ventricular performance.

Adrenergic alpha-Antagonists↗
PubMed1981

Contractile function in chronic gradually developing subcoronary aortic stenosis.

Whether hypertrophied cardiac muscle functions normally or abnormally is a point of controversy in the literature. Most animal studies showing depressed performance of hypertrophied cardiac muscle have used experimental methods in which hypertrophy was produced by acutely imposing a pressure overload on the left or right ventricle, which may cause myocardial injury. To assess the possibility that chronic, slowly developing hypertrophy is associated with normal myocardial function, we developed an experimental model in which increased afterload is imposed gradually on the left ventricle in the dog. A snug band was placed around the aorta beneath the left coronary artery in puppies without producing a stenosis. As the puppies grew, relative aortic stenosis developed as increased cardiac output flowed across that fixed outflow area. One group (group A) of six puppies was banded early, whereas a second group (group B, five puppies) was banded late and served as controls. Left ventricular weight (g) to body weight (kg) ratio remained normal in group B animals (3.9 +/- 0.14), whereas this ratio was increased to 5.3 +/- 0.24 (P < 0.001) in group A animals indicating development of moderate cardiac hypertrophy. Ejection fraction, dP/dt, Vcf, and stroke work per gram of myocardium were virtually identical in both groups. We conclude that moderate, gradually developing cardiac hypertrophy as produced by this model is associated with normal myocardial contractile performance.

Animals↗
PubMed1981

Prevention of nifedipine of abnormal coronary vasoconstriction in patients with coronary artery disease.

The hemodynamic and myocardial metabolic responses to the cold pressor test were studied in 15 patients with coronary artery disease and stable exertional angina. Every patient had abnormal coronary vasoconstriction during a control cold pressor test, even though 14 were receiving propranolol and 12 were receiving long acting nitrates. Mean coronary vascular resistance for the group increased 18 +/- 6% (SD) (from 0.80 +/- 0.12 to 0.94 +/- 0.20 mm Hg/ml/min, p less than 0.05); coronary sinus blood was unchanged, and the arterial-coronary sinus oxygen difference widened significantly (from 11.5 +/- 1.2 to 12.3 +/- 1.2 ml/100 ml, p less than 0.05). Four patients developed angina, accompanied in each instance by a negative arterial-coronary sinus lactate difference. After the administration of nifedipine (10 mg buccally) in 10 patients, the coronary vascular responses to a repeat cold pressor test were normal in each patient. Mean coronary sinus blood flow increased 27 +/- 12% (from 122 +/- 32 to 153 +/- 35 ml/min, p less than 0.05), coronary vascular resistance decreased 10 +/- 6% (from 0.85 +/- 0.16 to 0.76 +/- 0.16 mm Hg/ml/min, p less than 0.05), and the arterial-coronary sinus oxygen difference was unchanged. No patient experienced angina. The hemodynamic and coronary vascular responses to a repeat cold pressor test in five patients given placebo were unaltered from control responses. The protective effects of nifedipine were unaccompanied by any change in mean arterial pressure, left ventricular filling pressure or myocardial oxygen consumption either at rest or in response to the cold pressor test. Nifedipine appears to exert a selective antivasoconstrictor effect on the coronary vasculature.

Adult↗
PubMed1981

Acute effects of oral pirbuterol on myocardial oxygen metabolism and systemic hemodynamics in chronic congestive heart failure.

Pirbuterol hydrochloride, an orally effective beta-adrenergic agonist, improves hemodynamic abnormalities in patients with congestive heart failure, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow have not been characterized. We studied the effects of 20-30 mg of oral pirbuterol on myocardial metabolic and hemodynamic parameters in 12 patients (six with coronary artery disease) with chronic CHF refractory to standard medical therapy. Pirbuterol induced an increase in cardiac index (1.7 +/- 0.1 to 2.3 +/- 0.2 l/min/m2, p less than 0.05) and a fall in systemic vascular resistance (1884 +/- 118 to 1391 +/- 69 dyn-sec-cm-5, p less than 0.01) 2 hours after administration. Pulmonary capillary wedge pressure fell from arterial and right atrial pressures did not change. Heart rate remained constant. Arterial-coronary sinus oxygen content difference narrowed (from 12.9 +/- 0.4 to 11.1 +/- 0.3 vol%, p less than 0.05), while no significant change occurred in MVO2. Myocardial oxygen extraction ratio and myocardial lactate extraction ratio did not change, and no patient developed angina or electrocardiographic evidence of myocardial ischemia. Patients with coronary artery disease had hemodynamic and myocardial metabolic responses similar to those without coronary artery disease. Pirbuterol effects substantial acute hemodynamic improvement in patients with chronic congestive heart failure without increasing requirements for coronary blood flow or myocardial oxygen delivery and without provoking myocardial ischemia.

Adult↗
PubMed1981

Comparison of acute alterations in left ventricular relaxation and diastolic chamber stiffness induced by hypoxia and ischemia. Role of myocardial oxygen supply-demand imbalance.

To clarify conflicting reports concerning the effects of ischemia on left ventricular chamber stiffness, we compared the effects of hypoxia at constant coronary perfusion with those of global ischemia on left ventricular diastolic chamber stiffness using isolated, perfused rabbit hearts in which the left ventricle was contracting isovolumically. Since chamber volume was held constant, increases in left ventricular end diastolic pressure (LVEDP) reflected increases in chamber stiffness. At a control coronary flow rate (30 ml/min), 2 min of hypoxia and pacing tachycardia (4.0 Hz) produced major increases in postpacing LVEDP (10+/-1 to 24+/-3 mm Hg, P < 0.01) and the relaxation time constant, T, (40+/-4 to 224+/-37 ms, P < 0.001), while percent lactate extraction ratio became negative (+ 18+/-2 to -48+/-15%, P < 0.001). Coronary perfusion pressure decreased (72+/-5 to 52+/-3 mm Hg, P < 0.01), and since coronary flow was held constant, the fall in coronary perfusion pressure reflected coronary dilation and a decrease in coronary vascular resistance. Following an average of 71+/-6s reoxygenation and initial heart rate (2.0 Hz), LVEDP and relaxation time constant T returned to control. Hypoxia alone (without pacing tachycardia) produced similar although less marked changes (LVEDP, 10+/-1 to 20+/-3 mm Hg; and T, 32+/-3 to 119+/-22 ms; P < 0.01 for both) and there was a strong correlation between LVEDP and T (r = 0.82, P < 0.001). When a similar degree of coronary vasodilatation was induced with adenosine, no change in LVEDP occurred, indicating that the increase in end diastolic pressure observed during hypoxia was not secondary to vascular engorgement, but due to an acute effect of hypoxia on the diastolic behavior of the ventricular myocardium. In contrast, global ischemia produced by low coronary flow (12-15 ml/min) resulted in a decrease in LVEDP, as well as a marked fall in left ventricular systolic pressure. In 14 global ischemia experiments, pacing tachycardia led to a further decline in left ventricular systolic pressure, and no increase was noted in postpacing LVEDP. Changes in lactate extraction ratio were much smaller in magnitude than with hypoxia and constant coronary perfusion. In two experiments (one at normal coronary flow and one at 15 ml/min), left ventricular systolic pressure did not change markedly from control when tachycardia was superimposed, and postpacing LVEDP showed a marked rise (to > 25 mm Hg), which gradually recovered over 1-2 min at the control heart rate. From these results, we conclude that left ventricular chamber stiffness increases when myocardial O(2) demand exceeds supply. This change is usually masked in ischemic (reduced coronary flow) preparations, perhaps because of reduced turgor of the coronary vascular bed, marked reductions in systolic work (and therefore myocardial O(2) requirements), and local accumulation of hydrogen ion and metabolites following acute severe reduction of coronary flow. The increased chamber stiffness during hypoxia is accompanied by marked slowing of relaxation, with increased diastolic pressure relative to volume persisting throughout diastole.

Animals↗
PubMed1980

Hemodynamic effects of nitrous oxide administered during cardiac catheterization.

To assess the effects of nitrous oxide on hemodynamics and left ventricular function in man, 30 patients (24 of whom had coronary artery disease) were studied at the time of cardiac catheterization. Left ventricular peak-systolic pressure and end-diastolic volume showed no significant change during nitrous oxide inhalation. The maximum rate of pressure rise declined slightly, but left ventricular end-diastolic pressure and ejection fraction were unchanged. Heart rate and cardiac index declined modestly. The pressure-rate product and left ventricular minute work index decreased, suggesting a decline in myocardial oxygen requirements. These data suggest that nitrous oxide inhalation does not produce important depression of left ventricular performance. The consistent decrease in the determinants of myocardial oxygen demand suggests that use of this analgesic agent may be helpful in patients with coronary heart disease.

Adolescent↗
PubMed1980

The diagnostic accuracy of combined clinical and noninvasive cardiac evaluation: comparison with findings at cardiac catheterization.

The accuracy of combined clinical and noninvasive cardiac diagnostic evaluation was prospectively examined in 108 consecutive patients referred to the heart station for echocardiographic examination prior to cardiac catheterization. History, physical examination, scalar electrocardiology, chest roentgenography, phonocardiography and pulse recording, and M-mode echocardiography were employed by the heart station cardiologist, who assigned one or more diagnoses to each patient. In addition, one of three management strategies was proposed for each patient: 1) surgery without cardiac catheterization; 2) medical therapy without cardiac catheterization; or 3) cardiac catheterization for clarification of the diagnosis. The results of the combined clinical and noninvasive evaluation were independently reviewed for each patient and compared with the diagnosis determined by cardiac catheterization, results of cardiac surgery, and total hospital course. Diagnostic predictions employing combined clinical and noninvasive cardiac evaluation were completely correct in 86% of patients, and management strategy was correct in 97% of individuals. In approximately one-half of all patients full cardiac catheterization or coronary arteriography was recommended. All management strategy errors and two-thirds of diagnostic errors occurred in patients with mitral regurgitation, aortic regurgitation, or coronary artery disease. Combined clinical and noninvasive evaluation results in accurate diagnostic information adequate for the formulation of appropriate management strategies in the majority of patients, but many individuals with cardiac disease still require invasive evaluation for complete diagnosis.

Adolescent↗
PubMed1980

Oral amrinone in refractory congestive heart failure.

The acute effects of an oral preparation of amrinone, a recently synthesized cardiotonic agent, were assessed noninvasively in nine patients who had advanced heart failure that persisted despite treatment with digitalis, diuretic drugs and afterload-reducing agents. All patients demonstrated an improvement in left ventricular ejection fraction determined by radionuclide ventriculography (20.3 +/- 2.8 to 30.8 +/- 4.8 percent [mean +/- standard error of the mean], p less than 0.005) after a single dose of amrinone. Initial effects were seen within 1 hour, with the peak effect occurring at 1 to 3 hours; persistent effects were demonstrable at 4 to 6 hours. No change in blood pressure, heart rate or rhythm was observed, and there was no clinical evidence of myocardial ischemia. Continued benefit was demonstrated by radionuclide ventriculography in two patients treated for 1 and 6 weeks, respectively, although two other patients experienced major side effects with the chronic administration of amrinone. Although orally administered amrinone shows promise as a potentially useful agent in the treatment of advanced heart failure, the safety of this drug remains to be established.

Aged↗
PubMed1980

Cardiac hypertrophy: useful adaptation or pathologic process?

An extensive body of evidence supports the concept that cardiac hypertrophy and normal cardiac growth develop in response to increased hemodynamic loading and abnormal systolic and diastolic stresses at the myocardial fiber level. The pattern of hypertrophy reflects the nature of the inciting stress. Experimental studies indicate that if the stress is moderate, gradually applied, and the animal young and healthy, physiologic hypertrophy of muscle with normal contractility develops. In this circumstance, cardiac hypertrophy may be regarded as a useful adaptation to increased hemodynamic loading. When the inciting stress is severe, abruptly applied, or the animal old or debilitated, pathologic hypertrophy develops: in this circumstance, the cardiac muscle produced is abnormal and exhibits depressed contractility. Of particular clinical relevance is the intermediate situation which seems to develop in many patients with chronic left ventricular pressure-overload and perhaps also in left ventricular volume-overload. In this situation, chronic left ventricular pressure or volume overload is initially matched by adequate hypertrophy in the appropriate pattern. Eventually, in some patients, hypertrophy fails to keep pace with the hemodynamic overload so that a systolic stress imbalance occurs at the myocardial fiber level and left ventricular pump failure ensues. If this situation persists uncorrected, it is possible that the increasingly high wall stresses will convert physiologic to pathologic hypertrophy. The task of the clinician is to identify this intermediate stage and to correct the abnormal hemodynamic loading before the transition to pathologic hypertrophy becomes complete.

Adaptation, Physiological↗
PubMed1980

Clinical profile of restrictive cardiomyopathy.

The characteristic hemodynamic features of restrictive cardiomyopathy (normal or reduced cardiac index, normal ventricular systolic function, and "dip and plateau" early in diastole) are traditionally associated with pathologic evidence of inflammation, infiltration and fibrosis. Prognosis is usually poor. Nine patients with restrictive hemodynamic features were recently identified in our laboratory; six were males, three were females, and ages ranged from 23-57 years (mean 47 years). Only one was asymptomatic. Chest pain, dyspnea on exertion and fatigue were the most common symptoms. Echocardiography revealed various degrees of left ventricular wall thickening, but no significant pericardial effusion, pericardial thickening or calcification. Mean left ventricular end-diastolic pressure was 25 mm Hg, cardiac index 2.8 l/min/m2 and ejection fraction 0.63. Endomyocardial and pericardial biopsies, obtained in two patients, were normal. Follow-up (mean 22 months, range 16-42 months) revealed no cardiac deaths. These findings support the hypothesis that the restrictive hemodynamic profile does not necessarily indicate the presence of a specific pathologic process in the subendocardium or myocardium and that the prognosis is not necessarily ominous. The common pathophysiologic feature for this syndrome appears to be reduced ventricular diastolic compliance, but the etiology in many cases is unclear.

Adult↗
PubMed1980

Effects of amrinone on myocardial energy metabolism and hemodynamics in patients with severe congestive heart failure due to coronary artery disease.

Amrinone has been shown to exhibit a potent inotropic effect in patients with heart failure secondary to congestive cardiomyopathy, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) are unknown. Accordingly, the hemodynamic, myocardial metabolic and ECG responses to amrinone (2.5 mg/kg i.v. over 1 hour) were measured in nine patients with congestive heart failure secondary to coronary artery disease. Increases were observed in cardiac index (1.3 +/- 0.4 to 2.2 +/- 0.7 l/min/m2) and left ventricular stroke work (10.6 +/- 3.0 to 19.2 +/- 6.3 g-m/m2), and decreases in mean pulmonary wedge (31 +/- 5 to 26 +/- 4 mm Hg), mean pulmonary artery (44 +/- 8 to 36 +/- 7 mm Hg) and mean right atrial pressures (18 +/- 4 to 10 +/- 4 mm Hg), myocardial arteriovenous oxygen difference (129 +/- 19 to 109 +/- 17 ml/l), CBF (215 +/- 117 to 178 +/- 84 ml/min) and MVO2 (27 +/- 14 to 19 +/- 9 ml/min). All changes were significant (p less than 0.01). No significant changes occurred in aortic mean pressure, heart rate, myocardial lactate extraction or ECG, and no patient developed angina. In explaining the decline in MVO2, it is possible that the increase in contractility was more than offset by the reductions in preload and afterload. The amrinone-induced hemodynamic improvement in patients with congestive heart failure secondary to coronary artery disease was associated with reductions in MVO2 and CBF and no evidence of myocardial ischemia.

Aged↗
PubMed1980

Diastolic pressure-volume relations in the diseased heart.

Alterations in ventricular diastolic properties are commonly seen in the diseased heart, and have been extensively studied in coronary artery disease, congestive cardiomyopathy, and left ventricular hypertrophy due to pressure or volume overload. Acute increases in left ventricular (LV) diastolic pressure relative to volume occur regularly during the transient ischemia of angina pectoris and may contribute to the dyspnea and pulmonary congestion that commonly accompany this condition. Although the mechanism of this altered disastolic distensibility is debated, a substantial body of evidence favors a role for residual diastolic interaction between contractile elements in the ischemic heart. Congestive cardiomyopathy also appears to be associated with increased LV diastolic stiffness. While this may in part be related to fibrosis of the LV wall, shifts of the abnormal diastolic pressure-volume relation toward normal have been reported with sodium nitroprusside infusion or the beta-adrenergic agonist salbutamol, suggesting important contribution of physiologic factors to the increased resting LV stiffness in this condition. LV hypertrophy (LVH) is associated with increased effective diastolic chamber stiffness, but normalized LV diastolic stiffness is increased only in LVH due to chronic pressure overload. Possible explanations for these findings are discussed.

Adenosine Triphosphate↗