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Biomedical subjects

R M Zusman

Publications and source records attributed to R M Zusman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Left ventricular hypertrophy and performance: therapeutic options among the angiotensin-converting enzyme inhibitors.

The goal of antihypertensive therapy is the reduction in morbidity and mortality associated with high blood pressure. Despite our ability to reduce blood pressure, "standard" antihypertensive therapy has not produced a general decrease in coronary heart disease. This failure might be related to the adverse metabolic consequences of diuretics and beta-adrenergic receptor-blocking agents used in most clinical trials. In the hypertensive patient population, however, the principal physiologic abnormality is increased systemic vascular resistance. This increase in vascular tone leads to compensatory changes in cardiac function that result in left ventricular hypertrophy and diastolic filling abnormalities. Diastolic ventricular dysfunction is present in approximately 50% of asymptomatic hypertensive patients and might be a precursor of the syndrome of congestive heart failure with normal systolic ventricular function. In view of the prevalence of diastolic filling abnormalities in the hypertensive patient population, one should consider the effect of an antihypertensive drug on left ventricular function. In a comparison of the angiotensin-converting enzyme (ACE) inhibitors, captopril, lisinopril, and fosinopril, only fosinopril increased stroke volume, peak ejection rate, and peak filling rate, and decreased time to peak ejection rate. These favorable inotropic and lusitropic responses to fosinopril may reflect an effect on the myocardial renin-angiotensin cascade which is dependent upon the unique chemical structure of the fosinopril molecule.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Comparison of the cardiac and hemodynamic effects of lisinopril and atenolol in patients with hypertension: therapeutic implications.

The antihypertensive and hemodynamic effects of lisinopril and atenolol were evaluated in 21 patients with mild-to-moderate essential hypertension. Left ventricular systolic and diastolic performances were assessed prior to and following treatment by first-pass radionuclide cineangiography at rest and during peak upright bicycle exercise. Both lisinopril and atenolol treatment significantly reduced the blood pressure. Lisinopril therapy was associated with a reduction in systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes but no change in stroke volume, cardiac output, peak ejection rate, peak filling rate, time to peak ejection rate, or time to peak filling rate. In contrast, atenolol therapy was associated with an increase in end-diastolic volume and stroke volume but no change in cardiac output; the left ventricular peak ejection and peak filling rates were decreased by atenolol treatment. Although both lisinopril and atenolol each significantly reduced the blood pressure, lisinopril had no effect on left ventricular systolic or diastolic performance; in contrast, atenolol decreased both systolic and diastolic parameters of ventricular performance. Left ventricular function may be affected in significantly different ways despite apparent similarities in blood pressure control in patients who respond to angiotensin converting enzyme inhibition or beta-adrenergic receptor blockade. Differences in hemodynamic response to an antihypertensive agent may be important in the selection of a drug for the treatment of subsets of patients with cardiac function abnormalities.

Adult↗
PubMed1991

Nifedipine improves left ventricular function in patients with hypertension.

The effects of the nifedipine gastrointestinal therapeutic system (GITS) on blood pressure (BP), systemic vascular resistance (SVR), and left ventricular (LV) performance were determined in eight patients with essential hypertension. LV systolic and diastolic performance were assessed by first-pass radionuclide cineangiography at rest and during upright bicycle exercise after initial and long-term BP reduction. After initial treatment, end-diastolic volume (LVEDV) increased in association with an increase in stroke volume (SV), cardiac output (CO), and peak ejection rate. After long-term treatment, LVEDV decreased, SV and CO returned to pretreatment values, early diastolic filling fraction increased, and time to peak filling rate decreased. These hemodynamic changes are consistent with an initial predominant effect of vasodilation on LV function. With long-term treatment, the effects on LV diastolic performance are consistent with a positive lusitropic effect of nifedipine GITS. Nifedipine GITS is an effective agent for control of hypertension; its hemodynamic effects are consistent with both an effect on SVR due to decreased vascular smooth muscle contraction and a direct lusitropic effect on myocardial function.

Adult↗
PubMed1991

Neuropsychiatric considerations in the treatment of hypertension.

Algorithms have been developed to guide the treatment of simple hypertension. The basic algorithms are modified in the face of concurrent medical conditions, taking into account the various pharmacological effects of antihypertensive agents. This article reviews the neuropsychiatric effects of the major classes of antihypertensive agents (ganglionic blockers, centrally acting agents, diuretics, vasodilators, beta-blockers, calcium channel blockers and angiotensin converting enzyme inhibitors). The purported efficacy of some antihypertensive agents in the treatment of psychiatric conditions is also discussed. Beneficial as well as adverse neuropsychiatric effects are reviewed. In this way, guidelines for the treatment of hypertension are suggested which take into account a broad spectrum of neuropsychiatric considerations.

Antihypertensive Agents↗
PubMed1989

Nifedipine, but not propranolol, improves left ventricular systolic and diastolic function in patients with hypertension.

The effects of nifedipine and propranolol on cardiac function both at rest and at peak exercise were compared in 22 hypertensive patients whose diastolic blood pressures remained in excess of 95 mm Hg despite diuretic therapy. In this double-blind, placebo-controlled study, left ventricular systolic and diastolic function at rest and at peak exercise during bicycle ergometry was assessed by first-pass radionuclide angiography using the Baird Scinticor before and after treatment with either nifedipine or propranolol. Both agents effectively reduced blood pressure in the supine and upright positions and at peak exercise. Nifedipine was associated with a significant increase in cardiac output and stroke volume at rest and at peak exercise, while propranolol decreased cardiac output at rest and at peak exercise. Systemic vascular resistance decreased with nifedipine treatment at rest and at peak exercise, but increased significantly with propranolol. Nifedipine increased ejection fraction in patients at rest and also increased maximal oxygen consumption at peak exercise, while propranolol decreased maximal oxygen consumption at peak exercise. At rest and at peak exercise, nifedipine increased peak filling rate, but time to peak filling rate was not affected by either drug. The fraction of total diastolic filling at the midpoint of diastole was significantly increased by nifedipine therapy at rest but was not affected by propranolol therapy. Nifedipine significantly decreased atrial filling volume while propranolol had no effect. Propranolol therapy did not result in any improvement in left ventricular function. In contrast, nifedipine improved left ventricular systolic and diastolic function at rest and peak exercise. Future selection of an antihypertensive agent should include consideration of the impact of therapy on left ventricular function.

Adult↗
PubMed1989

Alternatives to traditional first-line antihypertensive treatment: unresolved questions and therapeutic dilemmas. A personal approach.

The best antihypertensive regimen for use in patients with mild-to-moderate hypertension has not been determined. When nonpharmacological treatment of hypertension fails, initial drug treatment with diuretic drugs, sympatholytic agents (including beta-adrenergic receptor blockers), or vasodilators will result in satisfactory blood pressure control. However, each of these therapies has effects that are independent of their antihypertensive activity and that should be considered before a selection is made for initial therapy. The adverse effects of diuretic agents and beta-adrenergic receptor-blocking drugs on plasma lipid profiles may diminish the beneficial effects of blood pressure reduction. On the other hand, the hypocholesterolemic effect of alpha-adrenergic receptor antagonists, the potential cardioprotective effect of angiotensin converting enzyme inhibitors, and the salutary effects of calcium channel blockers on left ventricular function are responses that would support the use of vasodilatory therapy. Vasodilating antihypertensive drugs may be more beneficial than "standard" therapy and should be considered for the initial treatment of newly diagnosed hypertensive patients.

Antihypertensive Agents↗
PubMed1989

Left ventricular function in hypertension. Relevance to the selection of antihypertensive therapy.

With the increasingly widespread recognition of the adverse side effects of traditional antihypertensive medications, alternative approaches to the treatment of uncomplicated hypertensive patients have been proposed. The use of vasodilator agents, calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and alpha-adrenergic receptor blockers results in blood pressure reduction without adverse metabolic consequences. Furthermore, vasodilatory agents reverse the principal physiological abnormality of hypertensive patients, that is, they reverse the increased systemic vascular resistance that characterizes these patients and, in so doing, may alleviate abnormalities of systolic and diastolic left ventricular performance. In particular, a comparison of the effects of nifedipine and propranolol on left ventricular (LV) function in patients with moderately severe hypertension revealed significant differences in their effects on cardiac function. Although both drugs reduced blood pressure to an identical degree, nifedipine therapy was associated with a decrease in systemic vascular resistance, an increase in cardiac output, and improved parameters of left ventricular contractile and diastolic function as measured by quantitative radionuclide ventriculography. Vasodilator therapy should be considered for the initial treatment of patients with uncomplicated essential hypertension.

Adaptation, Physiological↗
PubMed1987

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension.

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Age, race, diagnosis, and sodium effects on the pressor response to infused norepinephrine.

We studied the blood pressure responses to infused norepinephrine in 34 normotensive and 21 unmedicated subjects with essential hypertension. The two groups were similar in age, relative body weight, and urinary electrolyte excretion. Patients were studied on two extremes of dietary salt (200 mEq Na and 10 mEq Na per day). The dose-response curves were highly linear (p less than 0.00001) for both systolic and diastolic blood pressures. There was no evidence for an increased sensitivity to infused norepinephrine among the hypertensive subjects. On the other hand, older subjects had steeper slopes (p less than 0.005). Subjects on a high salt diet had steeper slopes than those on low salt diets (p less than 0.0025); this trend was especially apparent among blacks (p less than 0.005). Black and white hypertensive subjects responded to the high salt diet in opposite fashion: The blacks showed an increased pressor sensitivity (p less than 0.05), whereas the whites demonstrated a nonsignificant decreased pressor sensitivity. These results indicate that age, race, and salt effects must be meticulously controlled in studies of sympathetic nervous system physiology.

Adult↗
PubMed1987

Effects of converting-enzyme inhibitors on the renin-angiotensin-aldosterone, bradykinin, and arachidonic acid-prostaglandin systems: correlation of chemical structure and biologic activity.

The renin-angiotensin-aldosterone system plays an integral role in the control of BP and is mediated by enzymatic transformation of substances in the renin-angiotensin cascade. Inhibitors of various reactions in this cascade have been shown experimentally to reduce elevated BP. The first such compound to become available for clinical use was the angiotensin-converting enzyme inhibitor captopril. Captopril reduces BP, with the expected decrease in plasma angiotensin II concentration and increases in renin and angiotensin I levels, but there is also evidence for a non-renin-dependent mechanism of action. In particular, according to cell culture data, captopril stimulates an increase in the synthesis of vasodilatory prostaglandins. Because enalapril, another angiotensin-converting-enzyme inhibitor, does not augment in vitro synthesis of prostaglandins, this effect may be unique to the chemical structure of captopril rather than inherent to all such inhibitors. Studies using animal models of hypertension support this hypothesis. Captopril may also influence prostaglandin synthesis by reducing inactivation of bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Evaluation of bepridil for the treatment of angina pectoris: evidence for preservation of left ventricular function.

The efficacy of bepridil (400 mg once a day) was assessed in 15 patients with exertional angina pectoris. All 15 patients reported substantial clinical improvement during bepridil treatment compared with placebo treatment. Episodes of angina were 11.8 +/- 4.1 (mean +/- standard error of the mean)/week with placebo and 3.8 +/- 1.6 with bepridil (p less than 0.05); nitroglycerin use was 9.1 +/- 3.3 tablets/week with placebo and 3.5 +/- 1.7 with bepridil (p less than 0.05). Five of 15 patients receiving bepridil did not experience angina during treadmill exercise; in the remaining 10 patients, time to onset of angina during exercise was 5.7 +/- 0.9 minutes with bepridil as opposed to 4.5 +/- 0.8 minutes with placebo (p less than 0.05). Left ventricular (LV) performance at peak exercise as measured by first-pass radionuclide angiography revealed the ejection fraction to be 38 +/- 3% during placebo therapy and 47 +/- 4% during bepridil therapy (p less than 0.0025). End-diastolic LV volume was unchanged, but end-systolic volume was 136 +/- 11 and 117 +/- 13 ml (p less than 0.05) and stroke volume was 82 +/- 6 and 97 +/- 9 ml (p less than 0.05) during placebo and bepridil therapy, respectively. Heart rate at peak exercise was 136 +/- 3 beats/min with placebo and 128 +/- 3 beats/min with bepridil; however, blood pressure was unchanged. These studies demonstrate that bepridil results in significant clinical improvement and enhanced LV performance in patients with angina pectoris.

Angina Pectoris↗
PubMed1985

Effect of bepridil in patients with chronic stable angina: results of a multicenter trial.

The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.

Angina Pectoris↗
PubMed1985

Effect of prostacyclin on vascular capacity in the dog.

Since the discovery of prostacyclin (PGI2) in 1976, there has been great interest in its vascular effects and potential clinical applications. High infusion rates of PGI2 markedly depress arterial blood pressure both in animal studies and in clinical trials. This fall in pressure may result entirely from a decrease in arterial resistance. However, it is possible that the administration of PGI2 may decrease ventricular filling due to an increase in vascular capacity. To investigate whether or not PGI2 affects vascular capacity, we infused PGI2 intraarterially at both 10 and 25 micrograms/min into 15 dogs on total cardiopulmonary bypass. These infusions were associated with a 25 +/- 3 mmHg decrease in arterial pressure and an increase in vascular capacity of 155 +/- 29 ml (SE, P less than 0.005). This increase in capacity was greater (P less than 0.02) than the increase of 23 +/- 42 ml resulting from infusions of nitroglycerin into eight dogs at 2 mg/min, which produced a decrease in arterial pressure of 23 +/- 4 mmHg, which was the maximal effect that could be achieved. Neither bilateral cervical vagotomy nor beta adrenergic blockade with propranolol significantly diminished the increase in vascular capacity associated with infusions of PGI2. The results from studies in four eviscerated dogs indicated that PGI2 acts on both splanchnic and extrasplanchnic capacity vasculature. To compare the direct effects of PGI2 with those of nitroglycerin and nitroprusside on venous tone, we used an isolated canine spleen preparation. Infusions of PGI2 (100 mcg/min) increased spleen weight in this preparation by 9.0 +/- 2.4% (n = 10, P less than 0.001); this increase was significantly greater than increases of 3.6 +/- 2.2% (P less than 0.001) and 3.5 +/- 2.3% (P less than 0.001) caused by high dose infusions of nitroglycerin (1 mg/min) and nitroprusside (400 micrograms/min), respectively. Thus, PGI2 substantially increases vascular capacity by a mechanism that appears to involve a direct action on vascular smooth muscle. Furthermore, these results suggest that PGI2 might be useful in clinical conditions in which an increase in vascular capacity is indicated.

Animals↗
PubMed1984

The role of calcium in the stimulation of prostaglandin synthesis by vasopressin in rabbit renal-medullary interstitial cells in tissue culture.

The role of Ca2+ in the stimulation of prostaglandin (PG) biosynthesis by vasopressin was investigated in rabbit renal-medullary interstitial cells in tissue culture. A decrease in extracellular Ca2+ to less than 25 microM did not affect basal PGE2 production, but inhibited PGE2 synthesis stimulated by vasopressin, angiotensin and the Ca2+ ionophore A23187 by 55, 65 and 95% respectively. The study of vasopressin-stimulated PGE2 synthesis in the absence of extracellular Ca2+ demonstrated that: (a) hormone-sensitive phospholipase activity was inhibited as measured by [3H]arachidonic acid release; (b) the maximal rate of vasopressin-stimulated activity was decreased without a change in the vasopressin concentration that evoked half-maximal stimulation of PGE2 synthesis; and (c) the Ca2+-channel blocker verapamil and the Ca2+-calmodulin antagonist trifluoperazine mimicked the inhibitory effects of removing extracellular Ca2+. These agents had no effect in the absence of Ca2+. In contrast with their effects on vasopressin action, neither the removal of extracellular Ca2+ nor the addition of verapamil altered the ability of hyperosmotic mannitol to increase PGE2 synthesis. These data are consistent with the hypothesis that a component of vasopressin-stimulated PGE2 biosynthesis involves the influx of extracellular Ca2+, followed by the activation of Ca2+-calmodulin-stimulated phospholipase(s).

Angiotensin II↗