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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 163 records · Page 9Linked to original sources
PubMed1992

Rapid, accurate and simultaneous noninvasive assessment of right and left ventricular mass with nuclear magnetic resonance imaging using the snapshot gradient method.

Left ventricular, and possibly also right ventricular, mass is an important determinant of prognosis in cardiovascular disease. Consequently, noninvasive estimation of ventricular mass may be an important clinical investigation. The ideal technique for this purpose would be widely available and accurate, employ short study times and avoid exposure to contrast agents and radiation. Conventional nuclear magnetic resonance (NMR) imaging fulfills most of these criteria, but it is time-consuming and expensive. Moreover, its accuracy in estimating right ventricular mass has yet to be assessed. Accordingly, high speed NMR imaging using the snapshot gradient echo technique was used to assess right and left ventricular mass in 10 dogs and the results were compared with values obtained at autopsy, which ranged from 26.1 to 52.9 and 61 to 119.8 g, respectively. The mean absolute difference between the NMR imaging estimates and autopsy findings was 2 +/- 1.2 g (range 0.4 to 4.2) for right ventricular mass and 4.4 +/- 1.7 g (range 1.8 to 6.6) for left ventricular mass. Total NMR imaging time was less than or equal to 5 min. These data demonstrate that high speed NMR imaging can be used to accurately estimate right as well as left ventricular mass.

Animals↗
PubMed1992

Role of neurohumoral control of the circulation in determining exercise capacity in patients with heart failure.

The weak relationship between left ventricular function and exercise capacity in heart failure has stimulated interest in neurohumoral mechanisms as possibly contributing to exercise intolerance. Although chronic activation of neuroendocrine systems is characteristic of heart failure and is accompanied by impaired reflex responsiveness to physiologic stimuli, data from clinical trials do not support the hypothesis that the abnormal neurohumoral state is directly related to exercise intolerance. Thus, these systems may play an important role in the natural history of the disease and its high mortality, but they may not be critical to the impaired exercise capacity.

Blood Circulation↗
PubMed1992

First- and third-order models for determining arterial compliance.

BACKGROUND: Engineering models of the arterial vasculature have been used to describe vascular properties of resistance and compliance. These approaches have used either Fourier frequency analysis, based on transmission line equations, or time domain analysis of the circuit equations describing modified Windkessel models of the vasculature. DESIGN: A third-order, four-element modified Windkessel model can reproduce arterial pressure waveforms, including both exponential and oscillatory pressure decays observed during the diastolic portion of the cardiac cycle. METHOD: A method to determine both capacitive and oscillatory compliance of the arterial vasculature was developed, and the effect of these compliance properties on the blood pressure waveform was examined.

Arteries↗
PubMed1992

Abnormalities of vascular compliance in hypertension, aging and heart failure.

AIM: Diastolic arterial pulse wave analysis and a modified Windkessel model were used to evaluate the vascular response to hypertension, heart failure and aging. RESULTS: Compared to age-matched normal subjects, arterial compliance was reduced in patients with hypertension and heart failure, particularly in the vessels that contribute to resonances or oscillations in the pulse wave. In elderly subjects, the capacitive function of the arteries and compliance of the smaller arteries that contribute to oscillations were both reduced. CONCLUSION: These small-vessel structural or functional abnormalities may serve as a marker for disease and for the response to therapy.

Aging↗
PubMed1991

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.

BACKGROUND: To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS: Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS: The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Adolescent↗
PubMed1991

Future directions in vasodilator therapy for heart failure.

Vasodilator therapy has become a major pharmacologic approach for improving left ventricular function, and consequently, vasodilator drugs are being used increasingly in the treatment of heart failure. Ideally, vasodilator drugs used in the long-term management of heart failure should show clearly defined pharmacodynamic effects. These include reduced impedance to left ventricular ejection, increased venous capacitance, increased left ventricular ejection fraction and reduced heart size, absence of neurohormonal stimulation, and slowed progression of left ventricular dysfunction. The mechanisms of action and sites of activity of the various vasodilator drugs currently available vary considerably, and none as yet has proved ideal for the treatment of heart failure or hypertension. The complexity surrounding the multiple vasoconstrictor mechanisms involved in heart failure has led to a rationale for combined vasodilator therapy and certain combinations are discussed. From a therapeutic standpoint, the development of drugs with multiple mechanisms of action is particularly attractive. Flosequinan is a new vasodilator agent whose cellular mechanism of action remains uncertain. Flosequinan has the advantage of being able to relax both arterial and venous beds and as such may be particularly beneficial in the treatment of heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Reduced vascular compliance as a marker for essential hypertension.

In 38 patients with established essential hypertension and 32 age-matched normotensive control subjects proximal and distal arterial compliance were determined by computer-based assessment of the diastolic decay of a brachial arterial tracing and a modified Windkessel model of the circulation. In the hypertensive subjects compared to the normotensive subjects mean arterial pressure was 25% higher (P less than .001), systemic vascular resistance 23% higher (P less than .01), proximal compliance 19% lower (P less than .01), and distal compliance 72% lower (P less than .001). The reduction in distal compliance was highly age-dependent. In the youngest age range (45 to 54 years) little overlap appeared between hypertensive and normotensive groups, whereas in the oldest subjects studied (65 to 75 years) distal compliance was comparably low in the two groups. Thus, distal vascular compliance provides a sensitive and specific marker for the abnormal vasculature associated with hypertension and may be particularly useful in identifying the disease in young individuals with borderline blood pressure.

Aged↗
PubMed1991

Lessons from V-HeFT: questions for V-HeFT II and the future therapy of heart failure.

V-HeFT, the first mortality trial in patients with heart failure, has provided important insights regarding trial design, including patient selection and efficacy criteria. Planning of V-HeFT II, the trial comparing hydralazine-isosorbide dinitrate and enalapril, has raised additional issues regarding the power to detect mortality effects and the relative value of non-mortality endpoints for efficacy. V-HeFT has demonstrated that some vasodilator regimens can prolong life in heart failure. Hydralazine + isosorbide dinitrate reduced mortality by 27% compared to placebo in patients treated with digoxin and diuretics. The possibility of a non-vasodilator mechanism for long-term benefit of these interventions is raised by the apparently poor relationship between the magnitude of vasodilation and the favorable long-term effects. These issues need to be explored in subsequent trials. In future long-term trials, however, the need for background therapy with drugs that have been effective in reducing mortality will make the identification of life prolongation from new therapies more difficult to demonstrate.

Enalapril↗
PubMed1990

Mechanisms in heart failure and the role of angiotensin-converting enzyme inhibition.

The four major diagnostic criteria for the syndrome of congestive heart failure are left ventricular dysfunction, exercise intolerance, pulmonary congestion or edema and ventricular arrhythmias. Activation of norepinephrine, angiotensin II, vasopressin and atrial natriuretic peptide may be a key factor in the vasoconstriction and increased impedance to left ventricular ejection in heart failure. Interventions that interfere with these vasoconstrictor mechanisms should have a salutary effect on left ventricular performance. Treatment with angiotensin-converting enzyme (ACE) inhibitors, alpha-adrenoceptor blockers and vasopressin antagonists has resulted in hemodynamic benefits, but it has been more difficult to demonstrate long-term clinical effectiveness. Reductions in mortality have been demonstrated in patients with heart failure treated with vasodilators and ACE inhibitors. Improvement in the quality of life and prolongation of life are the only two appropriate goals in the management of heart failure. Further understanding of the role of angiotensin II and its interference by ACE inhibition in the tissue processes of heart failure is needed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Neuroendocrine activation after acute myocardial infarction.

Neuroendocrine response after acute myocardial infarction (MI) results in activation of the sympathetic nervous system, the renin-angiotensin system, and vasopressin and atrial natriuretic peptide release. The net effect of this response is vasoconstriction, cardiac stimulation and regional flow redistribution that may have a favorable effect in some situations and a deleterious effect in others. The possible adverse effects of vasoconstriction were studied in a Veterans Administration Cooperative Study that evaluated a 48-hour infusion of sodium nitroprusside in the setting of acute MI. In the presence of mild, probably primarily diastolic left ventricular dysfunction, nitroprusside appeared to have an adverse effect on long-term survival. However, in the presence of more severe, probably predominantly systolic dysfunction, nitroprusside had a favorable effect on the prognosis. Therefore, the decision of whether to accept or inhibit neuroendocrine activation in acute MI probably depends on the severity of the disease and the timing of the therapeutic intervals.

Atrial Natriuretic Factor↗
PubMed1990

Hemodynamic and renal effects of atrial natriuretic peptide in congestive heart failure.

The hemodynamic and renal effects of anaritide (human atrial natriuretic peptide 102-126), a synthetic analog of atrial natriuretic peptide, were evaluated in 35 patients with chronic New York Heart Association class II to IV heart failure. There were 32 men and 3 women, aged 33 to 75 (mean +/- standard error of the mean 56 +/- 2) years. In the first phase of the study, right-sided heart catheterization was performed, and anaritide was administered as 1-hour infusions. The rate of the infusion varied among patients from 0.03 to 0.3 micrograms/kg/min. In response to anaritide, there were decreases in mean systemic arterial (94 +/- 2 to 87 +/- 2 mm Hg), right atrial (10 +/- 1 to 8 +/- 1 mm Hg), mean pulmonary arterial (33 +/- 2 to 28 +/- 2 mm Hg) and pulmonary artery wedge (22 +/- 2 to 15 +/- 2 mm Hg) pressures (all p less than 0.05). Cardiac index increased (2.39 +/- 0.15 to 2.62 +/- 0.15 liters/min/m2, p less than 0.05) and heart rate was unchanged. Systemic vascular resistance decreased significantly, but pulmonary vascular resistance was unchanged. There were increases in urine volume (1.6 +/- 0.2 to 2.3 +/- 0.4 ml/min), sodium excretion (47 +/- 13 to 74 +/- 20 muEq/min) and fractional excretion of sodium (0.41 +/- 0.11 to 0.59 +/- 0.14%, all p less than 0.05), while potassium excretion and creatinine clearance did not change. In the second phase of the study, patients received 2-hour infusions of anaritide (0.03 to 0.6 micrograms/kg/min) and placebo with noninvasive monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Systemic and regional hemodynamic effects of alpha-adrenoceptor blockade in chronic left ventricular dysfunction in the conscious dog.

In seven dogs with long-standing left ventricular dysfunction induced 16 weeks earlier by repetitive transmyocardial direct current (DC) shock, the acute hemodynamic effect of the alpha 1-adrenoceptor antagonist urapidil was studied. Left ventricular end-diastolic pressure (LVEDP) was significantly increased from preshock levels at the time of study and cardiac output was reduced. Plasma norepinephrine was significantly increased from control levels and was not altered by urapidil infusion. The mean arterial pressure fell in response to alpha 1-blockade from 111 to 85 mm Hg, the LVEDP fell from 16 to 9 mm Hg, and cardiac output increased from 2.90 to 3.70 L/min (all p less than 0.01). Regional blood flows measured by microsphere injection revealed an increase in blood flow to skeletal muscle, which had not been significantly decreased by the left ventricular dysfunction in this model, and further decreases in splanchnic flow, which was already depressed compared with that in normal dogs. Therefore acute alpha-adrenoceptor blockade improves central hemodynamics in experimental heart failure but does not normalize the resting blood flow maldistribution in this model.

Adrenergic alpha-Antagonists↗
PubMed1990

Marked spontaneous improvement in ejection fraction in patients with congestive heart failure.

PURPOSE: The overall prognosis for patients with congestive heart failure is poor. Defining specific populations that might demonstrate improved survival has been difficult. We therefore examined our patient database for patients with congestive heart failure who demonstrated sustained improvement in left ventricular function and associated resolution of signs and symptoms of congestive heart failure. PATIENTS AND METHODS: We identified 11 patients with severe congestive heart failure (average ejection fraction 21.9 +/- 4.23% (+/- SD) who developed spontaneous, marked improvement over a period of follow-up lasting 4.25 +/- 1.49 years. All 11 patients were initially symptomatic with exertional dyspnea and fatigue for a minimum duration of 3 months. They form a subset of a larger group of 97 patients with chronic congestive heart failure that we have followed with sequential ejection fraction measurements. All 11 patients were treated with digitalis diuretics, and either converting-enzyme inhibitors or a combination of isosorbide dinitrate and hydralazine. Ten of the 11 patients had a history consistent with chronic alcoholism, and each reportedly abstained from alcohol during follow-up. RESULTS: During the follow-up period, the average ejection fraction improved in 11 patients from 21.9 +/- 4.23% to 56.64 +/- 10.22%. Late follow-up indicates an average ejection fraction of 52.6 +/- 8.55% for the group. Congestive heart failure resolved in each case. CONCLUSIONS: We conclude that selected patients with severe congestive heart failure can markedly improve their left ventricular function in association with complete resolution of heart failure. This appears to be particularly evident in those patients with chronic alcoholism who subsequently abstain.

Aged↗