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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 199 records · Page 11Linked to original sources
PubMed1988

OPC-8212 in the treatment of congestive heart failure: results of a pilot study.

To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invasive hemodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with moderate to severe congestive heart failure. There were no significant changes from baseline in heart rate (83 +/- 8 beats/min), mean arterial pressure (70 +/- 15 mmHg), pulmonary wedge pressure (18 +/- 7 mmHg), or cardiac index (2.3 +/- 0.4 L/min/m2) following treatment with OPC-8212. Both exercise duration (5.3 +/- 1.6 min) and peak oxygen consumption (12.0 +/- 2.9 mL/kg/min) were unchanged by OPC-8212. Two independent patient self-assessment scores, the Sickness Impact Profile and the Minnesota Living with Heart Failure Questionnaire, showed improvements from 6.8 to 5.4 and 49 to 38, respectively (both p less than .05), suggesting that the patients reported an improvement in daily functioning. The median ventricular premature contraction count and frequency were reduced from 1,118 beats to 243 beats (p less than 0.05) and 11/1,000 beats to 2.4/1,000 beats (0.05 less than p less than 0.10), respectively. Two patients developed agranulocytosis during longer-term treatment following this 1-month study. These data demonstrate that OPC-8212 did not have significant effects on hemodynamics or exercise tolerance. However, the improvement in patient self-assessment scores and the trend for improvement in ventricular arrhythmia profiles suggest that OPC-8212 may have some benefit for patients with congestive heart failure, but additional placebo-controlled, double-blind studies are necessary.

Aged↗
PubMed1988

Sequential neurohumoral measurements in patients with congestive heart failure.

Patients with chronic congestive heart failure are known to have increased plasma norepinephrine and plasma renin activity. In order to evaluate neurohumoral changes over time, we measured plasma norepinephrine and plasma renin activity at baseline and sequentially during follow-up in 49 patients with chronic, stable congestive heart failure. All patients were treated with digitalis and diuretics. Converting enzyme inhibitor therapy was prescribed as adjunctive therapy in 22 patients, while 10 patients were taking hydralazine and/or isosorbide dinitrate, seven were taking prazosin, and 10 had no adjunctive therapy. Patients were divided into those taking converting enzyme inhibitors (group I, n = 22) and those not taking converting enzyme inhibitors (group II, n = 27). Group I was followed for a median (25th to 75th percentiles) of 24.3 (18 to 27.9) months, while group II was followed for 18.7 (11.9 to 36.5) months. Results indicate that patients in group I demonstrate a significant positive trend for rise in plasma norepinephrine of 11.7 pg/ml per month (7.8 to 15 pg/ml per month, 95% confidence interval). Patients in group II also demonstrated a significant positive trend in plasma norepinephrine over time of 6.6 pg/ml per month (2.2 to 11.1 pg/ml per month). Moreover, there was a progressive trend upward in plasma renin activity over time in group II (median 0.34 ng/ml/hr per month; range 0.13 to 0.54). The data indicate that there is a significant trend of neurohumoral activation over time in patients with chronic, clinically stable congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Effect of vasodilator therapy on mortality in chronic congestive heart failure.

The reduction of mortality in patients with chronic congestive heart failure treated with the vasodilator regimen hydralazine and isosorbide dinitrate compared to those treated with placebo or prazosin in the Veterans Administration Cooperative Study (V-HeFT) was examined in order to explore the possible mechanism of the favourable effect. Similar efficacy in coronary and non-coronary disease patients tends to discount a prominent effect on myocardial perfusion. The most likely explanation for the prolonged survival on the effective vasodilator regimen is that these drugs tend to increase left ventricular ejection fraction, probably by a sustained effect on preload and impedance.

Clinical Trials as Topic↗
PubMed1988

Current therapy of the failing heart.

Myocardial dysfunction eventuating in systolic and diastolic pump function abnormalities is a consequence of a wide variety of cardiac diseases. The symptoms that develop in this syndrome appear to be related as much to peripheral and neurohormonal mechanisms as to the underlying pathological and cardiac functional abnormality. Relief of symptoms, slowing of the progression of the cardiac functional abnormality, and prolongation of life provide the major agenda for the physician faced with the management of these patients. Judicious use of vasodilators, diuretics, digoxin, dietary therapy, and exercise therapy can relieve symptoms and improve the quality of life in most patients suffering from this syndrome. Recent evidence that vasodilator drugs can prolong life now provides the physician with further justification for routine use of this class of compounds. The eventual solution to the high mortality in this common disease process may be prevention of the development of overt heart failure by more prompt recognition and early treatment of the signs of ventricular dysfunction. This possibility must await the completion of current and proposed clinical trials.

Exercise↗
PubMed1988

Arterial vascular compliance response to vasodilators by Fourier and pulse contour analysis.

Vasodilator drugs are widely used in the management of cardiovascular disease. They decrease systemic vascular resistance, but they also may influence vascular arterial compliance. This study evaluated the effects of three vasodilators--nitroprusside, nitroglycerin, and hydralazine--on vascular compliance using impedance parameters determined by pulse contour and Fourier analyses. The open chest study was performed on anesthetized dogs. Mean arterial pressure decreased by a minimum of 20% after vasodilator intervention. The decrease in systemic vascular resistance was significant (p less than 0.01) only after hydralazine treatment. Proximal compliance increased after administration of all drugs, but the increase was not statistically significant. Distal compliance determined by pulse contour analysis increased by 60 to 120% after all three drug treatments (p less than 0.05 for nitroprusside, p less than 0.02 for nitroglycerin and hydralazine). Characteristic impedance from Fourier analysis responded variably, and changes were not statistically significant. The sensitivity of changes in distal compliance as a marker for the vascular effect of these drugs suggests that it might be used as a more reliable guide than blood pressure or vascular resistance in monitoring clinical response to such intervention. The more traditional measure of characteristic impedance provides a vascular measurement that is less sensitive than distal compliance to the effects of these vasodilator drugs.

Animals↗
PubMed1987

Role of nitrates in congestive heart failure.

The systemic vasoconstriction that is characteristic of patients with congestive heart failure involves arteriolar constriction, reduction in arterial compliance and reduction in venous capacitance, all of which contribute to the increased impedance and increased preload that aggravate the hemodynamic abnormality. Nitrates are effective in increasing arterial compliance and venous capacitance and thus have a favorable acute hemodynamic effect in heart failure. Long-term studies suggest that this favorable effect is maintained in response to high dose oral isosorbide dinitrate therapy and that it is associated with relief of symptoms and improved exercise tolerance. When combined with hydralazine, isosorbide dinitrate therapy has been shown in the Veterans Administration study to prolong survival in patients with class II and III congestive heart failure. Therefore, long-term nitrate therapy appears to have an important potential in patients with heart failure. It may now be appropriate to use nitrates not only to relieve symptoms, but also to improve long-term outlook in this syndrome.

Dosage Forms↗
PubMed1987

Role of drugs for systemic hypertension and their effect on the heart.

The effects of hypertension on the heart include the development of left ventricular hypertrophy, impairment of left ventricular function leading to heart failure and accelerated coronary atherosclerosis leading to ischemic heart disease. The precise role of hypertension in precipitating these cardiac events is poorly understood, and the effect of antihypertensive drugs in preventing or reversing these abnormalities is surprisingly unclear. Current understanding of the pathophysiology and therapeutic responses of these cardiac manifestations of hypertension will be examined.

Antihypertensive Agents↗
PubMed1987

Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure.

Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 +/- 472 micrograms/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 +/- 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 +/- 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p less than 0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.

Adult↗
PubMed1987

Normalization of sympathetic nervous system function after orthotopic cardiac transplant in man.

Plasma norepinephrine (PNE) levels are significantly elevated in patients with endstage congestive heart failure. To assess whether this abnormality is reversible, 32 patients were studied before and 3 to 9 months after orthotopic cardiac transplantation. PNE decreased after the transplant procedure form 739 +/- 363 to 301 +/- 161 pg/ml (p less than .05). In 13 patients, PNE was measured sequentially during the first 3 months after the transplant procedure. PNE decreased from 590 +/- 293 to 321 +/- 208 pg/ml at 2 weeks and remained stable at 1 month (308 +/- 239 pg/ml), 2 months (307 +/- 196 pg/ml), and 3 months (331 +/- 131 pg/ml), even while arterial hypertension developed. No correlation was found between PNE, systolic, diastolic, or mean arterial pressure and cyclosporine A blood levels. These data demonstrate that normalization of plasma levels of norepinephrine occurs shortly after cardiac transplantation in man. This decrease in PNE is probably independent of immunosuppression therapy. Finally, the development of arterial hypertension in cyclosporine A-treated cardiac transplant patients is not due to activation or persistent activation of the sympathetic nervous system.

Adult↗