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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 271 records · Page 15Linked to original sources
PubMed1983

The acute response of plasma norepinephrine, renin activity, and arginine vasopressin to short-term nitroprusside and nitroprusside withdrawal in patients with congestive heart failure.

Activation of the sympathetic nervous system, manifested by an increase in heart rate and circulating plasma norepinephrine, can occur in normal subjects when they are given vasodilators. The extent to which this activation occurs in patients with congestive heart failure (CHF) and whether this activation could account for the hemodynamic rebound sometimes observed following abrupt withdrawal of nitroprusside in such patients are unclear. We prospectively and retrospectively studied the effects of nitroprusside on plasma norepinephrine in 38 patients with CHF to determine if acute vasodilator therapy activates this vasoconstrictor system during or following such treatment. Thirty-six of these patients also had plasma renin activity (PRA) measured and plasma arginine vasopressin was measured in 12 patients. Baseline supine plasma norepinephrine (714 +/- 72 pg/ml, +/- SEM), PRA (15 +/- 2 ng/ml/hr), and arginine vasopressin (10 +/- 1 pg/ml) were increased at least twofold in the CHF patients. Nitroprusside (96 +/- 11 micrograms/min) was infused for 63 +/- 5 minutes after achieving an optimal hemodynamic response: cardiac index increased (2.01 +/- 0.08 to 2.67 +/- 0.1 L/min/m2, p less than 0.001), pulmonary artery wedge pressure decreased (25 +/- 1 to 16 +/- 1 mm Hg, p less than 0.001), mean arterial pressure decreased (83 +/- 1 to 72 +/- 1 mm Hg, p less than 0.001), and heart rate was unchanged. Plasma norepinephrine (632 +/- 43 pg/ml), PRA (18 +/- 3 ng/ml/hr), and arginine vasopressin (11 +/- 1 pg/ml) did not change significantly for the group during peak effect of the vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗
PubMed1983

The effects of bromocriptine in patients with congestive heart failure.

The sympathetic nervous system and the renin-angiotensin system are activated in patients with congestive heart failure (CHF) and could be contributing to excessive peripheral vasoconstriction and impaired myocardial performance. Bromocriptine, an orally active ergot alkaloid with dopaminergic receptor agonist actions, is known to lower plasma norepinephrine in humans. It could also possess direct vasodilator activity through vascular dopaminergic receptors. To assess the effects of bromocriptine on hemodynamic measurements, sympathetic nervous system activity, and the renin-angiotensin system in patients with heart failure, we measured standard hemodynamic parameters and plasma norepinephrine and plasma renin activity before and following a single oral dose of 2.5 mg of bromocriptine in 10 patients with chronic stable heart failure. The following statistically significant (p less than 0.01) peak responses were noted: plasma norepinephrine decreased from a mean +/- 1 SD of 581 +/- 194 to 366 +/- 181 pg/ml; mean heart rate declined from 87 +/- 16 to 78 +/- 17 bpm; mean blood pressure was reduced from 87 +/- 9 to 73 +/- 9 mm Hg; systemic vascular resistance decreased from 1494 +/- 361 to 1249 +/- 289 dynes X sec X cm-5; stroke volume index increased from 27 +/- 7 to 33 +/- 10 ml/beat/M2; left ventricular filling pressure decreased from 28 +/- 8 to 21 +/- 8 mm Hg; and mean right atrial pressure fell from 10 +/- 4 to 7 +/- 4 mm Hg. Plasma renin activity did not change significantly. All patients tolerated the drug well. Although the effects of bromocriptine on plasma norepinephrine may contribute to an improved hemodynamic state, other mechanisms of action are likely. A direct vasodilator effect via vascular dopaminergic receptor stimulation is possible. We conclude that bromocriptine improves the hemodynamic profile in heart failure acutely and that long-term studies are appropriate to better characterize the role of this agent.

Aged↗
PubMed1983

Regional blood flow response to orthostasis in patients with congestive heart failure.

To investigate the central and regional circulatory response to orthostasis in congestive heart failure, hemodynamic variables and forearm and hepatic blood flow were measured in 22 patients at supine rest and during a 65 degrees head-up tilt. Results were compared with those in nine normal subjects. Heart rate and mean arterial blood pressure increased during tilt in normal subjects, but not in patients with heart failure. Forearm blood flow decreased in normal subjects from 3.7 +/- 1.1 to 2.7 +/- 1.5 ml/min per 100 g (probability [p] less than 0.02), but did not change from a lower baseline (1.65 +/- 0.78 ml/min per 100 g) in patients. Forearm vascular resistance increased in normal subjects but not in patients. Hepatic blood flow did not change during tilt in either group, but hepatic vascular resistance increased in normal subjects from 0.37 +/- 0.13 to 0.47 +/- 0.15 U, (p less than 0.02). The increase was not seen in patients (1.2 +/- 1.1 to 1.4 +/- 1.0 U, p = not significant [NS] ). Total systemic resistance increased in patients from 1,848 +/- 560 to 2,132 +/- 731 dynes.s.cm-5 (p less than 0.005) indicating that resistance did increase in some vascular beds. Plasma norepinephrine also increased modestly in these patients from 665 +/- 377 to 761 +/- 379 pg/ml (p = 0.035), but individual changes in plasma norepinephrine did not correlate with changes in hepatic or forearm resistance. Thus, both the overall hemodynamic response and the regulation of regional blood flow and resistance differ in several respects in patients with congestive heart failure when compared with normal subjects. Changes in heart rate, blood pressure, forearm flow and forearm and hepatic vascular resistance are all blunted in patients. Reasons for the differences are not yet clear, but may be associated with abnormalities in reflex control of the circulation in patients with congestive heart failure.

Adult↗
PubMed1983

Hemodynamic and hormonal response to transdermal nitroglycerin in normal subjects and in patients with congestive heart failure.

The hemodynamic and hormonal responses to nitroglycerin administered transdermally in a gel-like matrix were evaluated in nine patients with severe congestive heart failure and in nine normal subjects. In normal subjects, peripheral vasodilation was accompanied by reflex sympathetic stimulation as reflected by an increase in heart rate and plasma norepinephrine. In patients with heart failure, nitroglycerin produced sustained hemodynamic effects that began 30 minutes after the application and fully persisted for at least 6 hours. A significant decrease in right and left ventricular filling pressures was associated with an increase in stroke index and a significant decrease in forearm and pulmonary vascular resistances. There was no change in heart rate and systemic arterial pressure or in plasma norepinephrine or plasma renin activity. After 24 hours, pressures had partially returned to control levels, but mean pulmonary artery pressure was still significantly lower than in the control period. After removal of the nitroglycerin, each patient exhibited a decrease in cardiac index and an increase, above the control values, in pulmonary and systemic arterial pressures and pulmonary, systemic and forearm vascular resistances. This transient rebound appeared to be unrelated to stimulation of the sympathetic or renin-angiotensin systems. Thus, transdermal absorption of this new form of nitroglycerin appears to provide a nitrate vascular effect that is sustained for 24 hours, but an endogenous vasoconstrictor effect may influence the hemodynamic response over the first 24 hours.

Administration, Topical↗
PubMed1983

Abnormal neurohumoral response to nitroprusside infusion in congestive heart failure.

Vasodilator drugs produce tachycardia and an increase in circulating plasma norepinephrine in normal subjects. In contrast, heart rate does not change when the same drugs are given to patients with congestive heart failure. To assess if this difference could be related to a different reflex activation of the sympathetic nervous system, the response of plasma norepinephrine to nitroprusside infusion and to head-up tilt was studied in 5 normal subjects and in 46 patients with chronic congestive heart failure. Norepinephrine and heart rate increased significantly during both stimuli in normal subjects but were unchanged during nitroprusside infusion for the entire group of patients with heart failure, with considerable variability in individual responses. In 21 patients (Group I) norepinephrine increased during nitroprusside infusion, while in the remaining 25 (Group II) norepinephrine decreased. The hemodynamic response to nitroprusside was similar in the two groups, thus suggesting that the different changes in plasma norepinephrine could not be explained on the basis of a different hemodynamic response to the drug. Plasma norepinephrine also did not change significantly in Group II during tilt, although the decrease in intracardiac pressure and the increase in peripheral resistance were similar to those in Group I who increased norepinephrine normally by 56%. These data indicate that a subset of patients with severe ventricular dysfunction have an abnormal humoral, reflex sympathetic response to changes in arterial or intracardiac pressure, or both. The higher mortality in Group II suggests that this alteration in the sympathetic response may be a marker of the severity and prognosis of heart failure.

Adult↗
PubMed1983

Impaired response of plasma vasopressin to orthostatic stress in patients with congestive heart failure.

Arginine vasopressin, a potent vasoconstrictor and regulator of body water, is frequently increased in the plasma of patients with congestive heart failure. Other neurohumoral control networks, such as the sympathetic nervous system and the renin-angiotensin system, also demonstrate increased activity in congestive heart failure, but fail to respond normally to physiologic stress, such as orthostatic tilt. To assess the response of plasma vasopressin to orthostasis in heart failure, vasopressin was measured before and at 10 and 45 minutes during passive upright tilt in 15 patients with congestive heart failure and their response was compared with that in 9 normal control subjects. Arginine vasopressin was measured by radioimmunoassay. In the normal subjects, plasma arginine vasopressin was 5.3 +/- 2.3 pg/ml at control, was unchanged at 10 minutes, but significantly increased to 7.0 +/- 2.5 pg/ml at 45 minutes (p less than 0.05). In contrast, patients with congestive heart failure showed no significant changes in arginine vasopressin levels from the control levels of 11.6 +/- 5.5 pg/ml. Both plasma norepinephrine and renin activity increased in the normal subjects, but failed to increase from higher baselines in patients with congestive heart failure. Thus, plasma arginine vasopressin, like plasma norepinephrine and renin activity, does not increase in response to upright tilt in patients with congestive heart failure. The explanation is not evident but could involve either abnormalities in reflex control of plasma vasopressin in congestive heart failure or in clearance of the hormone during orthostasis.

Adult↗
PubMed1983

Increased renal plasma flow in long-term enalapril treatment of hypertension.

The renal effects of long-term antihypertensive treatment with enalapril were evaluated in 34 subjects (age, 53 yr; range, 27 to 65) with mild, uncomplicated hypertension. After receiving placebo for 4 wk, subjects were randomly assigned to groups receiving incremental doses of enalapril (10, 20, or 40 mg/day for 4 wk each) in a single morning dose or two divided doses, or of placebo. One subject who received enalapril developed acute renal failure by the end of the study. There was no evidence of glomerular or tubular damage in the other subjects; as measured by 24-hr urinary protein excretion, urinary activity of N-acetyl-beta-D-glucosaminidase, and uric acid clearance. During treatment with enalapril, renal plasma flow (measured with 131I-iodohippurate sodium) and glomerular filtration rate increased by 12.1% and 6.8%. Changes in renal plasma flow correlated inversely with age and final mean arterial pressure and correlated positively with initial plasma renin activity of subjects. Except for an occasional idiosyncratic adverse reaction, enalapril is a safe and effective antihypertensive drug with the unique ability to increase renal function despite a fall in renal perfusion pressure.

Acute Kidney Injury↗
PubMed1983

Cardiac and hormonal effects of enalapril in hypertension.

Systolic time measurements, echocardiography, and bicycle exercise testing with cardiac output determinations (CO2 rebreathing) were used to evaluate cardiac performance in 16 male hypertensives at the end of a 4-wk placebo period and after 12 wk of treatment with increasing doses (maximum = 40 mg/day) of enalapril maleate (N = 11) and of placebo (N = 5). The effect of exercise on plasma renin activity (PRA) and plasma norepinephrine (NE) concentration was also measured. Mean arterial pressure was reduced by 10 mm Hg or more in all but one subject who received enalapril. In both the enalapril- and placebo-treated subjects, the preejection period/left ventricular ejection time ratio and fractional shortening of the left ventricle at rest and cardiac output and stroke volume during moderate exercise did not change during the study. Enalapril induced a compensatory rise in PRA (N = 10). Compared to plasma NE concentration, 1124 +/- 380 pg/ml (mean +/- SD), during exercise at the end of the initial placebo period, there was attenuation of the rise of plasma NE concentration, 851 +/- 290, at the same load of exercise during enalapril therapy. Unchanged cardiac performance despite effective long-term lowering of blood pressure with enalapril may relate to inhibition of angiotensin II-mediated facilitation of NE release from peripheral nerve endings.

Adult↗
PubMed1983

Hydralazine and the tourniquet test in renal vein renin sampling: a comparison.

A total of 36 salt-depleted patients with suspected renovascular hypertension received intravenous hydralazine and 36 were subjected to the tourniquet test at the time of renal vein renin sampling. Simultaneous bilateral renal vein samples were obtained sequentially over 30 minutes. Both measures resulted in an increase in renin secretion. The number of patients showing a positive ratio (greater than or equal to 1.5) between the angiographically abnormal kidney and the contralateral kidney increased in both groups. In the hydralazine group, 47% had positive ratios at 0 min compared with 80% following hydralazine administration. In the tourniquet group, 53% had positive ratios at 0 min compared with 78% afterward. In neither group did all patients have positive ratios throughout the entire sampling period. Hydralazine produced a greater increase in renin, but more variable results. It is concluded that salt depletion is inadequate for detection of a pressor kidney, and an additional stress is required. Multiple simultaneous samples should be obtained.

Blood Pressure↗
PubMed1983

A nonsurgical canine model of chronic left ventricular myocardial dysfunction.

A simple technique of producing left ventricular myocardial damage accompanied by chronic complete heart block in dogs is described. The method is accomplished by repetitive transmyocardial DC shock with a guide wire introduced percutaneously and positioned in the left ventricle along the intraventricular septum and an external paddle at the left ventricular apex. Twelve weeks after the procedure significant hemodynamic changes included a fall in heart rate from a control of 76 +/- 19 (SD) to 43 +/- 9 beats/min (P less than 0.001), a rise in left ventricular filling pressure from 9 +/- 4 to 28 +/- 10 mmHg (P less than 0.001), and a fall in cardiac output from 3.1 +/- 1 to 2.3 +/- 0.6 l/min (P less than 0.05). Weekly echocardiography revealed a progressive increase in left ventricular end-diastolic diameter from 3.56 +/- 0.72 to 4.84 +/- 0.47 cm (P less than 0.01). Survival rate was 70%. Therefore, this relatively noninvasive technique is an effective means of producing chronic left ventricular myocardial dysfunction in the dog.

Animals↗
PubMed1983

The neurohumoral and hemodynamic response to orthostatic tilt in patients with congestive heart failure.

Thirty-five patients with varying degrees of congestive heart failure were subjected to 60 degrees upright tilt. Eight of the patients with normal resting hemodynamics had elevated resting plasma norepinephrine levels (PNE) (p less than 0.001), but their response to upright tilt was similar to that in normal subjects: All had increases in heart rate, plasma norepinephrine (from 263 +/- 32 to 483 +/- 78 pg/mg, p less than 0.02) and plasma renin activity (from 4.8 +/- 0.9 to 13.7 +/- 7.6 ng/ml/hour, p less than 0.05). In 27 patients with high resting pulmonary wedge pressure and low cardiac index, resting PNE was higher (668 +/- 71 ng/ml), but PNE, plasma renin activity and heart rate did not increase significantly during tilt despite a fall in pulmonary capillary wedge pressure and cardiac index. In 18 of these patients, PNE rose during tilt, whereas in nine it did not change or fell; the resting hemodynamics and the hemodynamic response to tilt were not significantly different in these two groups. These data suggest that an abnormality of mechanoreceptor or baroreceptor function is common in patients with CHF. This abnormality corresponds in part to the severity of the resting hemodynamic abnormality, but among patients with severe CHF, the reflex neurohumoral abnormality may provide independent information about the severity of the disease.

Adult↗
PubMed1983

Calcium, vascular smooth muscle, and calcium entry blockers in hypertension.

Increases in vascular tone induced by an increase in cytosol calcium concentration may be important in the development of hypertension, myocardial ischemia, and other cardiovascular disorders. A heterogeneous group of compounds known as calcium entry blockers inhibit smooth muscle contraction induced by physiologic and pharmacologic stimuli by blocking transmembrane transport of calcium through membrane channels. These drugs may reduce blood pressure through effects on the heart, the venous capacitance vessels, the arterial resistance vessels, and the renin-angiotensin system. Although their efficacy in antihypertensive therapy may eventually prove to be nonspecific, their ability to interfere with a basic cellular mechanism for vasoconstriction makes these drugs attractive as potential specific treatment for the abnormal vasomotion in patients with hypertension.

Blood Pressure↗
PubMed1982

Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administration cooperative study.

Eight hundred twelve men with presumed acute myocardial infarction and left ventricular filling pressure of at least 12 mm Hg participated in a randomized double-blind placebo-controlled trial to assess the efficacy of a 48-hour infusion of sodium nitroprusside. The mortality rates at 21 days (10.4 per cent in the placebo group and 11.5 per cent in the nitroprusside group) and at 13 weeks (19.0 per cent and 17.0 per cent, respectively) were not significantly affected by treatment. The efficacy of nitroprusside was related to the time of treatment: the drug had a deleterious effect in patients whose infusions were started within nine hours of the onset of pain (mortality at 13 weeks, 24.2 per cent vs. 12.7 per cent; P = 0.025) and a beneficial effect in those whose infusions were begun later (mortality at 13 weeks, 14.4 per cent vs. 22.3 per cent; P = 0.04). Nitroprusside should probably not be used routinely in patients with high left ventricular filling pressures after acute myocardial infarction. However, the results in the patients given late treatment suggest that those with persistent pump failure might receive sustained benefit from short-term nitroprusside therapy.

Aged↗