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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 253 records · Page 14Linked to original sources
PubMed1984

Hemodynamic and regional blood flow response to captopril in congestive heart failure.

In 19 patients with moderate to severe congestive heart failure the over-all hemodynamic response to captopril was compared with its effect on regional blood flow. Ninety minutes after administering a single dose of captopril (25 to 150 mg), right atrial pressure decreased from 6.1 +/- 6.1 to 3.2 +/- 5.1 mm Hg (p less than 0.001), pulmonary artery pressure from 33.1 +/- 8.3 to 26.5 +/- 9.1 mm Hg (p less than 0.001), pulmonary capillary wedge pressure from 22.4 +/- 6.2 to 15.2 +/- 7.4 mm Hg to (p less than 0.001), mean arterial pressure from 77.2 +/- 8.0 to 66.5 +/- 13.7 mm Hg (p less than 0.001), and systemic vascular resistance from 1,630 +/- 503 to 1,233 +/- 443 dyne-s-cm-5 (p less than 0.001), and cardiac index increased from 2.0 +/- 0.6 to 2.4 +/- 0.7 l/minute/m2 (p less than 0.001). Despite the significant increase in cardiac index there was no increase in either hepatic blood flow (203 +/- 212 to 142 +/- 101 units, N.S.) or forearm blood flow (2.2 +/- 0.9 to 2.2 +/- 1.0 ml/100 g per minute, N.S.) after captopril. Similarly, the global reduction in systemic vascular resistance was not accompanied by a reduction in either hepatic vascular resistance (0.93 +/- 0.90 to 0.83 +/- 0.69 units, N.S.) or forearm vascular resistance (41.3 +/- 18.4 to 34.9 +/- 12.4 mm Hg/ml/100 g per minute, N.S.). The over-all improvement in hemodynamics that is seen when captopril is given to patients with severe heart failure does not apply uniformally to all vascular beds. The heterogeneous response reflects the variable vasoconstrictor part played by the renin-angiotensin system in regulating flow to individual regional circulations.

Adult↗
PubMed1984

High resolution proton NMR studies of perfused rat hearts.

High resolution 1H NMR spectra of perfused rat hearts have been obtained under normoxic, ischemic and hypoxic conditions. Several myocardial metabolites including taurine, carnitine, lactate and tissue glycerides are detected in the 1H NMR spectra. Changes in oxygen availability induce perturbations in the levels of some metabolites, in particular, lactate. Experiments with fasted rats and with substrate-free perfusion suggest that the glycerides detected in 1H spectra are metabolically mobilizable but have a slow rate of turnover. These results demonstrate that utility of 1H NMR in monitoring myocardial metabolism.

Animals↗
PubMed1984

Hemodynamic effects of a new inotropic agent, piroximone (MDL 19205), in patients with chronic heart failure.

The hemodynamic and neurohumoral effects of cummulative intravenous doses of piroximone (MDL 19205), a noncatecholamine, nonglycoside, imidazole derivative with positive inotropic and vasodilating properties, were studied in eight patients with severe congestive heart failure. A dose of 1.25 mg/kg in seven patients and 1.75 mg/kg in one patient increased cardiac index by 75% from 1.96 to 3.41 liters/min per m2 and decreased systemic vascular resistance (-41%), right atrial (-66%) and pulmonary wedge pressure (-35%) (all p less than 0.005). Mean arterial pressure was slightly reduced from 78 to 71 mm Hg (p less than 0.05) and forearm blood flow increased by 42%. Plasma norepinephrine decreased from 830 to 542 pg/ml (p less than 0.05) and plasma renin activity tended to increase. In four patients, dobutamine (15 micrograms/kg per min) produced a comparable increase in cardiac index (+100%), but less decrease in pulmonary wedge pressure (-21 versus -41%, p less than 0.05 versus piroximone) and, unlike piroximone, significantly increased heart rate (+22%, p less than 0.05 versus piroximone) and heart rate-blood pressure product (+30%, p less than 0.01 versus piroximone). In four other patients, a single intravenous dose of piroximone (1 mg/kg) resulted in a 35% increase in the first derivative of left ventricular pressure (dP/dt) from 796 to 1,068 mm Hg/s (p less than 0.01). Thus, piroximone is a potent inotropic agent with an acute hemodynamic profile that may be more favorable than that of dobutamine. Because the drug is orally absorbed, clinical trials of chronic efficacy are indicated.

Adult↗
PubMed1984

Acute hemodynamic and hormonal response to indoramin in congestive heart failure.

Acute hemodynamic and hormonal responses to a single dose of indoramin, an alpha 1-antagonist, were evaluated in 11 subjects with severe chronic congestive heart failure. A hemodynamic effect began within 1 hr of indoramin and persisted during the 6 hr of hemodynamic monitoring. Decreased right and left ventricular filling pressures were associated with increased stroke index and decreased pulmonary and systemic vascular resistances. Heart rate did not increase despite a fall in systemic arterial pressure. Forearm blood flow, forearm venous capacitance, and plasma norepinephrine levels were unchanged, whereas plasma renin activity rose from 12.7 +/- 17.4 to 16.6 +/- 20.4 ng/ml/hr. The only side effect was drowsiness in five of the 11 subjects. Our data demonstrate the acute effectiveness of indoramin in reducing ventricular preload and systemic vascular resistance in heart failure.

Adult↗
PubMed1984

Renal vein renin sampling in essential hypertension using hydralazine and the tourniquet test.

The results of renal vein renin sampling were assessed in 40 patients who had uncomplicated essential hypertension. All had normal creatinine clearance, intravenous pyelography, and arteriography. During sampling, renin release was stimulated in 29 patients with intravenous hydralazine and in 11 with the tourniquet blood trapping test. Simultaneous sequential renal vein samples were drawn over a 30-minute period. Positive renal vein renin ratios (greater than or equal to 1.5) were seen in 52% of the hydralazine group at 0 minutes and in 69% post-hydralazine. In the tourniquet group, 27% had a positive ratio at 0 minutes as compared with 64% post-tourniquets. A significant difference was found in renal vein plasma renin activity between the two kidneys (p greater than or equal to .0001). The asymmetry of renal vein renin activity and the large renal vein renin ratios in these two groups suggest the presence of true differences in renin secretion. These differences may be due to focal nephrosclerosis. The therapeutic significance of a positive renal vein renin ratio in the hypertensive patient should be determined in conjunction with arteriography.

Blood Volume↗
PubMed1984

Effect of increased intracardiac and arterial pressure on plasma vasopressin in humans.

The effects of loading cardiopulmonary and sinoaortic baroreceptors on plasma arginine vasopressin (AVP) levels were examined in 18 healthy young adults after a mild water restriction. Cardiopulmonary receptors were acutely loaded by volume expansion which increased central venous pressure (CVP) from 4.7 +/- 1.9 to 7.3 +/- 2.2 mmHg but did not change mean arterial blood pressure (MAP). Both receptor groups were acutely loaded by applications of lower body positive pressure, which induced a comparable increase in CVP and, in addition, raised MAP from 85 +/- 6.7 to 93 +/- 6.8 mmHg (P less than 0.001). There was evidence of reflex activation as forearm blood flow and heart rate increased during volume expansion while the increase in heart rate was blocked during lower body positive pressure. Neither intervention significantly altered the control AVP level of 4.6 +/- 1.4 pg/ml. An investigation of more prolonged stimulation of cardiopulmonary receptors was carried out using 1 h of head-down tilt. Again, despite increases in CVP (5.1 +/- 1.3 to 9.0 +/- 1.4 mmHg, P less than 0.005), AVP (5.7 +/- 2.4 pg/ml) did not decrease. MAP did not change during head-down tilt. There were no changes in osmolality throughout any of the studies. AVP levels in humans are therefore not responsive to moderate isosmotic loading of the cardiopulmonary and sinoaortic baroreceptors under conditions of mild water restriction.

Adult↗
PubMed1984

Regional differences in adrenergic function within the left ventricle.

Since ischemic heart disease (IHD) is inhomogeneous, the adrenergic response of the heart to ischemia or infarction could depend on the level of adrenergic supply within specific regions of the myocardium. Therefore we quantified myocardial norepinephrine (NE) content of tissue samples from 54 different sites in the left ventricle (LV) of four normal dogs using high-pressure liquid chromatography with electrochemical detection. Up to 10-fold differences in NE content occurred within a single LV. The NE distribution followed a consistent pattern, demonstrating a gradient from apex (avg minimum value of 162 ng/g of tissue) to base (avg maximum value 844 ng/g). No epicardial-to-endocardial gradient was present. In six other dogs a similar pattern was found in myocardial uptake of radioactively labeled NE and epinephrine assessed 2 min after intravenous injection. These results suggest that areas of high tissue NE represent regions rich in adrenergic supply and high in adrenergic activity, not merely NE stored in inactive pools. Samples from a human autopsy specimen suggest that these findings can be extrapolated to humans.

Animals↗
PubMed1984

Hemodynamic and clinical response to enalapril, a long-acting converting-enzyme inhibitor, in patients with congestive heart failure.

Enalapril, a new oral angiotensin converting-enzyme inhibitor, was administered to nine patients with severe congestive heart failure. Short-term hemodynamic response was noted within 2 hr and persisted for up to 24 hr. At peak effect mean arterial pressure fell from 83.4 +/- 10(SD) to 72.1 +/- 16.2 mm Hg (p less than .01), right atrial pressure from 13.6 +/- 6.0 to 10.4 +/- 7.5 mm Hg (p less than .01), pulmonary arterial pressure from 38.9 +/- 4.8 to 31.9 +/- 4.8 mm Hg (p less than .01), pulmonary capillary wedge pressure from 28.2 +/- 3.5 to 22.1 +/- 5.1 mm Hg (p less than .01), and total pulmonary resistance from 875 +/- 304 to 697 +/- 291 dynes-sec-cm-5 (p less than .05). Cardiac index was not changed, but there was a significant redistribution of regional blood flow with an increase of renal blood flow after enalapril. Plasma renin activity rose significantly from 6.2 to 28.6 ng/ml/hr, whereas plasma norepinephrine did not change after enalapril. Seven patients were treated with enalapril for 4 weeks. Five patients reported symptomatic improvement. Five of six patients tested had an increase in both exercise time (NS) and maximum oxygen consumption (NS). Repeat hemodynamic evaluation in six patients after long-term enalapril therapy showed a persistent effect with significant reductions in right atrial pressure from 13.8 +/- 7.2 to 7.1 +/- 4.7 mm Hg and in mean arterial pressure from 82.5 +/- 10.4 to 76.6 +/- 5.3 mm Hg and a significant increase in cardiac index from 2.1 +/- 0.5 to 2.5 +/- 0.5 l/min/m2 (all p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Hemodynamic effects of nifedipine at rest and during exercise in primary pulmonary hypertension.

The potential short-term pulmonary vasodilator effect of a calcium-channel blocker, nifedipine, was tested in seven patients with primary pulmonary hypertension. Nifedipine (20 mg) produced a significant (p less than 0.01) and persistent decrease in mean pulmonary arterial pressure (58.1 +/- 14.3 to 48.6 +/- 16.3 mm Hg) and pulmonary vascular resistance (1,070 +/- 260 to 695 +/- 266 dynes X sec X cm-5). Cardiac index increased from 2.5 +/- 0.6 to 3.3 +/- 0.8 L/min/m2 (p less than 0.01), and heart rate was unchanged despite a fall in systemic pressure. In three patients tested during exercise on a bicycle, nifedipine resulted in an increase in the duration of exercise in two and a blunting of the exercise-induced increase in pulmonary pressure in all three. Long-term treatment was initiated in five of the seven patients and in two additional patients who did not receive nifedipine in the short-term study; all but one experienced symptomatic improvement. A persistent hemodynamic improvement was observed in three of the four patients restudied after long-term therapy. In conclusion, this study demonstrated the short-term beneficial hemodynamic effects of nifedipine, both at rest and during exercise. A more extensive long-term follow-up is necessary to establish the usefulness of this drug in the treatment of primary pulmonary hypertension.

Adolescent↗
PubMed1984

The neurohumoral axis in congestive heart failure.

The incidence of congestive heart failure is increasing in the United States. This common syndrome is characterized not only by impaired ventricular function but also by an increase in some endogenous vasoconstrictor substances, including norepinephrine, angiotensin II, and arginine vasopressin. Although activation of the systems that release these substances is presumed to be compensatory (to maintain perfusion pressure during inadequate flow), the sympathetic nervous system, renin-angiotensin-aldosterone system, and arginine vasopressin may contribute to the pathogenesis of the syndrome. The excessive vasoconstriction present in heart failure likely produces a further burden on the failing myocardium. New strategies in therapy are being developed to counteract the activation of vasoconstrictor forces in congestive heart failure. Data indicate that selective blockade of the renin-angiotensin system is useful. Preliminary data suggest that inhibition of the sympathetic nervous system may be helpful, and inhibition of vasopressin in animals with heart failure is being studied. New and more selective therapy for heart failure may come from these studies.

Animals↗
PubMed1984

Acute hemodynamic effects of nitrendipine in chronic congestive heart failure.

The acute hemodynamic response to a single oral dose of nitrendipine (10-20 mg) was evaluated in eight subjects with severe chronic congestive heart failure during right heart catheterization. A hemodynamic effect began within 1 h. At peak effect (1-2 h after drug administration), mean arterial pressure fell from 84.0 +/- 9.2 to 76.0 +/- 9.2 mm Hg (mean +/- SD), right arterial pressure from 10.6 +/- 5.9 to 8.0 +/- 7.1 mm Hg, mean pulmonary arterial pressure from 35.5 +/- 9.2 to 30.1 +/- 9.4 mm Hg, pulmonary wedge pressure from 23.6 +/- 6.7 to 17.7 +/- 6.3 mm Hg, and cardiac index rose from 1.91 +/- 0.38 to 2.45 +/- 0.34 L/min/m2. Heart rate did not change (85 +/- 18 to 82 +/- 18 beats/min) despite the significant fall in arterial pressure. Systemic and pulmonary vascular resistances fell significantly. Whereas forearm blood flow increased from 1.44 +/- 0.52 to 2.06 +/- 0.41 ml/min/100 g (p less than 0.05), hepatic and renal blood flows were unchanged. This study demonstrates the acute effectiveness of nitrendipine in reducing ventricular preload and impedance in heart failure and in increasing cardiac output that appears to be preferentially directed to the skeletal bed. The left-upward shift of the Frank-Starling curve suggests the absence of any clinically important negative inotropic effect of nitrendipine. Nitrendipine therefore may be a useful agent for vasodilator therapy of heart failure.

Adult↗
PubMed1984

Quantitative analysis of postmortem changes in myocardial norepinephrine using HPLC with electrochemical detection.

Myocardial adrenergic function may be important in the pathophysiology of many cardiac abnormalities, and quantitative analysis of catecholamines in cardiac tissue can provide insight in the role of adrenergic neurons in specific disorders. Our purpose was to determine the stability of myocardial catecholamines postmortem to assess the validity of using postmortem samples to represent premorbid conditions and to provide information applicable to proper handling of biopsy specimens. Serial myocardial samples were obtained postmortem in rats and dogs for which norepinephrine and dopamine levels were analyzed using high-pressure liquid chromatography with electrochemical detection. No significant differences in catecholamine content were found between samples taken immediately after death and those taken 15 minutes later. Thereafter, a progressive decline in catecholamines was observed. We conclude that biopsy or postmortem samples frozen within 15 minutes of death will accurately reflect premortem catecholamine values.

Animals↗
PubMed1984

Free and conjugated plasma catecholamines in patients with congestive heart failure.

Conjugation is an important mechanism in the deactivation process of circulating catecholamines, because most of the circulating catecholamines are found in the conjugated rather than the free form. To determine whether a defect in conjugation might account for some of the elevated free plasma norepinephrine in patients with CHF, we measured free and conjugated circulating catecholamines in 12 patients with chronic CHF. These measurements were also obtained in eight age-matched control subjects without clinical heart disease. The data demonstrate that the free plasma norepinephrine in patients with heart failure (566 +/- 227 (SD) pg/ml) is significantly greater than the free plasma norepinephrine in normal age-matched control subjects (337 +/- 148 pg/ml, p less than 0.05). The amount of free circulating epinephrine in the patients with heart failure (51 +/- 25 pg/ml) is similar to that in the control population (46 +/- 50 pg/ml), whereas the free circulating dopamine content is greater in the heart failure population (36 +/- 21 pg/ml) compared with normal (17 +/- 15 pg/ml, p less than 0.05). Although the absolute conjugated catecholamines are also increased in patients with heart failure, the percent conjugation of norepinephrine in heart failure (73%) did not vary from control values (71%). The percent conjugation of epinephrine in the group with heart failure (81%) was similar to that in the control group (76%), as was the percent conjugation of dopamine in the two groups (99%). Therefore, it is unlikely that a defect in conjugation of catecholamines is contributing to the excessive free plasma norepinephrine found in patients with congestive heart failure.

Adult↗
PubMed1983

Elevated left ventricular myocardial dopamine in preterminal idiopathic dilated cardiomyopathy.

The adrenergic nervous system is chronically activated in patients with congestive heart failure (CHF). One consequence of this is depletion of the normally high levels of myocardial norepinephrine. In this study, myocardial norepinephrine and dopamine concentrations from the left ventricular walls of 3 patients undergoing cardiac transplantation for severe refractory CHF are reported. The dopamine/norepinephrine ratios were high in all 3 patients (29, 58 and 26%). This finding supports data from animal studies suggesting a change in the rate-limiting step for myocardial norepinephrine synthesis in CHF. Conversion of tyrosine to dopa by tyrosine hydroxylase is replaced as the rate-limiting step by inability to hydroxylate dopamine to norepinephrine. Thus, dopamine accumulates while norepinephrine is depleted.

Adult↗