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Biomedical subjects

J N Cohn

Publications and source records attributed to J N Cohn.

At least 343 records · Page 19Linked to original sources
PubMed1978

Hemodynamic effects of trimazosin in patients with left ventricular failure.

Trimazosin is a new quinazoline derivative vasodilator previously thought to act primarily on resistance vessels. Vasodilators characteristically improve hemodynamics in patients with left ventricular failure. Trimazosin in single oral doses of 100 to 300 mg was given to 6 patients with class III-IV congestive heart failure due to ischemic or primary cardiomyopathy and hemodynamics were monitored for 4 hr. Onset of action was apparent at 1 hr, with peak effects occurring at 1 to 3 hr and significant effects persisting at 4 hr. At peak, mean systemic arterial pressure fell from 91.2 +/- 4.8 (SEM) to 82.5 +/- 2.5 mm Hg (p less than 0.05), heart rate was unchanged, and cardiac index (by dye dilution) was up to 2.12 +/- 0.27 from 1.76 +/- 0.33 L/min/m2 (NS). Right heart pressures (by Swan-Ganz catheterization) were reduced, right atrial, 11.3 +/- 2.1 to 8.7 +/- 1.6 mm Hg (p less than 0.02), mean pulmonary arterial pressure, 40.7 +/- 4.6 to 33.8 +/- 4.8 mm Hg (p less than 0.01), and pulmonary arterial wedge, 30.7 +/- 4.5 to 23.8 +/- 5.0 mm Hg (p less than 0.01). Forearm venous capacitance, by occlusion plethysmography, increased from 0.83 +/- 0.18 ml/100 gm to 1.12 +/- 0.22 ml/100 gm after trimazosin (p less than 0.01). Trimazosin is an orally effective vasodilator that acts on both resistance and capacitance vessels in patients with congestive heart failure.

Aged↗
PubMed1978

Hemodynamic responsiveness to short- and long-acting vasodilators in left ventricular failure.

Vasodilators acutely reduce afterload and improve hemodynamics in congestive heart failure. Intravenous nitroprusside reduces left ventricular filling pressure and increases cardiac output while modestly reducing blood pressure and not changing heart rate in patients with heart failure in whom this response is characteristic. Comparably reduced blood pressure during nitroprusside infusion in normal subjects or hypertensive patients without failure results in a decrease in cardiac output and tachycardia. Long-acting vasodilators are also effective in patients with congestive heart failure. Nitrates, predominant venodilators, decrease left ventricular filling pressure as much as nitroprusside does, but increase cardiac output less. Hydralazine, an arterial dilator, increases cardiac output similarly to nitroprusside but decreases filling pressure less. Combining hydralazine with nitrates results in hemodynamic effects almost identical to those of nitroprusside. The quinazoline derivatives, trimazosin and prazosin, are also effective vasodilators, which act on both arteries and veins in patients with congestive heart failure. The hemodynamic response to vasodilators is influenced by the underlying hemodynamic status, as the change in cardiac output is directly related to base line ventricular filling pressure as well as systemic vascular resistance, and inversely related to the base line cardiac output. Response to vasodilators does not appear to be altered by age, diabetes, acute myocardial infarction or the cause of congestive myocardiopathy.

Blood Pressure↗
PubMed1978

Selection of vasodilator, inotropic or combined therapy for the management of heart failure.

Vasodilator and inotropic drugs work through independent mechanisms in augmenting left ventricular pump function in patients with heart failure. The selection between these two classes of pharmacologic agents for an individual patient may be based on the control blood pressure as well as the underlying disease. Although vasodilator drugs are easiest and safest to employ in patients with normal or high arterial presure levels, even in relatively hypotensive subjects (systolic arterial pressure less than 105 mm Hg), a salutary hemodynamic effect can be achieved without an undue decrease in pressure. Inotropic drugs may be safest to administer to patients without coronary artery disease, but the oxygen-consuming effect of these drugs need not necessarily have an adverse effect on patients with ischemic heart disease. Combined vasodilator and inotropic drug therapy is the most potent pharmacologic means of restoring pump function in patients with severe heart failure. The long-term use of vasodilator and inotropic drugs in the treatment of heart failure is dependent on the availability of agents that will produce a sustained hemodynamic effect. Hydralazine, nitrates and prazosin have been employed alone or in combination and provide a promising approach to vasodilator treatment of heart failure. Better and more selective oral inotropic agents are needed to allow this therapeutic modality to be employed optimally.

Blood Pressure↗
PubMed1978

Comparative haemodynamic and metabolic effects of vasodilator and inotropic agents in experimental myocardial infarction.

Following coronary embolisation and onset of left ventricular failure 27 awake dogs were randomly assigned to infusion of saline (controls), nitroprusside, or dobutamine (a new inotropic agent). Nitroprusside and dobutamine both increased cardiac output and lowered left ventricular filling pressure while raising coronary sinus flow. Dobutamine, however, increased myocardial oxygen consumption whereas nitroprusside reduced it. Therefore vasidilators may be more beneficial than inotropic agents in acute myocardial infarction.

Animals↗
PubMed1978

Left and right ventricular dimensions during ventricular fibrillation in the dog.

Ventricular dimensions by surface echocardiography and intraventricular pressures were monitored in 27 dogs before and during ventricular fibrillation (VF) induced by coronary embolization (nine dogs), potassium infusion (nine dogs) and calcium infusion (nine dogs). Left ventricular diameter (LVD) fell by an average of 10.3 mm during the first 30 s after the onset of VF induced by ischemia or potassium and remained smaller than the prefibrillation end-diastolic LVD during the ensuing 10 min. LVD fell during calcium infusion, and after the onset of VF it remained only slightly larger than the preinfusion end-systolic LVD. Right ventricular (RV) diameter increased progressively for the first 2 min during VF an average of 15.9 mm. The failure of LV size to increase during VF was explained by a pressure gradient inhibiting LV filling during the early phase of VF. Despite progressive RV filling, pressure in the more compliant RV remained lower than in the LV, which exhibited reduced compliance during VF. Therefore, cardiac dilation during VF appears to be confined to the RV, and inhibition to LV filling is an important feature of the syndrome.

Animals↗
PubMed1978

Early redistribution of thallium-201 after temporary ischemia.

To define the time course of redistribution of thallium-201 (201Tl), ischemia was induced in seven pigs by temporary occlusion of the circumflex coronary artery. After 1 1/2 min of occlusion 201Tl and labeled microspheres were injected into the left atrium. Flow was re-established 4 min after occlusion. Prior to reflow, the relative activities of 201Tl and microspheres in the ischemic area were similar, but as early as 5 min after reflow the relative 201Tl activity was considerably higher than the relative microsphere activity and from 15 to 105 min after reflow, relative 201Tl activity (averabe 69% of that in normal myocardium) continued to be higher than relative microsphere activity (average 6% of normal). Myocardial arteriovenous differences for 201Tl were followed sequentially after 201Tl injection in normal dogs and in dogs with temporary coronary occlusions. The results suggested both loss of 201Tl from normal myocardium beginning 10 min after 201Tl injection and increased extraction of 201Tl from the blood pool immediately after release of a transient occlusion. Redistribution of 201Tl therefore begins very soon after relief of myocardial ischemia and even a short delay in initiating myocardial imaging may decrease the sensitivity of the technique for detecting transient ischemia.

Animals↗
PubMed1978

Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure.

In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2--39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 +/- 1.3 (SEM) to 20.3 +/- 1.4 mm Hg (P less than 0.001), CO rose from 3.94 +/- 0.23 to 4.75 +/- 0.31 l/min (P less than 0.001), MAP fell from 87.5 +/- 3.8 to 77.9 +/- 4.1 mm Hg (P less than 0.001) and SVR from 1619 +/- 148 to 1252 +/- 137 dyne-sec-cm-5 (P less than 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 +/- 3.4 to 37.9 +/- 7.7 ng/ml/hr, P less than 0.05) but plasma norepinephrine fell (619.1 +/- 103.6 to 449.7 +/- 75.7, P less than 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.

Adult↗
PubMed1978

Myocardial damage after repetitive direct current shock in the dog: correlation between left ventricular end-diastolic pressure and extent of myocardial necrosis.

Acute myocardial necrosis was produced in 27 anesthetized dogs by repetitive DC 75 joule shock delivered with one electrode in the left ventricular cavity and the other on the left chest wall. A total of 1 shock/kg body weight delivered at 10 sec intervals resulted in discrete anterior wall necrosis of 7% to 31% (mean, 17.6%) of the mass of left ventricular myocardium. After some transient bradycardia, normal sinus rhythm was restored. Depression of left ventricular function 15 min after shock (rise in LVEDP from 4.0 +/- 1.5 to 17 +/- 2 mm Hg and fall in cardiac output from 2.29 +/- 0.24 to 1.82 +/- 0.12 L/min) recovered only slightly during the ensuing 2 hr. A significant correlation (r=0.85) was observed between the LVEDP at 2 hr after shock and the extent of necrosis determined histochemically and histologically at the time of sacrifice 3 hr after shock. Thus, in this form of acute myocardial damage, pump dysfunction is closely related to the area of necrosis.

Animals↗
PubMed1977

Heart disease in the hypertensive patient.

Uncontrolled hypertension increases the workload of the left ventricle causing the development of hypertrophy and an increase in myocardial oxygen consumption that may precipitate ischemia because of inadequate oxygen delivery related to accelerated coronary atherosclerosis. Control of the hypertension should prevent the further development of hypertrophy, delay the development of fibrosis and possibly also slow the rate of development of atherosclerosis. Furthermore, when myocardial function is impaired because of hypertrophy or other myocardial diseases, the level of blood pressure becomes an important determinant of left ventricular performance. Regardless of the level of arterial pressure, vasodilator drugs that lower arterial pressure may result in marked improvement in left ventricular performance and relief of symptoms of left ventricular failure. Therefore, control of blood pressure in the presence of heart disease may involve treatment of normotensive patients to bring them into a lower normotensive range as well as the more traditional treatment of hypertensives to bring them into the normotensive range. Although this scenario is consistent with conventional wisdom and clinical experience, intricacies of the relationship between hypertension, hypertrophy, myocardial oxygen delivery, atherosclerosis and intramyocardial blood flow distribution remain poorly understood. Until these aspects of the natural history of heart disease are better worked out therapy will remain largely empirical.

Cardiomegaly↗
PubMed1977

Evaluation of early myocardial ischemia with thallium-201 in the pig.

Thallium-201 was found to be a reliable agent for detecting decreased myocardial perfusion in domestic pigs 1-4 hours after acute coronary occlusion. Substantial variation in myocardial-to-liver count ratios and diagnostic quality was observed in serial images performed in 3 normal pigs, although areas of 1-4 hours-old myocardial ischemia produced by acute circumflex coronary artery ligation in 6 pigs could be reliably detected by in vivo 201Ti imaging. After intravenous 201Ti administration, the animals were sacrificed and sections of normal and ischemic myocardium were counted in a scintillation well counter. The activity in the ischemic area in pigs averaged 12% of the activity in the normal area, and varied over a narrow range; in dogs the activity averaged 62% of normal, and varied over a wide range. The pig was a more consistent model than the dog.

Animals↗
PubMed1977

Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects.

Labetalol was administered to six hypertensive subjects in increasing doses for seven days. A decrease in both supine and standing arterial pressure and heart rate was observed with no change in cardiac output and few side effects. Exercise tolerance was unaltered by the drug, but the heart rate and arterial pressure response to exercise were significantly blunted. The infusion rate of isoproterenol required to produce tachycardia was increased sevenfold by 800 mg/day labetalol and tenfold by 1600 mg/day. More than twice the control dose of phenylephrine was required during labetalol therapy to produce a rise in diastolic arterial pressure reflex tachycardia to amyl nitrite-induced hypotension was attenuated. These studies indingina pectoris.

Adrenergic alpha-Antagonists↗
PubMed1977

Serial serum creatine phosphokinase MB isoenzyme activity after myocardial infarction. Studies in the baboon and man.

Serum CPK-MB iosenzyme activity was measured serially after mercury embolization of the left circumflex coronary artery in five baboons and after clinical acute myocardial infarction (AMI) in 20 patients. The calculated amount of enzyme released into the baboons' circulation (CPK-MBR) correlated well (r = 0.991) with the amount of MB isoenzyme depleted from the myocardium (CPK-MBD) when a previously determined decay constant (Kd) was used, but not when Kd was calculated from individual curves or when CPK-MM values were used. In clinical AMI, CPK-MMR averaged 97% (0 to 350%) greater than CPK-MBR, probably because of release of MM isoenzyme from nonmyocardial sources. The mean Kd for CPK-MB in patients (0.0012 min-1) was significantly (P less than 0.01) lower than that obtained in the baboon following bolus injections (0.0018 min-1), probably reflecting delayed myocardial release of enzyme. Therefore, in both experimental and clinical AMI, serial samples for CPK-MB activity, but not total or CPK-MM activity, could provide an accurate index of myocardial enzyme depletion.

Animals↗
PubMed1977

Comparative hemodynamic effects of inotropic and vasodilator drugs in severe heart failure.

In 12 patients with severe congestive heart failure (CHF) due to ischemic heart disease or nonischemic cardiomyopathy the hemodynamic response to intravenous infusion of sodium nitroprusside (N) was compared to that of dobutamine (D) 10 microgram/kg/min. D and N produced comparable increases in cardiac output (CO) (2.8 to 5.8 L/min and 2.9 to 5.0 L/min, respectively), but, compared to N, D caused a higher arterial pressure (99.3 vs 86.2 mm Hg, P less than 0.01) and heart rate (102.5 vs 95.3, P less than 0.05) and less reduction in pulmonary wedge pressure (PWP) (28.9 to 20.2 mm Hg vs 29.1 to 16.6 mm Hg, P less than 0.05). In five additional patients N and D were studied separately and then were infused together. The combination resulted in a higher CO, lower PWP and greater reduction in systemic and pulmonary vascular resistances than either drug alone. Brachial arterial infusion of nitroprusside produced prominent forearm vasodilation in a dose less than 10% of the systemic dose, whereas vasodilation with dobutamine was only modest even when 50% of the systemic dose was infused. Therefore, potent inotropic and vasodilator drugs produce similar and additive augmentation to left ventricular performance in heart failure. Reduction in vascular resistance with dobutamine probably is largely of reflex origin, but the vasodilation itself may be an important determinant of the rise in cardiac output.

Blood Pressure↗