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Biomedical subjects

Y Hasin

Publications and source records attributed to Y Hasin.

At least 109 records · Page 6Linked to original sources

Prevention of myocardial damage in acute myocardial ischemia by early treatment with intravenous streptokinase.

We evaluated the effectiveness of early intravenous administration of 750,000 units of streptokinase in 53 patients with acute myocardial ischemia treated by a mobile-care unit at home (9 patients) or in the hospital (44 patients). Treatment was begun an average (+/- S.D.) of 1.7 +/- 0.8 hours from the onset of pain. Non-Q-wave infarctions developed subsequently in eight patients, whereas all the others had typical Q-wave infarct patterns. In 81 per cent of the patients the infarct-related artery was patent at angiography performed four to nine days after admission. Vessel patency was independent of the time of treatment, but residual left ventricular function was time dependent. Patients treated less than 1.5 hours after the onset of pain had a significantly higher ejection fraction (56 +/- 15 vs. 47 +/- 14 per cent; P less than 0.05) and infarct-related regional ejection fraction (51 +/- 19 vs. 34 +/- 20 per cent; P less than 0.01) and a lower QRS score (5.6 +/- 4.9 vs. 8.6 +/- 5.5; P less than 0.01) than patients receiving treatment between 1.5 and 4 hours after the onset of pain. Patients treated earlier by the mobile-care unit also had better-preserved left ventricular function than patients treated in the hospital. We conclude that thrombolytic therapy with streptokinase is most effective if given within the first 1.5 hours after the onset of symptoms of acute myocardial infarction.

Adult↗

Systolic properties of normal and septic isolated rat hearts. The effect of branched chain amino acids.

Systolic properties and coronary flow were studied in Langendorff preparations of normal and septic rat hearts paced at 100, 200, 300, and 400 beats per minute. In addition, the effects of amino acid formulations differing in their branched chain amino acid (BCAA) concentration in normal and septic rat hearts were investigated. Our experiments demonstrated the following: in the normal isolated rat heart, Krebs plus glucose and Krebs plus glucose plus 42% BCAA are most effective in maintaining systolic properties, while Krebs plus glucose plus 15% or 100% BCAA were considerably less effective. Sepsis results in a significant decrease in the systolic properties of the isolated rat heart, and in a loss of the negative linear correlation between contractility and heart rate, probably the result of a diminishing intracellular load of contractile calcium. In the isolated septic rat heart, mechanical washout during perfusion has a beneficial effect, suggesting the presence of a myocardial depressant substance in sepsis. The use of a balanced amino acid mixture containing 42% BCAA exerts the greatest benefit in maintaining systolic properties and in improving coronary flow in the isolated septic rat heart.

Amino Acids, Branched-Chain↗

The different effects of leucine, isoleucine, and valine on systolic properties of the normal and septic isolated rat heart.

Protein turnover in cardiac and skeletal muscle is affected by the provision of amino acids, particularly the branched chain amino acids (BCAA). The effect of each of the BCAA, valine, leucine, and isoleucine, on the systolic function of isolated normal or septic rat heart perfused as a Langendorff preparation was examined. Thirty normal control and 28 septic rats (cecal ligation and puncture) were perfused with either Krebs + 8.5 mM glucose or Krebs + 5.0 mM glucose and 3.5 mM valine, leucine, or isoleucine. Septic hearts perfused with Krebs + 8.5 mM glucose exhibited developed force (DF) and force velocity (dF/dt) levels which were reduced to an average of 45 and 50%, respectively, compared to normal controls, and improved by 35% during 60 min perfusion over measurements made at time zero. In normal hearts DF and dF/dt decreased significantly during perfusion with leucine (27%) and isoleucine (20%). In sepsis, perfusion with leucine and isoleucine resulted in a mild improvement in systolic function. However, valine was far less effective than leucine and isoleucine in maintaining systolic function in sepsis, due apparently to valine being a less efficient energy substrate for the cardiac muscle in a state of severe energy deficit. Thus, valine, leucine, and isoleucine seem to exert different effects on the systolic function of normal and septic isolated rat hearts.

Amino Acids, Branched-Chain↗

Sodium pump inhibition, enhanced calcium influx via sodium-calcium exchange, and positive inotropic response in cultured heart cells.

The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydroouabain, 5 X 10(-5)M, and extracellular potassium of 1.0 mM all induced similar and prominent positive inotropic effects. These effects were accompanied, in each case, by 40-50% inhibition of the rate of active uptake of 42K and by similar increases in steady state sodium content. Stimulation of the rate of 45Ca uptake on exposure to zero extracellular sodium occurred in response to extracellular potassium (1.0 mM) or to glycoside concentrations that induced a positive inotropic effect and sodium-potassium pump inhibition. Reactivation of the sodium pump after return from 1.0 to 4.0 mM extracellular potassium was rapid and was associated with membrane hyperpolarization and slowing of spontaneous beating rate. With pump reactivation under these circumstances, the time course of disappearance of stimulation of sodium-calcium exchange on exposure to zero extracellular sodium was similar to the time course of loss of the positive inotropic effect. Under physiological conditions (4.0 mM extracellular potassium), exposure to positively inotropic but nontoxic concentrations of ouabain or dihydroouabain caused a small but consistent increase in unidirectional calcium influx, but had no discernible effect on calcium efflux. Since similar inotropic effects were produced for comparable degrees of glycoside or low extracellular potassium-induced sodium pump inhibition and increases in cellular sodium content, sodium pump inhibition rather than a glycoside-specific change in calcium binding appears to underlie the inotropic response. These findings are further consistent with the view that the primary mechanism of the positive inotropic effects of digitalis and low extracellular potassium in this experimental preparation is sodium pump inhibition resulting in increased intracellular sodium. We suggest that increased calcium influx via sodium-calcium exchange is the principal mechanism whereby increased intracellular sodium results in enhanced calcium availability to the myofibrils, but an additional effect on calcium efflux is not excluded.

Animals↗

Cytotoxic T lymphocytes and natural killer cell activity in the course of mengo virus infection of mice.

Inbred C57BL/6 mice were inoculated intraperitoneally (i.p.) with mengo virus. The activity of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells were measured during the first 22 days following infection. The CTL response began 7 days after virus inoculation, persisted for at least 22 days and was related to the dose of the virus inoculated. NK cell activity was elevated within 24 hr, reached its peak level on the fourth day and declined to normal levels on the eleventh day after exposure to the virus. These results suggest that NK cells represent the first cellular immune response to restrict mengo virus spread while specific CTL appear later and are probably responsible for further restriction, elimination and prevention of the viral disease.

Animals↗

Selective killing of carcinoma cells "in vitro" by lipophilic-cationic compounds: a cellular basis.

Lipophilic positively-charged compounds are facilitated across biological membranes by the transmembrane potential of intact cells. One such compound, rhodamine 123, has recently been shown to be selectively toxic toward a variety of transformed (carcinoma), epithelial cells in vitro (Lampidis et al., 1982; Bernal et al., 1982; Lampidis et al., 1983). A mechanism that could account for the selectivity of this agent would be a difference in the plasma membrane potential between normal and carcinoma cells. We report here that a significantly higher transmembrane potential has been found in a pair of carcinoma (83 mV for human breast and -99 mV for human cervix) as compared to normal (-56 mV for marsupial kidney and -48 mV for monkey kidney) epithelial cell lines. We also identified 3 other positively-charged lipophilic compounds, safranin 0, rhodamine 6G and tetraphenylphosphonium chloride (TPP+), which show selective toxicity toward carcinoma cells in vitro, while an uncharged lipophilic analog, rhodamine 116, does not. These data suggest that the higher plasma membrane potential of carcinoma cells may in part contribute to the preferential accumulation and selective toxicity of the lipophilic cationic compounds we have examined. An extension of this concept to an in vivo environment could lead to a class of cationic compounds which selectively exploit differences between normal and carcinoma cells.

Animals↗

Restoration and maintenance of sinus rhythm after mitral valve surgery for mitral stenosis.

The preoperative clinical, echocardiographic, hemodynamic and surgical data were studied from 40 consecutive patients with pure mitral stenosis and chronic atrial fibrillation who underwent surgical correction of mitral stenosis. After surgery, the patients had cardioversion of atrial fibrillation. The data of 24 patients who maintained sinus rhythm (SR) for more than 3 months (success group) were compared with the data of the 16 patients who failed to maintain SR for more than 3 months (failure group). The patients in the success group were younger (mean age 38 +/- 12 vs 47 +/- 13 years, p less than 0.05), had symptoms for a shorter time (3.0 +/- 4.3 vs 6.4 +/- 5.0 years, p less than 0.02) and had a smaller preoperative echocardiographic left atrial (LA) size (4.9 +/- 0.9 vs 5.5 +/- 1.0 cm, p less than 0.03). The correlation between duration of SR after cardioversion (range 0 to 12 months) and the preoperative data were examined with the use of the "all-possible-subsets-regression" software. The best subset of predictors of successful cardioversion included echocardiographic LA size, functional capacity, duration of symptoms and echocardiographic left ventricular fractional shortening. Patients with symptoms for more than 3 years and echocardiographic LA size of more than 5.2 cm had low rate of successful cardioversion; in this subset of patients, postoperative cardioversion should be avoided.

Adult↗

Two-channel ECG monitoring in the coronary care unit.

We describe the installation and clinical application of a two-channel monitoring system in the intensive coronary care unit using a single patient cable and two exchangeable ECG modules. Routine use of this system during a period of three years has shown that it has many advantages in the precise documentation and diagnosis of transient cardiac arrhythmias and for the recognition and localization of ischemic episodes.

Arrhythmias, Cardiac↗

Regional and global left ventricular function during intra-aortic balloon counterpulsation in patients with acute myocardial infarction shock.

We evaluated the improvement in hemodynamic and left ventricular (LV) function in 15 patients with acute myocardial infarction and cardiogenic shock, who were treated with intraaortic balloon counterpulsation (IABP). They were studied by flow-directed right heart catheterization and nuclear angiography. IABP decreased LV end-diastolic volume from 134 to 114 ml and LV end-systolic volume from 100 to 72 ml. LV stroke volume increased from 34 to 42 ml and cardiac output from 3.0 to 3.6 L/min. Global LV ejection fraction increased from 27.6% to 36.1%, and this was due to improvement in regional ejection fraction in ischemic areas. Pulmonary capillary wedge pressure and pulmonary blood volume decreased. Right ventricular ejection fraction also increased significantly. IABP improved LV function in acute myocardial infarction.

Adult↗

Effects of calcium flux inhibitors on contracture and calcium content during inhibition of high energy phosphate production in cultured heart cells.

The effects of inhibition of oxidative phosphorylation by 1 mM cyanide (CN) and of glycolysis by 20 mM 2-deoxyglucose (2DG) on contraction and relaxation of cultured monolayers of chick embryo heart cells were determined. Exposure to these agents first induced a gradual decline in contractility and a transient impairment of relaxation. Spontaneous beating then ceased, associated with increased relaxation, followed by a marked and prolonged contracture. This contracture was completely reversible after washout of metabolic inhibitors. The effects of calcium flux inhibitors on the time course of development of contracture were studied. Verapamil, which inhibits Ca influx via the slow Ca channel, delayed the onset of contracture when used in pretreatment, but had no effect if added to cultures after exposure to CN + 2DG. Lanthanum, which inhibits Ca influx both via the slow Ca channel and via Na-Ca exchange, delayed onset of contracture if added after exposure to CN and 2DG, but accelerated contracture if added prior to treatment with CN + 2DG. Cellular exchangeable calcium content, measured after exposure to CN and 2DG for the same time period that produced contracture, was reduced compared to the control level while unidirectional Ca influx rate was not measurably altered. Exchangeable Ca content was unaffected by pretreatment with verapamil and La, but was reduced if cells were exposed to La after metabolic inhibition. These findings suggest that after metabolic inhibition intracellular storage capacity for Ca+ is reduced in cultured heart cells. Ca influx via the slow Ca channel after metabolic inhibition does not appear to contribute to development of contracture in this model system. However, Ca entry via Na-Ca exchange may accelerate cellular contracture developing after metabolic inhibition of ATP production.

Adenosine Triphosphate↗

Electrophysiologic and mechanical effects of metabolic inhibition of high-energy phosphate production in cultured chick embryo ventricular cells.

The early electrophysiological and mechanical effects of metabolic inhibition of high energy phosphate production were studied in cultured chick embryo heart cells. Selective inhibition of either glycolysis by 2-deoxyglucose in the presence of acetate or of oxidative phosphorylation by cyanide showed different effects. 2-deoxyglucose induced pronounced reduction in maximal diastolic potential and prolongation of excitation contraction delay, with only a moderate decrease of contractility and with only minimal changes in action potential duration. Cyanide, on the other hand, induced a profound negative inotropic effect and caused slowing of relaxation, shortening of action potential duration, a decrease in the upstroke of the action potential, and only a moderate decrease in the diastolic membrane potential. Exposure to 2-deoxyglucose and cyanide combined produced effects consistent with inhibition of both metabolic pathways. These observations are consistent with the hypothesis that these two metabolic pathways may have specific roles in fueling several energy-demanding functions of the myocardial cell.

Adenosine Triphosphate↗

Myocardial metabolic inhibition and membrane potential, contraction, and potassium uptake.

Interruption of synthesis of ATP during hypoxia or ischemia can produce membrane depolarization that may be related to inhibition of Na+-K+-ATPase. To examine this hypothesis, the effects of exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN), to 20 mM 2-deoxy-D-glucose (2-DG), to CN + 2-DG, and to ouabain (10(-3) M) on contraction, membrane potential, and 42K uptake were determined. CN produced moderate membrane depolarization and electromechanical uncoupling within 2 min. 2-DG caused marked membrane depolarization with a transient negative inotropic effect. Exposure to CN + 2-DG produced marked depolarization (-38 mV) and mechanical arrest of the cells in a relaxed state. Ouabain produced marked depolarization (-39 mV) and contracture of the cells. Uptake of 42K was inhibited by 10(-3) M ouabain within seconds. However, CN + 2-DG produced no inhibition of 42K uptake within the first 2 min of exposure, and inhibition of the Na pump by CN + 2-DG required 30 min to develop fully. Exposure to CN alone produced no inhibition of 42K uptake, whereas moderate inhibition was produced by 2-DG alone even when substrate for oxidative phosphorylation was provided. We conclude that the acute effects of inhibition of glycolysis and oxidative phosphorylation on membrane potential and contraction in these cells are not due to inhibition of the Na pump and that during partial metabolic inhibition active univalent cation transport in these cells is relatively dependent on ATP derived from glycolysis, whereas contraction is more dependent on ATP supplied by oxidative phosphorylation.

Animals↗

Verapamil in ventricular tachycardia.

We compared the effects of verapamil to high dose procainamide on the rate of inducible and spontaneously occurring ventricular tachycardia (VT) in 10 patients. Verapamil induced a significant increase in the rate of tachycardia (R-R interval decreased from 278 +/- 54 to 233 +/- 32 ms, mean +/- SD; p less than 0.025 by paired t test) while procainamide slowed the tachycardia (mean R-R interval was 328 +/- 72 ms, p less than 0.02). Verapamil prevented the induction of sustained VT and was effective as chronic oral antiarrhythmic therapy in 2 patients. The accelerated VT culminated in ventricular fibrillation in 1 patient. It is assumed that verapamil may have either increased conduction velocity or shortened the reentrant cycle. This may be related either to a primary effect of the drug or secondary to increased catecholamine stimulation due to a vasodilatory effect.

Adolescent↗

Acute electrocardiographic changes induced by amsacrine.

The ECG effect of amsacrine (m-AMSA) was evaluated in 12 consecutive patients with leukemia. m-AMSA induced a significant prolongation of the Q-T interval (msecs, mean +/- SE) before (448 +/- 13) and 1 hour after (512 +/- 12) treatment (P . 0.0001, paired t test), without concomitant changes in the P-R interval, QRS duration, and heart rate. This selective cardiotoxic effect appeared to be transient and was noted towards the end of the iv drug administration, but was not present 24 hours later. No cardiac arrhythmias were noted during continuous monitoring. Nevertheless, it is assumed that the prolongation of the Q-T interval may represent a state of increased vulnerability to rhythm disturbances. Special care should be taken to avoid factors that may prolong the Q-T interval (hypokalemia, ischemia, or premedication with phenothiazine) during the administration of m-AMSA.

Acute Disease↗

Acute myocardial infarction with normal coronary arteriogram after mantle field radiation therapy for Hodgkin's disease.

A case of an acute myocardial infarction occurring in a 19-year-old woman, 27 months after mantle radiotherapy for Stage II-A Hodgkin's disease is described. The coronary arteriogram demonstrated patent and normal coronary arteries, but the echocardiogram revealed pericarditis. The clinical course was further complicated by variant type of angina pectoris which could not be prevented by treatment with vasodilators, but subsided promptly to corticosteroid therapy. It is suggested that radiation induced pericarditis triggered coronary vasospasm leading to the myocardial infarction and to variant angina pectoris.

Adolescent↗