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Biomedical subjects

N S Dhalla

Publications and source records attributed to N S Dhalla.

At least 271 records · Page 15Linked to original sources
PubMed1980

Subcellular Ca2+ transport in different areas of dog heart.

Calcium transport and ATPase activities were determined in the heavy and mitochondrial fractions isolated from the left and right atria as well as ventricles of dogs. Ultrastructural distribution of these organelles in different areas of the myocardium was also examined. Calcium binding, calcium uptake, and calcium ATPase activities of the atrial microsomes were lower than those of the ventricles. On the other hand, mitochondrial calcium binding and uptake activities in the right atrium were higher than those in other areas. The mitochondrial total ATPase activities in the atria were also higher than those in the ventricles. Mitochondrial as well as microsomal yields from ventricles were significantly higher. Size and number of mitochondria in the ventricles were greater whereas no striking difference in the distribution of sarcoplasmic reticulum was apparent in different areas of the heart. Poorly developed calcium transport functions in the atrial microsomes may be one of the factors responsible for the generation of lower contractile force in this tissue in comparison with the ventricle.

Adenosine Triphosphatases↗
PubMed1980

Contractile failure and recovery in rat hearts perfused with Na+- or K+-free medium.

Ca2+ or K+ concentrations during Na+-free perfusion and Ca2+ or Na+ concentrations during K+-free perfusion were varied and the effects on the contractile force were recorded during failure as well as recovery of the hearts. The initial positive inotropic effect of zero Na+ was directly related to the Ca2+ or K+ concentration of the medium. Time time of failure was not affected by changes in Ca2+ concentrations of the Na+-free medium whereas lowering of K+ concentration prolonged the time of failure. The initial negative inotropic effect of perfusion with zero K+ was increased by low Ca2+ and was changed to a positive effect by high Ca2+; the time of failure was inversely related to the Ca2+ concentration. Lowering of Na+ in zero K+ medium caused fibrillation of the heart. The recovery upon reperfusion with control medium of Na+-deprived hearts was improved by a reduction in Ca2+ concentration during Na+-free perfusion and was adversely affected by increased Ca2+. Increases or decreases in K+ during Na+-free perfusion reduced recovery. The length of the fibrillation period was affected in a characteristic manner by changes in Ca2+ or K+ concentrations. The recovery of the K+-deprived hearts was also influenced by changes in Ca2+ or Na+ concentrations during K+-free perfusion. In addition to altering the electrical properties of the myocardium, the early effect of Na+ or K+ lack appears to be on the Ca2+ movements across the sarcolemma and this is followed by the intracellular Ca2+ overload. The study emphasizes the importance of a proper balance between the Na+, K+, and Ca2+ concentrations for normal functioning of the heart.

Animals↗
PubMed1980

Subcellular calcium transport during contractile failure and recovery in heart perfused with Na-free medium.

Perfusion of isolated rat hearts with Na-free medium resulted in an immediate increase in contractile force followed by a decline and complete loss of contractile force within 25 s. The recovery of the contractile force upon reperfusion was only partial if the duration of Na-free perfusions was 10 min or longer. Ca binding and uptake activities of mitochondria obtained from hearts perfused with Na-free medium did not change significantly. However, Ca binding and uptake activities of microsomes were depressed after 5 min of perfusion. The critical concentration of Na in the perfusion medium for inducing these changes was found to be less than 35 mM. The microsomal Ca-ATPase activity was decreased after 10 min of Na-free perfusion. Only partial recovery of microsomal Ca uptake was observed upon reperfusion of hearts preperfused with Na-free medium for 20 min or longer whereas Ca-ATPase activity in these hearts did not recover at all. These results suggest that the defect in the microsomal Ca transport may be secondary to the development of contractile failure and may partially be associated with the inability of Na-depleted hearts to recover fully their contractile force.

Adenosine Triphosphatases↗
PubMed1980

Cardiac effects of beta-adrenergic receptor antagonists: beta-moderators versus beta-blockers.

Two adrenergic receptor antagonists, acebutolol and propranolol, were observed to depress rabbit heart contractile force and adrenaline-stimulated adenylate cyclase activity at 1 X 10-(5) to 1 X 10-(3) M and 1 X 10-(6) to 1 X 10-(3) M concentrations, respectively. Acebutolol depressed sarcoplasmic reticular and mitochondrial calcium uptake at 5 X 10-(3) to 10-(2) M concentrations. On the other hand, propranolol was found to decrease calcium uptake activities of sarcoplasmic reticular and mitochondrial fractions at 1 X 10-(4) to 1 X 10-(2) M and 1 X 10-(3) to 1 X 10-(2) M concentrations, respectively. On the basis of these results with calcium transport systems, it is proposed that beta-antagonists with a mild depressant effect, such as acebutolol, may be called beta-moderators, whereas those with a strong effect, such as propranolol, may be called beta-blockers.

Acebutolol↗
PubMed1980

Species-related difference in the heart sarcolemmal enzyme activities.

The sarcolemmal membranes were isolated by the hypotonic shock-LiBr treatment method from rat, guinea pig, rabbit, and dog hearts and their various biochemical activities were measured. The Mg2+-ATPase, Ca2+-ATPase, and 5'-nucleotidase were most active in rat heart homogenates as well as sarcolemmal membranes, whereas the adenylate cyclase and Na+, K+-ATPase were most active in guinea pig heart preparations. ATP-independent calcium binding activity of rat heart sarcolemma was the same as that of guinea pig heart membrane, whereas ATP-dependent calcium binding of rat heart preparation was negligible. Treatment of sarcolemma with 0.6 M KCl increased the adenylate cyclase and Na+, K+-ATPase activity in rat heart, but these activities were unaltered or decreased in other species. The gel electrophoretic pattern of protein bands and phospholipid composition of rat heart sarcolemma were different from those of guinea pig heart. Sarcolemma isolated from hearts by sucrose gradient method also showed species-dependent difference in the membrane-bound enzyme activities. These results have been interpreted to suggest species-related difference in calcium movements across sarcolemma and this may contribute to determining species-dependent difference in the regulation of myocardial calcium metabolism.

Adenosine Triphosphatases↗
PubMed1980

Role of catecholamines in the genesis of arrhythmias.

Catecholamines play a major role in the induction of cardiac rhythm disorders. The effects of catecholamines are caused by activation of beta-receptors in the heart and appear to be mediated by the cyclic AMP/protein kinase system. Increased rate of spontaneous diastolic depolarization of cardiac fibers on exposure to endogenous or exogenous catecholamine activity leads to tachyarrhythmias. Because of non-uniform distribution of sympathetic nerve endings, activation of the sympathetic nerve system may result in non-uniform reduction in the refractory period leading to re-entrant excitation. Under abnormal conditions myocardium may become more sensitive to catecholamines. In ischemia, sympathetic stimulation causes more local differences in refractory period and a greater tendency to fibrillate. Following acute coronary ligation there is a direct relationship between rhythm disturbance and levels of myocardial catecholamines. Catecholamines not only cause arrhythmia but also contribute to the development of digitalis-induced arrhythmias. The role of catecholamines in the genesis of certain cardiac arrhythmias is further supported by the fact that beta-blocking drugs which antagonize sympathetic activity are effective for treating various types of acute arrhythmias and for prevention of recurrent arrhythmias.

Arrhythmias, Cardiac↗
PubMed1980

Effects of dl-erythro-1-phenoxy-3-[(3,4-dimethoxyphenethyl)-amino]-butan-2-ol (PS-6) on rat heart sarcolemma.

Effects of dl-erythro-1-phenoxy-3-[(3,4-dimethoxyphenethyl)-amino]-butan-2-ol (PS-6) on ATPase and calcium binding activities of rat heart sarcolemma as well as adenylate cyclase of both sarcolemma and heart washed particles were studied under in vitro conditions. PS-6 at concentrations of 10(-7) mol/l or higher inhibited Na+-K+ ATPase and calcium binding activities significantly. The inhibition of calcium binding activity was dependent upon the concentration of calcium in the incubation medium with greater percentage inhibition seen at lower concentrations. While basal adenylate cyclase activity was not affected by 10(-7)--10(-4) mol/l, isoprenaline stimulated adenylate cyclase activity was inhibited by 10(-6) mol/l or higher concentrations of PS-6. At 10(-3) mol/l PS-6 a more generalized inhibitory effect was seen, with all parameters studied being inhibited. These results suggest that sarcolemma is one of the sites for the cardiac actions of PS-6.

Adenosine Triphosphatases↗
PubMed1980

Effects of adrenochrome on calcium accumulating and adenosine triphosphatase activities of the rat heart microsomes.

The influence of adrenochrome (1-100 microgram/ml or 5.6 x 10(-6)-5.4 x 10(-4) M) on microsomal calcium binding, calcium uptake and Ca++-stimulated Mg++-dependent adenosine triphosphatase (ATPase) activities was studied in vitro. Adrenochrome decreased microsomal calcium binding, calcium uptake and Ca++-stimulated Mg++-dependent ATPase activities. The inhibitory effect of adrenochrome on microsomal calcium uptake activity of the isolated membrane was independent of pH (6.0-8.0), calcium concentrations (10-200 muM), protein concentration (0.02-0.10 mg/ml), temperature (25-37 degrees C) and incubation time (2-30 min). Kinetic study of calcium uptake activity in different concentrations of ATP showed that the inhibition was of a mixed type. Perfusion of hearts with adrenochrome resulted in marked depression in contractile force and the microsomal fraction obtained from these hearts showed depressed calcium binding, calcium uptake and Ca++-stimulated Mg++-dependent ATPase activities. The depression in microsomal The influence of adrenochrome (1-100 microgram/ml or 5.6 x 10(-6)-an irreversible nature. It is proposed that cardiodepressant action of adrenochrome may partly be explained on the basis of its inhibitory effect on the calcium transporting ability of the sarcoplasmic reticulum.

Adrenochrome↗
PubMed1980

Structure-function relationship in heart sarcolemma.

Dependence on the membrane lipids of sarcolemmal structure as well as functions was examined by incubating isolated rat heart sarcolemma with phospholipase A, C, or D. Conventional as well as negatively stained electron microscope preparations of the treated membranes revealed structural changes. Ca2+ binding and Na+, K+-ATPase activity were depressed following treatment of the membranes with any of the phospholipases whereas Ca2+-ATPase activity was not affected. Adenylate cyclase activity was increased by low concentration (25 micrograms/mg of protein) of phospholipase A, and a definite inhibition of the enzyme was noticed when the concentration of the phospholipase A was increased to 250 micrograms/mg of protein. Phospholipases C and D had no significant effect on the adenylate cyclase activity. Percentage of phospholipids hydrolyzed was more after phospholipase A treatments. These results provide evidence regarding the involvement of lipids in the membrane structure and functions.

Animals↗
PubMed1980

Changes in contractile function and endogenous fuel supply in rat heart upon perfusion with substrate-free medium.

Isolated rat hearts were perfused with aerobic substrate-free medium for different intervals during which changes in functional and metabolic events were examined. The contractile force was maintained for 30 min but thereafter declined toward zero over a period of 90 min. Before the onset of contractile failure, glycogen decreased by 60% of the control value, various intermediates of glycolytic flux, hexosephosphates, and triosephosphates, except dihydroxyacetone phosphate, reached their lowest level, and hydration of the myocardium became maximal. Furthermore, the phosphate potential, creatine phosphate (CrP), ATP, and oxygen consumption decreased by 60%, 45%, 10%, and 18%, respectively, before the onset of contractile failure. A progressive decrease in citrate, isocitrate, alpha-ketoglutarate, and malate was observed during a 2-hr perfusion period, but a slight increase in the levels of oxaloacetate and acetyl-CoA was apparent at 30 and 60 min, respectively. The early phase of contractile failure (30-60 min) was associated with an increase in the free fatty acid (FFA) and AMP levels, whereas the late phase (90-120 min) was characterized by an increase in resting tension and a decrease in oxygen consumption. The complete failure of the heart to generate contractile force at 120 min of perfusion occurred when about 40% of the glycogen and ATP contents and about 25% of the creatine phosphate and triglyceride contents were still present. Therefore, contractile failure of the hearts perfused with substrate-free medium may be caused by an insufficiency of the mechanisms responsible for the mobilization of endogenous glycogen and triglycerides as well as for the generation and utilization of ATP.

Acetyl Coenzyme A↗
PubMed1980

Calcium paradox. Dependence of reperfusion-induced changes on the extracellular calcium concentration.

The effects of different extracellular calcium concentrations on the changes in myocardial Ca2+ content ([Ca2+]m), ultrastructure, and contractile force (CF) associated with the calcium paradox phenomenon were examined in isolated perfused rat hearts. In the first series of experiments, the hearts were perfused for 5 min with various calcium concentrations (0, 0.025, 0.05, 0.1, 0.25, 0.5, 1.25 mM) followed by 5 min of reperfusion with normal medium (1.25 mM Ca2+). Reperfusion-induced changes in the above parameters were prevented if the calcium concentration was 0.1 mM or higher. Reducing the calcium concentration to 0.05 mM or less resulted in an increase in [Ca2+]m and partial or no recovery of CF upon reperfusion. In the second series of experiments, hearts perfused for 5 min with Ca2+-free medium were reperfused for 5 min with different calcium concentrations (0.025, 0.05, 0.1, 0.25, 0.5, 1.0, 1.25, 2.5, 4.0 mM). Reperfusion-induced increases in [Ca2+]m, the degree of contracture, and ultrastructural damage were dependent upon the external calcium concentration. A sevenfold increase in [Ca2+]m, loss of cell-to-cell contacts, disruption and loss of mitochondria, and poor definition of A and I bands were observed after reperfusion with 4 mM Ca2+. The changes observed appear to be associated with the extent of calcium overload and are related to the extracellular calcium concentration.

Animals↗
PubMed1980

Protection against adrenochrome-induced myocardial damage by various pharmacological interventions.

Perfusion of the isolated rat heart with Krebs-Henseleit solution containing adrenochrome (25 or 50 mg/l), and oxidation product of catechalmines, resulted in contractile failure and myocardial necrosis. Various pharmacological agents known to protect the myocardium against catecholamine-induced necrosis were also found to be effective against adrenochrome-induced changes in the ultrastructure of the isolated perfused rat heart. The alpha-receptor-blocking drugs tolazoline and Dibenamine (dibenzylchlorethamine), and the adrenergic neurone-blocking agents guanethidine and bretylium did not alter the development of contractile failure and necrosis due to adrenochrome. The beta-receptor-blocking compounds propranolol and practolol effectively protected the heart from adrenochrome-induced necrotic damage, and partially prevented contractile failure. The hydrazine-type monoamine oxidase inhibitor iproniazid completely prevented ultrastructural damage and partially maintained contractile-force development in adrenochrome perfused hearts. The non-hydrazine-type monoamine oxidase inhibitor tranylcypromine partially protected the isolated rat heart against adrenochrome necrosis, but disruption of mitochondrial structure was still seen. Tranylcypromine did not significantly improve contractile force development during adrenochrome perfusion. The calcium antagonist D-600 reduced the severity of adrenochrome-induced ultrastructural damage. These results provide strong support for the view that catecholamine-induced cardiotoxicity is mediated through the formation of adrenochrome.

Adrenochrome↗
PubMed1980

Modification of adrenochrome-induced cardiac contractile failure and cell damage by changes in cation concentrations.

Adrenochrome has been shown to produce cardiac necrosis as well as failure in the isolated rat hearts. These effects of adrenochrome were influenced by alterations in the Ca2+, Na+, K+, and Mg2+ concentrations of the perfusion medium. Increasing the Ca2+ or K+ concentration or decreasing the Na+ concentration of the adrenochrome-containing perfusion medium partially maintained contractile force but increased the severity of ultrastructural damage. Reducing the K+ concentration of the medium did not alter the failure of contractile force development but increased the severity of ultrastructural damage due to adrenochrome. Reducing the Ca2+ or increasing the Mg2+ concentration of the perfusion medium completely prevented myocardial necrosis due to adrenochrome. Omission of Mg2+ from the perfusion medium neither altered the time course of contractile failure nor effected the severity of necrosis due to adrenochrome. These results for the most part parallel the influence of similar ionic interventions on the severity of necrosis produced by excessive amount of catecholamines.

Adrenochrome↗
PubMed1979

Effects of some antiarrhythmic agents on dog heart mitochondrial oxidative phosphorylation.

Significant decreases in state 3 oxygen consumption, respiratory control index (RCI), ADP : O ratio and phosphorylation rate were observed in the presence of 0.1-1.0 mM quinidine; 0.5 mM or greater concentrations elevated state 4 oxygen consumption. Lidocaine (1-2.5 mM) also depressed RCI and increased state 4 oxygen consumption but procaine amide (1-2.5 mM) was without effect. It is suggested that cardiodepression by quinidine may be associated with its ability to impair mitochondrial metabolism.

Adenosine Diphosphate↗