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Biomedical subjects

N S Dhalla

Publications and source records attributed to N S Dhalla.

At least 307 records · Page 17Linked to original sources
PubMed1977

Calcium-linked changes in myocardial metabolism in the isolated perfused rat heart.

Rat hearts were perfused for 40 min with aerobic medium containing different concentrations of calcium (0-5 mM) and their abilities to take up and oxidize glucose, and to produce lactate and glycerol were examined in addition to measuring glycogen, lipids, cyclic AMP, and high energy phosphate stores. Increasing the concentration of calcium was found to decrease myocardial glycogen but increase glucose uptake, glucose oxidation, and lactate release. A decrease in myocardial triglycerides and an increase in free fatty acid contents as well as glycerol release without any changes in cholesterol and phospholipid contents were observed upon increasing the concentration of external calcium. In comparison with the hearts perfused with Ca2+-free medium, the levels of creatine phosphate and ATP were lower and that of ADP higher in hearts perfused with medium containing 5 mM calcium. No differences in AMP and cyclic AMP contents were seen among hearts perfused with different concentrations of calcium. The contractile activity initially increased upon increasing the concentration of calcium from 1.25 to 5 mM and then declined towards the control level. The hearts were unable to generate contractile force in the absence of calcium, whereas the contractile force decreased and then began to recover upon perfusing the hearts with 0.31 mM calcium. These results indicate that elevated levels of intracellular calcium stimulate glycogenolytic, glycolytic, and lipolytic processes in myocardium directly.

Adenine Nucleotides↗
PubMed1976

Alterations in myocardial function during bacterial infective cardiomyopathy.

The status of myocardial function in rabbits subjected to cardiac catheterization and infection with Streptococcus viridans was assessed at 3 and 6 days. Sham-operated control animals as well as uninfected catheterized animals were used for comparison. Although left heart hypertrophy and interstitial edema were evident in both uninfected and infected animals, the infected animals exhibited in addition mononuclear cell infiltration and muscle degeneration as well as lung congestion and accumulation of pleural fluid. Both uninfected and infected animals has elevated levels of serum creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase as well as electrocardiographic abnormalities such as increased amplitude of the ORS complex and flattening or inversion of the T wave. Unlike findings in the uninfected animals, the serum calcium, magnesium and sodium levels were slightly but significantly decreased and serum potassium levels were increased in the infected rabbits. Both heart rate and pulse pressure were higher in 6 day uninfected and 3 day infected animals whereas 6 day infected animals showed a decrease in heart rate. In comparison to the sham-operated control rabbits and the uninfected animals, the infected animals exhibited depression in the rates of left ventricular pressure development and relaxation as well as prolongation in time for half relaxation in situ. Relative maximal contractile element velocity extrapolated from intraventricular pressure-velocity curves was decreased by 24, 52 and 76 percent, respectively, of control values in the uninfected hearts and those with 3 and 6 days of infection. The isolated perfused hearts from infected animals also generated less contractile force and showed a decrease in the rates of contraction and relaxation, but half-relaxation time was increased. These results demonstrate myocardial dysfunction during experimental bacterial endocarditis and provide evidence that infective cardiomyopathy is associated with heart failure.

Alkaline Phosphatase↗
PubMed1976

Comparison of heart sarcolemmal enzyme activities in normal and cardiomyopathic (UM-X7.1) hamsters.

1. The activities of some membrane-bound enzymes such as adenylate cyclase, Na+ + K+-stimulated adenosine triphosphatase (Na+ + K+-ATPase), Ca2+-stimulated ATPase and Mg2+-stimulated ATPase were examined in heart sarcolemmal fractions from control and cardiomyopathic hamsters at different stages of heart failure. 2. The basal adenylate cyclase activity in sarcolemma from cardiomyopathic animals with early, moderate and late stages of heart failure was not different from the control values whereas the sodium fluoride- and catecholamine-stimulated adenylate cyclase activities were depressed in cardiomyopathic sarcolemma at moderate and late stages. 3. The sarcolemmal Na+ + K+-ATPase activity was decreased and the non-specific phosphatase activity was increased at early, moderate and late stages of heart failure. 4. The sarcolemmal Ca2+-ATPase activity was decreased at moderate and late stages whereas the Mg2+-ATPase activity was decreased at the late stages of heart failure only. 5. A marked decrease was found in calcium binding by heart sarcolemma from cardiomyopathic hamsters at late stages of failure. 6. These results suggest that dramatic sarcolemmal changes are associated with heart failure, and support the view that membrane abnormalities play a crucial role in the development of myocardial dysfunction, cyclase, calcium binding, heart failure, heart membranes, sarcolemmal enzymes.

Adenosine Triphosphatases↗
PubMed1976

Calcium binding and ATPase activities of heart sarcolemma.

Rat heart sarcolemma prepared by the hypotonic shock-LiBr treatment method was found to bind calcium by a concentration-dependent and saturable process. The calcium binding values at 50 muM and 1.25 mM Ca2+ concentrations were about 30 and 250 nmoles/mg protein, respectively. Both Mg2+ and ATP inhibited calcium binding and no evidence for energy-linked calcium binding with sarcolemmn was found. z sn the other hand, maximal ATP hydrolysis by heart sarcolemma was seen at 4 mM Mg2+ or Ca2+. The Ca2+-ATPase LEO) of Ca2+ failed to stimulate ATP hydrolysis in the presence of various concentrations of Mg-ATP. These results indicate the absence of a "calcium pump" mechanism in the heart sarcolemmal membrane preparation employed in this study.

Adenosine Triphosphatases↗
PubMed1976

Comparison of the actions of acebutolol, practolol and propranolol on calcium transport by heart microsomes and mitochondria.

1 The effects of acebutolol, practolol and propranolol (0,5-3 mM) on calcium uptake, calcium binding and ATPase activities of the rabbit and rat heart microsomal and mitochondrial fractions were investigated. 2 Dose-response and time course experiments revealed that propranolol greatly inhibited microsomal and mitochondrial calcium uptake whereas both acebutolol and practolol showed slight depressant effects. 3 The ATPase activities of microsomal and mitochondrial fractions were decreased by acebutolol, practolol and propranolol; however, the latter agent was more effective than the other two. 4 The inhibitory effects of acebutolol, practolol and propranolol on mitochondria and microsomes were not antagonized by adrenaline. 5 Propranolol decreased calcium binding by the microsomal fraction only, whereas acebutolol and practolol had no effect on microsomal or mitochondrial calcium binding. 6 The sensitivity of the rabbit heart subcellular fractions to the beta-adrenoceptor blocking drugs was similar to that of the rat heart; however, the calcium uptake and ATPase activities of microsomes were more sensitive to propranolol than mitochondria in both species. 7 Perfusion of rat hearts with 0.2-1 mM propranolol decreased contractile force, and microsomal and mitochondrial fractions obtained from these hearts accummulated less calcium in comparison to the control. On the other hand, acebutolol and practolol (0.2-1nM) had no appreciable effects on contractile force or subcellular fractions under similar conditions. 8 The negative inotropic effect of propranolol may partly be due to its inhibitory actions on calcium transport by subcellular organelles of the myocardium; the depressant action of propranolol on calcium transport is unlikely to be due to its beta-adrenoceptor blocking property.

Acebutolol↗
PubMed1976

Excitation-contraction coupling in heart. XIX. Effect of hypoxia on calcium transport by subcellular particles in the isolated perfused rat heart.

To examine the role of changes in calcium transport by subcellular particles in the pathogenesis of contractile failure due to oxygen lack, both mitochondrial and microsomal fractions were obtained from the isolated hypoxic rat hearts and their calcium binding and uptake abilities were determined by the Millipore filtration technique. The contractile force decreased by about 40, 60 and 70% of the control within 5, 10 and 30 min respectively, of perfusing the heart with hypoxic medium containing glucose. In hearts perfused for 10 min with hypoxic medium containing glucose, calcium binding and uptake by the microsomal fraction decreased significantly. However, mitochondrial calcium binding, but not uptake, decreased significantly on perfusing the hearts with hypoxic medium containing glucose for 20 to 30 min when the microsomal calcium transport was markedly depressed. Reduction in contractile force, calcium binding and uptake by the microsomal fraction as well as calcium binding by mitochondria of hearts made hypoxic for 30 min recovered towards normal upon reperfusion with control medium for 15 min. On the other hand, omitting glucose from the hypoxic medium significantly decreased calcium binding by mitochondrial and microsomal fractions within 10 min of perfusion in comparison to the control and accelerated the effects of hypoxia upon contractile force and microsomal calcium uptake. In contrast to the hypoxic hearts, the mitochondrial calcium uptake decreased significantly and the magnitude of depression in the microsomal calcium binding was appreciably greater in hearts made to fail to a comparable degree upon perfusion with substrate-free medium. The observed defects in calcium transporting properties of microsomal and mitochondrial membranes appear secondary to the contactile failure in hypoxic hearts.

Adenosine Triphosphatases↗
PubMed1976

Subcellular calcium transport in failing hearts due to calcium deficiency and overload.

Mitochondrial and heavy microsomal fractions were isolated from rat hearts perfused for different intervals with Ca2+-free medium, as well as from hearts reperfused with control medium after perfusion with Ca2+-free medium. Contractile failure due to intracellular calcium deficiency produced by perfusing the isolated rat hearts with Ca2+-free medium resulted in a marked decline of calcium binding and uptake activities of the mitochondrial fraction without any effect on the microsomal fraction. On the other hand, inability of the rat hearts to recover their contractile force due to intracellular calcium overload produced by reperfusion for 10 min with control medium after 5-20 min of perfusion with Ca2+-free medium was associated with decreased microsomal calcium-binding and uptake activities and increased mitochondrial calcium-binding and uptake activities. When the hearts perfused with Ca2+-free medium in the presence of low sodium (35 mM) for 5 min were reperfused with control medium, the contractile force recovered completely, and appreciable augmentation in mitochondrial calcium transport or depression in microsomal calcium transport as seen in conditions of intracellular calcium overload did not occur. These results suggest dramatic alterations in calcium-transporting properties of mitochondria and sarcoplasmic reticulum in hearts failing due to intracellular calcium deficiency and calcium overload, respectively.

Animals↗
PubMed1976

Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit.

We studied hearts from sham-operated and uninfected catheterized rabbits as well as from rabbits at early and late stages of cardiomyopathy and failure after 3 and 6 days of infection with Streptococcus viridans. No ultrastructural abnormalities or biochemical changes in membrane and myofibrillar activities were seen in 3-day uninfected hearts. In 6-day uninfected hearts there were decreased sarcolemmal M2+ ATPase, Na+-K+ ATPase, adenylate cyclase and calcium binding, microsomal calcium binding and uptake, and myofibrillar Ca2+-stimulated ATPase as well as increased mitochondrial calcium uptake. Slight ultrastructural changes also were apparent in 6-day uninfected hearts. At both early and late stages of infective cardiomyopathy and failure there were varying degrees of depression in sarcolemmal Mg2+ ATPase, Na+-K+ ATPase, adenylate cyclase and calcium binding, microsomal calcium binding, calcium uptake and basal ATPase, and myofibrillar Ca2+-stimulated ATPase activities. However, sarcolemmal Ca2+ ATPase and myofibrillar Mg2+ ATPase activities were decreased only after 6 days of infection. Mitochondrial calcium binding and uptake were increased in early stages but decreased in late stages of disease. Furthermore in infected hearts there were defects in mitrochondrial respiration and phosphorylation. Generalized severe myocardial cell damage involving myofibrils, mitochondria, and the sarcotubular system was seen only in late stages of infection. The results demonstrate impairment of different membrane and contractile protein functions as well as ultrastructural abnormalities in bacterial cardiomyopathic hearts which were absent or of lesser magnitude in hearts with only hypertrophy. The findings reported here suggest to use that there is an association between heart failure and changes in function of cellular components during bacterial infective cardiomyopathy.

Adenosine Triphosphatases↗
PubMed1976

Characterization of partially purified heart sarcolemmal Na+-K+-stimulated ATPase.

The Km value for the dog heart (Na+-K+)-ATPase was 0.31 mM (MgATP), whereas the values for the concentrations of K+ and Na+ varied from 1.2 to 2.7 mM and 12 to 20 mM for half-maximal activation, respectively. The concentrations of ouabain and calcium for 50 percent inhibition of (Na+-K+)-ATPase activity varied from 2.4 to 3.2 muM and 0.5 to 1.2 mM, respectively, the inhibitory effects of these agents were pH dependent. This preparation bound about 50 nmoles of 1-anilino-8-napthaline sulfonate (ANS)/mg of protein and exhibited fluorescence attributable to the ANS-enzyme complex. Cations such as Na+,K+,Ca++, and Mg++ increased ANS-enzyme fluorescence intensity and the number of ANS binding sites but decreased the apparent ANS binding constant. The enzyme activity, ANS binding, and ANS-enzyme fluorescence were decreased by phospholipase A, phospholipase C, and trypsin treatments. Although ouabain inhibited enzyme activity and ANS-enzyme fluorescence markedly, it caused only a slight depression in ANS binding. These results extend support for the allosteric nature of the cardiac (Na+-K+)-ATPase and provide evidence for conformational changes during its activation by Na+ and K+.

Adenosine Triphosphatases↗
PubMed1976

Role of sarcolemmal changes in cardiac pathophysiology.

Sarcolemmal Ca++-ATPase, Mg++-ATPase, and (Na+-K+)-ATPase activities were increased in late stages of heart failure in myopathic hamsters (BIO 14.6) without any changes in the adenylate cyclase activity. On the other hand, these hamsters at early and moderate stages of heart failure showed depressions in mitochondrial calcium binding and uptake and microsomal calcium binding. Sarcolemmal (Na+-K+)-ATPase was decreased in failing hearts because of substrate lack, oxygen lack, and perfusion with Ca++-free, Na+-free, or K+-free medium. Both Mg++-ATPase and Ca++-ATPase activities of sarcolemma did not change on perfusing the hearts with substrate-free, hypoxic, Na+-free, or K+-free medium. Adenylate cyclase activity decreased on substrate-free or Ca++-free perfusion. Intracellular calcium overload produced by perfusing the hearts with medium containing calcium after Ca++-free perfusion was associated with decrease in all the sarcolemmal-bound enzyme activities. All types of failing hearts employed in this study showed a dramatic shift in the electrolyte composition. Failure of the cardiac muscle to generate contractile force on treatment with trypsin was associated with defects in the functions of sarcolemma, mitochondria, and sarcoplasmic reticulum, whereas such an effect on treatment with phospholipase C was limited to alterations in the activities of sarcolemma. The data suggest that abnormality at the level of sarcolemma plays an important role in the pathogenesis of heart dysfunction; however, the degree and direction of alterations in the sarcolemmal functions seem to be dependent upon the type of heart failure.

Action Potentials↗
PubMed1976

Heart sarcolemma as a dynamic excitable membrane.

Sarcolemma consists of plasma and basement membranes and constitutes the real permeability barrier to the heart cell. It is considered to provide high electrical resistance and capacitance to heart cell and its properties are essentially similar to those of the other excitable membranes. Methods are now available for isolating heart sarcolemma with high specific activities of adenylate cyclase, (Na(+)-K(+) ATPase, Ca(++) ATPase, and Mg(++) APTase. These enzymes are considered to play an important role in heart function by regulating ion movements across sarcolemma as well as by providing signals for various metabolic processes. Sarcolemma possesses different hormone and drug receptors and any alteration in its composition could result in abnormal responses of the myocardium. We believe that heart failure is associated with sarcolemmal defects which can be detected by monitoring the activities of different membrane-bound enzymes and other related processes.

Adenosine Triphosphatases↗
PubMed1975

Concomitant changes in adenylate cyclase and cytolytic activities of lymphoid cells during graft versus host reaction.

Spleen cells from adult F1 hybrid mice undergoing the graft versus host reaction due to the inoculation of lymphoid cells of parental origin showed increased adenylate cyclase activity and cytolytic activity. A time-course study revealed that both the adenylate cyclase and cytolytic activities started increasing at Day 4 and reached maximum at Day 8 of initiation of the graft versus host reaction. Furthermore, the magnitude of both adenylate cyclase activation and cytolytic activity were dependent upon the number of parental cells injected into the F1 hybrid recipients. Elevated adenylate cyclase activity was also observed in spleen cells from irradiated animals undergoing the graft versus host reaction in which the nonspecific, but not the specific cytolytic activity was markedly depressed.

Adenylyl Cyclases↗