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Journal ArticleDOI

Intracellular Calcium and Myocardial Contractility

01 Aug 1970-Circulation Research (Lippincott Williams & Wilkins)-Vol. 27, Iss: 2, pp 235-247
TL;DR: In this paper, paired stimulation at 80/min augmented myocardial contractility with a gradually developing increase in total intracellular calcium and sodium, and a greater 45Ca uptake was also observed.
Abstract: Postextrasystolic potentiation was studied in the isolated perfused rabbit heart to determine its effect on intracellular calcium, sodium, and potassium concentration, 45Ca uptake, and calcium distribution in mitochondria and microsomes. Paired stimulation at 80/min augmented myocardial contractility with a gradually developing increase in total intracellular calcium and sodium. A greater 45Ca uptake was also observed and this was proportionate to the increase of intracellular calcium so that no change in exchangeable calcium occurred. A small but statistically insignificant increment was observed in mitochondrial and microsomal calcium. An increase of the rate of single stimuli to 160/min produced a minimal change in myocardial contractility compared to paired stimulation at 80/min, no change in total intracellular calcium, and a greater calcium uptake so that there was a significant increment in exchangeable calcium. Although these experiments do not identify the cellular processes responsible for the p...
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TL;DR: This review focuses only on permanent modifications in relation to clinical dysfunction in cardiac remodeling secondary to myocardial infarction and/or arterial hypertension and includes a special section on the senescent heart, since CR is mainly a disease of the elderly.
Abstract: Swynghedauw, Bernard. Molecular Mechanisms of Myocardial Remodeling. Physiol. Rev. 79: 215–262, 1999. — “Remodeling” implies changes that result in rearrangement of normally existing structures. Th...

1,489 citations

Journal ArticleDOI
TL;DR: Left ventricular pressure and volume during diastole reflect the interaction of ventricular elastic, viscous, and inertial properties, and the completeness of myocardial relazation, and may be impaired in the acutely ischemic ventricle.
Abstract: Left ventricular pressure and volume during diastole reflect the interaction of ventricular elastic, viscous, and inertial properties, and the completeness of myocardial relaxation. Myocar...

458 citations

Journal ArticleDOI
TL;DR: The results suggest compensatory increases in mitochondrial respiratory function during early hypertrophy and Alteration in intracellular calcium metabolism is suggested with a depression of calcium-binding activity of CRS preceding that of mitochondria.
Abstract: WOOD, AND ARNOLD SCHWARTZ. Mitochondria and sarcoplasmic reticulum function in cardA hypertrophy and failure. Am. J. Physiol. 224(3) : 497-502. 1973.-Mitochondria and “sarcoplasmic reticulum” cardiac relaxing system (CRS) were isolated from rabbit hearts that were in various stages of hypertrophy and failure induced by progressive stenosis of the ascending aorta. The latter was produced by Ameroid clips that gradually swell causing left ventricular overload. Left ventricular and peak isovolumic pressures were measured prior to removal of the hearts for biochemical studies. Mitochondria exhibited marked increases in respiratory activity during early stages of hypertrophy, followed by decreases during later stages. Density gradient analysis revealed alterations in mitochondrial populations during hypertrophy and failure. Mitochondrial calcium uptake was not significantly different in hypertrophied hearts compared to controls, but was markedly reduced in failing hearts. In addition, previously bound calcium was more easily “released” from mitochondria isolated from failing hearts than from control hearts. CRS from hypertrophied and failing hearts revealed significantly decreased rates and total binding of calcium. The results suggest compensatory increases in mitochondrial respiratory function during early hypertrophy. Alteration in intracellular calcium metabolism is suggested with a depression of calcium-binding activity of CRS preceding that of mitochondria.

213 citations

Journal ArticleDOI
TL;DR: It is concluded that patients with dilated cardiomyopathy may demonstrate little or no significant enhancement in systolic and diastolic function during atrial pacing tachycardia, suggesting a depression of both inotropic and lusitropic reserve.
Abstract: Previous reports have shown that increases in heart rate may result in enhanced left ventricular (LV) systolic and diastolic performance. To assess whether this phenomenon occurs in the presence of depressed LV function, the effects of pacing on LV pressure and volume were compared in seven patients with dilated cardiomyopathy (LV ejection fraction 0.19 +/- 0.11) and six patients with no or minimal coronary artery disease (LV ejection fraction 0.69 +/- 0.11). Patients with normal LV function demonstrated significant increases in LV peak-positive dP/dt, LV end-systolic pressure-volume ratio, LV peak filling rate, and a progressive leftward and downward shift of their pressure-volume diagrams, compatible with increased contractility and distensibility in response to pacing tachycardia. There was no change in LV peak-negative dP/dt or tau. Patients with dilated cardiomyopathy, in contrast, demonstrated no increase in either LV peak-positive dP/dt or the end-systolic pressure-volume ratio, and absence of a progressive leftward shift of their pressure-volume diagrams. Moreover, cardiomyopathy patients demonstrated no increase in LV peak-negative dP/dt or LV peak filling rate and a blunted downward shift of the diastolic limb of their pressure-volume diagrams. Tau, as determined from a derivative method, became abbreviated although never reaching control values. We conclude that patients with dilated cardiomyopathy may demonstrate little or no significant enhancement in systolic and diastolic function during atrial pacing tachycardia, suggesting a depression of both inotropic and lusitropic reserve.

176 citations

References
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Journal ArticleDOI
E. Racker1
TL;DR: A spectrophotometric method of measuring the enzymatic formation and disappearance of umaric and cis -aconitic acids is reported.

746 citations

Journal ArticleDOI
TL;DR: It is concluded that congestive heart failure is associated with extreme quantitative abnormalities of the intrinsic contractile state of each unit of heart muscle, which reflect a depression in the intensity of the active state.
Abstract: The contractile state of papillary muscles from hypertrophied and from failing right ventricles of cats with pulmonary artery constriction was studied. In muscles from failing hearts, the maximum velocity of shortening, active length-tension curves, and maximum rate of tension development were decreased, while the passive length-tension curves and the time from stimulation to peak tension were normal. The augmentation of isometric tension achieved by paired electrical stimulation, increasing frequency of contraction, and strophanthidin was reduced. In muscle from hearts without failure but with ventricular hypertrophy, there were qualitatively similar depressions of contractile function, although of lesser magnitude. It is concluded that congestive heart failure is associated with extreme quantitative abnormalities of the intrinsic contractile state of each unit of heart muscle, which reflect a depression in the intensity of the active state. Further, ventricular hypertrophy in the absence of failure is a...

497 citations

01 Jan 1969
TL;DR: ATP was the most effective of four nucleoside triphosphates in supporting calcium binding and uptake and mitochondria accumulated calcium at a rate faster than CRS.
Abstract: Cardiac relaxing system (CRS) and mitochondria were isolated by a modified rapid procedure from human, rabbit, and dog. Relaxing system (sarcoplasmic reticulum) was also isolated from white and red skeletal muscles for comparative purposes. Rapid kinetic measurements were made with a dualbeam spectrophotometric assay procedure. Maximum calcium binding (absence of oxalate), expressed as nmoles calcium/mg protein in 5 minutes at 25°C, for rabbit heart and red and white skeletal muscles were approximately 40, 58 and 170, respectively. The calcium binding constant for rabbit CRS was 2 X 10 (i M~'. The estimated initial binding rates (nmoles calcium/mg protein/minute) of cardiac, white and red skeletal muscle relaxing systems were 256, 1440 and 182, respectively. The rate constant (M~> sec1 ) of CRS was about 2400, which falls between white and red skeletal muscle preparations. Human cardiac muscle from recipients obtained at the time of transplantation yielded CRS with slower rates of accumulation of calcium and very little calcium release, compared to normal animal heart preparations. ATP was the most effective of four nucleoside triphosphates in supporting calcium binding and uptake. Calcium binding and release and calcium uptake of CRS were temperature-sensitive. The energies of activation of binding and uptake were 10.5 kcal mole" 1 and 22.5 kcal mole" 1 , respectively. Under specific conditions, heart mitochondria accumulated calcium at a rate faster than CRS. Mitochondria could also release accumulated calcium.

486 citations