[Dependency of Ca++-adsorption by isolated heart muscle mitochondria upon Na+- and K+-concentration as possible explanation for the inotropic effect of digitalis].
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Biomedical subjects
Publications and source records attributed to K Greeff.
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Whereas vanadate increases isometric force of contraction in stimulated rat left atria (EC50: 36.6 mumol/1), it decreases force of contraction in guinea-pigs (EC50: 4.7 mumol/1). Action potential duration at 90 and 30% repolarisation is decreased in guinea-pig atria by 70 and 60%, but in rat atria by only 40 and 7% respectively. Whereas the time course of the negative inotropic action is rapid and correlates with that of the shortening of the action potential, there is no relationship between action potential changes and the slowly developing positive intropic effect. Negative and positive inotropic actions seem to be the result of two superimposed processes, whose kinetics suggest an extra- and intracellular site of action. Na+, K+-ATPase prepared from rat and guinea-pig atria and ventricle is inhibited by vanadate to a similar extent: IC50 (mumol/1) rat: atria 1.05, ventricle 0.49; guinea-pig: atria 0.75, ventricle 0.62. This indicates that the discrepancy in inotropy cannot be explained by the different sensitivity of the Na+, K+-ATPase to vanadate.
In anesthetized cats vanadate (Na3VO4) up to 0.5 mg/kg increased blood pressure and left ventricular end-diastolic pressure (LVEDP) but decreased the force of contraction and heart rate. At 1 mg/kg, LVEDP increased markedly in parallel with an elevation of the ST segment of the electrocardiogram and a pronounced decrease in blood pressure; these effects were reversible within a few minutes. In isolated Langendorff heart preparations of guinea pigs perfused at constant pressure, vanadate decreased flow rate (EC50 = 5.3 mumoles/liter) and contractile force (EC50 = 6.9 mumoles/liter). Vanadate increased tension in isolated aortic strips of cats (EC50 = 115 mumoles/liter) and rabbits (EC50 = 435 mumoles/liter). Vanadate also increased the force of isometric contractions of papillary muscles of guinea pigs, cats, and rabbits, the EC50 values being 124, 110, or 66 mumoles/liter, respectively. We conclude that the negative ionotropic action of vanadate is brought about by marked coronary constriction occurring at concentrations which are too low to have a direct positive action on ventricular myocardium.
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