Ø. Ellingsen

Myocardial K+ repletion and rise in contractility after brief ischemic periods in the pig

Potassium loss from the myocardium during brief ischemic periods is well documented, but whether intrinsic myocardial mechanisms restore this loss during reperfusion is unclear. To address this question, we established a shunt from the coronary sinus to the right atrium in seven open-chest pigs. Shunt flow and arterial and coronary sinus potassium concentrations were measured continuously in order to determine myocardial potassium balance. Thirty, 60 and 120 s occlusions of the mid-LAD coronary artery were repeated four times each at 10 min intervals with reproducible metabolic and hemodynamic responses. A myocardial K+ reuptake amounting to 51 to 77% of K+ release during ischemia occurred between 20 and 140 s of reperfusion. The maximal rate of K+ reuptake was 1.4 (0.7 to 3.6), (median and 95% confidence interval), 4.3 (2.5 to 9.6) and 7.3 (4.9 to 13.4) mumol/100 g min after occlusion periods of 30, 60 and 120 s, respectively. Concomitant with the K+ reuptake a progressive rise in LV dP/dt occurred. Adrenoceptor stimulation could not explain these findings since catecholamine release declined during occlusion and reperfusion. We suggest that increased intracellular Na+ concentration in early reperfusion stimulates the Na,K-pump and favours Ca++ entry through Na+/Ca++ exchange, thereby mediating K+ reuptake and the rise in contractility.

Effects of hemodynamic variables on myocardial K+ balance during and after shortlasting ischemia

Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during and after a 90 s occlusion of a branch of the circumflex artery during control (CTR), during pacing tachycardia (PACE: 34% increase in heart rate), during proximal aortic constriction (AC; 28% increase in LVSP), and during isoprenaline infusion (ISO; 135% increase in LVdP/dt and 35% increase in heart rate). Ischemia-induced potassium loss increased significantly (40%) during ISO only. Higher basal metabolic rate, increased sarcolemmal K+ conductance, or ischemia-induced depression of a more active Na/K-pump during ISO are possible explanations to why increased K+ loss appeared in this situation. The maximal rate of post-ischemic potassium reuptake was not different from CTR during PACE and ISO, but it was reduced during AC, which might be due to persisting subendocardial ischemia in early reperfusion when ventricular wall stress is high. The extent of potassium restoration was not different from CTR during AC, PACE and ISO.

Cardiac Responses to Increased Contractility: Digital Simulation and Mathematical Analysis

Abstract By models of the circulation, we analyzed the responses to a rise in contractility in one chamber of the heart. The study was initiated because one-sided inotropic stimulation revealed different responses in the two ventricles of the in situ pig heart. In a simple two-compartment model of the circulation, both numerical data analysis and an analytical mathematical approach revealed that decrements in both maximal and minimal heart chamber volumes were to be expected when contractility was increased. This response also appeared in the right ventricle of the in situ pig heart when the effect of increased contractility in the right atrium was abolished by simultaneous atrial-and ventricular contraction. A computer-based seven compartment model of the circulation predicted these responses and offered two alternative explanations for the different-directed changes in left- and right ventricular end-diastolic volumes when the respective sides were inotropically stimulated. First, some degree of right ventricular dilation followed the rise in pulmonary artery pressure during elevations of right-side contractility. Second, right atrial function was better preserved than left atrial function; increased contractility in the right side of the heart caused end-diastolic dilation of the right ventricle both at normovolemia, and even more at hypervoemia, but this response vanished at hypovolemia.