Abstracts-part I (Continue in Part II)

Abstract

In the isolated heart, global, total ischemia is a zero flow-, low intracellular pH (pHi)-, zero workload-, zero substrate-, zero oxygen-and high intracellular Ca+ + (Cai)-situation. High-KCI cardioplegia dose-dependently decreases the membrane potential (AE) leading to Caioverload due to opening of Ca++-channels. Thus, high-KCI cardioplegia should allow isolation of the high Cai and zero-workload aspects of ischemic injury, while flow, pHi, substrate and oxygen delivery remain normal or close to normal. Purpose of this study was to define membrane potential-dependent changes of cardiac performance and Mgh-energy phosphate metabolism evoked by varying AE from normal (-90) to depolarized levels of -6 mV.Furthermore, we followed hearts during recovery (repolarization) following depolarization.Isolated rat hearts were perfused with phosphate-free glucose-containing (1 1 mM) oxygenated (95%02. 5%&02) Krebs-Henseleit (KH) buffer at 37 OC using a constant flow of 24+2 mllmin adjusted to yield a coronary perfusion pressure of 100 mmHg. Performance (LV balloon) was calculated as the rate-pressure product (RPP; IOammHglmin). On a Bruker 7 T MR system, 31P-NMR spectra were recorded at 7 min intervals by signalaveraging 210 FlDs using a pulse angle of 45 0 and a req@e time of 1.93 sec; spectra were corrected for partial saturation. Hearts (n=5 per group) were subjected to 21 min of Control (KCI=4.7 mM) perfusion, 56 min of high-KCI ([KCI] 30, 70, 90 or 110 mM) and 49 min of reeovery at normal (4.7 mM) KCI (Re-KH). According to the Nernst equation (AE = -RT/ZKF In KilKo'), AE was calculated to be -90, -40, -18, -11 and - Figure 1 shows typical spectra of a heart during control, at the end of low-AE (-6 mV) and at the end of recovery. Mean values are given in Figure 2 (ATP) and in the Table. Cardiac contractions immediately ceased at all low-AEs. During Re-KH, RPP recovered to 76f4, 68*10, 44k5 and 27f3 % of control after -40, -18, -11 and -6 mV, resp.; end-diastolic pressure (EDP; set to 10 mmHg during control) increased to 36k7, 33M, 50k6 and 80k6 at the end of low-AE and decreased to 11k2, 12f1, 21+2 and 49f9 mmHg at the end of Re-KH, resp. Thus, during Re-KH, mechanical recovery was inversely correlated to AE during injury. 40 mV did not deplete ATP (mM) or creatine phosphate (CP; mM). For the lower AE, ATP and CP decreased monotonically during cardioplegia with the rate of decline depending on AE; during Re-KH, ATP did not increase; CP showed some recovery but remained significantly depressed; inorganic phosphate (Pi; mM) increased under -18, -11 and -6 mV, but not under -40 mV. Due to high coronary flow, pHi showed only minor changes (0.18 pH units at most); however, there was a slight increase with -40 and -18 and a slight decrease with -6 mV; both effects were reversible with Re-KH.12 - -8Lowering AE by high-KCI cardioplegia causes depletion of high-energy phosphates and reduced post-cardioplegic systolic and diastolic (contracture) performance. The effect is potential-dependent and not an all-or-none phenomenon; ...