PROTECTIVE EFFECT OF AMILORIDE DURING HYPOTHERMIC HYPERKALEMIC PRESERVATION - A P-31 NMR-STUDY IN ISOLATED PIG HEARTS

To assess the possible role of Na+/H+ exchange in ischemia-reflow dama ge during cold preservation, pig hearts retrogradely perfused with Kre bs-Henseleit (KH) bicarbonate buffer were arrested by increasing [K+] (to 17 mM), cooled (10 degrees C) and subjected to no now ischemia for 15 h in the absence (C, n=5) and in the presence of 0.5 mM amiloride (A, n=5). A was added 7 min prior to ischemia and removed after 3 min reflow, P-31 nuclear magnetic resonance (NMR) spectra were continuousl y acquired and functional indices were assessed prior to and after isc hemia. Before reflow the levels of phosphocreatine (PCr), ATP, inorgan ic phosphate (Pi) + phosphomonoesters (PME) and cytosolic pH in C and A did not differ: C, 12+/-7, 56+/-13 427+/-75% of initial and 5.90+/-0 .20; A, 15+/-4, 82+/-21, 371+/-60% and 5.90+/-0.19, respectively; no c ontracture occurred. Upon renew with hyperkalemic buffer PCr recovery in A-treated hearts was greater than in C (73+/-21 v 49+/-13%, P<0.05) and parallel increases in left ventricular end diastolic (LVEDP) and perfusion pressure took place in both groups, however these parameters remained lower in A-treated hearts, Upon switching to KH buffer the o xygen uptake rate (VO2) was higher in A than in C (79+/-18 v 59+/-6%, P<0.05) whereas the differences in the pressure-rate product (PRP, 51/-21 in A v 38+/-11% in C) and LVEDP (16+/-11 in A v 24+/-7 mmHg in C) did not reach statistically significant levels, Adjusting LVEDP in bo th groups to the same levels (19+/-6 v 21+/-9 mmHg in C) by changing b alloon volume resulted in significant difference in PRP (61+/-19% v 42 +/-6% in C, P<0.02). The coronary resistance measured in beating heart s remained lower in A than in C (34.5+/-3.0 v 57+/-11 mmHg/(ml/min g), P=0.04). To estimate contractile and metabolic reserves post-ischemic hearts were challenged by increasing [Ca2+] in the perfusate from 1.0 to 1.6 mM. PRP and VO2 increased; PRP reached 71+/-32 (A) and 54+/-10 % (C) and VO2 remained higher in A: 90+/-16 (A) v 62+/-4% (C) (P=0.01) of preischemic levels. We suggest that Na+/H+ exchange may contribute to ischemia-reflow damage during cold preservation of isolated pig he arts. (C) 1995 Academic Press Limited