CONTRACTILE DYSFUNCTION CAUSED BY NORMOTHERMIC ISCHEMIA AND KCL ARREST IN THE ISOLATED PIG-HEART - A P-31 NMR-STUDY

The aims of this study were to assess (1) whether contractile dysfunct ion caused by ischaemia under hyperkalaemic conditions (''cardioplegic ischaemia'') is associated with impaired energy production or abnorma lities in regulation of contractility and (2) whether hyperkalaemia it self contributes to contractile dysfunction. We used P-31 and Na-23 NM R spectroscopy in conjunction with measurements of mechanical function and oxygen consumption in Langendorff perfused pig hearts to evaluate the mechanism of contractile failure caused by (1) total global cardi oplegic (17 mM [K+] ischaemia (36 degrees C, 50 min KCl arrest, 45 min ischaemia, 20 min reflow with high KCl) and (2) KCl arrest alone (115 min) without flow cessation. KCl arrest plus ischaemia and subsequent reperfusion (Group I) resulted in decreases in ATP (mean +/- S.D; 61 +/- 13% of initial, n=5; P<0.01) and pressure-rate product (PRP) (31 /- 9%, n=17; P=0.0001) while phosphocreatine (PCr), Pi, total creatine (Cr) and intracellular Naf levels were unaffected. KCl arrest itself (Group II, n=6) did not affect PCr, ATP or total Cr levels but decreas ed the PRP to 59 +/- 12% (P<0.001), Oxygen consumption rates (Vo(2)) w ere reduced in both groups to similar levels (67 +/- 18, P<0.01 and 77 +/- 13%, P<0.02, respectively). The efficiency of energy conversion t o mechanical work (PRP/Delta Vo(2)) decreased to 51 +/- 15 (P<0.001) a nd 67 +/- 13% (P<0.012) of initial levels, respectively. To assess met abolic and contractile reserves of post-ischaemic (n=7) and KCl-treate d (n=3) hearts, the effects of isoproterenol (Iso) and increased Ca2were compared with those in normal beating hearts (Group III, n=3). In all groups treatment with Iso (0.1 mu M) greatly increased PRP (to 52 6 +/- 116, 203 +/- 16 and 198 +/- 8% of the level prior to stimulation (baseline), P<0.01, respectively) and Vo(2) (162 +/- 9, 153 +/- 16 an d 128 +/- 10% of baseline, P<0.05, Respectively). Increasing [Ca2+] fr om 1 to 1.66 mM produced less stimulation than Iso: PRP increased to 1 95 +/- 23 156 +/- 13 and 163 +/- 22% (P<0.05) and Vo(2) increased to 1 38 +/- 22 (P<0.05), 115 +/- 4 and 120 +/- 10% of baseline in Groups I, II and III, respectively. We suggest that contractile dysfunction cau sed by ischaemia plus KCl arrest results from reversible disturbances in Ca-2+ handling and an energy wasting effect induced by ischaemia it self and irreversible disturbances in function of myofibrils induced b y hyperkalaemia. (C) 1995 Academic Press Limited