Metabolic and functional consequences of successive no-flow and sustained low-flow ischaemia a P-31 MRS study in rat hearts

Recently, a model of acute hibernation, based on successive no-now and low-flow ischaemia in the isolated rabbit heart has been described, In the present study this model was used in isolated rat hearts. P-31 NMR was used to follow the time course of intracellular pH (pH(i)) and high-energy phosphates; mechanical activity of the heart was assessed simultaneously. Control hearts were subjected to 180 min of low-flow ischaemia and 60 min of reperfusion (group A), In the acute hibernation group, low-flow was preceded by 5 min of no-flow ischaemia (group B). In group A contracture developed during low-now. The time to onset of contracture was 51 min (range: 28 to 123 min), In group B, contracture did not occur during low-dow ischaemia (P<0.01); recovery of left ventricular developed pressure and end-diastolic pressure was significantly better during the first 15 min of reperfusion (P<0.05). In group A pH(i) decreased from 7.06 +/- 0.04 to 6.64 +/- 0.14 during the first 30 min of low-flow. After contracture developed in this group two pH(i) values were measured amounting to 6.33 +/- 0.15 and 6.86 +/- 0.05 at the end of low-flow. At the end of reperfusion pH(i) was 6.29 +/- 0.05 and 7.09 +/- 0.06. In group B, pH(i) decreased from 7.08 +/- 0.03 to 6.55 +/- 0.03 during no-now ischaemia, During low-dow ischaemia, pH(i) increased to 6.73 +/- 0.05 and remained constant. During reperfusion pH(i) recovered to 7.06 +/- 0.03. In group A and B phosphocreatine (PCr) levels at the end of low-now ischaemia amounted to 13 +/- 8% and 26 +/- 6% of pre-ischaemic levels, respectively. During reperfusion, PCr recovery was better in group B: 67 +/- 12% v 23 +/- 11% (P<0.05). In group A and B, ATP levers at the end of low-flow ischaemia were 5 +/- 10% and 19 +/- 9%, respectively. The rate of ATP depletion during low-flow ischaemia was initially similar in both groups, but between 45 and 90 min ATP depletion still continued in group A, while this had leveled off in group B (P<0.01). During reperfusion no significant changes in ATP were observed, We propose that increased glucose transport and glycolytic flux are able to maintain ionic homeostasis and diastolic function when low-flow ischaemia is preceded by a short period of no-dow ischaemia. (C) 1996 Academic Press Limited