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

Recently, a model of acute hibernation, based on successive no-flow and low-flow ischaemia in the isolated rabbit heart has been described. In the present study this model was used in isolated rat hearts. 31P NMR was used to follow the time course of intracellular pH (pHi) 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-flow. The time to onset of contracture was 51 min (range: 28 to 123 min). In group B, contracture did not occur during low-flow 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 pHi 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 pHi 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 pHi was 6.29 +/- 0.05 and 7.09 +/- 0.06. In group B, pHi decreased from 7.08 +/- 0.03 to 6.55 +/- 0.03 during no-flow ischaemia. During low-flow ischaemia, pHi increased to 6.73 +/- 0.05 and remained constant. During reperfusion pHi recovered to 7.06 +/- 0.03. In group A and B phosphocreatine (PCr) levels at the end of low-flow 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 levels 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-flow ischaemia.