EFFECTS OF L-GLUTAMINE ON POSTISCHEMIC CARDIAC-FUNCTION - PROTECTION AND RESCUE

We investigated the effects of L-glutamine (0-20 mM) on cardiac functi on. The isolated perfused working rat heart (left atrial and aortic pr essures of 5 and 70 cm H2O, respectively) was subjected to 20 min of n ormothermic low-flow ischaemia followed by reperfusion for 35 min. In the absence of glutamine, ischaemia-reperfusion caused an immediate si gnificant (P<0.01) fall in cardiac output from 46 to 20 ml/min, with a further deterioration to 17 ml/min at 35 min reperfusion. Ischaemia a lso caused a significant (P<0.05) fall in myocardial glutamate from 2. 6 to 1.8 mu mol/g wet weight; and ischaemia-reperfusion caused signifi cant teach P<0.05) diminutions of myocardial ATP from 3.5 to 1.0 mu mo l/g wet weight and phosphocreatine from 4.8 to 1.5 mu mol/g wet weight and resulted in significant (P<0.05) accumulation of myocardial lacta te from 0.9 to 4.3 mu mol/g wet weight. Glutamine, present throughout the perfusion protocol (i.e. prior to ischaemia), at or above 1.25 mM, prevented the postischaemic diminution of cardiac output and the dele terious changes in myocardial metabolites. Post-ischaemic treatment wi th glutamine at 2.5 mM completely prevented the post-ischaemic diminut ion of cardiac output and restored the myocardial metabolites to norma l. Conclusions: glutamine may be suitable as a cardioprotective and re scue agent. These effects may be mediated by maintenance of myocardial glutamate, ATP and phosphocreatine: and prevention of lactate accumul ation. (C) 1998 Academic Press Limited.