The effects of
grisorixin, a monocarboxylic
ionophore, were studied on isolated working rat hearts perfused with a
suspension of washed pig erythrocytes (10% hematocrit).
Grisorixin (2.5 microM) induced a transient stimulation of heart work, maximal at 5 min, expressed by an increase in heart rate (+21%) and aortic flow (+17%) and by an increase in coronary flow, maximal
at 10 min (+47%). Concomitantly, myocardial Vo2 was slightly enhanced and the myocardial
creatine phosphate level dropped (2 min). The
lactate production increased by 82% (5 min) then dropped to the control value (10 min) and increased again till the 45th min (+211%), indicating a cardiac metabolic drift towards anaerobic glycolysis due to partial inhibition of the oxidative metabolism. Owing to its properties as an
ionophore,
grisorixin also induced a strong and rapid increase of
potassium concentration in the perfusate and a decrease of
sodium.
Grisorixin was tested on hearts submitted to 20 min of hypoxic conditions. The
hypoxia was rather mild and induced only very slight modifications of the ultrastructure. In the control series, heart rate and aortic flow decreased regularly while coronary flow and
lactate production increased. Upon reoxygenation, the heart performances were rapidly restored.
Grisorixin was administered according to four different protocols. When injected at the onset of
hypoxia or 5 min later, it was able to maintain the aortic flow during the first minutes and induce a higher coronary dilation. These beneficial effects were short-lasting and no deleterious effects were found on the ultrastructure of hearts subjected to
grisorixin whether after
hypoxia or after reoxygenation.