Modification of myocardial ischemic injury: a concentration response study of glucocorticoid supplementation during...

Reperfusion of the ischemic myocardium is routinely done during cardiac surgery and in the catheterization laboratory after acute regional ischemia. While reperfusion of the ischemic myocardium is necessary in order to regain full functional and biochemical recovery, the reperfusion by itself may aggravate the ischemic damage. Glucocorticoids have been shown to modify the outcome from ischemic injury in various experimental and clinical situations, but the results are conflicting. This protocol was performed using normothermic ischemic (30 minutes) isolated rat hearts, and postischemic reperfusion (30 minutes) with methylprednisolone sodium succinate (MPSS; 100-500-1,000 mg/L) was studied. All indices of myocardial function and all metabolic variables were significantly reduced after ischemia. MPSS (100 mg/L) improved dP/dTmax (recovery 68 +/- 3% v control 48 +/- 7%) and some of the other indices of left ventricular performance studied. MPSS (100 mg/L) also improved the tissue concentration of adenosine triphosphate (ATP) (13.8 +/- 0.5 mumol/g dry weight v control 11.3 +/- 0.8) and the total adenosine pool (16.8 +/- 0.7 mumol/g weight v control 13.9 +/- 0.8 mumol/g dry weight). MPSS (1,000 mg/L) impaired recovery of myocardial function (dP/dTmax, dP/dtmin, rate-pressure product [RPP]), increased tissue lactate (7.2 +/- 2.0 mumol/g dry weight v control 3.6 +/- 0.8), reduced glycogen (30.6 +/- 2.5 mumol/g dry weight v control 49.8 +/- 3.3), and energy charge (0.848 +/- 0.018 v control 0.890 +/- 0.010). It is concluded from the present experiments that modification of an ischemic injury by glucocorticoids given at the onset of reperfusion is possible, and that an optimal concentration of 100 mg/L exists for MPSS supplementation. MPSS in a concentration of 1,000 mg/L aggravated the reperfusion injury, probably by interference with cellular respiration.