Isoflurane and sodium nitroprusside reduce the depressant effects of protamine sulfate on isolated ischemic rat hearts

The administration of protamine sulfate (protamine) to reverse the action o f heparin is associated with adverse reactions. We studied the effects of p rotamine and isoflurane on isolated, perfused rat hearts previously subject ed to cardioplegic ischemia. Hearts were perfused with oxygenated Krebs-Hen seleit (KH) solution for 30 min, then subjected to cardioplegic ischemia fo r 30 min (KCl 16 mEq/L at 31 degrees C) and 5 min reperfusion. Drug exposur e lasted 15 min, and the recovery period was 60 min. Test groups were contr ol protamine (10 mu g/mL), isoflurane (1.5%), protamine + isoflurane, sodiu m nitroprusside (SNP) (2.5 ng/mL), and SNP + protamine. Left ventricular de veloped pressure (LVP), coronary flow, and myocardial oxygen consumption we re depressed by protamine to 30% +/- 4%, 47% +/- 4%, and 39% +/- 4% of base line (P < 0.001 versus control), respectively. Isoflurane and SNP afforded partial protection from the effects of protamine: LVP was 57% +/- 5% and 51 % +/- 3% of baseline, respectively (P < 0.05 versus protamine alone and con trol); coronary flow was 70% +/- 6% and 97% +/- 12% of baseline, respective ly (P < 0.05 versus protamine alone; P < 0.05 for isoflurane versus control ); and O-2 consumption was 69% +/- 6% and 88% +/- 15% of baseline, respecti vely (P < 0.05 versus protamine; P < 0.05 for isoflurane versus control). I n this model, protamine-induced myocardial depression and coronary vasocons triction were less pronounced in the presence of either isoflurane or SNP. Implications: We examined the interactions of isoflurane, sodium nitropruss ide, and protamine in a rat heart model and found that both isoflurane and sodium nitroprusside partially protect the heart from the depressant effect s of protamine. This finding is significant, as these drugs are often used in heart surgery.