Isoflurane and Sodium Nitroprusside Reduce the Depressant Effects of Protamine Sulfate on Isolated Ischemic Rat Hearts

Abstract

The administration of protamine sulfate (protamine) to reverse the action of heparin is associated with adverse reactions. We studied the effects of protamine and isoflurane on isolated, perfused rat hearts previously subjected to cardioplegic ischemia. Hearts were perfused with oxygenated Krebs-Henseleit (KH) solution for 30 min, then subjected to cardioplegic ischemia for 30 min (KCl 16 mEq/L at 31 degrees C) and 5 min reperfusion. Drug exposure lasted 15 min, and the recovery period was 60 min. Test groups were control, protamine (10 microg/mL), isoflurane (1.5%), protamine +/- isoflurane, sodium nitroprusside (SNP) (2.5 ng/mL), and SNP +/- protamine. Left ventricular developed pressure (LVP), coronary flow, and myocardial oxygen consumption were depressed by protamine to 30% +/- 4%, 47% +/- 4%, and 39% +/- 4% of baseline (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 control); coronary flow was 70% +/- 6% and 97% +/- 12% of baseline, respectively (P < 0.05 versus protamine alone; P < 0.05 for isoflurane versus control); and O2 consumption was 69% +/- 6% and 88% +/- 15% of baseline, respectively (P < 0.05 versus protamine; P < 0.05 for isoflurane versus control). In this model, protamine-induced myocardial depression and coronary vasoconstriction were less pronounced in the presence of either isoflurane or SNP. We examined the interactions of isoflurane, sodium nitroprusside, and protamine in a rat heart model and found that both isoflurane and sodium nitroprusside partially protect the heart from the depressant effects of protamine. This finding is significant, as these drugs are often used in heart surgery.