The effect and pharmacokinetics of nafamostat mesilate adjunct to cold nondepolarizing cardioplegia in a canine model of cardiac preservation.

We examined the effects of nafamostat mesilate (NM) on myocardial, biochemical, and functional changes in canine hearts. An isolated heart was preserved for 6 h at 5 degrees C and then reperfused for 2 h at 37 degrees C. NM wa added to the cardioplegic solution. At concentrations of both 10(-7) M (n = 8) and 10(-6) M (n = 6), NM was able to maintain myocardial cyclic adenosine monophosphate (cAMP) at a normal level and to reduce guanosine monophosphate (cGMP) concentrations at the end of both preservation and reperfusion. The serum N-acetyl-b-D-glucosaminidase (NAG) concentration during reperfusion was lower in hearts treated with NM 10(-6) or 10(-7) M than in those without NM (P < 0.05). Although NM failed to preserve myocardial concentrations of adenine nucleotide compounds, NM 10(-7) M maintained the +/- dp/dt of the left ventricle after reperfusion at the same level as in the nonischemic control group and better than NM 10(-6) M or no NM (P < 0.05). Myocardial uptake of NM 10(-5) M (higher concentration) was 55% +/- 8% (6-h preservation) and 29% +/- 15% (2-h reperfusion). We conclude that NM 10(-7) M adjunct to non-depolarizing solution does not preserve myocardial adenine nucleotide concentrations but does facilitate the recovery of left ventricular function. NM 10(-5) M (higher concentration) seems to have a high affinity for the myocardium and may depress the recovery of left ventricular function.