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°C and then reperfused for 2 h at 37°C. NM was 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 nondepolarizng 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.