Sunamori M, Yoshida T, Miyamoto H, Wang Y, Suzuki A
Department of Thoracic-Cardiovascular Surgery, Tokyo Medical and Dental University, School of Medicine, Japan.
Transpl Int. 1996;9(4):364-9. doi: 10.1007/BF00335696.
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.
我们研究了甲磺酸萘莫司他（NM）对犬心脏心肌、生化及功能变化的影响。将离体心脏在5℃保存6小时，然后在37℃再灌注2小时。NM被添加到心脏停搏液中。在10⁻⁷M（n = 8）和10⁻⁶M（n = 6）两种浓度下，NM能够在保存和再灌注结束时将心肌环磷酸腺苷（cAMP）维持在正常水平，并降低鸟苷单磷酸（cGMP）浓度。在再灌注期间，用10⁻⁶或10⁻⁷M NM处理的心脏中血清N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）浓度低于未用NM处理的心脏（P < 0.05）。尽管NM未能保存心肌中腺嘌呤核苷酸化合物的浓度，但10⁻⁷M的NM在再灌注后能将左心室的±dp/dt维持在与非缺血对照组相同的水平，且优于10⁻⁶M的NM或未用NM处理的情况（P < 0.05）。10⁻⁵M（较高浓度）的NM心肌摄取率在6小时保存时为55%±8%，在2小时再灌注时为29%±15%。我们得出结论，10⁻⁷M的NM添加到非去极化溶液中虽不能保存心肌腺嘌呤核苷酸浓度，但有助于左心室功能的恢复。10⁻⁵M（较高浓度）的NM似乎对心肌具有高亲和力，可能会抑制左心室功能的恢复。
