Pathophysiology of MNMS due to acute arterial occlusion and development of a local perfusion

对25只犬进行了肌肾病代谢综合征(MNMS)的研究。腹主动脉结扎缺血24小时后，松解结扎，于再灌流前从下腔静脉取血。再灌流即刻、再灌流后30分钟和60分钟。CPK、6-keto-PGF_1α、11-脱氢血栓素B_2在缺血再灌流过程中升高。白细胞(WBC)在再灌流后即刻升高，再灌流后30min下降。下一步，我们研究了大鼠离体股薄肌缺血2小时再灌流1小时后产生的自由基的时间进程和来源。用电子自旋共振(ESR)法测定自由基。自由基强度呈现两个高峰，第一个峰值出现在再灌流后3min(I/R3)，第二个峰值持续在再灌流后45min~60min。X0抑制剂(OPF-001 Ootsuka，日本)组和中性粒细胞减少大鼠组的ESR强度ATI/R3和I/R60均受到抑制。在I/R3、20、60时测定髓过氧化物酶(MPO)活性。MPO活性在I/R3和I/R60时的升高与自由基强度的两个峰值呈现相同的规律。因此，自由基的第一个ESR峰可能来自内皮细胞，第二个ESR峰可能来自中性粒细胞。然而，据推测，内皮细胞和中性粒细胞之间的相互作用始于再灌流的早期阶段(I/R3)。综上所述，WBC在骨骼肌缺血再灌注中起着非常重要的作用，具有WBC过滤器的局部灌流装置可能有助于预防MNMS。

Twenty-five dogs were used to investigate myonephropathic metabolic syndrome(MNMS). After 24-hour ischemia by ligation of abdominal aorta, the ligation was released and blood sample was taken from the vena cava before reperfusion. Just after reperfusion, 30 and 60 minutes after reperfusion. The levels of CPK, 6-keto PGF_1 alpha, 11-dehydrothromboxane B_2 were elevated during ischemia-reperfusion. White blood cell(WBC) increased just after reperfusion and decreased at 30 minutes after reperfusion. It is considered that this is because WBC migrate into the injured tissue.As the next step, we investigated the time course and the source of the free radicals generated in the rat isolated gracilis muscle after 2hr of ischemia followed by 1hr of reperfusion. Free radicals were measured by electron spin resonance(ESR). The intensity pattern of free radicals showed two peaks, the first peak was at 3min after reperfusion (I/R3) and the second peak lasted from 45min to 60min after reperfusion. The ESR intensities atI/R3 and I/R60 were inhibited in both X0 inhibitor(OPF-001 Ootsuka, Japan) group and neutropenia rat group. Myeloperoxidase(MPO) activity was also measured at I/R3,20,60. The increase at I/R3 and I/R60 in MPO activity showed the same pattern with the two peaks of free radical intensities. Therefore the first ESR peak of free radicals may be derived from the endothelial cells and the second ESR peak from the neutrophils. It is supposed, however, that an interaction between the endothelial cells and neutrophils starts at early phase(I/R3) of reperfusion.In conclusion, WBC play an very important role in ischemia-reperfusion in skeletal muscle and the local perfusion device with a filter for WBC may be useful to prevent MNMS.