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

用25只犬研究了肌肾病性代谢综合征（MNMS）。结扎腹主动脉缺血24小时后，松开结扎线，再灌注前从腔静脉取血。再灌注后即刻、再灌注后30分钟和60分钟。缺血再灌注期间CPK、6-酮PGF_1 α、11-去氢血栓烷B_2水平升高。白色血细胞（WBC）在再灌注后即刻升高，再灌注后30分钟下降。我们进一步研究了大鼠股薄肌缺血2 h再灌注1h后自由基产生的时间过程和来源。用电子自旋共振（ESR）测定自由基。自由基强度呈双峰型，第一峰出现在再灌注后3 min（I/R3），第二峰出现在再灌注后45 ~ 60 min。在X 0抑制剂（OPF-001 Ootsuka，Japan）组和中性粒细胞减少大鼠组中，I/R3和I/R60处的ESR强度均受到抑制。在I/R3、20、60时测定髓过氧化物酶（MPO）活性。I/R3和I/R60时MPO活性的增加与自由基强度的两个峰表现出相同的模式。因此，自由基的第一ESR峰可能来自内皮细胞，第二ESR峰可能来自中性粒细胞。结论：白细胞在骨骼肌缺血再灌注过程中起着重要作用，局部灌流装置对白细胞的过滤可能有助于预防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.