We tested the hypothesis that ischemic preconditioning (PC) of skeletal muscle provided tolerance to a subsequent ischemic event 24 h later, and that such protection was due to nitric oxide (NO). Male Wistar rats, anesthetized with halothane, were randomly assigned to groups: ischemic (no PC; n = 11), PC ( n = 11), PC + N-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l; n = 5), PC + N-nitro-d-arginine methyl ester (100 μmol/l; n= 4), PC + aminoguanidine (AMG; 100 μmol/l; n = 4), ischemic +l-NAME ( n= 4), or ischemic + AMG ( n = 4). PC consisted of 5× 10 min of ischemia and reperfusion, and, 24 h later, 2 h of ischemia were induced by a tourniquet applied to the limb. With the use of intravital microscopy, the number of perfused capillaries ( N pc) in the extensor digitorum longus (EDL) muscle was measured over a 90-min reperfusion period. The ratio of ethidium bromide- to bisbenzimide-labeled nuclei was used to estimate tissue injury. PC preserved N pc(23.6 ± 2.5) following 2 h of ischemia compared with sham muscles (11.5 ± 5.1), significantly elevating inducible NO synthase (iNOS) activity (81% increase), but did not afford protection to the parenchyma.l-NAME and AMG prevented ischemia-reperfusion-induced reduction in N pc in muscles without PC. However, after 90 min of reperfusion,l-NAME ( N pc = 15.0 ± 1.7), but not AMG ( N pc = 22.8 ± 3.1), significantly reduced the microvascular protection afforded by PC. We conclude that PC of the EDL muscle resulted, 24 h later, in protection to microvascular perfusion only, and that such protection was due to NO from sources other than iNOS.

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Intestinal ischaemia with ensuing gangrene has been a serious clinical problem. Delay in diagnosis has inevitably led to either massive gut resection or death. It has been shown that the bowel contains high concentrations of both organic and inorganic phosphate. With gut ischaemia, phosphate is released from the bowel and elevated concentrations may be measured in peripheral blood, peritoneal fluid and urine. Associated leucocytosis and acidosis constitute a diagnostic laboratory triad. The alteration in gut phosphate metabolism has been studied extensively in dogs and humans. Under hypoxic conditions, a time period exists before irretrievable gut necrosis ensues. During this vital interval serum phosphate is elevated. In 20 clinical cases an accurate diagnosis of bowel ischaemia was made utilizing phosphate measurements. Three cases had an early diagnosis which led to embolectomy with no loss of gut. Elevated serum phosphate is an accurate diagnostic finding in early cases of massive gut ischaemia. It is hoped that this simple test may help lower the staggering mortality and morbidity associated with massive intestinal ischaemia.

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