Contribution of myoglobin-induced increases in vascular resistance to shock decompensation in experimental Crush-syndrome in anesthetized rats.

Myoglobin is known to become nephrotoxic when released in greater amounts from skeletal muscle into the general circulation during shock. The present study deals with the question as to whether a myoglobin-induced increase in vascular tone additionally contributes to the detrimental role of this protein in hypovolemic shock. Anesthetized rats were subjected to 250 mg kg x h(-1) myoglobin infused i.v. during hemorrhagic hypotension of 50 mmHg. Shock survival time was measured, as were blood flow and vascular resistance in kidney, intestine, brain, and heart, using the microsphere method. Rats subjected to only myoglobin or hemorrhage survived a period of >120 min; in contrast, rats, exposed to both myoglobin and hemorrhage died at 68 +/- 9 min. When the animals subjected to only hemorrhage and to myoglobin/ hemorrhage were compared, significantly lower values were found in the latter group with respect to blood flow in the kidney (1.7 +/- 0.1 vs. 0.2 +/- 0.05 ml x min(-1) x g(-1)), small intestine (1.0 +/- 0.1 vs. 0.5 +/- 0.1 ml x min(-1) x g(-1)), cardiac output (112 +/- 5 vs. 62 +/- 10 ml(-1) x min(-1) x kg(-1)), and significantly higher values of total peripheral vascular resistance (0.45 +/- 0.02 vs. 0.81 +/- 0.12 mmHg x min x ml(-1) x kg) at 50 min of hypotension. It is assumed that these effects of myoglobin are induced by its ability to scavenge endogenous nitric oxide, because a modified, non-nitrosylable myoglobin was unable to induce such effects. The results support the view that a pathological release of myoglobin into the general circulation causes increases in vascular resistance of vital organs that may contribute to decompensation of tissue supply when occurring in hypovolemic shock.