Proteases and antiproteases in experimental low-flow states.

Abstract

Refractory hypotension due to hemorrhage, septicemia, or myocardial infarction continues to be a major cause of death. The mechanism responsible for the development of the so-called “irreversible phase” in low-flow states has been under investigation for a number of years. Many theories (1, 13, 15) have been advanced to explain why vigorous therapy aimed at volume replacement, reduction of peripheral resistance, and correction of acidosis often fails to save the patient. While it appears unlikely that any single factor in the pathophysiology of shock can account for the irreversibility mechanism, good evidence exists that hypercoagulability of the blood and capillary leakage play a prominent role. In addition, emphasis on myocardial depression (10) has been renewed as a major contributory factor to the mortality from shock. Recent studies (18) have suggested that a group of humoral agents called kinins are released or activated as a result of tissue trauma and intestinal ischemia. These agents have been shown to exert a damaging effect on the microcirculation (12) and have also been implicated in the myocardial depression following hemorrhage.