INCREASE OF MYOCARDIAL INHIBITORY G-PROTEINS IN CATECHOLAMINE-REFRACTORY SEPTIC SHOCK OR IN SEPTIC MULTIORGAN FAILURE

PURPOSE: The aim of the study was to investigate the mechanisms of myocardial catecholamine refractoriness in septic shock. METHODS: The inhibitory guanine nucleotide-binding proteins (Gi alpha) were studied with pertussis toxin labeling and radioimmunologically in myocardium from patients who died while in catecholamine-refractory septic shock and from patients who died of noncardiac disease. RESULTS: An increase by 62% (immunological Gi alpha) and 221% (pertussis toxin substrate) of myocardial Gi alpha was observed in patients with catecholamine-refractory shock compared with controls. The increases of Gi alpha were greater than those found in chronic heart failure reported earlier. CONCLUSIONS: An increase in the expression of Gi alpha could also be important in conditions other than chronic heart failure, eg, septic shock. An increase of Gi alpha could play a pathophysiologically relevant role in catecholamine refractoriness in septic shock and could provide a target for pharmacologic treatment in this condition.