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 nucleotidebinding proteins (Gia) 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 Gia) and 221% (pertussis toxin substrate) of myocardial Gia was observed in patients with catecholamine-refractory shock compared with controls. The increases of Gia were greater than those found in chronic heart failure reported earlier. Conclusions An increase in the expression of Gia could also be important in conditions other than chronic heart failure, eg, septic shock. An increase of Gia could play a pathophysiologically relevant role in catecholamine refractoriness in septic shock and could provide a target for pharmacologic treatment in this condition.