ObjectiveEscherichia colihemolysin has been implicated as an important pathogenic factor in extraintestinalE. coliinfections including sepsis. We investigated the effects of coronary administration ofE. colihemolysin on cardiac function in isolated rat hearts perfused at constant flow.DesignProspective, experimental study.SettingResearch laboratory at a university hospital.SubjectsIsolated hearts from male Wistar rats.InterventionsIsolated hearts were perfused with purifiedE. colihemolysin for 60 min.Measurements and Main ResultsLow concentrations of the toxin in the perfusate (0.1–0.2 hemolytic units/mL) caused a dose-dependent coronary vasoconstriction with a marked increase in coronary perfusion pressure, which was paralleled by a decrease in left ventricular developed pressure (and the maximum rate of left ventricular pressure increase). Moreover, 0.2 hemolytic units/mLE. colihemolysin evoked ventricular fibrillation within 10 mins of toxin application. These events were accompanied by the liberation of leukotrienes (LTC4, LTD4, LTE4, and LTB4), thromboxane A2, prostaglandin I2, and the cell necrosis markers lactate dehydrogenase and creatine kinase into the recirculating perfusate. The lipoxygenase inhibitor MK-886 fully blocked the toxin-induced coronary vasoconstrictor response and the loss of myocardial contractility and reduced the release of lactate dehydrogenase and creatine kinase. In contrast to this, the cyclooxygenase inhibitor indomethacin was entirely ineffective. In addition,E. colihemolysin elicited an increase in heart weight and left ventricular end-diastolic pressure, the latter again being suppressed by MK-886.ConclusionsLow doses ofE. colihemolysin cause strong coronary vasoconstriction, linked with loss of myocardial performance, release of cell injury enzymes, and electrical instability, with all events being largely attributable to toxin-elicited leukotriene generation in the coronary vasculature. Bacterial exotoxins such asE. colihemolysin thus may be implicated in the cardiac abnormalities encountered in septic shock.