Staphylococcal alpha toxin induced cardiac dysfunction

Myocardial dysfunction in isolated heart muscle preparations from Wistar rats was induced by low concentrations (3 hemolytic units/mL) of staphylococcal alpha toxin. Exposure of isolated, intact hearts to alpha toxin caused an increase in coronary perfusion pressure within 1 min that continued to rise throughout the experiment. Similar changes occurred with intraventricular systolic pressure. Diastolic pressure initially remained stable but increased after 5 to 6 mins of treatment. Coronary pressure increased approximately 68% while ventricular contractile response was altered 45%. Short exposure to alpha toxin, followed by perfusion with toxin-free buffer did not reverse the coronary vascular response. Pretreatment of the heart with the same concentration of alpha toxoid blocked alpha toxin. Tension development in isolated atria was insensitive to 3 hemolytic units/mL of alpha toxin but it was altered by 12 hemolytic units/mL. Proteinaceous extracts from ventricular cardiac muscle inhibited alpha toxin fourfold more than extracts from atrial tissue. These data demonstrate that purified alpha toxin, administered in low concentrations to cardiac muscle with an intact vascular supply, irreversibly changes pump function primarily through vascular constriction. Direct effects on cardiac muscle tissue could only be observed with substantially higher toxin concentrations. The mechanism of action appears to be mediated through a binding or receptor response that is more sensitive in ventricular than atrial muscle.