Affiliation:
1. From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany.
Abstract
Background
—Cardiac performance is severely depressed in septic shock. Endotoxin has been implicated as the causative agent in Gram-negative sepsis, but similar abnormalities are encountered in Gram-positive sepsis. We investigated the influence of the major exotoxin of
Staphylococcus aureus,
staphylococcal α-toxin, in isolated perfused rat hearts.
Methods and Results
—α-Toxin 0.25 to 1 μg/mL caused a dose-dependent increase in coronary perfusion pressure that more than doubled. In parallel, we noted a decrease in left ventricular developed pressure and the maximum rate of left ventricular pressure rise (dP/dt
max
), dropping to a minimum of <60% of control. These changes were accompanied by a liberation of thromboxane A
2
and prostacyclin into the coronary effluent. The release of creatine kinase, lactate dehydrogenase, potassium, and lactate did not surpass control heart values, and leukotrienes were also not detected. Indomethacin, acetylsalicylic acid, and the thromboxane receptor antagonist daltroban fully blocked the α-toxin–induced coronary vasoconstrictor response and the decrease in left ventricular developed pressure and dP/dt
max
, whereas the lipoxygenase inhibitor nordihydroguaiaretic acid, the platelet activating factor antagonist WEB 2086, and the α-adrenergic antagonist phentolamine were entirely ineffective. Inhibition of nitric oxide synthase even enhanced the α-toxin–induced increase in coronary perfusion pressure and the loss in myocardial performance.
Conclusions
—Purified staphylococcal α-toxin provokes coronary vasoconstriction and loss in myocardial contractility. The responses appear to be largely attributable to the generation of thromboxane and are even enhanced when the endogenous nitric oxide synthesis is blocked. Bacterial exotoxins, such as staphylococcal α-toxin, may thus be implicated in the loss of cardiac performance encountered in Gram-positive septic shock.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
61 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献