title: Myocardial dysfunction in endotoxin- and E. coli-induced shock: pathophysiological mechanisms.
abstract: Experimental studies have documented that myocardial dysfunction is precipitated between 3 and 6 hr after endotoxin or E. coli. This finding has now been confirmed in human septic shock. A "Hinshaw-modified" isolated working left ventricle preparation has been used to document and assess the degree of failure. It was found that the failure is often severe and reversible only temporarily by adrenergic agents but reversible by digoxin or insulin. The cause of the failure has not been identified, but evidence is presented against a myocardial depressant factor (MDF) being the causative factor. Hearts subjected to a 2-4 hr period of hypotension on the threshold of failure show no signs of failure when subjected to blood circulating from an animal in splanchnic arterial occlusion shock. Hearts from pancreatectomized animals subjected to endotoxin shock with their source of MDF removed demonstrate the typical failure in 4-6 hr. Other factors are suggested that contribute to myocardial dysfunction: hypotension or nonuniform perfusion of subendocardial regions of the heart, depressed responsiveness to inotropic and chronotropic stimuli, intracardiac ionic and fluid disturbances, and increases in heart chamber and muscle stiffness. Since steroid/antibiotic therapy increases the probability (p less than 0.05) that an animal will survive lethal sepsis, investigating the effect of this therapy on myocardial function may aid in determining whether or not this degree of heart failure contributes in the animal to irreversible shock and death.
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004573:Electrolytes / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004927:Escherichia coli Infections / Q000503:physiopathology*; D005839:Gentamicins / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009201:Myocardial Depressant Factor / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D012772:Shock, Septic / Q000503:physiopathology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D004573:Electrolytes; D005839:Gentamicins; D009201:Myocardial Depressant Factor; D008776:Methylprednisolone Hemisuccinate