Myocardial dysfunction in a nonlethal, nonshock model of chronic endotoxemia.
Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Myocardial function was assessed after 6 and 30 hr of ET infusion and compared with control rats which received a saline infusion and were fasted to match the anorexia of ET rats. Cardiac output (CO) and coronary blood flow, measured by the radiolabeled microsphere method, and mean arterial blood pressure, heart rate, total peripheral resistance, and stroke volume, were determined in vivo. Treatment differences were limited to a 13% lower arterial pressure in ET rats after 30 hr of infusion. Myocardial function was evaluated in vitro in similarly treated rats with the isolated perfused working heart preparation; preload was altered by raising the left atrial filling pressure (LAFP) from 10 to 30 cm water. After both 6 and 30 hr of infusion, hearts from ET rats exhibited a significantly lower peak systolic pressure (PSP), CO, and coronary flow in response to increasing LAFP, and a greater oxygen consumption per unit of myocardial work (CO X PSP). Reduced in vitro work performance of hearts from endotoxemic rats was demonstrated early in the course of chronic endotoxemia and in the absence of in vivo evidence of cardiac dysfunction. Myocardial dysfunction, masked in vivo by compensatory mechanisms used to maintain adequate cardiovascular function, may be an important feature in the pathogenesis of both experimental endotoxemia and clinical gram-negative sepsis.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D004926:Escherichia coli; D006090:Gram-Negative Bacteria; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008863:Microspheres; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D018805:Sepsis / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D003692:Delayed-Action Preparations; D004731:Endotoxins