Cellular mechanisms of endotoxin-induced myocardial depression in rabbits.
We investigated the mechanisms by which endotoxic shock induces intrinsic myocardial depression by studying cardiac myocytes isolated from 10 anesthetized instrumented rabbits given 172 +/- 42 (mean +/- SD) micrograms/kg IV endotoxin. Left ventricular (LV) depression developed 4 +/- 1 hours after endotoxin administration, with a 15 +/- 4% increase in LV internal end-systolic diameter, measured with sonomicrometers at a matched LV end-systolic pressure of 65 +/- 10 mm Hg. Normal LV pressure, arterial PO2, and pH were maintained to minimize confounding effects of ischemia, hypoxia, and acidosis. Cardiac myocytes from endotoxin-exposed rabbits had less unloaded cell shortening and lower peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) at [Ca2+] levels ranging from 0.5 to 16 mM when compared with myocytes isolated from normal rabbits or rabbits undergoing an identical protocol but without exposure to endotoxin. At 2 mM [Ca2+], cell shortening was depressed by approximately 25% because of a decrease in action potential duration (207 +/- 70 versus 375 +/- 64 milliseconds). In contrast, there was only mild impairment of sarcoplasmic reticulum (SR) function. When myocytes were restimulated after rest periods of 4 to 480 seconds, the decrement in cell shortening (rest decay), peak -dL/dt and peak +dL/dt, and the recovery from rest decay were similar in myocytes from endotoxin-treated and normal rabbits. There was a greater decrement in cell shortening in the second beat of postrest recovery in myocytes from endotoxin-treated rabbits than in normal myocytes. This was partly due to a 12% decrement in action potential duration with rest decay, which did not occur in normal myocytes. The SR Ca2+ content assessed by contractures in 10 mM caffeine was similar in the two groups. We conclude that endotoxic shock produces a LV depression in vivo that persists in isolated myocytes studied in vitro. This intrinsic myocardial depression is largely related to endotoxin-mediated sarcolemmal alterations, which shorten action potential duration, and is not due to alterations in SR function.
Hung
J
J
Department of Medicine, University of California, San Diego.
Lew
W Y
WY
D000138:Acidosis / Q000139:chemically induced / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003864:Depression, Chemical; D004731:Endotoxins; D006321:Heart / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology*
D004731:Endotoxins; D002110:Caffeine