Endotoxin-induced left ventricular depression is blocked by
nitrogen mustard or dimethylthiourea in rabbits.
Nishikawa, Yasuhiro, and Wilbur Y. W. Lew.
Cardiology Division, Department of Medicine, Department of Veterans
Affairs Medical Center and University of California, San Diego, San
Diego, California 92161
APStracts 2:0111H, 1995.
We examined endotoxin-induced myocardial depression in 31 anesthetized
rabbits using left ventricular end-systolic and end-diastolic
pressure-volume relationships (sonomicrometers). In the control
group, endotoxin (100 [mu]g/kg i.v.) induced systolic depression
(>10% increase in end-systolic volume at matched end-systolic
pressure) in 9 of 16 and diastolic dilation (>10% increase in end
-diastolic volume at matched end-diastolic pressure) in 8 of 16
rabbits within 7 hours, unrelated to hypotension, acidosis or
hypoxia. Seven rabbits were pretreated with nitrogen mustard (1-2
mg/kg i.v. 4 and 2 days before) to decrease circulating neutrophils
and monocytes by 98%. Endotoxin did not induce systolic depression in
any rabbit (p=.01 compared with control) and diastolic dilation
developed in one rabbit (p=0.12). In eight rabbits pretreated with
dimethylthiourea (500 mg/kg i.v. 30 min before), an intracellular
free radical scavenger, systolic depression developed in one (p=.05)
and diastolic dilation in five (p=.44). We conclude that cells
inhibited by nitrogen mustard (e.g. neutrophils, monocytes, or
macrophages) mediate endotoxin-induced left ventricular systolic
depression. Dimethylthiourea inhibited endotoxin-induced systolic,
but not diastolic dysfunction.
Received 18 November 1994; accepted in final form 22 March 1995.
APS Manuscript Number H1032-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.