Endotoxin-induced left ventricular depression is blocked by nitrogen mustard or dimethylthiourea in rabbits.
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 micrograms/kg iv) 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 h, unrelated to hypotension, acidosis, or hypoxia. Seven rabbits were pretreated with nitrogen mustard (1-2 mg/kg iv 4 and 2 days before) to decrease circulating neutrophils and monocytes by 98%. Endotoxin did not induce systolic depression in any rabbit (P = 0.01 compared with control), and diastolic dilation developed in one rabbit (P = 0.12). In eight rabbits pretreated with dimethylthiourea (DMTU; 500 mg/kg iv 30 min before), an intracellular free radical scavenger, systolic depression developed in one (P = 0.05) and diastolic dilation in five (P = 0.44). We conclude that cells inhibited by nitrogen mustard (e.g., neutrophils, monocytes, or macrophages) mediate endotoxin-induced left ventricular systolic depression. DMTU inhibited endotoxin-induced systolic but not diastolic dysfunction.
Nishikawa
Y
Y
Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California 92161, USA.
Lew
W Y
WY
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology*; D011817:Rabbits; D013599:Systole; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects*
D004731:Endotoxins; D016166:Free Radical Scavengers; D008466:Mechlorethamine; C038983:1,3-dimethylthiourea; D013890:Thiourea