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 pressur e-volume relationships (sonomicrometers). In the control group, endoto xin (100 mu g/kg iv) induced systolic depression (> 10% increase in en d-systolic volume at matched end-systolic pressure) in 9 of 16 and dia stolic dilation (> 10% increase in end-diastolic volume at matched end -diastolic pressure) in 8 of 16 rabbits within 7 h, unrelated to hypot ension, acidosis, or hypoxia. Seven rabbits were pretreated with nitro gen mustard (1-2 mg/kg iv 4 and 2 days before) to decrease circulating neutrophils and monocytes by 98%. Endotoxin did not induce systolic d epression in any rabbit (P = 0.01 compared with control), and diastoli c dilation developed in one rabbit (P = 0.12). In eight rabbits pretre ated with dimethylthiourea (DMTU; 500 mg/kg iv 30 min before), an intr acellular free radical scavenger, systolic depression developed in one (P = 0.05) and diastolic dilation in five (P = 0.44). We conclude tha t cells inhibited by nitrogen mustard (e.g., neutrophils, monocytes, o r macrophages) mediate endotoxin-induced left ventricular systolic dep ression. DMTU inhibited endotoxin-induced systolic but not diastolic d ysfunction.