Myocardial morphometric changes related to decreased contractility after endotoxin.
Decreased ventricular contractility during sepsis lasts much longer than the half-lives of inflammatory mediators that have been suggested to be myocardial depressant factors. Our hypothesis is that blood-borne factors may also cause myocardial structural changes, including damage and death of myocytes, associated with decreased ventricular contractility. We tested this hypothesis in an isolated rabbit heart perfused by a support rabbit. Support rabbits received 1 mg/kg endotoxin i.v. over 30 min (endotoxin group, n = 7) or vehicle (control group, n = 6). The slope of the end-systolic pressure-volume relationship, Emax, was used to measure contractility of the isolated heart. Five hours after endotoxin infusion, Emax decreased by 17 +/- 7% (P < 0.03) compared with 0 +/- 2% in the control group. Quantitative morphometric analysis of isolated hearts from the endotoxin group demonstrated an increased volume fraction of myocardial capillaries occupied by leukocytes (15.7 +/- 3.5 vs. 3.0 +/- 0.7% in the control group, P < 0.05), structurally abnormal myocytes (7.6 +/- 3.6 vs. 0.8 +/- 0.4%, P < 0.05), and interstitial edema (23.2 +/- 5.2 vs. 14.3 +/- 2.1%, P < 0.05). We conclude that blood-borne factors cause myocardial structural changes that may contribute to decreased ventricular contractility and may explain the prolonged decrease in ventricular contractility during sepsis.
Goddard
C M
CM
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Allard
M F
MF
Hogg
J C
JC
Walley
K R
KR
D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D003326:Coronary Circulation; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology*; D011817:Rabbits
D004731:Endotoxins