Effect of sepsis and 3,5,3'-triiodothyronine replacement on myocardial integrity during oxidant challenge.
OBJECTIVE
To determine whether sepsis, with or without thyroid hormonal augmentation, induces myocardial tolerance to an oxidant challenge.


METHODS
A prospective, randomized, controlled animal trial.


METHODS
University research laboratory.


METHODS
Twenty male Sprague-Dawley rats.


METHODS
After anesthesia, animals underwent cecal ligation and puncture, with or without 3,5,3'-triiodothyronine replacement (3 ng/hr), or sham surgery. Twenty-four hours later, the heart was rapidly excised for retrograde Langendorff perfusion. Oxyradical challenge consisted of the addition of 200 microM of hydrogen peroxide to the perfusate for 60 mins.


RESULTS
Myocardial contractility and relaxation were continuously recorded. Perfusate glutathione and lactate dehydrogenase concentrations were determined enzymatically at 30-min intervals for 90 mins. Oxyradical perfusion alone significantly increased glutathione efflux and decreased myocardial contractility when compared with control animals. Prior cecal ligation and puncture decreased oxidant-mediated glutathione efflux and maintained myocardial contractility. 3,5,3'-triiodothyronine supplementation appeared to increase late cardiac contractility and cellular integrity during oxidant challenge. However, this increase was not statistically significant.


CONCLUSIONS
Antecedent septic challenge appears to induce tolerance to further myocardial oxyradical exposure and improves myocardial functional and biochemical integrity. Thyroid hormonal supplementation may provide a modest additional benefit in septic animals.
Davidson
S B
SB
Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
Dulchavsky
S A
SA
Diebel
L N
LN
Dutta
S
S
Cullen
W J
WJ
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D016877:Oxidants / Q000009:adverse effects*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D016877:Oxidants; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D007770:L-Lactate Dehydrogenase; D005978:Glutathione