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. Design: A prospective, randomized, controlled animal trial, Setting: University research laboratory. Subjects: Twenty male Sprague-Dawley rats. Interventions: 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 mu M of hydrogen peroxide to the perfusate for 60 mins. Measurements and Main 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.