ObjectiveTo determine whether sepsis, with or without thyroid hormonal augmentation, induces myocardial tolerance to an oxidant challenge.DesignA prospective, randomized, controlled animal trial.SettingUniversity research laboratory.SubjectsTwenty male Sprague-Dawley rats.InterventionsAfter anesthesia, animals underwent cecal ligation and puncture, with or without 3,5,3 prime-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 micro Meter of hydrogen peroxide to the perfusate for 60 mins.Measurements and Main ResultsMyocardial 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 prime-triiodothyronine supplementation appeared to increase late cardiac contractility and cellular integrity during oxidant challenge. However, this increase was not statistically significant.ConclusionsAntecedent 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.(Crit Care Med 1996; 24:850-854)