EFFECT OF SEPSIS AND 3,5,3'-TRIIODOTHYRONINE REPLACEMENT ON MYOCARDIAL INTEGRITY DURING OXIDANT CHALLENGE

Objective: To determine whether sepsis, with or without thyroid hormon al augmentation, induces myocardial tolerance to an oxidant challenge. Design: A prospective, randomized, controlled animal trial, Setting: University research laboratory. Subjects: Twenty male Sprague-Dawley r ats. 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 rapidl y excised for retrograde Langendorff perfusion, Oxyradical challenge c onsisted of the addition of 200 mu M of hydrogen peroxide to the perfu sate for 60 mins. Measurements and Main Results: Myocardial contractil ity and relaxation were continuously recorded, Perfusate glutathione a nd lactate dehydrogenase concentrations were determined enzymatically at 30 min intervals for 90 mins, Oxyradical perfusion alone significan tly increased glutathione efflux and decreased myocardial contractilit y when compared with control animals, Prior cecal ligation and punctur e decreased oxidant mediated glutathione efflux and maintained myocard ial contractility, 3,5,3'-triiodothyronine supplementation appeared to increase late cardiac contractility and cellular integrity during oxi dant challenge, However, this increase was not statistically significa nt. Conclusions: Antecedent septic challenge appears to induce toleran ce to further myocardial oxyradical exposure and improves myocardial f unctional and biochemical integrity, Thyroid hormonal supplementation may provide a modest additional benefit in septic animals.