As originally published in 1991: updated in 1998 by

Abstract

Although the interactions between thyroid hormone and the heart have been recognized for more than 150 years, and despite more than 10 years of experimental and clinical research during cardiac operations, the use of thyroid hormone supplementation to correct the triiodothyronine (T3) depleted state initiated by cardiopulmonary bypass remains controversial. It is generally accepted that cardiopulmonary bypass initiates a T3 depleted state that persists up to 24 hours postoperatively. The significance of this euthyroid sick state is unclear, however; whether this syndrome is pathologic, serves as a marker of the severity of illness, or is an adaptive response to stress remains uncertain. Numerous experiments have tested the hypothesis that thyroid hormone supplementation improves myocardial performance after injury [1Dyke C. The use of thyroid hormone in cardiac surgery.Curr Opin Cardiol. 1996; 11: 603-609Crossref PubMed Scopus (6) Google Scholar]. These data, using a variety of models, have nearly universally demonstrated that T3 supplementation after ischemic injury improves contractile performance. In an isolated rabbit or rat heart preparation, an in vivo porcine model, an ex vivo canine model, or isolated papillary muscle or myocytes, T3 supplementation has been demonstrated to augment contractility after ischemia. As we pointed out in our article in 1991 [2Dyke C.M. Yeh Jr, T. Lehman J.D. et al.Triiodothyronine-enhanced left ventricular function after ischemic injury.Ann Thorac Surg. 1991; 52: 14-19Abstract Full Text PDF PubMed Scopus (75) Google Scholar], which has been confirmed by others, it appears that T3 supplementation improves the contractile response only after ischemic injury, but does not affect the contractile response of normal, uninjured myocardium (as an inotrope such as epinephrine would). This observation has relevance when one considers the clinical experience of T3 supplementation during a cardiac operation. Despite the strong experimental evidence, it has proved very difficult to demonstrate an appreciable benefit of T3 supplementation in patients undergoing cardiac operations. In a randomized, placebo-controlled trial, Klemperer and associates [3Klemperer J.D. Klein I. Gomez M. et al.Thyroid hormone treatment after coronary artery bypass surgery.N Engl J Med. 1995; 33: 1522-1527Crossref Scopus (387) Google Scholar] demonstrated that T3 supplementation improved the cardiac index in the immediate postoperative period; however, inotropic requirements and clinical outcome were not different between groups. In a second large, randomized, double-blind, placebo-controlled trial, Bennett-Guerrero and colleagues [4Bennett-Guerrero E. Jimenez J.L. White W. et al.Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery a randomized double-blind, placebo-controlled trial.JAMA. 1996; 275: 687-692Crossref PubMed Google Scholar] did not show any improvement in either cardiac performance or clinical outcome in patients who received T3 compared with placebo. These studies contrast with another large clinical trial. At the most recent meeting of The American Association For Thoracic Surgery, Mullis-Jansson and associates [5Mullis-Jansson S, Argenziano M, Corwin S, et al. Intravenous T3 improves myocardial function and reduces morbidity after coronary bypass surgery: results of a double-blind, randomized trial. Presented at the 78th Annual Meeting of The American Association for Thoracic Surgery, Boston, MA, May 3–6, 1998.Google Scholar] reported a randomized, double-blind, placebo-controlled trial in which T3 supplementation significantly improved postoperative hemodynamics, reduced postoperative iotropic use, and significantly reduced postoperative morbidity and mortality. They did not demonstrate any difference in the incidence of atrial arrhythmias between groups. Although the experimental data are remarkably consistent and convincing, the clinical waters are more murky. One possible explanation for the seeming contrast between the experimental and clinical data may lie in the varying degrees of myocardial injury present during clinical trials. Experimental preparations are quite sensitive in discriminating changes in contractility as well as standardization of the degree of ischemic injury. Obviously the degree of myocardial injury after coronary bypass grafting is difficult to quantify and, in this era of excellent myocardial protection, is likely to be quite small. One might hypothesize that the benefit of T3 supplementation is directly proportional to the degree of ischemic injury suffered by the myocyte; in patients who are not acutely ischemic when they go to the operating room, clinical benefit of T3 supplementation is likely to be more difficult to demonstrate. There are patients, however, in whom T3 supplementation should be considered. Patients with ongoing ischemia who present emergently or after catheterization laboratory misadventures represent a sizeable population in whom T3 supplementation may be worthwhile. Similarly, brain-dead organ donors are good candidates for T3 supplementation as the subendocardial ischemic injury associated with brain death may be quite severe. It is unlikely that T3 supplementation will improve upon the already excellent results of elective cardiac surgical procedures performed today. However, T3 supplementation in the impaired or acutely injured ventricle remains an important therapeutic adjunct with significant clinical benefit.