EDITORIALS
Triiodothyronine: To Be or Not To Be, That Is the Question Richard E. Clark, MD Allegheny General Hospital, Pittsburgh, Pennsylvania
T
riiodothyronine (T,) has been suggested for the treatment of the postcardiotomy patient for more than 5 years. The initial studies, which came from Capetown, concerned brain-dead animals and patients and suggested that this hormone might be useful in cardiac and renal transplantation if given to the donor. Subsequent studies by Novitsky and associates [l, 21 in pigs and baboons placed on cardiopulmonary bypass and given global myocardial ischemia demonstrated significant efficacious effects in the former but fewer in the latter. The initial clinical data generated by this same principal investigator involved 10 cases of profound postcardiotomy low cardiac output and suggested a beneficial effect in weaning from assist devices and catecholamines [3]. No concurrent group of nontreated patients was used in that study. The more recent trial [4], which was randomized and blinded, demonstrated that patients with ejection fractions of 0.30 or less receiving coronary artery bypass operations had lower requirements for pressor and diuretic support but had no significant improvement in hemodynamic variables. Those patients with ejection fractions greater than See also page 10. 0.40 and given higher doses of T, over a longer interval (20 hours) had significantly increased cardiac outputs compared with the nontreated group, which had normal cardiac indices in the first 24 hours after operation [4]. The authors of that study concluded that ". . . the results . . . indicate that T-3 would be of benefit to all patients undergoing cardiopulmonary bypass for open heart surgery." In this issue Novitsky and associates [5] purport to show that T, is of value for the "stunned myocardium." However, they provide global data for a regional injury. There is no assurance that the drug effects reported were not the consequence of stimulation of the normal muscle rather than the ischemic-reperfused segment. The interpretation of efficacy based on the first derivative of the left ventricular pressure is fraught with hazard, especially when the two groups of animals were not similar with respect to the hemodynamic variables immediately before drug administration. Where does this brief summary of information leave the surgeon who is called upon to treat increasing numbers of Address reprint requests to Dr Clark, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212-9986.
0 1991 by The Society of Thoracic Surgeons
older patients with more advanced cardiac and multisystem disease, reoperative patients, and desperately sick newborns and neonates? Will the use of T, be of benefit to these and others who sustain varying degrees of myocardial injury during operation? Unfortunately, the data are not convincing that T, provides a rapid improvement in contractility in low cardiac output syndrome or signifi-. cantly improves damaged major organ metabolism. Very few prophylactic treatments given at the onset of reperfusion have been shown to be constantly effective in terms of amelioration of injury or salutory hemodynamic effects in randomized, blinded clinical trials. If T, increases contractile force through the mechanisms of activation and up-regulating of adenylcyclase and adenosine phosphate translocase to improve efficiency of the oxidative process without increasing oxygen consumption, the drug may be useful for our ever-increasing group of high-risk patients. Perhaps we are looking in the wrong place. Triiodothyronine is a potent metabolic activator of aerobic metabolism of all tissues. The striking features in the baboon and human trials were the implied effects on the kidney, water flux, and the peripheral tissues. The major effects of T, may well be in the noncardiac tissues that, in the very ill, markedly influence cardiac performance. Further careful animal and clinical studies of various organs and tissues will be necessary before the cardiac surgical community will accept T, as a silver bullet for postcardiotomy injury.
References 1. Novitsky D, Human PA, Cooper DKC. Inotropic effect of triiodothyronine following myocardial ischemia and cardiopulmonary bypass: an experimental study in pigs. Ann Thorac Surg 1988;45:50-5. 2. Novitsky D, Human PA, Cooper DKC. Effect of triiodothyronine (T3) on myocardial high energy phosphates and lactate following ischemic and cardiopulmonary bypass: an experimental study in baboons. J Thorac Cardiovasc Surg 1988;96: 600-7. 3. Novitsky D, Cooper DKC, Swanapoel A. Inotropic effect of triiodothyronine (T3) following myocardial ischemia and cardiopulmonary bypass: initial experience in patients undergoing open-heart surgery. Eur J Cardiothorac Surg 1989;3:140-5. 4. Novitsky D, Cooper DKC, Barton I, et al. Triiodothyronine as an inotropic agent after open heart surgery. J Thorac Cardiovasc Surg 1989;98:972-8. 5. Novitsky D, Matthews N, Shawley D, Cooper DKC, Zuhdi N. Triiodothyronine in the recovery of stunned myocardium in dogs. Ann Thorac Surg 1991;51:10-7.
Ann Thorac Surg 1991;51:5
0003-4975/91/$3.50
Triiodothyronine: To Be or Not To Be, That Is the Question Richard E. Clark, MD Allegheny General Hospital, Pittsburgh, Pennsylvania
T
riiodothyronine (T,) has been suggested for the treatment of the postcardiotomy patient for more than 5 years. The initial studies, which came from Capetown, concerned brain-dead animals and patients and suggested that this hormone might be useful in cardiac and renal transplantation if given to the donor. Subsequent studies by Novitsky and associates [l, 21 in pigs and baboons placed on cardiopulmonary bypass and given global myocardial ischemia demonstrated significant efficacious effects in the former but fewer in the latter. The initial clinical data generated by this same principal investigator involved 10 cases of profound postcardiotomy low cardiac output and suggested a beneficial effect in weaning from assist devices and catecholamines [3]. No concurrent group of nontreated patients was used in that study. The more recent trial [4], which was randomized and blinded, demonstrated that patients with ejection fractions of 0.30 or less receiving coronary artery bypass operations had lower requirements for pressor and diuretic support but had no significant improvement in hemodynamic variables. Those patients with ejection fractions greater than See also page 10. 0.40 and given higher doses of T, over a longer interval (20 hours) had significantly increased cardiac outputs compared with the nontreated group, which had normal cardiac indices in the first 24 hours after operation [4]. The authors of that study concluded that ". . . the results . . . indicate that T-3 would be of benefit to all patients undergoing cardiopulmonary bypass for open heart surgery." In this issue Novitsky and associates [5] purport to show that T, is of value for the "stunned myocardium." However, they provide global data for a regional injury. There is no assurance that the drug effects reported were not the consequence of stimulation of the normal muscle rather than the ischemic-reperfused segment. The interpretation of efficacy based on the first derivative of the left ventricular pressure is fraught with hazard, especially when the two groups of animals were not similar with respect to the hemodynamic variables immediately before drug administration. Where does this brief summary of information leave the surgeon who is called upon to treat increasing numbers of Address reprint requests to Dr Clark, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212-9986.
0 1991 by The Society of Thoracic Surgeons
older patients with more advanced cardiac and multisystem disease, reoperative patients, and desperately sick newborns and neonates? Will the use of T, be of benefit to these and others who sustain varying degrees of myocardial injury during operation? Unfortunately, the data are not convincing that T, provides a rapid improvement in contractility in low cardiac output syndrome or signifi-. cantly improves damaged major organ metabolism. Very few prophylactic treatments given at the onset of reperfusion have been shown to be constantly effective in terms of amelioration of injury or salutory hemodynamic effects in randomized, blinded clinical trials. If T, increases contractile force through the mechanisms of activation and up-regulating of adenylcyclase and adenosine phosphate translocase to improve efficiency of the oxidative process without increasing oxygen consumption, the drug may be useful for our ever-increasing group of high-risk patients. Perhaps we are looking in the wrong place. Triiodothyronine is a potent metabolic activator of aerobic metabolism of all tissues. The striking features in the baboon and human trials were the implied effects on the kidney, water flux, and the peripheral tissues. The major effects of T, may well be in the noncardiac tissues that, in the very ill, markedly influence cardiac performance. Further careful animal and clinical studies of various organs and tissues will be necessary before the cardiac surgical community will accept T, as a silver bullet for postcardiotomy injury.
References 1. Novitsky D, Human PA, Cooper DKC. Inotropic effect of triiodothyronine following myocardial ischemia and cardiopulmonary bypass: an experimental study in pigs. Ann Thorac Surg 1988;45:50-5. 2. Novitsky D, Human PA, Cooper DKC. Effect of triiodothyronine (T3) on myocardial high energy phosphates and lactate following ischemic and cardiopulmonary bypass: an experimental study in baboons. J Thorac Cardiovasc Surg 1988;96: 600-7. 3. Novitsky D, Cooper DKC, Swanapoel A. Inotropic effect of triiodothyronine (T3) following myocardial ischemia and cardiopulmonary bypass: initial experience in patients undergoing open-heart surgery. Eur J Cardiothorac Surg 1989;3:140-5. 4. Novitsky D, Cooper DKC, Barton I, et al. Triiodothyronine as an inotropic agent after open heart surgery. J Thorac Cardiovasc Surg 1989;98:972-8. 5. Novitsky D, Matthews N, Shawley D, Cooper DKC, Zuhdi N. Triiodothyronine in the recovery of stunned myocardium in dogs. Ann Thorac Surg 1991;51:10-7.
Ann Thorac Surg 1991;51:5
0003-4975/91/$3.50
