D.Novitzky, MD

Early Organ Injury Following Experimental Brain Death

Division of Cardiothoracic Surgery, University of South Florida

USA

The summary: The availability of organs procured from brain dead (BD) donors cannot meet an ever-increasing demand. As a result, a significant number of recipients will expire before a suitable organ becomes available. Thus on many occasions harvesting a suboptimal organ may increase the occurrence of adverse outcomes.

Hemodynamic, endocrine and metabolic studies conducted on BD animals have confirmed a sequence of adverse events, which eventually will lead to a suboptimal function of the donor heart and other organs. Immediately following the induction of BD there is an adrenergic storm. This includes the release of endogenous cathecholamines and toxic tissue levels of epinephrine, which induces an acute myocardial ischemic injury. Hearts examined in this state under light microscopy show patchy diffuse injury of the subendocardium, conduction tissue, coronary arteries and various forms of myocytes necrosis as well as mononuclear cell infiltration.

Examination under electron microscopy confirms the presence of acute scattered cellular injury affecting mainly the sarcomere and the mitochondria. Following the cathecolamine storm, there is a reduction of plasma free triiodothyronine (FT3), free levothyroxine (FT4), cortisol, antidiuretic hormone (ADH), adrenocortical stimulating hormone (ACTH), normal thyroid stimulating hormone (TSH) and marked elevation of reverse triiodothyronine(T3). These events cause progressive inhibition of aerobic metabolic pathways, and lead to a reduction of myocardial tissue glycogen, adenosine triphosphate (ATP), creatine phosphate (CP) and lactate accumulation. The structural and metabolically injured heart then exhibits a reduction in contractility. Moreover, studies have demonstrated that hormonal replacement (T3, cortisol and insulin) in BD animals results in metabolic, biochemical and cardiac contractility recovery.

A similar plasma thyroid profile is also observed in animals subjected to cardiopulmonary bypass (CPB). This is associated with a significant high-energy phosphate depletion and lactate accumulation. It has been demonstrated that therapy with T3 reverses this myocardial dysfunction.

The administration of T3, cortisol and insulin to human brain injured organ donors allows rapid metabolic and hemodynamic recovery. Studies have confirmed that therapy with T3 alone has proven to be as efficient as hormonal therapy. Initially T3 is administered to the human BD organ donor and later to both the donor and recipient at the time of cardiac reperfusion. This results in acceptable functional recovery in the recipient even in initially marginal organ donors originally on high doses of inotropic support. By replacing T3, hearts, which were not initially considered viable for cardiac transplantation, were harvested with good outcomes in the recipient. The potential reversal of this injury by administering thyroid hormone creates a larger donor organ pool.