Central sympathetic blockade ameliorates brain death-induced cardiotoxicity and associated changes in myocardial gene expression

Objective: Brain death results in cardiac injury and hemodynamic instability. After brain death, catecholamine levels surge in concert with increased expression of select myocardial gene products. Sympathetic blockade was used to investigate the effects of the adrenergic nervous system on myocardial gene expression in a rabbit model of brain death. Methods: A balloon expansion model of brain death in rabbits (n = 42) was used with and without sympathetic blockade (xylazine, acetylpromazine, and ketamine). Sham-operated and naive rabbits served as control animals. Over 4 hours, mean arterial pressure, heart rate, electrocardiographic results, catecholamine levels, myocardial histology, and messenger RNA levels were assessed. Results: Sympathetic blockade decreased basal catecholamine levels and blocked the catecholamine surge accompanying brain death. The typical hemodynamic instability, adverse electrocardiographic changes, and myocellular injury associated with brain death were all significantly decreased. Sympathetic blockade not only suppressed the previously reported increases in myocardial gene expression (cardiac and skeletal α-actin, egr-1, and heat shock protein 70) but also suppressed the expression of multiple other genes (α and β myosin heavy chain, calcium ATPase [sarcoplasmic reticulum Ca2+-adenosine triphosphatase pump, SERCA-2a], phospholamban [ryanodine receptor], and c-jun). Conclusion: Central sympathetic blockade minimizes the hemodynamic instability associated with brain death and neutralizes the increased expression of multiple myocardial gene products associated with brain death. J Thorac Cardiovasc Surg 2002;124:1087-98