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 alpha-actin, egr-1, and heat shock protein 70) but also suppressed the expression of multiple other genes (alpha and beta myosin heavy chain, calcium ATPase [sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase pump, SERCA-2a], phospholamban [ryanodine receptor], and c-jun).


CONCLUSIONS
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.
Yeh
Thomas
T
Jewish Hospital Cardiovascular Research Center at University of Louisville, Department of Surgery, Division of Cardiothoracic Surgery, University of Louisville, Louisville, KY 40202, USA.
Wechsler
Andrew S
AS
Graham
Laura
L
Loesser
Kathryn E
KE
Sica
Domenic A
DA
Wolfe
Luke
L
Jakoi
Emma R
ER
D000818:Animals; D001926:Brain Death; D004562:Electrocardiography; D004837:Epinephrine / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000502:physiology*; D020257:Ventricular Remodeling
D012333:RNA, Messenger; D009638:Norepinephrine; D004837:Epinephrine