Acute brain death alters left ventricular myocardial gene expression

Objectives: The depressed myocardial function observed in brain dead organ donors has been attributed to massive sympathetic discharge and catecholami ne cardiotoxicity, Because elevated catecholamines are associated with alte red myocardial gene expression, we investigated whether acute brain death f rom increased intracranial pressure alters the expression of myocardial gen e products important in contractility, Methods: A balloon expansion model w as used to increase intracranial pressure in rabbits (n = 22), At timed int ervals after brain death, mean arterial pressure, heart rate, electrocardio grams, histologic myocardial injury, and systemic catecholamines were asses sed. Messenger RNA levels encoding myofilaments, adrenergic receptors, sarc oplasmic reticulum proteins, transcription factors, and stress-induced prog rams were measured with blot hybridization of total left ventricular RNA. R esults: Increased intracranial pressure induced an immediate presser respon se that temporally coincided with diffuse electrocardiographic ST segment c hanges, Systemic epinephrine and norepinephrine levels concurrently increas ed (5- to 8-fold within 1 minute), then fell below baseline within 2 hours, and remained depressed at 4 hours. By 1 hour, histologic injury was eviden t. Four hours after the induction of increased intracranial pressure, level s of messenger RNA-encoding skeletal and cardiac alpha-actins, egr-1, and h eat shock protein 70 were significantly increased. Sham-operated animals di d not exhibit these changes. Conclusions: Select changes in myocardial gene expression occur in response to increased intracranial pressure and implic ate ventricular remodeling in the myocardial dysfunction associated with ac ute brain death.