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Updated: Aug 14, 2026
Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
Acute brain death alters left ventricular myocardial gene expression
T Yeh1, A S Wechsler, L J Graham
1Department of Surgery, University of Louisville, Ky 40202, USA.
Insights
Acute brain death alters myocardial gene expression, leading to ventricular remodeling and dysfunction. This study in rabbits shows increased intracranial pressure affects genes crucial for heart contractility.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Neurocritical Care
Background:
- Brain death is associated with myocardial dysfunction, often attributed to sympathetic overactivity and catecholamine toxicity.
- Elevated catecholamines can alter myocardial gene expression, potentially contributing to cardiac dysfunction.
Purpose of the Study:
- To investigate if acute brain death induced by increased intracranial pressure alters myocardial gene expression.
- To identify specific genes involved in myocardial contractility affected by brain death.
Main Methods:
- Rabbits underwent induced brain death via increased intracranial pressure using a balloon expansion model.
- Systemic hemodynamics, catecholamine levels, and myocardial gene expression (mRNA) were assessed at timed intervals.
- Histologic myocardial injury was evaluated to correlate with molecular changes.
Main Results:
- Increased intracranial pressure caused immediate pressor response and ST segment changes, with transiently elevated catecholamines.
- Histologic myocardial injury was observed within 1 hour.
- Four hours post-brain death, significant increases in mRNA for skeletal/cardiac alpha-actins, egr-1, and heat shock protein 70 were detected.
Conclusions:
- Acute brain death triggers specific changes in myocardial gene expression.
- These gene expression alterations suggest ventricular remodeling contributes to myocardial dysfunction in acute brain death.
Objectives:
The depressed myocardial function observed in brain dead organ donors has been attributed to massive sympathetic discharge and catecholamine cardiotoxicity. Because elevated catecholamines are associated with altered myocardial gene expression, we investigated whether acute brain death from increased intracranial pressure alters the expression of myocardial gene products important in contractility.
Methods:
A balloon expansion model was used to increase intracranial pressure in rabbits (n = 22). At timed intervals after brain death, mean arterial pressure, heart rate, electrocardiograms, histologic myocardial injury, and systemic catecholamines were assessed. Messenger RNA levels encoding myofilaments, adrenergic receptors, sarcoplasmic reticulum proteins, transcription factors, and stress-induced programs were measured with blot hybridization of total left ventricular RNA.
Results:
Increased intracranial pressure induced an immediate pressor response that temporally coincided with diffuse electrocardiographic ST segment changes. Systemic epinephrine and norepinephrine levels concurrently increased (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 evident. Four hours after the induction of increased intracranial pressure, levels of messenger RNA-encoding skeletal and cardiac alpha-actins, egr-1, and heat shock protein 70 were significantly increased. Sham-operated animals did not exhibit these changes.
Conclusions:
Select changes in myocardial gene expression occur in response to increased intracranial pressure and implicate ventricular remodeling in the myocardial dysfunction associated with acute brain death.
