A molecular approach to apoptosis in the human heart during brain death.

BACKGROUND

Brain death induces changes in tissues and organs destined for transplant at the cell, molecular, and endocrine level including cell death through apoptosis. This study was designed to examine apoptotic damage in cardiac tissue obtained from brain dead donors.

METHODS

Fifty tissue specimens from the left ventricles of individual donors were processed to evaluate changes in the expression levels of five genes involved in apoptosis (BAX, BCL2, CASPASE 3, CYTOCHROME C, and FAS) using the real time-polymerase chain reaction technique. Expression levels were quantified by the relative standard method and results normalized to the levels recorded for the endogenous control peptidylprolyl isomerase A. The HIF1alpha gene was also determined to check for the possibility of hypoxic damage. Control ventricular tissue specimens were obtained from patients undergoing mitral valve replacement.

RESULTS

Using a mixed linear model it was determined that the sample type (donor vs. control patient) significantly affected (P<0.0001) expression levels of the genes examined reflected by their Ct values. Three of the genes (BAX, CASPASE 3, and FAS) showed significantly higher (Student's t test, P<0.05) expression levels (4.89-, 7.85-, and 12.14-fold endogenous control values, respectively) in donors compared with control patients (2.31-, 2.64-, and 3.57-fold endogenous control values, respectively) indicating the activation of apoptosis during brain death.

CONCLUSION

Our findings suggest the possibility of using antiapoptosis agents to prevent cardiac injury and improve posttransplant behavior.