VARIABLE EFFECTS OF EXPLOSIVE OR GRADUAL INCREASE OF INTRACRANIAL-PRESSURE ON MYOCARDIAL STRUCTURE AND FUNCTION

Background. Studies done in potential donors for heart transplantation and in experimental animals have suggested that brain death can have major histopathological and functional effects on the myocardium. Methods and Results. We developed experimental models of brain death using dogs to study the hemodynamic and catecholamine changes, the extent of myocardial structural damage, and the recovery potential of donor hearts obtained from brain-dead donors. Brain death was caused by increasing the intracranial pressure (ICP) suddenly or gradually by injecting saline in an epidural Foley catheter. In a first series of experiments, dogs given a sudden rise in ICP (n=5) showed a hyperdynamic response and a 1,000-fold increase in the level of epinephrine after brain death. Histology revealed 93+/-2% of the myocardium to be severely ischemic. Dogs given a gradual rise in ICP (n=6) showed a lesser hyperdynamic response, almost 200-fold increase in the level of epinephrine after brain death, and mild ischemic damage to the myocardium (23+/-1%). In a second series, hearts obtained from brain-dead and non-brain-dead donors were transplanted in recipients, and the weaning and recovery potential were studied. All four recipients with hearts from non-brain-dead donors were weaned with good functional recovery. Also, all four recipients with hearts from brain-dead dogs given a gradual rise in ICP were weaned with only moderate functional recovery. However, only two of four recipients with hearts from donors given a sudden rise in ICP were weaned and showed poor functional recovery. Conclusions. Our results indicate that a sudden rise in ICP can cause irreversible myocardial damage.