Brain death-induced cardiac contractile dysfunction and long-term cardiac preservation. Rat heart studies of the effects of hypophysectomy.

BACKGROUND

Ischemic brain death induces cardiac contractile dysfunction, which may exclude the heart as a donor organ for transplantation; the mechanism is unknown. Since cerebral ischemia might alter pituitary function, we investigated the influence of hypophysectomy on basal contractile function, brain death-induced contractile malfunction, and the tolerance of the heart to hypothermic ischemic storage.

METHODS AND RESULTS

Rats were hypophysectomized and maintained for 5 days; during this time, left ventricular developed pressure (LVDP) fell to 70% of its control value (92 +/- 8 versus 132 +/- 6 mm Hg, P < .05). Diastolic function of isolated blood-perfused hearts 5 days after hypophysectomy was severely impaired (left ventricular volume at 12 mm Hg of end-diastolic pressure was 141 +/- 20 versus 250 +/- 30 microL in sham-operated control rats; P < .05). Brain death in nonhypophysectomized rats resulted in a transient increase in mean arterial pressure (from 112 +/- 4 to 180 +/- 7 mm Hg within the first 30 seconds) followed by a rapid decline to less than 50% of the control value (54 +/- 3 mm Hg after 5 minutes, P < .05). Changes in cardiac function were comparable (cardiac index fell from 34 +/- 2 to 17 +/- 1 mL/min per 100 g body weight, and stroke volume index fell from 82 +/- 5 to 41 +/- 4 microL per beat per 100 g body weight within 10 minutes; P < .05). Brain death in hypophysectomized rats resulted in a similar (but attenuated) biphasic response with arterial pressure (already reduced to 82 +/- 9 mm Hg as a consequence of hypophysectomy) transiently increasing to 144 +/- 9 mm Hg after 30 seconds and then falling to 52 +/- 5 mm Hg by 5 minutes. Finally, we assessed the effects of coincident hypophysectomy and brain death on the ability of the heart to recover from 6 hours of hypothermic (4 degrees C) ischemic storage. Brain death alone had no effect on the postischemic recovery of LVDP (133 +/- 14 versus 129 +/- 12 mm Hg at 8 mm Hg of end-diastolic pressure in the non-brain death group). LVDP in hearts from hypophysectomized rats with brain death recovered to only 84 +/- 13 mm Hg; however, this was virtually identical to the LVDP in hearts from hypophysectomized rats that had not been subjected to brain death (83 +/- 5 mm Hg) or had not even been exposed to hypothermic ischemia (83 +/- 10 mm Hg).

CONCLUSIONS

Hypophysectomy induces a deterioration of cardiac function that becomes apparent after 2 days. However, it does not exacerbate the cardiac dysfunction induced by brain death. Hearts from hypophysectomized animals, with or without brain death, recovered less well after prolonged hypothermic storage; nevertheless, the hearts recovered to preischemic levels, indicating that, although hypophysectomy impairs cardiac contractile function, it does not adversely influence the tolerance of the heart to hypothermic ischemia. Pituitary function may be an important factor in determining cardiac function without influencing resistance to ischemia or responses to brain injury.