Ventricular fibrillation is usually the terminal event preceding death in homeothermic mammals subjected to progressive cooling, and it is the major risk severly limiting the use of induced hypothermia under various clinical conditions. The results of a series of investigations on hibernators, and on cats subjected to certain pharmacological treatments, have strongly indicated that adrenergic mechanisms are involved in the development of hypothermic ventricular fibrillation, and this heart failure has been successfully prevented by interfering with such mechanisms. In the present study on cats it has been shown that bretylium, which blocks the transmitter release from peripheral adrenergic neurons, significantly lowered the body temperature at which ventricular fibrillation develops, when given in a dose of 10 or 20 mg/kg. Blood pressure was maintained with angiotensin, which affects the vascular smooth muscles without involving the adrenergic receptors. Adrenalectomy did not further improve the outcome of the results. When given in a dose of 30+50 mg/kg, bretylium was able to prevent the development of ventricular fibrillation in 11 out of 12 animals, which were cooled down to 17.7 - 16.6°C rectal temperature and subsequently rewarmed to normothermia without complications. Control animals receiving no pretreatment regularly developed ventricular fibrillation at about 21°C rectal temperature. The ventricular fibrillation could be reversed into regular heart activity by D(-)-INPEA (N-isopropyl-p-nitrophenylethanolamine), a specific β-adrenergic blocking agent; the L(+) -form of INPEA, having only minimal receptor blocking activity, was without effect. The results offer further evidence in favour of the view that the adrenergic nervous system, probably in the heart, is an important factor for the production of hypothermic ventricular fibrillation. © 1968.
