Preliminary observations on drug responses in viably frozen mammalian hearts

Abstract

Summary Whole isolated rat hearts were frozen at −20°C for 20 min using one of three cryoprotective agents: 15% DMSO in Ringer's solution, 6% high molecular weight dextran in saline, or 1.3% MgCl 2 in Ringer's solution. Also rat, guinea pig, rabbit, and dog hearts were frozen under similar conditions using 5% MgSO 4 as a cryoprotective agent. A series of rat hearts were frozen in Ringer's solution alone. Less than 10% of the hearts frozen in Ringer's solution resumed spontaneous atrial and ventricular contraction after thawing, while more than 85% of the hearts in each of the experimental groups met this criterion of survival. Typical pharmacological responses were elicited from thawed rat hearts receiving either DMSO, dextran, or MgCl 2 cryoprotection when tested with isoproterenol, MJ-1999 (a beta blocking agent), and ouabain. Magnesium ions seem to be potentially useful as cryoprotective agents. The mechanism of action of the agents used in this study is thought to be stabilization of macromolecules during freezing and prevention of bound water extraction leading to denaturation.