Effects of the administration of 2,3-butanedione monoxime during conventional cardiopulmonary resuscitation on ischaemic contracture and resuscitability in a pig model of out-of-hospital cardiac arrest.

Abstract

Ischaemic contracture compromises the haemodynamic effectiveness of cardiopulmonary resuscitation and resuscitability. 2,3-Butanedione monoxime (BDM) reduced ischaemic contracture by inhibiting actin-myosin crossbridge formation in an isolated heart model. We investigated the effects of BDM on ischaemic contracture and resuscitation outcomes in a pig model of out-of-hospital cardiac arrest (OHCA). After 15min of untreated ventricular fibrillation, followed by 8min of basic life support, 16 pigs were randomised to receive either 2mlkg(-1) of BDM solution (25gl(-1)) or 2mlkg(-1) of saline during advanced cardiac life support (ACLS). During the ACLS, the control group showed an increase in left ventricular (LV) wall thickness from 10.0mm (10.0-10.8) to 13.0mm (13.0-13.0) and a decrease in LV chamber area from 8.13cm(2) (7.59-9.29) to 7.47cm(2) (5.84-8.43). In contrast, the BDM group showed a decrease in the LV wall thickness from 10mm (9.0-10.8) to 8.5mm (7.0-9.8) and an increase in the LV chamber area from 9.86cm(2) (7.22-12.39) to 12.15 cm(2) (8.02-14.40). Mixed model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Spontaneous circulation was restored in four (50%) animals in the control group and in eight (100%) animals in the BDM group (p=0.077). All the resuscitated animals survived during an intensive care period of 4h. BDM administered during cardiopulmonary resuscitation reversed ischaemic contracture in a pig model of OHCA.