Suppression of ischaemia-induced VF by intraventricular balloon inflation in the rat isolated heart

CDE Wilder, RI Masoud, D Yazar, MJ Curtis. King\'s College London, London, UK

In a previous study we tested the hypothesis that increasing ventricular load, by inflation of an intraventricular balloon (IVB) in the rat Langendorff model, would increase susceptibility to regional ischaemia-induced ventricular fibrillation (VF). When the zone of left regional ischaemia (IZ) was made small to give a low control incidence of VF (VF% per group), we found a non-significant paradoxical reduction in VF% (1). In the present study, using the same model, we tested whether this observation was robust, by making IZs large (>45% of total ventricular weight), to increase control incidence of VF and the scope to detect protection.

Male Wistar rat (200-250g) hearts were perfused with Krebs’ buffer modified to contain 3mM K+. Diastolic (Dia) and developed (Dev) pressure (mmHg) were measured 1 min before (-1), 10 and 120 min after the start of 120 min of ischaemia (left coronary ligation). Hearts were randomized to one of three groups: no IVB, IVB minimally inflated (<0.01 ml; IVB min), or IVB inflation (~0.12 ml) to give Dev >100mmHg (n = 12/group). In a separate study, in order to test whether IVB inflation impairs the ability of an established antiarrhythmic drug to obtain benefit in the model, we tested the actions of 0.6µM verapamil (2) in hearts with no IVB, ‘IVB min’ or IVB inflation (n = 12/group). In a third study, using the same model, coronary effluent lactate was measured electrochemically (YSI 2300 STAT Plus™ lactate analyser) to examine whether endocardial ischaemia (3), inadvertently induced by IVB inflation, accounts for the antiarrhythmic effect (n = 12/group). To test for IVB inflation-induced lactate release, IVBs were deflated and removed after 25 min ischaemia, and data were compared with the effects of reperfusion (at 30 min), and vs. time-matched control hearts with no IVB.

IVB inflation significantly reduced VF% and a 5 point arrhythmia score (table; *p <0.05 vs. no IVB and IVB min groups). IVB inflation increased Dia and Dev pressures (table; *p <0.05 vs. IVB min). Ischaemia lowered Dev in hearts with IVB inflation (table; p <0.05). Verapamil abolished VF in all hearts regardless of IVB presence or inflation. A small increase in coronary effluent lactate occurred after IVB removal during ischaemia (0.78±0.06 µmol/45 sec vs. 0.50±0.04 µmol/45 sec in controls) but this was small vs. the increase in the same groups during the first min of reperfusion (4.43±0.48 µmol/45 sec vs. 3.20±0.37 µmol/45 sec in controls). In conclusion, IVB inflation strongly suppresses ischaemia-induced VF in hearts with large IZs, perhaps as a consequence of production of endocardial damage as suggested by the small increase in lactate upon IVB removal, but it did not affect drug-induced VF suppression.

(1) Crook CDE and Curtis MJ (2012). pA2 online 10: abstract 183P. http://www.pA182online.org/abstracts/Vol110Issue184abst183P.pdf

(2) Farkas A et al. (1999). Br J Pharmacol 128: 41-50

(3) Stanley WC (2001). Eur Heart J Suppl 3: O2-O7