Proceedings of The Physiological Society

University of Cambridge (2004) J Physiol 555P, PC8


The effect of hypoxia on electrical restitution and inducibility of ventricular fibrillation in the isolated rabbit heart

Vanlata H. Patel, Kieran E. Brack, Suman Kundu, Peter Taggart†, John H. Coote and G. Andre Ng

Department of Cardiovascular Sciences, University of Leicester, * Department of Physiology, University of Birmingham and †Department of Cardiology, University College Hospital London, UK

The mechanisms underlying the induction, maintenance and termination of ventricular fibrillation (VF) remain poorly understood, despite being a major cause of sudden death. Signs of myocardial injury are absent in many cases of sudden death even in the presence of coronary artery disease suggesting that mechanisms such as ischaemia or hypoxia rather than infarction may be involved. VF initiation is suggested to be related with the slope of the restitution curve (Garfinkel et al. 2000). This study examines the effects of hypoxia on electrical restitution and inducibility of VF in the isolated rabbit heart.

Adult male NZW rabbits (2.0-2.5 kg, n = 7) were humanely killed with an overdose of Sagatal (I.V.). Hearts were isolated and Langendorff perfused (35ml min-1, 37 °C). Monophasic Action Potential was recorded from the left ventricular free wall and duration (MAPD) was measured at 90 % repolarisation. Standard restitution was obtained with right ventricular pacing using a 20 beat drive train (S1, 300 ms), followed by an extra stimuli (S2) down to the effective refractory period (ERP). S2-MAPD were plotted against preceding diastolic intervals (DI) and fitted to an exponential curve with maximum slope measured. VF threshold (VFT) was determined as the minimum current required to induce VF using a train of 30 stimuli (30 ms interval). Measurements were made during Tyrode perfusion bubbled with 95 %O2/5 %CO2 (Baseline) followed by Tyrode perfusion bubbled with 95 %N2/5 %C02 (Hypoxia). Results (mean ± S.E.M.) were analysed using ANOVA.

Hypoxia significantly (P < 0.001) reduced heart rate (165±8 to 116±4 bpm), left ventricular pressure (94 ± 6 to 45±7 mmHg), aortic perfusion pressure (58±3 to 42±4 mmHg), ERP and maximum MAPD (MAPDMax). VFT was significantly lower whilst the restitution curve was flatter (Fig. 1) and maximum slope significantly decreased during hypoxia (table).

Electrical restitution curve is flatter during hypoxia with less reduction in MAPD at short diastolic intervals when compared to baseline. This suggests that the increased susceptibility of the heart to VF during hypoxia cannot be explained by the slope of the restitution curve alone.

This study is supported by the British Heart Foundation

Where applicable, experiments conform with Society ethical requirements