Effect of glycolytic inhibitors on the sinoatrial node, atrium and atrioventricular node in the rabbit heart

Abstract

The effect of unspecific noncompetitive (iodoacetic acid; IAA) and of specific competitive (deoxyglucose) glycolytic inhibitors were studied under aerobic and anaerobic conditions in the isolated sinoatrial (SA) node, right atrium and atrioventricular (AV) node of the rabbit heart. Transmembrane action potentials were recorded simultaneously with the His bundle electrogram. Under aerobic conditions ( Po 2 460 mmHg), 7.5 × 10 −5 m IAA caused no significant alterations of sinus rate, intraatrial and AV nodal conduction. Under hypoxic conditions ( Po 2 40 mmHg), 7.5 × 10 −5 m IAA resulted in rapid and complete abolition of the SA and AV nodal electrical activity and in a more delayed atrial inexcitability. Similar changes were never observed in the presence of hypoxia alone. Higher concentrations of IAA (5 × 10 −4 m) severely depressed the sinus rate and the AV nodal conduction already under aerobic conditions. The action potential amplitude and the rate of diastolic depolarization of the SA nodal fibers was significantly reduced, the maximum diastolic potential remained unchanged. In atrial fibers, 5 × 10 −4 m IAA caused predominantly shortening of the action potential duration but had less marked and delayed depressant effects on the action potential amplitude. Electrophysiologic abnormalities included Mobitz type II sinoatrial block. The electrophysiological effects of deoxyglucose (50 m m) under aerobic and hypoxic conditions resembled those obtained with 7.5 × 10 −5 m IAA. The results suggest that the “normal” nodal function is predominantly related to aerobic metabolism but that under hypoxic conditions glycolytic energy production can effectively contribute to the maintenance of nodal electrical activity. Also that the specific relation between cardiac metabolism and electrical activity of nodal and atrial cells may at least partly be explained by the particular electrical membrane properties of the various fiber types.