Electrophysiologic Effects of Reduced Oxygen Supply on the Transmembrane Potential and Membrane Current Systems of the Rabbit Atrioventricular Node

Effects of ischemia on atrioventricular (AV) conduction were studied in 11 isolated, perfused rabbit hearts by reducing the coronary flow from 17 to 8.5 mllmin. Within 10 minutes, all the hearts showed a 2 o AV block, with significant prolongation of intraatrial (16%), intra-A V nodal (223%) and His-Purkinje (23%) conduction times before the 2 o A V block developed. Effects of hypoxia were studied in 7 spontaneously beating small (0.2 x 0.2 x 0.1 mm) A V nodal preparations. When pO2 of the perfusate was reduced from 550 to 30 mmHg, the preparations showed a slowing of firing from 122 to 112/min and a reduction of the maximal diastolic potential (from - 67 to - 63 m V) as well as the maximal rate of depolarization (from 17 to 14 V /sec). Action potential duration was unchanged. When pO2 was further reduced to 19 mmHg, all preparations ceased their firing (n = 5). This was accompanied by hyperpolarization and an increased resting tension even in a Ca++ free medium containing 5 mM EGTA, suggesting increased intracellular Ca++ concentration possibly by Ca++ release from mitochondria and/or sarcoplasmic reticulum. Voltage clamp experiments (n = 5) by double microelectrode techniques revealed that hypoxia reduced the slow inward current by 28% and outward K+ current tail minimally, although the background current flowed outwardly by 3–5 nA. These results suggest that hypoxia depresses A V nodal conduction by reducing the slow inward current and increasing intracellular resistance, and depresses automaticity by reducing the slow inward current and shifting the background current outwardly.