Shigenobu Yamada

Electrophysiologic effects of disopyramide studied in a hypoxic canine purkinje fiber model

Under normal (95% + 5% CO2) and hypoxic (95% N2 + 5% CO2) perfusions, electrophysiologic effects of disopyramide phosphate (5 microgram/ml) on canine Purkinje fibers were studied using microelectrode techniques. In the presence of normal oxygenation, disopyramide decreased the action potential amplitude and maximal rate of phase 0 depolarization, and lowered the level of plateau. The action potential duration at 80% of repolarization was prolonged in fibers initially having shorter durations, whereas it was shortened in fibers with longer durations, making the repolarization process more uniform. Addition of disopyramide under hypoxia similarly decreased the amplitude and upstroke velocity of action potential, and tended to reverse hypoxia-induced shortening of the refractory period. The maximal diastolic potential was altered by neither hypoxia nor disopyramide alone, but was significantly decreased by the combination of these two factors. Disopyramide prolonged the effective refractory period more than the action potential duration. From these results, antiarrhythmic effects of disopyramide under hypoxia appear to depend on (1) depressed conduction and resultant conversion of unidirectional block to bidirectional block abolishing reentry, and (2) decreased vulnerability due to decreased inhomogeneity of repolarization. Usefulness of this experimental model in studying electrophysiologic action of antiarrhythmic agents in ischemic hearts is also suggested.

Does A-H interval accurately represent intranodal conduction time during ectopic rhythms?*****

In order to determine whether the A-H interval of the His bundle electrogram accurately represents the AV nodal conduction time under various conditions, His bundle and coronary sinus electrograms were recorded in isolated perfused rabbit hearts, with atrial stimulation from eight different sites. The S-A (stimulus to the A wave) interval was significantly longer, whereas the A-H interval was shorter on stimulations from the coronary sinus and the left atrium than on sinus nodal stimulation. Stimulations from the fossa ovalis and right atrial appendage did not significantly alter the A-H interval. The effective and functional refractory periods of the AV node were almost identical with stimulations from the sinus node, low right atrial appendage, low left atrial appendage or the ostium of coronary sinus. Mapping of the excitation process with microelectrodes revealed that the activation times in low interatrial septal fibers bordering the His bundle [abbreviated as AP(III)] was closest to the A wave as compared with the activation in the ostium of the coronary sinus [AP(I)] or near the AN region [AP(II)] on stimulation from both sinus nodal and coronary sinus regions. On sinus nodal stimulation, AP(III) preceded AP(I) and AP(II) but lagged behind the A wave by 6 msec, whereas AP(III) preceded the A wave by 5 msec on coronary sinus stimulation. Thus, the A-H interval may not always accurately represent the intranodal conduction time, as relative timing of atrial activation responsible for the A wave and that of invasion of the AV node by the atrial wavefront can be grossly altered by different atrial excitation patterns.

2P-504 Development of an animal model for spontaneous myocardial infarction (WHHLMI rabbit)

OBJECTIVE Coronary heart disease is the most common cause of death in developed countries. However, there are no suitable animal models that mimic spontaneous myocardial infarction in humans. In this study, we attempted to obtain a rabbit strain with spontaneous myocardial infarction by selective breeding of coronary atherosclerosis-prone Watanabe heritable hyperlipidemic (WHHL) rabbits, designated as WHHLMI rabbits. METHODS AND RESULTS WHHLMI rabbits were characterized by the high incidence of fatal myocardial infarction at ages 11 to 35 months, being increased from 23% to 97% after the selective breeding. The ECG on WHHLMI rabbits showed a typical feature of myocardial infarction. Histological examination of hearts from suddenly deceased WHHLMI rabbits revealed old myocardial infarction accompanied by fresh myocardial lesions. The culprit coronary arteries exhibited severe atheromatous plaques (>90% lumen area stenosis), suggesting that coronary atherosclerosis is responsible for myocardial infarction observed in WHHLMI rabbits. In addition, the coronary plaques showed vulnerable features including macrophage-rich thin cap and large necrotic core. CONCLUSIONS To the best of our knowledge, this is the first report of spontaneous myocardial infarction in rabbits, and it is suggested that this WHHLMI rabbit strain will be a useful animal model to study human myocardial infarction.