Ischaemia, action potentials, and refractoriness.

The study by Sutton and colleagues in this issue is the first to measure in humans the changes in the left ventricular refractory period and the duration of the ventricular monophasic action potential during the first minutes of acute ischaemia. 1 As the authors mention, the experimental data on this subject are rather confusing. Most studies report on a shortening of the refractory period, but lengthening, shortening followed by lengthening, and lengthening followed by shortening have been reported as well. The classical method to determine refractory period duration is to pace the heart with a train of regular stimuli, and to introduce after every eighth to 10th basic stimulus a premature stimulus that is stronger than the basic stimulus. The shortest coupling interval of the premature stimulus that results in a propagated response is then defined as the refractory period at the site of stimulation. The discrepancies between the various experimental studies can be attributed to the use of diVerent current strengths of the premature stimulus (usually 2–4 times diastolic threshold, but intensities of 10–15 times diastolic threshold have been used as well 2), and to the type of ischaemia—global or regional. During ischaemia the diastolic threshold for excitation increases several fold; therefore, the intensity of the premature stimuli necessary to elicit a response is usually continuously increased during the development of ischae-mia. In experimental models of regional ischaemia, the use of strong currents may lead to excitation of tissue at a considerable distance from the stimulating electrode. 3 In the " lateral border zone " , where ischaemic cells are exposed to much lower extracellular potassium (K +) concentrations than in the " central ischaemic zone " , current requirements may even be less than in normal myocardium. 4 Because in this lateral border zone, action potentials are shorter than those in normal myocardium, 5 high currents delivered to the central ischaemic zone may excite tissue in the lateral border at short coupling intervals, and one may erroneously conclude that refractory periods during ischaemia shorten. Since action potentials in the central ischaemic zone shorten as well, the conclusion may be drawn that the normal relation between action potential duration and refractory period is maintained during ischaemia. Experimental studies, in which microelectrode recordings were made as close as possible to the stimulating electrode, have shown that during ischaemia this relation is lost and that so-called post-repolarisation refractoriness develops, where recovery …