SUMMARY The arrhythmogenic role of increased dispersion of repolarization (dispersion) was studied in 23 open-chest dogs using six simultaneously recorded monophasic action potentials (MAPs) from the ventricular surface and programmed ventricular premature stimulation (VPS). Increased dispersion was induced by generalized hypothermia (29°C) and regional warm blood (38430C) perfusion through a coronary artery branch. Hypothermia and regional warm blood perfusion increased maximum dispersion from 13 + 10 to 111 ± 16 msec (p < 0.001), predominantly because of the increased MAP duration difference (10 15 vs 97 ± 16 msec, p < 0.001). The maximal difference between activation times was not significantly changed, but the QRS duration increased from 47 ± 6 to 52 ± 7 msec (p < 0.01). Ventricular arrhythmia did not occur spontaneously but was induced by a single VPS in all 23 dogs during hypothermia and regional warm blood perfusion when dispersion reached a critical magnitude. The critical magnitude of dispersion required to induce ventricular arrhythmia was documented in 16 dogs by stepwise increments or decrements of dispersion. In four dogs, an increase in atrial pacing rate of 24 beats/mm prevented induction of ventricular arrhythmia by decreasing dispersion from a critical magnitude of 103 5 msec to a nonarrhythmogenic value of 86 ± 9 msec (p < 0.05). In six dogs, we compared the stimulation sitedependent effects of VPS applied in the region with short and long MAPs. In all dogs, ventricular arrhythmia was inducible only by VPS from the region with a short MAP. Premature impulses from this region propagated more slowly than those from the region with a long MAP. Our results show that the large dispersion of repolarization facilitates the development of a conduction delay necessary to induce sustained arrhythmia by an early premature stimulus applied at the site with a short MAP.STRONG experimental evidence links the vulnerability of ventricular myocardium to arrhythmia with increased temporal dispersion of refractoriness. '-5 Conversely, it is believed that one of the beneficial effects of antiarrhythmic drugs relates to their ability to decrease dispersion. ed predominantly from differences in MAP duration. MethodsWe studied 23 mongrel dogs that weighed 19.1-32.7 kg and were anesthetized with i.v. sodium pentobarbital, 30 mg/kg. The chest was opened by a midsternal incision, and the dogs were ventilated with a Harvard respirator. The heart was suspended in a pericardial cradle. The sinus node was crushed and a bipolar Grass E2B platinum electrode was attached to the right atrial appendage for pacing at 100-1 58 beats/min (mean 119 + 13 beats/min). In 13 dogs, the pacing rate was maintained constant throughout the entire experiment at an average of 116 ± 10 beats/min (range 100-140 beats/min), and in 10 dogs the pacing rate during hypothermia (see below) was slower than control, averaging 113 ± 7 beats/min (range 100-120 beats/min).Six suction electrodes were applied to record MAPs using the technique described prev...

To explain the mechanism of arrhythmias dependent predominantly on increased dispersion of repolarization, we created a model in which increased dispersion was induced by means of generalized hypothermia (29 degrees C) and regional warm blood (38-43 degrees C) perfusion (RWBP) via a coronary artery branch. In 23 open-chest dogs, hypothermia plus RWBP increased maximum dispersion of repolarization from 13 +/- 10 to 111 +/- 16 ms (P less than 0.001) due predominantly to the increased monophasic action potential duration (MAP) difference of six simultaneously recorded MAP's from the ventricular surface, from 10 +/- 15 to 97 +/- 16 ms (P less than 0.001). The maximal difference between activation times was not significantly changed while QRS duration increased from 47 +/- 6 to 52 +/- 7 ms (P less than 0.01). Ventricular arrhythmia (VA) did not occur spontaneously but was induced by a single ventricular premature stimulus (VPS) in all 23 dogs during hypothermia plus RWBP when dispersion reached a critical magnitude. The requirement of this critical magnitude of dispersion for the induction of VA was documented in 16 dogs by means of stepwise increments or decrements of dispersion. In four dogs an increase in atrial pacing rate by 24 beats/min-1 prevented induction of VA by decreasing dispersion from a critical magnitude of 103 +/- 5 ms to a nonarrhythmogenic value of 86 +/- 9 ms (P less than 0.05). In six dogs, we compared the stimulation-site dependent effects of VPS applied in the region with short and long MAPD. In all dogs VA was inducible only by VPS from the region with short MAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

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