The Effect of Sympathomimetic Amines on the Ventricular Fibrillation Threshold in the Rabbit Isolated Heart

Abstract

1The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 370C by applying a single 10 ms pulse of current during the vulnerable period of late systole. The arrhythmia induced was either fibrillation or a rapid tachycardia. 2 The catecholamines adrenaline, noradrenaline and isoprenaline, but not dopamine, when infused at rates which produced similar moderate effects on cardiac rate and force, significantly lowered the VFT; it was reduced slightly more by adrenaline than by the other two. Phenylephrine and methoxamine were ineffective. Only those sympathomimetic amines which lowered the VFT also shortened the vulnerable time, i.e. minimal time after the R-wave of the ECG at which the pulse had to be applied to induce the arrhythmia. 3 The lowering effect of adrenaline on the VFT was not influenced by phentolamine but was blocked by propranolol and pindolol. 4 Chloroform potentiated the lowering effect of adrenaline, but not that of isoprenaline, on the VFT. Carbachol did not alter the effect of adrenaline on the VFT. 5 The results indicate that adrenaline, noradrenaline and isoprenaline lower the VFT by a direct action on the cardiac musculature and that this effect is mediated via ,-adrenoceptors.

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

“…Epinephrine enhances automaticity, lowers fibrillation thresholds [17,18,27,29,30] and increases extrasystoles [28,31]. The effects on the action potential vary, but epinephrine alters calcium handling and increases the likelihood of delayed after-depolarizations [32][33][34][35].…”

The Effect of Anoxia on the Ventricular Fibrillation Threshold in the Rabbit Isolated Heart

“…The effect of the released catecholamines in the whole animal, however, are complex as have shown that infused adrenaline first lowers and then raises the VFT in the dog. Although anoxia causes the release of noradrenaline in the rabbit isolated perfused heart (Wollenberger & Shahab, 1965) and noradrenaline lowers the VFT (Murnaghan, 1975), the released noradrenaline cannot be responsible for the fall in the VFT induced by anoxia because the effect is not prevented by blockade of the,-adrenoceptors by propranolol or pindolol or by previous depletion of noradrenaline in the heart by reserpine.…”

“…Additional evidence that the release of noradrenaline is not responsible for the fall in the VFT during anoxia is the fact that the fall was not prevented by previous treatment with reserpine (VFT change ratios of 0.44, 0.50 and 0.29 in three trials in one heart). The 1-blockers alone in 15 trials did not significantly alter the VFT change ratio (0.95 ± 0.11) but have been shown to block the lowering effect of noradrenaline on the VFT (Murnaghan, 1975).…”

“…The possibility that this mechanism could account for or influence the change in the VFT produced by anoxia had to be considered. However, when incorporated in the McEwen's solution adenosine (5 Mm) alone (20 trials), or 10 Mm dipyridamole alone (24 trials), which protects the former from destruction (Berne, 1966), or both combined (2 trials) failed to alter significantly the VFT change ratio (0.82 ± 0.09, (Wollenberger & Shahab, 1965) and when infused into it has been shown to lower the VFT (Murnaghan, 1975). However, this mechanism does not appear to be responsible for the fall in the VFT during anoxia because when the ,B-adrenoceptors were blocked with propranolol (2 ,uM) or pindolol in 7 trials the VFT was still significantly reduced by anoxia (0.66 ± 0.07; P< 0.01).…”

“…Since the introduction of isoprenaline inhala- Since both isoprenaline (Murnaghan, 1975) Table 2 show that the vulnerable time was significantly shortened by anoxia alone or when combined with dipyridamole or adenosine and also by adenosine alone despite the fact that the heart rate was slowed in all cases. Dipyridamole alone or when combined with adenosine did not significantly alter the vulnerable time.…”