The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 37 degrees C 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. Gassing the McEwen's solution with 5% CO2 in N2 (anoxia) instead of with carbogen caused a negative inotropic and chronotropic effect and significantly lowered the VFT. Although anoxia releases noradrenaline from the heart the effect of anoxia on the VFT was not prevented by beta-adrenoceptor blockade with propranolol or pindolol or by previous treatment with reserpine. 3. Perfusion with adenosine (5 muM) which is released from the heart muscle by anoxia, or with dipyridamole (10 muM) which protects the adenosine from binding or destruction by the tissues, or with both combined failed to alter the VFT significantly. Furthermore neither adenosine nor dipyridamole significantly altered the effect of anoxia on the VFT. 4. Anoxia, adenosine and dipyridamole significantly increased the duration of the induced arrhythmia when compared with that of the controls. 5. Anoxia and adenosine significantly shortened the vulnerable time, i.e., the minimal time after the R-wave of the ECG at which the pulse had to be applied to induce the arrhythmia. 6. Perfusion with the McEwen's solution gassed with 5% CO2 in air (hypoxia) significantly lowered the VFT but the effect was not as great as with anoxia. Isoprenaline when infused lowered the VFT but this effect was not potentiated by hypoxia. 7. The results indicate that (a) anoxia lowers the VFT in the perfused isolated heart of the rabbit and that this effect is not due to adenosine or noradrenaline released by the anoxia and (b) hypoxia does not sensitize the heart to the arrhythmic effect of isoprenaline.
