The autonomic pathways mediating the bradycardia response to facial immersion (FI) have not been fully elaborated in man. By means of parasympathetic and sympathetic blockade we studied the heart rate response to FI in nine highly trained young swimmers, at rest and during dynamic cycle exercise. With no blockade, heart rate at rest declined with FI 36 +/- 18%. Under beta-blockade with propranolol or alpha-blockade with phentolamine FI produced a similar decrement. Atropine reduced the response. During exercise FI produced 48 +/- 9% decline without blockade. The response was similar with beta-blockade, but was completely abolished with atropine. Systolic blood pressure responses to FI measured by cuff in three subjects were small and bore no relation to the heart rate response. The results are compatible with parasympathetic efferent mediation of the heart rate response to FI. They are incompatible with a role for sympathetic mediation except as a complex interaction between parasympathetic and sympathetic influences. Hypertension and other sympathetic responses to FI do not play a role in production of bradycardia, but are apparently incidental effects. The heart rate decrement produced by FI increases with greater steady-state heart rate.

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Background— Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. Methods and Results— VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls ( P =0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21±6 s versus 181±57 s in controls, P =0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P =0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts ( P =0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 μmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024±0.013 versus 0.12±0.02 arbitrary unit [200-ms cycle length], P =0.001). Conclusions— Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.

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Rationale: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF.Objective: We addressed the hypotheses that there is regional disease-related expression of K ATP channels in human cardiomyopathic hearts and that K ATP channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. Methods and Results:In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 mol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K ATP subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P‫.)620.0؍‬ After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P‫,)100.0؍‬ which was attenuated by glibenclamide. There was greater gene expression of all K ATP subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (⌬ERP Transmural ‫؍‬ERP Epicardium ؊ERP Endocardium ) was verified with pacing protocols. ⌬ERP Transmural in control was 5؎2 ms and increased to 36؎5 ms with ischemia. This effect was greatly attenuated by glibenclamide (⌬ERP Transmural for glibenclamide؉ischemia‫4؎9.4؍‬ ms, P‫910.0؍‬ versus control ischemia). Key Words: ventricular fibrillation Ⅲ arrhythmia Ⅲ potassium channels Ⅲ glibenclamide V entricular fibrillation (VF), once established, rarely self-terminates. The factors that tend to maintain reentry in fibrillating myocardium include increases in spatial dispersion of refractoriness and time-dependent alteration of refractory periods, which may occur in a spatially heterogeneous manner. 1-4 VF leads to global ischemia and resultant activation of cardiac K ATP channels, which shorten action potential duration and refractoriness. 5 If the expression and/or function of K ATP channels is heterogeneous, VF-induced ischemic K ATP channel activation may also result in increasing spatiotemporal dispersion of refractoriness, providing conditions that are conducive for sustaining VF after its initiation. Thus, K ATP channel blockade may prevent shortening of refractoriness and cause attenuation of spatiotemporal dispersion of refractoriness during early VF, thereby forestalling VF perpetuation. In some conditions, such as ischemic cardiomyopathy, it has been suggested that the expression of K ATP subunits is altered in infarct border zone. 6 We have previously presented preliminary data suggesting that that there is altered expression of K ATP channel subunits in human cardiomyopathic hearts compared with normal hearts. 7 It is not known if there is spatial heterogeneity and/or altered expression of ...

Out of 12 patients in whom phenylephrine terminated ventricular tachycardia, four were selected for detailed studies of its mechanism of action. Pretreatment with edrophonium (15-20 mg, i.v.) decreased, while atropine (2.4 mg, i.v.) increased by at least a factor of two, the dose of phenylephrine required to break ventricular tachycardia. Carotid sinus massage following pretreatment with edrophonium in unusually high (15-20 mg, i.v.) doses broke ventricular tachycardia in all four patients. The evidence presented supports the assumption that a vagal mechanism caused both instances of termination. These findings significantly alter our interpretation of vagal interventions in the bedside clinical diagnosis of wide QRS complex tachycardias.

Nine patients with recurrent ventricular tachycardia (VT) that could be repeatedly terminated by a Valsalva maneuver are described. In two, the tachycardia would cease for only a few seconds and then resume, whereas in seven, the tachycardia could be permanently and reproducibly terminated with a Valsalva maneuver. In all patients the tachycardia ended during the strain phase of the Valsalva maneuver, when blood pressure and radiographic measurement indicated that cardiac dimensions had been reduced dramatically. The speed with which the Valsalva maneuver terminated VT incresed in direct proportion to the strain pressure. Maneuvers such as standing or nitroglycerin, which independently reduce cardiac dimensions, enhanced the potency of the Valsalva maneuvers. Pretreatment with atropine or propranolol in four patients did not alter the response of VT to the Valsalva maneuver. Thus, it appears that a strong Valsalva maneuver can terminate some forms of VT, most likely related to an abrupt reduction in cardiac dimensions.

Vasodepressor reactions were induced in 27 rats by a combination of inferior vena caval occlusion and an infusion of isoproterenol. A vasodepressor reaction was defined as paradoxical heart rate slowing during inferior vena caval occlusion. The R-R intervals were measured at 5-s intervals before, during, and after 60 s of inferior vena caval occlusion. The purpose of this study was to examine the role of the right and left vagus nerve and the right and left stellate ganglia in this reflex. Under control conditions inferior vena caval occlusion accelerated the rate (R-R, -15.9 +/- 0.9 ms). During an infusion of isoproterenol (0.5-1.0 micrograms.min-1), inferior vena caval occlusion produced paradoxical rate slowing, i.e., a vasodepressor reaction (R-R, +75.0 +/- 2.2 ms). The vasodepressor reaction was examined during inferior vena caval occlusion and isoproterenol under the following additional states: atropine methyl bromide or right vagotomy did not alter the reaction; left vagotomy eliminated the reaction; and right or left stellectomy greatly reduced the vasodepressor reaction. We conclude the following: (1) left vagal afferents mediate the vasodepressor reaction; (2) cardiac sympathetic fibers participate in the vasodepressor reaction by withdrawing efferent tone through the right stellate ganglion, and by generating the afferent signal, which triggers the vasodepressor reaction through the left stellate ganglion.