Ventricular stimulation threshold

DelBufalo AGA, Schlaepfer J, Fromer M et al. Acute and long-term ventricular stimulation thresholds with a new, Iridium oxide-coated electrode. PACE 1993 16 1240-1244. 

Barium ion is a muscle poison causing stimulation and then paralysis. Initial symptoms are gastrointestinal, including nausea, vomiting, colic, and diarrhea, followed by myocardial and general muscular stimulation with tingling in the extremities. Severe cases continue to loss of tendon reflexes, general muscular paralysis, and death from respiratory arrest or ventricular fibrillation. Threshold of a toxic dose in humans is reported to be about 0.2-0.5 g Ba absorbed from the gut the lethal dose is 3 g Ba. 

Pharmacology Therapeutic concentrations of lidocaine attenuate phase 4 diastolic depolarization, decrease automaticity and cause a decrease or no change in excitability and membrane responsiveness. Action potential duration and effective refractory period (ERP) of Purkinje fibers and ventricular muscle are decreased, while the ratio of ERP to action potential duration is increased. Lidocaine raises ventricular fibrillation threshold. AV nodal conduction time is unchanged or shortened. Lidocaine increases the electrical stimulation threshold of the ventricle during diastole. 

The administration of berberine (1-4 mg/kg, i.v.) to rabbits was observed to significantly and dose-dependently elevate the ventricular fibrillation threshold (VFT) induced by electrical stimulation. Neither reserpine nor vagotomy exerted any influence on the increase of VFT with berberine, which implies that the anti-arrhythmic action is most likely due to a direct activity on the myocardium, without involvement of the autonomic nervous system. The pronounced effect of the alkaloid on action potentials in the rabbit myocardium in vivo resulted in the reduction in the maximal velocity of depolarization (V ). At higher dosage, berberine produced a prolongation in action potential duration at both 90 and 100% repolarization, in addition to a more potent decrease in V. These results may thus contribute to the effectiveness of berberine against myocardial arrhythmias [256]. 

Vulnerability to ventricular arrhythmias. There is the theoretical risk of ventricular fibrillation whenever a pacemaker stimulus is delivered into the vulnerable period of the ventricle. Experimentally, the ventricular fibrillation threshold is lower with bipolar stimulation than with conventional unipolar cathodal stimulation. Despite these laboratory observations, no clinical differences between permanent unipolar and bipolar systems have been reported with respect to the risk of inducing ventricular arrhythmias. 

Ventricular stimulation by NIPS is done using the same protocols that are employed for standard invasive electrophysiologic testing (46). If ventricular tachycardia is induced, the effectiveness of ATP protocols is assessed. At the end of the study the ability of the ICD to detect and treat ventricular fibrillation can be evaluated. Ventricular fibrillation can usually be induced by ultrarapid ventricular pacing (30-50 stimuli/s) or an appropriately timed low-energy shock on the T wave. The defibrillation threshold can be evaluated using the methods outlined in Chap. 8. 

Berberine has antifibrillatory activity, elevating the ventricular fibrillation threshold to electrical stimulation in anesthetized cats. Berberine also has anticonvulsant, sedative, uterine stimulant, and numerous other activities (see goldenseal). 

Endogenous norepinephrine stimulates cardiac beta receptors. Receptor-linked cAMP-dependent protein kinases phosphorylate calcium channels to increase intracellular calcium. Elevated intracellular calcium increases conduction velocity (phase 0) and decreases the threshold potential in normal SA and AV node cells (see Figure 12.13). Beta blockers slow spontaneous conduction velocity in the SA node by approximately 10-20 percent. In addition, beta blockers can slow conduction velocity while increasing the refractory period of the AV node. These effects control the ventricular rate in atrial fibrillation or flutter and terminate paroxysmal supraventricular tachycardias. They are also safer, although somewhat less effective, than other drugs for suppression of premature ventricular complexes (PVCs). Drugs in this class approved by the FDA for treatment of various arrhythmias include propranolol, acebutolol, and esmolol. Problems with the beta blockers include drowsiness, fatigue, impotence, and depressed ventricular performance. 

Interest in the antiarrhythmic activity of quaternary ammonium compounds continues. Unlike bretylium (11a). its o-iodobenzyl trimethyl-ammonium analog (UM-360, lib) did not inhibit release of norepinephrine from sympathetic nerve endings and did not cause adrenergic stimulation on its own.UM-36O effectively antagonized ventricular arrhythmias produced by ouabain in dogs, an action bretylium did not possess. Both agents elevated the threshold to electrically induced ventricular fibrillation. The same group of workers also studied the profile of a quaternary propan-2-ol derivative (UM- 2h, 12). ° In contrast to tertiary compounds of... 

Although the effect is smaller than that observed in the atrium, ACh produces a negative inotropic effect in the ventricle. This inhibition is most apparent when there is concomitant adrenergic stimulation or underlying sympathetic tone. ACh suppresses automaticity of Purkinje fibers and increases the threshold for ventricular fibrillation. To the extent that the ventricle receives cholinergic innervation, sympathetic and vagal nerve terminals lie in close proximity, and muscarinic receptors are believed to exist at presynaptic as well as postsynaptic sites. 

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