Metabolic determinants of defibrillation. Role of adenosine.
Metabolic determinants of defibrillation. Role of adenosine.
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除颤的代谢决定因素。
作者：
Bruce B. Lerman;E. Engelstein
背景
心脏骤停结局的唯一最重要决定因素是在递送高能量电击之前的室颤（VF）持续时间，因为VF持续时间对除颤阈值（DFT）有不利影响。虽然已经提出了代谢机制，但缺氧、代谢性酸中毒或代谢性酸中毒不会对DFT产生不利影响。然而，由于（1）缺氧时儿茶酚胺和腺苷水平显著增加，（2）外源性儿茶酚胺降低DFT，（3）腺苷是儿茶酚胺对心室肌电生理作用的有效拮抗剂，我们假设在长时间VF期间释放腺苷对DFT产生不利影响，并且这种影响通过抗肾上腺素能机制发生。
方法和结果
在输注腺苷（300 μ g.kg-1. min-1）和双嘧达莫（0.25 mg/kg）（一种腺苷摄取阻滞剂）期间，在犬中测定DFT，该方案导致心肌流出液中的腺苷水平相当于VF 5分钟后达到的水平。腺苷使每只狗的经胸DFT增加了49 +/- 14%（n = 21）（平均值+/- SEM），另一组10只狗的经心肌DFT增加了103 +/-16%，P = .0003。预先给予腺苷A1受体拮抗剂8-环戊基茶碱（CPT）5 mg/kg，可完全阻断腺苷对DFT的影响。腺苷对DFT的影响也在失神经状态下进行了检查（普萘洛尔0.2 mg/kg加双侧迷走神经切断术）。与其在神经支配条件下的作用相反，腺苷在去神经支配时对相同犬的DFT没有影响，49 +/- 11对53 +/- 10 J（P = NS）。
结论
腺苷显著增加经胸和经心肌DFT，这种效应由A1腺苷心肌受体通过抗肾上腺素能机制介导。这些结果表明，增强释放的腺苷在VF可能有不利影响，除颤和心肌内输送的特定A1腺苷拮抗剂在VF可能有利于除颤，并显着降低除颤阈值。
BACKGROUND
The single most important determinant of cardiac arrest outcome is the duration of ventricular fibrillation (VF) preceding delivery of a high-energy shock, because of the adverse effect of VF duration on defibrillation threshold (DFT). Although a metabolic mechanism has been proposed, hypoxia, metabolic acidosis, or alkalosis do not adversely affect DFT. However, since (1) catecholamines and adenosine levels are markedly increased during hypoxia, (2) exogenous catecholamines decrease DFT, and (3) adenosine is a potent antagonist of the electrophysiological effects of catecholamines on ventricular myocardium, we hypothesized that release of adenosine during prolonged VF adversely affects DFT and that this effect occurs through an antiadrenergic mechanism.
METHODS AND RESULTS
DFT was determined in dogs during infusion of adenosine (300 micrograms.kg-1.min-1) and dipyridamole (0.25 mg/kg), an adenosine uptake blocker, a regimen that resulted in adenosine levels in the myocardial effluent equivalent to those achieved after 5 minutes of VF. Adenosine increased transthoracic DFT in each dog by 49 +/- 14% (n = 21) (mean +/- SEM) and transmyocardial DFT in a separate group of 10 dogs by 103 +/- 16%, P = .0003. Pretreatment with the specific A1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) 5 mg/kg completely abolished the effects of adenosine on DFT. The effects of adenosine on DFT were also examined in the denervated state (propranolol 0.2 mg/kg plus bilateral vagotomy). In contrast to its effect in the innervated condition, adenosine had no effect on DFT in the same dogs when denervated, 49 +/- 11 versus 53 +/- 10 J (P = NS).
CONCLUSIONS
Adenosine significantly increases transthoracic and transmyocardial DFT, effects that are mediated by the A1 adenosine myocardial receptor through an antiadrenergic mechanism. These results suggest that enhanced release of adenosine during VF may have a deleterious effect on defibrillation and that intramyocardial delivery of a specific A1 adenosine antagonist during VF may facilitate defibrillation and significantly reduce defibrillation threshold.
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