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  • Title: Endogenous adenosine is an antiarrhythmic agent.
    Author: Conti JB, Belardinelli L, Utterback DB, Curtis AB.
    Journal: Circulation; 1995 Mar 15; 91(6):1761-7. PubMed ID: 7882485.
    Abstract:
    BACKGROUND: Adenosine administered intravenously terminates supraventricular tachycardias (SVT) involving the AV node as part of the reentrant circuit. Dipyridamole increases interstitial myocardial levels of this nucleoside. This study was designed to determine whether intravenous dipyridamole increases coronary sinus plasma adenosine concentrations ([Ado]cs) in humans to levels sufficient to alter electrophysiological parameters and terminate SVT. METHODS AND RESULTS: A custom-designed catheter and syringe for sampling blood for measurement of [Ado]cs was placed in the coronary sinuses of 7 patients. [Ado]cs and refractory periods and conduction characteristics of the atrium and AV node were determined after autonomic blockade and dipyridamole infusion (5 micrograms.kg-1.min-1 after a loading dose of 0.56 mg/kg). The atrial effective and functional refractory periods remained unchanged after dipyridamole infusion. In contrast, the AV nodal functional refractory period increased from 350 +/- 32 to 381 +/- 41 milliseconds (P = .03); the Wenckebach cycle length also increased from 309 +/- 47 to 350 +/- 57 milliseconds (P < .0001). Coincident with these changes, [ADO]cs increased from 0.18 +/- 0.11 to 0.31 +/- 0.12 mumol/L (P = .02). In another 10 patients with AV or AV nodal reentrant tachycardia, SVT was induced, and coronary sinus blood samples were drawn. Dipyridamole was infused, and coronary sinus blood samples were obtained after 15 minutes or coincident with termination of SVT. Mean [ADO]cs increased from 0.17 +/- 0.06 mumol/L during SVT to 0.38 +/- 0.21 mumol/L after dipyridamole (P = .02). Mean tachycardia cycle length increased from 334 +/- 132 to 375 +/- 139 milliseconds (P = .02); this effect was confined to the AV node, as demonstrated by an increase in AH interval from 171 +/- 144 to 214 +/- 140 milliseconds (P = .003). SVT terminated with the infusion of dipyridamole in 4 of the 10 patients. CONCLUSIONS: Administration of dipyridamole is associated with elevation of [ADO]cs, with coincident prolongation of the mean Wenckebach cycle length and AV nodal functional refractory period. During SVT, dipyridamole leads to prolongation of the AH interval and tachycardia cycle length and to an increase in [ADO]cs, with termination of SVT in four patients. These results support the hypothesis that adenosine may function as an endogenous antiarrhythmic metabolite.
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