Release of Adenosine from Human Hearts during Angina Induced by Rapid Atrial Pacing

Abstract

A B S T R A C T This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = ±9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K+, but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na+.There was no detectable release of adenosine by hearts during pacing or exercise in three control groups of patients: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure.The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.A preliminary abstract of this work appeared in: 1971. Circulation. 44(Suppl. II): 65.

Evidence for adenosine mediation of atrioventricular block in the ischemic canine myocardium.

“…It is even more likely to have greater production of adenosine by cardiac cells under conditions of increased myocardial oxygen demand when blood flow and oxygen availability are limited. Consistent with this concept is the observation that angina pectoris induced by rapid atrial pacing in patients with coronary artery disease is accompanied by release of adenosine into the coronary siniius blood (25). This situation is somewhat similar to the one observed in the seven dogs in which rapid atrial pacing after impairment of the blood supply to the A-V node (by AVNA cannulation) induced second degree A-V block.…”

Adenosine stimulates respiration in man.

“…Hypoxia leads to increased adenosine production in a number of organs (Fox et al, 1974;Winn et al, 1979;Dobson et al, 1971) but it is not known if this occurs in the carotid body. Hypoxia may cause adenosine triphosphate stored in the carotid body (Bock, 1980) to be released and degraded to adenosine and so stimulate respiration.…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…Under normal conditions, A-delta fibres, which are myelinated, elicit a rapid sharp type of pain, whereas C-fibres which are unmyelinated evoke a late, dull pain that lasts longer (Millan, 1999). Substances such as kinins, nitric oxide, histamine, prostanoids, adenosine and serotonin act on the sensory fibres (Braszko and Kościelak, 1975;Fox et al, 1974;Hütter and Strein, 1988;Rosenthal, 1977). Nociceptive information is relayed onto laminae I, II and IV-VIII within the ten laminae of the dorsal horn of spinal cord (Molander and Grant, 1986;Swett and Woolf, 1985).…”