Extracellular ATP excites ischemically sensitive cardiac sympathetic afferents

Abstract

Cardiac sympathetic afferents are activated during myocardial ischemia, a complex process that leads to release of a number of mediators including extracellular adenosine 5′‐triphosphate (ATP). Also, ATP can elicit pain in animal models by stimulating somatic sensory nerve fibers. We therefore hypothesized that ATP stimulates ischemically sensitive cardiac afferents. Nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Receptive fields of 10 afferents (CV= 0.32–1.77 m/s) were identified in the left ventricle with a stimulating electrode. Five min of myocardial ischemia stimulated all 10 C‐fibers cardiac afferents, increasing their activity from 0.59±0.26 to 2.48±0.42 imp/s. Epicardial application of ATP (0.5–1 μmol), αβ‐meATP (0.2–0.5 μmol), and ADP (0.5–1 μmol) each stimulated 4 cardiac afferents, increasing the activity of these afferents by 356%, 435% and 178%, respectively. Administration of PPADS (30 mg/kg, iv), a P2 receptor antagonist, eliminated the responses of 3 other cardiac afferents to epicardial ATP, αβ‐meATP and ADP. PPADS also attenuated the ischemia‐related increase in activity of 3 separate afferents by 41%. These preliminary data suggest that extracellular ATP contributes to stimulation of cardiac sympathetic afferents during myocardial ischemia through a P2 receptor mechanism. (Supported by NIH HL66217)