Opioids modulate cardiac spinal afferent responses to ischemia and other mediators

Abstract

Cardiac spinal afferents are activated during myocardial ischemia. Although recent observations show that myocardial ischemia increases the concentrations of opioid peptides and that stimulation of peripheral opioid receptors inhibits chemical‐induced visceral and somatic nociception, the role of opioids in afferent signaling duirng pathophysiological events is unclear. Thus, we hypothesized that peripheral opioids modulate cardiac spinal afferent activity during myocardial ischemia. Nerve activity of single‐unit cardiac afferents in anesthetized cats was recorded from the left sympathetic chain (T2 – T5). Thirty‐three ischemically sensitive afferents (CV=0.34–3.90 m/s) with receptive fields in the left ventricle were identified by their responses to five min of regional ischemia. The responses of these afferents to repeat ischemia or ischemic mediators were further studied. First, epicardial application of naloxone (80 μmol), a non‐selective opioid receptor antagonist, enhanced the responses of 7 cardiac afferents to recurrent myocardial ischemia by 35%, whereas epicardial application of saline did not alter responses of 6 other afferents to repeat ischemia. Second, epicardial naloxone respectively facilitated the responses of other ischemically sensitive cardiac afferents to ATP (n=5) by 54% and bradykinin (BK, n=5) by 52%. In contrast, in the absence of naloxone, the afferents consistently responded to repeated application of ATP (n=5) or BK (n=5). These data suggest that peripheral opioid peptides modulate cardiac spinal afferents responses to ischemia and ischemic mediators like ATP and bradykinin. (Supported by NIH HL66217)