ISCHEMIA-SENSITIVE AND REPERFUSION-SENSITIVE CARDIAC SYMPATHETIC AFFERENTS - INFLUENCE OF H2O2 AND HYDROXYL RADICALS

Activation of cardiac sympathetic affferents leads to excitatory cardi ovascular reflexes and pain during myocardial ischemia. We hypothesize d that cardiac sympathetic afferents are activated by reactive oxygen species produced during ischemia and reperfusion. Single-unit nerve ac tivity of 55 afferents was recorded from the left paravertebral sympat hetic chain (T-1-T-4) in cats anesthetized with alpha-chloralose. Rece ptive fields of all afferents were located on the right or left ventri cle. Mechanical and chemical sensitivities of each afferent ending wer e evaluated by von Frey hairs, cardiac distension, and local applicati on of bradykinin (BK, 142 pmol) or H2O2 (7.5-15 mu mol) to the recepti ve field. Thirty-one afferents (56%) were responsive to bradykinin (BK ), H2O2, and ischemia (2 or 10 min). Deferoxamine (Def, 10-100 mg/kg), dimethylthiourea (DMTU, 10-100 mg/kg), or iron-loaded Def(10 mg/kg) w ere employed to evaluate the role of H2O2 and hydroxyl radicals (. OH) in activating these afferents (10A delta and 21C fibers) during ische mia and reperfusion. Treatment with the nonspecific scavenger DMTU (n = 10) significantly diminished the increase in discharge activity evok ed by ischemia and reperfusion. Treatment with Def also significantly attenuated the responses during ischemia and reperfusion. Thus reactiv e oxygen species, particularly . OH, activate a group of cardiac sympa thetic A delta- and C-fiber afferents during myocardial ischemia and r eperfusion and may play an important role in mediating cardiovascular sympathetic reflex responses and/or pain transmission.