Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals.
Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are known to be produced during prolonged ischemia and reperfusion, contribute to this afferent excitation. We recorded activity from 47 chemosensitive vagal afferent fibers in 31 rats; the endings of these fibers were located in the left ventricle. Chemosensitive endings were identified with topical applications of capsaicin (10 micrograms) to the surface of the heart. Reactivity of the endings to oxygen-derived free radicals was assessed by topical application of H2O2 (3 to 9 mumol). Activity of the vagal fibers was recorded during 30 minutes of occlusion of the left anterior descending coronary artery (LAD) and 10 minutes of subsequent reperfusion. The activity of chemosensitive endings within the ischemic zone increased in the first 2 minutes of LAD occlusion from 2.2 +/- 0.4 to 4.3 +/- 0.9 impulses per second (107 +/- 30% increase, P < .05). This increased activity waned after 3 to 5 minutes of occlusion. Endings outside the ischemic zone did not increase, their activity at the beginning of ischemia. Reperfusion caused a rapid elevation of activity only in chemosensitive fibers whose endings were found to respond to topical H2O2. The reperfusion-sensitive endings were located both within and outside the ischemic zone of the left ventricle. Indomethacin (5 mg/kg i.v., 20 minutes before occlusion) effectively prevented activation of chemosensitive afferent endings at the beginning of LAD occlusion regardless of their sensitivity to H2O2 but had no effect on the activation at reperfusion.
Ustinova
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Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha.
Schultz
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D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000294:innervation*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D006861:Hydrogen Peroxide; D003676:Deferoxamine; D007213:Indomethacin