Activation of cardiac vagal afferents in ischemia and reperfusion: Prostaglandins versus oxygen-derived free radicals

Elena E. Ustinova, Harold D. Schultz

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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 μg) 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 μmol). 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 IV, 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. The antioxidant deferoxamine (20 mg/kg IV, 20 minutes before occlusion) had no effect on the activation of the chemosensitive fibers at the onset of ischemia, although it completely prevented their activation at reperfusion. We propose that there are two different mechanisms that activate chemosensitive afferent vagal fibers in the rat heart during ischemia and reperfusion. The first causes excitation of these endings at the onset of ischemia and is mediated by prostaglandin synthesis within the ischemic zone. The second mechanism leads to a more widespread activation of chemosensitive afferents in the left ventricle by 30 minutes of ischemia and at the moment of reperfusion and is mediated by oxygen-derived free radical formation.

Original languageEnglish (US)
Pages (from-to)904-911
Number of pages8
JournalCirculation Research
Volume74
Issue number5
DOIs
StatePublished - May 1994

Fingerprint

Reperfusion
Free Radicals
Prostaglandins
Ischemia
Oxygen
Heart Ventricles
Myocardial Reperfusion
Deferoxamine
Nerve Endings
Capsaicin
Indomethacin
Myocardial Ischemia
Reflex
Coronary Vessels
Antioxidants

Keywords

  • antioxidants
  • cardiac chemosensitive endings
  • myocardial ischemia
  • oxygen radicals
  • prostaglandins
  • reperfusion
  • ventricular C fibers

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Activation of cardiac vagal afferents in ischemia and reperfusion : Prostaglandins versus oxygen-derived free radicals. / Ustinova, Elena E.; Schultz, Harold D.

In: Circulation Research, Vol. 74, No. 5, 05.1994, p. 904-911.

Research output: Contribution to journalArticle

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N2 - 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 μg) 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 μmol). 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 IV, 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. The antioxidant deferoxamine (20 mg/kg IV, 20 minutes before occlusion) had no effect on the activation of the chemosensitive fibers at the onset of ischemia, although it completely prevented their activation at reperfusion. We propose that there are two different mechanisms that activate chemosensitive afferent vagal fibers in the rat heart during ischemia and reperfusion. The first causes excitation of these endings at the onset of ischemia and is mediated by prostaglandin synthesis within the ischemic zone. The second mechanism leads to a more widespread activation of chemosensitive afferents in the left ventricle by 30 minutes of ischemia and at the moment of reperfusion and is mediated by oxygen-derived free radical formation.

AB - 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 μg) 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 μmol). 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 IV, 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. The antioxidant deferoxamine (20 mg/kg IV, 20 minutes before occlusion) had no effect on the activation of the chemosensitive fibers at the onset of ischemia, although it completely prevented their activation at reperfusion. We propose that there are two different mechanisms that activate chemosensitive afferent vagal fibers in the rat heart during ischemia and reperfusion. The first causes excitation of these endings at the onset of ischemia and is mediated by prostaglandin synthesis within the ischemic zone. The second mechanism leads to a more widespread activation of chemosensitive afferents in the left ventricle by 30 minutes of ischemia and at the moment of reperfusion and is mediated by oxygen-derived free radical formation.

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