Reflex responses to myocardial ischemia and reperfusion. Role of prostaglandins.
Powerful vasodepressor and cardioinhibitory reflexes are activated in humans during inferior wall myocardial ischemia or infarction and during restoration of flow to the ischemic region. Experiments in dogs have demonstrated that these responses are due to stimulation of afferent vagal fibers that are located mainly in the inferior wall of the heart. Prostaglandins are released during myocardial ischemia and possibly during reperfusion. Prostaglandins stimulate chemosensitive but not mechanosensitive endings in the ventricles. Our studies determined whether blockade of prostaglandin synthesis with indomethacin or sodium meclofenamate decreased the reflex inhibitory responses to coronary occlusion and reperfusion. Experiments were done in alpha-chloralose-anesthetized dogs after sinoaortic baroreceptor denervation. Occlusion of the circumflex coronary artery for 5 minutes resulted in decreases in arterial pressure and in renal sympathetic nerve activity. During the first 5 minutes after release of the occlusion, renal nerve activity remained inhibited. After treatment with indomethacin (n = 6, 5 mg/kg i.v.) or sodium meclofenamate (n = 3, 4 mg/kg i.v.), coronary occlusion resulted in significantly less inhibition of renal nerve activity. Renal nerve activity returned to control during the first minute of reperfusion. In six additional experiments the responses to coronary occlusion and reperfusion were not altered by treatment with vehicle. Our data suggest that prostaglandins serve as the major stimulus to ventricular sensory endings during myocardial ischemia and reperfusion. Our data further suggest that reflex inhibitory responses during ischemia and reperfusion are due mainly to stimulation of chemosensitive endings.
Thames
M D
MD
Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Minisi
A J
AJ
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D006321:Heart / Q000294:innervation*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000294:innervation; D008465:Mechanoreceptors / Q000502:physiology; D008469:Meclofenamic Acid / Q000494:pharmacology; D015425:Myocardial Reperfusion; D011453:Prostaglandins / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology
D011453:Prostaglandins; D008469:Meclofenamic Acid; D007213:Indomethacin