Prostaglandins and myocardial noradrenaline overflow after sympathetic nerve stimulation during ischemia and reperfusion.
The effects of a stable prostacyclin mimetic, iloprost (30 nmol/l), and of indomethacin (3 mumol/l) on ischemia-plus-reperfusion-induced changes in myocardial hemodynamics and sympathetic nerve function were examined in Langendorff-perfused rabbit heart isolated except for the postganglionic sympathetic cardiac nerves. Noradrenaline overflow was measured during an initial 1-min period of nerve stimulation (S1), compared with an identical stimulation (S2) made after 2 h of low-flow ischemia followed by a 30-min reperfusion period. Myocardial catecholamine content of left ventricular tissue was also measured. Pretreatment with iloprost, indomethacin, or vehicle began 10 min before ischemia. Global ischemia plus reperfusion reduced myocardial catecholamine content by 19% (vehicle), and the reduction was greater in indomethacin-pretreated hearts (37%, p less than 0.05), whereas iloprost increased tissue noradrenaline 18% above vehicle control (p less than 0.05). Initially, nerve stimulation-induced noradrenaline overflow ranged from 213 to 247 pmoles, and was significantly reduced after ischemia and reperfusion, the difference (S1-S2) being 198 pmoles (vehicle) and 117 pmoles (indomethacin), but only 44 pmoles after iloprost pretreatment (all groups p less than 0.01). In addition, iloprost improved the recovery of active systolic pressure development, coronary perfusion and left ventricular compliance on reperfusion, whereas a tendency toward further deterioration was observed in indomethacin-pretreated hearts. The results suggest that iloprost may protect both myocardial muscle and nerve cells from ischemia-plus-reperfusion injury. Preservation of myocardial catecholamine levels and sympathetic nerve responsiveness may contribute to improved recovery of reperfused ischemic myocardium.
Schrör
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Funke
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D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004558:Electric Stimulation; D011464:Epoprostenol / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D016285:Iloprost; D007213:Indomethacin / Q000494:pharmacology; D009200:Myocardial Contraction; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000502:physiology*
D011453:Prostaglandins; D011464:Epoprostenol; D016285:Iloprost; D009638:Norepinephrine; D007213:Indomethacin