Clonidine prevents the sympathetic initiation and aggravation of poststenotic myocardial ischemia.
We studied the effects of clonidine (10 micrograms/kg i.v.) on the positive feedback between poststenotic myocardial ischemia and cardiac sympathetic nerve activation and on the initiation of poststenotic myocardial ischemia during bilateral carotid occlusion in 12 anesthetized, open-chest dogs. During 20 min of acute severe coronary stenosis, cardiac sympathetic nerve activity increased by 24 +/- 6%, poststenotic coronary resistance increased from 0.45 +/- 0.05 to 0.61 +/- 0.08 mm Hg . min . 100 g/ml, and the poststenotic myocardial lactate consumption of 25 +/- 6 mumol/min . 100 g at 1 min of stenosis was reversed to a net lactate production of 8 +/- 3 mumol/min . 100 g after 20 min of stenosis. An additional 60-s bilateral carotid occlusion increased cardiac sympathetic nerve activity furthermore to 157 +/- 7% of control, increased poststenotic coronary resistance to 0.84 +/- 0.14 mm Hg . min . 100 g/ml, and increased the net lactate production to 22 +/- 6 mumol/min . 100 g. With heart rate and left ventricular pressure kept constant, clonidine decreased cardiac sympathetic nerve activity to 21 +/- 6% of control and prevented any further sympathetic activation during 20 min of coronary stenosis and bilateral carotid occlusion. Conversely, poststenotic coronary resistance and myocardial lactate consumption remained unchanged. Intracoronary clonidine (100 micrograms) in five of the 12 dogs increased poststenotic coronary resistance from 0.47 +/- 0.04 to 0.61 +/- 0.05 mm Hg . min . 100 g/ml and reversed the myocardial lactate consumption of 36 +/- 4 mumol/min . 100 g to a net lactate production of 7 +/- 5 mumol/min . 100 g. Our results suggest that clonidine can, by a central nervous action, prevent the sympathetic initiation and aggravation of poststenotic myocardial ischemia and may thus be effective in the treatment of exertional angina.
G
G
Heusch
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J
Schipke
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V
Thämer
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D003000:Clonidine / Q000494:pharmacology*; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology*; D004285:Dogs; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
D007773:Lactates; D003000:Clonidine