The prototype serotonin 5-HT 1B/1D agonist sumatriptan increases the severity of myocardial ischemia during atrial pacing in dogs with coronary artery stenosis.
The triptans, serotonin 5-HT 1B/1D agonists exemplified by sumatriptan, are an effective class of migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans have been shown to constrict human coronary artery in vitro, and there have been case reports of myocardial infarction in patients using sumatriptan. However, preclinical in vivo studies with sumatriptan in normal dogs have failed to demonstrate an effect on coronary flow. The present studies were conducted in a canine model in which regional myocardial ischemia was evoked by atrial pacing in the presence of a 40% stenosis of the left anterior descending coronary artery. Ischemic severity was quantified by changes in local epicardial electrograms (EGs) recorded in the ischemic zone. The intra-atrial administration of 10 microg x kg x min sumatriptan variably but not significantly increased the severity of regional ischemia (pre- vs. posttreatment: Delta EG: 2.00 +/- 0.17 vs. 3.05 +/- 1.15 mV). Sumatriptan at 30 microg x kg x min significantly increased ischemic severity (Delta EG: 1.88 +/- 0.19 vs. 3.32 +/- 0.58 mV, P < 0.05) concomitant with a significant reduction in coronary blood flow (8.9 +/- 0.5 vs. 7.2 +/- 0.8 mL/min, P < 0.05). These results demonstrate that a reduction in coronary flow with proischemic consequence can be modeled preclinically with sumatriptan in a canine model of cardiac stress.
Department of Integrative Systems Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA. joseph_lynch@merck.com
Joseph J
JJ
Lynch
Gary L
GL
Stump
Stefanie A
SA
Kane
Christopher P
CP
Regan
D000818:Animals; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D023921:Coronary Stenosis / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D058825:Serotonin 5-HT1 Receptor Agonists; D018170:Sumatriptan / Q000009:adverse effects* / Q000627:therapeutic use; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000627:therapeutic use
D058825:Serotonin 5-HT1 Receptor Agonists; D014662:Vasoconstrictor Agents; D018170:Sumatriptan