Gaspardone A, Crea F, Tomai F, Versaci F, Iamele M, Gioffrè G, Chiariello L, Gioffrè P A
Divisione di Cardiochirurgia, Università di Roma Tor Vergata, Italy.
J Am Coll Cardiol. 1995 Jan;25(1):251-7. doi: 10.1016/0735-1097(94)00352-q.
This study attempted to establish whether bamiphylline, a selective antagonist of A1 adenosine receptors, prevents the algogenic effects of adenosine in humans.
Experimental findings indicate that the sympathoexcitatory response elicited by adenosine is mediated by A1 receptors.
An intrailiac infusion of increasing doses (from 125 to 2,000 micrograms/min) of adenosine was given to 20 patients. Adenosine infusion was then repeated after intrailiac infusion of either bamiphylline or saline solution. In 14 other patients with angina, increasing doses of adenosine (from 108 to 1,728 micrograms/min) were infused into the left coronary artery. Adenosine infusion was then repeated after the intravenous infusion of either bamiphylline or placebo. Coronary blood flow velocity was monitored by a Doppler catheter. Data relative to pain severity are expressed as median and all other data as mean value +/- 1 SD.
Bamiphylline prolonged the time to pain onset caused by the intrailiac adenosine infusion from 444 +/- 96 to 749 +/- 120 s (p < 0.001) and reduced pain severity from 45 to 24 mm (p < 0.01). After placebo infusion, the time to pain onset and pain severity were similar to that of baseline (428 +/- 112 vs. 430 +/- 104 s, p = 0.87 and 44 vs. 43 mm, p = 0.67, respectively). Bamiphylline prolonged the time to pain onset caused by intracoronary adenosine infusion from 519 +/- 128 to 603 +/- 146 s (p < 0.01) and reduced pain severity from 58 to 28 mm (p < 0.02). After placebo infusion, the time to pain onset and pain severity were similar to that at baseline (542 +/- 87 vs. 551 +/- 79 s, p = 0.14 and 55 vs. 50 mm, p = 0.61). Maximal coronary blood flow velocities before and after bamiphylline administration were similar (47 +/- 22 vs. 49 +/- 24 cm/s, p = 0.36) as well as before and after placebo administrtion (40 +/- 20 vs. 41 +/- 20 cm/s, p = 0.07).
Bamiphylline reduces adenosine-induced muscular and cardiac pain but does not affect adenosine-induced coronary vasodilation. These findings indicate that at the dose used in this study, bamiphylline does not detectably block vascular A2-receptor-mediated adenosine effects in humans, which suggests that the muscular and cardiac algogenic effects of adenosine are mediated mainly by A1 receptors.
本研究试图确定A1腺苷受体的选择性拮抗剂巴米茶碱是否能预防腺苷对人体产生的致痛作用。
实验结果表明，腺苷引发的交感神经兴奋反应由A1受体介导。
对20例患者进行髂内动脉输注递增剂量（从125至2000微克/分钟）的腺苷。然后在髂内动脉输注巴米茶碱或生理盐水后重复输注腺苷。在另外14例心绞痛患者中，将递增剂量（从108至1728微克/分钟）的腺苷注入左冠状动脉。然后在静脉输注巴米茶碱或安慰剂后重复输注腺苷。用多普勒导管监测冠状动脉血流速度。与疼痛严重程度相关的数据以中位数表示，所有其他数据以平均值±1标准差表示。
巴米茶碱使髂内腺苷输注引起的疼痛发作时间从444±96秒延长至749±120秒（p<0.001），并使疼痛严重程度从45毫米降至24毫米（p<0.01）。安慰剂输注后，疼痛发作时间和疼痛严重程度与基线时相似（分别为428±112秒对430±104秒，p = 0.87；44毫米对43毫米，p = 0.67）。巴米茶碱使冠状动脉内腺苷输注引起的疼痛发作时间从519±128秒延长至603±146秒（p<0.01），并使疼痛严重程度从58毫米降至28毫米（p<0.02）。安慰剂输注后，疼痛发作时间和疼痛严重程度与基线时相似（分别为542±87秒对551±79秒，p = 0.14；55毫米对50毫米，p = 0.61）。巴米茶碱给药前后的最大冠状动脉血流速度相似（47±22对49±24厘米/秒，p = 0.36），安慰剂给药前后也相似（40±20对41±20厘米/秒，p = 0.07）。
巴米茶碱可减轻腺苷引起的肌肉和心脏疼痛，但不影响腺苷引起的冠状动脉血管舒张。这些发现表明，在本研究使用的剂量下，巴米茶碱在人体中未检测到对血管A2受体介导的腺苷效应的阻断作用，这表明腺苷的肌肉和心脏致痛作用主要由A1受体介导。
