Kawamura A, Fujiwara H, Ishida M, Takemura G, Kida M, Uegaito T, Tanaka M, Kawai C
Department of Internal Medicine, Kyoto University Hospital, Japan.
Cardiovasc Res. 1990 Dec;24(12):1013-9. doi: 10.1093/cvr/24.12.1013.
Protective effects of nipradilol, a newly synthesised vasodilating beta adrenoceptor antagonist, isosorbide dinitrate, and bunazosin on coronary artery constriction induced by intracoronary injection of acetylcholine were determined by coronary arteriography and compared in vivo in pigs.
Acetylcholine (12.5, 25, 50, 100 and 200 micrograms) was given into the right coronary artery under left ventricular pacing to maintain constant systemic haemodynamics. Percentage narrowing of the major epicardial coronary artery was used as an indicator of constriction of the large coronary arteries, and the time required for the contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery (blood flow delay) was used as an indicator of constriction of the small coronary arteries.
15 farm pigs weighing 80 to 90 kg were used.
A marked blood flow delay of over 7.0 s (control: less than or equal to 1.8 s) with less than 34% narrowing of the epicardial major coronary artery was observed in 13 of 15 pigs with 12.5-50 micrograms of acetylcholine, and in the other two pigs with 100 micrograms of acetylcholine. When marked blood flow delay occurred, the perfused right ventricular myocardium became macroscopically anaemic (ischaemic). Over 75% narrowing of the major epicardial coronary artery was induced in six of the 15 pigs, and over 50% narrowing in 12, with marked blood flow delay with 100 to 200 micrograms of acetylcholine. However, after intracoronary infusion of 10 micrograms of nipradilol, acetylcholine induced narrowing in the epicardial major coronary artery was significantly reduced from 44-79% in control to 19-37% despite 200 micrograms of acetylcholine, though the time delay in coronary blood flow did not change significantly. By pretreatment with intracoronary isosorbide dinitrate (2.5 mg), the percent narrowing of the large coronary artery and the time delay in coronary blood flow were significantly reduced (narrowing from 32-84% to 10-27%; time delay from 7.6-41.6 s to 2.7-22.7 s). Pretreatment with intracoronary bunazosin, an alpha 1 adrenoceptor antagonist (100 micrograms), showed no protective effect on narrowing of the epicardial major coronary artery or blood flow delay.
Isosorbide dinitrate prevents coronary artery constriction induced by acetylcholine in swine. Nipradilol prevents large, but not small, coronary artery constriction, probably through a direct nitrate like vasodilating action.
通过冠状动脉造影术测定新合成的血管舒张性β肾上腺素受体拮抗剂尼普地洛、硝酸异山梨酯和布那唑嗪对冠状动脉内注射乙酰胆碱诱导的冠状动脉收缩的保护作用，并在猪体内进行比较。
在左心室起搏下将乙酰胆碱（12.5、25、50、100和200微克）注入右冠状动脉，以维持恒定的全身血流动力学。主要心外膜冠状动脉的狭窄百分比用作大冠状动脉收缩的指标，造影剂从右冠状动脉口到达后降支冠状动脉所需的时间（血流延迟）用作小冠状动脉收缩的指标。
使用15头体重80至90千克的农场猪。
15头猪中有13头在注射12.5 - 50微克乙酰胆碱时，观察到明显的血流延迟超过7.0秒（对照组：小于或等于1.8秒），心外膜主要冠状动脉狭窄小于34%，另外两头猪注射100微克乙酰胆碱时也出现这种情况。当出现明显的血流延迟时，灌注的右心室心肌在宏观上变得贫血（缺血）。15头猪中有6头在注射100至200微克乙酰胆碱时，心外膜主要冠状动脉狭窄超过75%，12头超过50%，伴有明显的血流延迟。然而，冠状动脉内注入10微克尼普地洛后，尽管使用了200微克乙酰胆碱，乙酰胆碱诱导的心外膜主要冠状动脉狭窄仍从对照组的44 - 79%显著降低至19 - 37%，尽管冠状动脉血流的时间延迟没有明显变化。通过冠状动脉内预处理硝酸异山梨酯（2.5毫克），大冠状动脉的狭窄百分比和冠状动脉血流的时间延迟均显著降低（狭窄从32 - 84%降至10 - 27%；时间延迟从7.6 - 41.6秒降至2.7 - 22.7秒）。冠状动脉内预处理α1肾上腺素受体拮抗剂布那唑嗪（100微克）对心外膜主要冠状动脉狭窄或血流延迟无保护作用。
硝酸异山梨酯可预防猪体内乙酰胆碱诱导的冠状动脉收缩。尼普地洛可预防大冠状动脉收缩，但不能预防小冠状动脉收缩，可能是通过类似硝酸酯的直接血管舒张作用。
