Takeuchi M, Nohtomi Y, Kuroiwa A
Second Department of Internal Medicine, University of Occupational and Environment Health, Kitakyushu, Japan.
Cathet Cardiovasc Diagn. 1996 Oct;39(2):126-30. doi: 10.1002/(SICI)1097-0304(199610)39:2<126::AID-CCD4>3.0.CO;2-H.
Although intracoronary papaverine has been widely used for the measurement of coronary flow reserve, little is known concerning whether papaverine may produce deleterious metabolic changes in humans. We investigated the effect of papaverine on lactate metabolism in 28 patients with normal coronary arteries. We continuously monitored phasic coronary flow velocity in the proximal left anterior descending coronary artery using Doppler guidewire. We also obtained paired samples of arterial and coronary sinus blood for the measurement of lactate at control and at 1 min after administration of 10 mg of intracoronary papaverine. There were no serious side effects during papaverine infusion. Sixteen patients showed ST-T abnormalities after papaverine. The QTc interval increased from 450 +/- 42 msec to 571 +/- 58 msec (P < 0.001). Average peak velocity increased significantly (% increase: 198.5 +/- 87.8%, range: 27.8-374.1%) after papaverine. Although intracoronary papaverine produced no significant change in arterial lactate levels (8.5 +/- 4.0-8.8 +/- 5.0 mg/ml), it induced a significant increase in coronary sinus lactate levels (5.4 +/- 3.2-15.3 +/- 8.2 mg/ml, P < 0.001). Lactate extraction ratio decreased significantly (36.4 +/- 18.4--82.2 +/- 58.4%, P < 0.001), and all patients showed net lactate production (-3.9--198.0%) after papaverine. There was weak but significant correlation between lactate extraction ratio after papaverine and coronary flow reserve (R2 = 0.15, P < 0.05). There was no correlation between lactate extraction ratio and QTc interval after papaverine. The mean value of lactate extraction ratio was not different in patients with ST-T abnormalities induced by papaverine compared to those without. These results demonstrate that intracoronary papaverine induces myocardial lactate production irrespective of the degree of coronary flow reserve and electrocardiographic changes in patients with normal coronary arteries. A safer and more reliable agent is needed for the measurement of coronary flow reserve.
尽管冠状动脉内注射罂粟碱已被广泛用于测量冠状动脉血流储备,但关于罂粟碱是否会在人体内产生有害的代谢变化却知之甚少。我们研究了罂粟碱对28例冠状动脉正常患者乳酸代谢的影响。我们使用多普勒导丝连续监测左前降支冠状动脉近端的阶段性冠状动脉血流速度。我们还采集了动脉血和冠状窦血的配对样本,用于在对照时以及冠状动脉内注射10mg罂粟碱后1分钟测量乳酸。罂粟碱输注过程中未出现严重副作用。16例患者在注射罂粟碱后出现ST-T异常。QTc间期从450±42毫秒增加到571±58毫秒(P<0.001)。注射罂粟碱后平均峰值速度显著增加(增加百分比:198.5±87.8%,范围:27.8 - 374.1%)。尽管冠状动脉内注射罂粟碱后动脉血乳酸水平无显著变化(8.5±4.0 - 8.8±5.0mg/ml),但它导致冠状窦血乳酸水平显著升高(5.4±3.2 - 15.3±8.2mg/ml,P<0.001)。乳酸摄取率显著降低(36.4±18.4 - -82.2±58.4%,P<0.001),所有患者在注射罂粟碱后均出现净乳酸生成(-3.9 - -198.0%)。注射罂粟碱后的乳酸摄取率与冠状动脉血流储备之间存在微弱但显著的相关性(R2 = 0.15,P<0.05)。注射罂粟碱后的乳酸摄取率与QTc间期之间无相关性。与未出现ST-T异常的患者相比,注射罂粟碱导致ST-T异常的患者乳酸摄取率平均值无差异。这些结果表明,冠状动脉内注射罂粟碱会导致心肌乳酸生成,而与冠状动脉血流储备程度和冠状动脉正常患者的心电图变化无关。测量冠状动脉血流储备需要一种更安全、更可靠的药物。