Núñez B D, Miao L, Wang Y, Núñez M M, Klein M A, Sellke F W, Ross J N, Susulic V, Paik G Y, Carrozza J P
Charles A. Dana Research Institute, Boston, Mass.
Circ Res. 1994 Feb;74(2):281-90. doi: 10.1161/01.res.74.2.281.
The purpose of the present study was to determine the maximal coronary flow reserve (CFR) before and after the administration of successive cocaine doses (0.1, 0.5, 3, and 7 mg/kg IV) for 2 minutes at 10-minute intervals in eight miniature swine. CFR was assessed by the administration of adenosine (0.03, 0.3, and 3 mg IC). Hemodynamic and flow measurements were performed 3 minutes after each dose. Coronary flow (CF) was measured with a Doppler-tipped wire in the proximal left anterior descending coronary artery (LAD). Also, microvessels were dissected, and vessel diameters were measured by a videoelectronic dimension analyzer. In vivo, LAD CF increased fourfold, CFR increased twofold, and coronary vascular resistance (CVR) decreased fourfold after the administration of adenosine. In contrast, LAD CF decreased threefold, CFR decreased onefold, and CVR increased sixfold 3 minutes after the administration of cocaine. Adenosine (3 mg) was repeated 4 minutes after the administration of cocaine, and LAD CF increased 1.4-fold, CVR increased 2.5-fold, and CFR decreased onefold. Thus, adenosine partially reversed the potent cocaine constrictor effect. In vitro, 10(-9) mol/L cocaine decreased the diameter of the coronary microvessels from 129 +/- 12 to 127 +/- 12 microns, and 10(-4) mol/L cocaine decreased coronary microvessel diameter to 114 +/- 15 microns (P < .05). In conclusion, cocaine in vivo decreases CFR, and consistent with the in vivo effect, cocaine in vitro produced constriction of vessels < 200 microns. These results indicate that cocaine can produce profound microvascular spasm. This may contribute to the ischemia/infarction reported in patients who abuse cocaine and who are subsequently found to have normal epicardial coronary arteries.
本研究的目的是确定在八只小型猪中，以10分钟的间隔连续静脉注射可卡因剂量（0.1、0.5、3和7mg/kg）2分钟前后的最大冠状动脉血流储备（CFR）。通过注射腺苷（0.03、0.3和3mg冠状动脉内注射）来评估CFR。在每次给药后3分钟进行血流动力学和血流测量。用置于左冠状动脉前降支近端的多普勒导丝测量冠状动脉血流（CF）。此外，解剖微血管，并用视频电子尺寸分析仪测量血管直径。在体内，注射腺苷后，左冠状动脉前降支血流增加四倍，CFR增加两倍，冠状动脉血管阻力（CVR）降低四倍。相比之下，注射可卡因3分钟后，左冠状动脉前降支血流减少三倍，CFR减少一倍，CVR增加六倍。在注射可卡因4分钟后重复注射腺苷（3mg），左冠状动脉前降支血流增加1.4倍，CVR增加2.5倍，CFR减少一倍。因此，腺苷部分逆转了可卡因的强效收缩效应。在体外，10⁻⁹mol/L可卡因使冠状动脉微血管直径从129±12微米减小到127±12微米，10⁻⁴mol/L可卡因使冠状动脉微血管直径减小到114±15微米（P<0.05）。总之，可卡因在体内降低CFR，并且与体内效应一致，可卡因在体外使直径<200微米的血管收缩。这些结果表明可卡因可引起严重的微血管痉挛。这可能有助于解释滥用可卡因且随后被发现心外膜冠状动脉正常的患者中所报道的缺血/梗死情况。
