Abstract
1. Systemic and coronary haemodynamics were measured in 6 Yorkshire swine and 6 Yucatan miniature swine under isoflurane anaesthesia to investigate the influence of cocaine following its intravenous administration at 1, 3 and 7 mg kg-1. 2. Cocaine in Yorkshire swine decreased mean arterial pressure and rate pressure product (systolic pressure x heart rate), suggesting a cardiac depressant effect, whereas cocaine in Yucatan miniature swine increased these parameters, consistent with a hyperadrenergic state. 3. Cocaine in both Yorkshire swine and Yucatan miniature swine decreased coronary blood flow and coronary flow reserve, and increased coronary vascular resistance. 4. A modest generalized epicardial coronary artery constriction was observed by angiography, without evidence of focal spasm. 5. Our results confirm a marked vasoconstrictor effect of cocaine on the coronary arterial circulation, predominantly distal to the epicardial coronary arteries, but also indicate important differences in the systemic cardiovascular responses to the drug between two closely related strains of animals within the same species. Due to the similarities between the swine and human coronary arterial vasculature, we suggest that vasoconstriction in the coronary microcirculation may produce cardiac toxicity in man.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abel F. L., Wilson S. P., Zhao R. R., Fennell W. H. Cocaine depresses the canine myocardium. Circ Shock. 1989 Aug;28(4):309–319. [PubMed] [Google Scholar]
- Beckman K. J., Parker R. B., Hariman R. J., Gallastegui J. L., Javaid J. I., Bauman J. L. Hemodynamic and electrophysiological actions of cocaine. Effects of sodium bicarbonate as an antidote in dogs. Circulation. 1991 May;83(5):1799–1807. doi: 10.1161/01.cir.83.5.1799. [DOI] [PubMed] [Google Scholar]
- Bradley A. B., Morgan K. G. Alterations in cytoplasmic calcium sensitivity during porcine coronary artery contractions as detected by aequorin. J Physiol. 1987 Apr;385:437–448. doi: 10.1113/jphysiol.1987.sp016500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Catravas J. D., Waters I. W. Acute cocaine intoxication in the conscious dog: studies on the mechanism of lethality. J Pharmacol Exp Ther. 1981 May;217(2):350–356. [PubMed] [Google Scholar]
- Catravas J. D., Waters I. W., Walz M. A., Davis W. M. Acute cocaine intoxication in the conscious dog: pathophysiologic profile of acute lethality. Arch Int Pharmacodyn Ther. 1978 Oct;235(2):328–340. [PubMed] [Google Scholar]
- Egashira K., Pipers F. S., Morgan J. P. Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis. J Clin Invest. 1991 Oct;88(4):1307–1314. doi: 10.1172/JCI115435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Egashira K., Tomoike H., Yamamoto Y., Yamada A., Hayashi Y., Nakamura M. Histamine-induced coronary spasm in regions of intimal thickening in miniature pigs: roles of serum cholesterol and spontaneous or induced intimal thickening. Circulation. 1986 Oct;74(4):826–837. doi: 10.1161/01.cir.74.4.826. [DOI] [PubMed] [Google Scholar]
- Fraker T. D., Jr, Temesy-Armos P. N., Brewster P. S., Wilkerson R. D. Mechanism of cocaine-induced myocardial depression in dogs. Circulation. 1990 Mar;81(3):1012–1016. doi: 10.1161/01.cir.81.3.1012. [DOI] [PubMed] [Google Scholar]
- Ginsburg R., Bristow M. R., Harrison D. C., Stinson E. B. Studies with isolated human coronary arteries. Some general observations, potential mediators of spasm, role of calcium antagonists. Chest. 1980 Jul;78(1 Suppl):180–186. [PubMed] [Google Scholar]
- Gonzalez F. A., Byrd L. D. Physiological effects of cocaine in the squirrel monkey. Life Sci. 1977 Nov 15;21(10):1417–1424. doi: 10.1016/0024-3205(77)90195-3. [DOI] [PubMed] [Google Scholar]
- Graham M. H., Abboud F. M., Eckstein J. W. Effect of cocaine on cardiovascular responses in intact dogs. J Pharmacol Exp Ther. 1965 Oct;150(1):46–52. [PubMed] [Google Scholar]
- Hale S. L., Alker K. J., Rezkalla S. H., Eisenhauer A. C., Kloner R. A. Nifedipine protects the heart from the acute deleterious effects of cocaine if administered before but not after cocaine. Circulation. 1991 Apr;83(4):1437–1443. doi: 10.1161/01.cir.83.4.1437. [DOI] [PubMed] [Google Scholar]
- Hayes S. N., Moyer T. P., Morley D., Bove A. A. Intravenous cocaine causes epicardial coronary vasoconstriction in the intact dog. Am Heart J. 1991 Jun;121(6 Pt 1):1639–1648. doi: 10.1016/0002-8703(91)90007-5. [DOI] [PubMed] [Google Scholar]
- Hollander J. E., Carter W. A., Hoffman R. S. Use of phentolamine for cocaine-induced myocardial ischemia. N Engl J Med. 1992 Jul 30;327(5):361–361. doi: 10.1056/NEJM199207303270517. [DOI] [PubMed] [Google Scholar]
- Isner J. M., Chokshi S. K. Cardiovascular complications of cocaine. Curr Probl Cardiol. 1991 Feb;16(2):89–123. doi: 10.1016/0146-2806(91)90013-z. [DOI] [PubMed] [Google Scholar]
- Isner J. M., Estes N. A., 3rd, Thompson P. D., Costanzo-Nordin M. R., Subramanian R., Miller G., Katsas G., Sweeney K., Sturner W. Q. Acute cardiac events temporally related to cocaine abuse. N Engl J Med. 1986 Dec 4;315(23):1438–1443. doi: 10.1056/NEJM198612043152302. [DOI] [PubMed] [Google Scholar]
- Koerker R. L., Moran N. C. An evaluation of the inability of cocaine to potentiate the responses to cardiac sympathetic nerve stimulation in the dog. J Pharmacol Exp Ther. 1971 Sep;178(3):482–496. [PubMed] [Google Scholar]
- Kossowsky W. A., Lyon A. F. Cocaine and acute myocardial infarction. A probable connection. Chest. 1984 Nov;86(5):729–731. doi: 10.1378/chest.86.5.729. [DOI] [PubMed] [Google Scholar]
- Lan Y. H., McKeith F. K., Novakofski J., Carr T. R. Carcass and muscle characteristics of Yorkshire, Meishan, Yorkshire x Meishan, Meishan x Yorkshire, Fengjing x Yorkshire, and Minzhu x Yorkshire pigs. J Anim Sci. 1993 Dec;71(12):3344–3349. doi: 10.2527/1993.71123344x. [DOI] [PubMed] [Google Scholar]
- Lange R. A., Cigarroa R. G., Yancy C. W., Jr, Willard J. E., Popma J. J., Sills M. N., McBride W., Kim A. S., Hillis L. D. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med. 1989 Dec 7;321(23):1557–1562. doi: 10.1056/NEJM198912073212301. [DOI] [PubMed] [Google Scholar]
- Moreland R. S., Bohr D. F. Adrenergic control of coronary arteries. Fed Proc. 1984 Nov;43(14):2857–2861. [PubMed] [Google Scholar]
- Nanji A. A., Filipenko J. D. Asystole and ventricular fibrillation associated with cocaine intoxication. Chest. 1984 Jan;85(1):132–133. doi: 10.1378/chest.85.1.132. [DOI] [PubMed] [Google Scholar]
- Núez B. D., Miao L., Kuntz R. E., Ross J. N., Gladstone S., Baim D. S., Gordon P. C., Morgan J. P., Carrozza J. P., Jr Cardiogenic shock induced by cocaine in swine with normal coronary arteries. Cardiovasc Res. 1994 Jan;28(1):105–111. doi: 10.1093/cvr/28.1.105. [DOI] [PubMed] [Google Scholar]
- Núez B. D., Miao L., Wang Y., Núez M. M., Klein M. A., Sellke F. W., Ross J. N., Susulic V., Paik G. Y., Carrozza J. P. Cocaine-induced microvascular spasm in Yucatan miniature swine. In vivo and in vitro evidence of spasm. Circ Res. 1994 Feb;74(2):281–290. doi: 10.1161/01.res.74.2.281. [DOI] [PubMed] [Google Scholar]
- Perreault C. L., Hague N. L., Ransil B. J., Morgan J. P. The effects of cocaine on intracellular Ca2+ handling and myofilament Ca2+ responsiveness of ferret ventricular myocardium. Br J Pharmacol. 1990 Nov;101(3):679–685. doi: 10.1111/j.1476-5381.1990.tb14140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rezkalla S. H., Hale S., Kloner R. A. Cocaine-induced heart diseases. Am Heart J. 1990 Dec;120(6 Pt 1):1403–1408. doi: 10.1016/0002-8703(90)90255-v. [DOI] [PubMed] [Google Scholar]
- Schwartz A. B., Janzen D., Jones R. T., Boyle W. Electrocardiographic and hemodynamic effects of intravenous cocaine in awake and anesthetized dogs. J Electrocardiol. 1989 Apr;22(2):159–166. doi: 10.1016/0022-0736(89)90086-1. [DOI] [PubMed] [Google Scholar]
- Shimokawa H., Tomoike H., Nabeyama S., Yamamoto H., Araki H., Nakamura M., Ishii Y., Tanaka K. Coronary artery spasm induced in atherosclerotic miniature swine. Science. 1983 Aug 5;221(4610):560–562. doi: 10.1126/science.6408736. [DOI] [PubMed] [Google Scholar]
- Stambler B. S., Komamura K., Ihara T., Shannon R. P. Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs. Circulation. 1993 May;87(5):1687–1697. doi: 10.1161/01.cir.87.5.1687. [DOI] [PubMed] [Google Scholar]
- Wang S. Y., Nunez B. D., Morgan J. P., Dai H. B., Ross J. N., Sellke F. W. Cocaine and the porcine coronary microcirculation: effects of chronic cocaine exposure and hypercholesterolemia. J Cardiothorac Vasc Anesth. 1995 Jun;9(3):290–296. doi: 10.1016/s1053-0770(05)80323-4. [DOI] [PubMed] [Google Scholar]
- Wetli C. V., Wright R. K. Death caused by recreational cocaine use. JAMA. 1979 Jun 8;241(23):2519–2522. [PubMed] [Google Scholar]
- Wilkerson R. D. Cardiovascular effects of cocaine in conscious dogs: importance of fully functional autonomic and central nervous systems. J Pharmacol Exp Ther. 1988 Aug;246(2):466–471. [PubMed] [Google Scholar]
- Yamamoto Y., Tomoike H., Egashira K., Kobayashi T., Kawasaki T., Nakamura M. Pathogenesis of coronary artery spasm in miniature swine with regional intimal thickening after balloon denudation. Circ Res. 1987 Jan;60(1):113–121. doi: 10.1161/01.res.60.1.113. [DOI] [PubMed] [Google Scholar]
- Zimmerman F. H., Gustafson G. M., Kemp H. G., Jr Recurrent myocardial infarction associated with cocaine abuse in a young man with normal coronary arteries: evidence for coronary artery spasm culminating in thrombosis. J Am Coll Cardiol. 1987 Apr;9(4):964–968. doi: 10.1016/s0735-1097(87)80256-5. [DOI] [PubMed] [Google Scholar]