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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Feb;108(2):342–347. doi: 10.1111/j.1476-5381.1993.tb12807.x

Allopurinol and amlodipine improve coronary vasodilatation after myocardial ischaemia and reperfusion in anaesthetized dogs.

C G Sobey 1, R A Dalipram 1, O L Woodman 1
PMCID: PMC1907964  PMID: 8448585

Abstract

1. We have assessed the effect of allopurinol, amlodipine and propranolol pretreatment on both endothelium-dependent and endothelium-independent coronary vasodilatation in vivo, by comparing pre-ischaemic responses with those measured after 60 min of coronary artery occlusion and 30 min of reperfusion in anaesthetized dogs. 2. In 15 untreated dogs ischaemia and reperfusion attenuated the increases in coronary blood flow produced by either acetylcholine (0.01-0.05 micrograms kg-1, i.a.) or glyceryl trinitrate (0.05-0.2 micrograms kg-1, i.a.), to an average of 39 +/- 4% and 42 +/- 5% of the pre-ischaemic control response, respectively (both P < 0.05). 3. In 5 dogs treated with allopurinol (25 mg kg-1, orally, 24 h previously, plus 50 mg kg-1, i.v., 5 min before occlusion), the increases in coronary blood flow after ischaemia and reperfusion (acetylcholine: 78 +/- 12%, glyceryl trinitrate: 60 +/- 3% of pre-ischaemic response) were significantly larger than post-ischaemic responses in untreated dogs (both P < 0.05). 4. Similarly, amlodipine treatment (3 micrograms kg-1 min-1, i.v., starting 90 min before occlusion) in 5 dogs improved post-ischaemic increases in blood flow (acetylcholine: 58.5%, glyceryl trinitrate: 66 +/- 6% of pre-ischaemic response, significantly greater than post-ischaemic responses in untreated dogs, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Ambrosio G., Becker L. C., Hutchins G. M., Weisman H. F., Weisfeldt M. L. Reduction in experimental infarct size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury. Circulation. 1986 Dec;74(6):1424–1433. doi: 10.1161/01.cir.74.6.1424. [DOI] [PubMed] [Google Scholar]
  2. Capecchi P. L., Pasini F. L., Pasqui A. L., Orrico A., Ceccatelli L., Acciavatti A., Galigani C., Pieragalli D., Di Perri T. Allopurinol prevents ischaemia-dependent haemorheological changes. Eur J Clin Pharmacol. 1988;35(5):475–481. doi: 10.1007/BF00558241. [DOI] [PubMed] [Google Scholar]
  3. Chambers D. J., Braimbridge M. V., Hearse D. J. Free radicals and cardioplegia: allopurinol and oxypurinol reduce myocardial injury following ischemic arrest. Ann Thorac Surg. 1987 Sep;44(3):291–297. doi: 10.1016/s0003-4975(10)62076-0. [DOI] [PubMed] [Google Scholar]
  4. Chu A., Chambers D. E., Lin C. C., Kuehl W. D., Cobb F. R. Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia. Circ Res. 1990 Jun;66(6):1484–1490. doi: 10.1161/01.res.66.6.1484. [DOI] [PubMed] [Google Scholar]
  5. Engler R. L., Schmid-Schönbein G. W., Pavelec R. S. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol. 1983 Apr;111(1):98–111. [PMC free article] [PubMed] [Google Scholar]
  6. Engler R. Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. Fed Proc. 1987 May 15;46(7):2407–2412. [PubMed] [Google Scholar]
  7. Irita K., Fujita I., Takeshige K., Minakami S., Yoshitake J. Calcium channel antagonist induced inhibition of superoxide production in human neutrophils. Mechanisms independent of antagonizing calcium influx. Biochem Pharmacol. 1986 Oct 15;35(20):3465–3471. doi: 10.1016/0006-2952(86)90613-1. [DOI] [PubMed] [Google Scholar]
  8. Jolly S. R., Kane W. J., Bailie M. B., Abrams G. D., Lucchesi B. R. Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ Res. 1984 Mar;54(3):277–285. doi: 10.1161/01.res.54.3.277. [DOI] [PubMed] [Google Scholar]
  9. Jones H. P., Grisham M. B., Bose S. K., Shannon V. A., Schott A., McCord J. M. Effect of allopurinol on neutrophil superoxide production, chemotaxis, or degranulation. Biochem Pharmacol. 1985 Oct 15;34(20):3673–3676. doi: 10.1016/0006-2952(85)90229-1. [DOI] [PubMed] [Google Scholar]
  10. Jouvin-Marche E., Cerrina J., Coëffier E., Duroux P., Benveniste J. Effect of the Ca2+ antagonist nifedipine on the release of platelet-activating factor (PAF-acether), slow-reacting substance and beta-glucuronidase from human neutrophils. Eur J Pharmacol. 1983 Apr 22;89(1-2):19–26. doi: 10.1016/0014-2999(83)90603-9. [DOI] [PubMed] [Google Scholar]
  11. Kloner R. A., Ganote C. E., Jennings R. B. The "no-reflow" phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974 Dec;54(6):1496–1508. doi: 10.1172/JCI107898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ku D. D. Coronary vascular reactivity after acute myocardial ischemia. Science. 1982 Nov 5;218(4572):576–578. doi: 10.1126/science.7123259. [DOI] [PubMed] [Google Scholar]
  13. Lefer A. M., Johnson G., 3rd, Ma X. L., Tsao P. S., Thomas G. R. Cardioprotective and endothelial protective effects of [Ala-IL8]77 in a rabbit model of myocardial ischaemia and reperfusion. Br J Pharmacol. 1991 May;103(1):1153–1159. doi: 10.1111/j.1476-5381.1991.tb12316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lucchesi B. R., Burmeister W. E., Lomas T. E., Abrams G. D. Ischemic changes in the canine heart as affected by the dimethyl quaternary analog of propranolol, UM-272 (SC-27761). J Pharmacol Exp Ther. 1976 Nov;199(2):310–328. [PubMed] [Google Scholar]
  15. Mehta J. L., Lawson D. L., Nichols W. W. Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A. Am J Physiol. 1989 Oct;257(4 Pt 2):H1240–H1246. doi: 10.1152/ajpheart.1989.257.4.H1240. [DOI] [PubMed] [Google Scholar]
  16. Mehta J. L., Nichols W. W., Donnelly W. H., Lawson D. L., Saldeen T. G. Impaired canine coronary vasodilator response to acetylcholine and bradykinin after occlusion-reperfusion. Circ Res. 1989 Jan;64(1):43–54. doi: 10.1161/01.res.64.1.43. [DOI] [PubMed] [Google Scholar]
  17. Mehta J. L., Nichols W. W., Donnelly W. H., Lawson D. L., Thompson L., ter Riet M., Saldeen T. G. Protection by superoxide dismutase from myocardial dysfunction and attenuation of vasodilator reserve after coronary occlusion and reperfusion in dog. Circ Res. 1989 Nov;65(5):1283–1295. doi: 10.1161/01.res.65.5.1283. [DOI] [PubMed] [Google Scholar]
  18. Mullane K. M., Read N., Salmon J. A., Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs. J Pharmacol Exp Ther. 1984 Feb;228(2):510–522. [PubMed] [Google Scholar]
  19. Nayler W. G., Ferrari R., Williams A. Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. Am J Cardiol. 1980 Aug;46(2):242–248. doi: 10.1016/0002-9149(80)90064-8. [DOI] [PubMed] [Google Scholar]
  20. Nichols W. W., Mehta J. L., Donnelly W. H., Lawson D., Thompson L., ter Riet M. Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins. J Mol Cell Cardiol. 1988 Oct;20(10):943–954. doi: 10.1016/s0022-2828(88)80148-2. [DOI] [PubMed] [Google Scholar]
  21. Przyklenk K., Kloner R. A. "Reperfusion injury" by oxygen-derived free radicals? Effect of superoxide dismutase plus catalase, given at the time of reperfusion, on myocardial infarct size, contractile function, coronary microvasculature, and regional myocardial blood flow. Circ Res. 1989 Jan;64(1):86–96. doi: 10.1161/01.res.64.1.86. [DOI] [PubMed] [Google Scholar]
  22. Romson J. L., Hook B. G., Kunkel S. L., Abrams G. D., Schork M. A., Lucchesi B. R. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation. 1983 May;67(5):1016–1023. doi: 10.1161/01.cir.67.5.1016. [DOI] [PubMed] [Google Scholar]
  23. Seitelberger R., Zwölfer W., Huber S., Schwarzacher S., Binder T. M., Peschl F., Spatt J., Holzinger C., Podesser B., Buxbaum P. Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. Circulation. 1991 Feb;83(2):460–468. doi: 10.1161/01.cir.83.2.460. [DOI] [PubMed] [Google Scholar]
  24. Sheridan F. M., Dauber I. M., McMurtry I. F., Lesnefsky E. J., Horwitz L. D. Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion. Circ Res. 1991 Dec;69(6):1566–1574. doi: 10.1161/01.res.69.6.1566. [DOI] [PubMed] [Google Scholar]
  25. Sobey C. G., Dalipram R. A., Dusting G. J., Woodman O. L. Impaired endothelium-dependent relaxation of dog coronary arteries after myocardial ischaemia and reperfusion: prevention by amlodipine, propranolol and allopurinol. Br J Pharmacol. 1992 Mar;105(3):557–562. doi: 10.1111/j.1476-5381.1992.tb09018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tamura Y., Chi L. G., Driscoll E. M., Jr, Hoff P. T., Freeman B. A., Gallagher K. P., Lucchesi B. R. Superoxide dismutase conjugated to polyethylene glycol provides sustained protection against myocardial ischemia/reperfusion injury in canine heart. Circ Res. 1988 Nov;63(5):944–959. doi: 10.1161/01.res.63.5.944. [DOI] [PubMed] [Google Scholar]
  27. VanBenthuysen K. M., McMurtry I. F., Horwitz L. D. Reperfusion after acute coronary occlusion in dogs impairs endothelium-dependent relaxation to acetylcholine and augments contractile reactivity in vitro. J Clin Invest. 1987 Jan;79(1):265–274. doi: 10.1172/JCI112793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vanhaecke J., Flameng W., Borgers M., Jang I. K., Van de Werf F., De Geest H. Evidence for decreased coronary flow reserve in viable postischemic myocardium. Circ Res. 1990 Nov;67(5):1201–1210. doi: 10.1161/01.res.67.5.1201. [DOI] [PubMed] [Google Scholar]
  29. Werns S. W., Shea M. J., Mitsos S. E., Dysko R. C., Fantone J. C., Schork M. A., Abrams G. D., Pitt B., Lucchesi B. R. Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart. Circulation. 1986 Mar;73(3):518–524. doi: 10.1161/01.cir.73.3.518. [DOI] [PubMed] [Google Scholar]
  30. Werns S. W., Simpson P. J., Mickelson J. K., Shea M. J., Pitt B., Lucchesi B. R. Sustained limitation by superoxide dismutase of canine myocardial injury due to regional ischemia followed by reperfusion. J Cardiovasc Pharmacol. 1988 Jan;11(1):36–44. doi: 10.1097/00005344-198801000-00006. [DOI] [PubMed] [Google Scholar]

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