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. 1974 Jan;29(1):38–50. doi: 10.1136/thx.29.1.38

An experimental evaluation of continuous normothermic, intermittent hypothermic, and intermittent normothermic coronary perfusion

A Hedley Brown 1,1, M V Braimbridge 1, Sally Darracott 1,2, J Chayen 1,3, H Kasap 1,4
PMCID: PMC470402  PMID: 4274933

Abstract

Hedley Brown, A., Braimbridge, M. V., Darracott, Sally, Chayen, J., and Kasap, H. (1974).Thorax, 29, 38-50. An experimental evaluation of continuous normothermic, intermittent hypothermic, and intermittent normothermic coronary perfusion. Coronary perfusion and hypothermia both have disadvantages, and excellent clinical results are obtained without them, though short operations, spontaneous cooling of unperfused hearts, hyperglycaemia, heparinization, and young and cyanotic subjects may allow more tolerance of ischaemia. Functional, macroscopic, histological, ultrastructural, chemical, and metabolic evidence of the inadvisability of ischaemia, especially of hypertrophied hearts, abounds, though statistical support and histochemical proof are lacking.

Isovolumic function tests permit accurate assessment of compliance. Succinic dehydrogenase distribution is the most relevant enzyme assay of myocardial transport; freed phospholipids indicate cellular membrane disorganization. Adenosinetriphosphate response of myosin (myocardial ATP ase) is shown quantitatively by change of birefringence. Ventricular oedema may be detected by changes in weight. These tests were used to compare continuous normothermic, intermittent hypothermic, and intermittent normothermic perfusion over two hours in isolated, cross-perfused canine hearts. Isolated hearts are very sensitive to imperfections of maintenance, but cross-perfusion minimizes perfusion-induced deterioration.

Normothermic continuously perfused hearts performed significantly better than intermittently perfused hearts, among which cooled hearts functioned better than normothermic hearts after two hours. Succinic dehydrogenase and acid haematein tests showed significant benefit from cooling during intermittent perfusion. The experimental preparation and techniques of assessment proved sensitive enough to demonstrate these differences, though cooling preserved cellular enzymes better than it did function. This work gives histochemical and statistical support to existing evidence that intermittent ischaemia for two hours can be ameliorated by moderate hypothermia but is not as effective for myocardial maintenance as constant perfusion with normal blood.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott W. M. Viability assays as applied to the cryopreservation of hearts and kidneys. Cryobiology. 1969 May-Jun;5(6):454–462. doi: 10.1016/s0011-2240(69)80112-4. [DOI] [PubMed] [Google Scholar]
  2. Angell W. W., Rikkers L., Dong E., Jr, Shumway N. E. Organ viability with hypothermia. J Thorac Cardiovasc Surg. 1969 Nov;58(5):619–passim. [PubMed] [Google Scholar]
  3. BRAIMBRIDGE M. V., CREIGHTON R. EXPERIMENTAL STUDIES OF INCREASED ATMOSPHERIC PRESSURE ON MYOCARDIAL ISCHEMIA AFTER CORONARY LIGATION. J Thorac Cardiovasc Surg. 1964 May;47:685–686. [PubMed] [Google Scholar]
  4. Barnes R. W., Mohri H., Merendino K. A. Experimental aortic valve homotransplantation without cardiopulmonary bypass. Surgery. 1968 Sep;64(3):647–652. [PubMed] [Google Scholar]
  5. Benzing G., 3rd, Helmsworth J., Stockert J., Kaplan S. Human myocardial performance during surgical treatment of cardiac defects. J Thorac Cardiovasc Surg. 1970 Jun;59(6):800–809. [PubMed] [Google Scholar]
  6. Blackstone E. H., Evans R. H., Eckner F. A., Drake A., Moulder P. V. Perfusion-induced myocardial injury. J Thorac Cardiovasc Surg. 1968 Nov;56(5):689–698. [PubMed] [Google Scholar]
  7. Brantigan J. W., Gott V. L., Perna A. M. Intramyocardial gas tensions during anoxic cardiac arrest. Surg Forum. 1970;21:152–153. [PubMed] [Google Scholar]
  8. Brown A. H., Braimbridge M. V., Niles N. R., Gerbode F., Aguilar M. J. The effect of excesively high pefusion pressures on the histology, histochemistry, birefringence, and function of the myocardium. J Thorac Cardiovasc Surg. 1969 Nov;58(5):655–663. [PubMed] [Google Scholar]
  9. Bulloch R. T., Pearce M. B., Murphy M. L., Jenkins B. J., Davis J. L. Myocardial lesions in idiopathic and alcoholic cardiomyopathy. Study by ventricular septal biopsy. Am J Cardiol. 1972 Jan;29(1):15–25. doi: 10.1016/0002-9149(72)90410-9. [DOI] [PubMed] [Google Scholar]
  10. CAULFIELD J., KLIONSKY B. Myocardial ischemia and early infarction: an electron microscopic study. Am J Pathol. 1959 May-Jun;35(3):489–523. [PMC free article] [PubMed] [Google Scholar]
  11. CROSS C. E., RIEBEN P. A., SALISBURY P. F. Influence of coronary perfusion and myocardial edema on pressure-volume diagram of left ventricle. Am J Physiol. 1961 Jul;201:102–108. doi: 10.1152/ajplegacy.1961.201.1.102. [DOI] [PubMed] [Google Scholar]
  12. Calman K. C., Quin R. O., Macpherson S. G., Bell P. R. The effect of pH and infusion volume on organ preservation. Br J Surg. 1971 Nov;58(11):865–866. [PubMed] [Google Scholar]
  13. Chayen J., Altmann F. P., Bitensky L., Braimbridge M. V., Kadas T., Wells P. J. A study of the changes in hydrogen transport in an isolated rat heart preparation. J R Microsc Soc. 1966 Dec;86(2):151–158. doi: 10.1111/j.1365-2818.1966.tb05333.x. [DOI] [PubMed] [Google Scholar]
  14. Childs J. W., Lower R. R. Preservation of the heart. Prog Cardiovasc Dis. 1969 Sep;12(2):149–163. doi: 10.1016/0033-0620(69)90014-0. [DOI] [PubMed] [Google Scholar]
  15. Colapinto N. D., Silver M. D. Prosthetic heart valve replacement. Causes of early postoperative death. J Thorac Cardiovasc Surg. 1971 Jun;61(6):938–944. [PubMed] [Google Scholar]
  16. Diamond G., Forrester J. S. Effect of coronary artery disease and acute myocardial infarction on left ventricular compliance in man. Circulation. 1972 Jan;45(1):11–19. doi: 10.1161/01.cir.45.1.11. [DOI] [PubMed] [Google Scholar]
  17. EBERT P. A., GREENFIELD L. J., AUSTEN W. G., MORROW A. G. Experimental comparison of methods for protecting the heart during aortic occlusion. Ann Surg. 1962 Jan;155:25–32. doi: 10.1097/00000658-196201000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Enright L. P., Staroscik R. N., Reis R. L. Left ventricular function after occlusion of the ascending aorta: assessments of various methods for myocardial protection. J Thorac Cardiovasc Surg. 1970 Nov;60(5):737–745. [PubMed] [Google Scholar]
  19. Ferrans V. J., Hibbs R. G., Walsh J. J., Burch G. E. Histochemical and electron microscopical studies on the cardiac necroses produced by sympathomimetic agents. Ann N Y Acad Sci. 1969 Jan 31;156(1):309–332. doi: 10.1111/j.1749-6632.1969.tb16737.x. [DOI] [PubMed] [Google Scholar]
  20. GREENBERG J. J., EDMUNDS L. H., Jr, BROWN R. B. Myocardial metabolism and postarrest function in the cold and chemically arrested heart. Surgery. 1960 Jul;48:31–42. [PubMed] [Google Scholar]
  21. Gardner T. J., Brantigan J. W., Perna A. M., Bender H. W., Brawley R. K., Gott V. L. Intramyocardial gas tensions in the human heart during coronary artery-saphenous vein bypass. J Thorac Cardiovasc Surg. 1971 Dec;62(6):844–850. [PubMed] [Google Scholar]
  22. Goldman B. S., Trimble A. S., Sheverini M. A., Teasdale S. J., Silver M. D., Elliott G. E. Functional and metabolic effects of anoxic cardiac arrest. Ann Thorac Surg. 1971 Feb;11(2):122–132. doi: 10.1016/s0003-4975(10)65426-4. [DOI] [PubMed] [Google Scholar]
  23. HALL D. P., SINGAL S. A., MORETZ W. H., BRACKNEY E. L., BUTLER W. F., MALOY W. C., BERNSTEIN V., ELLISON R. G. Myocardial metabolism during elective cardiac arrest determined by biochemical analysis of multiple cardiac biopsies. Surg Forum. 1960;10:540–543. [PubMed] [Google Scholar]
  24. Holdefer W. F., Edwards W. S., 3rd Ventricular performance characteristics in a metabolically supported isolated heart preparation: a model for evaluating cardiac storage methods. Surg Forum. 1968;19:225–227. [PubMed] [Google Scholar]
  25. KAY E. B., NOGUEIRA C., SUZUKI A., POSTIGO J., MENDELSOHN D. Myocardial protection during aortic valvular surgery. Ann Surg. 1961 Dec;154(6):159–164. doi: 10.1097/00000658-196112000-00021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. KOBERNICK S. D., MANDELL G. H., ZIRKIN R. M., HASHIMOTO Y. SUCCINIC DEHYDROGENASE DEFICIENCY IN IDIOPATHIC CARDIOMEGALY. Am J Pathol. 1963 Oct;43:661–675. [PMC free article] [PubMed] [Google Scholar]
  27. Karz A. M. Effects of interrupted coronary flow upon myocardial metabolism and contractility. Prog Cardiovasc Dis. 1968 Mar;10(5):450–465. doi: 10.1016/s0033-0620(68)80003-9. [DOI] [PubMed] [Google Scholar]
  28. Kent S. P. Intracellular plasma protein: a manifestation of cell injury in myocardial ischemia. Nature. 1966 Jun 18;210(5042):1279–1281. doi: 10.1038/2101279b0. [DOI] [PubMed] [Google Scholar]
  29. LOWER R. R., STOFER R. C., HURLEY E. J., DONG E., Jr, COHN R. B., SHUMWAY N. E. Successful homotransplantation of the canine heart after anoxic preservation for seven hours. Am J Surg. 1962 Aug;104:302–306. doi: 10.1016/0002-9610(62)90332-x. [DOI] [PubMed] [Google Scholar]
  30. Levitsky S., Sloane R. E., Mullin E. M., McIntosh C. L., Morrow A. G. Normothermic myocardial anoxia. Effects on the canine heart with left ventricular outflow obstruction. Ann Thorac Surg. 1971 Mar;11(3):229–237. doi: 10.1016/s0003-4975(10)65443-4. [DOI] [PubMed] [Google Scholar]
  31. Levitsky S., Williams W. H., Detmer D. E., McIntosh C. L., Morrow A. G. A functional evaluation of the preserved heart. J Thorac Cardiovasc Surg. 1970 Nov;60(5):625–635. [PubMed] [Google Scholar]
  32. Lie J. T., Holley K. E., Kampa W. R., Titus J. L. New histochemical method for morphologic diagnosis of early stages of myocardial ischemia. Mayo Clin Proc. 1971 May;46(5):319–327. [PubMed] [Google Scholar]
  33. Littler W. A., Meade J. B., Evans C. C., Davies G. Serum aspartate transaminase changes following open-heart surgery with ischaemic arrest (with and without coronary artery perfusion). Thorax. 1972 Jan;27(1):102–104. doi: 10.1136/thx.27.1.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Londe S. P. The isolated perfused heart: its physiology and metabolism. Surg Forum. 1969;20:159–161. [PubMed] [Google Scholar]
  35. Martino R. A., Kissack A. S., Stuckey J. H., Kavaler F., Fisher V. J. Myocardial function after electrically induced ventricular fibrillation. Am J Cardiol. 1969 Oct;24(4):537–543. doi: 10.1016/0002-9149(69)90497-4. [DOI] [PubMed] [Google Scholar]
  36. Moffitt E. A., Rosevear J. W., McGoon D. C. Myocardial metabolism during hypothermic coronary perfusion in man. Acta Anaesthesiol Scand Suppl. 1966;23:696–703. doi: 10.1111/j.1399-6576.1966.tb01084.x. [DOI] [PubMed] [Google Scholar]
  37. Moffitt E. A., Sessler A. D., Molnar G. D., McGoon D. C. Normothermia versus hypothermia for whole-body perfusion: effects on myocardial and body metabolism. Anesth Analg. 1971 Jul-Aug;50(4):505–516. [PubMed] [Google Scholar]
  38. Mohri H. Application of the electric pace maker of the heart under hypothermia. Experimental study on the maintenance of the cardiac action under deep hypothermia (16 degree C. below). J Cardiovasc Surg (Torino) 1965 Sep-Oct;6(5):379–393. [PubMed] [Google Scholar]
  39. Morales A. R., Fine G., Taber R. E. Cardiac surgery and myocardial necrosis. Arch Pathol. 1967 Jan;83(1):71–79. [PubMed] [Google Scholar]
  40. Mundth E. D., Sokol D. M., Levine F. H., Austen W. G. Preservation of myocardial function during extended periods of coronary ischemia. Surg Forum. 1969;20:176–178. [PubMed] [Google Scholar]
  41. Niles N. R., Barnhouse D. L. The acid hematein stain and myocardial damage. Arch Pathol. 1967 May;83(5):407–410. [PubMed] [Google Scholar]
  42. Pitzele S., Sze S., Dobell A. R. Hypothermic plasma perfusion of the isolated heart. Surgery. 1971 Sep;70(3):407–412. [PubMed] [Google Scholar]
  43. Ramsey H. W., De la Torre A., Linhart J. W., Wheat M. W., Jr Complications of coronary artery perfusion. J Thorac Cardiovasc Surg. 1967 Nov;54(5):714–718. [PubMed] [Google Scholar]
  44. Reichenbach D. D., Benditt E. P. Myofibrillar degeneration. A response of the myocardial cell to injury. Arch Pathol. 1968 Feb;85(2):189–199. [PubMed] [Google Scholar]
  45. Reul G. J., Morris G. C., Jr, Howell J. F., Crawford E. S., Sandiford F. M., Wukasch D. C. The safety of ischemic cardiac arrest in distal coronary artery bypass. J Thorac Cardiovasc Surg. 1971 Oct;62(4):511–521. [PubMed] [Google Scholar]
  46. Robicsek F., Tam W., Daugherty H. K., Mullen D. C. Myocardial protection during open-heart surgery. Coronary perfusion versus topical cardiac hypothermia. Ann Thorac Surg. 1970 Oct;10(4):340–353. doi: 10.1016/s0003-4975(10)65612-3. [DOI] [PubMed] [Google Scholar]
  47. Robinson R. G., Wilder J. R., Deysine M. Radioactive detection of experimental abscesses. Surg Forum. 1969;20:58–60. [PubMed] [Google Scholar]
  48. SALISBURY P. F., CROSS C. E., KATSUHARA K., RIEBEN P. A. Factors which initiate or influence edema in the isolated dog's heart. Circ Res. 1961 May;9:601–606. doi: 10.1161/01.res.9.3.601. [DOI] [PubMed] [Google Scholar]
  49. SHAW R. F., MOSHER P., ROSS J., Jr, JOSEPH J. I., LEE A. S. Physiologic principles of coronary perfusion. J Thorac Cardiovasc Surg. 1962 Nov;44:608–616. [PubMed] [Google Scholar]
  50. Sanmarco M. E., Marquez L. A., Hall C., Philips C. M., Gash A., Davila J. C. Myocardial contractility following cardiopulmonary bypass with and without myocardial ischemia. Ann Thorac Surg. 1969 Sep;8(3):237–251. doi: 10.1016/s0003-4975(10)66234-0. [DOI] [PubMed] [Google Scholar]
  51. Sarin C. L., Hall R. W., Ross D. N. Effects of extracorporeal circulation on left ventricular function with and without anoxic arrest. J Thorac Cardiovasc Surg. 1968 Sep;56(3):395–400. [PubMed] [Google Scholar]
  52. Silcox A. A., Poulter L. W., Bitensky L., Chayen J. An examination of some factors affecting histological preservation in frozen sections of unfixed tissue. J R Microsc Soc. 1965 Dec;85(4):559–564. doi: 10.1111/j.1365-2818.1965.tb02156.x. [DOI] [PubMed] [Google Scholar]
  53. Singh H. M., Horton E. H. Myocardial damage and valve replacements. Thorax. 1971 Jan;26(1):89–93. doi: 10.1136/thx.26.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Swynghedauw B., Bouveret P., Durand M., Hatt P. Y., Lemaire F., Piguet V. Myofibrillar and actomyosin adenosine-tri-phosphatase in experimental aortic insufficiency. Cardiovasc Res. 1971 Oct;5(4):458–468. doi: 10.1093/cvr/5.4.458. [DOI] [PubMed] [Google Scholar]
  55. Trimble A. S., Bigelow W. G., Wigle E. D., Silver M. D. Coronary ostial stenosis: a late complication of coronary perfusion in open-heart surgery. J Thorac Cardiovasc Surg. 1969 Jun;57(6):792–795. [PubMed] [Google Scholar]
  56. URSCHEL H. C., Jr, GREENBERG J. J. Differential hypothermic cardioplegia. Surg Forum. 1960;10:506–509. [PubMed] [Google Scholar]
  57. Ullal S. R. Cardiac lymph and lymphatics. Experimental observations and clinical significance. Ann R Coll Surg Engl. 1972 Nov;51(5):282–298. [PMC free article] [PubMed] [Google Scholar]
  58. Vasko J. S. Preservation of myocardial function during open heart surgery. Am J Surg. 1967 May;113(5):589–591. doi: 10.1016/0002-9610(67)90303-0. [DOI] [PubMed] [Google Scholar]
  59. Veress B., Kerényi T., Hüttner I., Jellinek H. The phases of muscle necrosis. J Pathol Bacteriol. 1966 Oct;92(2):511–517. doi: 10.1002/path.1700920229. [DOI] [PubMed] [Google Scholar]
  60. Verma K., King D. W. Succinic dehydrogenase and isocitric dehydrogenase activities in vitamin E-sufficient and -deficient fetal rats. Experientia. 1966 Mar 15;22(3):164–165. doi: 10.1007/BF01897711. [DOI] [PubMed] [Google Scholar]
  61. Vitali Mazza L., Anversa P., Morgutti L., Toso A. Changes of the myocardial ultrastructure during open heart surgery with extracorporeal circulation. J Cardiovasc Surg (Torino) 1969 May-Jun;10(3):212–228. [PubMed] [Google Scholar]
  62. Webb W. R. Cardiac preservation. Current methods. Cryobiology. 1969 May-Jun;5(6):423–428. doi: 10.1016/s0011-2240(69)80108-2. [DOI] [PubMed] [Google Scholar]
  63. Webb W. R., Sugg W. L., Ecker R. R. Heart preservation and transplantation. Experimental and clinical studies. Am J Cardiol. 1968 Dec;22(6):820–825. doi: 10.1016/0002-9149(68)90177-x. [DOI] [PubMed] [Google Scholar]
  64. Willman V. L., Barner H. B. Anatomical and physiological considerations in cardiac preservation. Cryobiology. 1969 May-Jun;5(6):413–422. doi: 10.1016/s0011-2240(69)80107-0. [DOI] [PubMed] [Google Scholar]
  65. YANG W. C. ANAEROBIC FUNCTIONAL ACTIVITY OF ISOLATED RABBIT ATRIA. Am J Physiol. 1963 Oct;205:781–784. doi: 10.1152/ajplegacy.1963.205.4.781. [DOI] [PubMed] [Google Scholar]

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