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Isolated Heart Preparations, Problems, and Pitfalls

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Animal Models in Cardiovascular Research

Abstract

Isolated heart preparations allow many biochemical, physiological, morphological, and pharmacological indices to be evaluated without the confounding effects of other organs, the systemic circulation, and a host of potential confounding responses such as circulating neurohumeral substances. Researchers were able to independently study the role of temperature, oxygen, calcium ions, electrical activity, and autonomic nervous system effects and, more recently, the role of specific genetic variables. When hearts of small laboratory animals are used, the preparations are highly reproducible and can be used quickly in large numbers at relatively low cost. Historically research conducted on isolated hearts led to the discovery of chemical transmission of vagal stimulation, and the importance of preload and afterload to cardiac function. Other important advances include significant understanding of ischemia-reperfusion injury, cell-based therapy, and heart preservation.

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References

  1. Zimmer HG. Who discovered the frank-starling mechanism? News Physiol Sci. 2002;17:181–184.

    PubMed  Google Scholar 

  2. Bowditch HP. Uber die eigenthumlichkeiten der reizbarkeit, welche die muskelfasem des herzens zeigen. berichte uber die verhandlungen der koniglich sachsischen gesellschaft zu leipzig. Mathematisch-Physische Classe. 1871;23:652–689.

    Google Scholar 

  3. Frank O. Dynamik des herzmuskels. Z Biol. 1895;32:370–437.

    Google Scholar 

  4. Frank O. Die grundform des arteriellen pulses. erste abhandlung. mathematische analyse. Z Biol. 1898;37:483–526.

    Google Scholar 

  5. Howell WH, Cooke E. Action of the inorganic salts of serum, milk, gastric juice, etc., upon the isolated working heart, with remarks upon the causation of the heart-beat. J Physiol. 1893;14:198–220.

    PubMed  CAS  Google Scholar 

  6. Howell WH, Duke WW. Experiments on the isolated mammalian heart to show the relation of the inorganic salts to the action of the accelerator and inhibitory nerves. J Physiol. 1906;35:131–150.

    PubMed  CAS  Google Scholar 

  7. Langendorff O. Untersuchungen am uberlebenden saugethierherzen. Pflugers Arch. 1895;61:291–332.

    Article  Google Scholar 

  8. Skrzypiec-Spring M, Grotthus B, Szelag A, Schulz R. Isolated heart perfusion according to Langendorff-still viable in the new millennium. J Pharmacol Toxicol Methods. 2007;55:113–126.

    Article  PubMed  CAS  Google Scholar 

  9. Knowlton FP, Starling EH. The influence of variations in temperature and blood-pressure on the performance of the isolated mammalian heart. J Physiol. 1912;44:206–219.

    PubMed  CAS  Google Scholar 

  10. Starling EH, Visscher MB. The regulation of the energy output of the heart. J Physiol. 1927;62:243–261.

    PubMed  CAS  Google Scholar 

  11. Sutherland FJ, Hearse DJ. The isolated blood and perfusion fluid perfused heart. Pharmacol Res. 2000;41:613–627.

    Article  Google Scholar 

  12. Sutherland FJ, Shattock MJ, Baker KE, Hearse DJ. Mouse isolated perfused heart: Characteristics and cautions. Clin Exp Pharmacol Physiol. 2003;30:867–878.

    Article  Google Scholar 

  13. Grocott-Mason R, Anning P, Evans H, Lewis MJ, Shah AM. Modulation of left ventricular relaxation in isolated ejecting heart by endogenous nitric oxide. Am J Physiol. 1994;267:H1804–H1813.

    PubMed  CAS  Google Scholar 

  14. Heindl B, Reichle FM, Zahler S, Conzen PF, Becker BF. Sevoflurane and isoflurane protect the reperfused guinea pig heart by reducing postischemic adhesion of polymorphonuclear neutrophils. Anesthesiology. 1999;91:521–530.

    Article  PubMed  CAS  Google Scholar 

  15. How OJ, Aasum E, Kunnathu S, Severson DL, Myhre ES, Larsen TS. Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts. Am J Physiol Heart Circ Physiol. 2005;288:H2979–H2985.

    Article  PubMed  CAS  Google Scholar 

  16. Petrucci Junior O, Oliveira PP, Carmo MR, Vieira RW, Braile DM. Standardization of an isolated pig heart preparation with parabiotic circulation: Methodological considerations. Braz J Med Biol Res. 2003;36:649–659.

    Article  PubMed  CAS  Google Scholar 

  17. Taegtmeyer H, Hems R, Krebs HA. Utilization of energy-providing substrates in the isolated working rat heart. Biochem J. 1980;186:701–711.

    PubMed  CAS  Google Scholar 

  18. Gillis AM, Kulisz E, Mathison HJ. Cardiac electrophysiological variables in blood-perfused and buffer-perfused, isolated, working rabbit heart. Am J Physiol. 1996;271:H784–H789.

    PubMed  CAS  Google Scholar 

  19. Werner JC, Sicard RE, Schuler HG. Palmitate oxidation by isolated working fetal and newborn pig hearts. Am J Physiol. 1989;256:E315–E321.

    PubMed  CAS  Google Scholar 

  20. Casali C, Obadia JF, Canet E, et al. Design of an isolated pig heart preparation for positron emission tomography and magnetic resonance imaging. Invest Radiol. 1997;32:713–720.

    Article  PubMed  CAS  Google Scholar 

  21. Modersohn D, Eddicks S, Grosse-Siestrup C, Ast I, Holinski S, Konertz W. Isolated hemoperfused heart model of slaughterhouse pigs. Int J Artif Organs. 2001;24:215–221.

    PubMed  CAS  Google Scholar 

  22. Gaffin RD, Gokulan K, Sacchettini JC, et al. Changes in end-to-end interactions of tropomyosin affect mouse cardiac muscle dynamics. Am J Physiol Heart Circ Physiol. 2006;291:H552–H563.

    Article  PubMed  CAS  Google Scholar 

  23. Igic R. The isolated perfused “working” rat heart: A new method. J Pharmacol Toxicol Methods. 1996;35:63–67.

    Article  PubMed  CAS  Google Scholar 

  24. Burkhoff D, van der Velde E, Kass D, Baan J, Maughan WL, Sagawa K. Accuracy of volume measurement by conductance catheter in isolated, ejecting canine hearts. Circulation. 1985;72:440–447.

    Article  PubMed  CAS  Google Scholar 

  25. Weber KT, Janicki JS, Reeves RC, Hefner LL, Reeves TJ. Determinants of stroke volume in the isolated canine heart. J Appl Physiol. 1974;37:742–747.

    PubMed  CAS  Google Scholar 

  26. Demmy TL, Magovern GJ, Kao RL. Isolated biventricular working rat heart preparation. Ann Thorac Surg. 1992;54:915–920.

    Article  PubMed  CAS  Google Scholar 

  27. Demmy TL, Curtis JJ, Kao R, Schmaltz RA, Walls JT. Load-insensitive measurements from an isolated perfused biventricular working rat heart. J Biomed Sci. 1997;4:111–119.

    Article  PubMed  Google Scholar 

  28. Segel LD. The development of alcohol-induced cardiac dysfunction in the rat. Alcohol Alcohol. 1988;23:391–401.

    PubMed  CAS  Google Scholar 

  29. Itoi T, Lopaschuk GD. The contribution of glycolysis, glucose oxidation, lactate oxidation, and fatty acid oxidation to ATP production in isolated biventricular working hearts from 2-week-old rabbits. Pediatr Res. 1993;34:735–741.

    Article  PubMed  CAS  Google Scholar 

  30. Briest W, Elsner C, Hemker J, Muller-Strahl G, Zimmer HG. Norepinephrine-induced expression of cytokines in isolated biventricular working rat hearts. Mol Cell Biochem. 2003;245:69–76.

    Article  PubMed  CAS  Google Scholar 

  31. Sigg DC, Iaizzo PA. In vivo versus in vitro comparison of swine cardiac performance: Induction of cardiodepression with halothane. Eur J Pharmacol. 2006;543:97–107.

    Article  PubMed  CAS  Google Scholar 

  32. Miller WP, Shimamoto N, Nellis SH, Liedtke AJ. Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts. Am J Physiol. 1987;253:H1271–H1278.

    PubMed  CAS  Google Scholar 

  33. Yokoyama H, Imagawa JI, Satoh K, Taira N, Tamahashi N. Isolated dog hearts prepared in cold tyrode solution and reperfused with arterial blood are functionally and ultrastructurally normal. Tohoku J Exp Med. 1988;156:121–134.

    Article  PubMed  CAS  Google Scholar 

  34. Araki Y, Usui A, Kawaguchi O, et al. Pressure-volume relationship in isolated working heart with crystalloid perfusate in swine and imaging the valve motion. Eur J Cardiothorac Surg. 2005;28:435–442.

    Article  PubMed  Google Scholar 

  35. Chinchoy E, Soule CL, Houlton AJ, et al. Isolated four-chamber working swine heart model. Ann Thorac Surg. 2000;70:1607–1614.

    Article  PubMed  CAS  Google Scholar 

  36. Krebs HA, Henseleit K. Untersuchungen ueber die harnstoffbildung im tierkoerper. Hoppe-Seyler’s Zeitschrift fur Physiologische Chemie. 1932;210:33–36.

    Article  CAS  Google Scholar 

  37. Neubauer S, Ingwall JS. The isolated, buffer-perfused ferret heart: A new model for the study of cardiac physiology and metabolism. Lab Anim. 1991;25:348–353.

    Article  PubMed  CAS  Google Scholar 

  38. Yang A, Sonin D, Jones L, Barry WH, Liang BT. A beneficial role of cardiac P2X4 receptors in heart failure: Rescue of the calsequestrin overexpression model of cardiomyopathy. Am J Physiol Heart Circ Physiol. 2004;287:H1096–H1103.

    Article  PubMed  CAS  Google Scholar 

  39. Tikh EI, Fenton RA, Dobson JG, Jr. Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts. Am J Physiol Heart Circ Physiol. 2006;290:H348–H356.

    Article  PubMed  CAS  Google Scholar 

  40. Anderson SE, Liu H, Beyschau A, Cala PM. Effects of cold cardioplegia on pH, Na and Ca in newborn rabbit hearts. Am J Physiol Heart Circ Physiol. 2006;290:H1090–H1097.

    Article  PubMed  CAS  Google Scholar 

  41. Fujita S, Roerig DL, Chung WW, Bosnjak ZJ, Stowe DF. Volatile anesthetics do not alter bradykinin-induced release of nitric oxide or L-citrulline in crystalloid perfused guinea pig hearts. Anesthesiology. 1998;89:421–433.

    Article  PubMed  CAS  Google Scholar 

  42. Kameyama T, Chen Z, Bell SP, Fabian J, LeWinter MM. Mechanoenergetic studies in isolated mouse hearts. Am J Physiol. 1998;274:H366–H374.

    PubMed  CAS  Google Scholar 

  43. Martin SM, Laks H, Drinkwater DC, et al. Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia. Biomater Artif Cells Immobilization Biotechnol. 1992;20:985–989.

    PubMed  CAS  Google Scholar 

  44. Cornelissen AJ, Spaan JA, Dankelman J, Chan CC, Yin FC. Evidence for stretch-induced resistance increase of proximal coronary microcirculation. Am J Physiol Heart Circ Physiol. 2001;281:H2687–H2696.

    PubMed  CAS  Google Scholar 

  45. Kawabata H, Sugiyama K, Katori R. Effect of acetylsalicylic acid on metabolism and contractility in the ischemic reperfused heart. Jpn Circ J. 1996;60:961–971.

    Article  PubMed  CAS  Google Scholar 

  46. Snyder DS, Harasawa Y, Sagawa K, Hunter WC. Effects of pentobarbital on inotropic state of isolated canine left ventricle. Heart Vessels. 1993;8:128–135.

    Article  PubMed  CAS  Google Scholar 

  47. Segel LD, Ensunsa JL. Albumin improves stability and longevity of perfluorochemical-perfused hearts. Am J Physiol. 1988;254:H1105–H1112.

    PubMed  CAS  Google Scholar 

  48. Weng ZC, Nicolosi AC, Detwiler PW, et al. Effects of crystalloid, blood, and university of Wisconsin perfusates on weight, water content, and left ventricular compliance in an edema-prone, isolated porcine heart model. J Thorac Cardiovasc Surg. 1992;103:504–513.

    PubMed  CAS  Google Scholar 

  49. Walters HL, III, Digerness SB, Naftel DC, Waggoner JR, III, Blackstone EH, Kirklin JW. The response to ischemia in blood perfused vs. crystalloid perfused isolated rat heart preparations. J Mol Cell Cardiol. 1992;24:1063–1077.

    Article  PubMed  Google Scholar 

  50. Wetstein L, Rastegar H, Barlow CH, Harken AH. Delineation of myocardial ischemia in an isolated blood-perfused rabbit heart preparation. J Surg Res. 1984;37:285–289.

    Article  PubMed  CAS  Google Scholar 

  51. Fukunami M, Hearse DJ. The inotropic consequences of cooling: Studies in the isolated rat heart. Heart Vessels. 1989;5:1–9.

    Article  PubMed  CAS  Google Scholar 

  52. Cave AC, Hearse DJ. Ischaemic preconditioning and contractile function: Studies with normothermic and hypothermic global ischaemia. J Mol Cell Cardiol. 1992;24:1113–1123.

    Article  PubMed  CAS  Google Scholar 

  53. Wu K, Zhang J, Fu J, et al. Novel technique for blood circuit reconstruction in mouse heart transplantation model. Microsurgery. 2006;26:594–598.

    Article  PubMed  CAS  Google Scholar 

  54. Wang D, Opelz G, Terness P. A simplified technique for heart transplantation in rats: Abdominal vessel branch-sparing and modified venotomy. Microsurgery. 2006;26:470–472.

    Article  PubMed  Google Scholar 

  55. Wu G, Pfeiffer S, Schroder C, et al. Coagulation cascade activation triggers early failure of pig hearts expressing human complement regulatory genes. Xenotransplantation. 2007;14:34–47.

    Article  PubMed  Google Scholar 

  56. Moser B, Szabolcs MJ, Ankersmit HJ, et al. Blockade of RAGE suppresses alloimmune reactions in vitro and delays allograft rejection in murine heart transplantation. Am J Transplant. 2007;7:293–302.

    Article  PubMed  CAS  Google Scholar 

  57. Byrne GW, Davies WR, Oi K, et al. Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival. Transplantation. 2006;82:1787–1791.

    Article  PubMed  Google Scholar 

  58. Schnickel GT, Hsieh GR, Garcia C, Shefizadeh A, Fishbein MC, Ardehali A. Role of CXCR3 and CCR5 in allograft rejection. Transplant Proc. 2006;38:3221–3224.

    Article  PubMed  CAS  Google Scholar 

  59. Li S, Salgar SK, Thanikachalam M, et al. CTLA4-ig-based conditioning regimen to induce tolerance to cardiac allografts. J Surg Res. 2006;136:238–246.

    Article  PubMed  CAS  Google Scholar 

  60. Hirai H, Shibata T, Aoyama T, Yoshiyama M, Omura T, Suehiro S. Activation of mitogen-activated protein kinases, activator protein-1, and nuclear factor-kappaB during acute rejection after heterotopic heart transplantation in rats. Osaka City Med J. 2006;52:9–19.

    PubMed  CAS  Google Scholar 

  61. Kapp JA, Honjo K, Kapp LM, Xu X, Cozier A, Bucy RP. TCR transgenic CD8+ T cells activated in the presence of TGF-beta express FoxP3 and mediate linked suppression of primary immune responses and cardiac allograft rejection. Int Immunol. 2006;18:1549–1562.

    Article  PubMed  CAS  Google Scholar 

  62. Oshima K, Cui G, Tung T, Okotie O, Laks H, Sen L. Exogenous IL-10 overexpression reduces perforin production by activated allogenic CD8+ cells and prolongs cardiac allograft survival. Am J Physiol Heart Circ Physiol. 2007;292:H277–H284.

    Article  PubMed  CAS  Google Scholar 

  63. Doenst T, Bugger H, Leippert S, Barleon B, Marme D, Beyersdorf F. Differential gene expression in response to ventricular unloading in rat and human myocardium. Thorac Cardiovasc Surg. 2006;54:381–387.

    Article  PubMed  CAS  Google Scholar 

  64. Oriyanhan W, Tsuneyoshi H, Nishina T, Matsuoka S, Ikeda T, Komeda M. Determination of optimal duration of mechanical unloading for failing hearts to achieve bridge to recovery in a rat heterotopic heart transplantation model. J Heart Lung Transplant. 2007;26:16–23.

    Article  PubMed  Google Scholar 

  65. Minatoya Y, Ito K, Kagaya Y, et al. Depressed contractile reserve and impaired calcium handling of cardiac myocytes from chronically unloaded hearts are ameliorated with the administration of physiological treatment dose of T3 in rats. Acta Physiol (Oxf). 2007;189:221–231.

    Article  CAS  Google Scholar 

  66. Roy N, Friehs I, Cowan DB, Zurakowski D, McGowan FX, del Nido PJ. Dopamine induces postischemic cardiomyocyte apoptosis in vivo: An effect ameliorated by propofol. Ann Thorac Surg. 2006;82:2192–2199.

    Article  PubMed  Google Scholar 

  67. Perrault LP, Aubin MC, Malo O, et al. Status of the endothelium-derived hyperpolarizing factor pathway in coronary arteries after heterotopic heart transplantation. J Heart Lung Transplant. 2007;26:48–55.

    Article  PubMed  Google Scholar 

  68. Li TS, Suzuki R, Ueda K, Murata T, Hamano K. Analysis of the origin and population dynamics of cardiac progenitor cells in a donor heart model. Stem Cells. 2007;25:911–917.

    Article  PubMed  CAS  Google Scholar 

  69. Dedja A, Zaglia T, Dall’Olmo L, et al. Hybrid cardiomyocytes derived by cell fusion in heterotopic cardiac xenografts. FASEB J. 2006;20:2534–2536.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Veterinary Biosciences, University of Illinois, Urbana Champaign College of Veterinary Medicine, 2001 S. Lincoln Ave., Urbana, IL, 61802, USA

    David R. Gross (Professor Emeritus)

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Gross, D.R. (2009). Isolated Heart Preparations, Problems, and Pitfalls. In: Animal Models in Cardiovascular Research. Springer, New York, NY. https://doi.org/10.1007/978-0-387-95962-7_6

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