Subscribe to RSS
Large-Animal Biventricular Working Heart Perfusion System with Low Priming Volume—Comparison between in vivo and ex vivo Cardiac Function
28 October 2015
24 January 2016
04 April 2016 (online)
Background Existing large-animal, ex vivo, cardiac perfusion models are restricted in their ability to establish an ischemia/reperfusion condition as seen in cardiac surgery or transplantation. Other working heart systems only challenge one ventricle or require a substantially larger priming volume. We describe a novel biventricular cardiac perfusion system with reduced priming volume.
Methods Juvenile pig hearts were cardiopleged, explanted, and reperfused ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as perfusate (minimal priming volume 350 mL). After 15 minutes of Langendorff perfusion (LM), the system was switched into a biventricular working mode (WM) and studied for 3 hours.
Results During reperfusion, complete unloading of both ventricles and constant-pressure coronary perfusion was achieved. During working mode perfusion, the preload and afterload pressure of both ventricles was controlled within the targeted physiologic range. Functional parameters such as left ventricular work index were reduced in ex vivo working mode (in vivo: 787 ± 186 vs. 1 h WM 498 ± 66 mm Hg·mL/g·min; p < 0.01), but remained stable throughout the following study period (3 h WM 517 ± 103 mm Hg·mL/g·min; p = 0.63). Along with the elevated workload during WM, myocardial metabolism and oxygen consumption increased compared with LM (0.021 ± 0.08 vs. 0.06 ± 0.01 mL/min/g; 1 h after reperfusion). Histologic examination of the myocardium revealed no structural damage.
Conclusion In the ex vivo perfusion system, stable hemodynamic and metabolic conditions can be established for a period of 3 hours while functional and blood parameters are easily accessible. Moreover, because of the minimal priming volume, the novel ex vivo cardiac perfusion circuit allows for autologous perfusion, using the limited amount of blood available from the organ donating animal.
- 1 van Rijk-Zwikker GL, Schipperheyn JJ, Huysmans HA, Bruschke AV. Influence of mitral valve prosthesis or rigid mitral ring on left ventricular pump function. A study on exposed and isolated blood-perfused porcine hearts. Circulation 1989; 80 (3 Pt 1): I1-I7
- 2 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 (2–3): 111-119
- 3 Demmy TL, Magovern GJ, Kao RL. Isolated biventricular working rat heart preparation. Ann Thorac Surg 1992; 54 (05) 915-920
- 4 Proctor E, Parker R. Preservation of isolated heart for 72 hours. BMJ 1968; 4 (5626): 296-298
- 5 Colah S, Freed DH, Mundt P. , et al. Ex vivo perfusion of the swine heart as a method for pre-transplant assessment. Perfusion 2012; 27 (05) 408-413
- 6 Collins MJ, Moainie SL, Griffith BP, Poston RS. Preserving and evaluating hearts with ex vivo machine perfusion: an avenue to improve early graft performance and expand the donor pool. Eur J Cardiothorac Surg 2008; 34 (02) 318-325
- 7 Ardehali A, Esmailian F, Deng M. , et al. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet 2015; 385: 2577-2584
- 8 Kimose HH, Ravkilde J, Helligsø P, Knudsen M, Baandrup U. Influence of pre-existing ischemia on recovery from chemical cardioplegia. A study on pig hearts in an isolated blood-perfused model. Scand J Thorac Cardiovasc Surg 1992; 26 (01) 23-31
- 9 Kung EO, Taylor CA. Development of a physical Windkessel module to re-create in-vivo vascular flow impedance for in-vitro experiments. Cardiovasc Eng Technol 2011; 2 (01) 2-14
- 10 Kaul TK, Fields BL. Postoperative acute refractory right ventricular failure: incidence, pathogenesis, management and prognosis. Cardiovasc Surg 2000; 8 (01) 1-9
- 11 Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg 2009; 108 (02) 422-433
- 12 Raina A, Seetha Rammohan HR, Gertz ZM, Rame JE, Woo YJ, Kirkpatrick JN. Postoperative right ventricular failure after left ventricular assist device placement is predicted by preoperative echocardiographic structural, hemodynamic, and functional parameters. J Card Fail 2013; 19 (01) 16-24
- 13 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 (03) 435-442
- 14 Haghighi K, Kolokathis F, Pater L. , et al. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J Clin Invest 2003; 111 (06) 869-876
- 15 Ginis I, Luo Y, Miura T. , et al. Differences between human and mouse embryonic stem cells. Dev Biol 2004; 269 (02) 360-380
- 16 Lescan M, Scheule A, Neumann B. , et al. Beneficial effects on cardiac performance and cardioprotective properties of milrinone after cold ischemia. J Cardiovasc Dis Diagn 2013; 1: 124
- 17 Chinchoy E, Soule CL, Houlton AJ. , et al. Isolated four-chamber working swine heart model. Ann Thorac Surg 2000; 70 (05) 1607-1614
- 18 Dunning JJ, Pierson III RN, Braidley PC, White DJ, Wallwork J. A comparison of the performance of pig hearts perfused with pig or human blood using an ex-vivo working heart model. Eur J Cardiothorac Surg 1994; 8 (04) 204-206
- 19 Schechter MA, Southerland KW, Feger BJ. , et al. An isolated working heart system for large animal models. J Vis Exp 2014;11(88)
- 20 García Sáez D, Elbetanony A, Lezberg P. , et al. Ex vivo heart perfusion after cardiocirculatory death: a porcine model. J Surg Res 2015; 195 (01) 311-314