Long-term survival of patients with a single ventricle palliated with a Fontan procedure is still limited. No curative treatment options are available. To investigate the pathophysiology and potential treatment options, such as mechanical circulatory support (MCS), appropriate large animal models are required. The aim of this review was to analyze all full-text manuscripts presenting approaches for an extracardiac total cavopulmonary connection (TCPC) animal model to identify the feasibility and limitations in the acute and chronic setting.
Methods:
A literature search was performed for full-text publications presenting large animal models with extracardiac TCPCs on Pubmed and Embase. Out of 454 reviewed papers, 23 manuscripts fulfilled the inclusion criteria. Surgical procedures were categorized and hemodynamic changes at the transition from the biventricular to the univentricular condition analyzed.
Results:
Surgical procedures varied especially regarding coronary venous flow handling and anatomic shape of the TCPC. In most studies (n = 14), the main pulmonary artery was clamped and the coronary venous flow redirected by additional surgical interventions. Only in five reports, the caval veins were connected to the right pulmonary artery to create a true TCPC shape, whereas in all others (n = 18), the veins were connected to the main pulmonary artery. An elevated pulmonary vascular resistance was identified as a limiting hemodynamic factor for TCPC completion in healthy animals.
Conclusions:
A variety of acute TCPC animal models were successfully established with and without MCS, reflecting the most important hemodynamic features of a Fontan circulation; however, chronic animal models were not reported.
De LevalMRDeanfieldJE. Four decades of Fontan palliation. Nat Rev Cardiol. 2010;7(9):520–527.
2.
AtzAMZakVMahonyL. Longitudinal outcomes of patients with single ventricle after the Fontan procedure. J Am Coll Cardiol. 2017;69(22):2735–2744.
3.
d’UdekemYIyengarAJGalatiJC. Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand. Circulation. 2014;130(11 suppl 1):S32–S38.
4.
MarcellettiCFHanleyFLMavroudisC. Revision of previous Fontan connections to total extracardiac cavopulmonary anastomosis: a multicenter experience. J Thorac Cardiovasc Surg. 2000;119(2):340–346.
5.
GewilligMBrownSC. The Fontan circulation after 45 years: update in physiology. Heart. 2016;102(14):1081–1086.
6.
DealBJJacobsML. Education in heart management of the failing Fontan circulation. Heart. 2012;98(14):1098–1104.
7.
GoldbergDJShaddyRERavishankarCRychikJ. The failing Fontan: etiology, diagnosis and management. Expert Rev Cardiovasc Ther. 2011;9(6):785–793.
8.
CooperRJMiltonCTKlopfensteinTJJordonDJ. Effect of corn processing on degradable intake protein requirement of finishing cattle. J Anim Sci. 2002;80(1):242–247.
9.
BennettJW. Regional body surface area of sheep. J Agric Sci. 1973;81(3):429–432.
10.
KakuKMatsudaHKanekoM. Experimental complete right heart bypass. Proposal of a new model and acute hemodynamic assessment with vasoactive drugs in dogs. J Thorac Cardiovasc Surg. 1990;99(1):161–166.
11.
MacéLDervanianPWeissMDanielJPLosayJNeveuxJY. Hemodynamics of different degrees of right heart bypass: experimental assessment. Ann Thorac Surg. 1995;60(5):1230–1237.
12.
NawaSIrieHTakataKSugawaraETeramotoS. Development of a new experimental model for total exclusion of the right heart without the aid of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1989;97(1):130–134.
SzabóGBuhmannVGrafA. Ventricular energetics after the Fontan operation: contractility-afterload mismatch. J Thorac Cardiovasc Surg. 2003;125(5):1061–1069.
15.
TanoueYSeseAUenoYJohKHijiiT. Bidirectional Glenn procedure improves the mechanical efficiency of a total cavopulmonary connection in high-risk Fontan candidates. Circulation. 2001;103(17):2176–2180.
16.
GandolfoFBrancaccioGDonatielloS. Mechanically assisted total cavopulmonary connection with an axial flow pump: computational and in vivo study. Artif Organs. 2016;40(1):43–49.
17.
KocyildırimEDurOSoranOTuzunEMillerMWHouslerGJ. Pulsatile venous waveform quality in Fontan circulation—clinical implications, venous assists options and the future. Anadolu Kardiyol Derg. 2012;12(5):420–426.
18.
MyersCDBoydJHPressonRG. Neonatal cavopulmonary assist: pulsatile versus steady-flow pulmonary perfusion. Ann Thorac Surg. 2006;81(1):257–263.
19.
RiemerRKAmirGReichenbachSHReinhartzO. Mechanical support of total cavopulmonary connection with an axial flow pump. J Thorac Cardiovasc Surg. 2005;130(2):351–354.
20.
RodefeldMDBoydJHMyersCD. Cavopulmonary assist: circulatory support for the univentricular Fontan circulation. Ann Thorac Surg. 2003;76(6):1911–1916.
21.
RodefeldMDBoydJHMyersCDPressonRGWagnerWWBrownJW. Cavopulmonary assist in the neonate: an alternative strategy for single-ventricle palliation. J Thorac Cardiovasc Surg. 2004;127(3):705–711.
22.
SwartzMFDiVincentiLSmithK. A modified LVAD technique to augment caval and pulmonary arterial blood flow in the “failing Fontan” circulation. J Card Surg. 2017;32(2):126–132.
23.
TsudaSSasakiTMaedaKRiemerRKReichenbachSHReinhartzO. Recovery during mid-term mechanical support of Fontan circulation in sheep. ASAIO J. 2009;55(4):406–411.
24.
WangDPlunkettMLynchJZhouXBallard-CroftCZwischenbergerJB. Wang-zwische double-lumen cannula leads to total cavopulmonary support in a failing Fontan sheep model. Ann Thorac Surg. 2011;91(6):1956–1960.
25.
WangDPlunkettMGaoG. A practical and less invasive total cavopulmonary connection sheep model. ASAIO J. 2014;60(2):178–182.
26.
WangDGaoGPlunkettM. A paired membrane umbrella double-lumen cannula ensures consistent cavopulmonary assistance in a Fontan sheep model. J Thorac Cardiovasc Surg. 2014;148(3):1041–1047.
27.
DerkGLaksHBiniwaleR. Novel techniques of mechanical circulatory support for the right heart and Fontan circulation. Int J Cardiol. 2014;176(3):828–832.
28.
KanakisMMitropoulosFKatsimpoulasM. Experimentally modified Fontan circulation in an adolescent pig model without the use of cardiopulmonary bypass. Med Sci Monit. 2011;17(1):BR10–BR15.
29.
KlautzRJMVan Rijk-ZwikkerGLSteendijkPWildeJTeitelDFBaanJ. Acute elevation of coronary venous pressure does not affect left ventricular contractility in the normal and stressed swine heart: implications for the Fontan operation. J Thorac Cardiovasc Surg. 1997;114(4):560–567.
30.
MacéLDervanianPBourriezA. Changes in venous return parameters associated with univentricular Fontan circulations. Am J Physiol Circ Physiol. 2000;279(5):H2335–H2343.
31.
SinhaPDeutschNRatnayakaK. Effect of mechanical assistance of the systemic ventricle in single ventricle circulation with cavopulmonary connection. J Thorac Cardiovasc Surg. 2014;147(4):1271–1275.
32.
WeiXSanchezPGLiuY. Mechanical circulatory support of a univentricular Fontan circulation with a continuous axial-flow pump in a piglet model. ASAIO J. 2015;61(2):196–201.
33.
Van PuyveldeJRegaFMinamiT. Creation of the Fontan circulation in sheep: a survival model. Proceedings of the 51st Annual Meeting of the Association for European Paediatric and Congenital Cardiology; Lyon, France, 2017.
MarkovitzLJSavageEBRatcliffeMB. Large animal model of left ventricular aneurysm. Ann Thorac Surg. 1989;48(6):838–845.
36.
RodefeldMDCoatsBFisherT. Cavopulmonary assist for the univentricular Fontan circulation: von Kármán viscous impeller pump. J Thorac Cardiovasc Surg. 2010;140(3):529–536.
37.
GraneggerMSchweigerMSchmid DanersMMeboldtMHüblerM. Cavopulmonary mechanical circulatory support in Fontan patients and the need for physiologic control: a computational study with a closed-loop exercise model. Int J Artif Organs. 2018;41(5):261–268.
38.
LeviDSDanonSGordonB. Creation of transcatheter aortopulmonary and cavopulmonary shunts using magnetic catheters: feasibility study in swine. Pediatr Cardiol. 2009;30(4):397–403.
HausdorfGSchneiderMKonertzW. Surgical preconditioning and completion of total cavopulmonary connection by interventional cardiac catheterisation: a new concept. Heart. 1996;75(4):403–409.
41.
McMahonCJEl SaidHGMullinsCE. Transcatheter creation of an atriopulmonary communication in the hemi-Fontan or Glenn circulation. Cardiol Young. 2002;12(2):196–199.
42.
BoudjemlineYMalekzadeh-MilaniSVan SteenbergheM. Novel method of surgical preparation for transcatheter completion of Fontan circulation: creation of an extracardiac pathway. Arch Cardiovasc Dis. 2014;107(6-7):371–380.
43.
GerelliSVan SteenbergheMPatelMVan AerschotIBoudjemlineY. Feasibility of creating a novel animal heart model to test transcatheter techniques for a cavocaval connection that mimics a Fontan completion. J Thorac Cardiovasc Surg. 2013;146(2):408–412.
44.
BoudjemlineYGerelliSVan SteenbergheMPatelMMalekzadeh-MilaniSBonnetD. Feasibility of transcatheter techniques for intracardiac and extracardiac cavocaval connection in principle for Fontan completion in chronic animal models. Eur J Cardio-Thoracic Surg. 2013;43(4):856–860.
45.
MettonOCalvarusoDStosBBen AliWBoudjemlineY. A new surgical technique for transcatheter Fontan completion. Eur J Cardio-Thoracic Surg. 2011;39(1):81–85.
46.
SallehuddinAMesnedABarakatiMFayyadhMAFadleyFAl-HaleesZ. Fontan completion without surgery. Eur J Cardio-Thoracic Surg. 2007;32(2):195–200.
47.
KonstantinovIEAlexi-MeskishviliVV. Intracardiac covered stent for transcatheter completion of the total cavopulmonary connection: anatomical, physiological and technical considerations. Scand Cardiovasc J. 2006;40(2):71–75.
48.
KonstantinovIEBensonLNCaldaroneCA. A simple surgical technique for interventional transcatheter completion of the total cavopulmonary connection. J Thorac Cardiovasc Surg. 2005;129(1):210–212.
49.
SizarovAde BakkerBSKleinKOhlerthS. Building foundations for transcatheter intervascular anastomoses: 3D anatomy of the great vessels in large experimental animals. Interact Cardiovasc Thorac Surg. 2014;19(4):543–551.
50.
SchubertSPetersBBergerF. Interventional re-opening of a PDA for reverse potts shunt circulation after ADO i implantation in a child. Catheter Cardiovasc Interv. 2017;89(4):E133–E136.
51.
PrabhuSAndersonBWardCKarlTAlphonsoN. A simplified technique for interventional extracardiac Fontan. World J Pediatr Congenit Heart Surg. 2017;8(1):92–98.
52.
SizarovABoudjemlineY. Novel materials and devices in the transcatheter creation of vascular anastomosis—The future comes slowly (part 2). Arch Cardiovasc Dis. 2016;109(4):286–295.
