Pediatric cardiopulmonary bypass adaptations for long-term survival of baboons undergoing pulmonary artery replacement.

Cardiopulmonary bypass (CPB) protocols of the baboon (Papio cynocephalus anubis) are limited to obtaining experimental data without concern for long-term survival. In the evaluation of pulmonary artery tissue engineered heart valves (TEHVs), pediatric CPB methods are adapted to accommodate the animals' unique physiology enabling survival up to 6 months until elective sacrifice. Aortic access was by a 14F arterial cannula and atrial access by a single 24F venous cannula.The CPB circuit includes a 3.3 L/min flow rated oxygenator, 1/4" x %" arterial-venous loop, 3/8" raceway, and bubble trap. The prime contains 700 mL Plasma-Lyte, 700 units heparin, 5 mL of 50% dextrose, and 20 mg amiodarone. Heparinization (200 u/kg) targets an activated clotting time of 350 seconds. Normothermic CPB was initiated at a 2.5 L/m2/min cardiac index with a mean arterial pressure of 55-80 mmHg. Weaning was monitored with transesophageal echocardiogram. Post-CPB circuit blood was re-infused. Chest tubes were removed with cessation of bleeding. Extubation was performed upon spontaneous breathing. The animals were conscious and upright 3 hours post-CPB. Bioprosthetic valves or TEHVs were implanted as pulmonary replacements in 20 baboons: weight = 27.5 +/- 5.6 kg, height = 73 +/- 7 cm, body surface area = 0.77 m2 +/- 0.08, mean blood flow = 1.973 +/- .254 L/min, core temperature = 37.1 +/- .1 degree C, and CPB time = 60 +/- 40 minutes. No acidosis accompanied CPB. Sixteen animals survived, four expired. Three died of right ventricular failure and one of an anaphylactoid reaction. Surviving animals had normally functioning replacement valves and ventricles. Baboon CPB requires modifications to include high systemic blood pressure for adequate perfusion into small coronary arteries, careful CPB weaning to prevent ventricular distention, and drug and fluid interventions to abate variable venous return related to a muscularized spleno-splanchnic venous capacity.

[1]  C. Warnes,et al.  Adult congenital heart disease importance of the right ventricle. , 2009, Journal of the American College of Cardiology.

[2]  Richard A Hopkins,et al.  Decellularization reduces calcification while improving both durability and 1-year functional results of pulmonary homograft valves in juvenile sheep. , 2009, The Journal of thoracic and cardiovascular surgery.

[3]  P. Calow,et al.  Scientific Committee on Health and Environmental Risks opinion on: The need for non- human primates in biomedical research, production and testing of products and devices , 2009 .

[4]  Noi T. Tran,et al.  Potential of baboon endothelial progenitor cells for tissue engineered vascular grafts. , 2008, Journal of biomedical materials research. Part A.

[5]  R. Hopkins From cadaver harvested homograft valves to tissue-engineered valve conduits , 2006 .

[6]  Andrew L Rivard,et al.  The current state of in-vivo pre-clinical animal models for heart valve evaluation. , 2005, The Journal of heart valve disease.

[7]  F. Hanley,et al.  Preliminary results of fetal cardiac bypass in nonhuman primates. , 2005, The Journal of thoracic and cardiovascular surgery.

[8]  R. Hopkins Cardiac Reconstructions with Allograft Tissues , 2004 .

[9]  N. Domenech,et al.  Flow cytometry complement-mediated cytotoxicity assay detects baboon xenoantibodies directed to porcine epitopes undetected by hemolytic assay. , 2004, Transplant immunology.

[10]  K. Rogers,et al.  Smoothelin-positive cells in human and porcine semilunar valves , 2003, Histochemistry and Cell Biology.

[11]  A. Undar,et al.  Novel anti-factor D monoclonal antibody inhibits complement and leukocyte activation in a baboon model of cardiopulmonary bypass. , 2002, The Annals of thoracic surgery.

[12]  P. Zilla,et al.  Stentless bioprosthetic heart valve research: sheep versus primate model. , 2001, The Annals of thoracic surgery.

[13]  R. Michler,et al.  Use of a low-prime circuit for bloodless heart transplantation in xenotransplant of 5-7 kilogram primates. , 2000, The journal of extra-corporeal technology.

[14]  L. Edmunds,et al.  Platelet anesthesia with nitric oxide with or without eptifibatide during cardiopulmonary bypass in baboons. , 1999, The Journal of thoracic and cardiovascular surgery.

[15]  M. Oz,et al.  Selective anticoagulation with active site-blocked factor IXA suggests separate roles for intrinsic and extrinsic coagulation pathways in cardiopulmonary bypass. , 1998, The Journal of thoracic and cardiovascular surgery.

[16]  L. Edmunds,et al.  Integrilin prevents prolonged bleeding times after cardiopulmonary bypass. , 1998, The Annals of thoracic surgery.

[17]  R. Colman,et al.  A baboon model for hematologic studies of cardiopulmonary bypass. , 1997, The Journal of laboratory and clinical medicine.

[18]  R. Kennedy,et al.  The baboon as a nonhuman primate model for assessing the effects of maternal immunization with Haemophilus influenzae type b polysaccharide vaccines , 1997, Infection and immunity.

[19]  D. Shapiro Xenotransplantation , 1997, The Lancet.

[20]  B. Reicharta,et al.  Endothelialized biological heart valve prostheses in the non-human primate model , 1997 .

[21]  J. Gorman,et al.  Tirofiban provides "platelet anesthesia" during cardiopulmonary bypass in baboons. , 1997, The Journal of thoracic and cardiovascular surgery.

[22]  S. Gundry,et al.  Successful survival of primates receiving transplantation with "dead," nonbeating donor hearts. , 1995, The Journal of thoracic and cardiovascular surgery.

[23]  W. Young,et al.  Cerebral Blood Flow during Low‐flow Hypeithermic Cardiopulmonary Bypass in Baboons , 1994, Anesthesiology.

[24]  R. Michler,et al.  Laboratory evaluation of a low prime closed-circuit cardiopulmonary bypass system. , 1992, The journal of extra-corporeal technology.

[25]  P. Fourie,et al.  Preservation of myocardial function and biochemistry after blood and oxygenated crystalloid cardioplegia during cardiac arrest. , 1990, The Annals of thoracic surgery.

[26]  Montrey Rd,et al.  Hematologic, biochemical, and physiologic indices of the sacred baboon (Papio hamadryas). , 1977 .

[27]  D. Renquist,et al.  Hematologic, biochemical, and physiologic indices of the sacred baboon (Papio hamadryas). , 1977, Laboratory animal science.

[28]  C. Gale,et al.  Relationship of blood pressure and heart rate to body temperature in baboons. , 1972, The American journal of physiology.

[29]  C. A. Guenter,et al.  Hemodynamic characteristics and blood gas exchange in the normal baboon. , 1968, Journal of applied physiology.