Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation

Abstract

BackgroundPerioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO© heart solution (XHS) based cardioplegia.MethodsBaboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO © Perfusion system with XHS to which baboon RBCs were added.ResultsPCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.ConclusionBlood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.

The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?

“…The Maryland team had obtained encouraging results from pig orthotopic heart transplantation in baboons 2–4 . Using essentially the same genetically‐engineered pigs (with 10 genetic modifications) and immunosuppressive regimen (based on blockade of the CD40/CD154 co‐stimulation pathway), one would have anticipated an equally encouraging result from their first clinical effort, particularly as the high prevalence of a positive cross‐match against “triple‐knock‐out” (TKO) pigs, likely associated with a putative “4 th xenoantigen” recognized by nonhuman primates (NHP), 5–8 is not observed in humans.…”

Cardiac Xenotransplantation: Progress in Preclinical Models and Prospects for Clinical Translation

“…However, there has been a success in the OHTx with GTKO.hCD46.hTBM (3-GE) graft survival up to 6 months, despite these hurdles with the aid of non-ischemic continuous xenograft preservation ( 70 , 112 ). This has been observed by others as well, but the underlying mechanism in cardiac preservation preventing primary graft dysfunction in this setting is poorly understood ( 113 ).…”

Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months

“…[2][3][4][5][6] Our initial efforts to translate these results in a life-sustaining orthotopic heart transplantation (OHTx) failed within 48 h due to perioperative cardiac xenograft dysfunction (PCXD). 7,8 Recently, Längin et al overcame PCXD in OHTx with the same GE xenografts and immunosuppression as in our HHTx, with the addition of nonischemic cardiac preservation and anti-inflammatory agents. 3 However, survival was still limited due to observed diastolic failure from abnormal cardiac growth within 1 month.…”

“…Our initial efforts to translate these results in a life‐sustaining orthotopic heart transplantation (OHTx) failed within 48 h due to perioperative cardiac xenograft dysfunction (PCXD) 7,8 . Recently, Längin et al.…”