title: Extended ex vivo myocardial preservation in the beating state using a novel polyethylene glycolated bovine hemoglobin perfusate based solution.
abstract: Cardiac preservation for transplantation is generally limited by ischemic hypothermic storage of 4-6 hours. Earlier studies in the authors' laboratory have demonstrated that hypothermic perfusion preservation using a novel oxygen carrying hemoglobin solution may extend preservation times to 8 hours and decrease ischemic injury. The purpose of this study was to compare extended cardiac function after 12 and 24 hours of continuous hypothermic perfusion with a polyethylene glycolated bovine hemoglobin perfusate (PEG-Hb) solution to the clinical standard of hypothermic ischemic preservation. The hearts of 54 anesthetized and intubated New Zealand White rabbits were harvested after cold cardioplegic arrest. Group I (n = 12) hearts were perfused with a PEG-Hb solution at 20 degrees C and 30 mm Hg for 24 hours. Group II (n = 10) hearts were preserved similarly with PEG-Hb for 12 hours. Group III (n = 12) hearts were preserved for 8 hours with PEG-Hb; Group IV (n = 10) were preserved by cold ischemic storage for 4 hours at 4 degrees C; and Group V (n = 10) were tested after fresh extirpation. Left ventricular (LV) function was measured in the nonworking state at 15 minute, 1 hour, and 2 hour intervals after transfer to a standard crystalloid Langendorff circuit. Developed LV pressure at 0.5 ml LV volume was superior in Group II at early time points, yet it was similar in all preserved groups at 2 hours. +dP/dt(max) at 0.5 ml LV volume was consistent at all time points and greater in PEG-Hb preserved groups compared with Group V. -dP/dt(max) at 0.5 ml LV volume was significantly greater in Groups II and III compared with Group V initially (p < 0.05), but all were similar at the end of testing. Continuous perfusion preservation of rabbit hearts for time increments up to 24 hours with this novel PEG-Hb solution at 30 mm Hg and 20 degrees C yields LV function that is similar to 4 hours of ischemic hypothermic storage. Extended cardiac perfusion preservation with this PEG-Hb solution deserves further investigation in large animal transplant models.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Pharmacology, University of California, Irvine, Medical Center, Orange, California 92868, USA.
authors.forename: Blanding U
authors.initials: BU
authors.lastname: Jones
authors.forename: Dan L
authors.initials: DL
authors.lastname: Serna
authors.forename: Peter
authors.initials: P
authors.lastname: Smulowitz
authors.forename: Peter
authors.initials: P
authors.lastname: Connolly
authors.forename: Adam
authors.initials: A
authors.lastname: Farber
authors.forename: Gerry
authors.initials: G
authors.lastname: Beckham
authors.forename: Vineet
authors.initials: V
authors.lastname: Shrivastava
authors.forename: Chad
authors.initials: C
authors.lastname: Kahwaji
authors.forename: Earl
authors.initials: E
authors.lastname: Steward
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Purdy
authors.forename: W Lane
authors.initials: WL
authors.lastname: Parker
authors.forename: Berend
authors.initials: B
authors.lastname: Ages
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Milliken
mesh_terms: D000818:Animals; D002417:Cattle; D006321:Heart / Q000502:physiology; D006454:Hemoglobins; D066298:In Vitro Techniques; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010477:Perfusion; D011092:Polyethylene Glycols; D011817:Rabbits; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D006454:Hemoglobins; D019188:Organ Preservation Solutions; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols