title: Combining cariporide with glyceryl trinitrate optimizes cardiac preservation during porcine heart transplantation.
abstract: Sodium-hydrogen exchange inhibitors, such as cariporide, are potent cardioprotective agents, however, safety concerns have been raised about intravenously (i.v.) administered cariporide in humans. The aim of this study was to develop a preservation strategy that maintained cariporide's cardioprotective efficacy during heart transplantation while minimizing recipient exposure. We utilized a porcine model of orthotopic heart transplantation that incorporated donor brain death and 14 h static heart storage. Five groups were studied: control (CON), hearts stored in Celsior; CAR1, hearts stored in Celsior with donors and recipients receiving cariporide (2 mg/kg i.v.) prior to explantation and reperfusion, respectively; CAR2, hearts stored in Celsior supplemented with cariporide (10 mumol/L); GTN, hearts stored in Celsior supplemented with glyceryl trinitrate (GTN) (100 mg/L); and COMB, hearts stored in Celsior supplemented with cariporide (10 mumol/L) plus GTN (100 mg/L). A total of 5/5 CAR1 and 5/6 COMB recipients were weaned from cardiopulmonary bypass compared with 1/5 CON, 1/5 CAR2 and 0/5 GTN animals (p = 0.001). Hearts from the CAR1 and COMB groups demonstrated similar cardiac function and troponin release after transplantation. Supplementation of Celsior with cariporide plus GTN provided superior donor heart preservation to supplementation with either agent alone and equivalent preservation to that observed with systemic administration of cariporide to the donor and recipient.
authors: Transplant Program, The Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
authors: A J
authors: AJ
authors: Hing
authors: A
authors: A
authors: Watson
authors: M
authors: M
authors: Hicks
authors: L
authors: L
authors: Gao
authors: S C
authors: SC
authors: Faddy
authors: A C
authors: AC
authors: McMahon
authors: S H
authors: SH
authors: Kesteven
authors: M K
authors: MK
authors: Wilson
authors: P
authors: P
authors: Jansz
authors: M P
authors: MP
authors: Feneley
authors: P S
authors: PS
authors: Macdonald
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001835:Body Weight; D004187:Disaccharides / Q000008:administration & dosage; D004573:Electrolytes / Q000008:administration & dosage; D005971:Glutamates / Q000008:administration & dosage; D005978:Glutathione / Q000008:administration & dosage; D006146:Guanidines / Q000008:administration & dosage*; D016027:Heart Transplantation / Q000379:methods*; D006639:Histidine / Q000008:administration & dosage; D007511:Ischemia; D008353:Mannitol / Q000008:administration & dosage; D005996:Nitroglycerin / Q000008:administration & dosage*; D009926:Organ Preservation / Q000295:instrumentation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000517:prevention & control; D013450:Sulfones / Q000008:administration & dosage*; D013552:Swine; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000889:Anti-Arrhythmia Agents; C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D006146:Guanidines; D019188:Organ Preservation Solutions; D013450:Sulfones; D014665:Vasodilator Agents; D008353:Mannitol; D006639:Histidine; C093373:cariporide; D005996:Nitroglycerin; D005978:Glutathione