PMID- 11678462
OWN - NLM
STAT- MEDLINE
DCOM- 20020129
LR  - 20190921
IS  - 0886-0440 (Print)
IS  - 0886-0440 (Linking)
VI  - 15
IP  - 6
DP  - 2000 Nov-Dec
TI  - Extending myocardial viability during heart preservation with cyclosporine A.
PG  - 392-402
AB  - BACKGROUND AND AIM OF STUDY: Hypothermic preservation (PRES) of donor hearts is 
      limited to 12-14 hours for complete functional recovery after reperfusion. In a 
      canine heterotopic heart transplant model, 50% to 60% functional recovery 
      returned after 18 hours of PRES with University of Wisconsin (UW) solution. 
      Concomitant with functional changes were marked increases in apoptotic cells at 2 
      (2.69%) and 6 (5.98%) hours of reperfusion with a concomitant decrease in lamin 
      B1 (2% and 7.6%, respectively) with no evidence of necrotic cells. These results 
      suggested that blockade of apoptosis may prolong myocardial viability during PRES 
      and reperfusion. METHODS: Donor hearts were subjected to 18 and 24 hours of PRES 
      (2 degrees C to 4 degrees C) with and without cyclosporine A (CyS) treatment 
      (apoptosis blocker). CyS was given to the donor animal (10 mg/kg), in the PRES 
      solution (10(-5) mol/L), slowly infused during the PRES period (1 mL/min), and 
      also to the recipient animal (2.5 mg/kg). RESULTS: After 18 hours of PRES with 
      CyS, function returned to 100% within 1 hour and stayed at this level throughout 
      a 6-hour recovery period. Apoptotic myocytes were reduced (55%) after 18 hours 
      PRES with CyS treatment, and 6-hour reperfusion lamin B1 was reduced to only 
      3.7%. Twenty-four hour PRES in UW resulted in no functional recovery. However, 
      after CyS treatment, functional recovery returned to 100% after 4 hours of 
      reperfusion. Adenosine triphosphate (ATP) and creatine phosphate (CP) 
      concentrations were surprisingly the same with or without CyS treatment at 18 
      hours and lower with 24 hours. CONCLUSIONS: Use of CyS in the PRES solution 
      prolongs myocardial viability during donor heart PRES. The mechanism of action 
      may be associated with the mitochondrial permeability transition (MPT) pore via 
      cyclophilin D binding.
FAU - Masters, T N
AU  - Masters TN
AD  - Heineman Medical Research Center, Carolinas HealthCare System, Charlotte, North 
      Carolina, USA.
FAU - Fokin, A A
AU  - Fokin AA
FAU - Schaper, J
AU  - Schaper J
FAU - Lorenz-Meyer, S
AU  - Lorenz-Meyer S
FAU - Pool, L
AU  - Pool L
FAU - Gong, G
AU  - Gong G
FAU - Robicsek, F
AU  - Robicsek F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Card Surg
JT  - Journal of cardiac surgery
JID - 8908809
RN  - 0 (Insulin)
RN  - 0 (Organ Preservation Solutions)
RN  - 0 (University of Wisconsin-lactobionate solution)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - GAN16C9B8O (Glutathione)
RN  - K72T3FS567 (Adenosine)
RN  - N5O3QU595M (Raffinose)
SB  - IM
MH  - Adenosine
MH  - Allopurinol
MH  - Animals
MH  - Apoptosis
MH  - Cyclosporine
MH  - Dogs
MH  - Female
MH  - Glutathione
MH  - *Heart
MH  - Heart Transplantation
MH  - Insulin
MH  - Male
MH  - Myocardium/metabolism/pathology
MH  - Necrosis
MH  - *Organ Preservation
MH  - *Organ Preservation Solutions
MH  - Raffinose
MH  - Time Factors
EDAT- 2001/10/27 10:00
MHDA- 2002/01/30 10:01
CRDT- 2001/10/27 10:00
PHST- 2001/10/27 10:00 [pubmed]
PHST- 2002/01/30 10:01 [medline]
PHST- 2001/10/27 10:00 [entrez]
AID - 10.1111/j.1540-8191.2000.tb01299.x [doi]
PST - ppublish
SO  - J Card Surg. 2000 Nov-Dec;15(6):392-402. doi: 10.1111/j.1540-8191.2000.tb01299.x.