Pretreatment with a potassium-channel opener before prolonged cardiac storage: an evaluation in an experimental brain death model.
BACKGROUND
Pretreatment with a potassium-channel opener has been shown to improve functional recovery after long-term cardioplegic arrest. We evaluated whether pretreatment with the potassium-channel opener cromakalim is beneficial in a more clinically relevant experimental model of brain death in the rabbit.


METHODS
Four groups of rabbits were studied in a 2 x 2 factorial experiment (n = 8 per group). Rabbits were subjected to a sham operation or 90 minutes of brain death induced by inflating a subdurally placed balloon. Thirty minutes before heart explantation, rabbits received either no pretreatment or an intravenous injection of cromakalim, 30 microg/kg. Hearts then received 5 hours' hypothermic storage in St. Thomas' Hospital solution and were assessed on a buffer-perfused isolated heart preparation. Hemodynamic recovery, coronary flow, and creatine kinase release were determined after 60 minutes of reperfusion.


RESULTS
Systolic function and diastolic function were significantly altered in hearts explanted from brain-dead rabbits compared with hearts from rabbits having a sham operation. Cromakalim pretreatment had no significant effect on poststorage systolic or diastolic function of hearts explanted from brain-dead or sham-operation rabbits. Further, cromakalim pretreatment did not affect coronary flow or overall creatine kinase release during reperfusion. CONCLUSIONS; In vivo pretreatment of brain-dead rabbits or anesthetized rabbits with an intravenous injection of cromakalim had no significant effect on functional recovery of or enzymatic release from explanted hearts after 5 hours' hypothermic storage and 60 minutes' reperfusion. These findings underscore the importance of clinically relevant experimental models.
Kirsch
M
M
Centre de Recherches Chirurgicales Henri Mondor and the Pharmacie Centrale, Hôpital Henri Mondor, Créteil, France.
Bertrand
S
S
Garnier
J P
JP
Fernandez
C
C
Baufreton
C
C
Astier
A
A
Loisance
D
D
D000818:Animals; D001926:Brain Death / Q000378:metabolism; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D019806:Cromakalim / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D005069:Evaluation Studies as Topic; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009638:Norepinephrine / Q000097:blood; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011817:Rabbits; D014665:Vasodilator Agents / Q000627:therapeutic use*
D019188:Organ Preservation Solutions; D014665:Vasodilator Agents; D019806:Cromakalim; D003402:Creatine Kinase; D009638:Norepinephrine; D004837:Epinephrine