Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs.
Ischemia-reperfusion injury, a clinical problem during cardiac surgery, involves worsened adenosine trisphosphate (ATP) generation and damage to the heart. We studied carbon monoxide (CO) pretreatment, proven valuable in rodents but not previously tested in large animals, for its effects on pig hearts subjected to cardiopulmonary bypass with cardioplegic arrest. Hearts of CO-treated pigs showed significantly higher ATP and phosphocreatine levels, less interstitial edema, and apoptosis of cardiomyocytes and required fewer defibrillations after bypass. We conclude that treatment with CO improves the energy status, prevents edema formation and apoptosis, and facilitates recovery in a clinically relevant model of cardiopulmonary bypass surgery.
Lavitrano
Marialuisa
M
Department Medicina Sperimentale Ambientale e Biotecnologie Mediche, University of Milano-Bicocca, Via Cadore, 48, 20052 Monza, Milano, Italy. marialuisa.lavitrano@unimib.it
Smolenski
Ryszard T
RT
Musumeci
Antonino
A
Maccherini
Massimo
M
Slominska
Ewa
E
Di Florio
Ernesto
E
Bracco
Adele
A
Mancini
Antonio
A
Stassi
Giorgio
G
Patti
Mariella
M
Giovannoni
Roberto
R
Froio
Alberto
A
Simeone
Felicetta
F
Forni
Monica
M
Bacci
Maria Laura
ML
D'Alise
Giuseppe
G
Cozzi
Emanuele
E
Otterbein
Leo E
LE
Yacoub
Magdi H
MH
Bach
Fritz H
FH
Calise
Fulvio
F
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002248:Carbon Monoxide / Q000494:pharmacology* / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000517:prevention & control; D004554:Electric Countershock; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D034421:Sus scrofa
D002316:Cardiotonic Agents; D009243:NAD; D000249:Adenosine Monophosphate; D009249:NADP; D000244:Adenosine Diphosphate; D002248:Carbon Monoxide; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate