Molecular indices of apoptosis after intermittent blood and crystalloid cardioplegia.
BACKGROUND
We investigated whether intermittent blood and crystalloid cardioplegia differentially affect myocardial apoptosis and apoptosis gene-related proteins.


RESULTS
Rabbit hearts were perfused with Krebs-Henseleit buffer on a Langendorff apparatus. Control hearts (n=6) were perfused for 120 minutes without cardioplegic ischemia. Hearts were arrested for 60 minutes with warm (37 degrees C) crystalloid cardioplegia (iW-CCP) (n=8) or with warm blood cardioplegia (iW-BCP) (n=8) administered intermittently. In cold (0 to 4 degrees C) groups, hearts were arrested for 60 minutes with cold crystalloid cardioplegia (iC-CCP; n=8) or with cold blood cardioplegia (iC-BCP; n=6) administered intermittently. The hearts were reperfused for 30 minutes with Krebs-Henseleit buffer. iC-BCP significantly preserved the recovery of left ventricular and microvascular function compared with the other 3 experimental groups. There were no significant differences in total protein levels of caspase 3, Bcl-2, Bad, and Bax among the groups. iC-BCP significantly induced greater phosphorylation of Bad (5.6+/-0.8-fold) as compared with the other 3 groups (3.4+/-0.6-fold in iC-CCP, P<0.05; 2.5+/-0.3 in iW-BCP, P<0.05; and 1.4+/-0.2 in iW-CCP, P<0.01). iC-BCP induced less caspase 3 activation and apoptosis than the other 3 groups.


CONCLUSIONS
iC-BCP is superior to the other cardioplegic solutions in increasing the phosphorylation of Bad, inhibiting the activation of caspase 3, and preventing apoptosis. These effects of iC-BCP were associated with preserved left ventricular function and endothelium-dependent relaxation of coronary microvessels.
Feng
Jun
J
Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Bianchi
Cesario
C
Sandmeyer
Jennifer L
JL
Li
Jianyi
J
Sellke
Frank W
FW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D001769:Blood; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D003080:Cold Temperature; D004730:Endothelium, Vascular / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced / Q000009:adverse effects* / Q000379:methods; D020287:In Situ Nick-End Labeling; D008833:Microcirculation / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017680:Potassium Compounds / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D013696:Temperature; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051025:bcl-Associated Death Protein / Q000032:analysis / Q000378:metabolism
D015415:Biomarkers; D002314:Cardioplegic Solutions; D020030:Nitric Oxide Donors; D017680:Potassium Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C018369:potassium cardioplegic solution; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D053148:Caspase 3; D020169:Caspases