Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression.
OBJECTIVE
Whether the CK-MB reducing effect of ischemic preconditioning (IP) by unstable angina within 24 to 48 hours before CABG is achieved by early or by delayed preconditioning of left ventricular myocardium in humans is unknown. We investigated whether IP is associated with phosphorylation of p38 MAPK (characteristic for early preconditioning) or with increased protein expression of HSP-72 (characteristic for delayed preconditioning) at the time of CABG in patients.


METHODS
Nineteen patients were grouped according to the occurrence of ischemic episodes within 48 hours before CABG. The patients without angina were assigned to the control group (CON, n = 10) whereas patients who had experienced angina within 48 hours before CABG were assigned to the preconditioned group (IP, n = 9). The effect of IP on the CABG induced maximal release of creatine kinase (CK) and CK-MB was examined. Left ventricular biopsy specimens taken immediately before cross clamping from ischemic (ISCH) and from reference (REF) areas were processed to analyze p38 MAPK phosphorylation and HSP-72-protein expression.


RESULTS
While IP significantly reduced CK-MB (18.7 +/- 1.3 vs. 13.8 +/- 1.5 U/L, mean +/- SEM, p < 0.05), it only tended to reduce CK (292.7 +/- 32.8 vs. 274.1+/-31.1 U/L, p = NS, mean +/- SEM). CK-MB release for any given cross-clamp time was significantly reduced by IP (regression lines: CON, y= 0.4x+ 2, r= 0.8; IP, y= 0.1x+ 10, r= 0.2; p < 0.01, ANCOVA). There was no effect of IP on left ventricular p38 MAPK phosphorylation. IP increased left ventricular HSP-72-protein expression in ischemic areas when compared to reference areas (1.78 +/- 0.35 vs. 2.58 +/- 0.65, REF vs. ISCH, PhosphorImager units x10(6), mean +/- SEM, p < 0.05, ANCOVA).


CONCLUSIONS
Thus, in the human left ventricular myocardium there is a second window of protection lasting for at least 48 hours, while at that time the early phase of preconditioning has already gone.
Vahlhaus
Christian
C
Department of Cardiology and Angiology, Hospital of the University of Münster, Germany. Vahlhaus@uni_muenster.de
Neumann
Joachim
J
Lüss
Hartmut
H
Wenzelburger
Frauke
F
Tjan
Tony D T
TD
Hammel
Dieter
D
Scheld
Hans H
HH
Schmitz
Wilhelm
W
Breithardt
Günter
G
Wichter
Thomas
T
D000789:Angina, Unstable / Q000378:metabolism* / Q000503:physiopathology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D001026:Coronary Artery Bypass; D052279:Creatine Kinase, MB Form / Q000378:metabolism*; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006352:Heart Ventricles; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D050884:HSP72 Heat-Shock Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D052279:Creatine Kinase, MB Form; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases