Ischemic Preconditioning by Unstable Angina Reduces the Release of CK-MB Following CABG and Stimulates Left Ventricular HSP-72 Protein Expression

Abstract

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. 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. 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). 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.