Kinetics of heat shock protein 70 synthesis in the human heart after cold cardioplegic arrest.
OBJECTIVE
Protection of the myocardium against ischemia/reperfusion injury is a major challenge in cardiac surgery and cardiology. A cardioprotective role of heat shock proteins (Hsp), in particular Hsp 70, against ischemia has been demonstrated. A prerequisite for clinical exploitation of high Hsp 70 levels in the heart during ischemia is the determination of the efficacy and the kinetics of cardiac Hsp synthesis in vivo.


METHODS
We examined Hsp 70 and other immediate early genes, that are induced by cardioplegia and reperfusion, in right atrial biopsies taken from 15 patients during coronary artery bypass grafting. Specimens were obtained before cardioplegia and after ending of reperfusion and subsequently studied by immunohistochemistry and Western blot analyses.


RESULTS
Overall Hsp 70 increased 2.0+/-1.1-fold (P<0.01) in the nucleus as well as in the cytosol of myocytes and endothelial cells during open-heart surgery. As determined by comparison to a dilution series of recombinant protein, Hsp 70 levels amounted up to 6 per thousand of total cellular protein. The increase of Hsp 70 correlated well with the duration of cardioplegia and reperfusion (P<0.005) showing a markedly accelerated increase at periods longer than 2 h. Further, the immediate early gene c-Fos also increased 2.4+/-2.2-fold during open-heart surgery (P<0.05), whereas other members of the Hsp family, like Hsp 27 and Hsp 90, showed no significant changes in protein levels during cardioplegia and reperfusion.


CONCLUSIONS
These findings demonstrate that protein levels of Hsp 70 in the myocardium increase to significant amounts within few hours after induction. The optimum time point for induction of Hsp 70 appears to be at least 2 h before open-heart surgery.
Department of Thoracic and Cardiovascular Surgery, University Hospital, 93042 Regensburg, Germany. jschmitt@genetics.harvard.edu
J P
JP
Schmitt
H
H
Schunkert
D E
DE
Birnbaum
H
H
Aebert
D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D003080:Cold Temperature; D001026:Coronary Artery Bypass; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006324:Heart Arrest, Induced / Q000379:methods; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016760:Proto-Oncogene Proteins c-fos