Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass

强力霉素降低心脏基质金属蛋白酶-2 活性,但不能改善接受心肺旁路术的冠状动脉搭桥患者再灌注期间的心肌功能障碍

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作者:Costas J Schulze, Michele M Castro, Arulmozhi D Kandasamy, Jonathan Cena, Courtney Bryden, Shoa H Wang, Arvind Koshal, Ross T Tsuyuki, Barry A Finegan, Richard Schulz

Conclusions

Although doxycycline did not improve myocardial stunning following coronary artery bypass graft surgery with cardiopulmonary bypass, it reduced cardiac matrix metalloproteinase-2 activity in these patients. A larger trial and/or higher dose of doxycycline may yet be warranted.

Results

Left ventricular stroke work index was examined prior to cardiopulmonary bypass and at 24 hours reperfusion. Right atrial biopsies were collected before cardiopulmonary bypass and 10 minutes after aortic cross-clamp release to determine matrix metalloproteinase-2 activity and troponin I level. Blood was collected to determine matrix metalloproteinase activity and interleukin-6, C-reactive protein, and troponin I levels. Cardiac 72-kDa matrix metalloproteinase-2 activity was lower upon reperfusion in biopsies from the doxycycline group (p = 0.01), and the increase of matrix metalloproteinase-2 activity in the placebo group due to reperfusion did not appear in the doxycycline group (p = 0.05). Doxycycline, however, did not ameliorate cardiac mechanical dysfunction following reperfusion or the cardiopulmonary bypass-coronary artery bypass graft-induced increased plasma matrix metalloproteinase-9, interleukin-6, and C-reactive protein levels. Cardiopulmonary bypass-coronary artery bypass graft or doxycycline did not change tissue or plasma troponin I levels at 10 minutes reperfusion. Conclusions: Although doxycycline did not improve myocardial stunning following coronary artery bypass graft surgery with cardiopulmonary bypass, it reduced cardiac matrix metalloproteinase-2 activity in these patients. A larger trial and/or higher dose of doxycycline may yet be warranted.

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