Document Detail

Warm ischemia provokes inflammation and regional hypercoagulability within the heart during off-pump coronary artery bypass: a possible target for serine protease inhibition.
MedLine Citation:
PMID:  18068996     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Accumulating evidence suggests that a hypercoagulable state influences early graft failure after off-pump coronary artery bypass (OPCAB). We hypothesized that regional myocardial ischemia caused by obligatory periods of coronary occlusion during OPCAB is an important trigger for this prothrombotic state.
METHODS: Using a series of biomarkers, 60 consecutive patients undergoing OPCAB were monitored for myocardial injury (myoglobin), inflammation (TNF-alpha, IL-8) and thrombosis (thrombin generation-F1.2, contact activation pathway-FXII-a, platelet derived microparticles-via flow cytometry). The transcardiac gradients of these markers were determined by assaying both arterial and coronary sinus blood just after protamine administration. Intramyocardial pH was monitored continuously during coronary occlusion in a subset (N=30 grafts, 11 patients). The influence of management strategies affecting hemostasis (e.g. antiplatelet therapy, anti-fibrinolytics, peak activated clotting time (ACT) during heparinization) was analyzed.
RESULTS: Ischemic injury, depicted by the transcardiac myoglobin gradient, significantly correlated with intramyocardial acidosis during coronary occlusion (R=0.96, p<0.0001) and predicted the transcardiac gradients of TNF-alpha (R=0.83, p<0.001) and F1.2 (R=0.72, p<0.0001). Transcardiac F1.2 strongly correlated with TNF-alpha (R=0.73, p=0.01) and IL-8 (R=0.51, p=0.02). Patients receiving aprotinin (N=20) showed significantly lower transcardiac gradients for myoglobin (4.1+/-7.5% vs 72.9+/-108.8% change, p=0.002), F1.2 (31+/-37% vs 89+/-149%, p=0.03), FXII-a (2.6+/-4.1% vs 19.2+/-34%, p=0.04) and microparticles (7+/-3.9% vs 12.9+/-8%, p=0.01).
CONCLUSIONS: Strong correlations between myocardial ischemia and the transcardiac gradients of markers for inflammation and thrombosis suggest that even brief episodes of coronary occlusion in the beating heart may have pathophysiologic consequences. Aprotinin, but not other factors that influence the coagulation system, appears to mitigate this process during OPCAB.
Zachary N Kon; Emile N Brown; Michael C Grant; Toshinaga Ozeki; Nicholas S Burris; Michael J Collins; Michael H Kwon; Robert S Poston
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  33     ISSN:  1010-7940     ISO Abbreviation:  Eur J Cardiothorac Surg     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-21     Completed Date:  2008-08-19     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  215-21     Citation Subset:  IM    
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MeSH Terms
Acidosis / complications,  epidemiology
Aprotinin / pharmacology,  therapeutic use
Coronary Artery Bypass, Off-Pump / methods*
Graft Occlusion, Vascular / blood,  etiology*
Intraoperative Care / methods
Middle Aged
Myocarditis / etiology*
Myoglobin / blood,  drug effects
Platelet Activation / drug effects
Prospective Studies
Serine Proteinase Inhibitors / pharmacology,  therapeutic use
Thrombophilia / blood,  etiology*,  prevention & control
Thrombosis / blood
Tumor Necrosis Factor-alpha / blood
Warm Ischemia / adverse effects*
Grant Support
Reg. No./Substance:
0/Myoglobin; 0/Serine Proteinase Inhibitors; 0/Tumor Necrosis Factor-alpha; 9087-70-1/Aprotinin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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