Abstract
The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.
Highlights
Cardiopulmonary bypass (CPB) assisted open-heart surgery allows the surgeon to work in a quiet and bloodless operating field and is mandatory in many routine types of cardiac surgery
Disrupted microvascular blood flow is usually seen after revascularization procedures but is present after protected ischemia-reperfusion injury (I-RI) (Boyle et al, 1996; Verrier and Morgan, 1998; Wong et al, 2013)
No direct effect of thymosin beta 4 (TB4) treatment was observed on these parameters (Table 2)
Summary
Cardiopulmonary bypass (CPB) assisted open-heart surgery allows the surgeon to work in a quiet and bloodless operating field and is mandatory in many routine types of cardiac surgery. During CPB the heart is stopped and isolated from the blood circulation while protected from ischemia with cardioplegic solution. The return of myocardial blood flow (MBF) leads to reperfusion injury causing further damage to the heart. Ischemia-reperfusion injury (I-RI) can be identified by biomarkers for cardiomyocyte death, reduced cardiac function and the incidence. Disrupted microvascular blood flow is usually seen after revascularization procedures but is present after protected I-RI (Boyle et al, 1996; Verrier and Morgan, 1998; Wong et al, 2013). Extracorporeal circulation causes a systemic inflammatory response that can lead to organ dysfunction and hemodynamic instability (Hausenloy et al, 2013). Different approaches to minimize the effects of myocardial I-RI have been studied extensively, there is, little agreement regarding the most optimal cardioprotective strategy in heart surgery. High-risk patients could benefit from more effective methods attenuating I-RI (Bolli et al, 2004)
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