Yen Chu

Impaired Endothelium-Dependent Relaxation After Cardiac Global Ischemia and Reperfusion: Role of Warm Blood Cardioplegia ☆

OBJECTIVES Experiments were designed to determine whether coronary endothelial dysfunction after cardiac global ischemia and reperfusion could be prevented by warm blood cardioplegic solution. BACKGROUND The coronary endothelium produces endothelium-derived relaxing factor (EDRF) to prevent vasospasm and thrombosis. After ischemia and reperfusion, endothelium-dependent relaxation (EDR) is diminished as a result of G-protein dysfunction. METHODS Dogs were exposed to extracorporeal circulation in 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The heart was ischemic for 120 min while continuous warm blood cardioplegic solution (group 1) or intermittent cold (4 degrees C) crystalloid cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 min of reperfusion. RESULTS Endothelium-derived relaxation in response to acetylcholine, adenosine diphosphate and sodium fluoride of the coronary rings of group 1 was significantly different from that of groups 2 and 3 but was not significantly different from that of group 4. In contrast, EDR in response to the receptor-independent calcium ionophore agonist A23187 was not significantly different between the four groups. Scanning electron microscopic studies showed that platelet adhesion and aggregation, area of microthrombi, disruption of endothelial cells and separation of the intercellular junction could be found in coronary segments of groups 2 and 3 but not in vessels of groups 1 and 4. CONCLUSIONS These experiments suggest that cardiac global ischemia and reperfusion impair receptor-mediated release of EDRF from the coronary endothelium with G-protein dysfunction. This type of coronary endothelial dysfunction can be prevented by continuous anterograde infusion of warm blood cardioplegic solution during global ischemia.

Continuous antegrade warm blood cardioplegia attenuates augmented coronary endothelium–dependent contraction after cardiac global ischemia and reperfusion

BACKGROUND Experiments were designed to evaluate the effect of warm blood cardioplegia on endothelium-dependent contraction of the coronary endothelium after cardiac global ischemia and reperfusion. METHOD Dogs (n = 12 in each group) were exposed to extracorporeal circulation with the body temperature at 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The ascending aorta was crossclamped for 120 minutes while continuous infusion of warm blood cardioplegec solution (group 1) or intermittent infusion of cold (4 degrees C) crystalloid cardioplegic solution (group 2) was performed via the coronary arteries through the aortic root. Cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 minutes of reperfusion. Reperfused (groups 1, 2, and 3) and control (group 4) coronary arteries were then harvested for study. RESULTS Perfusate hypoxia caused endothelium-dependent contraction in the arteries of all four groups that could be attenuated by NG-monomethyl-L-arginine (L-NMMA) or L-NMMA plus D-arginine, but not by L-NMMA plus L-arginine or endothelin receptor A and B antagonist PD 145065. The endothelium-dependent contraction results in groups 2 and 3 (75% +/- 4% and 80% +/- 5%, respectively) were significantly greater than those in groups 1 and 4 (15% +/- 3% and 18% +/- 5%, respectively). Scanning electron microscope studies showed that platelet adhesion and aggregation, areas of microthrombi, disruption of endothelial cells, and separation of the intercellular junction could be found in coronary segments from groups 2 and 3, but not in vessels from groups 1 and 4. CONCLUSION These experiments suggest that global ischemia and reperfusion enhances hypoxia-mediated endothelium-dependent contraction of the coronary endothelium and damages the ultrastructure. These kinds of changes can be prevented by continuous antegrade infusion of warm blood cardioplegic solution during global ischemia.

Effects of SEA0400 on arrhythmogenicity in a Langendorff-perfused 1-month myocardial infarction rabbit model.

The effects of SEA0400, a Na+/Ca2+ exchanger (NCX) blocker, on dynamic factors and arrhythmogenic alternans in 1‐month myocardial infarction (MI) hearts remain unknown.

Inhomogeneous downregulation of I Na underlies piceatannol proarrhythmic mechanism in regional ischemia-reperfusion: CHANG et al.

Piceatannol, a grape‐derived polyphenol, has been linked to proarrhythmic properties by aggravating inhomogeneous conduction delay in the ischemia‐reperfusion (IR) zone to enhance arrhythmogenic alternans in heart failure (HF) rabbits. The underlying molecular mechanisms of piceatannol‐induced conduction disturbance were unclear in this model.

Microenvironment of saphenous vein graft preservation prior to coronary artery bypass grafting

OBJECTIVES The best preservation solution for a free vascular graft prior to coronary artery bypass grafting (CABG) remains controversial. The aim of this investigation was to evaluate the microenvironment of the human saphenous vein graft when preserved in normal saline (NS) solution or autologous heparinized whole blood (AWB). METHODS Between January 2014 and December 2014, 21 patients who underwent CABG were enrolled and a total of 162 saphenous vein graft rings were collected. NS and AWB were used to investigate the influence of the microenvironment. The hypoxia, oxidative stress and vascular apoptosis were assayed by western blot, and endothelial integrity was assessed by immunohistochemical analysis. RESULTS The level of PaO2 in AWB was lower than that in NS (median: 100.5 mmHg vs 185.8 mmHg, P = 0.004). This hypoxic condition led to the production of more hypoxia-inducible factor-1 (median: 60.1% vs 15.1%, P = 0.008) and endothelial nitric oxide synthase (median: 52.6% vs 25%, P = 0.046) within 30 min of preservation time. The fact that higher levels of glutathione peroxidase resulted in the preservation of AWB suggests that it is beneficial to boost the vascular antioxidant defense with lower levels of NOX2. AWB led to increased Bcl-2, reduced cytochrome c and cleaved 85 kDa poly ADP-ribose polymerase apoptotic fragments. CONCLUSIONS We concluded that AWB possesses a microenvironment that is superior to that of NS for saphenous vein graft preservation prior to CABG.

Calsyntenin-1, clusterin and neutrophil gelatinase-associated lipocalin are candidate serological biomarkers for lung adenocarcinoma

It has been drawn attention that secreted proteins with signal peptide from cancer cells provide new potential biomarkers of cancer. In this study, three lung adenocarcinoma cell lines and serum samples from 20 patients were used for identifying potential serologic tumor biomarker with proteomic and bioinformatics approaches. One-dimensional electrophoresis, and identified with mass spectrometry and database research were performed. We found17 secreted proteins in common, while another 17 proteins with signal peptide were identified in all three lung adenocarcinoma cell lines alone with patient samples. With matching these two groups of identified proteins, calsyntenin-1 (CLSTN1), clusterin (CLU) and neutrophil gelatinase-associated lipocalin (NGAL) were found highly secreted from both cell lines and serum with unique signal peptides. Therefore, in our study, we demonstrated that cancer cells secret specific proteins to the environment that may serve as unique markers for cancer diagnosis. To combination of proteomic study with bioinformatic prediction on signal peptides, higher expression level of CLSTN1, CLU and NGAL were found and may be new solid serologic biomarkers for patients with lung adenocarcinoma.