Mingxin Gao

Impact of Obstructive Sleep Apnea Syndrome on Endothelial Function, Arterial Stiffening, and Serum Inflammatory Markers: An Updated Meta‐analysis and Metaregression of 18 Studies

Background Obstructive sleep apnea syndrome (OSAS) has been indicated to contribute to the development of cardiovascular disease; however, the underlying mechanism remains unclear. This study aimed to test the hypothesis that OSAS may be associated with cardiovascular disease by elevating serum levels of inflammatory markers and causing arterial stiffening and endothelial dysfunction. Methods and Results Related scientific reports published from January 1, 2006, to June 30, 2015, were searched in the following electronic literature databases: PubMed, Excerpta Medica Database, ISI Web of Science, Directory of Open Access Journals, and the Cochrane Library. The association of OSAS with serum levels of inflammatory markers, endothelial dysfunction, and arterial stiffening were investigated. Overall, 18 eligible articles containing 736 patients with OSAS and 424 healthy persons were included in this meta‐analysis. Flow‐mediated dilation in patients with moderate–severe OSAS was significantly lower than that in controls (standardized mean difference −1.02, 95% CI −1.31 to −0.73, P<0.0001). Carotid‐femoral pulse wave velocity (standardized mean difference 0.45, 95% CI 0.21–0.69, P<0.0001), augmentation index (standardized mean difference 0.57, 95% CI 0.25–0.90, P<0.0001), and serum levels of high‐sensitivity C‐reactive protein and C‐reactive protein (standardized mean difference 0.58, 95% CI 0.42–0.73, P<0.0001) were significantly higher in patients with OSAS than in controls. Conclusion OSAS, particularly moderate–severe OSAS, appeared to reduce endothelial function, increase arterial stiffness, and cause chronic inflammation, leading to the development of cardiovascular disease.

Preoperative Statin Therapy and Renal Outcomes After Cardiac Surgery: A Meta-analysis and Meta-regression of 59,771 Patients

BACKGROUND The purpose of this study was to investigate the effects of preoperative statin therapy (PST) on short- and long-term renal dysfunction after cardiac surgery. METHODS We searched for reports that investigated the effects of PST on renal outcomes after cardiac surgery in the electronic literature databases PubMed, Ovid, and Elsevier. RESULTS Twenty-six reports including 59,771 patients were selected for meta-analysis. The meta-analysis revealed that PST significantly reduced the incidence of postoperative renal dysfunction (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84-0.95; P < 0.0001) without significant heterogeneity (I(2) = 28.1%; P = 0.093). PST also significantly reduced the need for postoperative renal replacement therapy (OR = 0.76; 95% CI, 0.62-0.92; z = 2.77; P = 0.006); particularly in the subgroup of patients who underwent isolated coronary artery bypass grafting, the rate of renal replacement therapy was reduced by 56% (OR, 0.44; 95% CI, 0.30-0.66; z = 4.08; P < 0.0001) with low heterogeneity (I(2) = 18.7%; P = 0.297). Meta-analysis for the outcome of acute kidney injury (AKI) revealed that PST reduced the incidence of postoperative AKI by 13% (OR, 0.87; 95% CI, 0.80-0.94; P = 0.001) and 7% (OR, 0.93; 95% CI, 0.86-0.99; P = 0.031), respectively, for subgroups of patients whose AKI was evaluated using the Acute Kidney Injury Network (AKIN) or the Risk, Injury, Failure, Loss, and End Stage (RIFLE) criteria, without significant heterogeneity for either. CONCLUSIONS PST might be a promising therapy to reduce renal complications after cardiac surgery although large-scaled randomized controlled trials are needed to further verify the conclusion.

Short- and Long-Term Patient Outcomes From Combined Coronary Endarterectomy and Coronary Artery Bypass Grafting: A Meta-Analysis of 63,730 Patients (PRISMA).

AbstractThis meta-analysis aimed to compare the short- and long-term outcomes in patients undergoing combined coronary endarterectomy and coronary artery bypass grafting (CE + CABG) versus isolated CABG, and particularly to examine subgroup patients with high-risk profile and patients with diffuse disease in the left anterior descending artery (LAD).Studies published between January 1, 1970 and May 31, 2015 were searched in the literature databases, including Ovid Medline, Embase, PubMed, and ISI Web of Science.A total of 30 eligible studies including 63,730 patients were analyzed.Five authors extracted data from the included studies independently.Meta-analysis on the total patients revealed that CE + CABG was associated with significantly increased 30-day postoperative all-cause mortality compared with isolated CABG (OR = 1.86, 95% CI: 1.66–2.08, z = 10.99, P < 0.0001). Subgroup analysis on patients with high-risk profile and patients with diffuse disease in the LAD showed that 30-day mortality after CE + CABG was 2.6 folds (OR = 2.60, 95% CI: 1.39–4.86, z = 2.99, P = 0.003) and 3.93 folds (OR = 3.93, 95% CI: 1.40–11.0, z = 2.60, P = 0.009) of that after isolated CABG in the respective subgroup. In contrast, the mortality was comparable in CE + off-pump CABG and CE + on-pump CABG groups (OR = 0.53, 95% CI: 0.18–1.55, z = 1.16, P = 0.248). In addition, the incidences of perioperative myocardial infarction (MI) and 30-day postoperative complications, including low output syndrome (LOS), MI, ventricular tachycardia (VT), and renal dysfunction after CE + CABG were significantly higher than those after isolated CABG (all P < 0.05). In high-risk patient subgroup, CE + CABG significantly increased the incidences of postoperative LOS, MI, and renal function compared with isolated CABG (all P < 0.05). The incidence of perioperative myocardial after CE + CABG was 2.86 and 2.92 times of that after isolated CABG in high-risk patients and patients with diffuse disease in LAD, respectively. Analysis on the recent reports (published later than 2000) showed consistent results as the analysis including all the eligible reports. Long-term survival was comparable in CE + CABG and isolated CABG groups (hazardous ratio = 1.16, 95% CI: 0.32–4.22, z = 0.23, P = 0.819).CE + CABG appears to be associated with poor short-term outcomes, particularly in high-risk patients and patients with diffuse disease in the LAD.

Targeting the proinflammatory cytokine tumor necrosis factor-α to alleviate cardiopulmonary bypass-induced lung injury (Review)

Pulmonary dysfunction is one of the most frequent complications associated with cardiopulmonary bypass (CPB). Multiple factors, including the contact of blood with the artificial surface of the CPB circuit, ischemia‑reperfusion and lung ventilator arrest elicit inflammatory reactions, consequently resulting in CPB‑induced lung injury. The proinflammatory cytokine tumor necrosis factor‑α (TNF‑α) has been demonstrated to have a critical role in mediating CPB‑induced pulmonary inflammation. The present review evaluated previous studies and summarized the effects of CPB on TNF‑α level in the serum and lung tissue of patients and animal models of CPB, the underlying mechanism of TNF‑α‑mediated lung injury and the therapeutic strategies for the inhibition of TNF‑α activity and production to attenuate CPB‑induced lung injury. TNF‑α level in the serum and lung tissue is significantly increased during and following CPB. TNF‑α mediates CPB‑induced lung damage by directly inducing apoptosis in alveolar epithelial cells and lung endothelial cells and by indirectly modulating the function of immune cells, including monocytes and macrophages. A functional neutralizing antibody to TNF‑α can reduce pulmonary TNF‑α production and attenuate CPB‑induced lung injury in a rabbit model of CPB. Inhibition of TNF‑α function and production using a neutralizing antibody to TNF‑α appears to be a promising therapeutic strategy to alleviate CPB‑induced lung injury.

Pulmonary Artery Perfusion with Anti-Tumor Necrosis Factor Alpha Antibody Reduces Cardiopulmonary Bypass-Induced Inflammatory Lung Injury in a Rabbit Model

Inflammatory lung injury is one of the main complications associated with cardiopulmonary bypass (CPB). Tumor necrosis factor-α (TNF-α) is one of the key factors mediating the CPB-induced inflammatory reactions. Our previous studies have shown that endotracheal administration of anti-tumor necrosis factor-α antibody (TNF-α Ab) produces some beneficial effects on lung in a rabbit CPB model. In this study, we further examined the effects of pulmonary artery perfusion with TNF-α Ab (27 ng/kg) on lung tissue integrity and pulmonary inflammation during CPB and investigated the mechanism underlying the TNF-α Ab-mediated effects in a rabbit model of CPB. Our results from transmission electron microscopy showed that the perfusion with TNF-α Ab alleviated CPB-induced histopathological changes in lung tissue. The perfusion with TNF-α Ab also prevented CPB-induced pulmonary edema and improved oxygenation index. Parameters indicating pulmonary inflammation, including neutrophil count and plasma TNF-α and malondialdehyde (MDA) levels, were significantly reduced during CPB by pulmonary artery perfusion with TNF-α Ab, suggesting that the perfusion with TNF-α Ab reduces CPB-induced pulmonary inflammation. We further investigated the molecular mechanism underlying the protective effects of TNF-α Ab on lung. Our quantitative RT-PCR analysis revealed that pulmonary artery perfusion with TNF-α Ab significantly decreased TNF-α expression in lung tissue during CPB. The apoptotic index in lung tissue and the expression of proteins that play stimulatory roles in apoptosis pathways including the fas ligand (FasL) and Bax were markedly reduced during CPB by the perfusion with TNF-α Ab. In contrast, the expression of Bcl-2, which plays an inhibitory role in apoptosis pathways, was significantly increased during CPB by the perfusion with TNF-α Ab, indicating that the perfusion with TNF-α Ab significantly reduces CPB-induced apoptosis in lung. Thus, our study suggests that pulmonary artery perfusion with TNF-α Ab might be a promising approach for attenuating CPB-induced inflammatory lung injury.

Distal end side-to-side anastomoses of sequential vein graft to small target coronary arteries improve intraoperative graft flow

BackgroundEnd-to-side anastomoses to connect the distal end of the great saphenous vein (GSV) to small target coronary arteries are commonly performed in sequential coronary artery bypass grafting (CABG). However, the oversize diameter ratio between the GSV and small target vessels at end-to-side anastomoses might induce adverse hemodynamic condition. The purpose of this study was to describe a distal end side-to-side anastomosis technique and retrospectively compare the effect of distal end side-to-side versus end-to-side anastomosis on graft flow characteristics.MethodsWe performed side-to-side anastomoses to connect the distal end of the GSV to small target vessels on 30 patients undergoing off-pump sequential CABG in our hospital between October 2012 and July 2013. Among the 30 patients, end-to-side anastomoses at the distal end of the GSV were initially performed on 14 patients; however, due to poor graft flow, those anastomoses were revised into side-to-side anastomoses. We retrospectively compared the intraoperative graft flow characteristics of the end-to-side versus side-to-side anastomoses in the 14 patients. The patient outcomes were also evaluated.ResultsWe found that the side-to-side anastomosis reconstruction improved intraoperative flow and reduced pulsatility index in all the 14 patients significantly. The 16 patients who had the distal end side-to-side anastomoses performed directly also exhibited satisfactory intraoperative graft flow. Three-month postoperative outcomes for all the patients were satisfactory.ConclusionsSide-to-side anastomosis at the distal end of sequential vein grafts might be a promising strategy to connect small target coronary arteries to the GSV.

The application of intraoperative transit time flow measurement to accurately assess anastomotic quality in sequential vein grafting.

OBJECTIVES Intraoperative transit time flow measurement (TTFM) is widely used to assess anastomotic quality in coronary artery bypass grafting (CABG). However, in sequential vein grafting, the flow characteristics collected by the conventional TTFM method are usually associated with total graft flow and might not accurately indicate the quality of every distal anastomosis in a sequential graft. The purpose of our study was to examine a new TTFM method that could assess the quality of each distal anastomosis in a sequential graft more reliably than the conventional TTFM approach. METHODS Two TTFM methods were tested in 84 patients who underwent sequential saphenous off-pump CABG in Beijing An Zhen Hospital between April and August 2012. In the conventional TTFM method, normal blood flow in the sequential graft was maintained during the measurement, and the flow probe was placed a few centimetres above the anastomosis to be evaluated. In the new method, blood flow in the sequential graft was temporarily reduced during the measurement by placing an atraumatic bulldog clamp at the graft a few centimetres distal to the anastomosis to be evaluated, while the position of the flow probe remained the same as in the conventional method. This new TTFM method was named the flow reduction TTFM. Graft flow parameters measured by both methods were compared. RESULTS Compared with the conventional TTFM, the flow reduction TTFM resulted in significantly lower mean graft blood flow (P < 0.05); in contrast, yielded significantly higher pulsatility index (P < 0.05). Diastolic filling was not significantly different between the two methods and was >50% in both cases. Interestingly, the flow reduction TTFM identified two defective middle distal anastomoses that the conventional TTFM failed to detect. Graft flows near the defective distal anastomoses were improved substantially after revision. CONCLUSIONS In this study, we found that temporary reduction of graft flow during TTFM seemed to enhance the sensitivity of TTFM to less-than-critical anastomotic defects in a sequential graft and to improve the overall accuracy of the intraoperative assessment of anastomotic quality in sequential vein grafting.

Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting

OBJECTIVES Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. METHODS Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C-C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P < 0.01). CONCLUSION Perivenous application of α-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.

Epicardial unipolar radiofrequency ablation for left ventricular aneurysm related ventricular arrhythmia

We report a case of a 62-year-old Chinese man with typical triple-vessel lesions and apical left ventricular aneurysm accompanied with ventricular tachycardia. Off-pump coronary artery bypass (OPCAB) grafting was performed in combination with epicardial unipolar radiofrequency ablation and linear closure of left ventricular aneurysm. The patient recovered well without postoperative complications. Holter monitoring showed no recurrence of the ventricular arrhythmia and the attack frequency of arrhythmia decreased significantly. The patient has been angina-free for 25 months since the operation and shows increasing exercise tolerance. Thus, left ventricular aneurysm plication combined with epicardial unipolar radiofrequency ablation during OPCAB may be beneficial for patients with ventricular aneurysm and preoperative malignant ventricular arrhythmia.

Outcomes of middle cardiac vein arterialization via internal mammary/thoracic artery anastomosis.

Objective Cardiac vein arterialization is seldom applied for treating right coronary artery disease. This study aimed to improve outcomes of cardiac vein arterialization in a porcine model using intramammary artery anastomosis. Methods A chronic, stenotic coronary artery model was established in 12 of 14 Chinese experimental miniature pigs of either sex, which were randomly divided into equal control (n = 6) and experimental (n = 6) groups. In experimental animals, blood flow was reconstructed in the right coronary artery using intramammary artery. Arterialization involved dissection of right internal mammary artery from bifurcation to apex of thorax followed by end-to-side anastomosis of internal mammary artery and middle cardiac vein plus posterior descending branch of right coronary artery. Intraoperative heart rate was maintained at 110 beats/min. Graft flow assessment and echocardiography were performed when blood pressure and heart rate normalized. Results The experimental group had significantly higher mean endocardial and epicardial blood flow postoperatively than control group (mean endocardial blood flow: 0.37 vs. 0.14 ml/(g*min), p<0.001; mean epicardial blood flow: 0.29 vs. 0.22, p = 0.014). Transmural blood flow was also higher in experimental group than in control group (0.33 vs. 0.19, p<0.001); ejection fraction increased from 0.46% at baseline to 0.51% (p = 0.0038) at 6 hours postoperatively, and mean blood flow of internal mammary artery was 44.50, perfusion index 0.73 at postoperative 6 months, 43.33 and 0.80 at 3 months. Conclusion Successful cardiac vein arterialization via intramammary artery in a porcine model suggests that this may be a viable method for reconstructing blood flow in chronic, severe coronary artery disease.