Short-term and long-term outcomes of on-pump beating-heart coronary artery bypass surgery in dialysis and non-dialysis patients: a retrospective study in a single center.

BACKGROUND: This study aimed to evaluate the short-term and long-term outcomes of dialysis and non-dialysis patients after On-pump beating-heart coronary artery bypass grafting (OPBH-CABG). METHODS: We retrospectively reviewed medical records of 659 patients underwent OPBH-CABG at our hospital from 2009 to 2019, including 549 non-dialysis patients and 110 dialysis patients. Outcomes were in-hospital mortality, length of stay, surgical complications, post-CABG reintervention, and late mortality. The median follow-up was 3.88 years in non-dialysis patients and 2.24 years in dialysis patients. Propensity matching analysis was performed. RESULTS: After 1:1 matching, dialysis patients had significantly longer length of stay (14 (11-18) vs. 12 (10-15), p = 0.016), higher rates of myocardial infarction (16.85% vs. 6.74%, p = 0.037) and late mortality (25.93% vs. 9.4%, p = 0.005) after CABG compared to non-dialysis patients. No significant differences were observed in in-hospital mortality, complications, or post-CABG reintervention rate between dialysis and non-dialysis groups. CONCLUSIONS: OPBH-CABG could achieve comparable surgical mortality, surgical complication rates, and long-term revascularization in dialysis patients as those in non-dialysis patients. The results show that OPBH-CABG is a safe and effective surgical option for dialysis patients.

Treatment of intragraft stenosis in hemodialysis grafts with Supera stents: A retrospective study.

PURPOSE: To report the patency rates after implantation of an interwoven nitinol stent to salvage failing arteriovenous grafts (AVGs) caused by intragraft stenoses. METHODS: Between May 2018 and May 2020, 21 Supera stents were placed in 20 patients (18 women; mean age: 79.9 years) who had a failing AVG due to repeat intragraft stenoses. Recurrent AVG dysfunction with same intragraft stenosis within 3 months after first time angioplasty was a criterion for stenting. Those with concurrent treatment for other lesions were excluded. RESULTS: The technical success rate was 100%. Intragraft stenoses were treated at a median of 19.7 (interquartile range: 6-36) months after graft creation. Access circuit primary patency rates after stent placement were 84% and 35% at 6 and 12 months, respectively. Access circuit secondary patency rates were 100% at 6 and 12 months and 89% at 18 months. Only one patient presented with graft failure due to proximal drainage vein occlusion. The target lesion patency rates were 100% at 6 months and 75% at 12 months. The rate of reintervention for intragraft lesion was 0.15 procedures per year. Stent distortion did not occur under regular cannulation. CONCLUSION: The interwoven nitinol stent is a promising treatment for failing AVGs with recurrent intragraft stenoses. The 1-year access circuit primary, secondary, and target lesion patency rates were acceptable, with a low reintervention rate. Stent fracture does not occur in areas of needle puncture.

Use of modified-NUTRIC score to assess nutritional risk in surgical intensive care unit.

BACKGROUND: Modified Nutrition Risk in the Critically Ill (m-NUTRIC) score is used to evaluate the nutritional risk of patients in intensive care units (ICUs). This study aimed to investigate whether m-NUTRIC can be used as a predictive factor related to the outcome of patients in surgical ICU (SICU) and to identify which patients will benefit from aggressive nutritional intervention according to the results of m-NUTRIC score. METHODS: A total of 205 patients who were admitted to surgical ICU (SICU) with ventilator use for more than 24 hours were enrolled. The m-NUTRIC score data were calculated the day when the patients were admitted to SICU. Patients were divided into two groups according to their m-NUTRIC score: the low-risk group (<5 points, 116 patients) and the high risk group (≥5 points, 89 patients). RESULTS: In this study, a total of 205 patients were enrolled for analysis, including patients in the low-risk group (n = 116) and those in the high risk group (n = 89). The mean duration of ventilator use was 3.6 ± 6.5 days, and average SICU stays for all patients was 5.1 ± 7.4 days. The SICU mortality was significantly higher in the high-risk group (10.3% vs 1.7%). Comparison between survivals and nonsurvivals was carried out, and the data showed that the AKI, Vasopressors, SOFA, APACHE-II, m-NUTRIC score, and shock patient were all significantly associated with higher mortality. The multivariate analysis revealed that acute kidney injury (OR = 13.16; 95% confidence intervals = 3.69-46.92; p < 0.0001) and m-NUTRIC score were independent factors of ICU mortality in these patients. A receiver operating characteristic curve was used to calculate the area under the curve, which was 0.801. The data indicated that high m-NUTRIC score were significantly associated with SICU mortality with the cutoff score > 4 (sensitivity = 90.5%, specificity = 62.3%, p < 0.001). CONCLUSION: We found in this study that the high m-NUTRIC score is an independent factor of ICU mortality, and m-NUTRIC score can be used as an initial screening tool for nutritional assessment in patients admitted to surgical ICU. Further investigations to evaluate whether the aggressive nutritional intervention would be beneficial in the SICU patients with higher m-NUTRIC score is mandatory.

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia.

BACKGROUND/PURPOSE: TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. METHODS: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O2 to induce hypoxia. RESULTS: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-α (TNF-α) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-α antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-α from cardiomyocytes. Exogenous administration of TNF-α recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-α antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-α, JNK, and the GADD153 pathway. CONCLUSION: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia.

Endovascular stent-graft treatment for graft-vein anastomotic stenosis in haemodialysis patients with arteriovenous grafts.

BACKGROUND: In this study, we investigated the patency of endovascular stent grafts in haemodialysis patients with arteriovenous grafts, the modes of patency loss, and the risk factors for re-intervention. PATIENTS AND METHODS: Haemodialysis patients with graft-vein anastomotic stenosis of their arteriovenous grafts who were treated with endovascular stent-grafts between 2008 and 2013 were entered into this retrospective study. Primary and secondary patency, modes of patency loss, and risk factors for intervention were recorded. RESULTS: Cumulative circuit primary patency rates decreased from 40.0% at 6 months to 7.3% at 24 months. Cumulative target lesion primary patency rates decreased from 72.1% at 6 months to 22.0% at 24 months. Cumulative secondary patency rates decreased from 81.3% at 12 months to 31.6% at 36 months. Patients with a history of cerebrovascular accident had a significantly higher risk of secondary patency loss, and graft puncture site stenosis jeopardised the results of stent-graft treatment. CONCLUSIONS: Our data can help to improve outcomes in haemodialysis patients treated with stent-grafts for venous anastomosis of an arteriovenous graft.

Initial Experience of Modified Four-Branched Graft Technique and Antegrade TEVAR in Acute Type A Aortic Dissection.

BACKGROUND: We report the initial experience of modified four-branched graft technique for proximal aorta and arch repair, feasibly combined with antegrade thoracic endovascular aortic repair (TEVAR) to extend distal aortic reconstruction in acute type A aortic dissection. METHODS: From 2011 to 2013, 12 consecutive patients with acute type A aortic dissection were indicated for arch surgery and underwent surgical replacement of proximal aorta, arch replacement or debranching procedure, and concomitant TEVAR for distal aortic repair. RESULTS: A good surgical field was obtained in all patients. No major complications developed but two hospital deaths were attributed to end-organs damage preoperatively. Good and fast remodeling of thoracic descending aorta was demonstrated in 11 patients in postoperative CT imaging and no aneurysmal dilatation of visceral aorta had been observed in 10 patients during follow-up periods. CONCLUSION: Modified four-branched graft technique facilitated proximal aorta and arch repair, and provided excellent neurological outcome and favorable short-term results. Single-stage operation combined with antegrade TEVAR is feasible and effective to extend the repair down to the descending aorta, and thus achieved good remodeling of thoracic descending aorta.

Renal dysfunction and the risk of postoperative atrial fibrillation after cardiac surgery: role beyond the CHA2DS2-VASc score.

AIMS: To investigate whether renal dysfunction is a useful predictor of postoperative atrial fibrillation (POAF) after cardiac surgery. We also aimed to determine whether the addition of renal dysfunction into the scoring system could improve diagnostic accuracy of the CHA2DS2-VASc score to predict POAF. METHODS AND RESULTS: The study prospectively enrolled 350 consecutive patients who underwent cardiac surgery. Echocardiography was performed before cardiac surgery. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL min(-1) 1.73 m(-2). All patients were monitored with continuous electrocardiographic telemetry for the occurrence of POAF until the day of hospital dismissal. Postoperative atrial fibrillation occurred in 103 of 350 patients (29%). Patients with POAF was associated with longer intensive care unit stay compared with those without POAF (3.7 ± 2.2 vs. 3.1 ± 1.4 days, P = 0.002). Both the CHA2DS2-VASc score and renal dysfunction were independent predictors of POAF in multivariate analysis. Renal dysfunction can further stratify patients with a CHA2DS2-VASc score of 0 or 1 into two groups with different POAF rates (3.1% vs. 68.8%, P < 0.001). A new scoring system (R-CHA2DS2-VASc score) derived by assigning an additional point representing renal dysfunction to the CHA2DS2-VASc score could improve its predictive accuracy. The area under the receiver operating characteristic curve increased from 0.68 to 0.71 (P < 0.001). Furthermore, the rate of left ventricular diastolic dysfunction also increased with increasing renal dysfunction. CONCLUSION: Renal dysfunction, associated with left ventricular diastolic dysfunction, was a significant risk factor for POAF after cardiac surgery and may improve the diagnostic accuracy of the CHA2DS2-VASc score.

Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase/transient receptor potential vanilloid 1 pathway.

Hypoxic preconditioning (HPC) protects rat hearts against ischemia-reperfusion (IR) injury. However, the role of transient receptor potential vanilloid 1 (TRPV1) in HPC-mediated cardioprotection remains unknown. TRPV1 is activated by endovanilloid 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which is synthesized by arachidonate 12-lipoxygenase (ALOX12). Therefore, we examined whether HPC protects the myocardium against IR via the ALOX12/TRPV1 pathway. Compared to hearts of rats kept in room air, the hearts of rats kept in air with 10 % oxygen for 4 weeks had better post-ischemic recovery and less tissue damage when subjected to 30-min global ischemia and 4-h reflow in a Langendorff apparatus. Capsazepine, a specific TRPV1 blocker, administered 5 min before reperfusion markedly attenuated the effects of HPC, confirming that TRPV1 is a downstream effector in HPC-mediated cardioprotection. HPC resulted in the upregulation of ALOX12 and myocardial 12(S)-HETE, and prevented IR-induced 12(S)-HETE reduction. In addition, sarcolemmal ALOX12 expression in HPC hearts mainly co-localized with TRPV1 expression. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-α-cyanocinnamate or baicalein abrogated the effects of HPC, baicalein also decreased 12(S)-HETE expression. Mimicking HPC by given 12(S)-HETE or capsaicin to baicalien-treated hearts enhanced cardiac recovery during reperfusion. The cardiac protein kinase C (PKC) isoforms α, δ, ε, and ζ were preferentially expressed in the sarcolemmal membrane of HPC-treated hearts, indicating their high intrinsic activation state. Capsazepine or co-treatment with baicalein attenuated translocation of PKCα, PKCδ and PKCε, but not that of PKCζ. We conclude that HPC reduces heart susceptibly to IR via ALOX12/TRPV1/PKC pathway, as shown by increased 12(S)-HETE expression in HPC hearts.

Association between renal function, diastolic dysfunction, and postoperative atrial fibrillation following cardiac surgery.

BACKGROUND: Renal dysfunction is associated with a higher rate of atrial fibrillation in clinical practice. This study investigated the associations between renal function, left ventricular (LV) diastolic dysfunction, and postoperative atrial fibrillation (POAF). METHODS AND RESULTS: A total of 265 consecutive patients who underwent cardiac surgery were prospectively enrolled in the study. Echocardiography was performed before cardiac surgery. The patients were divided into 3 groups based on estimated glomerular filtration rate (eGFR) (group 1, ≥90ml·min(-1)·1.73m(-2); group 2, 60-90ml·min(-1)·1.73m(-2); and group 3, <60ml·min(-1)·1.73m(-2)). POAF occurred in 83 of 265 patients (31.3%). The rate of new-onset POAF increased from 15.2% (12/79) in group 1 to 27.8% (27/97) in group 2 and 49.4% (44/89) in group 3 (P<0.001). Further, with increasing renal dysfunction from groups 1 to 3, the rate of LV diastolic dysfunction - defined as E/e' >15 - also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%; P<0.001). Absolute eGFR was significantly correlated with E/e' ratio (r=-0.39, P<0.001). Renal function remained as the independent predictor of POAF on multivariate analysis (odds ratio, 1.90; 95% confidence interval: 1.26-2.87; P=0.002). CONCLUSIONS: In patients undergoing cardiac surgery, decreased eGFR was associated with an increased rate of LV diastolic dysfunction with a subsequent increase in the rate of POAF.

Association Between Renal Function, Diastolic Dysfunction, and Postoperative Atrial Fibrillation Following Cardiac Surgery.

Background: Renal dysfunction is associated with a higher rate of atrial fibrillation in clinical practice. This study investigated the associations between renal function, left ventricular (LV) diastolic dysfunction, and postoperative atrial fibrillation (POAF). Methods and Results: A total of 265 consecutive patients who underwent cardiac surgery were prospectively enrolled in the study. Echocardiography was performed before cardiac surgery. The patients were divided into 3 groups based on estimated glomerular filtration rate (eGFR) (group 1, ≥90ml·min-1·1.73m-2; group 2, 60-90ml·min-1·1.73m-2; and group 3, <60ml·min-1·1.73m-2). POAF occurred in 83 of 265 patients (31.3%). The rate of new-onset POAF increased from 15.2% (12/79) in group 1 to 27.8% (27/97) in group 2 and 49.4% (44/89) in group 3 (P<0.001). Further, with increasing renal dysfunction from groups 1 to 3, the rate of LV diastolic dysfunction - defined as E/e' >15 - also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%; P<0.001). Absolute eGFR was significantly correlated with E/e' ratio (r=-0.39, P<0.001). Renal function remained as the independent predictor of POAF on multivariate analysis (odds ratio, 1.90; 95% confidence interval: 1.26-2.87; P=0.002). Conclusions: In patients undergoing cardiac surgery, decreased eGFR was associated with an increased rate of LV diastolic dysfunction with a subsequent increase in the rate of POAF.

Clinical utility of CHADS2 and CHA2DS2-VASc scoring systems for predicting postoperative atrial fibrillation after cardiac surgery.

OBJECTIVES: The presence of postoperative atrial fibrillation predicts a higher short- and long-term mortality rates; however, no scoring system has been used to discriminate patients at high risk for this complication. The aim of this study was to investigate whether the CHADS2 and CHA2DS2-VASc scores are useful risk assessment tools for new-onset atrial fibrillation after cardiac surgery. METHODS: A total of 277 consecutive patients who underwent cardiac surgery were prospectively included in this risk stratification study. We calculated the CHADS2 and CHA2DS2-VASc scores from the data collected. The primary end point was the development of postoperative atrial fibrillation within 30 days after cardiac surgery. RESULTS: Eighty-four (30%) of the patients had postoperative atrial fibrillation at a median of 2 days (range, 0-27 days) after cardiac surgery. The CHADS2 and CHA2DS2-VASc scores were significant predictors of postoperative atrial fibrillation in separate multivariate regression analyses. The Kaplan-Meier analysis obtained a higher postoperative atrial fibrillation rate when based on the CHADS2 and CHA2DS2-VASc scores of at least 2 than when based on scores less than 2 (both log rank, P < .001). In addition, the CHA2DS2-VASc scores could be used to further stratify the patients with CHADS2 scores of 0 or 1 into 2 groups with different postoperative atrial fibrillation rates at a cutoff value of 2 (12% vs 32%; P = .01). CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores were predictive of postoperative atrial fibrillation after cardiac surgery and may be helpful for identifying high-risk patients.

Endovascular stent graft repair for a Salmonella-infected aneurysm of thoracic aorta.

Thoracic endovascular aneurysm repair using stent graft has been reported as a feasible and effective treatment for aortic aneurysm. However, its application for treating infected aortic aneurysms is still controversial and less reported. We report a 74-year-old male diabetic patient diagnosed with Salmonella-infected aortic aneurysm, who was successfully treated with endovascular stent graft repair followed by a 2-month course of intravenous antibiotics and long-term oral antibiotic therapy. Sequential computed tomography scans demonstrated the shrinkage of the aneurysm and no evidence of relapse 11 months later.

Erythropoietin alleviates post-ischemic injury of rat hearts by attenuating nitrosative stress.

AIMS: Nitrosative stress caused by ischemia contributes to poor functional recovery in hearts. A previous study showed that recombinant human erythropoietin (EPO) activates the Janus-tyrosine kinase 2/extracellular signal-regulated kinase (Jak2/ERK) pathway to protect myocardium against ischemia/reperfusion (IR) injury. However, it is not clear how pro-survival signals triggered by EPO affect the nitric oxide (NO) system in post-ischemic myocardial tissue. MAIN METHODS: Isolated rat hearts were subjected to IR injury and changes in protein expression in the myocardium were evaluated by immunostaining. KEY FINDINGS: Compared with untreated hearts, EPO-treated IR hearts showed significant improvements in contractility and reduced myocardial injury and infarction; this was associated with attenuated caspase-3 activation. Excess formation of NO metabolites and nitrotyrosine, which cause nitrosative stress, was markedly suppressed by EPO. The mechanism underlying EPO-mediated alleviation of nitrosative stress was related to an increase in arginase II expression and to the suppression of heat shock protein 90 (HSP90)-dependent upregulation of endothelial and inducible NO synthase (NOS). Myocardial EPO content was restored after EPO treatment, which in turn recruited signal transducer and activator of transcription (STAT) 3 protein and induced ERK signaling downstream of Jak2, which increased arginase II levels and suppressed HSP90 expression, respectively. Inhibition of STAT3 and ERK specifically reversed the effects of EPO on arginase II and HSP90 expression. SIGNIFICANCE: These results indicate that EPO triggers the Jak2-STAT3/ERK pathway to restore the balance between arginase and NOS and, thus, reduces nitrosative stress. This may form the basis of myocardial protection following IR.

Mechanosensitive transient receptor potential vanilloid type 1 channels contribute to vascular remodeling of rat fistula veins.

OBJECTIVE: We previously showed that matrix metalloproteinases (MMPs) contribute to tremendous blood flow-induced venous wall thickening during the maturation of an arteriovenous fistula (AVF). However, how veins in the fistula sense a dramatic change in the blood flow remains unknown. Because mechanosensitive transient receptor potential vanilloid channels (TRPVs) are present in the endothelium, we examined whether the Ca2+-permeable TRPVs play a role in remodeling of fistula veins. METHODS: The fistula veins were generated at femoral AVF of Wistar rats. Changes in the hemodynamics and the width and internal radius of the iliac vein were studied at 3, 7, 14, and 28 days, then the iliac vein was removed and examined for changes in wall thickness and protein or mRNA expression by immunofluorecent stain, Western blot, or real time PCR. Changes in MMP2 activity was examined by gelatin zymography. Two ligatures were performed in iliac vein to prevent venodilatation to confirm the effect of dramatic changes in hemodynamics on TRPV expression. The specific role of TRPV was studied in another group of fistula veins given with capsazepine via a subcutaneous mini-osmotic pump for 28 days. RESULTS: The fistula veins demonstrated high flow/wall shear stress (WSS), wall thickening, and venodilatation compared with control veins. The WSS increase was positively correlated with upregulation of TRPV1, but not TRPV4. Narrowing fistula veins prevented TRPV1 upregulation, indicating that high flow directly upregulates TRPV1. We examined the underlying signaling components and found that enhanced Ca2+/calmodulin-dependent protein kinase II (CaMK II) activity upregulated endothelial nitric oxide synthase (eNOS) and downregulated arginase I in the fistula veins. These changes were reversed by a CaMK II inhibitor. The relative levels of eNOS and arginase I activity consequently augmented NO formation, which coincided with an increase in MMP2 activity. Chronic inhibition of TRPV1 in the fistula veins by capsazepine showed no effect on high flow and TRPV1 expression, but markedly attenuated WSS, which was concomitantly associated with attenuation of CaMK II activity, NO-dependent MMP2 activation, and remodeling. CONCLUSION: These findings indicate that TRPV1 is essential in the remodeling of AVFs and that WSS leads to TRPV1 upregulation, which then enhances remodeling, therefore, inhibition of TRPV1 pathway may prolong the lifespan of an AVF by decreasing WSS and vein wall remodeling.

Pericardial fluid and serum levels of vascular endothelial growth factor and endostatin in patients with or without coronary artery disease.

BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) and endostatin are related to ischemic heart disease. This study investigated pericardial fluid and serum levels of VEGF and endostatin in patients with or without ischemic heart disease. METHODS: A total of 39 patients (24 patients in the CAD group with significant coronary artery disease; 15 patients in the non-CAD group without coronary artery disease) undergoing open heart surgery were enrolled. In the CAD group, patients were classified according to good coronary collateralization (Group A; n = 11) or poor coronary collateralization (Group B; n = 13). Pericardial fluid and serum samples were obtained at the time of surgery. VEGF and endostatin were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of endostatin in both serum and pericardial fluid were significantly lower in the CAD group than in the non-CAD group (130.5 +/- 37.3 ng/mL vs. 172.4 +/- 37.8 ng/mL and 119.0 +/- 25.0 ng/mL vs. 143.0 +/- 23.5 ng/mL). The concentration of serum VEGF in the CAD group (92.6 +/- 18.2 pg/mL) was significantly higher than that in the non-CAD group (75.2 +/- 22.3 pg/mL). The concentration of serum VEGF in Group A (100.1 +/- 20.7 pg/mL) was significantly higher than that in Group B (84.3 +/- 12.4 pg/mL). The levels of pericardial fluid VEGF, serum and pericardial fluid endostatin were not significantly different between Groups A and B. CONCLUSION: Patients with coronary artery disease have lower serum and pericardial fluid levels of endostatin and higher serum levels of VEGF. Serum level VEGF, but not endostatin, is associated with good or poor collateralization in patients with coronary artery disease.

Temporal and spatial expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of myocardial ischemia with or without reperfusion.

BACKGROUND AND PURPOSE: Although hypoxia-inducible factor-1alpha (HIF-1alpha) plays a major role in the prevention of myocardial ischemia, the temporal and spatial patterns of expression of HIF-1alpha in myocardial ischemia-reperfusion are not well known. This study examined the role of HIF-1alpha and vascular endothelial growth factor (VEGF) in myocardial ischemia-reperfusion. METHODS: Adult Wistar rats were studied after ligation of the left anterior descending coronary artery (LAD) for 30 min and then after reperfusion. HIF-1alpha and VEGF were measured immediately after relief of occlusion and at 30 min, 1, 3, 6, and 24 h after reperfusion. HIF-1alpha and VEGF proteins were also measured 6 h after permanent occlusion of the LAD. RESULTS: HIF-1alpha and VEGF mRNA increased 1.8- and 1.4-fold, respectively, immediately after relief of occlusion and reached a maximum of 4.3- and 2.3-fold, respectively, at 3 h after reperfusion and remained elevated up to 24 h. HIF-1alpha and VEGF proteins increased immediately after relief of ischemia. HIF-1alpha protein significantly increased from 0.5 h to 24 h after reperfusion and VEGF protein significantly increased from 1 h to 6 h after reperfusion compared to the sham control. Administration of HIF-1alpha antisense oligonucleotide before ligation of the LAD significantly inhibited VEGF protein expression induced by ischemia-reperfusion. Immunohistochemical study showed increased immunoreactivity of HIF-1alpha and VEGF in the jeopardized myocardium after ischemia-reperfusion. HIF-1alpha and VEGF proteins were increased at 6 h after permanent occlusion of the LAD. CONCLUSIONS: This study demonstrated that HIF-1alpha and VEGF were co-induced in a temporal and spatial pattern after ischemia-reperfusion in the rat ventricular myocardium.

Spontaneous rupture of left ventricular true aneurysm.

The rupture of left ventricular true aneurysm is a rare event. We report the case of a 52-year-old man who presented to the emergency department with cardiac tamponade that was due to a ruptured left ventricular true aneurysm. An emergency operation was successfully performed to address this rare event.

A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity.

Warfarin, a commonly prescribed anticoagulant, exhibited large inter-individual and inter-ethnic differences in the dose required for its anticoagulation effect. Asian populations, including Chinese, require a much lower maintenance dose than Caucasians, for which the mechanisms still remain unknown. We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (< or = 1.5 mg/day, n = 11) or resistance (> or = 6.0 mg/day, n = 5), 104 randomly selected Chinese patients receiving warfarin, 95 normal Chinese controls and 92 normal Caucasians. We identified three CYP2C9 variants, CYP2C9*3, T299A and P382L, in four warfarin-sensitive patients. A novel VKORC1 promoter polymorphism (-1639 G > A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients. The resistant patients were either AG or GG. Among the 104 randomly selected Chinese patients receiving warfarin, AA genotype also had lower dose than the AG/GG genotype (P < 0.0001). Frequencies of AA, AG and GG genotypes were comparable in Chinese patients receiving warfarin (79.7, 17.6 and 2.7%) and normal Chinese controls (82, 18 and 0%), but differed significantly from Caucasians (14, 47 and 39%) (P < 0.0001). The promoter polymorphism abolished the E-box consensus sequences and dual luciferase assay revealed that VOKRC1 promoter with the G allele had a 44% increase of activity when compared with the A allele. The differences in allele frequencies of A/G allele and its levels of VKORC1 promoter activity may underscore the inter-individual differences in warfarin dosage as well as inter-ethnic differences between Chinese and Caucasians.

Carvedilol modulates the expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of volume-overload heart failure.

BACKGROUND: The use of beta-blockers has emerged as a beneficial treatment for congestive heart failure. Hypoxia-inducible factor-1alpha (HIF-1alpha) is tightly regulated in the ventricular myocardium. However, the expression of HIF-1alpha in chronic heart failure resulting from volume overload and after treatment with beta-blocker is little known. METHODS AND RESULTS: To test the hypothesis that HIF-1alpha plays a role in the failing myocardium because of volume overload, an aorta-caval shunt was created for 4 weeks in adult Sprague-Dawley rats to induce volume-overload heart failure. Carvedilol at 50 mg/kg body weight per day after surgery was given. The heart weight and body weight ratio increased from 2.6 +/- 0.3 in the sham group to 3.9 +/- 0.7 (P < .001) in the shunt group. Left ventricular end-diastolic dimension increased from 6.5 +/- 0.5 mm to 8.7 +/- 0.6 mm (P < .001). Treatment with carvedilol in the shunt group reversed the heart weight and ventricular dimension to the baseline values. Western blot showed that HIF-1alpha, vascular endothelial growth factor (VEGF), and brain natriuretic peptide (BNP) proteins were upregulated and nerve growth factor-beta (NGF-beta) downregulated in the shunt group. Real-time polymerase chain reaction showed that mRNA of HIF-1alpha, VEGF, and BNP increased and mRNA of NGF-beta decreased in the shunt group. Treatment with carvedilol reversed both protein and mRNA of HIF-1alpha, VEGF, BNP, and NGF-beta to the baseline values. Increased immunohistochemical labeling of HIF-1alpha, VEGF, and BNP in the ventricular myocardium was observed in the shunt group and carvedilol again normalized the labeling. CONCLUSION: HIF-1alpha and VEGF mRNA and protein expression were upregulated in the rat model of volume-overload heart failure. Treatment with carvedilol is associated with a reversal of abnormal regulation of HIF-1alpha and VEGF in the failing ventricular myocardium.

Spontaneous cardiac rupture.

An 83-year-old woman had a sudden onset of loss of consciousness with no detectable blood pressure. Pulseless electrical activity was present in the electrocardiogram and massive pericardial effusion was found by echocardiography. Emergent subxiphoid pericardiotomy and drainage was immediately performed to release the cardiac tamponade at bedside and was followed by rushing the patient to the operating room for exploration. As a result a ruptured hole was identified on the posterior-lateral wall of the left ventricle and the defect was successfully repaired. The patient had an uneventful postoperative recovery and received postoperative study by cardiac catheterization, which disclosed coronary artery disease.