Inflammation-induced sialin mediates nitrate efflux in dysfunctional endothelium affecting NO bioavailability.

AIM: The mechanism of NO bioavailability in endothelial dysfunction, the trigger for atherogenesis is still unclear as exogenous nitrate therapy fails to alleviate endothelial dysfunction. Recently, sialin, a nitrate transporter, has been linked to affect tissue nitrate/nitrite levels. Hence, we investigated the role of sialin in NO bioavailability in endothelial dysfunction. METHODS: Serum-starved HUVECs were stimulated with either TNFα or AT-2 for 24 h either alone or in the presence of autophagy inducer or autophagy inhibitor alone. Nitric oxide, nitrite, and nitrate levels were measured in cell supernatant and cell lysate. Quantitative real-time PCR, Annexin V-PI, and monocyte adhesion assays were performed. Immunofluorescence staining for sialin, vWF, and LC3 was performed. STRING database was used to create protein interacting partners for sialin. RESULTS: Sialin is strongly expressed in activated EC in vitro and atherosclerotic plaque as well as tumor neo-vessel ECs. Sialin mediates nitrate ion efflux and is negatively regulated by autophagy via mTOR pathway. Blocking sialin enhances NO bioavailability, autophagy, cell survival, and eNOS expression while decreasing monocyte adhesion. PPI shows LGALS8 to directly interact with sialin and regulate autophagy, cell-cell adhesion, and apoptosis. CONCLUSION: Sialin is a potential novel therapeutic target for treating endothelial dysfunction in atherosclerosis and cancer.

Comparison of Left Ventricular Global Longitudinal Strain with Ejection Fraction as a Predictor for Peri-operative IABP Insertion in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A Pilot Study.

Background: Prophylactic use of intra-aortic balloon pump (IABP) mainly depends on left ventricular (LV) systolic function. Global longitudinal strain (GLS) is a robust prognostic parameter for LV strain. It has proved to be more sensitive than LV ejection fraction (EF) as a measure of LV systolic function and is a strong predictor of outcome. Aim: To determine whether GLS can be used as a reliable marker and its cut-off value for IABP insertion in patients undergoing elective off-pump coronary artery bypass grafting (OPCABG). Settings and Design: A prospective observational clinical study which included 100 adult patients scheduled for elective OPCABG. Materials and Methods: Two-dimensional (2D) speckle tracking echocardiography (STE)-estimated GLS was computed and compared with LV EF measured by three dimensional (3D) echocardiography for the insertion of IABP. The intensive care unit (ICU) parameters were correlated with echocardiographic parameters to predict early post-operative outcome. Results: IABP insertion correlates better with GLS (post-revascularization > pre-revascularization) than with 3D LV EF. Receiver operating characteristic (ROC) curve analysis revealed the highest area under the curve (AUC, 0.972) with a cut-off value of > -9.8% for GLS compared to 3D LV EF (AUC, 0.938) with a cut-off value of ≤ 44%. ICU parameters show better correlation with E/e'> GLS > WMSI than 3D LV EF. Conclusion: GLS is a better predictor of IABP insertion compared to 3D LV EF in patients undergoing OPCABG.

Differential effect of basal vitamin D status in monocrotaline induced pulmonary arterial hypertension in normal and vitamin D deficient rats: Possible involvement of eNOS/TGF-ß/α-SMA signaling pathways.

Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-ß (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- ß significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity.

Pleuropulmonary blastoma masquerading as pneumothorax in a patient with a ventricular septal defect.

Pleuropulmonary blastoma is a rare pediatric primary lung tumor. We report a case of a child with Down syndrome and a large ventricular septal defect presenting with pleuropulmonary blastoma initially misdiagnosed as spontaneous pneumothorax. Following tube thoracostomy drainage of the pneumothorax, the child underwent surgical closure of the ventricular septal defect. However, the postoperative period was complicated by recurrent left pleural collection requiring prolonged intercostal tube drainage and two thoracotomies to evacuate the necrotic pleural material. The biopsy of the necrotic material was suggestive of type III pleuropulmonary blastoma. In view of the high propensity of metastasis associated with this variant of a tumor, the patient was started on chemotherapy. This case report highlights the possibility of pleuropulmonary blastoma presenting as pneumothorax and emphasizes the need to consider the etiology, before intervening in a child presenting with spontaneous pneumothorax.

Bivalirudin anticoagulation in neonates and infants undergoing cardiac surgery.

OBJECTIVES: To determine the dosage of bivalirudin as the anticoagulant for cardiac surgery in neonates and infants. DESIGN: Pilot study. SETTING: Tertiary-care hospital. PARTICIPANTS: Twenty-five neonates and infants with congenital heart disease (CHD) undergoing cardiac surgery. INTERVENTIONS: The children received a 1 mg/kg bivalirudin bolus followed by a 2.5 mg/kg/h infusion as the anticoagulant for cardiac surgery. The dose was adjusted subsequently to maintain an activated clotting time (ACT) >480 s. MEASUREMENTS AND MAIN RESULTS: The mean age and weight were 5.3 months and 5.2 kg, respectively. Out of the 25 children, 16 were cyanotic. Baseline rotational thromboelastometry (ROTEM) (Tem Innovations GmbH, Munich, Germany) analysis revealed an underlying coagulation defect across EXTEM, INTEM, FIBTEM, and ADPTEM parameters. The dose of anticoagulant required was 1 mg/kg, followed by a 2.2 ± 0.4 mg/kg/h infusion. Only 1 child required an additional bolus dose. The ACT remained elevated for 4 hours after discontinuation of infusion. The mean 24-h postoperative chest tube drainage was 92 ± 36 mL. Excessive bleeding occurred in 4 children, 1 of whom required re-exploration. The platelet count remained low for 5 days, and, postoperatively, the prothrombin time and activated partial thromboplastin time remained low for 2 days. CONCLUSIONS: Effective anticoagulation was achieved with bivalirudin in the neonates and infants undergoing cardiac surgery. The dose required to maintain an ACT >480 s was 1.0 mg/kg, followed by 2.2 ± 0.4 mg/kg/h. The ACT remained elevated for 4 h after the discontinuation of bivalirudin infusion, resulting in an increased chest-tube output in some patients. Randomized, controlled trials are needed to further evaluate the safety of bivalirudin in the neonates and infants with complex congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass.

Ivabradine Versus Amiodarone in the Management of Postoperative Junctional Ectopic Tachycardia: A Randomized, Open-Label, Noninferiority Study.

OBJECTIVES: This study sought to compare the efficacy of ivabradine and amiodarone in the management of postoperative junctional ectopic tachycardia (JET) after cardiac surgery in children. BACKGROUND: JET is a serious arrhythmia occurring in children after cardiac surgery and requires aggressive management. Amiodarone has been conventionally used in its treatment. Recent studies have reported the utility of ivabradine in this regard. METHODS: In this open-label randomized controlled trial, 94 children (age ≤18 years) who developed postoperative JET were allocated to receive either amiodarone or ivabradine. The primary endpoint was restoration of normal sinus rhythm. RESULTS: Sinus rhythm was achieved in 43 out of the 46 patients (93.5%) in the amiodarone group and 46 out of the 48 patients (95.8%) in the ivabradine group (mean difference of treatment effect: 2.3%; 95% confidence interval: -6.7% to 11.5%). The median (interquartile range) time taken to achieve sinus rhythm conversion was similar in both the groups: 21.5 (17-30.2) hours versus 22 (13.4-38.5) hours (p = 0.36)]. The time taken to rate control of JET was significantly less in the amiodarone group: median 7.0 (5.5-9.5) hours versus 8.0 (5.8-10.8) hours (p = 0.02)]. No drug-related adverse events were observed in the ivabradine group. CONCLUSIONS: Oral ivabradine is not inferior to intravenous amiodarone in converting postoperative JET to sinus rhythm. There was no difference in time taken to sinus rhythm conversion between the groups, although the rate control was earlier in patients who received amiodarone. Monotherapy with ivabradine may be considered as an alternative to amiodarone in the management of postoperative JET. (Comparison of Two Drugs, Ivabradine and Amiodarone, in the Management of Junctional Ectopic Tachycardia, an Abnormality in Cardiac Rhythm in Patients Under 18 years Who Undergo Cardiac Surgery: CTRI/2018/08/015182).

Transesophageal Echocardiographic Estimation of Coronary Sinus Blood Flow for Predicting Favorable Postoperative Transit Time Coronary Graft Flow Measurements: A Pilot Study.

BACKGROUND: Augmentation of coronary artery flow by surgical grafting increases coronary sinus blood flow (CSBF), which can be quantified on transesophageal echocardiography (TEE). However, transit time flowmetry (TTF) technology remains the most used intraoperative technique for coronary artery graft assessment. The purpose of the present pilot study was to evaluate the predictive value of TEE-based CSBF estimation for identifying favorable TTF graft measurements. DESIGN: Prospective observational study. SETTING: Single university hospital. PATIENTS: Forty patients undergoing triple vessel coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS: CSBF was assessed on TEE examination before and after revascularization, estimating the percentage increase in CSBF (∆CSBF). Postoperative TTF graft measurements were averaged to compute mean diastolic filling (DF) and pulsatility index (PI). Subjects were grouped based on favorable (PI ≤ 3, DF ≥ 50%) and unfavorable (PI > 3, DF < 50%) parameters. The group with PI ≤ 3 (n = 32) had significantly higher ∆CSBF compared with the group with PI > 3 (n = 8) (38.22% ± 12.05%, 13.75% ± 3.37%, p < 0.001). ∆CSBF was higher in the DF ≥ 50% group (n = 35) (36.40 ± 12.99) in contrast to DF < 50% group (n = 5) (11.80 ± 2.59%). A strong negative and significantly positive correlation was observed between ∆CSBF with PI, DF (r = -0.903, 0.571, respectively, p < 0.001). A ∆CSBF ≥15.5% was found to predict a mean PI ≤ 3 and DF ≥ 50% with sensitivity and specificity of 100% and 62.5% for PI and 100% and 100% for DF. A ∆CSBF ≥19% demonstrated a sensitivity and specificity of 100% and 100%, 100% and 91.4% for prediction of PI ≤ 3 and DF ≥ 50%, respectively. CONCLUSION: TEE-based demonstration of an augmented CSBF can ensure favorable TTF graft parameters, guiding the adequacy of surgical revascularization.

Beneficial effects of fenofibrate in pulmonary hypertension in rats.

Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50 mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats. After 3 days of giving MCT, sildenafil (175 µg/kg, orally) and FF (120 mg/kg, orally) were given for 25 days. Echocardiography, hemodynamic parameters, fulton's index, histopathology, oxidative stress parameters, inflammatory markers, Bcl2/Bax gene expression ratio in the right ventricle, and protein expression for NOX-1 in lungs were studied in all the groups. FF has shown to prevent decrease in ratio of pulmonary artery acceleration time to ejection time, increase in ratio of right ventricular outflow tract dimension to aortic outflow dimension, rise in right ventricular systolic pressure, right ventricular hypertrophy, increase in the percentage medial wall thickness (%MWT), increase in oxidative stress and inflammation, increase in NADPH oxidase-1 (NOX-1) expression, and decrease in mRNA expression of Bcl2/Bax ratio caused by MCT. To conclude, FF prevented MCT-induced PH in rats by various mechanisms. It might be helpful in preventing PH in patients who are likely to develop PH.

Dual drainage total anomalous pulmonary venous connection: a rare mixed variant.

The mixed type of total anomalous pulmonary venous connection is the least common variant, occurring in approximately 5% of all patients. Dual drainage through a common venous confluence is much rarer. Computed tomography to delineate the exact pulmonary venous anatomy is a must in such cases. Correct preoperative recognition and intraoperative confirmation to check the drainage of all 4 pulmonary veins is essential in all cases of total anomalous pulmonary venous connection. We report the case of an adult patient with dual drainage to coronary sinus and left vertical vein to innominate vein.

Beneficial Effect of Ocimum sanctum (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

BACKGROUND: The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective. METHODS: Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue. RESULTS: OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT. CONCLUSION: The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil.

A Comparison of the Strain and Tissue Doppler-Based Indices as Echocardiographic Correlates of the Left Ventricular Filling Pressures.

OBJECTIVES: Diastolic strain and strain rate, combined with E (peak transmitral velocity), have been proposed as novel noninvasive predictors of left ventricle (LV) filling pressures, avoiding angulation errors inherent to tissue Doppler indices (TDI). The primary objective was to study the correlation of strain-based indices (SBI) and TDI with pulmonary artery catheter-derived LV end-diastolic pressures (LVEDP). The secondary aim was to determine appropriate cut-off of indices to predict LVEDP ≥15 mmHg. DESIGN: A prospective observational clinical study. SETTING: Single university hospital. PARTICIPANTS: One hundred twenty adults with preserved ejection fraction (EF) undergoing coronary artery bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-dimensional speckle-tracking echocardiography estimated global longitudinal diastolic strain (Ds) and strain rate (DSr) at peak mitral filling to compute E/Ds and E/10DSr. TDI was measured as the ratio of E and e' (mitral annular diastolic velocity). E/e', E/Ds, and E/10DSr were significantly higher (p < 0.001) in patients with LVEDP ≥15 mm Hg (31/120). Correlation of E/Ds, E/10DSr with LVEDP was R = 0.86 and 0.88 (p < 0.001), respectively, compared with a correlation of R = 0.63 (p < 0.001) for E/e'. SBI correlated well with LVEDP ≥15 mm Hg compared with TDI. E/Ds ≥11 and E/10DSr ≥12 had higher sensitivity and specificity (96.77%, 93.26%; 100%, 96.63%, respectively; area under the curve [AUC] = 0.99) than E/e'≥13 (74%,75%; AUC = 0.84) for prediction of LVEDP ≥15 mmHg. SBI accurately predicted elevated LVEDP in the indeterminate zone of 8

Is endothelin gene polymorphism associated with postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting?

BACKGROUND: The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of ß-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET-1) gene which is thought to have a pro-arrhythmogenic effect. AIM: This study aims to investigate the relationship between plasma ET-1 concentrations, ET-1 gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and occurrence of AF in patients undergoing CABG. METHODOLOGY: Ninety-eight nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG were selected for the present study. All patients were genotyped for three single nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using an ET immunoassay. RESULTS: Plasma ET-1 concentrations were higher in AF+ group (P = 0.001) as compared to AF- group. The allele frequencies between AF+ and AF- group were significantly different only with respect to the Lys198Asn (G/T) SNP of the ET-1 gene. CONCLUSION: The study described the possible correlation of polymorphism of ET gene in CABG population from India. The ET-1 gene might play a disease-modifying role in atrial fibrillation.

Does sleep quality affects the immediate clinical outcome in patients undergoing coronary artery bypass grafting: A clinico-biochemical correlation.

OBJECTIVE: Poor sleep quality is emerging as high prevalence among the patients suffering from cardiometabolic disturbances. The vascular polypeptide endothelin 1 (ET-1) is involved in many of the health disorders. However, its potential involvement in patients having poor sleep quality along with cardiovascular problem is limited. The present study was formulated to conduct a prospective analysis of the relationship between ET-1 and in hospital outcome in sleep disorder patients undergoing routine coronary artery bypass grafting (CABG). METHODS: A total of 156 patients were enrolled and divided into two groups based on the Pittsburg Sleep Quality Index (PSQI) of ≤5 (Group I, n = 101) or >5 (Group II, n = 55). Blood sample was collected before anesthesia induction (ET-1a) and at 48 h (ET-1b) to analyze the plasma ET-1 and blood sugar level. The patients were monitored for any intraoperative adverse events and postoperative complications during their hospital stay. RESULTS: Both groups were comparable in relation to age, sex, incidence of smoking and alcohol consumption. The distribution of comorbid conditions was also similar in both groups. The ET-1 level was higher in Group II than Group I before anesthesia induction as well as 48 h postoperatively (4.5 ± 1.75 vs. 10.61 ± 9.3, P = 0.001; 2.08 ± 1.3 vs. 8.3 ± 9.86, P = 0.0001, respectively). The Group II patients had a longer duration of mechanical ventilation (14.6 ± 12.05 vs. 10.1 ± 8.19, P = 0.001), Intensive Care Unit stay (2.08 ± 0.95 vs. 2.7 ± 1.45, P = 0016) and hospital stay (5.98 ± 1.73 vs. 7.8 ± 3.66, P = 0.0001, respectively). The high number of patients from Group II required inotrope and intra-aortic balloon pump support while compared with Group I (P ≤ 0.05 in each). The overall postoperative complication rate was significantly higher among patients with PSQI of >5 (Group II) except the rate of infection and neurological complications which was similar among both group of patients. The postoperative in hospital mortality was nil in Group I and 3.6% in Group II (P = 0.05). There was a strong relationship between PSQI and ET-1 at both the time points. CONCLUSION: Poor sleep quality associated with a higher incidence of adverse perioperative events in patients undergoing elective CABG. There exists a potential link between poor sleep quality and ET-1 in these groups of patients.

Goal-directed therapy improves the outcome of high-risk cardiac patients undergoing off-pump coronary artery bypass.

BACKGROUND: There has been a constant emphasis on developing management strategies to improve the outcome of high-risk cardiac patients undergoing surgical revascularization. The performance of coronary artery bypass surgery on an off-pump coronary artery bypass (OPCAB) avoids the risks associated with extra-corporeal circulation. The preliminary results of goal-directed therapy (GDT) for hemodynamic management of high-risk cardiac surgical patients are encouraging. The present study was conducted to study the outcome benefits with the combined use of GDT with OPCAB as compared to the conventional hemodynamic management. MATERIAL AND METHOD: Patients with the European System for Cardiac Operative Risk Evaluation ≥3 scheduled for OPCAB were randomly divided into two groups; the control and GDT groups. The GDT group included the monitoring and optimization of advanced parameters, including cardiac index (CI), systemic vascular resistance index, oxygen delivery index, stroke volume variation; continuous central venous oxygen saturation (ScVO 2 ), global end-diastolic volume, and extravascular lung water (EVLW), using FloTrac™ , PreSep™ , and EV-1000 ® monitoring panels, in addition to the conventional hemodynamic management in the control group. The hemodynamic parameters were continuously monitored for 48 h in Intensive Care Unit (ICU) and corrected according to GDT protocol. A total of 163 patients consented for the study. RESULT: Seventy-five patients were assigned to the GDT group and 88 patients were in the control group. In view of 9 exclusions from the GDT group and 12 exclusions from control group, 66 patients in the GDT group and 76 patients in control group completed the study. CONCLUSION: The length of stay in hospital (LOS-H) (7.42 ± 1.48 vs. 5.61 ± 1.11 days, P < 0.001) and ICU stay (4.2 ± 0.82 vs. 2.53 ± 0.56 days, P < 0.001) were significantly lower in the GDT group as compared to control group. The duration of inotropes (3.24 ± 0.73 vs. 2.89 ± 0.68 h, P = 0.005) was also significantly lower in the GDT group. The two groups did not differ in duration of ventilated hours, mortality, and other complications. The parameters such as ScVO 2 , CI, and EVLW had a strong negative and positive correlation with the LOS-H with r values of - 0.331, -0.319, and 0.798, respectively. The study elucidates the role of a goal-directed hemodynamic optimization for improved outcome in high-risk cardiac patients undergoing OPCAB.

Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH. AIM OF THE STUDY: The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated. MATERIALS AND METHODS: The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150-200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively. RESULTS: MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil. CONCLUSIONS: Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening.

Echocardiographic Predictors of Immediate Postoperative Outcomes in Patients With Severe Left Ventricular Systolic Dysfunction Undergoing On-Pump Coronary Artery Bypass Grafting.

OBJECTIVES: The postoperative course following on-pump coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) systolic dysfunction is often unpredictable. Therefore, the aim of this study was to identify predictors of poor postoperative outcome in this subset of patients. DESIGN: Prospective observational study SETTING: Single university hospital PARTICIPANTS: Forty patients with severe LV systolic dysfunction undergoing isolated on-pump CABG INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Comprehensive transesophageal echocardiographic examination was performed to obtain the indices of systolic and diastolic LV function after induction of anesthesia. A poor postoperative outcome was defined as patient death or vasoactive inotropic score≥20 for at least 6 hours and/or requiring intra-aortic balloon counterpulsation and/or mechanical ventilation for≥24 hours. Poor postoperative outcome was observed in 40% (16/40) of patients. Patients with poor postoperative outcomes had a significantly higher systolic dyssynchrony index, septal-lateral delay with a significantly lower global longitudinal strain and isovolumic acceleration, end-diastolic volume, end-systolic volume, and lateral and medial mitral annulus systolic velocity. In a binary logistic regression model, global longitudinal strain (odds ratio, 1.5, confidence interval [CI] 95%, 1.19-1.88, p = 0.001), septal-lateral delay (odds ratio, 1.02, 95% CI, 1.01-1.03; p = 0.001) and systolic dyssychrony index (odds ratio, 1.3, 95% CI, 1.13-1.48; p = 0.000) were found to be predictors of poor postoperative outcome. CONCLUSION: Global longitudinal strain, systolic dyssynchrony index, and septal-lateral delay were reliable and accurate predictors of adverse outcomes in patients with severe LV systolic dysfunction undergoing on-pump CABG.

Modified Blalock Taussig shunt: comparison between neonates, infants and older children.

OBJECTIVE: The aim was to compare various pre-and post-operative parameters and to identify the predictors of mortality in neonates, infants, and older children undergoing Modified Blalock Taussig shunt (MBTS). MATERIALS AND METHODS: Medical records of 134 children who underwent MBTS over a period of 2 years through thoracotomy were reviewed. Children were divided into three groups-neonates, infants, and older children. For analysis, various pre-and post-operative variables were recorded, including complications and mortality. RESULTS: The increase in PaO 2 and SaO 2 levels after surgery was similar and statistically significant in all the three groups. The requirement of adrenaline, duration of ventilation and mortality was significantly higher in neonates. The overall mortality and infant mortality was 4.5% and 8%, respectively. CONCLUSION: Neonates are at increased risk of complications and mortality compared with older children. Age (<30 days), weight (<3 kg), packed red blood cells transfusion >6 ml/kg, mechanical ventilation >24 h and post shunt increase in PaO 2 (P Diff) <25% of baseline PaO 2 are independent predictors of mortality in children undergoing MBTS.