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Biomedical subjects

Jai Raman

Publications and source records attributed to Jai Raman.

10 recordsLinked to original sources

Single-stranded DNA-binding proteins PURalpha and PURbeta bind to a purine-rich negative regulatory element of the alpha-myosin heavy chain gene and control transcriptional and translational regulation of the gene expression. Implications in the repression of alpha-myosin heavy chain during heart failure.

The alpha-myosin heavy chain is a principal molecule of the thick filament of the sarcomere, expressed primarily in cardiac myocytes. The mechanism for its cardiac-restricted expression is not yet fully understood. We previously identified a purine-rich negative regulatory (PNR) element in the first intron of the gene, which is essential for its cardiac-specific expression (Gupta, M., Zak, R., Libermann, T. A., and Gupta, M. P. (1998) Mol. Cell. Biol. 18, 7243-7258). In this study we cloned and characterized muscle and non-muscle factors that bind to this element. We show that two single-stranded DNA-binding proteins of the PUR family, PURalpha and PURbeta, which are derived from cardiac myocytes, bind to the plus strand of the PNR element. In functional assays, PURalpha and PURbeta repressed alpha-myosin heavy chain (alpha-MHC) gene expression in the presence of upstream regulatory sequences of the gene. However, from HeLa cells an Ets family of protein, Ets-related protein (ERP), binds to double-stranded PNR element. The ERP.PNR complex inhibited the activity of the basal transcription complex from homologous as well as heterologous promoters in a PNR position-independent manner, suggesting that ERP acts as a silencer of alpha-MHC gene expression in non-muscle cells. We also show that PUR proteins are capable of binding to alpha-MHC mRNA and attenuate its translational efficiency. Furthermore, we show robust expression of PUR proteins in failing hearts where alpha-MHC mRNA levels are suppressed. Together, these results reveal that (i) PUR proteins participate in transcriptional as well as translational regulation of alpha-MHC expression in cardiac myocytes and (ii) ERP may be involved in cardiac-restricted expression of the alpha-MHC gene by preventing its expression in non-muscle cells.

Animals↗

Norepinephrine for hypotensive vasodilatation after cardiac surgery: impact on renal function.

OBJECTIVES: Norepinephrine use in patients after cardiac surgery is controversial because of the fear that norepinephrine might decrease kidney function through regional vasoconstriction. Accordingly, we studied the renal effects of norepinephrine use for hypotensive vasodilatation after cardiac surgery. DESIGN AND SETTING: Retrospective controlled study in the cardiothoracic ICU of tertiary hospital. PATIENTS. 100 cardiac surgery patients with post-operative hypotensive vasodilatation and 100 control cardiac surgery patients. INTERVENTION: Treatment of hypotension (MAP<70 mmHg) with continuous norepinephrine infusion. MEASUREMENTS AND RESULTS: We collected data on demographic and surgical characteristics, haemodynamics, serum creatinine and mortality. Just after surgery the norepinephrine group had a significantly higher mean central venous pressure, lower mean arterial pressure, and lower systemic vascular resistance index with a similarly elevated mean cardiac index. Despite norepinephrine administration at a mean peak dose of 7.3+/-6.4 micro g/min the mean post-operative change in creatinine was not different between two groups on days 0, 2 or 4 after surgery. CONCLUSIONS: Norepinephrine does not increase post-operative serum creatinine concentrations in patients with hypotensive vasodilatation after cardiac surgery. Concerns related to its potential adverse effects on the kidney function in this setting appear unjustified.

Aged↗

Mitral regurgitation: comparison between edge-to-edge repair and valve replacement.

Mitral regurgitation due to bileaflet prolapse and ischemic causes can be difficult to repair. Midterm experience of the Alfieri edge-to-edge repair as an alternative to valve replacement is reported. Twenty-six patients with severe mitral regurgitation underwent the Alfieri repair between January 1998 and December 2000 (group 1); 15 cases were due to bileaflet prolapse and 7 were of ischemic origin. During the same period, valve replacement was performed in 36 patients (group 2), 20 of whom had similar indications. Follow-up was complete to a mean of 15 months (range, 1-28 months). There was no early death in either group. During follow-up, there was no reoperation in group 1, while 2 patients in group 2 required reoperations due to prosthetic valve endocarditis. There were 4 major thromboembolic or bleeding events in group 2, and none in group 1. All patients in group 1 had trivial to mild mitral regurgitation on follow-up echocardiography. The mean mitral valve gradient was significantly higher in group 2 compared to group 1 (7.2 versus 3.2 mm Hg, p = 0.001). The edge-to-edge repair is associated with good early and midterm results. Long-term follow-up is required to evaluate the durability of this technique.

Aged↗

Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation.

BACKGROUND: Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist, yet the specific relationship between these arrhythmias, and particularly whether sustained AFL leads to AF, is unknown. METHODS AND RESULTS: We investigated the electrophysiological consequences of chronic AFL using an ovine anatomic right atrial Y-lesion model. AFL was induced in 7 animals, and 4 remained in sinus rhythm (controls). Sheep were monitored for spontaneous conversion of AFL to AF. Six of 7 sheep sustained AFL for 28 days. In 1 of 7 sheep, spontaneous conversion of AFL to AF occurred on day 5. AFL produced a highly significant fall in right and left atrial refractoriness (AERP, P<0.001), with 74+/-10% of the reduction occurring by day 3. Right atrial conduction velocity also fell significantly (baseline 89+/-9 cm/s versus day 28 64+/-14 cm/s, P<0.001) but over a slower time course. AERP and conduction velocity changes coincided with a characteristic biphasic decrease and increase in the AFL cycle length. The excitable gap (percent of AFL cycle length) increased from 13+/-3% at baseline to 46+/-8% by day 28 (P<0.001). Sustained AF (>30 seconds) was not inducible at baseline but after 28 days of AFL could be induced in 6 of 6 sheep by critically timed single or multiple extrastimuli delivered either in sinus rhythm or AFL. There was no significant change in any parameter in control sheep. CONCLUSIONS: In this model, AFL produced electrical remodeling and the substrate for sustained AF. However, spontaneous conversion to AF was uncommon, and the development of AF was dependent on specific triggers.

Animals↗

Post radial artery harvest hand perception: postoperative 12-month follow-up results.

The 12-months' follow-up results for radial artery harvest in relation to complications are reported and compared with the postoperative 3-months' results. The postoperative wound problems of 155 patients who underwent coronary artery bypass grafting with radial artery harvesting were assessed using a questionnaire at 3 and 12 months after surgery. The questionnaire contained 9 statements concerning hand and forearm problems in daily life. The answers were graded in 7 levels. An answer of higher than grade 3 (mild symptoms) was regarded as a significant symptom. No hand ischemic complications was observed. In the 12 month-study, 152 patients (98.1%) were normal. Hand pain and numbness occurred in 25 patients (16.1 %) and 33 patients (21.3%), respectively, at 3 months and were markedly improved at 12 months (pain: 13 (8.4%), p = 0.045, numbness: 20 (12.9%), p = 0.069). Total scores for all questions also significantly decreased at 12 months (10.2 +/- 3.5) compared with 3 months (11.1 +/- 3.9) postoperatively (mean +/- SD, p = 0.0003). Radial artery harvest was quite acceptable from the patient's perception, although a few patients had numbness and pain in the 3 months after surgery. Those complications significantly improve in the later postoperative phase.

Coronary Artery Bypass↗

Post harvest wound infection and patient's perception: comparative study between radial artery and saphenous vein harvest sites.

INTRODUCTION: Despite renewed clinical interest in radial artery grafts (RA) for coronary artery bypass grafting, there is a paucity of controlled prospective data on its efficacy. We report on the rate of harvest related complications from a randomized radial artery study. METHODS: Two hundred eighty nine patients were divided into two groups. Group 1 received RA grafts (n=154 patients) and Group 2 (n=135 patients) received saphenous vein grafts (SVG). Postoperative wound problems were assessed using a questionnaire. Postoperative harvest site infections were also carefully documented. RESULTS: In group 1, 6 of 154 (3.9%) patients had harvest site wound infections. Five of them improved by antibiotic therapy alone. In group 2, 24 of 135 (17.8%) patients had harvest site wound infections (p=0.001 vs. group 1). Fifteen of these patients needed redressing due to discharge from the wound. One hundred forty-nine patients (96.7%) in group 1 answered that their hand function was normal on the questionnaire. Concerns and discomfort about the arm scars in the group 1 were of a similar value of 5.2% (8/154), respectively. In group 2, the incidence of those about the leg were 7.4% (10/135) and 11.9% (16/135), respectively. Although there was no significant difference in concerns about the scar, discomfort was significantly higher in group 2 compared with group 1 (p=0.0139). CONCLUSIONS: RA harvest is associated with fewer wound infections and scar discomfort than SVG harvest. Radial artery harvest is almost acceptable in terms of a patient's perception. However, there are still patients who have some symptoms in the forearm after RA harvest. Long-term follow-up is necessary for patient's hand function.

Aged↗

Avoiding the pump in tricuspid valve endocarditis--vegetectomy under inflow occlusion.

BACKGROUND: Surgical treatment of tricuspid valve endocarditis (TVE) ranges from vegetectomy to valve replacement with the use of cardiopulmonary bypass (CPB), accompanied by risks of systemic and lung complications. We present our experience with tricuspid valve vegetectomy under inflow occlusion without CPB. METHODS: Between July 1998 and July 2001, seven patients with a mean age of 26 years underwent tricuspid valve vegetectomy under vena caval inflow occlusion (VCIO). Five patients were intravenous drug users. None of them had left-sided heart valve involvement. The clinical indications for operating were recurrent septic pulmonary emboli with significant bilateral lung infiltrates and intractable infection with signs of severe systemic sepsis, despite treatment with appropriate intravenous antibiotics for a mean duration of 126 hours. The echocardiographic indication was very large localized >1 cm vegetations in all patients. Six patients had methicillin sensitive staphylococcus aureus and one had streptococcus viridans positive blood cultures. Five patients had postoperative high volume veno-venous hemofiltration (HVVF). RESULTS: There were no deaths. VCIO time did not exceed 2 minutes (range time was 45 seconds to 2 minutes). All patients had resolution of sepsis and improvement in respiratory status within 48 hours. Five patients had trivial and two moderate tricuspid regurgitation. Six patients were discharged home within 14 days with no long-term sequelae. One patient required long-term dialysis for renal failure. One patient required a late thoracotomy for drainage of a loculated empyema. CONCLUSIONS: Tricuspid valve vegetectomy can be performed safely under VCIO. HVVF promotes removal of inflammatory mediators, thus improving recovery.

Adolescent↗

Radial artery 2000--risk analysis of mortality for coronary bypass surgery with radial artery.

BACKGROUND: The aim of this study is to review our experience with using more than 2,000 RAs over the last seven years, and to assess the medium-term outcome in terms of morbidity and mortality. METHODS: Between June 1994 and June 2001, a total of 2,024 RAs have been used in 1,613 patients. The mean duration of follow-up was 40.1 months and ranged from one to 88 months. We assessed the results of postoperative mortality and morbidity, RA graft patency, coronary event free rate, and actuarial survival rate. Specifically, the independent predictors of early and late mortalities were examined. RESULTS: Perioperative myocardial infarction was indicated in 0.8%, stroke in 1.6%, respectively. Overall hospital mortality was 35 patients (2.4%). RA patency rate was 98.1%. Coronary event free rate and actuarial survival rates at seven years were 99.6% and 95.1%, respectively. Multivariate logistic regression analysis detected an ejection fraction of less than 30% (p=0.0009), re-exploration (p=0.02), and stroke (p=0.03) as significant independent predictors of operative mortality. The use of saphenous vein graft (p=0.0417) and renal impairment (p=0.0045) were significant independent predictors of late mortality. CONCLUSIONS: Our seven-year experience of CABG with RA suggested that the use of RA was safe and had excellent results in postoperative graft patency and low incidence of complications. This study suggested that the use of RA instead of the saphenous vein graft made a better outcome for late survival in the patients undergoing CABG.

Adult↗

Passive ventricular constraint.

Heart failure (HF) is a progressive degenerative and malignant syndrome with a large number of aetiologies including coronary artery disease, chronic hypertension, exposure to toxins, bacteria and viruses and in a significant percentage of HF patients, the causal mechanism is unclear. The HF trail of morbidity and mortality is well documented and is characterised by step-like periods of relative symptomatic stability, compensation, separated by decompensatory episodes. The homeostatic response to the decline in cardiac function is diverse and involves most organs. There is an increase in resting rate, intra-cardiac hormone production (catecholamines, aldosterone, etc.) and in particular structural changes occur with increased mass and dilatation (dilated cardiomyopathy, DCM). DCM is associated with decreased cardiac output, contractility and energy efficiency and an increase in pro-arrhythmia and conduction defects. Kass et al. (Circulation 91(9) (1995) 2314) first demonstrated in patients who had undergone a dynamic cardio-myoplasty procedure, that, preventing further dilatation in DCM was beneficial and that the improved cardiovascular status was largely independent of muscle stimulation. We hypothesised that this outcome could be achieved by implanting a fabric cardiac support device around both ventricles to the AV junction. Subsequently, it was shown by us and others (Kass et al., 1995) (Cardiovasc. Res. 44(3) (1999) 549); (Ann. Thorac. Surg. 70(4) (2000) 1275) (in different animal models of DCM) that passive ventricular constraint prevented further dilatation, initiated left ventricular volume reduction and reversed the decline in ejection fraction, mitral valve integrity and left ventricular contractility, when compared with untreated controls. Subsequent European and North American clinical trials in patients with DCM of varying aetiologies have shown equal promise and an absence of device related complications (Circulation 104(12 Suppl. 1) (2001) I270); (Ann. Thorac. Cardiovasc. Surg. 7(5) (2001) 278). The mechanisms behind this improvement have yet to be fully clarified however the support generated by the device upon the right and ventricular freewall would lower wall tension. Not only is passive ventricular constraint a very promising treatment modality for heart failure and DCM it should provide a useful research tool for the study of the role of ventricular dilatation in the progression of heart failure.

Animals↗