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Biomedical subjects

S Muralidharan

Publications and source records attributed to S Muralidharan.

At least 19 recordsLinked to original sources
PubMed1995

Photolabile "caged" adrenergic receptor agonists and related model compounds.

The synthesis and photochemical characterization of caged derivatives of the adrenergic receptor agonists phenylephrine, epinephrine and isoproterenol are described. These compounds were prepared using 2-nitrobenzyl or substituted 2-nitrobenzyl photolabile protecting groups, and were designed to allow agonist concentration jumps to be made during pharmacological/physiological experiments. The advantage of this approach over conventional methods for changing the concentrations of agonists near receptors in mechanistic studies is the exquisite spatial and temporal resolution afforded by the use of light. Flash photolysis experiments revealed that photorelease is more than two orders of magnitude faster when the 2-nitrobenzyl group is attached to the beta-amino group rather than one of the phenolic oxygens of the catecholamine. For the caged phenylephrine derivatives, for example, the rate constants of release from the N-linked and O-linked derivatives are 1.8 x 10(4) s-1 and 1.1 x 10(2) s-1 respectively. However, the quantum yields of photorelease from the N-linked and O-linked derivatives are similar. In addition, several model compounds were prepared to allow examination of the effects of substituents on the aromatic ring and benzylic carbon (of the 2-nitrobenzyl moiety) on the rates and efficiencies of photorelease. These studies revealed that, although substituents had little effect on the rates of photorelease from the N-linked caged derivatives, electron-donating groups on the 2-nitrobenzyl ring increased the quantum yield of release by approximately fourfold, from 0.10 to 0.40. A summary of the studies completed to evaluate the biological properties of the caged adrenergic receptor agonists is also presented.

Adrenergic Agonists↗
PubMed1992

Cryopreserved allograft veins as alternative coronary artery bypass conduits: early phase results.

Traditional autologous conduits are sometimes unavailable or unsuitable to permit total revascularization during coronary artery bypass grafting. In these patients the results of using nonautologous alternative conduits has been disappointing. Encouraged by the excellent long-term results seen with cryopreserved allograft valves, a clinical protocol was developed to evaluate the use of a commercially cryopreserved allograft saphenous vein (CPV). Our protocol consisted of using CPV when left internal mammary arteries and autologous saphenous vein grafts were unavailable or unsuitable for complete revascularization. Blood group (ABO) typed CPVs were thawed and implanted as required using standard surgical techniques. From December 1989 through June 1991, 19 of 1,602 patients who underwent coronary revascularization had CPVs implanted (1.2%). There were no operative deaths. An attempt was made to evaluate the patency of all grafts with coronary arteriography or ultrafast computed tomographic scans. Fourteen patients were available for patency evaluation. Patency rate in the 14 patients studied at a mean of 7 +/- 2 months (range, 2 to 16 months) were: internal mammary artery, 93% (14/15); saphenous vein graft, 80% (4/5); and CPV, 41% (7/17). The patency of the CPV was significantly less than the patency rate for the saphenous vein and internal mammary artery (p = 0.004). We conclude that the short-term patency rate of CPVs is inferior to that of autologous vessels. Due to its poor patency, we recommend that CPV should only be used when no other autologous conduit is available.

Aged↗
PubMed1992

Physical manipulation of subcutaneously implanted cardiac muscle in rat increased plasma atrial natriuretic peptide concentration.

UNLABELLED: To examine the effects of physical stretch on cardiac muscle endocrine activity, the authors transplanted whole neonatal hearts subcutaneously into the back and the ears of the correspondent mother (n = 9). Seven days later, physical manipulation was applied on the implanted heart by stretching the skin and the subcutaneous tissue encasing the implanted cardiac muscle, for a period of five to ten minutes. Such manipulation was repeated approximately every seven days postoperatively for a total of two to four times for each rat. The plasma atrial natriuretic peptide (ANP) levels were measured by radioimmunoassay prior to and immediately following manipulation. Postmanipulation plasma ANP levels were found to increase from the premanipulation levels. At two weeks postimplant, the average increase was 290% with the highest single-specimen increase being nearly twelvefold. The increases observed at two and three weeks following implantation had Signed Rank Test p values of 0.015 and 0.042 respectively. The viability of the implanted hearts was confirmed by cell culture. Light microscopic immunocytochemistry detected ANP immunoreactivity in the implanted cardiocytes. The elevated plasma ANP concentration induced by the manipulation appeared to be correlated with the functional status of the implanted cardiocytes. IN CONCLUSION: (1) Subcutaneously transplanted neonatal myocardiocytes survived for at least three to four weeks while retaining the ability to produce ANP. (2) Physical manipulation of implanted heart induced ANP release. Therefore, cardiac ANP production and release is indeed stimulated by physical stretching.

Animals↗
PubMed1992

Effect of adenosine triphosphate on the postischemic left ventricular function of the immature myocardium.

In this study, the effect of exogenous adenosine triphosphate (ATP) on the immature myocardium was evaluated. Isolated working neonatal rabbit hearts were perfused aerobically for 15 min with Krebs-Henseleit buffer (KHB) at 37 degrees C, and then arrested with St. Thomas solution (STS) in group 1 and STS containing 500 mumol/L of ATP in group 2 at 4 degrees to 6 degrees C and maintained at 10 degrees to 14 degrees C for 60 min. Hearts were reperfused with KHB aerobically at 37 degrees C for 15 min. Each heart served as its own control before and after arrest. Systolic function was significantly depressed in group 1 compared with group 2. There was a significant decrease in the peak left ventricular (LV) systolic pressure in group 1 (preischemia mean [PIM] 54 mm Hg to postischemia mean [PoIM] 42 mm Hg, Student's t test p = 0.007) than in group 2 (PIM 66 to PoIM 62 mm Hg, p = 0.5). The LV pulse pressure decreased in group 1 (PIM 72 to PoIM 54 mm Hg, p = 0.02) but not in group 2 (PIM 84 to PoIM 86 mm Hg, p = 0.9) and the rate of rise of LV pressure (dP/dT) in group 2 improved (PIM 5718 to PoIM 6926 mm Hg, p = 0.4) compared with group 1 (PIM 7021 to PoIM 4125 mm Hg, p = 0.008). The PoIM LV flow (LVF) was greater in group 2 than group 1 (LVF group 1 = 2.7 ml/min, group 2 = 4.5 ml/min). Diastolic pressures were not significantly different in the two groups. Our findings suggest that the incorporation of ATP in STS has a significant effect in improving postischemic LV systolic function in neonatal rabbit hearts.

Adenosine Triphosphate↗
PubMed1992

The experimental relationship between leaflet clearance and orientation of the St. Jude Medical valve in the mitral position.

The optimal orientation of the St. Jude Medical mechanical prosthesis in the mitral position has not yet been determined. While in the majority of cases the valve can perform satisfactorily regardless of valve orientation, certain circumstances can increase the risk of leaflet impingement. These valves are commonly implanted with their leaflets oriented parallel to the anatomic axis of the native leaflets (anatomic orientation) or with their prosthetic leaflets perpendicular to the axis of the native leaflets (antianatomic orientation). To determine the influence of valve orientation on the clearance from the prosthetic leaflet to the posterior ventricular wall, we calculated the clearances on all available models of the St. Jude Medical mitral valve. Clearances were computed from measurements of valve dimensions with use of an electronic caliper. In all cases the clearance in antianatomic orientation was at least 49.5% greater (mean 59%, range 49.5% to 77.5%) than in anatomic orientation.

Heart Valve Prosthesis↗
PubMed1991

A new biological membrane for pericardial closure.

In an attempt to develop a new and better biological membrane for the pericardium, we evaluated the use of glutaraldehyde treated human amniotic membrane (AM) and compared it to polytetraflouroethylene (PTFE) membrane as a pericardial substitute. Four dogs underwent a right thoracotomy. Two 4 x 3-cm portions of pericardium, 3-4 cm apart, were excised in each animal and both sites replaced with a similar sized patch of 0.8% glutaraldehyde-treated AM and 0.2-mm PTFE membrane respectively. The AM was sutured to the pericardial defect with its smooth surface facing the epicardium. After 18 weeks, the materials were evaluated. The AM patches revealed minimal extrapericardial and no epicardial adhesion. The PTFE patches had moderate to severe epicardial adhesions and severe extrapericardial adhesions. Histopathological examination of AM patches revealed that the integrity of the AM was preserved, however, neovascularization and slight lymphocytic infiltration were observed. In the PTFE patches, there were severe inflammatory infiltration and fibroblast proliferation into both surfaces. AM patches by virtue of their low immunogenicity evoke very minimal host to graft reaction. These AM grafts, however, tear easily unless carefully sutured. Improved methods of treatment may improve suturing strength. We conclude that AM performs satisfactorily and is superior to PTFE as a pericardial substitute.

Amnion↗
PubMed1991

Percutaneous transluminal subclavian angioplasty in a patient with postoperative angina.

Subclavian artery stenosis is a rare cause of angina in patients who have undergone coronary revascularization using the internal mammary artery. The traditional approach to this problem is surgical revascularization of the subclavian artery with a bypass graft. We report the successful treatment of a patient with this condition using percutaneous transluminal subclavian artery angioplasty, obviating an additional surgical procedure.

Aged↗
PubMed1991

Permanent transfemoral pacemaker insertion after repair of congenital heart disease.

In certain patients with anomalies of systemic venous connection, traditional transvenous pacemaker lead insertion may not be technically feasible. We report the use of the femoral venous approach to insert a permanent pacemaker in a patient with congenital heart disease who had undergone two previous cardiac operations and had persistent anomalies of the superior systemic venous circulation. We recommend that the femoral venous approach be considered in select patients requiring permanent pacing.

Adult↗
PubMed1991

Detection of endothelin-like immunoreactivity in epithelium and fibroblasts of the human umbilical cord.

We studied tissue sections of freshly obtained full-term and premature human umbilical cords using polyclonal antibody to endothelin and immunocytochemistry. Endothelin immunoreactivity was detected in the cytoplasm of epithelial cells and primitive fibroblasts, but not in the endothelial cells of both full-term and premature umbilical cords. Immunoelectron microscopy using indirect immunogold staining technique localized endothelin immunoreactivity to the cytoplasm of the epithelial cells and fibroblasts but not confined to any particular structures. No endothelin immunoreactivity was detected in the nucleus or on the cell membrane. Pre-absorption tests with synthetic endothelin-1, -2, and -3 independently established that the immunoreactivity represented endothelin-1 and -2, but not -3. The presence of endothelin-1 and -2-like immunoreactive materials in epithelial cells and fibroblasts of human umbilical cord suggests a role of endothelin in parturition.

Cytoplasm↗
PubMed1991

The cryopreserved stented pulmonary homograft valve in the tricuspid position.

This study was designed to evaluate the early phase events occurring in a stented pulmonary homograft valve implanted in the tricuspid position. A human pulmonary homograft was sterilized in antibiotic solution for 48 hours and cryopreserved in liquid nitrogen (-176 degrees C). Following thawing and trimming, the pulmonary valve was mounted on a Dacron cloth-covered Delrin stent and implanted into the tricuspid position in 3-month-old sheep, for a mean of 95 +/- 5 days. Seven animals were studied. Morphological assessment indicated good structural tissue preservation despite a decrease in viable fibroblasts noted in the distal part of the leaflets. The collagen fibers remained unchanged, and no tissue calcification was found. Viability of the mounted homograft was evaluated using an in vitro tissue culture method, and the viable cells underwent chromosomal analysis to identify whether they originated from the donor or host. Cells with 56 chromosomes, a number intrinsic to sheep cells, were cultured from the donor recipient junctional area. Hemodynamic and angiographic data, which were collected at the time of both implantation and explantation, revealed no functional deterioration of the implanted valve over 3 months. At the time of explantation, six of the seven valves were competent and no cusp retraction or thickening was noted. The seventh valve had deteriorated due to endocarditis. We conclude that stented cryopreserved pulmonary homografts may be useful as bioprostheses in the tricuspid position.

Animals↗
PubMed1991

Phrenic nerve injury. A prospective study.

In cardiac surgery, topical iced saline solution slush has become an important adjunct in maintaining myocardial hypothermia during cardioplegic arrest. One complication of this technique is phrenic nerve injury (PNI). In an attempt to reduce the incidence of PNI, a prospective study was undertaken to evaluate the impact of phrenic nerve insulation on PNI during cardiac surgery. Seventy-six consecutive patients who underwent coronary revascularization constituted the control group (CG) and were compared with 76 patients who underwent a similar procedure with the addition of phrenic nerve insulation. In the intervention group (IG), a foam insulation pad was placed between the heart and the pericardium in an effort to reduce exposure of the phrenic nerve to iced saline solution slush. There was no difference in major demographic descriptors or operative variables between the CG and the IG, except that the internal mammary artery was used more frequently in the IG (64 percent vs 36 percent, p = 0.0006). The in-hospital mortality was similar between the groups (CG, 0.0 percent; IG, 1.3 percent; p = 1.0); however, the incidence of roentgenographically diagnosed PNI was much greater in the CG (14/76 patients [18 percent] vs 0/76 patients [0 percent]; p = 0.0006). Patients with and without PNI were similar with regard to age, gender, aortic cross clamp time, cardiopulmonary bypass time, and number of grafts (p greater than 0.05). All unilateral PNI occurred on the left. Three patients with bilateral PNI required tracheostomy and prolonged mechanical ventilation. In-hospital mortality was similar for patients with and without PNI (0 percent vs 0.7 percent), but mean postoperative hospital stay for patients with clinically diagnosed PNI was longer than for those without PNI (32 vs 11 days, p = 0.04). This prospective study demonstrates that the incidence of PNI can be significantly reduced by the routine use of phrenic nerve insulation.

Adult↗
PubMed1991

Novel system for percutaneous cardiopulmonary bypass.

Percutaneous cardiopulmonary bypass (PCPB) has recently come to the forefront of medicine as a technique for resuscitating and supporting patients in various clinical situations. Current systems utilize small-diameter cannulas to aspirate blood under high suction into the cardiopulmonary bypass circuit. Aspiration-based systems have several disadvantages including risk of air embolism, blood hemolysis, and cavitation. Additionally, they are suboptimal for use during open-heart surgical procedures. A system with a venous cannula that employs gravity drainage has been evaluated. Once advanced into position over a guide-wire, the stylet is removed, causing the basket near the end of the cannula to expand. Blood flows into the cannula from side holes and the basket region, which prevents the vessel wall or atrium from collapsing around the catheter and impeding venous drainage. Hemodynamic, hematologic, and histologic examinations were performed on eight anesthetized mongrel dogs during 2 h of PCPB. All animals exhibited adequate tissue perfusion and right and left heart decompression. All animals were successfully weaned from PCPB and after 30 min exhibited normal myocardial function. No ischemic changes were observed in the heart, lung, kidney, or liver by light and electron microscopy. We conclude that full PCPB can be satisfactorily achieved by using a novel percutaneous venous cannula and gravity drainage.

Animals↗
PubMed1983

Results of surgical treatment of ventricular septal defects with pulmonary hypertension.

Two hundred and twenty-five consecutive patients with interventricular septal defect and associated pulmonary hypertension have undergone corrective surgery at the Christian Medical College Hospital. The mean preoperative systolic pulmonary artery pressure was 70.5 (range 31-136) mm Hg and the calculated pulmonary vascular resistance ranged from 300 to 1680 dyn/s cm-5. A paracoronary right ventriculotomy was the approach of choice. Profound hypothermia and circulatory arrest were not used, even in 12 patients weighing under 10 kg. Among the older children and young adolescents there were 27 who had a calculated pulmonary vascular resistance of over 800 dyn/s cm-1 and their mortality was 22%, which is good when compared with that of other series. It is evident that both the early and the late death rate after surgery increase with the age of the patient, especially in those with associated pulmonary hypertension. In 69 patients studied after repair recatheterisation showed no residual defect by oximetry. The fall in the pulmonary artery pressures after surgery has been striking in most patients. The late death rate was 2.5%. The surviving patients are leading normal, active lives.

Adolescent↗
PubMed1983

Closed mitral valvotomy: early results and long-term follow-up of 3724 consecutive patients.

Between 1956 and 1980 closed mitral valvotomies were performed in 3724 consecutive patients (male:female ratio 1.1:1) with mitral stenoses. Their ages ranged from 6 to 69 years, with a mean (SD) of 27.3 (9.3). Mitral stenosis in the younger age group is a unique condition and a great majority of these patients rapidly develop significant pulmonary hypertension and congestive cardiac failure. In this study a large number of subjects belonged to functional class IV (41.5%). Hospital mortality was 1.5% over the last 5 years. After valvotomy, 11 patients (0.3%) developed severe mitral regurgitation that made valve replacement necessary in the immediate postoperative period. Early postoperative embolism occurred in 0.4% of those who were in atrial fibrillation and had preoperative anticoagulation whereas it occurred in 0.95% of those in sinus rhythm who had no anticoagulation. Late postoperative embolism occurred at a rate of 0.3 to 1.6 per 1000 patients per year over a 20 year period. Rheumatic reactivity occurred at a rate of 1.3 to 2.2 per 1000 patients per year during the same period. Rate of occurrence of restenosis varied from 4.2 to 11.4 per 1000 patients per year between the fifth and fifteenth year of follow-up. Closed transventricular revalvotomy for restenosis was accomplished in 130 subjects with a 6.7% mortality. Excellent symptomatic improvement was evident in 86% of long-term survivors at the end of 15 years. Actuarial survival was 95%, 93.1%, 89.5%, and 84.2% at 6, 12, 18, and 24 years, respectively, after closed mitral valvotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1983

Mitral valve replacement in the young patient with rheumatic heart disease. Early and late results in 118 subjects.

During a 14 year period, 118 young patients between 9 and 20 years of age underwent mitral valve replacement. In view of the acknowledged advantage of durability and minimal thrombogenicity, we chose the Starr-Edwards valve prosthesis in the large majority of our subjects. Other prostheses have also been used. Hospital mortality has been only 3% in the past 5 years. Frail, severely incapacitated children and adolescents have had an impressive spurt in growth and weight and have returned to normal activities. Nine of the patients have had a normal pregnancy and have borne children. The remarkable clinical improvement has been corroborated by hemodynamic benefit. Follow-up over a period 1 to 15 years (mean 5.09 +/- 3.3) showed a very low incidence of embolic phenomena. In Third World countries, rheumatic heart disease continues to be a daunting challenge with pronounced disability resulting in death. Mitral valve replacement in the young subject with significant rheumatic valve disease should not be delayed until severe pulmonary vascular changes and myocardial damage pose a major deterrent.

Adolescent↗