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Biomedical subjects

S Muralidharan

Publications and source records attributed to S Muralidharan.

At least 19 recordsLinked to original sources
PubMed1996

Esmolol and percutaneous cardiopulmonary bypass enhance myocardial salvage during ischemia in a dog model.

Despite recent advances in techniques of reperfusion for acute myocardial ischemia, myocardial salvage remains suboptimal. Beta-blockers have been shown to limit infarct size during acute ischemia, but their negative inotropic properties have limited their use. Cardiopulmonary bypass is an attractive technique for cardiac resuscitation because it can stabilize a hemodynamically compromised patient and potentially reduce myocardial oxygen consumption. In an attempt to maximize myocardial salvage in the setting of acute ischemia, the combination of esmolol, an ultrashort-acting beta-blocker, with percutaneous cardiopulmonary bypass was evaluated. Four groups of instrumented dogs underwent 2 hours of myocardial ischemia induced by occlusion of the proximal left anterior descending coronary artery, followed by 1 hour of reperfusion. Throughout the period of ischemia and reperfusion, esmolol plus percutaneous cardiopulmonary bypass was compared with esmolol alone, percutaneous cardiopulmonary bypass alone, and control conditions. After the reperfusion period, the extent of infarction of the left ventricle at risk was determined. Four animals had intractable arrhythmias: one in the esmolol plus bypass group, one in the esmolol group, and two in the control group. The extent of infarction of the left ventricle at risk was significantly reduced in the esmolol plus bypass group (30%) compared with bypass alone (52%), with esmolol alone (54%), and with the control groups (59%; p < 0.05). We conclude that in this experimental model the combination of esmolol with bypass improves myocardial salvage after ischemia and reperfusion.

Adrenergic beta-Antagonists↗
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↗
PubMed1993

"Caged" phenylephrine: development and application to probe the mechanism of alpha-receptor-mediated vasoconstriction.

A "caged" analogue of the alpha-adrenergic receptor agonist phenylephrine (PE) was prepared by exploiting the 2-nitrobenzyl protecting group and using a synthetic procedure developed to permit preferential derivatization at the amino group. On isolated adult rat mesenteric arterioles, caged-PE had no measurable effects at concentrations up to 100 microM; 0.5-ms light flashes in the presence of caged-PE, however, produced marked and dose-dependent vasoconstriction. Flash-induced vasoconstrictions were blocked by the alpha-receptor antagonist phentolamine and were unaffected by the beta-receptor antagonist propranolol, indicating that the light-induced responses reflect the selective activation of alpha-adrenergic receptors. After a single flash, a large transient decrease in vessel diameter was recorded, and in most vessels, this was followed by a smaller, sustained constriction. The sustained component of the contraction was selectively eliminated when Ca2+ was removed from the bath, which suggests that different mechanisms underlie the transient and the sustained responses to PE. The responses to single flashes of varying intensities occurred with a mean latency of 460 ms, which is consistent with the intermediacy of several steps between alpha-receptor activation and contraction. We anticipate that it will be possible to extend this approach to develop caged analogues of other neurotransmitters for mechanistic and kinetic studies.

Animals↗
PubMed1993

Prophylactic procainamide for prevention of atrial fibrillation after coronary artery bypass grafting: a prospective, double-blind, randomized, placebo-controlled pilot study.

OBJECTIVE: To evaluate the effect of prophylactic procainamide on the frequency of postoperative atrial fibrillation in patients undergoing myocardial revascularization. DESIGN: Prospective, randomized, double-blind, placebo-controlled pilot study. SETTING: Surgical intensive care unit and wards at a university hospital affiliate. PATIENTS: A total of 46 patients undergoing myocardial revascularization. INTERVENTIONS: Twenty-two patients received procainamide (procainamide group) and 24 patients received placebo (control group). Procainamide was administered to the procainamide group within 1 hr of the patient's arrival in the intensive care unit and consisted of an intravenous loading dose (12 mg/kg) followed by a maintenance dose (2 mg/min) of procainamide. The control group received a similar volume of placebo. When the patient was able to take oral medication, the study drug was administered orally in a weight-adjusted dosage. MEASUREMENTS: Electrocardiograms (EKGs) were continuously monitored. Procainamide and N-acetyl procainamide serum concentrations were measured, and the dosages in the procainamide group were adjusted by an independent observer. The study drug was continued for 5 days or until an event occurred that resulted in dismissal from the study. MAIN RESULTS: The procainamide group and control group had similar preoperative demographic descriptors and operative variables, except for the mean left ventricular ejection fraction, which was lower in the control group than in the procainamide group (60% vs. 68%, p = .03 [Wilcoxon rank-sum test]). There were no hospital deaths. The number of episodes of postoperative atrial fibrillation was significantly reduced in the procainamide group (5 episodes in 129 patient days at risk [3.9%/day at risk]) compared with the control group (17 episodes in 161 patient days at risk [10.6%/day at risk], p = .04 [Fisher's exact test]). Complication rates were similar in both groups. CONCLUSIONS: In a pilot trial, prophylactic procainamide reduced the number of episodes of atrial fibrillation in patients after coronary artery bypass grafting. Procainamide also decreased the number of patients who experienced postoperative atrial fibrillation. However, due to the small sample size, this latter difference was not statistically significant. Further studies are needed to confirm this encouraging trend.

Aged↗
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↗