Biomedical subjects

V M Reddy

Publications and source records attributed to V M Reddy.

At least 109 records · Page 6Linked to original sources

PubMed1996

Altered endothelium-dependent responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

To investigate early endothelial function associated with increased pulmonary blood flow, vascular shunts were placed between the ascending aorta and main pulmonary artery in 18 late-gestation fetal sheep. Four weeks after delivery, the lambs were instrumented to measure vascular pressures and blood flows, and blood was collected to measure plasma concentrations of guanosine 3',5'-cyclic monophosphate [cGMP, the second messenger to nitric oxide (NO)-mediated vasodilation] and L-arginine (the precursor for NO synthesis). The responses to the endothelium-dependent vasodilators acetylcholine (ACh, 1.0 microgram/kg) and ATP (0.1 mg.kg-1.min-1), the endothelium-independent vasodilators M & B-22948 (a cGMP-specific phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled NO (40 ppm), and N omega-nitro-L-arginine (an inhibitor of NO synthase, 5 mg/kg) were then compared with responses in 12 age-matched controls. Vasodilator responses in control lambs were determined during pulmonary hypertension induced by U-46619 (a thromboxane A2 mimic). Shunted lambs displayed a selective impairment of endothelium-dependent pulmonary vasodilation, an augmented pulmonary vasoconstricting response to NO synthase inhibition, increased plasma cGMP concentrations, and decreased L-arginine concentrations. Taken together, these data suggest that lambs with pulmonary hypertension and increased pulmonary blood flow have early aberrations in endothelial function, as manifested by increased basal NO activity, that cannot be further increased by agonist-induced endothelium-dependent vasodilators.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1996

Fetal cardiac bypass using an in-line axial flow pump to minimize extracorporeal surface and avoid priming volume.

BACKGROUND: Progressive metabolic acidosis, hypoxia, and hypercarbia develop rapidly after fetal cardiac bypass mainly as a result of an increase in placental vascular resistance and a decrease in placental blood flow. A number of factors including fetal stress, priming substances, and extracorporeal surfaces have been identified as possible stimuli causing this placental dysfunction. The purpose of this study was to examine the effects of avoiding priming volume and minimizing extracorporeal surface area on placental hemodynamics and function. METHODS: Fetal sheep (n = 16) at 118 to 122 days of gestation were subjected to cardiac bypass for 30 minutes using either an in-line axial-flow pump (Hemopump group: n = 8, no prime) or a roller pump with a venous reservoir (control group: n = 8, priming volume = 150 mL). After bypass, the fetuses were observed for 90 minutes. Placental blood flow and combined ventricular output were continuously measured with ultrasonic flow probes, and fetal blood gases were measured at specific intervals. RESULTS: Three fetuses in the control group died during the study, whereas all 8 fetuses in the Hemopump group remained in stable condition throughout the study period. During and after bypass, placental blood flow was significantly higher (p < 0.0001) and placental vascular resistance was significantly lower (p < 0.0001) in the Hemopump group than in the control group. Arterial pH and partial pressure of arterial oxygen declined significantly less (p < 0.0001), and partial pressure of arterial carbon dioxide increased significantly less (p = 0.0002) in the Hemopump group than in the control group. CONCLUSIONS: Reducing the extracorporeal surface area and avoiding external priming substances preserves placental hemodynamics after fetal cardiac bypass. An in-line axial-flow pump is useful in miniaturizing the bypass circuits for potential use in fetal cardiac surgery.

Acidosis↗

PubMed1996

Homografts in congenital heart disease: current applications and future directions.

The first clinical use of homograft tissue in cardiovascular surgery was in 1948, when Gross used cadaveric arterial grafts to construct systemic to pulmonary artery shunts in patients with tetralogy of Fallot, and to repair coarctation of the aorta. Eighteen years later, a valved homograft was used for the first time in the treatment of congenital heart disease for reconstruction of the right ventricular outflow tract in a child with pulmonary atresia. Since these pioneering advances, valve and vascular homografts have become central to the management of congenital anomalies of the heart and great vessels. The primary use for homografts in congenital heart surgery today is establishment of a valved connection between the right ventricle and pulmonary arteries in children with tetralogy of Fallot with pulmonary atresia or other complicating factors, truncus arteriosus, transposition complexes, and double-outlet right ventricle, and in patients undergoing the Ross procedure. Homograft reconstruction of the left ventricular outflow tract has also been performed for many years in children with aortic insufficiency or recurrent aortic stenosis, but early homograft degeneration in young children has been a significant problem. Many surgeons are turning away from homografts in the systemic circulation in favor of the pulmonary autograft. Homograft is also widely used as a vascular patch material. In the present report, we discuss the various uses of homografts in congenital heart surgery, the benefits and drawbacks of homografts in young patients, and some of the future possibilities for homograft development and application in patients with congenital heart disease.

Adolescent↗

PubMed1996

The Ross procedure in children.

Although it has been almost 30 years since Ross described his technique for aortic valve replacement using the pulmonary autograft, only recently has there been widespread interest in the use of the Ross procedure for aortic valve replacement in children with congenital heart disease. Since July 1992 we have performed the Ross procedure in 46 patients, 40 of whom were < or = 18 years of age at the time of surgery. In 10 children the procedure was combined with Konno ventriculoplasty, and in 3 others a Ross-Konno procedure was used for biventricular repair of borderline hypoplastic left heart syndrome. The only early deaths were in two of the patients with borderline hypoplastic left heart syndrome. There has been no late mortality, and two patients have required reoperation: one for recurrent distal aortic arch obstruction, and one for moderate-severe autograft insufficiency. Freedom from reoperation at 30 months is 89%. Aside from one patient with moderate autograft insufficiency and eight with mild regurgitation, all patients have trace or no aortic insufficiency at follow-up ranging from 1 to 38 months (median 22 months). The Ross procedure is an important advance in the treatment of aortic valve disease in pediatric patients. It is the only available replacement for the aortic valve that has growth potential, and there is ample evidence that the pulmonary autograft holds up well in the systemic circulation.

Adolescent↗

PubMed1995

In utero placement of aortopulmonary shunts. A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs.

BACKGROUND: The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood. METHODS AND RESULTS: To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0-mm expanded polytetrafluoroethylene vascular graft in 11 late-gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary-to-systemic blood flow ratio of 2.2 +/- 1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial pressure (44.8 +/- 11.7 versus 16.2 +/- 2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased (P < .05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra-acinar arteries. CONCLUSIONS: In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with cogenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.

Animals↗

PubMed1995

Primary bidirectional superior cavopulmonary shunt in infants between 1 and 4 months of age.

The performance of a primary bidirectional superior cavopulmonary shunt procedure in early infancy is attractive because it minimizes the number of operations needed before a Fontan procedure, avoids ventricular volume overload and its sequelae, and eliminates pulmonary artery distortion. However, concerns over elevated or labile pulmonary vascular resistance have limited its use in the first few months of life. Nine patients aged 1 to 4 months (5 patients, < 2 months) have undergone a primary bidirectional superior cavopulmonary shunt procedure between October 1992 and March 1994. Primary diagnoses were tricuspid atresia (n = 4), asplenia syndrome (n = 2), polysplenia syndrome (n = 1), double-outlet right ventricle (n = 1), and double-inlet left ventricle (n = 1). Associated lesions of immediate surgical importance were total anomalous pulmonary veins (n = 2), a restrictive atrial septum (n = 4), bilateral superior venae cavae (n = 5), and patent ductus arteriosus (n = 5). The surgical procedure consisted of unilateral (n = 4) or bilateral (n = 5) bidirectional superior cavopulmonary shunt and the repair of associated lesions. Of significance, in 4 of our first 5 patients a very limited additional source of pulmonary blood flow was provided because of a low arterial oxygen tension immediately after cardiopulmonary bypass. Pleural effusions developed in 2 of these 4 patients. In subsequent patients cardiopulmonary bypass was not used whenever possible or, if it was needed, use of an extra source of pulmonary blood flow was avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1995

Extending the limits of the Ross procedure.

BACKGROUND: The potential for growth and the proven long-term durability of the native pulmonary valve make it ideal for replacement of the diseased aortic valve, especially in growing children. The use of the autologous pulmonary valve can be further extended to patients with complex left ventricular outflow tract obstruction and to neonates and infants. METHODS: Between June 1993 and May 1995, 35 patients underwent the Ross procedure at our center. Of these, 15 (43%) had complex left ventricular outflow tract obstruction and 7 (20%) were infants, including 3 neonates. The autologous pulmonary valve was implanted as a root replacement with coronary reimplantation in all patients. Additional left ventricular outflow tract procedures performed were ventricular myectomy in 7 patients and a Konno type aortoventriculoplasty in 11 patients. RESULTS: There was one early death in a patient with borderline hypoplastic left heart syndrome. At a median follow-up of 9 months (range, 0.2 to 22 months) there were no late deaths or reinterventions. The autologous pulmonary valve function was excellent, with 1 (2.8%) patient having moderate insufficiency. CONCLUSIONS: Autologous pulmonary valve is an excellent option for aortic valve replacement in all age groups. Its use can be readily extended to neonates, infants, and patients with complex left ventricular obstruction requiring additional left ventricular outflow tract procedures.

Adolescent↗

PubMed1995

Routine primary repair of tetralogy of Fallot in neonates and infants less than three months of age.

BACKGROUND: Although primary repair of tetralogy of Fallot is increasingly undertaken in infancy, complete repair is generally performed in only selected symptomatic neonates. METHODS: From July 1992 through March 1995, 30 consecutive neonates and young infants with tetralogy of Fallot underwent routine primary repair. Group I (n = 10) consisted of patients with tetralogy of Fallot and pulmonary atresia (n = 5) or severe pulmonary stenosis (n = 5) who were duct dependent and were repaired in the neonatal period. Group II (n = 11) consisted of patients who were asymptomatic with arterial oxygen saturation between 75% and 90% (adequate pulmonary blood flow). Group III (n = 9) consisted of patients with "pink" tetralogy of Fallot (arterial oxygen saturation > 90%). Patients in groups II and III were electively scheduled for repair at about 2 months of age. RESULTS: The postrepair peak systolic right ventricular-to-peak systolic left ventricular pressure ratio did not correlate (p = 0.96) with the branch pulmonary artery size. One patient died 2 months after operation, despite good hemodynamics, of uncontrollable diffuse subcutaneous edema due to familial distichiasis lymphedema syndrome. There were no late deaths. At a median follow-up of 19 months, 1 patient underwent balloon dilation of branch pulmonary arteries. Follow-up echocardiography revealed a 30 to 60 mm Hg right ventricle-to-pulmonary artery gradient in 3 patients. CONCLUSIONS: Excellent early and midterm results can be accomplished with routine primary repair of tetralogy of Fallot in early infancy regardless of age, symptomatic status, coronary anatomy, and the size of branch pulmonary arteries as long as they arborize normally.

Echocardiography↗

PubMed1995

Distribution of growth factors in subfoveal neovascular membranes in age-related macular degeneration and presumed ocular histoplasmosis syndrome.

PURPOSE: We performed a histopathologic and immunohistologic study to determine the macromolecular and cellular components of subfoveal neovascular membranes removed at the time of submacular surgery. METHODS: Subfoveal neovascular membranes were surgically removed from ten patients (seven with age-related macular degeneration and three with presumed ocular histoplasmosis syndrome). Tissues obtained were examined by light and electron microscopy to identify structural components. Immunohistochemical staining was then performed with monoclonal antibodies to various growth factors, including transforming growth factor-beta 1, basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor, as well as antibodies against procollagen 1 and phosphotyrosine residues. RESULTS: Most cells in subfoveal neovascular membranes are retinal pigment epithelial cells and cells resembling fibroblasts, with some vascular endothelial cells, lymphocytes, and macrophages. Basic fibroblasts growth factor was found in the extracellular matrix and in endothelial cells. Transforming growth factor-beta 1 was found in endothelial cells, fibroblasts, and retinal pigment epithelial cells. Procollagen 1 was found in protein-synthesizing fibroblasts, and phosphotyrosine residues were detected within fibroblasts, endothelial cells, and retinal pigment epithelial cells. CONCLUSIONS: Subfoveal neovascular membranes are neovascular complexes composed of retinal pigment epithelial cells, fibroblasts, vascular endothelial cells, and chronic inflammatory cells. Furthermore, transforming growth factor-beta 1 and basic fibroblast growth factor are present within the major cell types, which suggests a possible pathogenic role in the development of the neovascular complex.

Adult↗

PubMed1995

Quantitation of retinal ablation in proliferative diabetic retinopathy.

PURPOSE: We studied 294 eyes of 182 patients, to quantitate the amount of retinal ablation required for regression of proliferative diabetic retinopathy. METHODS: Eyes included in the study had two or more proliferative diabetic retinopathy risk factors, received panretinal photocoagulation, and had a minimum follow-up of one year. Laser photocoagulation or cryotherapy was given to eyes that failed to regress or had progression of retinopathy. Eyes treated by other physicians, treated with xenon arc photocoagulation, or undergoing laser treatment or vitrectomy for other retinal conditions were excluded. The total area of retina ablated was calculated and used as a quantitative measure of treatment. RESULTS: Regression was observed in 275 eyes (93%); 19 eyes (7%) failed to regress and eventually required vitrectomy. Panretinal photocoagulation alone successfully led to regression in 229 eyes (77%), whereas 46 eyes (15.6%) required both photocoagulation and peripheral anterior retinal cryotherapy. An average of 1.7 treatments per eye led to regression. Eyes were bimodally distributed by requirement for treatment, into low and high treatment groups. Low treatment eyes received an average of 510 mm2 of retinal ablation (2,600 500-microns burns), and high treatment eyes, 1,280 mm2 (6,500 500-microns burns). More extensive treatment was required with more retinopathy risk factors (P = .002 for four vs three risk factors and P = .0007 for four vs two risk factors); duration of diabetes mellitus longer than 15 years (P = .004), and onset of diabetes mellitus before 30 years of age (P = .0008). CONCLUSION: Patients with proliferative diabetic retinopathy should be treated aggressively with panretinal photocoagulation, cryotherapy, or both. The amount of initial treatment required for regression may be considerably more than that recommended by the Diabetic Retinopathy Study.

Adolescent↗

PubMed1995

Modified surgical techniques for relief of aortic obstruction in [S,L,L] hearts with rudimentary right ventricle and restrictive bulboventricular foramen.

Modified techniques of aortopulmonary anastomosis were performed in six neonates with atrioventricular and ventriculoarterial discordance [S,L,L], double-inlet left ventricle, and restrictive bulboventricular foramen area (mean index 1.10 cm2/m2) with unobstructed aortic arch (n = 3) or with hypoplasia (n = 2) or interruption (n = 1) of the aortic arch. In cases of unobstructed aortic arch, a flap of autogenous aortic tissue was used to augment the posterior aspect of the anastomosis of the main pulmonary artery to the ascending aorta, thus creating the potential for anastomotic growth; this technique is applicable regardless of the position of the ascending aorta relative to the main pulmonary artery. In case of levo-transposition of the aorta with hypoplasia or interruption of the aortic arch, a modified Norwood procedure was performed, in that the proximal ascending aorta was divided at the same level as the main pulmonary artery with subsequent homograft patch augmentation from the main pulmonary artery-ascending aorta anastomosis to the level of the proximal descending aorta; this technique avoids a spiraling incision of the aorta and therefore reduces the risk of torsion of the aortic root with its inherent risks of obstruction of the coronary circulation and aortic or pulmonary valve regurgitation. There was no early or late mortality. At a mean follow-up of 16 months, in all patients, there was unobstructed aortic outflow, as evidenced by echocardiographic absence of a significant ventricular-aortic systolic gradient (mean 4.5 +/- 4 mm Hg) and absence of distal aortic arch obstruction. There was no evidence of aortic or pulmonary valve regurgitation. The reported modified techniques provide effective relief of restrictive bulboventricular foramen and aortic obstruction in [S,L,L] hearts.

Anastomosis, Surgical↗

PubMed1995

Midline one-stage complete unifocalization and repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals.

Traditionally patients with pulmonary atresia, ventricular septal defect, diminutive or absent central pulmonary arteries, and multiple aortopulmonary collaterals have been managed by staged procedures necessitating multiple operations. We have taken a different approach to this lesion. Between August 1992 and March 1994, ten patients aged 1.43 months to 37.34 years (median 2.08 years) at the severe end of the morphologic spectrum of this lesion underwent a one-stage complete unifocalization and repair from a midline sternotomy approach. The median Nakata index of true pulmonary arteries was 50.0 (range 0 to 103.13) and they provided vascular supply to up to nine lung segments (median 5 segments). The number of collaterals per patient ranged from two to five with a median of four. The collaterals provided vascular supply to a median of 15 lung segments per patient (range 11 to 20). Complete unifocalization was achieved in all patients with emphasis on native tissue-to-tissue connections via anastomosis of collaterals to other collaterals and to the native pulmonary arteries. In only one patient (37.34 years old) was it necessary to use a non-native conduit for peripheral pulmonary artery reconstruction. The ventricular septal defect was left open in one patient (5 years old) because of diffuse distal hypoplasia and stenosis of the pulmonary arteries and the collaterals. The postrepair peak systolic right ventricular/left ventricular pressure ratio ranged from 0.31 to 0.58 (median 0.47). There were no early deaths. Complications were bleeding necessitating reexploration in one patient, phrenic nerve palsy in three patients, and severe bronchospasm in three patients. Follow-up (median 8 months, range 2 to 19 months) was complete in all patients. One patient was reoperated on for pseudoaneurysm of the central homograft conduit and then again for stenosis of the left lower lobe collateral. After this last operation at 13 months after the initial repair she died of a preventable cardiac arrest caused by pneumothorax. The patient with open ventricular septal defect underwent balloon dilation of the unifocalized pulmonary arteries, with a current pulmonary/systemic flow ratio of 1.4 to 1.8:1, and is awaiting ventricular septal defect closure. One other patient underwent balloon dilation of the reconstructed right pulmonary artery, with a good result. All survivors (9/10) are clinically doing well. This approach establishes normal cardiovascular physiology early in life, eliminates the need for multiple systemic-pulmonary artery shunts and use of prosthetic material, and minimizes the number of operations required.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1995

Human immunodeficiency virus and Mycobacterium avium complex coinfection of monocytoid cells results in reciprocal enhancement of multiplication.

Disseminated Mycobacterium avium complex (MAC) infection is an important opportunistic infection in AIDS patients. Because cells of macrophage lineage are targets for both human immunodeficiency virus (HIV) and MAC, the monocytoid cell line U937 was coinfected with both pathogens. Coinfected cultures had increased HIV replication (more than threefold at day 6) and an increased percentage of HIV-infected cells compared with cultures infected only with HIV. The kinetics of HIV replication were significantly increased in this coinfection system as measured by flow cytometry. When cells were infected concurrently, the rate of intracellular growth of MAC was not significantly affected. However, cells preinfected with HIV before infection with MAC showed significant enhancement of MAC growth compared with control cells. The kinetics of cell death were also increased in the coinfection system compared with singly infected controls. Thus, coinfection of monocytoid cells with HIV and MAC in vitro results in reciprocal enhancement of multiplication.

Cell Survival↗

PubMed1995

Enhancement of drug susceptibility of multi-drug resistant strains of Mycobacterium tuberculosis by ethambutol and dimethyl sulphoxide.

Strategies to augment conventional methods of drug delivery in treatment of multiple drug resistant tuberculosis are needed to achieve optimum results with available drugs. We have studied the effect of sub-minimum inhibitory concentrations (sub-MIC) of ethambutol and dimethyl sulphoxide on drug susceptibility of Mycobacterium tuberculosis strains both in vitro and in macrophages. At sub-MIC ethambutol between caused four and 64 fold increase in susceptibility to isoniazid rifampicin and streptomycin in four M. tuberculosis strains, resistant to these drugs. Incubation of the organisms with isoniazid and sub-MIC of dimethyl sulphoxide (2.5%) resulted in an eight-fold increase in susceptibility to the drug. Previous exposure of the organisms to sub-MIC of dimethyl sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC of sulphoxide also caused similar enhancement of susceptibility. Both ethambutol and dimethyl sulphoxide at the sub-MIC enhanced the activity of the anti-tuberculosis drugs against multiple drug resistant M. tuberculosis strains growing inside macrophages. Our data indicate that the agents which modify cell wall permeability can enhance the susceptibility of multiple drug resistant strains to drugs to which they were originally resistant. This could provide a new approach to treating drug resistant tuberculosis.

Cell Line↗

PubMed1995

Antimycobacterial activity of a new rifamycin derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (T9).

The antimycobacterial activities of a new rifampin (RIF) derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (To), against 20 susceptible and multidrug-resistant strains of Mycobacterium tuberculosis and 20 Mycobacterium avium complex (MAC) strains were investigated. The radiometric MICs of T9 for M. tuberculosis were significantly lower than those of RIF. The MICs of T9 and RIF at which 90% of the RIF-susceptible strains were inhibited were < or = 0.25 and < or = 0.5 micrograms/ml, respectively. Interestingly, T9 had lower MICs against some RIF-resistant M. tuberculosis strains. T9 had better activity against MAC strains, and the MIC at which 90% of the MAC strains were inhibited was < or = 0.125 micrograms/ml, and that of RIF was < or = 2.0 micrograms/ml. T9 also showed high in vitro bactericidal and intracellular activities which were significantly superior to those of RIF against both M. tuberculosis, and MAC strains. More importantly, T9 showed excellent in vivo activity against M. tuberculosis H37Rv compared with that of RIF in both the lungs and spleens of C57BL/6 mice, indicating the potential therapeutic value of T9 in the treatment of mycobacterial infections.

Animals↗

PubMed1995

Antituberculosis activity of clarithromycin.

Antituberculosis activity of clarithromycin (CLA), a macrolide antibiotic, was investigated in vitro, in macrophages, and in C57BL/6 mice, CLA showed high in vitro MICs (4 to > 16 micrograms/ml) for several strains of Mycobacterium tuberculosis and caused slight enhancement of activity of rifampin (RIF) against H37Rv but failed to increase the activity of either RIF or isoniazid (INH) against other strains. However, inside J774A.1 macrophages, CLA showed high activity and was synergistic with RIF against some strains of tubercle bacilli susceptible or resistant to INH and RIF. In the in vivo studies with a drug-susceptible strain (H37Rv), CLA protected mice from mortality due to tuberculosis for up to 8 weeks of observation. The CFU data for lungs and spleens revealed that the antituberculosis activity of CLA is inferior to those of INH and streptomycin. However, the activity of CLA when used alone or in combination was comparable to that of thiacetazone, indicating its potential usefulness as a secondary drug for the treatment of tuberculosis.

Animals↗

PubMed1995

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 pg/ml, P < 0.05). Pulmonary hypertension and increased pulmonary blood flow alters the response of ET-1 from pulmonary vasodilation to vasoconstriction. These altered responses suggest a role for ET-1 and its receptors in the pathogenesis of pulmonary hypertension secondary to increased pulmonary blood flow.

Animals↗

PubMed1995

Performance of right ventricle to pulmonary artery conduits after repair of truncus arteriosus: a comparison of Dacron-housed porcine valves and cryopreserved allografts.

Repair of complex congenital heart defects often requires the use of extracardiac conduits. These repairs can be technically accomplished with excellent early results. However, the long-term performance of various conduits is less than optimal. In this report, we examined the long-term outcome of xenograft valved Dacron conduits and cryopreserved allograft valved conduits used for reconstruction of the right ventricular outflow tract in young patients with truncus arteriosus. A retrospective review was performed on 222 patients who underwent primary surgical repair of truncus arteriosus between January 1975 and December 1994 using a xenograft valved synthetic conduit (group I; n = 175) or with a cryopreserved valved allograft conduit (group II; n = 47). Median age at repair was 121 days in group I and 70 days in group II; median weight of patients in both groups was the same (4.2 kg). Conduit-related early deaths occurred in 5.7% (10/175) of patients in group I and none in group II. In a cohort of age-matched patients, actuarial freedom from conduit-related reintervention at 5 years follow-up was significantly better (P = .037) for the cryopreserved valved allograft conduits when compared with xenograft valved synthetic conduits. However, this difference was not apparent by 7 years. Multivariate analysis showed conduit size (P = .0005) as a significant predictor of early conduit-related reintervention. This study shows that mid-term performance of cryopreserved allografts (which have the advantage of technical ease of insertion of availability of small sizes for use in neonates), is better than the xenograft Dacron conduits.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗