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Biomedical subjects

A M Moran

Publications and source records attributed to A M Moran.

26 records · Page 2Linked to original sources
PubMed1999

Impaired glucose transporter activity in pressure-overload hypertrophy is an early indicator of progression to failure.

BACKGROUND: Severe hypertrophy and heart failure are important risk factors in cardiac surgery. Early adaptive changes in hypertrophy include increased ventricular mass-to-cavity volume ratio (M/V ratio) and increased dependence on glucose for energy metabolism. However, glucose uptake is decreased in the late stages of hypertrophy when ventricular dilatation and failure are present. We hypothesized that impaired glucose uptake would be evident early in the progression of hypertrophy and associated with the onset of ventricular dilatation. METHODS AND RESULTS: Ten-day-old rabbits underwent banding of the descending aorta. Development of hypertrophy was followed by transthoracic echocardiography to measure left ventricular M/V ratio. Glucose uptake rate, as determined by (31)P-nuclear magnetic resonance spectroscopy measuring 2-deoxyglucose conversion to 2-deoxyglucose-6-phosphate, was measured in isolated perfused hearts obtained from banded rabbits when M/V ratio had increased by 15% from baseline (compensated hypertrophy) and by 30% from baseline (early-decompensated hypertrophy). In age-matched control animals, the rate of glucose uptake was 0.61+/-0.08 micromol x g of wet weight(-1) x 30 min(-1) (mean+/-SEM). With a 15% M/V ratio increase, glucose uptake rate remained at control levels (0.6+/-0.05 micromol x g of wet weight(-1) x 30 min(-1)), compared with hearts with 30% increased M/V ratios, where glucose uptake was significantly lower (0.42+/-0.05 micromol x g of wet weight(-1) x 30 min(-1); P</=0.05). Glucose transporter protein expression was the same in all groups. CONCLUSIONS: Glucose uptake rate is maintained during compensated hypertrophy. However, coinciding with severe hypertrophy, preceding ventricular dilatation, and glucose transporter protein downregulation, glucose uptake is significantly decreased. Because of the increased dependence of the hypertrophied hearts on glucose use, we speculate that this impairment may be a contributing factor in the progression to failure.

Animals↗
PubMed1999

Valved homograft conduit repair of the right heart in early infancy.

BACKGROUND: Valved homograft conduit repair in neonates and young infants creates a physiologically normal biventricular circulation, and unlike shunts, avoids surgery on the branch pulmonary. METHODS: Retrospective chart review was used for 84 patients operated on between 1990 and 1995 (mean age 26+/-28 days, mean weight 3.3+/-0.8 kg) undergoing homograft conduit repair in the first 3 months of life. Cases were divided into simple and complex, eg, absent pulmonary valve syndrome or associated interrupted arch. Mean homograft size was 9.0+/-2 mm. RESULTS: Early mortality was 4.7% (simple) and 30% (complex). Mean hospital stay was 18 days. Mean follow-up was 34 months. Thirty-seven (47%) patients underwent conduit replacement. Median time to reoperation was 3.1 years. Mean size of replacement homograft was 17+/-2 mm. There were no deaths at reoperation. Mean hospital stay at conduit change was 6.3 days. Probability of survival at 5 years is 75%. CONCLUSIONS: Biventricular repair employing a conduit can be performed safely in noncomplex anomalies in the first 3 months of life. Time interval until repeat surgery is relatively short but equal or greater than that with most palliative procedures.

Bioprosthesis↗
PubMed1999

Tissue engineering of autologous aorta using a new biodegradable polymer.

BACKGROUND: Ovine pulmonary valve leaflets and pulmonary arteries have been tissue-engineered (TE) from autologous cells and biodegradable polyglycolic acid (PGA)-polyglactin copolymers. Use of this cell-polymer construct in the systemic circulation resulted in aneurysm formation. This study evaluates a TE vascular graft in the systemic circulation which is based on a new copolymer of PGA and polyhydroxyalkanoate (PHA). METHODS: Ovine carotid arteries were harvested, expanded in vitro, and seeded onto 7-mm diameter PHA-PGA tubular scaffolds. The autologous cell-polymer vascular constructs were used to replace 3-4 cm abdominal aortic segments in lambs (group TE, n = 7). In a control group (n = 4), aortic segments were replaced with acellular polymer tubes. Vascular patency was evaluated with echography. All control animals were sacrificed when the grafts became occluded. Animals in TE group were sacrificed at 10 days (n = 1), 3 (n = 3), and 5 months (n = 3). Explanted TE conduits were evaluated for collagen content, deoxyribonucleic acid (DNA) content, structural and ultrastructural examination, mechanical strength, and matrix metalloproteinase (MMP) activity. RESULTS: The 4 control conduits became occluded at 1, 2, 55, and 101 days. All TE grafts remained patent, and no aneurysms developed by the time of sacrifice. There was one mild stenosis at the anastomotic site after 5 months postoperatively. The percent collagen and DNA contents approached the native aorta over time (% collagen = 25.7%+/-3.4 [3 months] vs 99.6%+/-11.7 [5 months], p < 0.05; and % DNA = 30.8%+/-6.0 [3 months] vs 150.5%+/-16.9 [5 months], p < 0.05). Histology demonstrated elastic fibers in the medial layer and endothelial specific von Willebrand factor on the luminal surface. The mechanical strain-stress curve of the TE aorta approached that of the native vessel. A 66 kDa MMP-2 was found in the TE and native aorta but not in control group. CONCLUSIONS: Autologous aortic grafts with biological characteristics resembling the native aorta can be created using TE approach. This may allow the development of "live" vascular grafts.

Animals↗
PubMed1998

Glucose transporter upregulation improves ischemic tolerance in hypertrophied failing heart.

BACKGROUND: Achieving successful myocardial preservation of hypertrophied hearts remains a difficult problem. Despite reportedly higher glycolytic potential, we have achieved limited benefit in hypertrophied hearts with strategies that successfully promote anaerobic glycolysis and long-term ischemic preservation in nonhypertrophied models. We therefore tested the hypotheses that (l) glucose transport into myocytes is a critical limiting factor in hypertrophied heart and (2) stimulation of glucose transport with vanadyl sulfate would improve postischemic recovery. METHODS AND RESULTS: Left ventricular hypertrophy in rabbits was created by aortic banding of 7- to 10-day-old rabbits. At 4 weeks of age, 1 group of animals received oral vanadyl sulfate for 3 to 4 weeks. Glucose transport (measured by the conversion of 2-deoxyglucose to 2-deoxyglucose-6-phosphate; 31P-nuclear magnetic resonance), myocardial glucose transporter content (GLUT-1 and GLUT-4 by immunoblotting), and functional recovery from ischemia-reperfusion (isolated perfused Langendorff model) were measured. Myocardial glucose transport rate was significantly reduced in hypertrophied hearts without significant reductions in glucose transporter content; these hearts were significantly less tolerant of ischemia-reperfusion than age-matched controls. Vanadyl sulfate normalized glucose transport rate and improved tolerance to ischemia-reperfusion so that postischemic function equaled that seen in controls. Lactate production during ischemia, an indication of anaerobic glycolysis, was significantly higher in hearts from vanadate-treated animals. CONCLUSIONS: Despite reportedly higher glycolytic enzyme activities, maximal glucose transport appears to be reduced and is rate limiting in hypertrophied heart. Stimulation of membrane glucose transport with vanadyl sulfate significantly improved glycolytic flux and ischemic preservation in hypertrophied hearts.

Adaptation, Physiological↗
PubMed1998

Development of a double-chambered right ventricle after repair of tetralogy of Fallot.

OBJECTIVES: We sought to determine the frequency, etiology and progressive nature of midcavity obstruction in patients after primary repair of tetralogy of Fallot (TOF). BACKGROUND: Midcavity obstruction (double-chambered right ventricle [DCRV]) represents a significant portion of reoperations in patients who have had TOF repair. This group is still poorly defined. METHODS: A retrospective review of clinical, echocardiographic and catheterization data for all patients with TOF who later underwent reoperation for DCRV was performed. RESULTS: Between 1973 and 1995, 552 children <2 years of age underwent primary TOF repair (median age 6.7 months). Long-term follow-up (median 50 months) was available in 308 children. Of these, 17 children subsequently developed DCRV requiring reoperation. The median age at initial operation was 7.9 months. During a median follow-up interval of 43.2 months, murmur intensity increased in all patients, and the average subpulmonary gradient at catheterization increased from 24+/-10 to 80+/-27 mm Hg in seven children (p = 0.002) and at Doppler echocardiography from 14+/-16 to 89+/-18 mm Hg in five children (p = 0.002). Before reoperation, 6 of the 17 children were symptomatic. During the operation (median age 55.4 months), obstruction was relieved by incision of hypertrophied anomalous muscle bundles in all 17 patients, with prominent fibrosis noted in 8 patients. Excessive septal and parietal hypertrophy was noted in one child. No new transannular patches were required. Recurrent obstruction has reappeared in 3 of these 17 children during follow-up. CONCLUSIONS: DCRV is a medium-term complication of TOF repair in infants, with a minimal incidence of 3.1% (95% CI 1.8% to 4.9%). The condition is progressive and is due to anomalous muscle bundle hypertrophy or fibrosis, or both, which may represent displaced insertion of a moderator band. Further reobstruction does occur; continued careful follow-up is therefore essential.

Disease Progression↗
PubMed1998

Verapamil therapy in infants with hypertrophic cardiomyopathy.

We sought to evaluate the safety and efficacy of acute and chronic treatment with verapamil in infants with hypertrophic cardiomyopathy. Prior studies have shown an improvement in adults with hypertrophic cardiomyopathy who were treated with verapamil. Acutely, it reduced the degree of left ventricular outflow tract obstruction. Chronic therapy was associated with an improvement in symptoms and increased long-term survival. To date, no data are available on the efficacy of this drug in infants with hypertrophic cardiomyopathy. We evaluated prospectively the safety and efficacy of verapamil in infants. The acute and chronic effects of verapamil on infants with an echocardiographic diagnosis of hypertrophic cardiomyopathy were evaluated at a single institution between 1980 and 1994, with long-term follow-up available until 1996. Acute effects of an intravenous bolus of 0.1 mg/kg and infusion at 0.007 mg/kg/min were evaluated, where possible, in the cardiac catheterization laboratory. Oral verapamil at 3-5 mg/kg/day was started after catheterization. Follow-up included serial clinical, echocardiographic and Holter monitoring. A total of 22 patients were studied, 17 having a presumed diagnosis of primary hypertrophic cardiomyopathy including three with Noonan's syndrome. Acute infusion of the drug was well tolerated by all, without adverse electrophysiological effects. Haemodynamic effects were consistent with a negative inotropic action with significant falls in cardiac index (4.6+/-1.2 to 4.1+/-0.9 l/min/m2), systolic blood pressure (88+/-16 to 82+/-14 mmHg) and gradient across the left ventricular outflow tract (nine patients 48.2+/-30.4 to 28.4+/-24.1 mmHg). End-diastolic pressure was unchanged (14.0+/-6.8 to 13.9+/-4.7 mmHg). Three patients with primary hypertrophic cardiomyopathy died (two while being treated). In the group with primary hypertrophic cardiomyopathy continuing with long-term treatment, follow-up revealed regression in two, progression in three (two died) and stability in 10. For those treated, there was a trend towards improvement in clinical status. Verapamil is well tolerated acutely in infants with hypertrophic cardiomyopathy. The outcome was considerably better in these patients compared with prior reports, though careful long-term assessment is needed.

Administration, Oral↗
PubMed1995

Intracranial vascular malformations.

Intracranial vascular malformations are nonneoplastic developmental anomalies that present a variety of clinical patterns, ranging from asymptomatic to fatal intracranial hemorrhage. A practicing radiologist can expect to encounter these abnormalities, which include capillary telangiectasias, venous angiomas (also called developmental venous anomalies), cavernous angiomas, and arteriovenous malformations. The imaging findings that characterize these lesions are reviewed in this article, along with their pathological and clinical features.

Brain↗