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Biomedical subjects

D R Clarke

Publications and source records attributed to D R Clarke.

At least 19 recordsLinked to original sources
PubMed2001

Reoperative homograft right ventricular outflow tract reconstruction.

BACKGROUND: Homografts are implanted in the right ventricular outflow tract (RVOT) of children, with the knowledge that reoperation might be required. We reviewed 14 years of homograft RVOT reconstruction to assess the feasibility of homograft replacement and to determine risk factors for homograft survival. METHODS: From February 1985 through March 1999, 223 children (age 5 days to 16.9 years) underwent primary RVOT reconstruction with an aortic or pulmonary homograft. Of these, 35 patients underwent homograft explant at the implanting hospital with insertion of a second homograft from 2 months to 13.3 years after the first implantation. The primary operation and reoperation patient groups were compared with regard to incidence of early death, late death, homograft-related intervention without explant, and homograft explant. RESULTS: Actuarial survival and event-free curves for initial and replacement homografts were not significantly different. Univariable analysis was performed for the following risk factors: weight (p < 0.0001), age (p < 0.003), homograft diameter (p < 0.0001), homograft type (p < 0.01), surgery date (not significant [NS]), gender (NS), Blood Group match (NS), and type of distal anastomosis (NS). Multivariable analysis of significant univariable risks revealed small homograft diameter to be a significant risk factor (p < 0.001) for replacement. CONCLUSIONS: The RVOT homografts eventually require replacement. Patient and homograft survival for replacement homografts is similar to primary homografts. Reoperative homograft RVOT reconstruction is possible, with reasonably low morbidity and mortality.

Adolescent↗
PubMed2001

Emergency pulmonary autograft mitral valve replacement in a child.

Mitral valve replacement in small children imposes significant clinical difficulties because of the relatively small mechanical prosthetic valves required and the need for lifelong anticoagulation therapy. A child weighing 10.4 kg presented with thrombosis of her 19-mm mechanical mitral prosthesis 4 weeks after implantation despite appropriate oral anticoagulation therapy. An emergency mitral valve replacement with a pulmonary autograft was successfully performed with encouraging short-term results.

Emergencies↗
PubMed2001

Transformation of nonvascular acellular tissue matrices into durable vascular conduits.

BACKGROUND: Prosthetic grafts commonly used for vascular reconstruction are limited to synthetics and cross-linked tissue grafts. Within these devices, graft infections are common, compliance mismatch is significant, and handling qualities are poor. Natural biological tissues that are unfixed have been shown to resist infections and be durable and compliant. A natural biological matrix that could be remodeled appropriately after implantation would be a desirable graft for vascular reconstruction. METHODS: SynerGraft tissue engineering strategies have been used to minimize antigenicity and produce stable unfixed vascular grafts from nonvascular bovine tissues. These grafts have replaced the abdominal aortas of 8 dogs that have been followed for up to 10 months. RESULTS: Early evaluation indicates rapid recellularization by recipient smooth muscle actin positive cells, which become arranged circumferentially, into the media. Arterioles were present in the adventitial areas and endothelial cells were seen to cover lumenal surfaces. After 10 months, grafts were patent and not aneurysmal. CONCLUSIONS: These data indicate that SynerGraft processing of animal tissues is capable of producing stable vascular conduits that exhibit long-term functionality in other species.

Animals↗
PubMed2001

Recellularization of heart valve grafts by a process of adaptive remodeling.

The objective of this study was to investigate if function and durability of connective tissue grafts stems from in vivo revascularization and recellularization. Viability is important for durable valve performance, demonstrated by pulmonary autografts. A pattern of in vivo recellularization occurs in xenogeneic or allogeneic heart valves decellularized prior to implantation, dictated by the tissue matrix and functional biomechanics. Porcine or sheep heart valves were decellularized with the SynerGraft antigen reduction process (a common treatment process to remove all histologically demonstrable leaflet cells), and implanted as pulmonary (n = 11) or aortic valve (n = 9) replacements in sheep. Sheep allograft pulmonary valves (n = 4) were implanted as pulmonary valve replacements. Recellularization was evaluated histologically after 3, 4, 5, 6, and 11 months, with cell phenotypes identified using specific antibodies. SynerGraft heart valves were progressively recellularized beginning with an initial cellular infiltrate, and subsequent repopulation with mature interstitial cells. This process occurs in the conduit and then in the leaflet, and is associated with revascularization of the graft. Functional, fully developed fibrocytes, actively synthesizing type I procollagen (antibody probe) were present within 3 months. As the process matured cell density and distribution became similar to native valve leaflets with localization of smooth muscle actin positive cells at the ventricularis/spongiosa interface. After 11 months, leaflet explants had no detectable inflammatory cells, were as much as 80% repopulated, and had a distribution of smooth muscle actin positive cells similar to that of the natural leaflet. SynerGraft- treated heart valve implants are repopulated by a process typical of adaptive remodeling following implantation. This antigen reduction treatment is the first successful tissue engineering effort obtaining an implant with mature recipient cells capable of matrix protein synthesis. Normal early valve function and durability is maintained.

Animals↗
PubMed2000

Transpecies heart valve transplant: advanced studies of a bioengineered xeno-autograft.

BACKGROUND: Tissue engineering approaches utilizing biomechanically suitable cell-conductive matrixes should extend xenograft heart valve performance, durability, and growth potential to an extent presently attained only by the pulmonary autograft. To test this hypothesis, we developed an acellular, unfixed porcine aortic valve-based construct. The performance of this valve has been evaluated in vitro under simulated aortic conditions, as a pulmonary valve replacement in sheep, and in aortic and pulmonary valve replacement in humans. METHODS: SynerGraft porcine heart valves (CryoLife Inc, Kennesaw, GA) were constructed from porcine noncoronary aortic valve cusp units consisting of aorta, noncoronary aortic leaflet, and attached anterior mitral leaflet (AML). After treatment to remove all histologically demonstrable leaflet cells and substantially reduce porcine cell-related immunoreactivity, three valve cusps were matched and sewn to form a symmetrical root utilizing the AML remnants as the inflow conduit. SynerGraft valves were evaluated by in vitro hydrodynamics, and by in vivo implants in the right ventricular outflow tract of weanling sheep for up to 336 days. Cryopreserved allograft valves served as control valves in both in vitro and in vivo evaluations. Valves were also implanted as aortic valve replacements in humans. RESULTS: In vitro pulsatile flow testing of the SynerGraft porcine valves demonstrated excellent valve function with large effective orifice areas and low gradients equivalent to a normal human aortic valve. Implants in sheep right ventricular outflow tracts showed stable leaflets with up to 80% of matrix recellularization with host fibroblasts and/or myofibroblasts, and with no leaflet calcification over 150 days, and minimal deposition at 336 days. Echocardiography studies showed normal hemodynamic performance during the implantation period. The human implants have proven functional for over 9 months. CONCLUSIONS: A unique heart valve construct has been engineered to achieve the equivalent of an autograft. Short-term durability of these novel implants demonstrates for the first time the possibility of an engineered autograft.

Animals↗
PubMed1998

Infant heart transplantation: improved intermediate results.

OBJECTIVES: Our objectives were to (1) review our experience with heart transplants in infants (age < 6 months), (2) delineate risk factors for 30-day mortality, and (3) compare outcomes between our early and recent experience. METHODS: Records of all infants listed for transplantation in our center before September 1996 were analyzed. Early and recent comparisons were made between chronologic halves of the accrual period. Univariate analysis was used to analyze potential risk factors for 30-day mortality (categorical variables, Fisher's exact test; continuous variables, nonparametric Wilcoxon rank-sum test). Multivariable analysis included univariate variables with p values < or = 0.10. Actuarial survivals were estimated (Kaplan-Meier) and compared by the log-rank test. RESULTS: Fifty-one of the 60 infants listed for transplantation were operated on (waiting list mortality 15%). Thirty-day mortality was 18% overall, 30% in the first 3 years and 10% in the last 3 years (p = 0.07). Sepsis was the commonest cause of early death (4/9). Univariate analysis suggested four potential risk factors for early death: preoperative mechanical ventilation (p = 0.01), prior sternotomy (p = 0.002), preoperative inotropic drugs (p = 0.08), and warm ischemia time (p = 0.08). Multivariable analysis indicated that prior sternotomy (p = 0.01) was an independent risk factor for 30-day mortality. Actuarial survivals were 80%, 78%, and 70% at 1, 2, and 3 years, and these figures improved between early and recent groups (p = 0.05). Late deaths were most commonly due to acute rejection (3/5). CONCLUSIONS: Results of heart transplantation in infancy improve with experience. Prior sternotomy increases initial risk. Intermediate-term survival for infants with end-stage heart disease is excellent.

Case-Control Studies↗
PubMed1997

Modified ultrafiltration attenuates dilutional coagulopathy in pediatric open heart operations.

BACKGROUND: Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children. METHODS: Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration. RESULTS: Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% +/- 6% to 31% +/- 9%), fibrinogen (65 +/- 29 to 101 +/- 45 mg/dL), and total plasma proteins (2.7 +/- 0.3 to 4.9 +/- 0.7 g/dL), but no change (p = 0.129) in platelet count. CONCLUSIONS: We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.

Blood Coagulation Disorders↗
PubMed1997

Mechanical and chemical consequences of the residual stresses in plasma sprayed hydroxyapatite coatings.

The residual stresses in thick hydroxyapatite coatings, deposited by plasma spraying, have been determined experimentally using Raman piezo-spectroscopy. The stress dependence of the centre position of the 980 cm 1 Raman band, owing to the symmetric stretching of the phosphate ion, PO3(4), has been established and found to be 2.47 cm 3 GPa 1. Using this calibration, the residual stresses in hydroxyapatite coatings deposited onto Ti-6A1-4V substrates in air have been found to be 100 MPa (tensile), whereas those deposited in a vacuum have been found to be 60 MPa (compressive). Although desirable from a mechanical point of view, it is shown that coating under residual compression are thermodynamically more stable and, hence, the dissolution of the ionic species, necessary in the exchange between bone and hydroxyapatite coating, can be impeded. It is calculated that for the coating under examination the stresses have an effect comparable with almost an order of magnitude change of the [OH] concentration. The analysis explains the dissolution behaviour of hydroxyapatite coatings subject to cyclic stress reported previously.

Biocompatible Materials↗
PubMed1996

LVOT pseudoaneurysm: a late complication of extended aortic root replacement.

The aortic allograft has become a valuable tool for repair of complex left ventricular outflow tract defects. These operations can be performed with low morbidity and mortality; however, complications do occur. In this report, we describe a pseudoaneurysm of the left ventricular outflow tract-homograft anastomosis that presented 3 years after extended aortic root replacement.

Aneurysm, False↗
PubMed1995

Adaptation of an ECMO team in the era of successful alternative therapies for neonatal pulmonary failure.

Neonates with persistent pulmonary hypertension show severe hypoxemia that requires a variety of therapeutic modalities. When patients do not respond to conventional medical management that includes hyperventilation, inotropic support, and vasodilating agents, treatment with extracorporeal membrane oxygenation (ECMO) may be used. More recently, high-frequency oscillatory ventilation and nitric oxide inhalation have been used in these infants and have impacted the need for ECMO. In light of these changes in therapy, the authors reviewed the 6-year clinical experience of an ECMO team to assess trends in patient population and outcome and document adaptation of the medical professionals to a new treatment era. Between 1988 and 1993, 88 neonates who met the institutional criteria were placed on venoarterial ECMO. Oscillatory ventilation was locally introduced in 1991 and nitric oxide treatment in 1992. Patient outcomes for the 1988 to 1990 period were compared with those for 1991 to 1993. Analyses included indication for ECMO therapy, length and complexity of the run, length of hospital stay, and cost of patient care. During the first 3 years, 65 patients were placed on ECMO, compared with 23 patients during the 3 years after introduction of oscillatory ventilation and nitric oxide therapy (P < .001). The length of ECMO therapy increased from a mean of 128 hours to 190 hours (P = .005), and the average hospital stay, likewise, increased from 27 days to 42 days. The total cost of care increased by approximately $40,000 per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗
PubMed1995

Ten year experience with pulmonary allografts in children.

Infants who have undergone pulmonary valve allograft reconstruction of the right ventricular outflow tract experience an increased incidence of allograft fibrocalcification and valvar insufficiency compared to older allograft recipients. Since April 1985, 186 cryopreserved pulmonary valve allografts have been used for right ventricular outflow tract reconstruction in pediatric patients at The Children's Hospital and the University of Colorado Health Sciences Center in Denver. One hundred and forty-six patients were one to 18.4 years of age (mean age: 5.0 years) and 40 children were younger than one year of age at operation (mean age: 4.4 months). In the older patient group, there were 15 hospital deaths (10%) and one child with dilated cardiomyopathy and cardiac failure underwent cardiac transplantation two days postoperatively. One hundred and thirty operative survivors have been followed clinically for a mean of 4.6 years. One child was lost to follow up and one patient with myocardial dysfunction required cardiac transplant 3.8 years postoperatively. There have been five late deaths (4%), one of which resulted from accidental trauma. Five children (4%) have undergone reoperation to replace their valve allograft at 1.3 to 9.8 years after the initial allograft procedure. In the infant group, there were nine hospital deaths (23%). During follow up averaging 3.0 years, there have been nine late deaths (29%) and five children (16%) have undergone valve allograft explant 2.0 months to 3.5 years following implantation. Allografts are technically desirable in small children for whom surgical repair alternatives are limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pulmonary arteriovenous malformation in the newborn: a familial case.

Pulmonary arteriovenous malformation (PAVM) is a rare cause of cyanosis in the newborn with nine previously reported cases. Typical signs at presentation include cyanosis, murmur, and congestive heart failure. Abnormality on chest x-ray is common with cardiomegaly, oligemia, and focal pulmonary density. There is a male predominance, unlike older children and adults with PAVM. Familial cases of PAVM have been reported with Osler-Weber-Rendu syndrome. We report a familial case of PAVM presenting in the newborn.

Arteriovenous Malformations↗
PubMed1993

Allograft degeneration in infant pulmonary valve allograft recipients.

Infants who have undergone pulmonary valve allograft reconstruction of their right ventricular outflow tract (RVOT), experience an increased incidence of allograft fibrocalcification and valvar insufficiency, compared to older children. Since 1985, 137 pediatric patients have received a cryopreserved pulmonary valve allograft to repair their RVOT. One hundred and five patients were 1 year of age or more and 32 were younger than 1 year at operation. In the former group, there were 11 hospital deaths (10%). Ninety-four operative survivors have been followed clinically for one month to 7.2 years (mean: 3.4 years). One patient required cardiac transplant secondary to myocardial dysfunction. There have been three late deaths (3%), and two children (2%) have undergone reoperation to replace the allograft. In the infant group, there were eight hospital deaths (25%). During 1 month to 6.8 years (mean: 2.2 years) of clinical follow up, there have been six late deaths (25%), and four children (22%) have required allograft explant. The most common indication for reoperation has been allograft fibrocalcification and valvar insufficiency. The relatively high incidence of early allograft failure in infants, which may have an immunologic etiology, has prompted consideration of nonviable allografts or low dose cyclosporine as alternatives when surgical reconstruction of the RVOT is required in children younger than 1 year of age.

Adolescent↗
PubMed1993

Conduit reconstruction of the right ventricular outflow tract. Lessons learned in a twelve-year experience.

From September 1979 to July 1991, a total of 163 patients have undergone valved conduit reconstruction of the right ventricular outflow tract when a right ventricle-pulmonary artery connection was absent or right ventricular outflow tract enlargement was required. From September 1979 through October 1984, 24 porcine valved conduits were implanted with an operative mortality of 38% (9/24). There were no early failures, but by 9 years after the operation 9 of 15 survivors (60%) had severe conduit obstruction, which resulted in death in 2 patients and reoperation in 6. From May 1985 to June 1991, 24 patients received cryopreserved aortic allografts to correct congenital anomalies. Operative mortality was 25% (6/24) and, again, early conduit function was good. There were 4 (22%) late deaths that were not related to the aortic allograft. At a mean follow-up of 3.4 years, 11 of the 13 survivors (85%) had allograft calcification and 8 of the 13 (62%) had mild to moderate conduit stenosis or regurgitation, or both; two of them required conduit replacement. Distal anastomotic problems that might have been avoided with bifurcated pulmonary allografts were apparent in 4 (36%) patients. Cryopreserved pulmonary allografts were placed in 115 patients between April 1985 and January 1991, with 18 (16%) operative deaths. Late deaths that were not allograft related occurred in 7 of 97 surviving patients (7%). Six patients (6%) underwent reoperation, 2 because of primary pulmonary allograft failure. The 84 remaining patients are free of symptoms with little or no allograft calcification or echocardiographic evidence of significant conduit stenosis or regurgitation. Experience with porcine valved conduits and aortic and pulmonary allografts suggests that pulmonary allografts are the conduit of choice for right ventricular outflow tract reconstruction.

Adolescent↗
PubMed1993

Degeneration of aortic valve allografts in young recipients.

Aortic allograft fibrocalcification and valvular insufficiency have been observed in patients less than 3 years of age at initial replacement of the left ventricular outflow tract. From June 1985 through May 1992, 47 children have undergone aortic root replacement with cryopreserved aortic valve allografts. Thirty-three children were 3 years of age or older and 14 were less than 3 years of age at operation. In the older patient group, there were three (9%) hospital deaths and one child underwent cardiac transplantation 30 hours after aortic root replacement because of left ventricular failure. Clinical follow-up of the 29 surviving older children is from 4 months to 6.6 years (mean 3.0 years). One patient was lost to follow-up. Two children (7%) have required reoperation, but primary allograft degeneration was not observed. In the younger patient group, there were three (21%) hospital deaths. Follow-up ranged from 2.5 months to 4.7 years (mean 2.3 years). Among 11 operative survivors, one late death resulted from a pulmonary embolus. Seven of 10 (70%) remaining allograft recipients had progressive allograft calcification or insufficiency. Six of them have required reoperation to explant the allograft, and one child is currently receiving cyclosporine therapy with the original valve allograft. The cause of allograft failure is possibly immunologic. The prevalence of early aortic valve allograft degeneration has prompted the consideration of nonviable allografts or xenografts, pulmonary autografts, or minimal immunosuppression as alternatives when left ventricular outflow tract reconstruction is necessary in children less than 3 years of age.

Adolescent↗
PubMed1992

Cryopreserved allograft repair of aortic hypoplasia and interrupted aortic arch.

Mortality for interruption of the aortic arch approaches 100% within the first year of life if untreated. Prostaglandin E1 can stabilize the patient's condition in anticipation of surgical palliation, but total repair is required for long-term survival. Successful complete repair of type B interrupted aortic arch, hypoplasia of the left ventricular outflow tract, and ventricular septal defect was possible using a cryopreserved allograft in a child who previously had undergone unusual palliation.

Aorta, Thoracic↗