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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

At least 163 records · Page 9Linked to original sources

Coarctation of the aorta in infants and children: 25 years of experience.

Repair of coarctation of the aorta was performed in 334 patients ranging from less than a year to 16 years of age at Children's Hospital of Pittsburgh from 1953 to 1977. Resection and end-to-end anastomosis were performed in 310, interposition grafts in 7, and other procedures in 17. There were 41 operative deaths among the 95 infants less than 1 year old (43% mortality); all of these infants had associated cardiac anomalies. Only 1 operative death occurred in patients older than a year (0.4% mortality). No hospital deaths occurred in patients with isolated coarctation of the aorta. Eleven late deaths were due to associated anomalies (7) and unrelated or unknown causes (4). Postoperatively, hemorrhage occurred in 7, paradoxical or persistent hypertension in 128, postcoarctectomy syndrome in 32, neurological problems in 14, pulmonary complications in 53, and infections in 12 patients. Restenosis occurred in 26 patients (8%); only 10 have required reoperation. Residual hypertension was present in 28 of 264 patients (11%). Mortality from coarctation resection remains high in infants, but is minimal in children older than 1 year. Based on minimizing the risk of restenosis and residual hypertension, elective repair of coarctation is recommended when the patient is about 6 years of age.

Adolescent↗

Role of longitudinal diffusion in the extravascular pulmonary space on parameter estimates derived from data of multiple indicator dilution.

A mathematical model of transcapillary exchange has been developed that considers in detail the role of axial diffusion in the extravascular tissue region on estimates of such physiological parameters as lung water (VE) and pulmonary capillary permeability-surface area products (PS), obtained from multiple indicator dilution studies. The experimental cases considered correspond to two animal models of pulmonary oedema in which the integrity of the pulmonary capillary membrane is disrupted and the effects of extravascular axial diffusion may be important. A novel feature of the computational scheme is the use of an Array Processor in the solution of the governing equations, initial and boundary conditions. Computer time is reduced to 2-3 min for parameter identification, thereby allowing a wide range of values for extravascular axial diffusion coefficients (D'/L2) to be studied at little computational expense. The results indicate that diffusion in the extravascular region does not influence parameter estimates for PS to urea. A statistical correlation is suggested between values for VE, PS to water, and D'/L2.

Animals↗

Cardiac transplantation with cyclosporin A and prednisone.

Influenced by continuing improvement in results from Stanford, cardiac transplantation was resumed at the University Health Center of Pittsburgh in June 1980. Cyclosporin A (CyA) became available to the authors early in 1981. This report describes the preliminary experience with 21 patients who were treated between March 1981 and April 10, 1982 with cyclosporin A and low-dose steroids. Age ranged from eight to 53 years, median 46 years. Median age of ten patients disabled because of idiopathic myocardiopathy was 33 years; it was 45 years in the 11 suffering from ischemic heart disease. Sixteen of the 21 patients survived. Eleven have survived for three months, if which six have survived for six months, giving a cumulative survival of 74 and 66%, respectively. Four died perioperatively; one died at six weeks and one at four months. Hyperacute rejection resulted in one death at 12 hours even though the warm and cold lymphocytotoxic crossmatch for T and B cells was negative as evaluated by trypan blue. The two late deaths were related to infection. No late death has occurred because of rejection, and a unique feature is that three recipients with a lymphocytotoxic mismatch did not develop hyperacute rejection. The number of infectious episodes and nonviral infections appears to be less than that associated with the use of azathiaprine and larger doses of steroids. Cyclosporin A (5-10 mg/kg/d) and low-dose prednisone (rapidly tapered in seven days from 200 mg to 15-20 mg/d) is effective in preventing early morbid rejection of the transplanted heart.

Adolescent↗

Protein adsorption in vitro onto biomaterial surfaces covered with ULTI carbon.

A study is presented which describes the adsorption in vitro of albumin and fibrinogen onto a mini-shunt oxygenation unit. The unit is characterized by flow through 10 etched microchannel conduits with a microporous membrane and conduits are pretreated with a uniform layer of ULTI carbon and evaluated for the steady-state and time varying kinetics of protein adsorption. Corresponding results for oxygenator components not pretreated with ULTI carbon are also included.

Adsorption↗

Pulmonary valvulotomy alone for pulmonary stenosis: results in children with and without muscular infundibular hypertrophy.

Pulmonary valvulotomy for valvular pulmonic stenosis has been performed in 78 children at the Children's Hospital of Pittsburgh. Although 27 patients had muscular hypertrophy of the infundibulum, a muscle resection was employed in only one child. Examinations 2 to 18 years after operation have not demonstrated electrocardiographic (ECG) or clinical evidence of persistent right ventricular hypertension, indicating resolution of the muscular outflow tract narrowing. Systolic right ventricular pressure averaged 30 mm Hg in 10 patients at postoperative catheterization: Six of these patients had peak right ventricular pressures greater than 100 mm Hg immediately after valvulotomy. The diameter of the infundibulum in systole was compared to valve ring diameter and expressed as a ratio (I/V). This correlated with the preoperative and intraoperative right ventricular pressures, but did not identify patients who might fail to resolve secondary muscular hypertrophy. A murmur of pulmonary regurgitation was present in 70% of the patients after operation, but was without clinical significance. In the absence of fixed infundibular obstruction or excessive right ventricular hypertension above 200 mm Hg, resection of infundibular hypertrophy is not recommended.

Adolescent↗

Numerical simulation of the transient transport of inert gases in lung tissue.

A numerical simulation of the transport of xenon gas into healthy and oedematous lung tissue is described. The lung is modelled as four parallel tissue layers; alveolar membrane, interstitial fluid, capillary membrane, and blood, surrounded by a uniform air space. Using a finite difference representation of the governing diffusion equations, the concentration distribution of Xe gas in each of the layers of tissue is obtained for a step change in the Xe concentration in the air space. The effect of a thickening of the interstitial fluid layer, found in pulmonary oedema, on the kinetics of Xe transport is also considered. Computational findings indicate that a good approximation to the steady state profiles for Xe in the layers of tissue can be obtained simply by assuming that instantaneous equilibrium exists (as described by Henry's Law) between the lung tissue and surrounding air space. This same finding is documented even when the thickness of the interstitial fluid layer is increased by a factor of 40 above baseline values. The results suggest that the reduction in gas exchange which occurs in pulmonary oedema is caused by fluid flow into the alveoli, rather than a true diffusion deficit caused by a thicker alveolar-capillary barrier. The relationship of the present findings to those which would be obtained for more physiological input functions of Xe gas into the air space in also discussed.

Biological Transport↗

Towards an evaluation of the accuracy of ventilatory rate constants derived from dynamic computer-assisted tomographic measurements.

Dynamic computer-assisted tomographic (CT) measurements using non-radioactive xenon gas have recently been employed along with a simple model of pulmonary transport to derive ventilation rate constants (K) in small tissue volumes. Inherent in the model description is the assumption that instantaneous diffusion equilibrium occurs between inhaled Xe gas and lung tissue. The validity of this assumption as it relates to the accuracy of the derived values of K has been considered for both normal and oedematous tissue, the latter characterised by a severe widening of the interstitial fluid space. It was found that only a small error in the predicted values for K results, when the simple model is applied to the dynamic cT measurements of xenon enhancement.

Models, Structural↗

Lead systems for internal ventricular fibrillation.

We examined the feasibility of using a standby automatic implantable defibrillator and established thresholds for internal defibrillation. The implantable defibrillator senses ventricular fibrillation and delivers an electrical impulse for defibrillation. Two lead systems for the device have been investigated. System I consists of two 12-cm2 silicone-covered titanium mesh patches attached to the atrial and diaphragmatic pericardial surfaces. System II has an identical diaphragmatic patch and a titanium spring catheter, with a 12-cm2 surface area of conductivity, placed transvenously in the right atrium. Both systems were implanted by thoracotomy in 12 dogs (mean weight 20 kg) and by a subxiphoid approach in 10 pigs (mean weight 20 kg). The defibrillation threshold (lowest energy required for 80% success) was determined periodically for 54 weeks in the dogs (615 trials) and at 6 weeks for the pigs (100 trials). In dogs, the mean defibrillation threshold with system I leads at 4 weeks was 10.5 J and did not change significantly over a 54-week period (p greater than 0.05). Similar results were obtained in the pig at 4 weeks. The defibrillation thresholds for both lead systems in dogs and pigs using a transpleural thoracotomy or a subxiphoid approach are satisfactory for an implantable defibrillator that produces 20-35 J.

Animals↗

Extracorporeal membrane oxygenation. Successful treatment of persistent fetal circulation following repair of congenital diaphragmatic hernia.

Four neonates (three having undergone repair of a congenital diaphragmatic hernia and developing a persistent fetal circulatory pattern and one having severe infant respiratory distress syndrome) have been supported with prolonged extracorporeal membrane oxygenation (ECMO) at Children's Hospital of Pittsburgh between December of 1979 and April of 1980. Three have survived. This encouraging experience indicates that the pattern of persistent fetal circulation in the newborn infant who has undergone repair of a diaphragmatic hernia can be successfully managed with ECMO even when efforts to lower pulmonary hypertension and improve oxygenation with vasodilators (tolazoline, phenothiazine, acetylcholine, or prostaglandin E1) and have been ineffective. The effectiveness and safety of ECMO is convincing enough to warrant its consideration as therapy for congenital diaphragmatic hernia and persistent fetal circulation prior to the use of vasodilators.

Blood Flow Velocity↗

Clinical experience with pediatric microporous oxygenator for profound hypothermia.

The Travenol TMO Total Bypass Membrane Oxygenator-Pediatric satisfactorily transfers oxygen and carbon dioxide under standardized conditions of operation during total high-flow bypass at normothermia or moderate hypothermia. This oxygenator has not been used at rates of flow less than 1 L/min or at temperatures below 23 degrees C. The current technique requires a venous and arterial pump with 5% recirculation to assure that pressure in the blood phase does not exceed the pressure above which blood may seep through the adhesive seals into the gas envelope. Conventional methods of perfusion were modified for use at profound hypothermia (18 degrees C) with low-flow bypass or circulatory arrest. Clinical experience with 22 children, preceded by six laboratory experiments, indicates that satisfactory control of arterial gases can be achieved and maintained.

Cardiopulmonary Bypass↗

Oxygen permeability of carbon-surfaced microporous membranes.

A study was conducted to measure the permeability to oxygen (PmO2) of microporous membranes coated with ultra-low-temperature isotropic (ULTI) carbon. Carbon-surfaced membranes were fabricated by application of a thin complete layer (0.7 to 1.7 microns thick) of ULTI carbon onto one surface of a microporous substrate. Based upon the average values of 27 measurements in a diffusion cell, a mean reduction in PmO2 of only 10% results following the treatment of the microporous substrate with ULTI carbon. The values for PmO2 are not dependent upon the thickness of the carbon film over the range of film thickness of 0.7 to 1.7 microns. When coupled with the known antithrombotic characteristics of ULTI carbon, an oxygenator incorporating carbon-surfaced microporous membranes has the potential for use in clinical extracorporeal membrane oxygenation (ECMO).

Acrylonitrile↗

Cardiopulmonary dynamics during arteriovenous perfusion: cardiac output, pulmonary arterial resistance, and right venticular stroke work.

The effects of arteriovenous perfusion on myocardial performance, pulmonary circulatory dynamics, and organ preservation were studied in dogs in order to evaluate the applicability of arteriovenous extracorporeal membrane oxygenation for partial respiratory support. Studies were made on normally oxygenated dogs, on dogs made hypoxic by oxygen deprivation and ventilatory depression, and on dogs with pulmonary injury and moderate pulmonary hypertension induced by injection of oleic acid into the right ventricle. The latter two groups were included to assess the changes that occur in cardiopulmonary dynamics in the presence of hypoxia and pulmonary hypertension. A microchannel membrane oxygenator was employed to provide partial respiratory support to the group of animals with pulmonary injury. The results indicate that no deleterious hemodynamic changes occurred in any of the groups of animals with arteriovenous flow for periods of up to 5 hours at rates corresponding to 20 to 35% of the total cardiac output. Adequate systemic oxygenation was provided by the microchannel oxygenator at these rates of arteriovenous perfusion.

Animals↗

Thromboresistant surface coatings for the measurement of cardiac output through continuous low flow peripheral A-V shunts.

The dilution technique for determining cardiac output using indocyanine green dye is limited in patients weighing less than 20 kg because of the obligatory volume loss. Reproducible achieved using the green dye dilution method by the establishment of a low flow peripheral arteriovenous shunt. The shunt materials were treated with thromboresistant agents--TDMAC (7%) and albumin (1 g/dl)--to facilitate the use of this technique without heparin. For A-V shunt flow rates of 8-30 cc/min reproducible values of cardiac output were obtained for up to 38 hours which were in good agreement with determinations made using the conventional technique of dye dilution.

Animals↗

Selected lobar injury after infusion of oleic acid.

A model of respiratory distress has been developed using sheep in which an isolated lobar injury is induced by infusion of oleic acid into a selected lobar artery. The directed insult permits acute and chronic phase study without the requirement of intensive pulmonary support. One hour after selective lobar injury the affected pulmonary venous oxygenation (Ppvo2) was reduced from greater than 310 to 66-90 Torr. Ppvo2 was most impaired at 48 h (40-55 Torr), but showed improvement by 96 h postinjury. Radionuclide estimates of lobar ventilation and perfusion demonstrated an initial fall in ventilation by 51% and corresponding 41% reduction in perfusion. By 24 h the depression of perfusion matched that of ventilation. Sequential light and scanning electron microscopy demonstrated the presence of a nonhomogeneous injury with areas of both complete parenchymal replacement by fibrous tissue and those with minimal architectural distortion. The selective injury model offers a useful methodology for the evaluation of the effects of various agents on the acute and chronic response of the lung to injury.

Acute Disease↗