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Biomedical subjects

S O Salley

Publications and source records attributed to S O Salley.

At least 19 recordsLinked to original sources
PubMed1995

Survival of composite chondrocutaneous grafts by vessel implantation: a study in the rabbit ear model.

Composite chondrocutaneous graft reconstruction or reattachment has limited applicability, is traditionally restricted to small segmental losses, and is dependent on the status of the recipient bed and graft periphery for successful revascularization. Surgical enhancement of composite graft survival was experimentally investigated in the rabbit ear model through transposition and appositional placement of an adjacent vascular pedicle. Fluorescein-derived surface-survival determinations, microangiographic vessel-counting methods, and histologic analysis were used to study the effects of vascular augmentation, pedicle design variations, and angiogenic substance in sixty 8-cm2, full-thickness auricular grafts. A statistically significant survival advantage was demonstrated for the implanted grafts, secondary to perivascular angiogenesis from the implanted pedicle.

Angiogenesis Inducing Agents↗
PubMed1994

Extracorporeal CO2 removal in a lung lavage model of respiratory failure.

Extracorporeal life support (ECLS) is a recognized treatment for neonatal respiratory distress unresponsive to other forms of therapy. Variations of this technique are being developed in an effort to extend its applicability and safety. Extracorporeal CO2 removal (ECCO2R) is one such modification that requires blood flows of 20% to 50% of cardiac output and therefore lends itself to percutaneous venous cannulation. The authors evaluated ECCO2R in conjunction with low-frequency ventilation, using a lung lavage-induced model of respiratory failure in rabbits. Six rabbits were lavaged an average of 9 times with 15 mL/kg Plasma-Lyte A at 37 degrees C via an endotracheal tube. Incremental ventilatory changes were made during lavage, to an FIO2 of 1.0, rate of 80, peak inspiratory pressure (PIP) of 37 cm H2O, and positive end-expiratory pressure (PEEP) of 4 cm H2O. Arterial blood gas values of PaO2 < 40 mm Hg and PaCO2 > 60 mm Hg resulted, meeting our criteria for respiratory failure. The rabbits were placed on veno-venous ECCO2R using a 0.8-m2 hollow fiber oxygenator and a commercially available double-lumen dialysis catheter. Blood flows of 10 to 20 mL/kg/min were used to manage CO2 removal. A low-frequency ventilation technique was employed using an FIO2 of 1.0 and a rate of 5 breaths per minute. PEEP was increased incrementally to maintain the PaO2 above 80 mm Hg. After initiation of ECCO2R, the arterial PaO2 increased to 165 +/- 109 mm Hg, with PEEP above 15 cm H2O, and PaCO2 decreased to 37 +/- 5 mm Hg, with a bypass flow rate of 15 mL/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Performance of plasma-perfused, microencapsulated hepatocytes: prospects for extracorporeal liver support.

The growing success of liver transplantation and the shortage of donor livers has turned attention to the possibility of utilizing hepatocytes within artificial liver support systems to allow time for donor livers to become available and to improve the condition of patients with hepatic failure. This study evaluated encapsulated hepatocytes, a technology which might allow the possibility of using xenogenic or human hepatoma cells. Rabbit hepatocytes were encapsulated using the ionic polysaccharides carboxymethylcellulose, chondroitin sulfate A, chitosan, and polygalacturonic acid. Encapsulated cells were maintained in perfusion culture for at least 6 days in heparinized, normal human plasma or in a defined culture medium. Parallel cultures of plated hepatocytes were also conducted. The metabolic capability of the cells was evaluated by following the rates of urea, albumin, and transferrin synthesis and the transformation rate of the drug antipyrine. Protein synthesis and ureogenesis in plasma were depressed from the levels expressed in defined culture medium. Drug detoxification as measured by antipyrine metabolism appeared to be enhanced in plasma. We conclude that encapsulated rabbit hepatocytes retain significant levels of function for at least 6 days of perfusion with human plasma, suggesting the feasibility of this technology as a potential method of short-term liver support.

Albumins↗
PubMed1991

ECMO without heparin: laboratory and clinical experience.

To evaluate the feasibility of long-term extracorporeal membrane oxygenation (ECMO) without heparin, we placed six lambs on standard venoarterial ECMO for 71 to 96 hours. Group 1 (3 animals) was given doses of heparin to maintain activated clotting times (ACT) greater than 400 seconds. No form of anticoagulant was used for the three animals in group 2. Blood flow was maintained at 60 mL/kg/min. No histological evidence of thrombosis was noted at necropsy. ACT, prothrombin time, and partial thromboplastin time were higher in group 1, and much lower, although still above normal in group 2. Fibrinogen was significantly lower in group 2 (75 +/- 35 v 219 +/- 64 mg/dL group 1), and, although the platelet count was lower in group 2 (142 +/- 76 x 10(3)/mm3 v 225 +/- 167 x 10(3)/mm3), it was clinically acceptable. These results encouraged us to discontinue heparin when faced with severe hemorrhage in four patients on ECMO, rather than withdraw support at a time when there was little chance of survival. Heparin was discontinued for 10.5 +/- 6 hours. The mean ACT was reduced from 220 +/- 23 seconds to 144 +/- 22 seconds. One patient, who required repair of gastric necrosis while on ECMO following repair of a congenital diaphragmatic hernia, survived and had a decrease in blood loss from 2 to 0 mL/kg/h after the heparin was discontinued. One of the three patients who died had an autopsy with no evidence of thrombosis. We conclude that it may be reasonable to discontinue heparin in the face of life-threatening hemorrhage while on ECMO.

Animals↗
PubMed1989

Regional blood flow distribution during extracorporeal membrane oxygenation in rabbits.

To study regional blood distribution during extracorporeal membrane oxygenation, we stabilized three groups of five rabbits each (3 to 5 kg) on venoarterial bypass at a flow rate of 30 ml/kg/min. Albumin aggregates (15 to 30 microns) labeled with technetium 99m were injected into the left ventricle during bypass (ventricle), the perfusion cannula during bypass (cannula), and the left ventricle with no bypass (control). Animals were put to death, organs were removed, and the percent distribution was determined with a gamma camera. The Student Newman-Keuls test was used for statistical comparisons. Distribution to both the heart and brain in the cannula group were decreased from control by 55% and 35%, respectively. Distribution to the brain in the ventricle group was also decreased from control by 39%. Intestinal distribution was elevated above control in the ventricle group by 37%, whereas musculoskeletal distribution was elevated 33% above control in the cannula group. No significant changes were noted for the kidneys, stomach, or liver. These data suggest that overall perfusion of some vital organs may be significantly reduced during low-flow extracorporeal membrane oxygenation, specifically in the case of the heart and brain, which may be deprived of oxygenated blood.

Animals↗
PubMed1989

Thrombin-stimulated effects on megakaryocytopoiesis and pulmonary-platelet interactions.

The effects of thrombin stimulation on megakaryocytopoiesis and pulmonary-platelet interactions were investigated before and after administration of the compound to 15 mongrel dogs. Each dog served as its own control. Thrombin was given to encourage the traffic of megakaryocytes into the lung and to study the thrombin-stimulated effects on megakaryocytopoiesis in the bone marrow. Our results showed that thrombin increased the numbers of bone marrow cells in general and megakaryocytes (MK) in particular. In addition, the maturation cycle of megakaryocytes was accelerated and the number of MK migrating into the central venous circulation was nearly doubled. Most of the circulating MK ultimately became sequestered in pulmonary capillaries, where platelets were shed into the arterial circulation. We conclude that thrombin has a major stimulatory effect on megakaryocytopoiesis in the bone marrow and that the lung plays an important role as a vascular filter and regulator of circulating platelet count.

Animals↗
PubMed1989

Extracorporeal membrane oxygenation without anticoagulation: a study using quantitative scanning electron microscopy.

In current clinical applications of extracorporeal circulation (ECC) of blood, heparin is administered to prevent thrombosis in the circuit and to eliminate thromboembolism in the patient. Systemic heparinization, however, causes impairment of normal coagulation properties and significantly increases the risks of major bleeding complications. It has been observed in the past that ECC may be performed in the absence of any systemic anticoagulants or material surface treatments. In this study, short-term extracorporeal membrane oxygenation (ECMO) was performed on rabbits in three groups. The animals in the first group received standard clinical dosages of heparin. No form of anticoagulation was used in the second group. The ECMO circuits in the third group were treated with an albumin-heparin complex surface-coating. Thrombosis in the extracorporeal circuit was evaluated by using quantitative scanning electron microscopy. The results indicated very few statistically significant differences between the three experimental systems in the amounts of blood components adhering to the surface. Considerably more platelet activation and attachment was noted in the systemic heparin group. These experiments failed to demonstrate any benefit of systemic heparinization in short-term ECMO. The findings from these experiments suggest that the current levels of systemic heparinization may be unwarranted, and they indicate that more controlled studies must be performed to determine optimal levels of anticoagulation for different applications of ECC.

Animals↗
PubMed1987

Analysis of the effects of inhaled diesel exhaust on the alveolar intravascular and interstitial cellular components of rodent lungs.

Transmission electron microscopy (TEM) was used to determine the effect of diesel engine exhaust (DEE) on the intravascular and interstitial cellular population of the lungs of exposed rats and guinea pigs. Animals with matched controls were subjected to environments of either 250, 750, 1500 or 6000 micrograms/m3 for either 2 weeks, 6 weeks, 10 weeks or 18 months. These animals were sacrificed immediately following the exposure periods and their lungs perfused with fixative. Following dissection, random stratified biopsies from the lungs of these animals were made. Ultrathin sections from the alveolar lung were prepared and conventionally processed for TEM and randomly photographed to compose a micrograph database. These micrographs were analyzed by point counting using a Zeiss MOP 3 Digital Image Analyzer. The results indicated no significant intravascular cellular response but a significant increase in the mononuclear population in the interstitium.

Animals↗
PubMed1981

Ultrastructure and morphometry of the alveolar lung of guinea pigs chronically exposed to diesel engine exhaust: six month's experience.

The impact of chronic inhalation of diesel exhaust (DE) on alveolar lung was studied in 24 Hartley guinea pigs. Groups were sacrificed sequentially at 2 weeks, 3 months and 6 months of exposure to either 750 micrograms or 1500 micrograms DE particles (DEP) per m3 along with age-matched concurrent controls. Although qualitative ultrastructural changes were noticed during this time interval and dosage schedule, there was no evidence of pathologic changes such as fibrosis or emphysema. The cellular uptake of DEP was striking. By 2 weeks three alveolar cell types (alveolar macrophages, epithelial type 1 cells and interstitial macrophages) plus one type of granulocytic leukocyte (eosinophils) confined DEP within phagosomes without evidence of cytotoxicity. A certain phagosomal DEP population had a bull's eye appearance and diameters of 0.0727 +/- 0.01 micron. Morphometric analysis applied to electron micrographs demonstrated that arithmetic mean tissue thickness of the air-blood barrier was generally increased (p less than 0.05) during DE exposure. For the 750 micrograms DE sets, the increase over control (1.56 micron) was 41% at 2 weeks, 46% at 3 months and 77% at 6 months while the 1500 micrograms DE set at 6 months exceeded control by 130%. Increases in absolute tissue volumes of interstitium and epithelial type 2 cells largely accounted for the increased tissue thickness. Harmonic mean tissue thickness for controls remained near 0.537 +/- 0.03 micron for the study interval, contrasting with values for 3 and 6 months 750 micrograms DE and 6 months 1500 micrograms DE sets which increased. However, the diffusion capacity of the lung determined morphometrically was not decreased in DE exposed sets. Although cellular uptake of DEP and increased prominence of secretory epithelium were dose/duration related, absence of linearity suggests adaptative responses.

Aerosols↗
PubMedDate not supplied

Complex coacervate microcapsules for mammalian cell culture and artificial organ development.

A number of combinations of anionic and cationic polymers, the majority being polysaccharides, were screened to determine their suitability for the development of alternative microcapsule formulations capable of supporting cells. The capsules were taken through a limited optimization and then evaluated on the bases of rupture strength, permeability to albumin, and ability of their components to promote the attachment, aggregation, and function of encapsulated rabbit hepatocytes. The widely used alginate-polylysine capsules were employed as a comparative standard in all tests. A number of the new formulations compared favorably with the standard, and some exhibited superior performance in specific areas. Hepatocyte function, as evaluated by the rate of urea synthesis, showed no significant differences between formulations over a 24-h test period. One formulation, composed of the polysaccharides (carboxymethyl)cellulose, chondroitin sulfate A, chitosan, and polygalacturonate, was found to be superior to alginate-polylysine capsules in the areas investigated and supported the long-term survival and growth of liver endothelial cells.

Animals↗
PubMedDate not supplied

Regional blood flow during extracorporeal membrane oxygenation in lambs.

To determine changes in blood flow to different organs during extracorporeal membrane oxygenation (ECMO), the authors performed venoarterial ECMO in four young lambs for 71-96 hr (Group 1). Macroaggregated albumin microspheres labeled with technetium 99m were injected through the perfusion cannula before termination of ECMO to determine percent of blood flow by measuring radioactivity from the microspheres lodged in specific organs. The control group (Group 2) consisted of three animals not on bypass; injections were made through a catheter placed in the left ventricle. Relative coronary blood flow from the perfusion cannula was significantly less than relative coronary blood flow in the control group, possibly because of cannula location. Renal flow from the perfusion cannula also was decreased. Contrary to observations in rabbits, cerebral perfusion did not decrease in the bypass group despite ligation of the carotid artery and the external jugular vein. There were no statistically significant differences between the two groups in the relative blood flow to other organs. The authors conclude that ECMO may significantly alter myocardial and renal perfusion, with minimal effects to other organs.

Animals↗
PubMedDate not supplied

Thermal, operational, and storage stability of immobilized carbonic anhydrase in membrane lungs.

The significant improvement in CO2 removal rates from blood through membrane lungs with EMCO and ECCO2R is achievable by means of the immobilization of carbonic anhydrase (CA) onto the membrane surface. The practical application of this technology requires that the enzyme be maintained for long periods without loss of activity. Thus, studies were performed to evaluate the thermal, operational, and storage stability of CA in a cellulose nitrate-encapsulated, silicone rubber membrane-immobilized form. Cellulose nitrate microcapsules containing 1000 micrograms/ml CA were prepared using a modified version of the method of Chang, and immobilized onto a 0.06 m2 section of commercial silicone rubber membrane material. The extent of enzyme activity in free solution and in the encapsulated form was determined after long-term storage at 4 degrees C, 37 degrees C, and 50 degrees C. Likewise, in an in vitro test circuit, CO2 removal efficiency in both CA treated and untreated membrane lungs was measured for extended time periods of 10 hr over a 10 day period. The thermal stability tests showed a significantly greater degree of retained enzyme activity in the encapsulated form, over the free enzyme in solution, at all temperatures. This was especially evident at higher temperatures and when the enzyme was stored for extended periods. In the operational stability tests, the CO2 removal efficiency of the treated membrane was not degraded, and stayed significantly higher than the untreated membrane for extended time periods. This further illustrates the potential for the use of the immobilized enzyme, carbonic anhydrase, for improved CO2 removal efficiency.

Acetazolamide↗
PubMedDate not supplied

Feasibility studies for a photosynthetic artificial lung. Optimization of parameters affecting photosynthesis.

As an alternative to conventional extracorporeal membrane oxygenation (ECMO) hardware, preliminary studies were conducted toward the development of a life support system based on biologic processes for the direct generation of O2 and removal of CO2 by the action of a photosynthetic organism. A high temperature strain of Chlorella pyrenoidosa, which functions optimally at 37 degrees C and pH 7.4, was cultured in a 3 I fermenter with artificial lighting provided with Hg-metal halide lights. The pH, total CO2 and partial pressure of oxygen (PO2) of the system were monitored at regular intervals using flow-through microelectrodes. The degree of importance of light intensity, substrate concentration, and cell density in the photosynthetic ability of Chlorella in batch culture were assessed over a 2 hour period. At high light intensities, the O2 production, CO2 removal, and pH changes were significantly greater than those at low irradiance levels. Over the range of HCO3- concentrations used in these experiments, the initial HCO3- levels did not appear to have a significant effect on the rates of O2 production/CO2 removal. The total amount of O2 produced/CO2 removed and pH changes were found to be greater with higher cell densities. Under more optimal culture conditions, it may be feasible to eventually interface this photobioreactor with blood across a semipermeable membrane and catalytically convert blood CO2 to O2 directly, needing only an adequate light source.

Artificial Organs↗
PubMedDate not supplied

Systemic toxic reactions to procaine penicillin G.

Systemic toxic were encountered in eight of 10,469 patients during or immediately following the intramuscular injection of 4,800,000 units of procaine penicillin G for the treatment of gonorrhea. Fear of imminent death, visual and auditory disturbances, violent combativeness, confusion, disorientation, and restlessness, disturbance in taste, cardiovascular changes, and grand mal seizures are the principal manifestations; these usually subside in two to 10 minutes spontaneously or after treatment. Symptoms and signs closely parallel systemic toxic reactions to local anesthetics. Pharmacokinetic analysis in dogs using 14C-procaine and 14C-procaine penicillin G showed rapid distribution of labeled drugs from plasma to cerebrospinal fluid for the intravenous as compared to the intramuscular route of administration. The animal studies were consistent with the hypothesis that the inadvertent intravenous administration of procaine penicillin G is responsible for the systemic toxic reactions. Plasma procainesterase (pseudocholinesterase) activity was assayed with an ultraviolet spectroscopic method. Substrates were procaine and procaine penicillin G. The plasma procainesterase activity of patients who had experienced systemic toxic reactions was significantly decreased as compared to that of controls, an observation not previously reported.

Adolescent↗
PubMedDate not supplied

Microencapsulated hepatocytes. Prospects for extracorporeal liver support.

To assess the potential for encapsulated hepatocytes as a bioartificial liver support system, rabbit hepatocytes were encapsulated within multicomponent capsules using a complex coacervation technique, and cultured both on plates and in a perfusion reactor. The urea synthesis rate and antipyrine and diazepam degradation rates were evaluated in each system over a 10 day period, and compared with standard plate-cultured hepatocyte efficacy. Urea synthesis rates were significantly higher in the perfusion cultures than in either of the plate culture environments, whereas drug degradation rates were not significantly different in any of the systems.

Animals↗
PubMedDate not supplied

Immobilized carbonic anhydrase in a membrane lung for enhanced CO2 removal.

The potential use of carbonic anhydrase (CA), immobilized within membrane lungs, to accelerate the removal of CO2 from blood was investigated. Using a variation on the technique of Chang, 500 micrograms/mL of CA was encapsulated in 5-20 microns cellulose nitrate microcapsules which were then immobilized onto a 0.1 m2 silicone rubber membrane. Using an in vitro test circuit, 0.68 mmol/m2/min of CO2 was removed from venous blood through an untreated membrane at steady state. With the CA-immobilized membrane, CO2 removal was enhanced to 1.09 mmol/m2/min. This technique has the potential of greatly improving the CO2 efficiency of commercial membrane lungs for ECCOR.

Carbon Dioxide↗
PubMedDate not supplied

CO2 removal for ventilatory support: a comparison of dialysis with and without carbonic anhydrase to a hollow fiber lung.

All CO2 in blood is in equilibrium, catalyzed by carbonic anhydrase (CA). This has prompted some investigators to consider treating ventilatory failure by using dialysis to remove HCO3-. Since there is at least 18 times more CO2 in the form of HCO3- than dissolved CO2, theoretically, lower blood flows could be used than with current extracorporeal support with artificial membrane lungs. HCO3- removal for ventilatory support has required alkalinization to compensate for the resulting acidosis and has been capable of removing 26 to 38 ml CO2/100 ml blood flow, compared to 14 ml CO2/100 ml for clinically employed silicone membrane lungs. We designed a HCO3- removal system using recirculation of dialysate through a membrane lung to remove CO2, rather than alkalinization of blood, and removed 8.8 ml CO2/100 ml. Adding CA improved this to 12.2 ml CO2/100 ml, but a conventional hollow fiber lung removed 30 ml CO2/100 ml. We conclude that the complexities of an HCO3- removal system may not be necessary with the advent of more efficient hollow fiber lungs.

Bicarbonates↗