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Biomedical subjects

R J Connolly

Publications and source records attributed to R J Connolly.

69 records · Page 4Linked to original sources

A rabbit model for evaluation of an extracorporeal LDL removal system.

Elevated levels of plasma low density lipoprotein cholesterol (LDL) are associated with an increased incidence of atherosclerosis and its sequelae. A decrease in LDL levels correlates with a reduction in atherosclerosis. Drug therapy and diet have been moderately successful in lowering cholesterol levels, but require significant periods of treatment. Furthermore, a patient with genetically high LDL levels, as in familial hypercholesterolemia, may need a more rapid and reliable method of decreasing serum LDL. The present study was designed to test a device which can rapidly remove LDL from the circulation. The device consists of a filter cartridge filled with semipermeable hollow fibers which have a proprietary acidic polymer (pap) immobilized on the blood/plasma contacting surfaces; this polymer has been reported to selectively bind LDL cholesterol. The device was evaluated in a hypercholesterolemic rabbit model. Reductions in LDL serum concentration, ranging from 1.4-25.3%, occurred in 6/6 studies. All animals survived the procedure. Autopsy results at 10 days showed normal histology. Binding of other proteins (HDL, albumin) were minimal and no hemolysis was observed. Results of this preliminary study demonstrate the feasibility of reducing serum LDL levels with a hollow fiber device.

Animals↗

Healing after arterial dilatation with radiofrequency thermal and nonthermal balloon angioplasty systems.

Thermal balloon angioplasty has been proposed as a means of reducing acute and delayed reclosure of arteries after percutaneous transluminal balloon angioplasty. A radiofrequency (rf) balloon catheter was used to perform thermal balloon angioplasty on canine arteries in vivo. The histologic appearance of rf-treated sites was compared with that of control sites treated by conventional percutaneous transluminal angioplasty. Acutely, rf-treated sites showed a reduced medial cellularity with preservation of internal elastic lamina except at the transitional zone between thermal injury and normal artery, where localized internal elastic lamina disruption was found. Nonthermal sites showed generalized disruption of internal elastic lamina and normal medial cellularity. Both thermal and nonthermal sites displayed a return of intimal cover commencing at 1 to 2 weeks and completed by 4 weeks. Diffuse myointimal hyperplasia appeared by 2 weeks after injury at breaks in the internal elastic lamina along the nonthermal vessels but was localized to the transitional zone in thermal injury sites. In rf-treated vessels, repopulation of the acellular thermally modified media had commenced by 4 weeks, and by 8 weeks the media was diffusely repopulated by spindle-shaped cells resembling smooth muscle cells lying between and aligned with preserved connective tissue laminae. Overall, the distribution and extent of the proliferative response after rf thermal balloon angioplasty were less than those seen after nonthermal balloon angioplasty. Thermal sites, which underwent reintimalization before medial cells returned, were considerably less prone to the development of myointimal hyperplasia. These results suggest that this modality may have beneficial effects on arterial healing after angioplasty.

Angiography↗

Effect of hyaluronic acid solution on healing of bowel anastomoses.

Hyaluronic acid (HA) solution has the ability to coat and lubricate serosal surfaces, and potentially prevent serosal trauma during surgery, which can result in the postoperative formation of adhesions in the abdomen. Previous animal studies utilizing HA have shown a reduction of intra-abdominal adhesion formation. Human clinical trials are currently underway. The prevention of adhesions could conceivably have deleterious effects on bowel anastomosis healing. As a result, solutions of HA were studied in rabbits to determine their effect on the healing of a bowel anastomosis. In 30 rabbits, test solutions of either HA (0.4 or 1.0%) or phosphate-buffered saline (PBS) as a control were instilled into the open peritoneal cavity just prior to the performance of small bowel anastomosis. At sacrifice 14 days later, intestinal bursting pressures were 110.5 +/- 16.0 mm Hg (SEM) in the PBS group, 108.5 +/- 15.2 mm Hg in the 0.4% HA group, and 138.7 +/- 14.1 mm Hg in the 1.0% group. Average bursting pressures among the three groups did not vary significantly (p > .05). Small sterile mucoceles formed at the anastomosis in 70% of the PBS group, in 10% of the 0.4% HA group, and in 30% of the 1.0% HA group. Histologic examination of specimens taken at the anastomosis did not reveal any differences in the level of healing between groups. HA solution, when instilled in the presence of a small bowel anastomosis in rabbits, does not appear to interfere with the healing process.

Anastomosis, Surgical↗

Novel antiadhesion barrier does not prevent anastomotic healing in a rabbit model.

Intraperitoneal adhesions following surgical procedures cause considerable morbidity. Hyaluronic acid/carboxymethylcellulose (HA/CMC) films have been shown to be effective agents in decreasing adhesion formation. However, when there is an inadvertent leak of bowel contents into the peritoneum due to incomplete anastomosis, adhesion formation about a defect in order to prevent further leakage and to promote healing of the wound is important for the prevention of morbidity and mortality. The purpose of this study was to determine if an antiadhesion film (HA/CMC) impairs these potentially beneficial adhesions to bowel anastomoses, thus predisposing them to enteric leaks with subsequent peritonitis. Sixty-four rabbits were divided in two groups, each undergoing a complete or partial (90% anastomosis to simulate anastomotic leak) large bowel anastomosis. Half of each of the above groups were treated by wrapping a HA/CMC film over the anastomosis and the other half were untreated controls. These two subgroups were then further divided equally and sacrificed at either 7 or 14 days for evaluation of anastomosis integrity and strength. The average anastomotic bursting pressures did not change significantly between those groups treated with HA/CMC when compared to untreated controls at 7 or 14 days or in the complete or partial anastomosis group (Student's t test). Adhesion formation to the anastomosis was not impaired in either group independent of HA/CMC film application. This study suggests that while HA/CMC film has been shown to decrease adhesions in other models, healing of a rabbit colonic anastomosis even in the presence of an anastomotic defect takes place, further suggesting that the stimulus for adhesion formation can overcome the antiadhesion properties of HA/CMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Pulmonary emboli from blood-biomaterial interaction.

The problem of surface thrombosis and subsequent embolization remains entrenched as a yet incompletely surmounted barrier to the development of truly satisfactory intravascular prosthetic devices. A baboon ex vivo shunt was used to determine the interaction of Indium-111 platelets and potential biomaterials. The uptake of Indium-111 platelets was monitored continuously by gamma camera scanning. Several of the materials tested demonstrated a saw-toothed pattern of platelet activity, with accumulation followed by rapid decline. Neither PTFE nor Dacron exhibited this pattern. Post shunt scans of the animals' chests showed discrete foci of platelet activity in the lungs, corresponding to each embolic event noted on the material's scan. In conclusion, the search for a smooth surface as a blood material interface may produce a material which accumulates and then sloughs significant platelet aggregates. It is crucial that these materials be subjected to vigorous testing to determine their safety prior to initiation of clinical trials.

Animals↗

Heterotopic heart transplantation: electrophysiologic changes during acute rejection.

To identify electrophysiologic (EP) measurements sensitive to heart transplant rejection, heterotopic thoracic heart transplantation was performed in 11 dogs. Endocardial biopsies were performed daily for up to 9 days, and the severity of rejection was classified as mild, moderate, or severe. Late diastolic thresholds; refractory periods of the left ventricle and right atrium; and conduction times from the right atrium to left atrium, left ventricle to right ventricle, and right atrium to right ventricle were measured daily in transplanted and recipient hearts. The amplitude of the left atrium and right ventricular electrograms was recorded daily. In the recipient hearts no significant EP changes were observed after the second postoperative day. Left ventricular and right atrial refractory periods in both hearts did not change. In the transplanted hearts the conduction times of the right and left atria (but not the conduction time of the left to right ventricles) and right atrium to right ventricle identified moderate rejection; right atrial diastolic threshold was a marker only for severe rejection. Amplitudes of the left atrial and right ventricular electrograms decrease significantly only with severe rejection. At postmortem histologic evidence for rejection was greater in the atria than the ventricles. EP changes in the atria and atrioventricular conduction are more sensitive indicators of acute rejection than ventricular EP changes and correlate with the histologic grade of rejection. None of the measurements evaluated, however, was shown to be a sensitive marker of mild rejection.

Acute Disease↗