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Biomedical subjects

R Connolly

Publications and source records attributed to R Connolly.

At least 19 recordsLinked to original sources
PubMed1990

Potential of radio-frequency balloon angioplasty: weld strengths, dose-response relationship, and correlative histology.

Previous studies have established the feasibility of combining tissue heat generated by radio-frequency (RF) current and mechanical pressure to manage problems of percutaneous transluminal angioplasty (PTA) that are thought to cause postangioplasty restenosis (PARS). In the current in vitro study of normal and atherosclerotic human aortic layers (intima-media and media-adventitia) separated artificially, the purposes were to identify a dose-response relationship between the total RF energy delivered and the resultant weld strength between vascular tissues and to study the histologic correlates. Twenty-eight control and 100 experimental specimens were evaluated. The mean weld strength for all specimens with no RF current (at 0 J) was 4.1 g +/- 2.0; at 100 J, 5.9 g +/- 2.8; at 200 J, 28.5 g +/- 3.3; at 300 J, 50.0 g +/- 5.5; and at 500 J, 82.0 g +/- 8.2. Inspection of treated specimens revealed vascular molding (depression in the surface corresponding in dimensions to those of the electrode gap in the treatment chamber). Histologic examination revealed necrosis in the region underlying the electrode gap, a hypocellular fusion zone, indistinct boundaries between welded specimen parts, and transition zones to normal histologic characteristics at either end of each specimen. RF energy combined with mechanical pressure produces dose-dependent thermal welds in artificially dissected vascular tissues, molding of vascular tissue, and cellular destruction in the media. These findings may have clinical application in the management or prevention of all forms of PARS in humans and in the treatment of spontaneous aortic dissection.

Angioplasty, Balloon↗
PubMed1989

Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets.

The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans.

Animals↗
PubMed1988

A new primate model for the study of intravenous thrombotic potential and its modification.

Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions.

Animals↗
PubMed1988

Radiofrequency balloon angioplasty. Rationale and proof of principle.

Post-angioplasty restenosis (PARS) in atherosclerotic lesions of medium and small arteries occurs in about one-third of cases in the first year following percutaneous transluminal angioplasty (PTA) (early PARS). PARS includes acute spasm, dissection with reclosure, elastic recoil, fibrocellular proliferative response, and progressive atheromatous disease. Fibrocellular proliferation (possibly initiated by platelet derived growth factor) is felt to be culpable in many cases of early PARS (months). Pharmacologic regimens, stents, and thermal welding of the intimal-medial cracks of PTA are among the interventions being developed to deal with PARS. Radiofrequency (RF) current as a source of thermal energy may be useful in combination with balloon angioplasty to reduce PARS. Ideally, this combination would (1) weld intimal-medial cracks of PTA; (2) mold plaque and normal vessel to increase lumen diameters without creating intimal-medial cracks; and (3) destroy medial smooth muscle cells and multipotential cells (cellular substrate of PARS). Canine in vivo studies have established the feasibility of RF-mediated vascular tissue welding. Human aortic specimens (N = 28) were manually dissected into intima-media and media-adventitia layers. Bipolar RF energy (650 KHz, total 300 J) and mechanical pressure (1 atm) (experimental group, N = 24) or mechanical pressure alone (control group, N = 4) were applied to the reapposed specimen layers in a special chamber. The chamber was modified with a bipolar electrode designed to reproduce that planned for an RF balloon angioplasty catheter. Welding was demonstrated in normal and atherosclerotic treated specimens (23/24 or 96%) but not controls (0/4).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1988

The systemic activation of platelets by Dacron grafts.

Dacron (polyester fiber), a stimulus to platelet aggregation in vitro, accumulates platelets to a greater extent in vivo than autogenous artery, polytetrafluoroethylene (PTFE) or human umbilical vein (HUV). We conducted a series of experiments using the ex vivo shunt in the baboon to determine whether or not systemic activation of platelet function was produced by a Dacron graft. Two 5 centimeter segments of 4 millimeter internal diameter graft materials were placed in series in the ex vivo shunt perfused at 25 milliliters per minute flow rate for two and one-half hours. Deposition of autologous Indium 111 labeled platelets was monitored. The ex vivo shunt procedures were divided into two groups, both with PTFE as the proximal graft: one with a distal Dacron graft (n = 21), the second with PTFE or HUV distally (n = 17). In this study, an increase in platelet deposition on the proximal PTFE graft represents systemic platelet activation caused by the distal graft. Increased platelet deposition on PTFE was noted at all time points in the presence of a Dacron graft (p less than 0.05). This property of Dacron has important clinical implications, potentially accelerating the progression of vascular disease, increasing the failure rate of composite grafts and subsequent arterial reconstruction.

Animals↗
PubMed1987

The effect of low molecular weight dextran on platelet deposition onto prosthetic materials.

Low molecular weight dextran (LMD) has recently been shown in a randomized, multicenter trial to improve early patency in difficult lower extremity vascular bypass. The question remained as to whether this effect was due to plasma volume expansion by LMD or to its effects on platelets and coagulation. To analyze this we have studied the effects of LMD on platelet-graft interactions using an ex vivo baboon shunt. Indium 111-labeled autologous platelet deposition on expanded polytetrafluoroethylene and knitted Dacron grafts was monitored at a flow rate of 25 ml/min for 21/2 hours. LMD was given by intravenous bolus at a dose of 5 ml/kg and was followed by a continuous infusion of 10 ml/hr. Flow through the shunt was started after the initial dextran bolus. Control studies were performed in a similar manner without dextran. An additional series of experiments was performed with a 5 to 10 ml/kg bolus of 5% human serum albumin to analyze the contribution of plasma volume expansion to platelet deposition in this model. The results revealed a significant (p less than 0.05) reduction in platelet deposition on both graft materials with the LMD infusion. No difference was seen between the control group and the albumin group. These studies provide direct in vivo evidence of the antiplatelet effect of LMD.

Albumins↗
PubMed1979

Tissue perfusion rate determined from the decay of oxygen-15 activity after photon activation in situ.

Rates of cerebral perfusion were obtained from measurements of the disappearance (wash-out) of oxygen-15 after in situ tissue activation with 45-million-volt x-rays. In an anesthetized cat, typical values were 90 milliliters per minute per 100 grams of tissue, with 55 percent wash-out. In a specific radiotherapy patient, the value was 65 milliliters per minute per 100 grams of tissue, with 63 percent wash-out of oxygen-15 through incorporation into tissue water.

Animals↗
PubMed1978

A comparison of moral reasoning in drug addicts and nonaddicts.

Assessed moral reasoning of 20 male addict patients and 17 nonprofessional male hospital employees by Kohlberg's methods. The mean level of moral reasoning of the drug addict group (2.97) was not found to differ significantly from that of the nonaddict comparison group (2.88). Furthermore, moral reasoning in addicts was not found to be related significantly to a number of background and personality characteristics. The findings, therefore, indicated that moral reasoning and moral behavior are not related significantly in drug addicts. It was concluded that the deviant behavior of this group is more likely the result of a deficiency in ego controls.

Adult↗
PubMed1978

Acepromazine-ketamine anesthesia in the rhesus monkey (Macaca mulatta).

Six adult male rhesus monkeys (Macaca mulatta) were anesthetized using a combination of acepromazine maleate and ketamine hydrochloride administered by intramuscular injection. This combination produced a smooth induction to anesthesia requiring less than 5 minutes. The average duration of anesthesia was slightly less than 1 hour and was safely prolonged with additional doses of ketamine. The depth of anesthesia was sufficient for minor surgical procedures and for precise radiological studies. No deleterious side effects were noted, and animals recovered completely in a short time.

Acepromazine↗