Biomedical subjects

G L Anderson

Publications and source records attributed to G L Anderson.

At least 37 records · Page 2Linked to original sources

PubMed1998

Activation of K-Cl cotransport by mild warming in guinea pig red cells.

Unidirectional, ouabain-insensitive K+ influx rose steeply with warming at temperatures above 37 degreesC in guinea pig erythrocytes incubated in isotonic medium. The only component of ouabain-insensitive K+ influx to show the same steep rise was K-Cl cotransport (Q10 of 10 between 37 and 41 degrees C); Na-K-Cl cotransport remained constant or declined and residual K+ influx in hypertonic medium with ouabain and bumetanide rose only gradually. Similar results were obtained for unidirectional K+ efflux. Thermal activation of K-Cl cotransport-mediated K+ influx was fully dependent on the presence of chloride in the medium; none occurred with nitrate replacing chloride. The increase of K+ influx through K-Cl cotransport from 37 to 41 degrees C was blocked by calyculin A, a phosphatase inhibitor. The Q10 of K-Cl cotransport fully activated by hydroxylamine and hypotonicity was about 2. The time course of K+ entry showed an immediate transition to a higher rate when cells were instantly warmed from 37 to 41 degrees C, but there was a 7-min time lag in returning to a lower rate when cells were cooled from 41 to 37 degrees C. These results indicate that the steepness of the response of K-Cl cotransport to mild warming is due to altered regulation of the transporter. Total unidirectional K+ influx was equal to total unidirectional K+ efflux at 37-45 degrees C, but K+ influx exceeded K+ efflux at 41 degrees C when K-Cl cotransport was inhibited by calyculin or prevented by hypertonic incubation. The net loss of K+ that results from the thermal activation of isosomotic K-Cl cotransport reported here would offset a tendency for cell swelling that could arise with warming through an imbalance of pump and leak for Na+ or for K+.

Animals↗

PubMed1998

Do leukocytes contribute to impaired microvascular tissue perfusion after arterial repair?

Impaired capillary perfusion may result in flap failure. Platelet emboli, polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free flap model. PMN concentrations were depleted using antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were isolated on a single neurovascular pedicle and after a simulated technically poor arterial anastomosis upstream and reperfusion, capillary perfusion was measured each hour for 6 hours. Even though the number of PMNs was significantly reduced in the animals treated with antineutrophil serum, capillary perfusion was not changed compared with controls. These results demonstrate that depleting circulating PMNs does not protect capillary perfusion in our model. These findings suggest that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.

Anastomosis, Surgical↗

PubMed1998

Evaluation of N,N-diethyl-m-toluamide (DEET) as a topical agent for preventing skin penetration by cercariae of Schistosoma mansoni.

The effect of skin application of N,N-diethyl-m-toluamide (DEET) on the penetration and migration behavior of cercariae of Schistosoma mansoni was evaluated in vitro and in vivo in a mouse model. These studies showed that DEET at concentrations of 7.5% or higher was 100% effective in immobilizing and killing cercariae of S. mansoni in vitro. Ultrastructural studies on such DEET-exposed cercariae showed transformative and degenerative changes involving both tegument and deeper parenchymal structures. Fatal tissue lesions were evident as early as 5 min postexposure to DEET, and became more extensive with increasing exposure time. Cutaneous application of DEET (as a pure chemical in isopropanol or as a commercial insect repellent preparation) was more than 99% effective in preventing entry of S. mansoni cercariae into the mouse tail skin. Radiolabeling and tracer studies confirmed that 7.5% DEET applied to the skin prior to infection was highly effective in preventing schistosomular migration to the lungs.

Administration, Topical↗

PubMed1997

Glucose-induced intestinal hyperemia is mediated by nitric oxide.

UNLABELLED: Glucose-induced absorptive hyperemia of the intestine has been well demonstrated through microsphere blood flow experiments. We have previously demonstrated that glucose, when applied topically to rat ileal epithelium, restores microvascular vessel diameters and blood flow following Escherichia coli bacteremia or hemorrhage/resuscitation. However, the mechanisms of this hyperemia are not completely understood. We hypothesize that nitric oxide is a mediator of the microvascular response to glucose exposure on the rat intestinal epithelium. METHODS: Male Sprague-Dawley rats, 200-225 g, were monitored for hemodynamic stability with mean arterial blood pressure and heart rate. A 2-cm segment of the terminal ileum with intact neurovascular supply was exposed for intravital videomicroscopy. Intestinal arteriolar diameters (A1D, inflow; and A3D, premucosal arterioles) and microvascular blood flow (A1Q) were measured following topical application of isoosmotic glucose or saline, with or without l-NAME (LN, 100 mM), a competitive inhibitor of nitric oxide synthase. Statistical analysis was performed by ANOVA followed by Tukey-Kramer honestly significant difference test. RESULTS: All data are expressed as mean percentage changes from baseline +/- standard error of the mean. Hemodynamic variables did not change during the experimental procedure and there were no significant differences among group baselines. Addition of isotonic glucose to the bath solution caused a significant increase in A3D that persisted throughout the experiment (at 30 min, 19.2 +/- 4.2 vs -3.9 +/- 4.5, P < 0.05). This vasodilation was blocked by topical administration of LN (3.1 +/- 2.9, P < 0.05). A1D remained at baseline levels (saline and glucose) or constricted (LN) in all groups. Topical LN also attenuated A1Q in both the saline and glucose groups. CONCLUSIONS: These data demonstrate that glucose-induced intestinal hyperemia is primarily characterized by premucosal A3 arteriole dilation in this model and that nitric oxide is a mediator of glucose-induced intestinal hyperemia. These findings suggest that either (1) glucose directly causes endothelial nitric oxide production or (2) epithelial cells transduce a vasodilatory signal through vascular endothelial-derived nitric oxide during postprandial intestinal hyperemia.

Analysis of Variance↗

PubMed1997

Inhibition of wound contraction with locally injected lathyrogenic drugs.

BACKGROUND: Previous studies using systematically administered lathyrogens to inhibit wound contractures have produced inconsistent results. The purpose of this study was to investigate the effects of lathyrogenic drugs on wound contraction when injected locally. METHODS: Two symmetrical full-thickness wounds were made on the dorsum of either side of hairless (hr/hr) mice; thus, each animal served as its own control. Animals were divided into groups receiving daily local injections of beta-aminopropionitrile or D-penicillamine, or both beta-aminopropionitrile and D-penicillamine and normal saline vehicle (control side) for 5 or 10 days. The rate of contraction was determined by serial measurements of the surface area of each wound during the treatment period. At the end of the treatment period, the wounds were excised en bloc with the chest wall and prepared for blinded histological analysis. Granulation tissue thickness, number of fibroblasts in granulation tissue per unit area, number of inflammatory cells (neutrophils, lymphocytes, macrophages and mast cells) in subjacent muscle per unit area, and collagen deposition in subjacent muscle were determined. RESULTS: Wound contraction, granulation tissue thickness, and collagen deposition in subjacent muscle were decreased only in wounds treated with beta-aminopropionitrile plus D-penicillamine. Collagen deposition in subjacent muscle was also decreased in wounds treated with D-penicillamine alone. Neither drug alone nor the combination affected the number of inflammatory cells in subjacent muscle. Body weight was not affected by the experimental procedures. CONCLUSIONS: The combination of beta-aminopropionitrile and D-penicillamine is potentially useful for inhibiting contracture formation when injected locally.

Aminopropionitrile↗

PubMed1997

Platelet-derived thromboxane A2 decreases microvascular perfusion after arterial repair.

Previous work suggests that cod liver oil helps to protect the microcirculation from the consequence of thromboembolic events. The possibility that altered synthesis of thromboxane A2 accounts for the protective effects seen with cod liver oil was investigated in the present study. This was done using the combined thromboxane A2 synthetase inhibitor and thromboxane A2-prostaglandin H2 receptor blocker R68070 (Ridogrel). A standardized microvascular injury was inflicted on the right iliac artery of the rat to generate emboli. The downstream cremaster muscle was used to visualize the passage of the ensuing emboli and to assess the effects of this arterial injury on capillary perfusion and arteriole diameters. The number of visible emboli was not changed by either cod liver oil diet or Ridogrel administration. However, capillary perfusion was preserved by using cod liver oil (n = 7) and was significantly increased by using Ridogrel (n = 7) in comparison with untreated controls (n = 7) in which capillary perfusion was decreased because of the emboli. The administration of Ridogrel to cod liver oil-treated animals (n = 7) provided no additive benefit. The percentage change in A-2 vessel diameters in cod liver oil-treated (n = 7) animals was no different from the control group (n = 7). Ridogrel (n = 7), on the other hand, produced a significant increase in A-3 vessel (n = 21) diameters, but its effects were comparatively less in the cod liver oil-treated animals (n = 7). The formation of platelet aggregates (emboli) appears relatively independent of thromboxane A2 in the rat. Ridogrel is very effective in protecting the microcirculation, and these effects appear to be mediated by A-3 vasodilatation, which, therefore, is at least partially thromboxane A2-dependent. The positive effects of cod liver oil may be mediated by a mechanism that reduces thromboxane A2 synthesis, but further studies are necessary.

Animals↗

PubMed1997

Effect of low dose aspirin on thrombus formation at arterial and venous microanastomoses and on the tissue microcirculation.

In free flap/replantation surgery, failure is usually associated with thrombotic occlusion of a microvascular anastomosis (risk zone I) or, on occasion, flow impairment in the microcirculation of the transferred or replanted tissue (risk zone II). The objective of this study is to describe the effect of low dose aspirin on blood flow at both risk zones in microvascular surgery. Risk zone I: In rat femoral arteries and veins, thrombus formation was measured at the anastomoses using transillumination and videomicroscopy. Forty male Wistar rats were assigned in equal numbers to four groups: either arterial or venous injury with either aspirin (5 mg/kg systemically) or saline treatment. We found that aspirin significantly reduces thrombus formation at the venous anastomosis (p = 0.001). Risk zone II: In the isolated rat cremaster muscle downstream from an arterial anastomosis, we measured capillary perfusion, arteriolar diameters, and the appearance of platelet emboli for 6 hours in the muscle microcirculation. Sixteen male Wistar rats in two equal groups received either aspirin (5 mg/kg systemically) or saline. We found that in aspirin-treated animals, capillary perfusion is significantly (p = 0.002) improved, whereas arteriolar diameters and emboli only slightly increased. In conclusion, low dose aspirin inhibits anastomotic venous thrombosis and improves microcirculatory perfusion in our rat model. These studies provide quantitative data confirming and clarifying the beneficial effects of low dose aspirin in microvascular surgery.

Anastomosis, Surgical↗

PubMed1997

Vascular delay in skeletal muscle: a model for microcirculatory studies.

Dynamic myoplasty is a relatively new use for muscle flaps and has led us to revisit the mechanisms of vascular delay as a means of optimizing blood supply to muscle flaps. Despite the well-documented effectiveness of vascular delay in skin flaps, vascular delay in muscle flaps has not been widely reported. Regardless of the many mechanisms postulated in the literature as contributors to the delay effect in skin, the one element common to all these hypotheses is the importance placed on changes in the microcirculation. Based on this factor, in the present study we developed and validated an animal model in which delay-induced microvascular changes could be measured in skeletal muscle flaps. We used the hairless mouse latissimus dorsi muscle flap because its vascular distribution is similar to that of humans and its thin structure will enable us in future studies to directly view and measure its microvasculature using videomicroscopy. In 12 animals, we found that delay significantly (p < 0.01) reduced necrosis of the distal part of the muscle from 57 +/- 9 percent in nondelayed flaps (n = 7) to 22 +/- 3 percent in delayed (n = 5) flaps. In these studies, we also determined that the hairless mouse latissimus dorsi muscle flap will serve as an excellent model for defining microvascular changes throughout delay.

Animals↗

PubMed1997

Blunt carotid artery injuries.

BACKGROUND: Blunt carotid artery trauma remains a rare but potentially devastating injury. Early detection and treatment remain the goals of management. Our objective was to identify patients sustaining blunt carotid injuries at a regional trauma center and report on the incidence, demographics, diagnostic workup, management, and outcome. STUDY DESIGN: A retrospective chart review was performed of patients sustaining blunt carotid artery injury between 1990 and 1996. RESULTS: Twenty patients were identified during the 7-year period. All patients suffered blunt trauma, with motor vehicle accidents being the most common mechanism, and the internal carotid the most frequently injured vessel. Associated injuries were present in all patients, with head (65%) or chest (65%) injuries being the most common. The combination of head and chest trauma (45%) was found to be associated with a 14-fold increase in the likelihood of carotid injury. Cerebral angiography was diagnostic in all patients and the majority were treated nonoperatively with anticoagulation. Twenty percent of patients were discharged with a normal neurologic exam, while 45% left with a significant neurologic deficit. Overall mortality was 5%. CONCLUSIONS: Blunt carotid injuries are rare but are associated with significant morbidity and mortality. The combination of craniofacial and chest wounds should raise the index of suspicion for blunt carotid injury. Anticoagulation was associated with the least morbidity.

Adolescent↗

PubMed1996

Inhibition of wound contraction with colchicine and D-penicillamine.

The effects of locally injected combined colchicine and D-penicillamine on wound contraction were investigated in a murine model. Two full-thickness excisional wounds were made on either side of the back of hairless (hr/hr) mice. A volume of 0.15 ml of colchicine, D-penicillamine, or combined colchicine and D-penicillamine in normal saline vehicle were injected daily into the wound on one side of the animal and 0.15 ml of vehicle alone was injected into the wound on the other side for 5 or 10 days; thus, each animal served as its own control. The surface area of each wound was measured on Days 0, 5, and 10 to determine an index of the rate of wound contraction. At the end of the experimental period (Day 5 or 10), wounds were excised en bloc from euthanized animals for histological studies. The following histological parameters were determined: the thickness of the granulation tissue, the number of fibroblasts in granulation tissue per unit area, and the number of inflammatory cells (neutrophils, lymphocytes, macrophages, mast cells) in subjacent muscle per unit area. Our data showed that after 5 days of treatment, wound contraction was significantly inhibited only in wounds treated with combined colchicine and D-penicillamine. Wound contraction was significantly inhibited even after 10 days of treatment with the combination. Histological studies revealed that although the thickness of the granulation tissue and the number of inflammatory cells in subjacent muscle were decreased by D-penicillamine alone, only combined colchicine and D-penicillamine decreased the thickness of the granulation tissue, fibroblasts in granulation tissue, and inflammatory cells in subjacent muscle. Our data suggests that very low concentrations of colchicine and D-penicillamine when combined and injected locally may be potentially useful in controlling surface scar formation.

Animals↗

PubMed1996

Characterization of microvascular vasoconstriction following ischemia/reperfusion in skeletal muscle using videomicroscopy.

This study investigated the possible contribution of microvascular vasoconstriction to no-reflow following ischemia/reperfusion in a mouse skeletal muscle model. Using paired cremaster muscles, arterioles of diameter 10-100 microns were directly viewed and measured by the use of an in vivo videomicroscopy before and after a 6-hr period of complete ischemia at 27 degrees C. Following ischemia/reperfusion, feeder and arcading arterioles constricted significantly to 54.5 and 62% of pre-ischemic baseline diameters respectively (P < .05). While the calcium antagonist diltiazem and nitroprusside were both able to reverse arteriolar constriction, endothelium-dependent acetylcholine-induced dilatation was markedly impaired following reperfusion (P < 0.05). Superoxide dismutase did not attenuate the microvascular response, suggesting that the mechanism is likely to be at least partly free radical-independent.

Acetylcholine↗

PubMed1996

In vitro platelet aggregation studies in microvascular surgery research: a method in the rat model.

There is now a growing awareness of the central role of platelet function in microvascular thrombosis. Platelet aggregation studies remain one of the most useful ways of studying platelet function and response to different stimuli. This brief communication highlights some of the main variables that can affect platelet aggregation in rats and emphasizes the existence of important differences in these variables compared with human platelet aggregation.

Anastomosis, Surgical↗

PubMed1996

Anatomy of the feeding blood vessels of the cremaster muscle in the rat.

Since the early seventies over 300 studies have used the cremaster muscle as a flap model, yet little has been reported on the upstream feeding vessels of this muscle. The purpose of this study was to investigate the anatomy of the cranial feeding vessels of the left and right cremaster muscle in Sprague-Dawley rats. An additional aim was to compare these results with the anatomy of the feeding vessels of the cremaster muscle in another strain (Wistar). To permit identification of the cranial feeding vessels, the pedicle was dissected very carefully and thereafter perfused with green dye, which was administered through a cannula placed in the distal femoral artery. In Sprague-Dawley rats it was found that the cremaster muscle in only 30% of the animals received its total blood supply through the superior external pudendal artery. In Wistar rats the same was true in less than 45%. The cremaster muscle of the rest of the animals appeared to receive its blood either in part or in total from the hypogastric trunk. We suggest that the name pudic-epigastric trunk be abandoned.

Animals↗

PubMed1996

Ischemia increases the angiogenic potency of basic fibroblast growth factor (FGF-2).

The aim of this study was to investigate the angiogenic response to exogenously administered basic fibroblast growth factor (FGF-2) in normal and ischemic skin, using the hairless mouse ear microcirculatory model. The hairless mouse ear is a well-established model for in vivo studies of skin microcirculation. Using this model, angiogenesis- and angiogenesis-associated changes in the microcirculation can be directly and continuously viewed and quantified in a variety of different experimental settings. To create ischemia in the mouse ear, all but one of the three to four feeding vessels nourishing the ear were ligated 3 days prior to a local subdermal injection of FGF-2 (9.3 + 1-0.5 mm/mm2) or saline into the dorsum of the ears. Angiogenesis was quantified by direct observation, at high magnification, of the injection site where increases in total vessel length (TVL) were measured repeatedly over 18 days following injection. We found a significant (P < 0.01) increase in TVL in normal and ischemic ears injected with FGF-2. Saline injection also induced a significant increase in TVL in ischemic ears. However, the angiogenic response to FGF-2 in ischemic ears was significantly stronger than saline alone in ischemic ears or saline or FGF-2 in normal ears. This response could be used clinically to accelerate angiogenesis and thus increase perfusion in ischemic tissue.

Animals↗

PubMed1996

Prefabricated jejunal free-tissue transfer for tracheal reconstruction: an experimental study.

Reconstruction of long-segment tracheal defects is a problem for the reconstructive surgeon. Difficulties arise with the use of prosthetic materials because of their propensity for infection and extrusion. Autologous tissue is limited by poor structural characteristics and technical complexity. We propose a simple composite bioprosthesis that, through a process of prefabrication and subsequent neovascularization, may provide a functional tracheal analogue superior to existing forms of reconstruction. Ten rats had composite flaps constructed by combining an isolated, perfused, mucosectomized segment with an outer covering of a ring-reinforced woven Dacron vascular graft. This unit remained in the intraabdominal milieu for 20 days and was then inspected for viability, incorporation of jejunum and graft, flexibility, and tolerance to negative pressure. Seven experimental animals survived the initial phase. The jejunal bioprostheses in all cases tolerated negative pressures to -200 mmHg, rotation of 180 degrees, and flexion to 90 degrees without collapse of the graft segments. Vascular casts and standard histologic examination showed neovascularization of the Dacron graft and dense fibrovascular ingrowth into the interstices of the graft. We conclude that prefabrication utilizing autologous and prosthetic components to create a single axial flap for transfer is a feasible solution to long-segment tracheal reconstruction. Neovascularization permeates the full thickness of the prosthetic component and is accompanied by dense fibrous ingrowth during the delay period. This neotracheal analogue also possesses structural characteristics similar to those of the native trachea and a durable submucosal layer that can support ingrowth of epithelium.

Animals↗

PubMed1996

Introduction of new technologies to the medical undergraduate curriculum.

The rate at which new educational technologies are introduced is growing at a tremendous pace. This is in large part due to the recommendations of the AAMC Steering Committee on the Evaluation of Medical Education which strongly supported the use of Medical Informatics technologies for education. Some institutions have attempted to implement these technologies; however, a scientific study has not yet been conducted to document their potential benefit. Our attempts to conduct such a study were met with obstacles of resistance from faculty, administration, and students. To overcome these obstacles we have developed a solution which addresses all of the resistance that we encountered. This solution is based upon three premises: 1) adjunct introduction, 2) multicenter studies, and 3) scientific educational benefit analyses.

Attitude to Computers↗

PubMed1995

Can varying flow velocity across an arterial anastomosis prevent thromboembolic injury?

In this study, simulated "poor" repairs applied to transverse incisions in the iliac arteries of 40 rats were the basis for comparing the effect of variations in blood flow on thromboembolism. Using vital microscopy and digital image processing, we performed 2 experiments. In the first experiment (n = 20), the reduction of post-repair blood flow by approximately 50% resulted in an 83% reduction in the total number of emboli appearing in the microcirculation of the cremaster muscle distal to the repair. In the second experiment (n = 20), the same reduction in blood flow typically resulted in larger repair-site thrombi which required significantly more time to grow to their maximum size. We conclude that reducing pedicle artery blood flow to approximately half in our rat model during reperfusion can protect the downstream microcirculation from embolic injury without increasing the incidence of thrombotic occlusion.

Anastomosis, Surgical↗

PubMed1995

Endothelin-1 expression in the small intestine during chronic peritonitis.

Endothelins (ET) have been demonstrated to mediate intestinal microvascular constriction during acute Escherichia coli bacteremia, however, their role during chronic infection is unknown. The purpose of this study was to determine whether ET-1 is synthesized in the small intestine in a more chronic peritonitis model. ET-1 mRNA levels of the terminal ileum in mice following cecal ligation and puncture (CLP) were compared to sham-operated animals and normal unoperated animals. ET gene expression was analyzed using differential reverse transcriptase chain reaction (RT-PCR) with co-amplification of beta-actin as an internal standard. To assess ET peptide expression, serum and intestinal tissue levels were measured using a specific enzyme immunoassay (ELISA). The pattern of ET-1 gene expression post-CLP with a single puncture of the cecum with a 23 ga. needle demonstrated a 3.6-fold increase at 8 h, and a return to sham levels by 24 h (374 +/- 64% at 8 h, p < .05, 128 +/- 13%). An increase of mRNA levels at 24 h post-CLP was observed with a double puncture with an 18 ga. needle (230 +/- 36%, p < .05) accompanied by an increase in serum ET levels (270 +/- 31%, p < .05) and higher tissue ET levels. These data indicate a time-dependent response of ET-1 gene expression in the terminal ileum post-CLP which is related to severity of infection.

Animals↗