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Biomedical subjects

A Gidlöf

Publications and source records attributed to A Gidlöf.

At least 19 recordsLinked to original sources
PubMed2000

Synthetic retinoids improve survival in rodent model of endotoxic shock.

OBJECTIVE: To investigate the effect of synthetic retinoids on septic shock induced by lipopolysaccharide (LPS) in rats. DESIGN: Randomised study. SETTINGS: University hospital laboratory, Sweden. ANIMALS AND INTERVENTIONS: 31 male Sprague Dawley rats randomised into four groups: controls, given vehicle alone (n = 6), LPS 6 mg/kg body weight alone (n = 12), and LPS 6 mg/kg but pretreated with the retinoic acid receptor-alpha (RAR-alpha) agonists CD336 (n = 6) and CD2081 (n = 7). MAIN OUTCOME MEASURES: Arterial blood pressure and heart rate measured hourly for four hours; mortality. RESULTS: LPS caused a pronounced fall in blood pressure within one hour of injection in all groups of rats. Of the 12 rats given LPS but not RAR-alpha agonists, 6 died before the end of the experiment. By contrast, all animal given either CD336 or CD2081 survived. The significantly improved survival was found despite no significant improvements in either mean arterial pressure or heart rate. CONCLUSION: Pretreatment with selective synthetic RAR-alpha agonists improves survival after LPS-induced septic shock in rats. These agents may have therapeutic potential in the treatment of septic shock in humans.

Animals↗
PubMed1999

Skeletal muscle tissue oxygen pressure distribution during early reperfusion after prolonged ischaemia.

OBJECTIVES: The aim of this study was to investigate the skeletal muscle tissue oxygen pressure (PtO2) distributions during early reperfusion (10-45 min) after prolonged ischaemia in a rat animal model. MATERIAL AND METHODS: Skeletal muscle ischaemia was induced in anaesthetised rats by applying a tourniquet on the left thigh for 3 h (group I) or 4 h (group II), and tissue oxygen pressure measurements were made after 10-45 min of reperfusion. Assessment of PtO2 was made by a multiwire Clark-type oxygen microelectrode, placed on the surface of the left tibialis anterior muscle. RESULTS: During reperfusion a similar PtO2 pattern was evaluated after both 3 and 4 h of total ischaemia, where the sum PtO2 distributions were shifted to the left associated with low tissue oxygen pressure values. After 10 min of reperfusion the median PtO2 was 0.28 kPa and 0.18 kPa, in groups I and II, respectively; after 45 min of reperfusion 0.61 kPa and 0.60 kPa, respectively. The median PtO2 in the non-ischaemic muscle in groups I and II were 2.19 and 2.17 Pa. CONCLUSION: The results show that local skeletal muscle oxygenation is severely impaired during the initial 45 min of reperfusion after both 3 and 4 h of total muscle ischaemia with a slow-reflow phenomenon generally present, despite pronounced needs.

Animals↗
PubMed1999

Skeletal muscle blood flow after prolonged tourniquet ischaemia and reperfusion with and without intervening reoxygenation: an experimental study in rats using laser Doppler perfusion imaging.

The total, safe, time available for operating during tourniquet ischaemia is thought to be prolonged by short, intervening episodes of reperfusion. However, animal experiments have suggested that this may cause a reduction of the postischaemic reperfusion injury. The purpose of the present study was to investigate the effect on final postischaemic reperfusion of intermittent, short periods of reperfusion compared with that of prolonged, continuous tourniquet ischaemia. A rat tourniquet model of total limb ischaemia and laser Doppler imaging to measure postischaemic microvascular perfusion in skeletal muscle was used in a total of 25 anaesthetised rats. Four were non-ischaemic controls. In 21 rats one hind leg was made totally ischaemic by a tourniquet. Fourteen were exposed to uninterrupted periods of either 1.5 hours or three hours, and seven to interrupted total ischaemia of three hours, with a 20 minutes reperfusion interval after 1.5 hours of ischaemia. The postischaemic blood flow was monitored 20 minutes after release of the tourniquet. Postischaemic skeletal muscle blood flow was significantly reduced after three hours of continuous ischaemia compared with the group that had an intervening short period of reoxygenation. The postischaemic reperfusion after three hours of ischaemia with a short reperfusion interval was not reduced after ischaemia compared with either that in controls or to that in the group exposed to only 1.5 hours of tourniquet ischaemia. These findings support the clinical practice of using intervening periods of reperfusion to prolong the total tourniquet time that can safely be used. There were no adverse effects on postischaemic reperfusion from intermittent reoxygenation.

Animals↗
PubMed1999

Retinoic acid regulates arterial smooth muscle cell proliferation and phenotypic features in vivo and in vitro through an RARalpha-dependent signaling pathway.

We have recently shown that all-trans retinoic acid (tRA) modulates arterial smooth muscle cell (SMC) morphologic features and biochemical composition in vitro. It has been proposed that different SMC phenotypes coexist in arteries, which may be retrieved in culture: hence, a differential action of tRA on distinct SMC subsets is conceivable. We have examined the effect of tRA on SMC proliferation, migration, plasminogen activator activity, and alpha-smooth muscle actin expression in 2 phenotypically different rat SMC populations, cultured respectively from the normal aortic media and from the intimal thickening (IT) after endothelial injury. tRA inhibited proliferation and increased migration and tissue-type plasminogen activator activity in both SMC populations, but decreased alpha-smooth muscle actin only in SMC cultured from the IT. The action of tRA is mediated by 2 families of nuclear receptors, RAR and RXR, each containing 3 isoforms, alpha, beta, and gamma. RAR and RAR-alpha agonists, but not RXR agonists, inhibited SMC proliferation in both cell populations and alpha-smooth muscle actin expression only in IT SMC. When administered intraperitoneally to balloon-injured rats, tRA and RAR-alpha agonists reduced the intimal hyperplasia in the carotid artery. Our results show that tRA and synthetic retinoids can affect the proliferation, migration, and differentiation of SMC in vitro. Furthermore, retinoids are able to reduce the IT induced by endothelial injury in vivo.

Animals↗
PubMed1996

Altered glutathione levels in ischemic and postischemic skeletal muscle: difference between severe and moderate ischemic insult.

The purpose of the present study was to investigate how the duration of ischemia and reperfusion affect the glutathione (GSH) levels in skeletal muscle and to assess the presence of oxidative stress by quantitating oxidized glutathione (GSSG) and the ratio of GSSG/GSH. The amounts of GSH and GSSG were quantitated in the tibialis anterior muscle of the rat hind limb after 2 and 4 hours of tourniquet ischemia and after 1 and 5 hours of reperfusion, and the levels were compared to those in nonischemic control tibialis anterior muscles. In muscles subjected to 2 hours of ischemia, the levels of GSH, GSSG, and the ratio GSSG/GSH did not differ significantly from those of nonischemic controls. After 4 hours of ischemia without reperfusion, the GSH levels were slightly increased, compared to controls (p < 0.05). After 1 hour of reperfusion following 4 hours of ischemia, the levels of GSH decreased by 50% compared to control (p < 0.01), and still after 5 hours of reperfusion the levels of GSH were 50% lower than control levels. The GSSG/ GSH ratio did not change during 1 and 5 hours of reperfusion compared to control. A major finding in this study was that, during reperfusion after severe ischemia of 4 hours, there was a marked depletion of glutathione, which was not seen after a moderate ischemic insult of 2 hours.

Animals↗
PubMed1996

Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes.

Since nitric oxide (NO) has been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were investigated in psoriatic skin by reverse transcriptase coupled to the polymerase chain reaction (PCR). The study showed that the mRNA expression of brain nitric oxide synthase (bNOS), one of two isoforms of cNOS, was weak in both psoriatic plaques lesions and uninvolved skin, while mRNA transcripts for the second isoform, endothelial nitric oxide synthase (eNOS), were not detectable using the present method. In contrast, the mRNA expression of iNOS was markedly increased in lesional skin as compared to uninvolved skin. Cultured human keratinocytes exposed to a combination of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) for 4 h, showed strong gene expression of iNOS, while in 24 h, the expression had returned to baseline expression. In summary, the study demonstrates that mRNA for the inducible form of NOS is over-expressed in psoriatic lesions. The cause of this may be the local presence of inflammatory cytokines. These findings imply that iNOS may play an important part in local regulation of NO synthesis in psoriasis and other inflammatory dermatoses.

Adult↗
PubMed1996

In situ microdialysis for monitoring of extracellular glutathione levels in normal, ischemic and post-ischemic skeletal muscle.

Microdialysis probes were inserted into the tibialis anterior muscle and into the femoral vein of anaesthetised Sprague-Dawley rats for monitoring of reduced (GSH) and oxidized (GSSG) extracellular glutathione. The dialysates were analysed using HPLC. The levels of GSH and GSSG were high immediately after implantation in the skeletal muscle and declined to steady state levels after 90 minutes into the same range as that found in the venous dialysate. Total ischemia was induced two hours after implantation of the dialysis probe after steady state levels had been reached. The extracellular levels of GSH increased during total ischemia and had doubled at the end of the ischemic period compared to preischemic values. During the following initial 30 minutes of reperfusion the levels increased further to four-fold the preischemic levels. The levels of GSSG also increased (100%) during the initial 30 minutes of reperfusion. The extracellular GSH levels remained elevated for 1 hour of reperfusion, but the GSSG levels returned to preischemic levels. The results indicate that intermittent hypoxia or anoxia in muscle tissue through hypoperfusion or ischemia decreases intracellular GSH stores by leakage, reducing the intracellular antioxidative capacity and increasing the risk for oxidative reperfusion injury upon final normalization of tissue blood supply.

Animals↗
PubMed1995

Laser-Doppler perfusion imaging of microvascular blood flow in rabbit tenuissimus muscle.

To evaluate a newly developed high-resolution laser-Doppler perfusion imager (HR-LDPI) for analysis of local tissue perfusion, blood flow measurements in the rabbit tenuissimus muscle were carried out in combination with intravital microscopic observation. The principle of the LDPI method is based on a low-power laser beam scan of the exposed tissue from which a two-dimensional color-coded perfusion map is created through computerized signal analysis. The perfusion of the tenuissimus muscle prepared for microscopic observation was analyzed in a 5 mm x 8 mm area as the muscle was exposed to atmospheric oxygen tension (Po2; 20 kPa), a low Po2 (approximately 3 kPa), and after vasodilatation induced by topical application of prostaglandin E2 (PGE2). In selected areas free from larger vessels, a significantly lower perfusion average reading was demonstrated under high Po2 conditions compared with low Po2 conditions (P < 0.05, n = 5 animals), and application of PGE2 gave rise to an average reading significantly higher than that at low Po2 (P < 0.01, n = 6 animals). The results were in good agreement with the flow changes observed microscopically, and the architecture of the microvascular network, as depicted by in vivo micrographs, was clearly recognizable in the perfusion images. In conclusion, blood flow changes in the rabbit tenuissimus muscle induced by various stimuli were quantitated with the HR-LDPI method and could be spatially resolved in great detail, illustrating the potential of using HR-LDPI for analysis of local blood flow and to reveal spatial perfusion heterogeneity in tissues.

Animals↗
PubMed1994

Different induction mechanisms of mRNA for inducible nitric oxide synthase in rat smooth muscle cells in culture and in aortic strips.

The expression of mRNA for the inducible form of nitric oxide synthase, (iNOS), was studied in rat aortic smooth muscle cells, (SMCs) in cell culture and in strips of rat aorta by reverse transcriptase coupled to the polymerase chain reaction. iNOS mRNA expression was weak in cultured SMCs when exposed to either interferon-gamma (IFN gamma) or lipopolysaccharide (LPS), but the combination LPS+IFN gamma enhanced the expression. In aortic strips LPS alone induced a pronounced expression, with no further increase by IFN gamma. Cycloheximide potentiated the expression of iNOS mRNA in SMCs in culture stimulated with LPS+IFN gamma but attenuated the response in aortic strips. The results indicate different cellular signaling pathways for the induction of iNOS mRNA by LPS and/or IFN gamma, in cultured SMCs and in rat aortic strips.

Amino Acid Oxidoreductases↗
PubMed1990

The relation of the post-ischemic reperfusion impairment to the severity of ischemia in the tibialis anterior muscle of the rat.

Hyperemic volume flow rates were followed during 15 minutes of post-ischemic reperfusion in tibialis anterior muscle of the rat after 1, 2 and 3 hours of tourniquet ischemia using the 133Xenon clearance technique. Results showed a no-reflow phenomenon after 2 and 3 hours of ischemia. There was a marked impairment in flow, seen immediately upon reperfusion as a reduction or abolishment of the initial peak of the normally brisk post-ischemic hyperemia. The impairment increased with increasing duration of ischemia. The range of maximal peak hyperemic flow rates was wide and median maximal peak flows were 43.1, 14.6 and 7.2 ml.min-1.100 g-1 after 1.2 and 3 hours, respectively. This reflow impairment was not caused by differences in arterial blood pressure at the start of perfusion or during the initial 2 minutes of perfusion. Venous hematocrit at the start of the reperfusion was not significantly different between the three groups. Total muscle water of 75.9% in control muscle increased to 79.7% after 3 hours of ischemia and 1 hour of reperfusion and reached a maximum of 85.7% after 5 hours of reperfusion, demonstrating that the no-reflow seen during the initial 15 minutes could not be caused by an increased tissue pressure due to rapidly developing reperfusion edema. Results indicate a microvascular hindrance in post-ischemic reperfusion.

Animals↗
PubMed1990

The effect of hypervolemic hemodilution and hyperoncotic infusions on the immediate reperfusion impairment in skeletal muscle of the rat after prolonged total ischemia.

The effect of hypervolemic hemodilution and hyperoncotic infusions on the reactive hyperemic volume flow rates during the initial minutes of post-ischemic reperfusion in the rat's tibialis anterior muscle after 1, 2 and 3 hours of tourniquet ischemia was studied using the 133Xenon clearance technique. Median maximal hyperemic peak reflow rates in muscle of non-infused, control animals upon release of a tourniquet were 56.5, 43.6 and 7.5 ml.min-1 x 100 g-1 respectively, demonstrating the development of a post-ischemic reperfusion impairment, a no-reflow phenomenon, that increased with the duration of the preceding period of ischemia. Rapid infusions of isotonic saline solutions over the last five minutes of tourniquet ischemia, aiming at increasing the circulating blood volume of the animals at start of the ischemic leg reperfusion by 2.0, 4.5, and 9.5 ml respectively, or by approximately 10%, 25% and 50%, gave no significant improvement in post-ischemic reperfusion, except in that following 3 hours of leg ischemia and after the two largest volumes. Rapid infusions of solutions of human albumin in a concentration of 200 mg.ml-1 to an amount approximately equalling 0.15, 0.40 and 0.75 g.kg-1 bodyweight till the moment the reperfusion was started, aiming to increase circulating albumin until the start of reperfusion by about 10%, 20% and 40%, significantly improved immediate peak hyperemic reperfusion in proportion to dose and more than doubled post-ischemic peak hyperemic reperfusion rates after the largest dose to 129.6, 102.6 and 39.1 ml.min-1 x 100 g-1 respectively. This improvement in initial post-ischemic hyperemia by hyperoncotic reperfusion may be of importance for achieving a rapid post-ischemic tissue oxygenation and for preventing tissue edema.

Albumins↗
PubMed1988

Fine structure of the human skeletal muscle capillary. A morphometric analysis.

Capillary dimensions in muscle biopsies from human musculus quadriceps femoris, sectioned at right angle to the muscle fibers, were analysed with a computerized planimetric technique giving distributions of dimensional parameters with statistics. Without corrections for estimated preparative shrinkage mean maximal diameter of lumen was 3.82 +/- 0.82 microns (5.31 +/- 1.14 micron shrinkage corrected), mean second maximal diameter, at right angle to maximal, 2.61 +/- 0.72 microns (3.62 +/- 1.00 microns corr.) and mean endothelial thickness in nuclear free sections 0.35 micron (0.49 micron corr.) micron. Using a capillarity of 360/mm2 for the human m. quadriceps femoris, the total surface area of skeletal muscle capillaries was calculated to be 5.50 X 10(3) cm2/100g and the total volume of the capillary network in the muscle to be 0.48 cm3/100g.

Adolescent↗
PubMed1988

The effect of prolonged total ischemia on the ultrastructure of human skeletal muscle capillaries. A morphometric analysis.

Human skeletal muscle shows reflow impairment after prolonged tourniquet ischemia of 1-3 hours, increasing with the duration of ischemia. A sample of 275 cross-sectioned capillary profiles from muscle biopsies of human m. quadriceps femoris made totally ischemic by tourniquet for 90-180 minutes (mean 110 min.) from 5 patients during surgery, show frequent evidence of ultrastructural damage to microvascular membranes and organelles. Frequency analyses demonstrate a significant increase in damage during ischemia (p = 0.03), but not increasing further following 5 min of reperfusion. One of the signs of ischemic damage was endothelial swelling, found in some endothelial cells, lying next to ultrastructurally intact ones. The swelling found cannot be explained by a general loss of volume control of the microvascular endothelium during ischemia, since a computerized morphometry on the entire sample shows a preserved capillary wall thickness during ischemia and following reperfusion. During reperfusion the capillaries dilate with an increase in median max. diameter from 3.4 micron (4.7 micron shrinkage-corrected) to 3.9 micron (5.4 corr.) (p less than 0.001), despite reported reperfusion impairment. However, since capillaries in skeletal muscle consist of 20-40 endothelial cells, a distribution of such localized endothelial swelling or luminal membrane changes in a few percent of the microvascular endothelial population after ischemia, trapping leucocytes, would affect microvascular hydraulic conductance to reperfusion.

Adult↗
PubMed1985

The effect of long-term circulatory occlusion on pH and energy metabolism of the quadriceps muscle in man.

The effect of up to 2.5 h circulatory occlusion on muscle pH and energy metabolism of the quadriceps muscle was studied in 13 patients operated on for an inveterate knee injury. Muscle samples were taken by the percutaneous needle biopsy technique at different times during the arterial occlusion and after restoration of circulation. Energy was provided by a complete utilization of phosphocreatine and by a low rate of glycolysis during 2 h of occlusion. The ATP level remained unchanged throughout the occlusion period. Muscle pH decreased from 7.0-7.1 to about 6.8 after 2 h occlusion. Muscle pH was essentially normalized within 20 min after restoration of the blood flow.

Adenosine Triphosphate↗
PubMed1982

Changes in serum phosphate and calcitonin concentrations during elective surgery of the knee.

Hypophosphataemia in connection with surgical trauma is most commonly ascribed to parenteral nutrition, glucose infusion, or haemodilution. We have earlier shown that patients with severe burns develop hypophosphataemia irrespective of such causes, and have introduced the theory that hypophosphataemia can result from the humoral response to trauma. In the present work, 10 otherwise healthy patients undergoing elective surgical treatment of old knee-ligament injuries were examined pre-, per-, and postoperatively with regard to phosphate, calcium, and magnesium homeostasis and hormones regulating this (parathyroid hormone, calcitonin, catecholamines). During operation we noted a significant and rapid fall in serum phosphate concentration, accompanied by increased secretion of calcitonin and catecholamines and a significant fall in serum magnesium. Unchanged fractional and total urinary phosphate excretion indicated that the fall in serum phosphate concentration was mainly due to prerenal causes.

Adolescent↗
PubMed1980

The occurrence of paracrystalline mitochondrial inclusions in normal human skeletal muscle.

Two different types of paracrystalline mitochondrial inclusions identical with or very similar to those already described in the literature for a variety of muscle diseases were found in human skeletal muscle biopsies obtained under general anesthesia before ischemia and after various periods of anoxia up to 150 min. As these crystalloids could be observed in seven of 14 healthy subjects and occurred in five of these seven cases either before or only 10 min after onset of ischemia, it is suggested that such mitochondrial inclusions develop not only under the influence of variant noxious stimuli, but may also represent a normal constituent of human skeletal muscle mitochondria.

Adolescent↗