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Biomedical subjects

L Mårtensson

Publications and source records attributed to L Mårtensson.

At least 37 records · Page 2Linked to original sources

Changes in plasma levels of vasoactive peptides during sequential bicarbonate hemodialysis.

The hemodynamic response to isolated ultrafiltration (IUF) is characterized by a vasoconstriction, while there is no significant change in peripheral vascular resistance during isovolemic bicarbonate hemodialysis (IVHD). The present investigation was designed to study the plasma levels of vasoactive regulatory peptides together with noradrenaline (NA) and plasma renin activity (PRA) in 11 patients during sequential hemodialysis (SQHD) - IUF for 60 min, followed by IVHD for 210 min. During IUF, the vasoconstrictors arginine vasopressin (AVP), gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY), NA and PRA increased. During IVHD, NPY and PRA remained unchanged on a higher level. A decrease in AVP below the baseline and in gamma 2-MSH and NA to the baseline levels occurred during IVHD. In the case of vasodilators, there were no changes in calcitonin gene-related peptide or motilin during SQHD. An increase in beta-endorphin (beta-END) occurred during IUF, followed by a decrease during IVHD. Substance P and vasoactive intestinal peptide were unchanged during IUF but decreased during IVHD. We conclude that SQHD is characterized by an increase in all the measured vasoconstrictors during IUF in response to loss of fluid, and by a decrease in some vasoconstrictors (AVP, gamma 2-MSH, NA) during IVHD. With the exception of beta-END, there were no changes or only minor ones in vasodilators during SQHD. There are changes in plasma levels of vasoactive substances during SQHD but the importance of these changes for the hemodynamic adaptation to ultrafiltration and dialysis needs to be studied further.

Adult↗

Increased pulmonary platelet sequestration due to infusion of cold saline during extracorporeal circulation.

We have previously documented that neutrophils (polymorphonuclear leukocytes) aggregate in the lungs 10-15 min after the start of dialysis. The aim of the present study was to investigate the corresponding platelet reaction and evaluate the effect of prewarmed priming solution on this reaction. The animals were divided into two groups, each consisting of 6 pigs. In group 1 the priming solution was prewarmed to 36-38 degrees C whereas it was maintained at room temperature in group 2. Platelets were selectively labelled with 111In-oxine. The activity over the lung was followed dynamically with a gamma camera and already after 2 min a significant difference in platelet sequestration showed between the groups. A significant increase in pulmonary vascular resistance was noted in group 2, but not in group 1. In conclusion, platelet aggregation occurs early on during dialysis in this model. The results also indicate that prewarming the priming solution attenuates the pulmonary platelet sequestration and also seems to decrease the changes in central hemodynamics.

Animals↗

Oleic acid-induced injuries in the guinea-pig. Effects of allopurinol on cell dynamics, erythrocyte-catalase and uric acid plasma levels.

1. Oleic acid was used to produce adult respiratory distress syndrome-like pulmonary microvascular injuries. The resulting injuries have previously indicated involvement of accumulating neutrophils (Hultkvist et al. 1988). Activated neutrophils release oxygen free radicals that may be possible to detect in the plasma. 2. The dynamics of neutrophils and platelets were studied in the guinea-pig after oleic acid-induced injury (0.03 ml/kg per 10 min). 3. As an indication of oxygen free radical activity, plasma levels of uric acid and red blood cell (RBC)-catalase, were analysed. 4. Allopurinol (10 mg/kg, i.p.) was given prior to oleic acid infusion to block the production of uric acid. 5. The neutropenia, in contrast to the thrombocytopenia seen at 15 min, was significantly inhibited in the allopurinol pretreated group compared with oleic acid and vehicle alone. 6. The blood plasma concentration of uric acid was significantly elevated after 15 min from start of experiment. Allopurinol pretreatment significantly reduced the uric acid plasma level. 7. The RBC catalase activity did not change with time within or between any groups. 8. The results indicate that sequestration of activated neutrophils in the microvasculature are to some extent oxygen free radical dependent.

Allopurinol↗

Absence of lung reactions after complement depletion during dialysis: an experimental study in pigs.

Sequestration of 111In-labeled neutrophils (polymorphonuclear leukocytes--PMNs) in the lungs during sham dialysis was studied dynamically using a gamma camera. Five animals were pretreated with cobra venom factor, naja naja (CVF), to achieve depletion of the complement system, mainly C5a. Seven animals were studied without pretreatment with CVF. Central hemodynamics and gas exchange were studied as well as neutrophil function using luminescence and aggregation. In the control group there was a significant sequestration of neutrophils in the lungs, which reached a maximum between 15 and 17 min after the start of hemodialysis. The peripheral neutrophil count decreased concomitantly. These changes were virtually absent in the CVF-treated group. PMN aggregation and luminescence were abolished in CVF-treated animals. Both pulmonary artery pressure and pulmonary vascular resistance increased significantly in the control group, whereas in the CVF group these parameters remained unchanged. There were no differences in blood gases, platelet count, or hematocrit between the groups. The results clearly indicate that the activation of neutrophils within minutes after the start of hemodialysis is greatly dependent on C5a activation because it can be abolished by C5a depletion. This activation is accompanied by changes in the pulmonary circulation with increases in pressure and resistance.

Animals↗

Portable closed loop feedback system for control of the blood glucose level in the pig.

To establish the difference in glucose consumption of healthy compared to diabetic pigs, a transportable system for the feedback control of insulin and glucose was used in conscious pigs. The system for controlling glucose levels, as well as glucose consumption, was easy to use and adjusted smoothly to rapid changes in insulin level. Five days prior to the first day of experiment, healthy animals were prepared with intravenous jugular catheters tunnelled subcutaneously to the neck. On the first day of experiment, measurements of glucose were continuously taken before and after food ingestion. The animals were rendered diabetic after 2 days using Alloxan and streptozotocin. The measurements were then repeated. To be able to obtain constant glucose levels of approximately 3 mmol during both fasting and postprandial periods requires only small glucose adjustment infusion in the diabetic pigs, as opposed to healthy ones. Using the described system, it would be possible to evaluate subclinical diabetes and control unstable diabetics with different therapeutic regimes.

Animals↗

External detection of pulmonary accumulation of indium-113m labelled transferrin in the guinea pig.

Accumulation of radioisotope labelled transferrin in the lungs of guinea pigs was determined with an external detection system. The method is based on the intravascular and extravascular distribution of indium-113m labelled transferrin compared with the intravascular distribution of technetium-99m labelled red blood cells. Guinea pigs were given iloprost, a prostacyclin analogue and potent pulmonary vasodilator, and noradrenaline, a pulmonary vasoconstrictor, in an attempt to increase and decrease respectively the blood volume in the lungs. Neither agent altered transferrin accumulation in the lung by comparison with a saline infusion. Iloprost infused before and after oleic acid infusion reduced macro-molecular leakage when compared with oleic acid alone. These data suggest that the double isotope method can distinguish between hydrostatic and injury induced pulmonary oedema.

Animals↗

Dynamic pulmonary accumulation of labelled neutrophils by blood membrane contact in the pig.

Nine anesthetized pigs were subjected to short (90 min) sham dialysis with blood membrane contact with the aim to select effects of the artificial surface during dialysis. The importance of the neutrophil (PMN) was investigated by the selective isotope labelling, dynamically followed by gamma-camera imaging and biochemical assays specifically oriented for PMN function. These assays included cell count, PMN aggregation, PMN luminescence, fibronectin and catalase activity. Additionally, pulmonary and systemic hemodynamics and acid base balance were monitored. Sham dialysis induced an accumulation of labelled PMN attaining a maximum between 15 and 17 min. This was coupled with a time-related neutropenia, pulmonary vasoconstriction, increased in vitro PMN aggregation and luminescence response. The neutrophil response abated by the end of dialysis. Cardiac output and arterial blood pressure declined to a steady level after 30 min of sham dialysis. There was an insignificant decrease in catalase activity. All other parameters remained unaltered. The results indicate that PMN accumulates in the pulmonary vessels, in association with neutropenia and activation. The transience of the event points to a protective mechanisms of humoral and/or cellular character.

Animals↗

Polymorphonuclear leucocyte sequestration in the lungs and liver following soft-tissue trauma: an in vivo study.

Neutrophils are thought to sequestrate in the lungs and the liver in association with shock. Indications for this have previously been demonstrated in different in vitro studies. In this experiment an in vivo technique for dynamic studies of pulmonary and liver neutrophil sequestration (PNT and LNT, respectively) is described. Autologous neutrophils from ten pigs were labelled with 111Indium-oxine. The pigs were placed under a scintillation camera for continuous recording of the activity distribution in the pigs during 105 minutes. Following a steady-state period of 15 minutes seven pigs were subjected to a standardized soft-tissue trauma. Three pigs were used as controls and not traumatized. Within 1-3 minutes after trauma the radioactivity over the lungs increased dramatically, indicating PNT. This was followed by a fast decrease but 90 minutes after trauma PNT levels were still significantly elevated. LNT showed a similar pattern, although the immediate increase was less dramatic. This study shows that PNT and LNT occur immediately after soft-tissue trauma and can be studied dynamically in vivo.

Animals↗

Model of pulmonary extravasation as an effect of neutropenia in endotoxic shock in guinea pigs.

A guinea pig model was developed to document the association of polymorphonuclear neutrophils (PMN) decrease with pulmonary leakage after a sublethal infusion of endotoxin (LPS Escherichia coli 0111:B4, 5 micrograms/min/kg). A control group was prepared in the same manner and given an infusion of vehicle alone. Severe leukopenia developed, mostly expressed in the neutrophil population. There was a decrease in RBC catalase and fibronectin. Plasma leakage in the lung followed the endotoxin infusion, which could indicate endothelial cell damage. The results from the present study suggest an activation of PMN in endotoxin-infused animals, degranulation and release of toxic oxygen species, resulting in pulmonary plasma extravasation.

Agranulocytosis↗

External 113Inm and 99Tcm radiation detection of lung edema induced by oleic acid in the guinea pig.

The establishment of a small animal model for studies of lung injury is in great demand. Therefore, a double radioisotope labeling method was applied to study the dynamics of lung injury with protein-rich edema in the anesthetized guinea pig. One external scintillation detector was placed over the lung and another over the heart, where they continuously sampled the energy spectrum of 113Inm labeled transferrin, a macromolecular marker, and 99Tcm labeled red blood cells (RBC), a blood pool marker. Lung injury was induced by i.v. oleic acid in doses of 0.03 and 0.06 ml/kg b.wt. infused for 10 min. We calculated the rate of increase of accumulated 113Inm-transferrin in the lung corrected for blood pool changes. Macromolecular leakage showed a graded response in regression line-slope (RLS) to oleic acid. Both oleic acid groups showed significantly different RLSs as compared to the saline control (mean +/- SD x 10(-3) min-1; 0.03 ml: 3.86 +/- 1.01 (n = 7); 0.06 ml: 10.75 +/- 4.06 (n = 6), and control 1.12 +/- 1.19 (n = 6]. Assays of changes of acid-base balance, cell dynamics, and lung wet-dry weight were in accordance with the occurrence of lung edema. The RLS was well correlated with the lung wet-dry weight (r = 0.98). We conclude that measurements of pulmonary edema in guinea pigs can be performed quantitatively with the aid of external detection of radiolabeled transferrin and RBC:s. Thus, the method could be useful in further studies on mechanisms and/or treatment of protein-rich lung edema.

Animals↗

Movement of oxygen, glucose, and lactate across the uterus of the awake near-term guinea pig.

In this study the uterine movement of oxygen, glucose, and lactate was quantitated in the awake late pregnant guinea pig. Mean uterine uptake of oxygen per kg of uterus with conceptus was 581 mumol min-1, which is comparable to the value reported for the awake near-term rabbit, but 30% higher than the value reported for the awake near-term sheep. Experiment-related anemia in some animals was associated with a reduced uterine oxygen uptake. The arteriovenous oxygen difference across the uterus correlated positively with the arterial oxygen content and the hemoglobin concentration and negatively with uteroplacental blood flow. Uterine oxygen uptake showed a positive correlation with both the arterial hemoglobin and the uteroplacental blood flow. Uterine lactate output accounted for 20% of uterine glucose uptake, assuming maternally derived glucose to be the only source for uterine lactate output. After correction for this lactate output, the uterine glucose uptake was 96.5 mumol min-1 X kg-1 of pregnant uterus. This value is 30% higher than in the awake near-term rabbit and more than twice as high as that in the awake near-term sheep. Nevertheless, because of the high uterine demand for substrates, this uterine glucose uptake could only cover 45% of the caloric requirements of the pregnant uterus. The late pregnant guinea pig fetus may derive as much as 55% of its caloric uptake for fat deposition and protein accretion. Therefore, it is likely that the nonglucose uterine caloric uptake in the late pregnant guinea pig consists predominantly of fat precursors and amino acids.

Anemia↗

The influence of 2,2',4,4',5,5'-hexachlorobiphenyl on the placental blood flow in guinea pigs at a late stage of gestation.

Three groups of primaparous pregnant guinea pigs were fed once daily with a total of either 0 (control group, n = 9), 3 (n = 8), or 30 mg (n = 9) of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) starting at Day 45 of gestation to evaluate the effects of HCB on placental perfusion. The guinea pigs were separated into their groups randomly. At Day 63 of gestation the organ blood flow was determined with microsphere technique in the awake animal. The results show a statistically significant decrease in the placental blood flow and an increase in the pulmonary blood flow in the animals fed with 30 mg HCB compared to the control groups. A higher incidence of resorptions in fetuses is shown in both treatment groups compared to the control group. It is concluded that ecologically relevant doses of polychlorinated biphenyls might cause a deterioration in the placental function by reducing its blood flow.

Animals↗

Effect of oestrogen and progesterone on the blood flow in the lower urinary tract of the rabbit.

The effects of oestrogen and of oestrogen combined with progesterone were examined on the fractional distribution of cardiac output (blood flow) in the genitourinary tissues of the female rabbit. Oestradiol treatment significantly increased blood perfusion in the uterus, vagina and urethra but caused no change in the perfusion of the urinary bladder or the kidneys. The wet weight of the uterus and vagina increased significantly and in the urethra there was a tendency to weight gain following oestradiol treatment. Progesterone treatment following oestrogen appeared to reduce the effect of oestrogen on both perfusion and weight gain.

Animals↗

Microsphere analysis of beta 2-adrenergic control of resistance in different vascular areas after hemorrhage.

In cats exposed to bleeding (exsanguination of 15 ml X kg bwt-1) the microsphere technique was used to determine regional vascular resistances in a large number of tissues before and after i.v. administration of the 'selective' beta 2-adrenoceptor antagonist ICI 118,551. beta 2-blockade significantly raised vascular resistance in the stomach (+ 26%), small (+ 25%) and large (+ 38%) intestine, pancreas (+ 29%), kidney (+ 39%), omental (+ 33%) and subcutaneous (+ 26%) fat, 'white' skeletal muscle (+ 19%), and skin (+ 24%). These findings indicate that, with intact beta-adrenoceptors, beta 2-adrenergic dilator interaction counteracted the hemorrhage evoked vasoconstrictor influences. beta 2-blockade also evoked quite a strong increase of total peripheral resistance (19%) and led to some redistribution of cardiac output. It is concluded that beta 2-adrenergic inhibition of vascular tone significantly seems to improve tissue perfusion during bleeding in several vascular areas. Such effects may be of special significance during severe hemorrhage. In the intestine, pancreas, and adipose tissue, for example, protection against excessive vasoconstriction may serve to minimize the severe metabolic disturbances with secondary release of toxic factors into the circulation reported during hemorrhagic shock.

Adrenergic beta-Antagonists↗