Search PubMed⌕ Search

Biomedical subjects

U Haglund

Publications and source records attributed to U Haglund.

At least 181 records · Page 10Linked to original sources

Posthypotensive generation of superoxide free radicals--possible role in the pathogenesis of the intestinal mucosal damage.

Graded small intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery. Specimens from the small intestine were studied at the end of the hypotensive period, 10 min and 60 min posthypotensively . Specimens obtained late during hypotension revealed characteristic mucosal damage in all cases. However, the intestinal mucosal damage was more pronounced in the specimens taken posthypotensively . This aggravation was prevented if the cats were given superoxide dismutase (SOD) during the hypotensive period. Further, the intestinal tissue concentration of total glutathione was reduced posthypotensively . It is suggested that the posthypotensive aggravation of the intestinal mucosal damage is caused by generation of cytotoxic oxygen free radicals. Data favouring the suggestion that the glutathione-glutathione peroxidase system is an important generator of free radicals in intestinal ischemia is presented.

Animals↗

Increased survival of endotoxin-injected dogs treated with methylprednisolone, naloxone, and ibuprofen.

The effects of methylprednisolone, naloxone, and ibuprofen--alone and in various combinations--on survival, blood pressure, hematocrit, and peripheral platelet and white blood cell counts were studied in a canine Escherichia coli endotoxin LD100 shock model. Treatment was started 10 minutes after shock induction. The dogs were kept on a respirator and given intravenous fluids for 4 hours, then disconnected from the respirator and allowed to recover. Dogs surviving 7 days were considered permanent survivors. All control animals died within 36 hours. Five of nine dogs receiving a combined treatment of methylprednisolone, naloxone, and ibuprofen were permanent survivors and showed no macroscopic abnormalities when autopsied. The combined treatment with methylprednisolone and ibuprofen also increased survival. Mortality was delayed in animals treated with methylprednisolone and naloxone. Dogs receiving ibuprofen, a cyclooxygenase inhibitor, had a rapid reversal of hypotension. Hematocrit and platelet counts were similar in all groups. The combined treatment caused an increase in the recovery rate of white blood cells.

Animals↗

The effect of serotonin inhibition on initial microvessel hemostasis and platelet aggregation in vivo.

The role of serotonin (5-HT) in initial microvascular hemostasis is not fully understood. This study was made to evaluate the effect on hemostatic plug formation and laser-induced arteriolar microembolism of different substances which counteract the effect of 5-HT. Hemostatic plug formation time and stability was measured in the rabbit mesenteric microcirculation and laser-induced embolism in the rabbit ear chamber. Ketanserine, a selective 5-HT2-receptor blocker shortened arteriolar hemostatic plug formation time. Dihydroergotamine, an unselective blocker (with 5-HT-and alpha-adrenergic receptor affinity) increased venular hemostatic plug formation time and also decreased the hemostatic plug stability. Laser-induced platelet embolism was unaltered after both ketanserine and dihydroergotamine administration. The magnitude of these changes seems to exclude an important effect of 5-HT in initial microvessel hemostasis or on platelet activity.

Animals↗

Genetic toxicity of dopamine.

The genetic toxicity of dopamine was studied in a battery of test systems including DNA single-strand break analysis in cultured human skin fibroblasts, the Salmonella/mammalian-microsome mutagenicity test, sister-chromatid exchange analysis in human lymphocytes, the mouse-lymphoma forward mutation assay, the sex-linked recessive lethal test in Drosophila melanogaster and the micronucleus test in mouse and rat. Dopamine at concentrations of 50-300 micrograms/ml induced DNA strand breaks in human fibroblasts. It also gave a positive response in the mouse-lymphoma forward mutation assay, where a dose-dependent increase in the frequency of mutant cells was observed in the presence of dopamine, 94-750 micrograms/ml. All other tests showed no response to dopamine. The dopamine-induced DNA strand breaks in human fibroblasts were inhibited by superoxide dismutase or dithiothreitol. Furthermore, dopamine caused nicking of circular Col El DNA and bound to calf thymus DNA in vitro. It is suggested that this genetic activity of dopamine in vitro relates to oxidation of dopamine and the generation of reactive oxygen radicals, semiquinones and quinones. It is unlikely that similar reactions would occur and cause genotoxic activity of dopamine in vivo.

Animals↗

The role of 5-hydroxytryptamine in the feline response to intravenous infusion of live E. coli.

A standardized septic shock was induced in cats by intravenous infusion of a live E. coli bacteria strain. The bacterial infusion induced a rapid haemodynamic response characterized mainly by a pulmonary arterial hypertension and a late phase characterized by systemic hypotension and hypodynamic circulation. Systemic arterial, pulmonary arterial, portal venous, left atrial pressures, max inspiratory-expiratory pressure difference in the trachea, aortic and intestinal blood flows were monitored. Arterial blood samples were taken for recording the number of circulating platelets and white blood cells and for determining the acid-base balance. The effect of pretreatment with ketanserin, a specific 5-hydroxytryptamine2 (5-HT2)-receptor blocker on these haemodynamic reactions was studied. In short term experiments on non-bacteriaemic control cats, ketanserin prevented the pulmonary hypertension induced by intravenous 5-HT infusions but not the increase in intestinal blood flow. Ketanserin induced a reduction of total peripheral (including intestinal) vascular resistance to blood flow but had no effect on aortic blood flow. After infusion of bacteria, ketanserin pretreated cats were more hypotensive due to a relative peripheral dilatation of the resistance vessels. Ketanserin pretreatment had no effect on the pulmonary vascular reactions, the tracheal pressure difference or the number of circulating platelets or white blood cells. Thus, except for a more pronounced hypotension early after bacterial infusion, ketanserin pretreatment did not influence the haemodynamic response. It is concluded that 5-HT is not of significant importance in the pathogenesis of the haemodynamic reactions following experimental bacteraemia.

Animals↗

Sympathetico-adrenergic influences on the small intestinal vascular reactions in experimental septic shock.

The objective of this study was to explore the vascular reactions in the small intestine and the possible role of sympathetico-adrenergic influences. The experiments were performed on 23 cats. The small intestinal blood flow was estimated using a drop counting technique. In one series of cats (n = 7) the small intestine and the adrenal glands had intact vascular and nervous supply (I), in another series (n = 7) the small intestine was sympathetically denervated and the adrenal vessels ligated (II), and in a third series (n = 9) the small intestine was innervated but the adrenal vessels ligated (III). The septic state was induced by i.v. infusion of live E. coli bacteria for two hours. The small intestinal blood flow decreased and intestinal blood flow resistance increased in all series within 3 min upon bacterial infusion. The intestinal vasoconstriction was maintained in cats with intestinal denervation as well as in cats with the adrenal vessels ligated, favouring that other humoral factors than catecholamines are involved. During the later phase of bacteremic shock the intestinal blood flow remained in the preseptic range in the series with a denervated small intestine and ligated adrenals as well as in intact cats, but declined gradually and significantly in cats with adrenal ligation only (III). This pattern of reactions favours a local rather than a remote sympathetico-adrenal influence.

Adrenalectomy↗

Effect of omeprazole--a gastric proton pump inhibitor--on pentagastrin stimulated acid secretion in man.

The effect of oral omeprazole on pentagastrin stimulated gastric acid secretion was studied in 11 healthy subjects. Doses of 20-80 mg produced dose dependent inhibition of acid secretion, with total suppression at the highest dose. Omeprazole was absorbed and eliminated from plasma rapidly and the inhibitory effect was related to the area under the plasma concentration time curve. The duration of action was long and single doses of 20 and 40 mg reduced acid secretion significantly for one and three days, respectively. Omeprazole in a dose of 15 mg given once daily for five days, suppressed acid secretion continuously, the inhibitory effect stabilising after three days at a predose inhibition of about 30% and a postdose inhibition of about 80%.

Adult↗

Intensive care treatment in septic shock.

Deaths in septic shock continue to occur at a high frequency despite current treatment programs. However, the mortality can be substantially decreased with a close bedside attendance of patients at risk and if the patient is transferred to an intensive care unit for intensive treatment and monitoring as soon as shock is suspected or established. The treatment program consists of adequate antibiotic administration in combination with massive doses of steroids and aggressive infusion therapy supplemented with cardiovascular drugs according to the hemodynamic response to the initial treatment.

Anti-Bacterial Agents↗

The effects of 5-HT blockade in graded intestinal vascular obstruction in the rat.

Intestinal vascular obstruction with an obstruction pressure of 120 cm of water for one hour induces a 75% mortality in rats. The mortality is associated with intestinal mucosal lesions, release of cardiotoxic material to the intestinal venous blood and trapping of platelets in the lungs. The present series of experiments was performed to study the role of released serotonin in the pathogenesis of the circulatory collapse that follows in this shock model. This was done by pretreating rats subjected to standardized intestinal vascular obstruction with Ketanserin, a selective 5-HT2 receptor blocking agent. It was found that Ketanserin reduced the increase in hematocrit otherwise induced but had no significant effect on mortality, trapping of platelets or the intestinal mucosal lesions. It is concluded that serotonin is probably not of significant importance in the pathogenesis of the circulatory collapse following intestinal vascular obstruction.

Animals↗

Cardiac output measurements with thermodilution and radioactive microspheres. A comparative study in cats.

Thermodilution and radioactive microsphere measurements are both commonly used methods for determination of cardiac output in experimental animals. However, no comparison has been made of these methods for cardiac output determination, which is why this study was made. In cats 65 simultaneous measurements of cardiac output with the two methods were performed. No difference in mean values was found and the coefficient of correlation was 0.955 (P less than 0.001). Only eight out of the 65 measurements differed more than 10%. Thermodilution measurements are suitable for repeated determinations and when immediate data are wanted. On the other hand radioactive microsphere measurements are preferable when data on tissue blood flow and blood flow distribution are desired as well. The high correlation found seems to allow cardiac output measurements with these two methods to be grouped together.

Animals↗

Gastric mycosis following gastric resection and vagotomy.

In a prospective five-year follow-up study of 289 consecutive patients subjected to antrectomy and gastroduodenostomy with or without vagotomy, 130 patients underwent gastroscopy. Gastric mycosis was present almost exclusively in patients subjected to combined antrectomy and vagotomy (36%). Gastric acidity seemed to be of only minor or no importance in the development of the mycosis. The residual volume in the gastric remnant was significantly higher in patients with gastric mycosis. The impaired emptying of the gastric remnant is most likely a vagotomy effect and may be the main reason for the development of gastric mycosis. A simple but effective method was developed to evacuate gastric yeast cell aggregates. Gastric mycosis seems to give rise to only slight symptoms, mainly nausea and foul-smelling belching, whereas the reflux of duodenal contents that often occurred in combination with gastric mycosis was more likely to cause gastritis and substantial discomfort.

Bile Reflux↗

The effects of secretagogues of isolated human gastric glands.

The function of isolated human gastric glands has been studied in vitro by measuring the 14C-aminopyrine accumulation (RAP) in basal, unstimulated, conditions and after stimulation with different secretagogues. A microscale technique was used which enabled determinations of RAP in tissue obtained as gastroscopic biopsies. In addition, oxyntic-gland-containing mucosa was obtained at gastric resections for gastric or prepyloric ulcer disease. Histamine and cAMP derivative both induced maximal stimulation; RAP was approximately three times larger than in basal states. Carbachol induced a smaller but still significant stimulation. Pentagastrin did not increase RAP above the unstimulated level. Combinations of histamine and carbachol or pentagastrin did not induce a larger response than carbachol alone. The peak acid response to pentagastrin or betazole in vivo did not correlate with the maximum RAP in vitro.

1-Methyl-3-isobutylxanthine↗

Cardiopulmonary function as related to intestinal mucosal lesions in experimental septic shock.

The purpose of the present investigation was to explore a possible relationship between cardiopulmonary function and small intestinal mucosal lesions in experimental septic shock. The filling pressure of the left ventricle of the heart (LVEDP) and the maximal pressure change during systole (max dP/dt) were monitored continuously by a tip-transducer catheter. The pulmonary and femoral arterial pressures and pressure changes in the trachea were recorded. The aortic blood flow was measured electromagnetically. Stroke volume, external cardiac work, and the pulmonary vascular resistance could be calculated. Twenty-two cats were made septic by i.v. infusion of live E. coli bacteria. Controls received saline i.v. After 2 hours of bacteremia, preload was increased by a rapid infusion of dextran to unmask cardiac dysfunction. Small intestinal specimens were taken for microscopical examination. The occurrence and the degree of mucosal damage was established. Thirteen cats had virtually normal mucosal appearances, whereas nine disclosed severe lesions. The loading procedure revealed a more pronounced cardiac dysfunction in cats with severe mucosal damage, compared to those without. Pulmonary vasoconstriction, bronchoconstriction, and impaired ventilation-perfusion ratio were also demonstrated, but these signs of pulmonary dysfunction did not differ when comparing animals with and without mucosal damage. A correlation between impaired cardiac function on one hand and hypotension--intestinal mucosal lesions on the other, suggests cardiotoxic material released from the damaged intestine as one contributing mechanism.

Animals↗

The effect of different anticholinergics on the gastric acid response to sham feeding in man.

Modified sham feeding by the chew and spit technique stimulates gastric acid secretion at a level about 50% of peak acid output. This response is vagal and can be totally blocked by vagotomy. The effect on the acid response to modified sham feeding produced by a quaternary amine, benzilonium bromide, and a presumably more selectively acting antimuscarinic drug, pirenzepine, was compared. The drugs were given 45 min and 10 min before the start of the sham feeding, respectively. Benzilonium bromide, 1 + 1 mg, blocked 73% of the acid response to sham feeding and pirenzepine, 10 + 10 mg, blocked 48% of the response. The difference was not statistically significant. The data confirm that a part, about one third, of the acid response to sham feeding is non-cholinergic, although it is vagal.

Adult↗