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Biomedical subjects

U Haglund

Publications and source records attributed to U Haglund.

At least 127 records · Page 7Linked to original sources
PubMed1988

The splanchnic organs as the source of toxic mediators in shock.

The splanchnic organs, and especially the pancreas and the small intestine, are susceptible to injury during ischemia and shock and the following reperfusion. This particular tissue injury is associated with a release of cardiotoxic and other toxic mediators which further aggravate the shock condition, leading to further tissue injury etc. Thereby a vicious circle is created, which is likely to contribute to collapse and death.

Bacterial Toxins↗
PubMed1987

Cardiac output and its distribution in peritonitis. (Septic) shock in the rat.

Cardiac output and its distribution were studied in rats made septic by an i.p. injection of live E. coli bacteria and in controls given an equivalent amount of saline. The E. coli injection was followed by signs of severe shock in eight of 12 rats. Control animals all survived with only minor changes in cardiac output and peripheral hemodynamics. Blood flow in shocked animals was characterized by a reduction of cardiac output, while myocardial and cerebral flows were not reduced. The intact circulation to the brain and to the heart in the shocked rats was at the expense of kidney, spleen, and skin blood flows.

Animals↗
PubMed1987

Do enkephalins participate in vagal activation of gastric acid secretion in man?

The effects of the anticholinergic drug benzilonium bromide and the opiate receptor blocker naloxone, given alone or in combination, on the acid secretory response and on plasma gastrin releasing peptide (GRP) response to sham feeding was tested in eight duodenal ulcer (DU) patients. Naloxone alone had no effect on the acid secretion after sham feeding. Benzilonium reduced basal acid secretion and the acid response to sham feeding but did not abolish the response. The combination of benzilonium and naloxone was not more effective than benzilonium alone. Neither drug, nor the combination had any effect on plasma GRP following sham feeding. It is concluded that enkephalins are unlikely to participate in the acid response to sham feeding in patients with DU.

Adult↗
PubMed1987

The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli.

Bacterial infusion in the cat, causing experimental septic shock, induces an early vascular response mainly characterized by pulmonary hypertension and intestinal vasoconstriction. Prostanoids are held to be important mediators of the pulmonary vascular reaction. This study was performed to explore the involvement of prostanoids in the central haemodynamics and the small intestinal vascular reactions in experimental septic shock. Aortic blood pressure was continuously monitored, as were aortic blood flow, the pressure in a. pulmonalis and the small intestinal venous outflow. All cats (n = 24) were given live E. coli (10(10) ml-1) as a continuous intravenous infusion. One series was pretreated with indomethacin, another with UK-38,485, a specific thromboxane A2 synthetase inhibitor, and a third series served as untreated control. The pulmonary hypertensive response was clearly attenuated in the two pretreated series, in fact abolished in the one given UK-38,485. The early intestinal vasoconstriction was eliminated in the two pretreated series. Later during bacteraemia, when untreated and indomethacin-pretreated cats showed intestinal vasoconstriction, UK-38-485-pretreated animals kept intestinal blood flow within the preseptic range. These data suggest that in the cat, thromboxane A2 is the prostanoid mediating the vascular reactions, not only in the lung but also in the small intestine.

Animals↗
PubMed1987

Histamine H2-receptor of human and rabbit parietal cells.

The histamine H2-receptor on the human parietal cell has been characterized by using dose-response curves and the negative logarithm of the molar concentration of an antagonist (pA2) analyses of cimetidine antagonism of betazole, histamine, and impromidine stimulation in isolated human and rabbit gastric glands. To evaluate the in vitro results, betazole-stimulated gastric acid secretion with and without cimetidine was also studied in healthy subjects. In the in vivo model, individual dose-response curves were shifted to the right with increasing cimetidine concentrations, but this was counteracted by increasing betazole doses, indicating competitive, reversible antagonism. The pA2 values ranged from 6.1 to 6.3. In isolated human gastric glands, impromidine was shown to be eight times more potent than histamine, indicating higher receptor affinity, but the maximally stimulated aminopyrine accumulation was the same as for histamine, and the pA2 values for cimetidine antagonism did not differ significantly, i.e., 5.7 (histamine) and 6.1 (impromidine). In isolated rabbit gastric glands, cimetidine inhibited the histamine- and impromidine-stimulated response with pA2 values of 6.0 and 7.3, respectively. Impromidine was shown to be approximately 100 times more potent than in human gastric glands, whereas histamine had the same potency. This confirms the role of the histamine H2-receptor and suggests a difference between the species concerning receptor affinity.

Adult↗
PubMed1987

Secretory state and acute gastric mucosal injury in sepsis.

Cats were subjected to a standardized 3-h septicemia by intravenous infusion of live Escherichia coli in an LD50 dose. The effect of pentagastrin stimulation on the development of gastric mucosal injury was studied. There was no hemodynamic difference between the series during septicemia. Thus, pentagastrin did not induce increased gastric blood flow during the period of E. coli infusion. Intraluminal gastric pH was lower in the series given pentagastrin during the last 2 h of septicemia. Nevertheless, the extent of gastric mucosal injury was similar in the two groups, whereas the depth of injury was, if anything, less pronounced in the pentagastrin-stimulated group.

Acute Disease↗
PubMed1987

Intestinal vascular obstruction shock in the rat. Effect of 2 dextran solutions on blood and plasma volumes, cardioinhibitory activity in blood and pulmonary platelet trapping.

Pathophysiologic mechanisms involved in the dextran effect on mortality in intestinal shock in rats were studied, using a standardized model for intestinal vascular obstruction. Both dextran 70 and dextran 40 (respective mean molecular weights 70 X 10(3) and 40 X 10(3) d) given to shocked rats reduced but did not prevent the cardioinhibitory action of intestinal venous plasma in vitro. Both dextrans prevented platelet trapping in the lungs. Reduction in blood and plasma volumes was found in shocked rats given saline or dextran 40, but not following dextran 70. These differences were found after 120 min, but not after 240 min, when all shocked groups had lower blood and plasma volumes than in non-shocked controls. The results indicate that several mechanisms influence the effect of dextran 70 on mortality of rats in intestinal shock. Previously observed difference in mortality rates after infusion of dextran 70 and dextran 40 could not be explained by mechanisms studied in this series of experiments.

Animals↗
PubMed1987

Coagulation and fibrinolytic reactions in experimental porcine septic shock: pretreatment with different antiplatelet factors.

The aim of this study was to investigate the influence on various hemostatic factors (alpha 2-macroglobulin, antiplasmin, antithrombin III, prothrombin-proconvertin activity, fibrinogen concentration, ethanol gelation test, and fibrinolytic activity on fibrin plates) of bacteremic shock in swine and the influence on these factors of drugs interfering with platelet function. Anesthetized pigs were given live Escherichia coli intravenously (n = 49) or Ringer's solution (n = 7) and were monitored for 3 hours. Pretreatment was given with indomethacin (n = 6), the TxA2 inhibitor UK 38 485 (n = 7), the prostacyclin analogue ZK 36 374 (n = 7), the 5HT antagonist ketanserin (n = 6), or ketanserin combined with UK 38 485 (n = 9) or dipyridamole (n = 8). Septic shock developed in all E. coli animals. There were decreased levels of platelets and leukocytes and activation of the coagulation/fibrinolytic systems by E. coli. Except for a slight attenuating effect on the antithrombin III (ketanserin and dipyridamole) and alpha 2-macroglobulin (ketanserin) decreases, there were no significant effects of the drugs. It is concluded that live E. coli induced several changes within the coagulation and fibrinolytic systems. Only minor effects were seen when different drugs influencing platelet function were given.

Animals↗
PubMed1987

Role of histamine H2 receptor antagonists in nonoperative management of gastroduodenal ulcer haemorrhage.

Acute massive gastroduodenal ulcer haemorrhage may be caused by peptic ulcers or acute stress ulcerations. The former is a clinical problem that is met with fairly frequently, associated with a mortality of 10-20%. Bleeding stress ulcerations are less common but have a still more serious prognosis. The histamine H2-receptor antagonist cimetidine has in one large study been demonstrated to reduce mortality in ulcer haemorrhage, and in other studies beneficial effects have been found in elderly patients; above all in elderly gastric ulcer patients. Other authors again find no beneficial effects. The inconsistent results can be due to the fact that other factors, such as high age, profuse bleeding, and concomitant disabling diseases, are more important for the outcome than inhibiting acid secretion with H2-receptor antagonists. In stress ulcers, H2-receptor antagonists have been shown to be effective as part in the prophylactic treatment. Antacids might be more effective, but high doses are often required.

Acute Disease↗
PubMed1987

Pulmonary vascular response to live Escherichia coli: influences of different antiplatelet substances.

The aim of this study was to investigate whether pretreatment with drugs that interfere with platelet functions in different ways could modify the pulmonary vascular response in a porcine septic shock model. Septic shock was induced by i.v. infusion of live Escherichia coli bacteria. Bacteriemic animals were divided into five groups: untreated or pretreated with a thromboxane-A2 synthetase inhibitor (UK 38 485), a serotonin-receptor antagonist (ketanserin), a combination of these two drugs, or a platelet antiaggregating drug (dipyridamole). E. coli induced significant pulmonary hemodynamic and respiratory changes. The pulmonary responses to E. coli infusion were attenuated after pretreatment with UK 38 485 but unaffected by prior administration of ketanserin or dipyridamole. The combined pretreatment did not attenuate the pulmonary hypertension or other pulmonary responses to E. coli more than UK 38 485 alone. Dipyridamole did not alter the pulmonary circulation after bacterial infusion. It was concluded that thromboxane-A2 is an important, but not the only, mediator of the pulmonary vascular response in septic-shocked pigs and that factors such as serotonin and platelet aggregability seem to be of minor, if any, importance for the hemodynamic response.

Animals↗
PubMed1987

Septic shock in the rat: activation of plasma proteolytic systems and effects of a kallikrein inhibitor/bradykinin antagonist (S-2441).

Septic shock was induced in rats by intraperitoneal injection of live Escherichia coli. Plasma prekallikrein, antithrombin III and plasminogen levels were studied with chromogenic peptide substrate assays. Decrease of all the studied plasma components occurred in all rats, but not until late in shock. S-2441, a kallikrein inhibitor/kinin antagonist, slightly delayed the fall in plasma prekallikrein, but no other effects were found. Rat survival was neither enhanced nor prolonged.

Animals↗
PubMed1987

On the pathophysiology of intestinal ischemic injury. Clinical review.

Intestinal ischemia induces a spectrum of injury from relatively subtle changes in mucosal capillary permeability to gross transmural infarction depending on severity and duration. There is basically two events that can induce intestinal tissue injury in ischemic states, namely hypoxia during the ischemic period and generation of oxygen free radicals following ischemia at reperfusion. In this paper we review data indicating that there is a continuum of injury from the least to the most severe, and by approaching the problem from this perspective we have, in addition, tentatively defined the roles of the two mechanisms in the development of various degrees of intestinal ischemic tissue injury.

Capillary Permeability↗
PubMed1986

The influence of ketanserin on hemostasis in vitro.

Ketanserin is a new selective 5-HT2 receptor blocker. It has been used to indirectly study the influence of serotonin on hemostatic function in vitro. Coagulation and fibrinolysis in vitro were not affected. In high doses adrenalin induced platelet aggregation was inhibited but no influence was seen on collagen or ADP induced aggregation. It can be concluded that it is not very likely that serotonin plays an important role in initial hemostasis. However, the findings ought to be confirmed in vivo.

Adenosine Diphosphate↗
PubMed1986

Intestinal vascular obstruction in the cat. Right heart function in a shock model.

Cardiovascular function was studied in a model of intestinal vascular obstruction in cats. To measure right ventricular end diastolic pressure and maximal dP/dt, a tip transducer catheter was placed into the right ventricle. The intestinal vascular obstruction resulted in shock with decreases of blood pressure, cardiac output, and external cardiac work. Small intestinal mucosal lesions were found in all shocked cats. At an increased preload to the heart, right ventricular function was depressed in shocked cats. The model corresponds to one used earlier in the rat, where cardioinhibitory activity in venous blood was found in vitro. In this corresponding model of intestinal shock in the cat a depressed function of the right ventricle of the heart was found in vivo.

Animals↗
PubMed1986

A single nighttime dose of ranitidine 300 mg versus ranitidine 150 mg twice daily in the acute treatment of duodenal ulcer: a European multicenter trial.

Six hundred and five patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine 300 mg at night or ranitidine 150 mg twice daily in a prospective double-blind multicenter trial conducted in nine European countries. Endoscopy at 4 weeks showed complete ulcer healing in 246 of 301 patients (82%) treated with ranitidine 150 mg b.i.d. and 230 of 304 patients (76%) treated with ranitidine 300 mg at night. Cumulative healing rates at 8 weeks were 95 and 94% respectively. Both treatment regimens were equally effective at rapidly reducing the incidence of ulcer-related symptoms. Adverse events were few and consistent with those reported in previous studies with ranitidine 150 mg twice daily. The results of this trial indicate that a single nighttime dose of ranitidine is an effective and safe alternative to the twice daily regimen in the acute treatment of duodenal ulcer.

Adult↗
PubMed1986

Mode of action, toxicity, pharmacokinetics, and efficacy of some new antiherpesvirus guanosine analogs related to buciclovir.

9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine (3HM-HBG), (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine ([+/-]2HM-HBG), and cis-9-(4-hydroxy-2-butenyl)guanine (2EN-HBG), new acyclic guanosine analogs structurally related to buciclovir (BCV [(R)-9-(3,4-dihydroxybutyl)guanine]), were evaluated in parallel with buciclovir as anti-herpes simplex virus (HSV) agents. In cell cultures, replication of different strains of HSV type 1 (HSV-1) and HSV-2 was inhibited at nontoxic drug concentrations. The concentrations giving 50% inhibition of plaque formation were, however, dependent on virus strain and cell type. In most cell types, the order of activity against HSV-1 strains was 3HM-HBG greater than (+/-)2HM-HBG greater than BCV greater than 2EN-HBG, whereas the drugs showed an approximately equivalent activity against HSV-2 strains in different cells. The cytotoxic effects of the drugs were also cell type dependent, the order of activity being BCV greater than 3HM-HBG = (+/-)2HM-HBG greater than 2EN-HBG. At growth-inhibitory concentrations, the guanosine analogs BCV, 3HM-HBG, and (+/-)2HM-HBG showed clastogenic effects in human lymphocytes, mainly because of the induction of chromatid breaks. When evaluated for their anti-HSV effects in systemic HSV-1 infections in mice, the order of activity was BCV = 3HM-HBG greater than (+/-)2HM-HBG greater than 2EN-HBG, and in mice infected systemically with HSV-2, only BCV and 3HM-HBG showed efficacy. The differences between efficacy in vitro and in vivo could be explained in part by differences in kinetics of the drugs in mouse plasma, as the more efficacious drugs, BCV and 3HM-HBG, showed lower clearances and longer half-lives than the less efficacious ones, (+/-)2HM-HBG and 2EN-HBG. When used topically against a cutaneous HSV-1 infection in guinea pigs, 3HM-HBG showed an effect equivalent to that of BCV, whereas (+/-)2HM-HBG and 2EN-HBG were inactive. Mechanistically, the guanosine analogs were characterized by a high affinity for the viral thymidine kinase and a low affinity fo a cellular thymidine kinase and by their inhibition of viral DNA synthesis in infected cells.

Acyclovir↗
PubMed1986

Effects of naloxone in intestinal shock in the rat.

The contribution of endogenous opioid peptides to the development of circulatory derangement in severe shock was studied using naloxone. A standardized intestinal shock was induced in rats by applying a pressure of 120 cm water on the mesenteric vessels for 60 min. The rats were then given either saline or naloxone. Mean arterial blood pressure improved and a less severe acidosis resulted in naloxone-treated animals compared to saline-treated. No differences were found in hematocrit, the degree of small intestinal mucosal lesions, or survival rates after 7 days comparing naloxone and saline treatment. Survival time increased after naloxone but not after saline treatment. The results support the hypothesis that endogenous opioid peptides contribute to cardiovascular collapse in intestinal shock.

Acid-Base Equilibrium↗