Hypoxia and reoxygenation--two mechanisms for tissue injury in ischemia and shock.
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Animals↗
Biomedical subjects
U Haglund
Publications and source records attributed to U Haglund.
Arachidonic acid cascade metabolites in porcine E. coli shock. Coagulation, fibrinolytic and hemodynamic response.
Cardiopulmonary hemodynamics and changes in various hemostatic factors (alpha 2M, alpha 2AP, AT III, prothrombin-proconvertin activity, fibrinogen concentration, ethanol gelation test and fibrinolytic activity on fibrin plates) were investigated in pigs during shock induced with live Escherichia coli. Anesthetized pigs were treated with indomethacin or with the combined cyclooxygenase/lipoxygenase inhibitor BW755C before the E. coli infusion or were left untreated as septic controls. Septic shock developed in all of these animals. Pretreatment attenuated the early deterioration of pulmonary circulation but did not modify the coagulation/fibrinolytic activation or the disturbed cardiopulmonary hemodynamics seen in the delayed phase of shock. The arachidonic acid cascade metabolites thus seems to mediate the early, but not the delayed cardiopulmonary reaction and to have minor importance for activation of coagulation and fibrinolysis in E. coli-shocked pigs.
Animals↗
Cardiopulmonary function as related to thromboxane A2 synthesis in experimental septic shock.
The aim of the present study was to explore the possible involvement of thromboxane A2(TxA2) in the development of cardiopulmonary dysfunction in experimental septic shock. Sepsis was induced in anesthetized cats by intravenous (i.v.) infusion of live Escherichia coli. One series (No. = 12) was pretreated with a specific TxA2 synthetase inhibitor, dazmegrel; another (No. = 8) served as a septic control series. In both series a systemic arterial hypotension developed after 2 hr; no differences in cardiac function were detected. After 2 hr bacteremia cardiac preload was increased by a rapid infusion of dextran. This showed that cardiac function was significantly more preserved in dazmegrel-pretreated cats compared with septic controls. Pretreatment with dazmegrel totally prevented the pulmonary vascular response to bacterial infusion. The pulmonary compliance decreased to 40% in controls but to only 75% in the dazmegrel series, and airway resistance increased to 300% and 140%, respectively. The ventilation-perfusion ratio was less impaired in the pretreated series. Pretreatment with dazmegrel abolished the increase in thromboxane B2 (TxB2), the stable metabolite of TxA2, seen in the untreated series. The rise in 6-keto-prostaglandin F1a (6-keto-PGF1a), the stable metabolite of prostaglandin I2PGI2, was evident in both series. We concluded that TxA2 is important for the impaired cardiac performance in septic shock. Furthermore, TxA2 is involved, but not as the only factor, in the development of pulmonary dysfunction.
Airway Resistance↗
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↗
[Sclerotherapy and/or surgery in bleeding esophageal varices?].
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Esophageal and Gastric Varices↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗