[Thoraco-abdominal aortic aneurysm--is surgery the solution?].
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Biomedical subjects
Publications and source records attributed to S Steen.
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The effect of intraportal infusion of norepinephrine (NE) on primary hemostasis in the cirrhotic rat was investigated at standardized liver trauma. Cirrhosis was induced by simultaneous administration of increasing amounts of carbontetrachloride (CCl4) and phenobarbitone. Infusion of norepinephrine took place after cannulation of the gastroduodenal vein. Intraportal infusion of NE resulted in a significant increase in arterial blood pressure and portal pressure in all animals. No difference was observed between cirrhotic and control rats. Cirrhotic animals bled longer and more profusely as compared with the controls. Infusion of NE resulted in significant decrease in bleeding time and blood loss. NE did not affect hematocrit, hemoglobin, platelet, or white cell count. Platelet aggregation was not influenced by the compound. In conclusion, intraportal infusion of NE proved effective in decreasing hemorrhage at liver trauma in cirrhotic rats.
The effect of the simultaneous administration of norepinephrine and 5-fluorouracil (5-FU) on the uptake of radiolabelled 5-FU by liver tumours was studied in rats. Three different concentrations of 5-FU were used (15, 1.5 and 0.15 microgram/g body weight). The drugs were infused over a 30 min period via the hepatic artery, following cannulation of the gastroduodenal artery. The radioactivity in liver tumour, normal liver, lungs and intestines was estimated by liquid scintillation counting. At all concentrations tested, an increased uptake of radioactive 5-FU was found in the tumour when norepinephrine was infused. Tumour/liver ratios also increased significantly in all these cases. No significant differences were noted between norepinephrine infused and control animals in the radioactivity in normal liver, lungs and intestines. The effects noted were possibly due to changes in blood flow within the liver, but the possibility of a direct effect of norepinephrine on DNA metabolism is discussed.
Concentration of superfluous blood in the oxygenator after the termination of a cardiopulmonary bypass was studied in 46 aortocoronary bypass patients. 15 patients were treated with a centrifugation system, the Haemonetics Cell Saver, 16 patients were treated with the Gambro Hollow Fibre Hemofilter and the remaining 15 patients received as much as possible from the untreated oxygenator contents and served as controls in a coagulation study. Both methods functioned well, the time consumption for operation of the two systems was similar. The products differed greatly as centrifugation revealed highly concentrated red cells in saline solution while hemofiltration produced protein-rich concentrated whole blood. A coagulation study of the patients who had received the concentrated products showed no signs of activation of the coagulation factors nor of the fibrinolytic system.
A pharmacological characterization of the postjunctional alpha-adrenoceptors in human superficial epigastric artery and vein was performed, using several alpha-adrenoceptor subtype selective agonists, and the antagonists prazosin (alpha 1) and rauwolscine (alpha 2). In the arteries prazosin fulfilled the criteria for a competitive antagonism in concentrations 10(-9)-10(-7) M, giving a pA2-value of 9.17 in the Schild plot. Rauwolscine in concentrations 10(-8)-10(-6) M caused less pronounced but significant dextral shifts of the noradrenaline (NA) concentration-response curves. In the veins rauwolscine behaved like a competitive antagonist (10(-8)-10(-7) M). The pA2-value was 9.16. Prazosin 10(-9) M displaced the NA concentration-response curve, but higher concentrations (10(-8) and 10(-7) M) caused no further displacement. Prazosin reduced the Emax-values in the veins. In the arteries the rank order of potency for the agonists was: cirazoline (alpha 1) greater than NA greater than naphazoline (alpha 2) greater than guanfacine (alpha 2) greater than phenylephrine (alpha 1). The intrinsic activities of clonidine (alpha 2), ST 587 (alpha 1), B-HT 920 (alpha 2) and B-HT 933 (alpha 2) were too low to allow meaningful comparisons to be made. The rank order of potency in the veins was: NA greater than clonidine (alpha 2) greater than naphazoline (alpha 2) greater than guanfacine (alpha 2) greater than phenylephrine (alpha 1) greater than B-HT 920 (alpha 2) greater than cirazoline (alpha 1) greater than B-HT 933 (alpha 2). The intrinsic activity of ST 587 was low.(ABSTRACT TRUNCATED AT 250 WORDS)
We investigated the effects of five different calcium-channel blockers (CCBs), verapamil, nifedipine, diltiazem, flunarizine and lidoflazine, on contractions evoked in vitro by noradrenaline (NA) in small human arteries and veins from the epigastric region. Vessels were obtained from patients without obvious vascular diseases undergoing surgery because of inguinal hernias. The human superficial epigastric artery has previously been shown to contain mainly alpha 1-adrenoceptors, whereas in the vein alpha 2-adrenoceptors predominate. In experiments where NA (10(-5) M) was added non-cumulatively, it was found that nifedipine was the most potent relaxant agent in both arteries and veins, but that this drug showed no preference for any type of vessel. In contrast verapamil (10(-6) M) and (10(-5) M) diltiazem, flunarizine and lidoflazine inhibited the NA-induced contractions to a significantly greater extent in the arteries than in the veins. Comparison between diltiazem and nifedipine on contractions induced by cumulative addition to NA showed that both drugs had significantly more depressive effects on arteries than on veins if the vessels were contracted by relatively high concentrations of NA (10(-6) and 10(-5) M). The results thus confirm the clinical finding that CCBs have more pronounced effects on the arterial than on the venous side of the circulation. They do not support the view that CCBs are more effective inhibitors of alpha 2- than alpha 1-adrenoceptor mediated contraction in isolated human blood vessels.
The effect of intraarterial, intraportal or simultaneous intraarterial and intraportal norepinephrine (NE) infusion on hemorrhage after standardized liver trauma was evaluated in the rat. Infusion of NE through a catheter in the gastroduodenal artery or/and vein, was started 5 min prior to the liver trauma and continued throughout the experiment. Blood pressure was continuously registered after cannulation of the femoral artery. Standardized liver trauma involved resection of the left anterior liver lobe. Bleeding time, blood loss from the traumatized liver surface, hemoglobin (Hb), hematocrit (Hct), platelet count (PC) and white blood cell count (WBC) were measured. Infusion of NE resulted in significant increase of blood pressure compared with controls. Infusion of NE (i.a., i.p., i.a. + i.p.) caused significant decrease in bleeding time and blood loss. Hb, Hct, PC and WBC were not affected. NE infusion proved effective in decreasing hemorrhage at liver trauma; the route of administration did not influence the results.
The rate of postoperative bleeding was studied in 32 patients with aortocoronary bypass surgery and in 18 with aortic valve replacement. In 12 of the 50 patients, more than 500 ml of shed mediastinal blood could be saved within 8 postoperative hours. Aerobic and anaerobic cultures of such blood were obtained from the suction reservoir in 20 cases 2, 4 and 6 hours postoperatively. The results were negative, apart from Staphylococcus albus in one 6-hour sample. The blood, which was in some degree hemolyzed, contained acceptable amounts of red cells and albumin. Alterations of the coagulation and fibrinolytic systems indicated massive proteolysis with degradation of the proteins to an extent that precluded coagulation. This proteolysis had taken place in the mediastinum, resulting in total defibrinogenation of the blood. The authors conclude that in about one-fourth of cases in cardiac surgery, postoperatively shed blood is worth saving for red cell and volume substitution.
A new autotransfusion system was evaluated postoperatively in six patients undergoing aortocoronary bypass surgery. A hollow fiber hemofilter was integrated in the system, making it possible to concentrate the shed blood. The device functioned well, 825 ml diluted mediastinal drainage blood with a hematocrit of 23 was concentrated to a volume of 475 ml with a hematocrit of 36 and retransfused. Proteins were preserved, thus albumin concentration increased from 23 to 37 g/l in the autotransfusate. No negative side effects were registered after autotransfusion. A thorough coagulation study after retransfusion did not reveal any sign of activation of the coagulation cascade, nor were there any signs of an increased fibrinolysis.
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Lymphatics from the human superficial groin removed at operation in 21 patients (one with lymphedema) were examined in vitro. Histochemically no nerves were identified with either specific catecholamine fluorescence or immunoreactivity to tyrosine hydroxylase or dopamine beta-hydroxylase. Ring preparations of the lymphatics were mounted in tissue baths and isometric induced contractions were recorded after administration of K+ (124 mM), acetylcholine, selected amines and prostanoids. Noradrenaline (NA), adrenaline, dopamine, and acetylcholine had no or only weak contractile effects. In some segments, serotonin induced contractions. Prostaglandin E2 showed no contractile effect and prostaglandin F2 alpha induced contraction in most of the tested lymphatics. The prostaglandin-endoperoxide analogue U44069 uniformly elicited marked concentration-dependent contraction. In the lymphatic segment from the patient with lymphedema, a slightly greater contractile response to NA and serotonin was observed. The results overall suggest an absence of sympathetic innervation and contraction-mediating alpha adrenergic receptors in human superficial groin lymphatics, and support that certain prostanoids may be important regulators of human lymphatic contractility.
Thirty rats were subjected to a standardized lethal hepatic and retrohepatic caval vein injury. The animals were divided into six groups. In addition to controls (I), the animals were treated with a pneumatic antishock garment (PASG) (II), massive intravenous (III), or intra-aortic (IV), saline infusion, or PASG in combination with either massive intravenous (V) or intra-aortic (VI) saline infusion. Intravenous and intra-aortic infusion of saline led to a median survival time of 13 min and 37 min, respectively, not statistically different from the control group. Nine of ten animals who had the combined treatment with PASG and infusion of saline developed a fulminant pulmonary edema. The treatment with PASG alone, however, prolonged survival time significantly from a median survival time of 10 min in the control group, to greater than 120 min in the treated group.
The effects of the alpha-adrenoceptor subtype-selective antagonists prazosin (alpha 1) and yohimbine (alpha 2) on the saphenous vein of six healthy male subjects were investigated in vivo. The drugs were infused locally into the congested (40 mmHg), long saphenous vein constricted by simultaneous local infusion of noradrenaline (NA). Prazosin 10(-9) M (concentration in the infusion solution, infusion rate 0.3 ml min-1) did not reduce the NA-induced venoconstriction, but at a concentration of 10(-8) M there was a significant reduction; in two subjects no response to NA could be elicited in the presence of 10(-8) M prazosin. Prazosin 10(-7) M caused no further reduction of the NA effect compared to that produced by 10(-8) M in three of the subjects, whereas in one, prazosin 10(-9), 10(-8) and 10(-7) M caused a dose-dependent blockade. Yohimbine, 10(-9), 10(-8) and 10(-7) M caused a dose-dependent reduction of the NA-induced venoconstriction in all subjects. The results suggest that the human saphenous vein is endowed with functionally important populations of both alpha 2- and alpha 1-adrenoceptors.
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Human omental arteries and veins are supplied with nerve fibers containing noradrenaline (NA) and neuropeptide Y (NPY); these two agents probably co-exist in perivascular sympathetic nerve fibers. Substance P (SP)- or vasoactive intestinal peptide (VIP)-containing fibers could not be detected. In studies on isolated omental vessels NA produced constriction. The results of blockade experiments suggest that human omental arteries are equipped predominantly with alpha 1-adrenoceptors and omental veins with a mixture of alpha 1- and alpha 2-adrenoceptors. NPY at a concentration of 10(-7) M or higher had a weak contractile effect on veins and virtually no effect on arteries. NPY at a concentration of 3 X 10(-8) M shifted the NA concentration response curve to the left in arteries (pD2 = 5.8 for NA versus 6.6. for NA in the presence of NPY; P less than 0.001) but not in veins. Both SP and VIP relaxed arteries precontracted with NA or prostaglandin F2 alpha (PGF2 alpha). The potency of SP as a relaxant agent was similar in arteries and veins; the effect of VIP was elicited at lower concentrations in veins than in arteries.
The postjunctional alpha-adrenoceptors in human long saphenous vein were characterized using alpha-adrenoceptor subtype selective agonists and antagonists. The order of potency for the alpha-adrenoceptor agonists used was: Clonidine (alpha 2) greater than BHT-920 (alpha 2) greater than naphazoline (alpha 2) greater than guanfacine (alpha 2) greater than cirazoline (alpha 1) greater than phenylephrine (alpha 1) greater than ST 587 (alpha 1) greater than BHT-933 (alpha 2). Clonidine had the same potency as noradrenaline (NA), but was 52 times more potent than phenylephrine (pEC50 7.09 and 5.37, respectively). Phenylephrine and guanfacine had intrinsic activities that did not differ from that of NA, whereas the intrinsic activities of the other agonists were significantly lower. The highly selective alpha 1-adrenoceptor antagonist prazosin in concentrations 10(-9)-10(-7) M was unable to cause a significant shift of the NA concentration response (cr) curve to the right. However, the alpha 2-adrenoceptor antagonists yohimbine and rauwolscine in concentrations 10(-8)-10(-6) M shifted the NA cr-curve towards higher concentrations. No concentration of any antagonist used significantly attenuated the maximum contraction. The slope of the regression line in the Schild plot differed significantly from unity for rauwolscine but not for yohimbine, and the pA2-values were 9.00 and 8.27, respectively. These results suggest that the contraction mediating alpha-adrenoceptors in the human saphenous vein are mainly of the alpha 2-type. However, the low slope value of the Schild plot for rauwolscine may indicate the presence of a small population of alpha 1-adrenoceptors.
The alpha-adrenoceptors in human omental arteries and veins were characterized and compared. In the arteries both prazosin (pA2 9.48) and rauwolscine (pA2 7.19) displaced the noradrenaline (NA) concentration-response (cr) curve towards higher concentrations without reduction of maximum. Neither clonidine, nor oxymetazoline had any consistent contractile effects. Phenylephrine had a lower potency than NA, but a similar intrinsic activity. In the veins, both prazosin (pA2 9.72) and rauwolscine (pA2 8.11) displaced the NA cr-curve towards higher concentrations, but also significantly depressed maximum. Clonidine and oxymetazoline contracted veins from 3 out of 7 and 4 out of 6 patients, respectively. Their pD2-values were similar to that of NA, but their intrinsic activities were significantly lower. NA was more potent than phenylephrine in these vessels, and there was no significant difference in intrinsic activity. The results suggest that in human omental arteries, the postjunctional alpha-adrenoceptors are mainly of the alpha 1-type, even if a small population of alpha 2-adrenoceptors cannot be excluded. In omental veins, there seems to be a functionally important population of postjunctional alpha 2-adrenoceptors occurring together with a population of alpha 1-adrenoceptors.
By means of selective agonists and antagonists for alpha 1- and alpha 2-receptors, the alpha-receptor subtypes in human groin arteries and veins were characterized and compared. In the arteries the alpha 1-receptor blocker prazosin caused a concentration-dependent parallel displacement of the noradrenaline (NA) concentration-response (cr) curve without reduction of maximum (pA2 = 9.86); the selective alpha 2-receptor antagonist rauwolscine in the concentration 10(-8) M caused a right-ward shift of the NA cr-curve without reduction of Emax, but 10(-7) M and 10(-6) M caused little or no further shift. In the veins, the two antagonists had the opposite effects. Rauwolscine caused a concentration-dependent right-ward shift of the NA cr-curve without depression of maximum (pA2 = 9.03); prazosin 10(-9) M significantly displaced the NA cr-curve, whereas 10(-8) M and 10(-7) M caused little or no further shift. The responses to the alpha 2-receptor agonist clonidine in the arteries were too small to allow calculations of pEC50 values; in the veins contractions were elicited in all vessel segments investigated (pEC50 = 6.24). Phenylephrine, selective for alpha 1-receptors, was significantly more potent in arteries than in veins. NA was significantly more potent in veins than in arteries. It is concluded that in human groin vessels, there is a functional predominance of alpha 1-receptors in the arteries and of alpha 2-receptors in the veins.