Biomedical subjects

J Vaage

Publications and source records attributed to J Vaage.

At least 109 records · Page 6Linked to original sources

PubMed1992

Toxic oxygen metabolites reduce inactivation of prostaglandin E2 in isolated perfused rat lungs.

The metabolic function of the lungs may be impaired in acute lung injuries. The present work examined the effect of toxic oxygen metabolites (TOM) on the pulmonary clearance of prostaglandin E2 (PGE2). Isolated rat lungs perfused with plasma were exposed to TOM, generated by xanthine oxidase (XO) and hypoxanthine (HX) in the perfusate. Inactivation of PGE2 was determined by superfusion bioassay technique. XO and HX (n = 6) reduced the inactivation of PGE2 from 78 +/- 4% (mean +/- SE) to 61 +/- 3%. This reduction was inhibited by the free radical scavengers superoxide dismutase and catalase, as well as by allopurinol, an inhibitor of XO. Neither hydrostatic lung edema nor perfusion per se decreased the inactivation of PGE2. Lungs pretreated with indomethacin still showed impaired PGE2 inactivation after exposure to XO and HX, indicating that a possible release of PGE2-like substances did not influence our findings. This study indicates that TOM may impair pulmonary metabolic function as shown by reduced inactivation of PGE2.

Animals↗

PubMed1991

Could treatment with scavengers of oxygen free radicals minimize complications in cardiac surgery?

Cardiac surgical complications may be caused by a plethora of events. Oxygen free radicals may participate in the pathophysiology of cardiopulmonary bypass and myocardial ischaemia-reperfusion injury. The evidence of free radical production during bypass is limited, and studies of the effect of free radical scavengers even more limited. Experimental work points towards a role of oxygen free radicals in reperfusion damage of the ischaemic myocardium, but clinical data are lacking. Hitherto the clinical availability of free radical scavengers/antioxidants has been scarse. At present more such drugs are becoming clinically applicable, and trials on their effect are highly warranted, in particular as an adjuvant in myocardial protection.

Animals↗

PubMed1991

Peri-tumor interleukin-2 causes systemic therapeutic effect via interferon-gamma induction.

This study compares the direct local therapeutic effects of multiple peri-tumor injections of interleukin-2 (IL-2) and interferon gamma (IFN-gamma), also the associated systemic therapeutic effects on distant untreated tumors resulting from the peritumor injections. The therapeutic effects were tested against intramammary implants of an immunogenic, syngeneic C3H mammary carcinoma. Peritumor IL-2 and IFN-gamma had nearly equal local and systemic therapeutic effects. In a comparison of the therapeutic effects of IL-2 and IFN-gamma injected systemically, only the IFN-gamma injections resulted in a significant number of cures. IL-2 and IFN-gamma did not have an additive effect when used in combination, suggesting that they have connected, rather than separate, paths of action in the anti-tumor immune response. The injection of anti-IFN-gamma-MAb abrogated the systemic therapeutic effect of peri-tumor IL-2, indicating that the systemic therapeutic effect was the result of IFN-gamma induction at the IL-2 injection site.

Animals↗

PubMed1991

Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery.

Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase. Only patients with fasting triglyceride (TG) levels greater than or equal to 1.6 mmol/l at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively. A threefold increase (p = 0.0001) of EPA was noted at pre- and postoperative follow-up. TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study. No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p less than 0.05) at end of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

[Extracorporeal membrane oxygenation. A therapeutic alternative in acute heart and/or pulmonary failure?].

Extracorporeal membrane oxygenation was introduced as a supplement ot mechanical ventilation in the treatment of two patients with severe acute respiratory failure and as heart assist in one patient with acute refractory cardiac failure after open heart surgery. The system includes a membrane oxygenator and a roller pump. The whole circuit is coated with partially degraded heparin covalently bound to the surface (Carmeda Bioactive Surface), reducing the need of systemic heparinization to a minimum. In the first case of acute respiratory failure a veno-venous bypass was employed, with cannulas in the right atrium and the femoral vein. Given a blood flow through the circuit of 2.5 l/min, ventilator settings could be favourably reduced. The patient was weaned off the bypass system after six days, off the ventilator after 120 days, and recovered completely. In two cases the system served as partial venoarterial bypass, and blood was returned to the ascending aorta. A 31 year-old male victim of a smoke inhalation lung injury was on bypass for four and a half days. He recovered completely after another 17 days of mechanical ventilation. A 68 year-old man with pump failure after cardiac surgery needed extracorporeal support as heart assist for seven days. On the eighth day he was weaned off intra-aortic balloon-pumping as well. Unfortunately, he died of septicemia, with multiple organ failure, 13 days later. The heparin-coated extracorporeal membrane oxygenation system may represent a major advancement in the treatment of critically ill patients in need of cardiopulmonary assist.

Acute Disease↗

PubMed1991

Immunotherapy of a mouse mammary carcinoma by sustained peritumor release of IL-2.

The purpose of this study was to compare the local and systemic therapeutic effects of Interleukin-2 (IL-2) used in 3 different preparations: suspended in PBS, suspended in 2% agar, and entrapped in multi-lamellar liposomes suspended in 2% agar. The liposomes were composed of phosphatidylglycerol and phosphatidylcholine in a 1:4 molar ratio. The net release of IL-2 in vitro (by ELISA assay) at 37 degrees C, measured at 4 hr, 2 days, and 10 days, was 50%, 75%, and 100% from agar, and 8%, 22%, and 33% from liposomes in agar. In the therapeutic tests, the IL-2 preparations were injected close to s.c. implants of the MC2 mouse mammary carcinoma. Four injections at weekly intervals of IL-2 in agar had as much local and systemic (against uninjected contralateral tumor implants in treated mice) therapeutic effect as the same total amount of IL-2 in PBS given in 20 daily injections over 4 weeks. The IL-2 liposome-gel preparation was most effective (p less than 0.05), probably due to the more sustained release of IL-2. Three injections of this preparation gave a fixed and sustained peritumor release of IL-2 which, at sub-toxic levels, resulted in both local and systemic therapeutic effects.

Animals↗

PubMed1991

Cardiac surgery and distribution of the leukocyte L1 protein-calprotectin.

Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and L1 (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myocardial arterio-venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of L1 increased during CPB from 344 +/- 71 micrograms/l (mean +/- SD) preoperatively to 5221 +/- 1267 micrograms/l at the end of CPB (P less than 0.001). Simultaneously, the number of circulating PMN also increased (from 4.4 +/- 0.4 x 10(9)/l to 9.1 +/- 1.2 x 10(9)/l (P less than 0.05)). There was a positive correlation between the mean number of circulating PMN and the plasma level of L1 at all sampling times during CPB (r = 0.93, P less than 0.05). A coronary sequestration of both L1 (P less than 0.006) and PMN (P less than 0.002) was found after 5 min reperfusion. This was not present at 15 and 30 min reperfusion. The coronary entrapment of L1 and PMN did not covary significantly, and was unrelated to both the time of cardioplegic arrest and the arterial levels of L1 and PMN. In conclusion, the increased plasma concentrations of PMN and L1 during CPB and the coronary sequestration of both PMN and L1 may be factors in the pathogenesis of reperfusion injury of the myocardium.

Adult↗

PubMed1991

Collagen production by macrophages in tumour encapsulation and dormancy.

Dormant and regressing implants of C3H mammary carcinoma MC2 were always found to be surrounded by a cellular fibrous capsule where macrophages and T cells predominated as the cellular elements. Macrophages were always closely associated with the collagen deposition, and stained with anti-collagen type I immuno-peroxidase in tissue sections. The capacities of macrophages and T-lymphocytes to function in collagen formation was investigated with the use of Nucleopore chambers implanted i.p. in normal mice. The procollagen that entered the chambers via the pores, was assumed to have been produced by the packed layer of peritoneal macrophages that adhered firmly to the outside of washed chambers. The adherent cells all stained with Mac-1 immuno-peroxidase, and phagocytosed yeast in short-term culture. The formation of collagen fibres in the chambers was enhanced if the chambers contained T lymphocytes. It appears that macrophages have the capacity to function as collagen producing cells in tumour encapsulation.

Animals↗

PubMed1991

Oxygen free radical-induced injury in isolated rat hearts: effects of ibuprofen and BW 755c.

Inhibitors of the arachidonic acid metabolism (AA) as well as scavengers of oxygen free radicals (OFR) have been shown to reduce myocardial infarct size. We investigated the effects of two inhibitors of AA metabolism on the cardiac effects of OFR. Isolated rat hearts were retrogradely perfused for 10 min with buffer containing hypoxanthine (HX, 1 mmol l-1) and xanthine oxidase (XOD: 24 U l-1) alone (n = 11), or with the addition of ibuprofen (IBU) (n = 6) (a cyclooxygenase inhibitor) or BW 755C (n = 6) (a dual inhibitor of cyclo-oxygenase and lipoxygenase). The hearts were observed for 30 min thereafter (total observation time 40 min). Left-ventricular pressures were measured by a balloon in the left ventricle. HX + XOD significantly reduced left-ventricular developed pressure (LVDP) and coronary flow (CF), but not heart rate. The reduction of LVDP and CF was not significantly ameliorated by the addition of IBU (7.6 x 10(-4) mol l-1) or BW 755C (2 x 10(-3) mmol l-1). OFR increased left-ventricular end-diastolic pressure (LVEDP) from (mean +/- SEM) 0 to 22 +/- 4 mmHg (10 min) and 30 +/- 5 mmHg (40 min). Upon addition of IBU, LVEDP increased from 0 to 24 +/- 8 mmHg and 17 +/- 6 mmHg at 10 and 40 min respectively. The addition of BW 755C almost completely inhibited the increase in LVEDP (1 +/- 1 mmHg and 3 +/- 3 mmHg at 10 min and 40 min). In conclusion, except for inhibition of OFR-induced diastolic dysfunction by BW 755C, neither BW 755C nor IBU appear to inhibit cardiac injury induced by OFR.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1991

Toxic oxygen metabolites induce vasoconstriction and bronchoconstriction in isolated, plasma-perfused rat lungs.

Effects of toxic oxygen metabolites (TOM) on the pulmonary vascular bed and airways were studied in isolated, plasma-perfused rat lungs. TOM were generated by xanthine oxidase (XO) (0.1 or 0.25 unit.ml-1) and hypoxanthine (HX) (1 mol.l-1). In vitro measurements by chemiluminescence indicated that the major oxygen metabolite generated by XO and HX was H2O2. Measurements of PO2 in the perfusate as an indicator of O2-consumption suggested that production of TOM by XO and HX was finished within 30 min. XO and HX induced an early dose-dependent bronchoconstriction and a late increase in transpulmonary pressure (Ptp). Pulmonary arterial pressure (Ppa) increased gradually and levelled off within 30 min with low-dose XO, but not with high-dose XO. As judged by weight increase of the lungs, interstitial edema occurred regularly. Allopurinol, an inhibitor of XO, blocked the lung responses caused by XO and HX. Catalase attenuated all lung responses induced by XO and HX, while superoxide dismutase had no effect. The hydroxyl radical scavenger dimethylsulfoxide abolished the increase in Ptp and attenuated the increase in Ppa, but did not consistently protect the lungs from edema development. This study shows that TOM induce vasoconstriction, bronchoconstriction and lung edema in plasma-perfused rat lungs, mainly due to generation of H2O2 and the hydroxyl radical.

Animals↗

PubMed1991

Toxic oxygen metabolites increase microvascular permeability in isolated perfused rat lungs: the effect of methylprednisolone.

Toxic oxygen metabolites (TOM) have been suggested to be mediators of permeability edema associated with the adult respiratory distress syndrome (ARDS). Because corticosteroids have possible beneficial effects in ARDS, we have examined the effect of methylprednisolone (MP) on TOM-induced lung edema in isolated, plasma-perfused rat lungs. TOM were generated by adding xanthine oxidase (XO) and hypoxanthine (HX) to the perfusate. Microvascular permeability was assessed by fluid filtration rate (FFR). FFR was determined before and 30 min after administration of XO and HX by measuring the weight increase of the lungs for the last 3 min during a standard 5 min elevation of the outlet pressure. MP was administered in two different ways: 1) Added to the perfusate 5 or 60 min before XO and HX (0.1 and 1 mg ml-1), and 2) given as pretreatment to the rats 12 and 2 hr before preparation of the lungs (40 mg kg -1). XO and HX significantly increased FFR compared to lungs perfused with untreated plasma. Pretreatment with MP significantly attenuated the increase in FFR caused by XO and HX. Addition of MP to the perfusate also inhibited the effect of TOM. This latter protection occurred irrespective of when MP was added before XO and HX. However, when the highest dose of MP was added 5 min before XO and HX, there was a loss of the protective effect. In summary, this study provides evidence that MP may directly prevent microvascular injury induced by TOM in isolated perfused rat lungs. The effect was dependent on the dose of MP applied, but not on when MP was administered prior to exposure to TOM.

Animals↗

PubMed1990

Activities of mitochondrial aspartate aminotransferase and creatine kinase isoenzyme MB in serum following coronary bypass surgery.

The mitochondrial isoenzyme of aspartate aminotransferase showed only slight increases in serum of twenty-seven patients after uncomplicated coronary bypass surgery, which contrasted the rapid and substantial increases in creatine kinase MB. In seven patients suffering perioperative infarction or serious complications, substantial increases in mitochondrial aspartate aminotransferase were detected and the elevations in creatine kinase MB were prolonged. Mitochondrial aspartate aminotransferase may appear as a specific marker of myocardial necrosis following coronary bypass surgery. The elevations of creatine kinase and creatine kinase MB were detected as early as 5 minutes after onset of coronary reperfusion and slightly higher activities were measured in coronary sinus blood than in systemic blood sampled simultaneously. Increases in mitochondrial aspartate aminotransferase, however, could first be measured 8 hours after reperfusion.

Aspartate Aminotransferases↗

PubMed1990

[Improved treatment of abdominal aortic aneurysms. Progress over 17 years].

During the period 1970-86, 155 men and 24 women were operated on for abdominal aortic aneurysms at the University Hospital in Tromsø. Elective operations were performed in 76 patients with an operative mortality of 5 (7%), impending rupture in 49, of whom 14 died (29%) and ruptured aneurysms in 54 patients, of whom 33 (61%) died. There has been a substantial increase in the number of patients per year admitted with abdominal aneurysms, from an average of 4.5 during the years 1970-76 inclusive, to over 20 during the years 1984-86. Operative and early postoperative mortality have been reduced and there has been no death following elective operations during the last three years of the reported period. Mortality was 8% for impending rupture and 45% for ruptured aneurysms. Electively abdominal aortic aneurysms can be operated safely even in patients over the age of 80. Ruptured aneurysms, however, still carry a high operative mortality in patients over the age of 70.

Age Factors↗

PubMed1990

[Arteria gastroepiploica dextra in coronary surgery. Complete revascularization in angina pectoris].

We have used the right gastroepiploic artery as a viable jump graft to the distal right coronary artery in two patients. The first patient was a 37 year-old man with recurrent angina after coronary bypass surgery with three vein grafts eight years previously. The second patient was a man aged 45 with angina in New York Heart Association Class III to IV. In both cases coronary angiography revealed severe triple vessel disease with multiple proximal and distal occlusions or stenosis. Both internal mammary arteries were also used in the two patients to revascularize the LAD and circumflex systems. Thus, a complete revascularization was achieved by use of only viable arteries as conduits. Both patients recovered well and were free from angina. At present only the first patient has had a postoperative angiogram, which showed good patency of the gastroepiploic artery jump graft. If the long-term patency of this type of graft is similar to that of the internal mammary arteries, it is another suitable arterial conduit for revascularization of the ischemic myocardium.

Adult↗

PubMed1990

Production of collagen type I by mouse peritoneal macrophages.

The origin and identity of the cells that accumulate and produce collagen in wound healing and in granulomatous and fibrotic processes have long remained unsettled. In this study, it was found that pure cultures of peritoneal macrophages produced hydroxy-L-proline not associated with Clq and produced detectable quantities of collagenase-digestible protein. Cultured macrophages synthesized collagen while retaining their phagocytic capacity. Immuno-blot analysis identified the collagen as Type I. This shows that macrophages have collagen-forming capacity and may be productive cells in pathologic collagen deposition.

Animals↗

PubMed1990

Oxygen free radical producing leukocytes cause functional depression of isolated rat hearts: role of leukotrienes.

Polymorphonuclear granulocytes PMN) are suggested mediators of myocardial ischemia-reperfusion injury. We have previously shown that activated PMN producing oxygen free radicals (OFR) in the coronary circulation are cardiodepressive. OFR may induce lipid peroxidation and production of eicosanoids. We have investigated the influence of cyclo-oxygenase and lipoxygenase inhibitors on the effects of activated, OFR producing PMN in the Langedorff rat heart model. Left ventricular developed pressure (LVDP) was measured by a balloon in the left ventricle. Human PMN and drugs were given into the aortic cannula for 10 min and the hearts were observed for 30 min thereafter. After infusion for 5 min OFR production in the cellular infusate was measured at the level of the aortic cannula by a chemiluminescence (CL) technique. Phorbol 12-myristate 13-acetate (PMA)-activated PMN (n = 8), produced a CL response of 27649 +/- 11048 counts (mean +/- S.E.M.), and reduced coronary flow (CF) to 53 +/- 6% (mean +/- S.E.M.) and LVDP to 38 +/- 9% of baseline values at the end of the observation period. Ibuprofen (n = 6), a cyclooxygenase (CO) inhibitor, neither influenced the CL response (31915 +/- 7563) of activated PMN, nor the reduction of CF and LVDP at this time. Although both BW 755C (n = 7), a dual inhibitor of CO and lipoxygenase (LO) (CF:90 +/- 4%, LVDP:99 +/- 6%) and diethylcarbamazine (DCM) (n = 8), a LO inhibitor (CF:88 +/- 11%, LVDP:87 +/- 4%), significantly inhibited the cardiodepressive effects of activated PMN. BW 755C alone abolished the CL response (431 +/- 158 counts), whereas DCM had no effect on CL (30105 +/- 1698 counts).(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1990

Granulocyte and eicosanoid gradients across the coronary circulation during myocardial reperfusion in cardiac surgery.

Polymorphonuclear granulocytes (PMN) and eicosanoids such as leukotrienes have been suggested as possible mediators of myocardial ischemia-reperfusion injury. We have investigated the gradients of PMN, 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) and leukotriene B4 (LTB4) across the coronary circulation during myocardial reperfusion after cold, cardioplegic arrest in cardiac surgery. Baseline values in arterial blood were 4.4 +/- 0.4 x 10(9)/l, 59 +/- 6 pg/ml and 149 +/- 27 pg/ml (mean +/- SEM) for PMN, 6-keto-PGF1 alpha and LTB4, respectively. They were significantly elevated during cardiopulmonary bypass (CPB). There was a positive correlation between the number of circulating PMN and LTB4 at all sample times during cardiopulmonary bypass (P less than 0.05). At 5 min reperfusion (CPB time: 122 +/- 8 min) PMN, 6-keto-PGF1 alpha and LTB4 were 6.2 +/- 0.5 x 10(9)/l, 696 +/- 117 pg/ml and 280 +/- 60 pg/ml, respectively. The PMN in coronary sinus blood were significantly lower (P less than 0.001) than in arterial blood at 5 min reperfusion, but not at 15 and 30 min. The concentrations of 6-keto-PGF1 alpha and LTB4 were significantly elevated in coronary sinus blood as compared to arterial blood after reperfusion for 5 min (P less than 0.05). Thereafter, no significant gradients were found across the heart, except at 30 min reperfusion when LTB4 was significantly lower in coronary sinus blood. Neither PMN sequestration nor 6-keto-PGF1 alpha and LTB4 production were significantly correlated to aortic cross clamp time.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery.

Accumulation of complement factors has been found to occur in the myocardium after infarction. We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium. In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass. Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10). From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB. Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05). The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05). No significant difference was found after 30 min of reperfusion. Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury.

Cardiopulmonary Bypass↗