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Biomedical subjects

K F Aronsen

Publications and source records attributed to K F Aronsen.

At least 19 recordsLinked to original sources
PubMed1989

Pharmacokinetics of intra-arterial mitomycin C with or without degradable starch microspheres (DSM) in the treatment of non-resectable liver cancer.

The effects of degradable starch microspheres (DSM) on mitomycin C pharmacokinetics and bone marrow toxicity were studied in a phase II multicenter study. Sixty-three patients with non-resectable primary or secondary liver cancer were randomized to receive either i.a. mitomycin C 15 mg/m2 first, followed 5 weeks later by mitomycin C 15 mg/m2 plus DSM 360 mg administered into the hepatic artery (group I) or the same treatments in the opposite sequence (group II). In 36 out of 47 patients who received at least 2 treatments, peripheral venous blood samples were analyzed for mitomycin C pharmacokinetics on a minimum of 2 paired courses. In all patients, the area under the concentration time curve (AUC) was significantly lower when the drug was co-administrated with DSM, but the terminal half-life (t1/2) of mitomycin C was unchanged. In group I the addition of DSM resulted in a significantly lowered AUC, but not in group II. The discrepancy between the 2 groups is probably due to differences in DSM-induced intra-hepatic shunting. The addition of DSM resulted in significantly higher platelet nadir values, but unchanged white blood cell count nadir value. In conclusion, DSM reduce the systemic exposure of mitomycin C and seem to lessen the haematologic toxicity judged from a less pronounced decrease in platelets.

Adult↗
PubMed1988

Influence of degradable starch microspheres (Spherex) on the retention of pertechnetate in a solitary rat liver tumor.

In a model of secondary liver cancer in the rat an evaluation was made of the influence of degradable starch microspheres (Spherex) on the drug retention in tumor and liver tissue. Sodium pertechnetate was used as a drug model substance and was injected into the hepatic artery alone or with degradable starch microspheres (DSM) in a dose of 6 or 12 mg. The distribution of pertechnetate was measured by a gamma-camera equipped with a high resolution collimator. In rats with liver tumor the total elimination of pertechnetate from the liver was delayed when compared to rats without tumor. The tumor concentration of pertechnetate was higher than that of the surrounding liver tissue, irrespective of the presence of DSM. With a DSM dose of 12 mg there was a significantly higher retention of pertechnetate in the tumor during the whole observation period compared to pertechnetate only. The results of this study indicates that DSM can be of value in regional liver chemotherapy to increase liver tumor drug exposure and to reduce systemic toxicity.

Animals↗
PubMed1986

The influence of degradable starch microspheres on liver uptake of 5-fluorouracil after hepatic artery injection in the rat.

The effect of degradable starch microspheres (DSM) on the distribution of 5-fluorouracil (5-FU) after hepatic artery injection was studied in normal rats. Carbon-14-labelled 5-FU was injected separately or together with DSM into the hepatic artery. Radioactivity was measured in liver tissue, bile, peripheral blood, and urine. When microspheres were added, the liver uptake of 5-FU was increased; its peak concentration in peripheral blood decreased, as did the early urinary excretion of radioactivity. The addition of degradable starch microspheres to hepatic artery injections of cytostatic drugs might be of value in increasing the drug concentration in tumour tissue and reducing systemic toxicity.

Animals↗
PubMed1986

Protease-antiprotease imbalance, hemodynamic and regional blood flow changes in experimental pancreatitis.

Pathologic proteolysis in pancreatitis is an important clue to understand the pathophysiology in pancreatitis. Impairment of pancreatic circulation is also important in the development of severe pancreatitis. In an attempt to study some of the biochemical and circulatory events in experimental pancreatitis in the pig the following experiments were undertaken. Pancreatic and splanchnic blood flow were studied in severe and mild pancreatitis with the microsphere method, together with cardiac output and mean arterial pressure. Kininogen, alpha-2-macroglobulin and alpha-1-proteinase inhibitor were measured in plasma and in peritoneal fluid. In severe pancreatitis consumption of kininogen in the peritoneal cavity was demonstrated together with a final lowering of the plasma protease inhibitors. This was accompanied by a rapid reduction of cardiac output and finally mean arterial blood pressure. Pancreatic blood flow was profoundly diminished in this group. No such changes were found in mild pancreatitis. It is concluded that pancreatic ischemia in pancreatitis is associated with protease-antiprotease imbalance.

Animals↗
PubMed1985

Gamma camera evaluation of the effects of degradable starch microspheres on arterial liver blood flow in the rat.

Degradable starch microspheres injected into an artery causes a temporary reduction of regional blood flow and improves the exposure of the organ to a drug injected simultaneously. The purpose of this study was to quantify this effect when microspheres are injected arterially into the liver of rats. As model substance radioactive pertechnetate ions (99TcmO4-) was used. The results were evaluated from external gamma camera measurements. The amounts of microspheres injected together with pertechnetate was 1.5-12 mg. When compared to injections of pertechnetate only, the integrated exposure of the liver to pertechnetate was increased by a factor of 1.4-2.4 when microspheres were added.

Animals↗
PubMed1985

Hepatic artery administration of degradable starch microspheres. I. Effect on energy charge and incorporation of precursors into rat liver nucleic acids.

The effects of hepatic artery administration of degradable starch microspheres on liver energy charge and nucleic acid anabolism were studied in rats. Liver energy charge was evaluated 20 and 60 min after the injection of degradable starch microspheres. As compared to controls the microspheres had no effect on liver energy charge. The incorporation of orotic acid, uracil, and thymidine into liver RNA or DNA was studied 1 h after hepatic artery injection of precursor alone or together with degradable starch microspheres. Orotic acid and uracil incorporation into RNA was studied in normal rats and the DNA incorporation of thymidine in animals with regenerating livers. Orotic acid and thymidine were given in trace amounts. Uracil was given in amounts corresponding to a therapeutic dose of 5-fluorouracil. The addition of microspheres had no effects on the incorporation of the nucleic acid precursors into RNA or DNA. Thus, in the normal liver degradable starch microspheres administered by the hepatic artery had no influence on liver energy charge or RNA anabolism in the liver. Also the microspheres had no negative effects on the DNA anabolism in proliferating liver cells.

Animals↗
PubMed1985

Circulatory effects of haemorrhage during sodium nitroprusside induced hypotension. A study in the rat.

The haemodynamic changes induced by acute moderate blood loss were investigated in rats during normotensive halothane anaesthesia and during sodium-nitroprusside-induced hypotensive anaesthesia, respectively. Following haemorrhage in the normotensive group, mean arterial blood pressure, heart rate and left cardiac work decreased. Cardiac output was reduced non-significantly. Blood flow was redistributed to favour cerebral, coronary, renal and hepatic circulation, mainly at the expense of blood flow to the carcass. Following haemorrhage in the hypotensive group, cardiac output increased significantly. Mean arterial pressure, heart rate and left cardiac work were unchanged. Absolute values for cerebral, coronary, renal and hepatic blood flow were maintained or even increased, while blood flow to the carcass was unchanged.

Animals↗
PubMed1985

Circulatory and renal effects of triglycyl-lysine-vasopressin and excision in experimental burns.

The circulatory and renal effects of a deep dermal burn, covering one third of the total body surface area were studied in 12 thiopentone/N2O anesthetized piglets. Central circulation and renal function was monitored during 24 h and regional blood flows were determined before burn, 5 and 24 h after burn using radioactively labeled microspheres. One group was treated conservatively with fluid infusion only (control group) and the other with fluids, intermittent injections of a long-acting hormonogen, triglycyl-lysine-vasopressin (TGLVP), and excision 5 h after burn. There was earlier circulatory recovery in the TGLVP excision group with significantly higher arterial blood pressure and cardiac output than in the controls. TGLVP induced a major redistribution of blood flows, favoring the liver at the expense of the gastrointestinal tract, carcass and skin, while the blood flows were unchanged to the brain, heart and kidneys. There were also increased excretions of sodium and potassium and a temporarily increased diuresis. The earlier circulatory stabilization and blood flow redistribution might have clinical implications in burn care.

Animals↗
PubMed1983

Pharmacodynamic and pharmacokinetic interactions between ketamine and diazepam.

Anaesthesia with continuous i.v. ketamine and 65% nitrous oxide in oxygen was given to a total of 49 patients undergoing major abdominal surgery. A control group was premedicated with atropine and other groups received in addition rectal diazepam or clorazepate i.v. For further patients had been on oral diazepam or barbiturates for 1-14 years; as premedication they received atropine alone. The anaesthetic technique gave good operative conditions in the 4 groups of patients. The haemodynamic stimulation of ketamine was significantly reduced in patients premedicated with diazepam. Psychotomimetic side effects were not prominent in any of the groups. Patients premedicated with diazepam required a lower rate of ketamine infusion as compared to controls during the initial 30 min of anaesthesia. The patients in the other groups did not differ from the control group in this respect. There were large differences in metabolic pattern between the groups. As compared to the controls, the patients on long-term diazepam or barbiturates had high concentrations of hydroxylated metabolites, with levels higher than that of norketamine. The patients pretreated with diazepam had very low plasma levels of hydroxylated metabolites. Clorazepate premedication did not significantly affect the metabolism of ketamine. The biological half-life of ketamine was significantly increased in the diazepam-treated group, and it was shortened in those on long term treatment with barbiturates or diazepam.

Aged↗
PubMed1983

Central haemodynamics and regional blood flow during halothane-nitrous oxide anaesthesia and controlled ventilation. An experimental study in the rat.

The haemodynamic effects of halothane-N2O/O2 anaesthesia with controlled ventilation were studied in rats, using the microsphere method. Mean arterial blood pressure was significantly reduced but only minor effects on cardiac output (CO), heart rate, and systemic vascular resistance were seen. During anaesthesia, there were significantly increased fractions of CO delivered to brain, lungs, small intestine and liver (hepatic artery), while the fractions to spleen, stomach and carcass were decreased. Fractional distribution and regional blood flow to heart, kidneys, adrenals and preportal area remained unchanged. When anaesthesia was prolonged from 60 to 90 min, no further changes in central or regional haemodynamics were seen. Considering the minor effects on central haemodynamics and the absence of changes in central and regional haemodynamics at 60 and 90 min, this anaesthesia model should be useful in experimental research.

Anesthesia, General↗
PubMed1983

Effects of lysine-vasopressin treatment on renal function in burned pigs.

The effects of lysine vasopressin (LVP) on renal excretory function and renal blood flow were studied in anesthetized and burned pigs either treated conservatively or by early excision 5 hours after burn. Renal perfusion was measured with radioactive microspheres. Diuresis and the urinary excretion of sodium and potassium were determined. Glomerular filtration rate (GFR) was measured either as the endogenous creatinine clearance rate or the clearance rate of 51Cr-EDTA. LVP-treatment in pharmacologic doses after burn caused larger diuresis, and larger sodium and potassium excretion rates than in unburned controls and animals submitted to burn only, Renal blood flow decreased significantly early after burn whether LVP was given or not. After burn, GFR was moderately higher in the LVP-treated pigs than in the animals submitted to burn only. After 24 hours S-creatinine was lower in the pigs treated by LVP and excision of the burned tissues after 5 hours, compared with the conservatively treated animals. This implies that an active surgical approach to full thickness skin burns might support renal function. LVP-induced intrarenal effects causing increased GFR and secondary medullary interstitial electrolyte concentration and osmolar changes could be the mechanisms causing the renal functional changes found in this investigation.

Animals↗
PubMed1983

Lysine-vasopressin in excisional treatment of burns in pigs. Decreased blood loss and earlier circulatory recovery.

The hemodynamics were monitored during 24 hours in piglets anesthetized with Pentothal-N2O/O2, submitted to 33% full-thickness skin burn and resuscitated with 2.4 ml/kg/% burn of 100 mmol NaCl in 2.5% glucose. Three groups were studied: (I) standardized burn, (II) standardized burn and excision after 5 hours, (III) standardized burn, excision and lysine-vasopressin (LVP) given as intravenous infusion in a vasopressor dose. All groups showed similar decrease of cardiac output (CO), which was about 30% 4 hours after burn. In the two groups with burn excision, however, CO recovery was earlier than in the conservatively treated group I. The improvement was significant between group III and group I. LVP led to higher CO fraction and greater blood flow to hepatic artery, reduced flow to proximal gastrointestinal tract and skin and unchanged flow to heart, kidneys and other organs 24 hours after burn. The mean blood loss during and after burn excision was greatly reduced in group III (50 g/25 kg) compared with group II (146 g/25 kg). The therapeutic implications of LVP in excisional burn treatment are discussed.

Animals↗
PubMed1982

Gastric blood flow, tissue gas tension and microvascular changes during hemorrhage-induced stress ulceration in the pig.

Various features of blood supply to the gastric mucosa were studied in the piglet stomach during stress ulceration induced by hemorrhagic shock. Gastric blood flow, as measured by the radioactive microsphere technique, significantly decreased during shock, but no major change occurred in the gastric function of total cardiac output. There was no difference in the magnitude of the decrease of mucosal blood flow between the nonulcerating antral mucosa and the more readily ulcerating corpus or fundic mucosa. At the same time, a significant decrease in tissue partial pressure of oxygen and increase in tissue partial pressure of carbon dioxide occurred, but again no difference was observed between the antrum and the corpus. Microangiographic studies demonstrated a clearly diminished filling of the arterial and capillary bed of the gastric mucosa during shock, suggesting intense vasoconstriction, thrombosis of the mucosal blood vessels, or both. These changes were more prominent in the corpus portion of the stomach than in the antrum. At the site of mucosal lesions, the filling defects persisted even after the shock, suggesting permanent thrombosis of the blood vessels.

Angiography↗
PubMed1982

The effects of lysine-vasopressin on hemodynamics during early post burn period in pigs.

In order to investigate the central and peripheral circulatory effects of a vasoactive drug, lysin vasopressin (LVP), in the early postburn period, 18 piglets were submitted to an experimental study. Anaesthesia was performed by thiopentone sodium as i.v. infusion and mechanically controlled ventilation via endotracheal intubation. Burn injury was brought about by heated metal stamps applied to the back and sides of the animals causing a full thickness skin burn corresponding to 32-35% of the total body surface area. Cardiac output decreased significantly after burn and so did organ blood flow, measured with radioactively labelled microspheres, especially after 4 hours. LVP-infusion did not further decrease cardiac output after burn but decreased the blood flow to the skin, carcass and proximal gastrointestinal tract. The liver perfusion was increased, while the flow in the other organs was not different from that in burned pigs not given LVP. The therapeutical implications are discussed.

Animals↗
PubMed1981

Haemodynamic effects of labetalol-induced hypotension in the anaesthetized dog.

Central haemodynamic changes and regional blood flow were studied using the microsphere technique, during labetalol-induced hypotension in dogs anaesthetized with pentobarbitone and fentanyl. Labetalol 15 mg kg-1 decreased mean arterial pressure from an average of 88 mm Hg to 47 mm Hg. Mean pulmonary arterial pressure was unchanged. Cardiac output was reduced by decrease in stroke volume, while heart rate remained unchanged. Myocardial blood flow decreased approximately in parallel with left ventricular work. Perfusion of the brain and kidneys was unchanged.

Animals↗
PubMed1979

Results of hepatic lobectomy for primary epithelial cancer in 31 adults.

Hepatic lobectomy for primary epithelial cancer was performed in 31 adults from 1964 through 1977 in the surgical departments of six Scandinavian hospitals. Twenty-three patients were discharged and had a 2 year survival rate of 62 per cent and a 5 year survival rate of 16 per cent. Alternatives to surgery have not yet emerged. Further progress requires centralization.

Adenoma, Bile Duct↗