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Biomedical subjects

R Larsson

Publications and source records attributed to R Larsson.

At least 235 records · Page 13Linked to original sources
PubMed1984

Reduced thrombogenic characteristics of expanded polytetrafluoroethylene and polyurethane arterial grafts after heparin bonding.

The effect of bonding of heparin, via a glutaraldehyde-stabilized ionic complex, on the early thrombogenicity of polyurethane (PU) and expanded polytetrafluoroethylene (PTFE) (Gore-tex) as well as covalent bonding of heparin on PTFE was studied in vivo. Grafts 6 cm long and 4 mm in diameter were placed in the carotid arteries of sheep and perfused for 4 hours at 25 ml/min in order to accelerate thrombus formation. The thrombogenicity was determined by calculation of the percent of the luminal surface free of thrombus and patency. In addition, 32P-labelled platelet accumulation was determined in some of the grafts. The stabilized ionic bonding of heparin significantly reduced the early thrombogenicity of PU but had little effect on PTFE grafts; but the thrombogenicity of the latter was markedly decreased following covalent bonding of heparin. A regional distribution of platelet accumulation was found with the distal anastomoses showing the highest platelet deposition. By choice of an appropriate method of heparinization, a significant reduction of the thrombogenicity of PU and PTFE grafts was achieved.

Animals↗
PubMed1983

Effect of glycosaminoglycans and antithrombin III on uptake and inhibition of thrombin by the vascular wall.

Thrombin binds to and is inactivated by the endothelium. The inactivation is potentiated by plasma. The present investigation was designed to clarify the role of vessel wall glycosaminoglycans (GAG) and plasma antithrombin III (AT III) in the inactivation and binding of thrombin by endothelium. Thrombin was shown to bind to vascular endothelium and artificial surfaces containing GAG:s. The binding could be inhibited on both types of surfaces by pretreating them with protamine. Thrombin bound to endothelium was rapidly inactivated in the presence of plasma but only slowly if the plasma was replaced by AT III, AT III-depleted plasma or a balanced salt solution. It is concluded that thrombin binds to vessel wall GAG:s and is inactivated by the endothelium. Potentiation of the inhibition of the endothelially bound thrombin by plasma is dependent upon presence of AT III but an additional plasma factor is also required.

Animals↗
PubMed1983

Hydroperoxide-dependent activation of p-phenetidine catalyzed by prostaglandin synthase and other peroxidases.

p-Phenetidine is metabolized by ram seminal vesicle (RSV) microsomes, horseradish peroxidase (HRP) and rat liver microsomes to protein-binding products. These reactions are very rapid and depend on the presence of arachidonic acid (AA) or various hydroperoxidases. The RSV- and HRP-mediated binding was inhibited more than 80% by the addition of reduced glutathione (1 mM) or the antioxidant butylated hydroxyanisole (0.5 mM). Indomethacin (100 microM) and acetylsalicylic acid (1 mM) reduced the AA-dependent reaction in RSV microsomes to less than 5% of control values. When hydrogen peroxide replaced AA, the RSV/H2O2-supported binding in the presence of 50 microM p-phenetidine proceeded at rates similar to that observed with RSV/AA. Unlike the AA-dependent reaction, the H2O2-supported reaction showed no inhibition of protein binding at higher p-phenetidine concns. The data in this report are consistent with a peroxidatic activation of p-phenetidine possibly involving an amine radical catalyzed by prostaglandin synthase (PGS) present in RSV microsomes as well as by other peroxidases. The mechanism for this activation and physiological implications are discussed.

Aminophenols↗
PubMed1983

Prizidilol, a combined vasodilatory and beta-adrenoceptor blocking drug, in primary hypertension. A long-term efficacy, tolerance and pharmacokinetic study.

After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP) less than 90 mmHg. Supine and standing BP recorded 24-27 h after drug intake decreased from 172 +/- 17/106 +/- 6 mmHg (mean +/- SD) and 167 +/- 18/111 +/- 8 mmHg, respectively, after placebo to 159 +/- 16/99 +/- 8 and 154 +/- 18/101 +/- 9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154 +/- 16/97 +/- 7 and 148 +/- 14/97 +/- 7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n = 9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0-8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12-15 h after dosing) as compared to the once daily regimen at 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1983

Interactions between magnesium and calcium in beta-cell-rich pancreatic islets.

Calcium-magnesium interactions, total amounts of intracellular magnesium, and insulin release were studied in beta-cell-rich pancreatic islets from ob/ob mice. Mg2+ inhibited the uptake of intracellular 45Ca and insulin release induced by glucose or high concentrations of potassium. Omission of Mg2+ from a Ca2+-deficient medium resulted in an increased efflux of 45Ca, whereas the characteristic glucose inhibition of the efflux was diminished. After addition of Mg2+ to a Mg2+-depleted medium, the glucose-stimulated 45Ca efflux was markedly reduced. Mg2+ inhibited the basal efflux of 45Ca, and this effect was preceded by a transient stimulation. Ca2+ but not Mg2+ stimulated 45Ca efflux in a medium depleted of Ca2+, Mg2+, and Na+. The data indicate that Mg2+ interferes with Ca2+ entry through voltage-dependent Ca2+ channels. Mg2+ may also inhibit the outward transport of Ca2+ from the cells at a site different from the Na+-Ca2+ countertransport mechanism. The total amount of intracellular magnesium remained unaffected by glucose and was not changed unless the ionic composition of the mediums were changed grossly. Under physiological conditions it is therefore unlikely that fluctuations in the intracellular Mg2+ concentration are part of the mechanism by which the functionally important Ca2+ is regulated.

Animals↗
PubMed1983

A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue.

A new method for the covalent binding of heparin to artificial surfaces has been developed. The heparinized surface releases insignificant amounts of heparin and can be regarded as stable. The blood contact properties as studied in vitro revealed that the surface was highly thromboresistant in terms of reduced platelet adhesion, surface catalyzed adsorption and inhibition of thrombin and capacity to prevent clotting of nonanticoagulated blood.

Blood Coagulation↗
PubMed1982

Pharmacokinetics of cimetidine and its sulphoxide metabolite during haemodialysis.

A single intravenous dose of cimetidine 200mg was administered to 6 patients with severe chronic renal failure one hour prior to haemodialysis. The plasma concentrations of cimetidine and its sulphoxide metabolite at the start of haemodialysis were 2.74 +/- 0.12 and 0.76 +/- 0.08 microgram/ml, and after dialysis for 4h 1.08 +/- 0.10 and 0.51 +/- 0.08 microgram/ml, respectively (mean +/- SE). The average haemodialysis clearance (ClHDa) of cimetidine during dialysis was 46-92 ml/min at a dialysate flow rate of 320 ml/min and blood flow rates in the 6 patients between 160-240 ml/min. The mean ClHDa of the sulphoxide metabolite was 44% higher than that of cimetidine, and ranged between 49-148 ml/min. During haemodialysis the mean plasma elimination half-life (t 1/2) of cimetidine was 3.24h (range 2.08-5.08) and of the sulphoxide metabolite 9.49h (range 4.70-14.39). There was a significant relationship between the elimination rate constant (beta) and ClHDa of the sulphoxide metabolite (p less than 0.01), but no such relationship was found between beta and ClHDa of cimetidine. The mean total amount of cimetidine eliminated during dialysis was 27.3mg (range 17.9-31.8), which was 9.0-15.9% of the given dose. Between 12.2-21.2mg (mean 15.3) of the sulphoxide metabolite was eliminated in the dialysate. Major adjustment of the dose of cimetidine on days of dialysis is not necessary.

Adult↗
PubMed1982

The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function.

1 The pharmacokinetics of cimetidine and its sulphoxide metabolite was studied after a single intravenous dose of 200 mg cimetidine in nine patients with normal renal function and ten patients with severe renal failure on regular haemodialysis and during continuous oral cimetidine treatment in ten patients with normal renal function and 31 patients with different degrees of renal failure. 2 In normal renal function a mean of 47.3% of the single intravenous dose was excreted as unchanged drug and 12.8% as cimetidine sulphoxide. The mean plasma elimination half-life (T1/2) of cimetidine was 2.0 h and of cimetidine sulphoxide 1.7 h. 3 In severe renal failure a mean of 2.2% of the single intravenous dose was excreted as unchanged drug and 0.5% as cimetidine sulphoxide. The mean plasma T1/2 of cimetidine was 3.9 h. The plasma concentrations of the sulphoxide metabolite increased successively with time after dosing and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients with different degrees of renal failure given reduced doses of cimetidine the plasma concentrations of the sulphoxide metabolite were higher with decreasing renal function. The mean plasma T1/2 of cimetidine was 3.1 h in mild renal dysfunction (creatinine clearance 50-75 ml/min) and 4.5 h in severe renal failure (creatinine clearance 5-15 ml/min) and of cimetidine sulphoxide 5.3 and 14.4 h respectively. 5 Toxicity studies of cimetidine sulphoxide may be needed to assess if high plasma concentrations of the sulphoxide metabolite in severe renal failure are of clinical significance.

Administration, Oral↗
PubMed1982

End-stage chronic renal failure due to total uterine prolapse.

Upper urinary dilatation caused by a protracted total uterine prolapse and resulting in end-stage chronic renal failure in a 66-year-old women is described. A gynecological examination is advised in females with renal insufficiency of unknown etiology.

Aged↗
PubMed1982

Computherm. A new device for measurement of coronary blood flow using the continuous thermodilution technique.

A new device for an automatic determination of coronary sinus blood flow using the thermodilution technique is presented. The measuring equipment consists of four main parts; a thermal dilution-catheter with two signal amplifiers of analogue type, an analogue/digital converter controlled by a microcomputer system, a pump for the control of the rate of injection flow and a control panel and display. The device has been tested in a model test with flow levels between 75 and 200 ml/min. The error between a number of measurements with all parameters unchanged except minor variations in temperatures was less than 5 per cent.

Computers↗
PubMed1982

Is Mg2+ important for the secretory function of the pancreatic beta-cells?

The interactions between Mg2+ and Ca2+ and the total content of magnesium were studied in beta-cell-rich pancreatic islets from ob/ob mice. High concentrations of Mg2+ inhibited basal intracellular 45Ca net uptake as well as that stimulated by K+ depolarization or Na+ omission, suggesting that Ca2+ and Mg2+ can compete for both the voltage-dependent Ca2+ and the Na+ channels. The magnesium content of the islets was remarkably stable being affected only under extreme conditions. It is suggested that the physiological stimulation of insulin secretion does not depend on dynamic fluctuations of magnesium metabolism.

Animals↗
PubMed1982

Continuous intra-arterial PO2 monitoring with a surface heparinized catheter electrode. A study of conformity in conventional blood gas analysis and of long-term electrode function in the non-heparinized dog.

Surface-heparinized catheter PO2 electrodes were used for continuous intra-arterial monitoring in non-heparinized dogs. During one-day experiments the read-out of the electrode monitoring unit was compared with that of conventional blood gas analysis. Furthermore, the electrodes were studied after long-term implantation. The intra-arterial PO2 electrodes have previously been reported to be linear in the gas phase, water phase and in heparinized blood. The present study demonstrates that the catheter electrodes remain linear after surface heparinization. As compared with the conventional blood gas analysis it was found that the desk analyser in the range PaO2 greater than 18 kPa underestimated the actual PaO2 as compared to the invasively monitored PaO2, but in the range below 7 kPa the desk analyser overestimated the PaO2. Surface-heparinized PO2 catheter electrodes were studied after up to 23 days of implantation. No coagulation phenomenon was found around the catheters, neither macroscopically nor by scanning electron microscopy. The electrical function withstood 7 days of implantation. After more extended periods the electrical leads were broken without any damage to the catheter itself. When compared with acutely implanted surface-heparinized electrodes, there was no difference in monitoring characteristics between the acutely implanted and the long-term implanted PO2 electrodes.

Animals↗
PubMed1981

Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension.

Single oral doses of 1.5, 3.0, 4.5 and 6.0 mg/kg prizidilol HCl, an antihypertensive with vasodilator and beta-adrenoceptor blocking actions, were given to 12 patients with primary hypertension on separate days. Systolic and diastolic blood pressure (BP) decreased after 4.5 and 6.0 mg/kg and systolic BP also after 3.0 mg/kg. The antihypertensive effect was evident in 1 to 2 hr with maximum effect in 4 to 5 hr (supine systolic BP 20 and diastolic 13 mm Hg after 6.0 mg/kg); the effect was sustained for more than 8 hr. An initial slight reduction in heart rate (HR) after 1 to 2 hr was followed by a slight rise after 6 to 8 hr. There were higher plasma drug levels and greater antihypertensive effects after the 6.0-mg/kg dose in slow acetylators (n = 5) than in rapid acetylators (n = 7). Due to its hydrazine moiety, prizidilol, like hydralazine, seems to be a substrate for the polymorphic N-acetyltransferase enzyme system.

Adrenergic beta-Antagonists↗
PubMed1981

Prizidilol (SKF 92657) in primary hypertension.

1. Prizidilol (SKF 92657), a new antihypertensive drug with combined precapillary vasodilator and non-selective beta-adrenoceptor-blocking actions, was given to 24 patients with essential hypertension in a placebo-controlled, dose-titration study, Incremental doses from 200 to 800 mg were given once daily. Supine and standing blood pressure measured 24--27 h after drug intake was reduced during treatment with prizidilol (400--800 mg/day). Slight but significant decreases in heart rate were seen after moderate doses (mean: 447 mg once daily) of prizidilol. A more pronounced blood pressure reduction was noticed 2--7 h after drug administration. 2. Maximal blood pressure reduction coincided with peak plasma concentration of prizidilol, which was measured by a newly developed assay. 3. Plasma renin activity and 24 h urinary excretion of aldosterone and methoxycatecholamines were reduced after the highest doses (mean: 700 mg once daily) of prizidilol. 4. Prizidilol was well tolerated, although dizziness and tiredness were reported by four patients and oedema by two.

Adult↗