The objective of the present study was to compare systemic and regional haemodynamics in a large series of spontaneously hypertensive rats (SHR, n=32) with normotensive Wistar-Kyoto rats (WKY, n=26) at the age of 12-16 weeks. All rats were anaesthetized with thiobutabarbital and the radioactively labelled microsphere method was used to evaluate regional blood flow with special emphasis on different cerebral areas. The high blood pressure in the SHR was mainly due to elevated total peripheral resistance, which was 90% higher in the SHR compared to the WKY. Furthermore, heart rate was 25% (p<0.001) higher, but the cardiac index was lower by 20% (p<0.01) in the SHR. Blood flow was significantly lower and vascular resistance higher in several organs such as the kidneys, other visceral organs, skeletal muscle and skin of the SHR compared to the WKY. On the contrary, blood flow in the myocardium was augmented by 40% (p<0.01) in the SHR. Blood flow was 20-50% higher in the cerebral cortex, thalamus and caudatus (p<0.05-0.001), but attenuated in the hypophysis of the SHR. In the pons, medulla and cerebellum, blood flow was similar in the two strains. In this large microsphere study, the basal cardiac index was lower in the SHR already at this relatively early stage of established hypertension. Despite this, increased blood flow in the above mentioned cerebral regions was found in the SHR compared to the WKY.
In a consecutive study of 21 renal transplant patients suffering from chronic vascular rejection (CVR) we added the beta-receptor-blocking drug carvedilol to their regular medication. The purpose was to investigate possible pharmacokinetic interactions between carvedilol and cyclosporine (CsA), since carvedilol will soon be used in clinical trials in renal transplant patients with CVR. On the first day of the study the patients received 6.25 mg of carvedilol added to their daily medication. The dose was increased stepwise to 50 mg while the doses of other beta-blocking drugs were decreased. The goal was to exchange atenolol with carvedilol at a ratio of 2:1 when substituting atenolol with carvedilol. The patients' blood pressure was the final determinant of the dose of carvedilol. The trough levels of CsA were measured on days 1, 14, 30, 90 and 180. It was found that the blood levels of CsA increased when carvedilol was introduced. Thus, the doses of CsA had to be reduced in order to keep the blood levels within the therapeutic range. At 90 d, the daily doses of CsA had been reduced from 3.7 +/- 0.3 to 3.0 +/- 0.2 mg/kg BW (p < 0.001). The present results suggest an interaction between carvedilol and CsA that demands a 20% average reduction of CsA doses to maintain the CsA blood levels within the therapeutic range. However, the interaction shows a great interindividual variation, calling for careful monitoring of the CsA blood levels.
Flow‐mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic‐receptor agonist have both frequently been used to evaluate endothelium‐dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor‐agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L ‐arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion.While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated ( r =0·70, P <0·01), FMD showed no relationship with the vasodilation evoked by MCh ( r =–0·03) or L ‐arginine ( r =0·04). The five‐fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations ( P <0·05) and a more than 11‐fold increase in forearm NOx‐release ( P <0·01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium‐independent vasodilation evoked by NO‐donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium‐dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO‐release.
In order to compare the effectiveness of aluminum removal in uremic patients during extracorporeal treatment, 17 patients with endstage renal failure were given a desferrioxamine infusion of 40 mg/kg body weight after an ordinary dialysis treatment. Forty-eight hours later 7 patients were treated with hemodialysis, 6 with hemofiltration and 4 with a combination of hemodialysis and hemoperfusion. The clearance of aluminum was measured at different intervals. It was found that the aluminum clearance was 75 + 18 ml/min in hemofiltration compared to 30 ± 10 ml/min in hemodialysis (p < 0.001). A combination of hemodialysis and hemoperfusion with a charcoal column containing 100 g activated charcoal in series gave a total aluminum clearance of 56 ± 11 ml/min. The total amount of aluminum in the ultrafiltrate after hemofiltration was found to be approximately 3 times as high (1,728 ± 156 μg) as the total amount of aluminum in the hemodialysis water that had passed a single pass system during a 4-hour dialysis (576 ± 104 μg). Our results indicate that hemofiltration or a combination of hemodialysis and hemoperfusion should be used to remove aluminum in patients with signs of severe aluminum accumulation such as encephalopathy or painful bone disease, because these methods are 2–3 times as effective as ordinary hemodialysis. In patients where aluminum has been accumulated but no severe symptoms occur hemodialysis gives a significant clearance of the aluminum desferrioxamine complex.
