Local regulation of subcutaneous blood flow and capillary filtration in limbs with occlusive arterial disease. Studies before and after arterial reconstruction

The aim of the study was to examine the local blood flow regulation and the capillary filtration rate in patients with occlusive arterial disease before and after arterial reconstructive surgery. Fourty-seven normal subjects and 99 patients were studied. Subcutaneous blood flow was measured on the forefoot by the local 133Xenon method. Forefoot arterial blood pressure was measured indirectly by cuff and strain-gauge technique. Capillary filtration rate was measured by strain-gauge plethysmography on the forefoot. The arterial and venous pressures of the forefoot were changed by elevating or lowering the foot in relation to heart level. In normal limbs autoregulation was demonstrated during elevation of the limb when blood flow remained almost constant despite the reduction in arterial and perfusion pressures. The local vasoconstrictor response to increased venous transmural pressure was demonstrated when the limb was lowered and blood flow decreased about 30% despite a constant perfusion pressure. In limbs with occlusive arterial disease both local blood flow regulation mechanisms became progressively more abnormal the severe the symptoms and the lower the distal blood pressure. Estimations of the changes in local vascular resistance suggested that the abnormalities in blood flow regulation in all but the severest cases are the result of changes in local perfusion pressure rather than the result of inability of the arteriolar smooth muscle to dilate and constrict in response to changes in arterial and venous pressures. After arterial reconstruction the two mechanisms generally normalized within about a week. However, disturbances occurred in some cases in the early postoperative period, possibly as the result of postoperative pain and stress. Postreconstructive hyperaemia developed in most limbs despite the early normalization of local blood flow regulation. Compared with normal limbs, the forefoot capillary filtration rate was reduced in limbs with occlusive arterial disease. In the early postoperative period the filtration rate remained reduced, but it increased to normal values within three months. Postreconstructive oedema developed independently of the normalization of blood flow regulation, and almost exclusively after femoro-distal by-pass surgery. The study supports the hypothesis that the postreconstructive oedema is a lymphoedema due to surgical trauma, rather than the result of microvascular derangement.     

Simultaneous measurements of capillary filtration and diffusion capacities during graded infusions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) into the rat hindquarter vascular bed

The relationships between capillary diffusion capacity (PS) for Cr-EDTA respective capillary filtration capacity (CFC) and vascular resistance during graded intraarterial infusions of NA and 5-HT into the artificially constant flow perfused rat hindquarter vascular bed were investigated. During maximal vasodilatation PS for Cr-EDTA was some 5.5-5.7 m//min × 100 g, CFC some 0.04 ml/min × mmHg × 100 g, while vascular resistance was 2.8 mmHg × ml^-1 × min × 100 g (PRU₁₀₀) and isogravimetric capillary pressure 12.8 mmHg on an average. Setting out from maximal vasodilatation, increasing doses of NA and 5-HT produced graded reductions in capillary surface area as reflected by progressive decreases in both PS for Cr-EDTA and CFC. These changes occurred simultaneously with progressive increases in both pre- and postcapillary resistances, causing elevations in both arterial and capillary hydrostatic pressures and hance in capillary fluid filtration at constant flow. Capillary hydrostatic pressure increased maximally to 45 mmHg (calculated for NA) and vascular resistance to some 21 mmHg × ml^-1 × min × 100 g on an average. PS for Cr-EDTA decreased maximally to some 0.7-1 ml/min × 100 g for both NA and 5-HT and, furthermore, the relationships between PS for Cr-EDTA and PRU₁₀₀ for NA respective 5-HT were almost identical. This was taken to indicate that capillary surface area for nutritional exchange is affected similarly by both drugs. However, the CFC-PRU₁₀₀ relationship was shifted towards some 30–50% higher CFC values for 5-HT than for NA at almost every level of vasoconstriction. This might suggest that 5-HT besides reducing capillary surface area also induces moderate increases in capillary permeability through increases in number and/or radius of large pores (gaps) (cf. Rippe, Kamiya& Folkow 1978). Even during NA-induced vasoconstriction, when virtually no changes in capillary permeability occurred, PS for Cr-EDTA was reduced to a relatively greater extent than CFC, the discrepancy being most pronounced during marked vasoconstriction. The significance of this finding is discussed.     

Cardiac output and its distribution through capillaries and A-V shunts in diving seals

Regional blood flow and cardiac output were determined by distribution of radioactive microspheres injected via catheter into the left ventricle during experimental diving and recovery in juvenile spotted seals (Phoca vitulina largha) and grey seals (Halichoerus grypus). Cardiac output was 9.7 L/min before diving, declined 90% during submersion and increased to 12.1 L/min after 40 s of recovery. Left ventricular myocardial perfusion declined from 179 ± 24 (21) to 25 ± 2 (6) ml/min · 100 g at 2 min submersion, and measured 23 ± 3 (8) after 10 min of submersion. Cerebral cortical flow was reduced from a pre-dive value of 115 ± 3 (15) to 40 ± 5 (3) and 49 ± 6 (3) at 2 and 5 min of diving, respectively, but increased to 253 ± 14 (4) ml/min · 100 g at 10 min along with elevated PCO₂ (84 torr) and lowered pH (7.10) in arterial blood. It remained at that level in recovery. Brain stem perfusion after 10 min submersion was still identical with control, but increased to 275% of control in recovery. Adrenal flow decreased to 34 and 27% of control at 2 and 5 min of diving, respectively. Recovery flow after 10 min of diving was 200% of control. Liver, kidney, fat, skin, and stomach were ischemic throughout the dive. Recovery flow increased slowly in these tissues. Skeletal muscle (M. psoas) was perfused at a low rate. (3 ml/min · 100 g) pre-dive and was ischemic during diving. Recovery muscle perfusion was variable at different sites (from 5 to 105 ml/min · 100 g). Pre-dive pulmonary capillary perfusion was 58 ± 8 (9) ml/min · 100 g, decreased to 7 ± 0 (3) ml/min · 100 g after 10 min of submersion, and had increased to 50% of pre-dive value after 40 s of recovery from a 10 min dive. Conclusions are: (1) previous information from implanted flow transducers was confirmed, (2) detailed data for discrete tissues elaborate the concept of selective redistribution of cardiac output in diving seals, (3) non-uniform reperfusion contributes to the maintenance of arterial presssure during recovery, and (4) substantial A-V shunting of cardiac output took place in the first 2–5 min of the dive, when total capillary/nutritive flow was low. Late in the dive, however, CO was routed through systemic capillaries mainly in the cerebral circulation and less than 15% through A-V shunts.     

Capillary filtration coefficient in the forearm of patients with essential hypertension

The capillary filtration coefficient (CFC) in the forearm was followed in patients with essential hypertension and compared with controls, using the method of venous occlusion plethysmography and simultaneous recording of intravenous pressure in the measured segment of the extremity. Arterial blood-pressure was obtained in the contralateral arm by auscultation. The CFC averaged 0.0039 +/- 0.009 ml/100 ml/min/mmHg and 0.0095 +/- 0.0018 ml/100 ml/min/mmHg in hypertensives and controls respectively. The relation between CFC and arterial blood-pressure values was inversely non-linear. The results suggest reduction of the capillary area due to hypertension and possibly functional or structural changes in the microcirculatory bed accompanying systemic blood-pressure increase.     

Plasma protein handling in the rat kidney: Micropuncture experiments in the acute heterologous phase of Anti-GBM-nephritis

Glomerular filtration and tubular uptake of plasma proteins have been studied in the rat using micropuncture techniques. 1. Under control conditions the glomerular capillary wall is an effective barrier, only 7.6 microgram/min x 100 g BW albumin have been measured as filtered load. Four to twelve hours after i.v. injection of anti-glomerular-basement membrane serum (anti-GBM-serum sieving coefficient phi and filtered load increased in a dose-dependent manner (phi albumin in controls = 0.27 x 10(-3), after injection of 0.5 ml Antiserum phi = 0.28 x 10(-3) and 1.0 ml Antiserum phi = 2.32 x 10(-3)). 2. The tubular reabsorption capacity is almost reached under control conditions and amounts to 5.6--10.7 microgram/min x 100 g BW for albumin. Only reduced GFR (0.36 +/- 0.07 ml/min x 100 g BW) and reduced tubular flow lead to increased tubular uptake under overload conditions (10.7 vs. 99.0 microgram albumin/min x 100 g BW). 3. Tubular reabsorption of so-called high-molecular-weight proteins seems to be a nonselective mechanism. The ratio Alb/Alb + Glob (89.9--93.1%) did not differ significantly at the individual puncture sites and in the final urine.     

Simultaneous measurements of capillary diffusion and filtration exchange during shifts in filtration-absorption and at graded alterations in the capillary permeability surface area products (PS).

The diffusion exchange of Cr-EDTA, using the single injection indicator diffusion method, was followed simultaneously with estimations of the capillary filtration capacity (CFC) in an "isogravimetric" rat hindquarter preparation during artificial perfusion and maximal dilatation. Measurements were performed at constant flow and during 1) shifts in filtration-absorbtion, 2) alterations of perfused capillary wall area (graded rarification of capillary network by microsphere injection) and 3) during alterations of permeability (i.a. infusion of histamine). At maximal vasodilatation CFC was 0.037 +/- 0.001 ml/min X mmHg X 100 g and PS for Cr-EDTA 5.67 +/- 0.13 ml/min X 100 g. During filtration or absorbtion, Cr-EDTA transfer from vessels to interstitium changed only slightly but the situation may well be different for solute transfer from interstitium to vessels. Alterations in capillary wall area resulted in proportional changes in PS for Cr-EDTA while the CFC changes were always relatively smaller. Histamine increased CFC some threefold with a marked increase in protein transfer, while PS for Cr-EDTA increased only marginally. This histamine effect could be ascribed mainly to an increase in the number of large pores which, because of their relative paucity, are of little importance for small molecular diffusion exchange but highly important for convective and macromolecular exchange.     

Factors affecting the maturation of glomerular filtration rate and renal plasma flow in the new-born dog

1. The maturation of glomerular filtration rate was studied by comparison of thirty-six new-born mongrel dogs aged 1-35 days with six adult dogs.2. Under mannitol diuresis, glomerular filtration rate (GFR) rose from 0.16 ml. min(-1).g kidney(-1) at 1 day of age to 0.34 ml. min(-1).g kidney(-1) at 1 month of age. Adult GFR averaged 0.68 ml. min(-1).g(-1). There was good correlation of GFR with arterial blood pressure (r = 0.76, P < 0.001). Part of the statistical correlation of GFR with blood pressure was found to be independent of the relationship between blood pressure and age.3. Acute increases or decreases in blood pressure resulted in parallel changes in GFR in the puppies. There was no change of GFR with change of blood pressure in adult dogs. Carotid artery clamping, independent of blood pressure changes, produced increased renal vascular resistance and decreased GFR in the pups.4. Renal plasma flow (RPF) increased from 0.70 ml. min(-1).g(-1) at 1 day of age to 1.80 ml. min(-1).g(-1) at 1 month and showed good correlation with blood pressure (r = 0.67, P < 0.001). Filtration fraction (GFR/RPF) and renal vascular resistance did not vary with age in the pup and were the same as those for the adult.5. These results support the hypothesis that maturation of GFR and RPF are closely related to maturation of arterial blood pressure in the mongrel dog. The factors other than blood pressure which also affect renal maturation in the dog still need to be more clearly defined.     

Skin capillary blood cell velocity in patients with arterial obliterative disease and polycythaemia: a disturbed reactive hyperaemia response

Nailfold skin capillary blood cell velocity (CBV) was studied at rest and during post-occlusive reactive hyperaemia after a 1 min arterial occlusion (PRH1) in: (i) both hands of patients with arterial obliterative disease (AOD) of one arm, (ii) patients with polycythaemia, before and after a moderate haemodilution and (iii) healthy controls. CBV was analysed by videophotometric cross-correlation utilizing the different optical densities produced by the passage of erythrocytes, leucocytes and plasma gaps through the monitored capillary. Resting CBV in the patients with unilateral AOD was similar in equivalent fingers of both hands. However, the time to peak (p)CBV during PRH was significantly prolonged in the low-pressure arm as compared to the contralateral arm. pCBV was also delayed in the patients with polycythaemia as compared to the healthy controls. This delay was not affected by the replacement of 500-750 ml of blood with the same amount of a 6% Dextran 70 solution. The mean capillary blood cell velocity during rest (rCBV) did not differ between controls and patients before or after the haemodilution. The prolonged time to pCBV in the polycythaemic patients may be attributed to increased blood viscosity that is presumably not significantly influenced by a moderate haemodilution using Dextran 70. The marked delay to pCBV observed distal to the arterial obstruction in patients with AOD probably is an effect of the lower arterial pressure, presumably involving an alteration of vascular smooth muscle function.     

Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats

The effects of nitric oxide synthase (NOS) inhibition (effected using L-NAME, 14 mg (kg body mass (BM))(-1), administered intravenously) on systemic and renal circulation and renal excretory function has been investigated in anaesthetized Wistar rats subjected to one of two different degrees of isotonic extracellular (EC) volume expansion (40 and 60 ml x kg(-1) (240 min)(-1)). The administration of L-NAME resulted in an increase in mean arterial blood pressure and total peripheral vascular resistance (TPR), and a significant reduction in cardiac output (CO) and the kidney fraction of CO in both experimental groups. The total renal blood flow (RBF) dropped from 557 + 43.4 to 149 +/- 13.1 ml x min(-1) (100 g BM)(-1) and from 592 +/- 45.9 to 191 +/- 16.3 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively. A redistribution of the intrarenal circulation from the medulla of the kidney toward the cortex may have occurred. The NOS inhibition induced a significant decrease in the glomerular filtration rate (GFR; from 1.18 +/- 0.10 to 0.53 +/- 0.08 ml x min(-1) (100 g BM)(-1) and from 1.26 +/- 0.07 to 0.73 +/- 0.08 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively), and the filtration fraction increased. The urine excretion dropped in parallel with the GFR, while the reduction in sodium and potassium excretion was more marked than that of the GFR, raising the possibility of a direct effect on the kidney tubules. The difference in EC volume expansion (the calculated increases in the EC volume in the last 90 min were 1.30 and 5.44% in the two time control groups and 3.66 and 7.45% in the two L-NAME-treated groups) did not induce any significant modification of the L-NAME effect.     

Measurement of water filtration in skeletal muscle in man by an osmotic transient method

Water filtration in the human forearm was determined with a new method using a hyperoncotic transient of albumin solution infused into the brachial artery. Baseline dilution of labelled albumin in deep forearm vein plasma in excess of the contribution from arterial blood and from infusate was assumed to originate from extravascular water filtered into the blood by the transient. The filtration coefficient (Fc) was determined as the ratio between filtered water and increase in colloid osmotic pressure in the blood samples, and gives the filtrative water permeability in the exchange areas of the microcirculation. In 10 normal volunteers, Fc was 0.00082 ml (ml mmHg)-1 (SD=0.00007). Multiplication of Fc by plasma flow in the forearm gave a filtration capacity (Kf) of 0.0036 ml (100 ml tissue min mmHg)-1 (SD=0.00137). This filtration capacity (Kf) represents that of fast flowing regions in the forearm muscles, but it is of the same order of magnitude as the capillary filtration coefficient (CFC) determined plethysmographically for the entire forearm by the venous stasis technique.     

Vascular recruitment in forearm muscles during exercise

Blood flow and filtration of water across the vascular bed in human forearm muscles were studied at rest and during graded exercise with a hand ergometer. Blood flow was measured by dye dilution and water filtration was determined after injection of hyperoncotic albumin solution (23%) in the brachial artery creating a tissue to blood ultrafiltration measureable as a dilution in the effluent blood. The filtration constants were expressed as a filtration coefficient Fc (ml water/ml plasma mmHg increase in oncotic pressure), and, multiplying by the plasma flow, as a filtration capacity Kf (ml water/100 ml tissue min mmHg increase in oncotic pressure). During the increase in plasma flow induced by exercise, Fc remained constant at about 0.0007, but Kf increased in parallel with the hyperaemia from 0.0031 to 0.038 when plasma flow increased from 4 to 48 ml (100 ml min)-1. The data suggest a more massive recruitment of exchange area during exercise (a factor 12) than suspected on the basis of ultrafiltration in animals made with the prolonged venous stasis technique (showing a factor 2-5). The estimated variability in exchange surface area indicates, that animal studies of muscle circulation, whether pertaining to capillary permeability or capillary filtration should gain by an independent estimate of the number of capillaries that are flowing during the particular experimental situation.     

Transcapillary passage of albumin, effects of tissue cooling and of increases in filtration and plasma colloid osmotic pressure.

'Initial' clearance of radiolabelled serum albumin was measured in the perfused, maximally vasodilated muscle vascular bed of rat hindquarters during tissue cooling, during increases in filtration and during changes in serum colloid osmotic pressure. Albumin clearance during ordinary serum perfusion at isogravimetry amounted to 0.03 ml/min times 100 g, increasing linearly with filtration rate to some 0.07 ml/min times 100 g at 0.5 ml/min times 100 g of filtration. During cooling from 36 degrees C to 14 degrees C both CFC and initial albumin clearance at isogravimetry decreased some 40%, in due proportion to the increased viscosity of the fluid. Increases of the colloid osmotic pressure of the perfusate correspondingly increased both the isogravimetric capillary pressure and 'initial' albumin clearance during isogravimetry.--It is concluded that even during isogravimetry the transmicrovascular albumin passage is to about 70 per cent due to filtration, and only some 30 per cent of transport at ordinary serum colloid osmotic pressure takes place by diffusion, both events presumably via 'large pores'. There was no evidence that transendothelial vesicular transport should to any significant extent contribute to the passage of albumin from vessels to tissue.     

Effects of noradrenaline on the transcapillary passage of albumin, fluid and CrEDTA in the perfused rat hindlimb

Isolated rat hindlimbs were artificially perfused with serum solutions, either during maximal vasodilatation induced by papaverine or during infusions of noradrenaline (NA) at concentrations of 0.5-3.5 microM. Transcapillary exchange was followed with three independent techniques: clearance of albumin, measured after tissue accumulation of radiolabelled tracer, capillary filtration capacity (CFC), determined gravimetrically, and the capillary diffusion capacity (PS) for CrEDTA, calculated from venous indicator dilution curves after single bolus injection of dyes. During maximal vasodilation, when resistance to flow was 2.3 +/- 0.1 PRU100, albumin clearance was 0.0241 +/- 0.0012 ml min-1 100 g-1, CFC was 0.0367 +/- 0.0009 ml min-1 mmHg-1 100 g-1 and PS for CrEDTA was 8.2 +/- 0.4 ml min-1 100 g-1. Noradrenaline given before radiolabelled albumin increased vascular tone and reduced all three capillary exchange parameters in parallel. Albumin clearance was reduced also when NA was given after the introduction of radiolabelled albumin. When NA raised vascular tone to a level largely corresponding to that in resting skeletal muscle (PRU100 = 14) albumin clearance was 0.0067 ml min-1 100 g-1, CFC was 0.0141 ml min-1 mmHg-1 100 g-1 and PS for CrEDTA was 2.4 ml min-1 100 g-1. These findings suggest that albumin is transported by convective mechanisms and that the hydrostatic pressures fall in the exchange vessels as a consequence of functional precapillary 'sphincter' activity. Further, albumin clearance seems to be the same in the artificially perfused rat hindlimbs as in intact animals, at comparable vascular resistances, suggesting that capillary permeability is not influenced by the present surgical procedure.     

Cerebral blood flow and oxygen consumption in the newborn dog

Cerebral blood flow (CBF), CBF responses to changes in arterial CO2 tension, and cerebral metabolic rate for oxygen (CMRO2) were measured in newborn dogs, by means of a modification of the Kety and Schmidt technique employing 133Xe. Mongrel dogs of 1-7 days of age were paralyzed and passively ventilated with 70% N2O and 30% O2. CBF was derived by analysis of paired serial 20-microliter samples of arterial and of cerebral venous blood from the superior sagittal sinus. At an arterial PCO2 of 36.9 +/- 3.7 Torr and a mean arterial blood pressure of 62 +/- 10 Torr, CBF was 23 +/- 8 ml/min per 100 g. The arteriovenous oxygen content difference averaged 5.6 vol%, and CMRO2 was 1.13 +/- 0.30 ml O2/min per 100 g. CBF increased or decreased by 0.58 ml/min/100 g per Torr change in PCO2. Our results suggest that in the newborn, basal CBF and CBF responses to CO2 are considerably lower than in the adult and parallel the lower metabolic needs of the newborn brain.     

The effect of stepwise arterial hypotension on blood flow and oxidative metabolism of the brain

Summary With the Kety-Schmidt-technique in ten dogs anaesthetized with 0.5% halothane, blood flow and oxidative metabolism of the brain were studied during stepwise lowering of CPP due to arterial hypotension at 71 and 41 torr. CBF remained constant (65.6 and 64.1 ml/100 g min) when CPP dropped from 98 to 71 torr, but at a CPP of 41 torr CBF fell to 32.2 ml/100 g min, i. e. to about 50% of the resting value. The CMR-oxygen did not change (4.20 and 4.38 ml/100 g min) when CPP was reduced from about 100 to about 70 torr, but decreased to 2.90 ml/100 g min, i. e. about 70% of the resting value in deep arterial hypotension.The uptake of glucose changed from 4.62 to 6.19 mg/100 g min as well as the output of CO₂ and lactate (from 4.64 to 6.57 ml/100 g min and from 0.33 to 1.62 mg/100 g min) when CPP was decreased to 71 torr. It could be demonstrated that at this CPP range the oxidative metabolism was unchanged. It was assumed that the increased uptake of glucose was only to form lactate, and that this non-hypoxic lactate production was responsible for the elevated CO₂ release. At a CPP range of 41 torr the metabolic rates of glucose and CO₂ decreased to 3.33 mg/100 g min and to 3.37 ml/100 g min, respectively, while the output of lactate remained relatively high (1.14 mg/100 g min). These findings support the assumption that at a CPP range of 41 torr the oxidative metabolism of the brain becomes insufficient. All findings demonstrate close interactions between cerebral flow blood and oxidative brain metabolism in arterial hypotension. In deep arterial hypotension respiratory acidosis has an effect on CBF. The increase of CBF is accompanied by an improvement of CMR-oxygen but not of CMR-glucose. Although CMR-lactate is reduced, the lactate/glucose index remains high.     

Calcium dependence of histamine-induced increases in capillary permeability in isolated perfused rat hindquarters

Experiments were performed on isolated maximally vasodilated perfused rat hindquarters to evaluate the role of calcium and magnesium for the capillary permeability increase(s) elicited by histamine. Changes in capillary permeability were quantified by determinations of capillary filtration coefficient (CFC) with gravimetric technique, and capillary diffusion capacity (PS) for vitamin B12 (MW = 1,355) with a single injection indicator dilution technique. During control, vascular resistance was 2.2 PRU100 at a flow of 9.4 ml min-1 per 100 g, and PS for B12 was 3.7 +/- 0.1 ml min-1 per 100 g, while CFC was 0.0377 +/- 0.0004 ml min-1 mmHg-1 per 100 g. Perfusion with 'Mg-free' solution for 1 h caused a 24% increase in CFC, while neither 'Ca-free' perfusion nor perfusion with verapamil (5 X 10(-5) M) nor felodipine (1 X 10(-6) M) induced any changes in CFC. Histamine (100-200 microM) caused in all preparations a 150-200% increase in CFC with only small changes in PS for B12. This histamine effect was absent after 1 h of 'Ca-free' perfusion and was partially blocked after 1 h of perfusion with 0.1 mM calcium, while the calcium antagonists verapamil and felodipine had no effects on the histamine-induced changes. The results imply that histamine exerts its action on the endothelial cells through a calcium-dependent process, probably involving low affinity calcium sites but this process could not be inhibited by the calcium antagonists used. Thus, endothelial cell contractility, which probably is responsible for the histamine-induced increase in capillary permeability, exhibits unique characteristics, differing from those of vascular smooth muscle.     

Regional expression of inducible nitric oxide synthase in the kidney stimulated by lipopolysaccharide in the rat

The renal medulla contains more mRNA of the inducible isoform of nitric oxide synthase (iNOS) than the cortex, which may be important in preventing ischaemic injury, since blood flow and tissue oxygen tension are normally low in this region. We examined the effects of the bacterial endotoxin E. coli lipopolysaccharide (LPS) on renal function and regional expression of iNOS in male Sprague-Dawley rats. In six rats, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 0.95 +/- 0.09 ml min(-1) g(-1) and 3.36 +/- 0.20 ml min(-1) g(-1), respectively, and decreased significantly to 0.35 +/- 0.09 and 1.74 +/- 0.54 ml min(-1) g(-1), respectively, 1 h after administration of LPS. In an additional seven rats, GFR and ERPF were 0.91 +/- 0.07 and 2.97 +/- 0.30 ml min(-1) g(-1), respectively, 18 h after LPS administration; these values were similar to those in control rats. In all rats, arterial pressure was stable throughout all study periods. In control rats, immunoblot analysis revealed expression of the iNOS protein in the cortex and more pronounced expression in the medulla. In rats studied 18 h after LPS treatment, there was a striking increase in the iNOS expression in the outer medulla. Immunohistochemical examination in the LPS-treated rats showed limited iNOS immunostaining in the cortex, localised to the vascular endothelium and macula densa; however, intense and widespread staining was noted in the tubular and vascular structures of the outer medulla. These findings demonstrated a differential constitutive expression of iNOS protein in different regions of the rat kidney, and marked augmentation of iNOS expression in the outer medulla by LPS.     

Transcapillary clearance of albumin in rat skeletal muscle monitored by external detection. Effects of alterations in capillary surface area

The effects of noradrenaline (NA)-induced vasoconstriction on the transcapillary passage of albumin was evaluated by an external detection technique, allowing repetitive measurements of albumin clearance (Cl) during various conditions (in the same animal). Six isolated rat hindquarters were perfused with serum-albumin solutions during maximal vasodilation (papaverine 90 microM) and Cl was determined at different net filtration rates (Fv) induced by elevations of venous pressure. Then, the perfusate was changed to one of similar composition but containing noradrenaline (2-4 microM), and the procedure of determining Cl vs. Fv was repeated. Tissue accumulation of [99mTc]albumin was expressed in terms of clearance, using the isogravimetric Cl of defined muscle samples during maximum vasodilation in separate experiments as reference, the latter being 0.0246 +/- 0.0012 ml min-1 per 100 g. Noradrenaline caused an increase in vascular resistance from 2 to 14 mmHg min 100 g ml-1, while the Cl vs. Fv relationship was shifted downwards in a fashion parallel with the control Cl vs. Fv curve. For Fv = 0, Cl was 0.0101 +/- 0.0014 ml min-1 per 100 g during NA challenge. The average reflection coefficient for albumin (sigma tot) was 0.92 +/- 0.01 irrespective of vascular tone. Thus, both albumin clearance and the capillary filtration coefficient (CFC) seem to vary in direct proportion to the capillary surface area available for exchange.     

Simultaneous measurements of capillary diffusion and filtration exchange during shifts in filtration-absorption and at graded alterations in the capillary permeability surface area product (PS)

The diffusion exchange of Cr-EDTA, using the single injection indicator diffusion method, was followed simultaneously with estimations of the capillary filtration capacity (CFC) in an “isogravimetric” rat hindquarter preparation during artificial perfusion and maximal dilatation. Measurements were performed at constant flow and during 1) shifts in filtration-absorbtion, 2) alterations of perfused capillary wall area (graded rarification of capillary network by microsphere injection) and 3) during alterations of permeability (i.a. infusion of histamine). At maximal vasodilatation CFC was 0.037 ± 0.001 ml/min × mmHg × 100 g and PS for Cr-EDTA 5.67 ± 0.13 ml/min × 100 g. During filtration or absorbtion, Cr-EDTA transfer from vessels to interstitium changed only slightly but the situation may well be different for solute transfer from interstitium to vessels. Alterations in capillary wall area resulted in proportional changes in PS for Cr-EDTA while the CFC changes were always relatively smaller. Histamine increased CFC some threefold with a marked increase in protein transfer, while PS for Cr-EDTA increased only marginally. This hista mine effect could be ascribed mainly to an increase in the number of large pores which, because of their relative paucity, are of little importance for small molecular diffusion exchange but highly important for convective and macromolecular exchange.     

Transcapillary fluid movement in human calf after drinking hypertonic saline

1. Transcapillary absorption of interstitial fluid was demonstrated with a pressure plethysmograph applied to the human calf after the ingestion of 200 ml. hypertonic (5.1%) saline. Capillary absorption began within 15 min after ingestion and lasted for about 2 hr. The maximum rate of absorption (0.019 ml./min. 100 ml. tissue) was attained 30-75 min after ingestion.2. The total amount of fluid absorbed into capillary blood vessels in the calf was 1.11 ml./100 ml. tissue. The amount of fluid thus absorbed in the whole body was estimated to be 677 ml.3. The capillary filtration coefficient (CFC) of the calf was also measured by the pressure plethysmograph. This was 0.0038 ml./min. mm Hg. 100 ml. tissue.4. The peak value of capillary absorption pressure was 5.2 mm Hg.5. The total osmotic pressure of the plasma rose by 12.6 m-osmole/kg H(2)O after ingestion. This rise was accompanied by transcapillary fluid absorption.6. The plasma protein concentration and packed cell volume were almost unchanged by ingestion, indicating that the plasma volume was unaltered.7. It was estimated that the net shift of fluid between intracellular and interstitial compartments during the period of transcapillary fluid absorption was very small.8. It is concluded that the volume of fluid moving from plasma into intestinal lumen is the same as that flowing from interstitial fluid into plasma, and that the transcapillary absorption is caused by a difference in osmotic pressure between the plasma and the interstitial fluid.