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Biomedical subjects

G Clausen

Publications and source records attributed to G Clausen.

At least 37 records · Page 2Linked to original sources
PubMed1984

Renal blood flow and vasodilatory ability prior to and following release of 24 hours bilateral ureteral obstruction in rats.

Increased renal vascular resistance (RVR) is evident after 24 hours of uni- and bilateral ureteral obstruction (UUO and BUO). However, to what extent the RVR increase is due to vascular damage versus functional vasoconstriction, or whether obstructed kidneys possess the ability to reduce RVR in response to vasodilatory stimuli, is not clear. During 24 hours of BUO renal blood flow (RBF), recorded electromagnetically, was reduced to about 70% of control and continued to fall by another 18% during 1/2-1 hour after release of BUO. Infusion of imidazole, a thromboxane A2 synthetase blocker, did not reduce RVR after release of BUO. Whereas RBF autoregulation in response to reduced perfusion pressure was impaired, maximal proportional renal vasodilation induced by acetylcholine was increased, both prior to and after release of BUO, as compared to control and UUO. These different renal vasodilatory responses indicate that the RVR increase during BUO is largely due to a functional vasoconstriction that impairs autoregulatory vasodilation. In contrast, the RVR increase during UUO is probably mainly due to structural damage which does not prevent autoregulation of the RBF level attained.

Acetylcholine↗
PubMed1983

Uptake of adriamycin by sarcoma transplants in the rat kidney: effects of renal arterial vs systemic constant rate infusion and of combination with ricin.

The uptake of adriamycin (Adm) by normal tissues and by sarcomas transplanted to both kidneys in rats was studied at 10 min following constant rate infusion of Adm 5 mg/kg body wt into one renal artery, during 3 and 10 min. Since the selectively infused kidney extracted only about 20% of the total dose, the present model provides a direct comparison of systemic versus selective i.a. infusions in each individual. Tumor Adm uptake was about 6 times higher on the selectively infused side. Adm uptake by tumor and normal renal tissue was proportional to the concentration X time product of Adm in arterial blood, in spite of highly different blood peak concentrations at different infusion rates. Ten-minute systemic intravenous infusion of the Adm dose, with concurrent infusion of ricin, 3 micrograms/kg, into one renal artery tended to increase Adm uptake by the tumors on both sides. This indicates a systemic rather than a local effect of ricin: ricin reduced Adm uptake by red blood cells and normal solid tissues and thus resulted in a delayed Adm clearance from the total plasma volume. In contrast, the relationship between tumor uptake and the concentration X time product of Adm in plasma was not affected by ricin, explaining the increased tumor uptake.

Animals↗
PubMed1983

Renal blood flow during unilateral ureteral obstruction. Effects of reduced perfusion pressure, acetylcholine, and thromboxane A2 blockers in obstructed and unobstructed rat kidneys.

Renal blood flow (RBF) is markedly reduced in kidneys with unilateral ureteral obstruction (UUO), possibly due to vascular constriction. Whether obstructive nephropathy is associated with impaired RBF autoregulation is unknown. We therefore investigated RBF autoregulation in obstructed and contralateral unobstructed rat kidneys during and following release of 24 h and 6 days of UUO, using stepwise reduction of renal arterial pressure and electromagnetic recording of RBF. The lower pressure limit of autoregulation was increased and the maximal vasodilatory ability in response to infusion of acetylcholine into the renal artery was reduced only in the unobstructed kidney at 24 h of UUO. Thus, we conclude that the vasodilatory reactions to both these maneuvres, previously observed to be markedly reduced during acutely elevated ureteral pressure (Hope & Clausen 1982), were reestablished: In the obstructed kidneys in less than 24 h (RBF approximately 70% of control) and in the contralateral unobstructed kidneys in less than 6 days (RBF approximately 140% of control). Infusion of the thromboxane A2 (TXA) synthetase inhibitors imidazole and 3-ethyl pyridine in controls and at 24 h and 6 days of UUO did not produce renal vasodilation. These results do not support the suggestion that TXA contributes directly to the increase in renal vascular resistance observed during or following release of UUO in the rat.

Acetylcholine↗
PubMed1983

Intrarenal flow of microspheres and red blood cells: skimming in slit and tube models.

Microspheres (MS) provide somewhat erroneous estimates of intrarenal blood flow distribution due to a variable MS skimming. The errors were computed from two sets of model experiments. Skimming of 3.5-, 10-, and 15-micron MS and normal and hardened red blood cells (RBC and HRBC, respectively) were studied in a slit model simulating an interlobular artery (ila) with variable diameter from 40 to 160 micron, having as a side branch of constant diameter one afferent arteriole with variable fractional flow. The corresponding afferent arteriole capture zones in the ila were determined in a tube model. All particles except 3.5-micron MS were skimmed, RBC having an effective diameter of 5 micron compared with 8 micron for HRBC. Skimming was greater in tubes than in slits at a given afferent arteriole flow fraction and was predominantly determined by the particle-to-ila diameter ratio. Intrarenal MS and RBC skimming in dog and rat kidneys was predicted on the basis of the number of afferent arterioles along the ila, ila diameter and tapering. The predictions agreed fairly well with available in vivo data. In conclusion, previously observed redistribution of MS, induced by vasodilation and vasoconstriction in the dog kidney, may be quantitatively ascribed to changes in the ila diameters and MS skimming in the inner cortex without redistribution of fractional blood flow between deep and superficial renal zones.

Animals↗
PubMed1983

The effect of hemorrhagic hypotension on total and local renal blood flow in the rat.

The effect of hemorrhagic hypotension (HH) on local and total renal blood flow was studied in rats. Cortical blood flow, measured as H2 gas clearance, was determined before and during HH with a mean arterial blood pressure of 50 mm Hg. During the initial 10-15 min of bleeding renal cortical vascular resistance was unchanged, and total renal blood flow autoregulatory ability was abolished. Cortical vascular resistance thereafter increased steadily to twice the control level after 90 min of HH. At this time, retransfusion of the shed blood improved cortical blood flow due to increased arterial blood pressure, not to reduced cortical vascular resistance. In a second group, total and local renal blood flows were obtained from 125I-iodoantipyrine uptake rate after 2 h of HH with arterial blood pressure maintained at 50 mm Hg. Total renal blood flow was reduced to 20% of control with no change in blood flow distribution between outer and inner cortical or medullary zones. Both cortical blood flow and intrazonal local renal blood flow heterogeneity had increased at the end of the HH period. However, ischemic and extremely low flow sectors comprising cortex and outer medulla were observed only in 1 of the 10 kidneys studied with the 125I-iodoantipyrine technique. In only 1 of 8 animals studied with the H2 gas method were intermittent sudden changes in cortical blood flow observed during HH. Since hematocrit tended to fall during HH, these observations support the concept that local flow intermittence is predominantly associated with high hematocrit shocks.

Animals↗
PubMed1982

Effect of adriamycin on blood flow in renal tumour and normal renal tissue.

The effect of adriamycin (Adm) on local blood flow was simultaneously measured in neoplastic tumour, diameter 3-5 mm, and intact tissue in rat kidneys using the H2 gas washout technique. Constant rate i.v. infusion of Adm, 0.3-6 mg/kg/min for 3-15 min, increased mean arterial blood pressure (AP) by 20%, a maximum already obtained at the lower infusion rate, without affecting heart rate. Control tumour flow averaged 0.9 (0.4-1.1) ml/min/g. Flow was inversely related to Adm infusion rate in both tissues, but tumour flow tended to be relatively less affected. In another series of experiments total renal blood flow (RBF) was recorded electromagnetically during constant rate infusion of Adm into the renal blood stream, 0.03-3 mg/kg/min for 3-20 min. AP increased and RBF decreased during the first 2 min of infusion, whereafter steady levels were maintained. Both parameters returned to control levels within 4 min after completed infusion, irrespective of infusion rate and duration. High i.a. infusion rates, 2-3 mg/kg/min, almost stopped RBF but gave no further AP increase (max at approximately 0.5 mg/kg/min), indicating a direct constrictor effect on renal vessels. On the other hand, the AP response persisted when renal circulation was excluded, suggesting a general pressor response evoked by Adm. A 60% RBF reduction was obtained by 1 mg/kg/min i.a. as compared to 4-6 mg/kg/min i.v. infusions. This indicates that a several times higher Adm concentration was maintained in renal blood during i.a. infusion. Taken together with the recovery time, this observation also suggests a post-infusion blood clearance of Adm with an initial half-time of about 2 min or less. This was confirmed in additional experiments where [3H]-labelled Adm was determined in timed blood samples.

Animals↗
PubMed1981

Incomplete and flow dependent extraction of 86Rb in the rat kidney. Errors in local flow estimation.

Renal uptake of 86Rb, lasting for 30s after intravenous bolus injection, and uptake of 15 micrometer radioactive microspheres (Ms) simultaneously injected in the left ventricle were measured in rats. Calculated from renal blood flow (RBF) determined by Ms and 86Rb clearance, the renal extraction ratio of 86Rb (ERb) was 0.81 +/- 0.07 (SD). With increasing RBF, ERb decreased significantly. Total body 86Rb extraction ratio nearly equalled ERb as determined 30s after injection. In another group of rats 86Rb was injected into an extracorporal circuit from the carotid artery perfusing the left kidney only. Renal recovery of 86Rb averaged 0.76 +/- 0.13 15-20s after injection. As in the first group, ERb was inversely related to RBF. At increased RBF, calculated local cortical flow is seriously underestimated unless ERb as well as ERb flow dependency are taken into account. However, the relative local flow rates calculated for cortical zones are not appreciably affected by ERb and its flow dependency.

Animals↗
PubMed1981

Total and local renal blood flow and filtration in the rat during reduced renal arterial blood pressure.

Discrepancies concerning the lower pressure limit of renal blood flow (RBF) autoregulation, different autoregulatory adjustments in deep and superficial renal zones and dissociation of RBF and filtrate production stimulated the present study. Autoregulation of renal blood flow was investigated at reduced renal arterial blood pressure (RAP) in Sprague-Dawley rats using 4 different flow methods: uptake of 125I-iodoantipyrine (I-Ap) and 86Rb, local detection of hydrogen gas washout rate (H2) and, in the autoperfused kidney, electromagnetic flowmetry (FM). With I-Ap and 86Rb, RBF was maintained at a RAP as low as 80 mmHg, compared to contralateral RBF. However, with the other two methods where each kidney serves as its own control, a 15% RBF reduction was obtained at this RAP. This discrepancy (p less than 0.001) infers a contralateral renal vasoconstriction during ipsilateral renal hypotension and vasodilation. Arterial blood pressure increased during unilateral renal hypotension, suggesting that contralateral renal constriction was part of a general increase in total body vascular resistance. Following abrupt RAP reduction RBF was immediately readjusted (2-3 s) and maintained for up to 40 min. No significant change in intrarenal blood flow distribution was observed with I-Ap. Superficial and deep cortical single nephron glomerular filtration rates were equally reduced at lowered RAP as determined by the ferrocyanide technique. However, a dissociation between the autoregulation of RBF and glomerular filtration rate (GFR) in the direction of less well maintained GFR was observed. Renal arterial acetylcholine infusion increased RBF by about 40% and effectively abolished RBF autoregulation.

Acetylcholine↗
PubMed1981

Distribution of blood flow in the dog kidney. III. Local uptake of 10 mum and 15 mum microspheres during renal vasodilation and constriction.

Recent studies indicate that intrarenal distribution of blood flow measured with microspheres (Ms) during control conditions depends on Ms size. We therefore compared local flow in outer and middle cortex (C1 and C2) and inner cortex plus the medulla (C3M) using 10.5-12.0 and 13.9-15.0 mum Ms (Ms 10 and Ms 15). One pair of Ms 10 and Ms 15 was injected during control and a second pair at 80% increased or 50% decreased total renal vascular conductance (RVC), as induced by infusion of acetylcholine (Ach) and angiotensin II (Ang) or noradrenaline (NA). All zones participated in dilation and constriction, as indicated by both Ms sizes. Ms 15 underestimated C3M flow as compared to Ms 10, by 19% during control or Ang, and by 3% during Ach (P less than 0.02). The C3M flow fractions increased during Ach and decreased during Ang, whereas NA gave greatly variable results, on average no change. Renal Ms extraction averaged 97.0 +/- 3% for Ms 10, 98.6 +/- 2.4% (S.D.) for Ms 15. About 8% of Ms 10 and less than 1% of Ms 15 were located in peritubular capillaries in each cortical zone. Neither total Ms extraction nor zonal extraglomerular Ms fraction changed over the present RVC range. Thus, the Ms 10 to Ms 15 differences as well as the observed redistribution must be due to differences in local entry of Ms into the afferent arterioles. However, steric restriction of Ms at arteriolar inlets did not play a significant role. The measured redistribution of fractional flow could in part be due to skimming of Ms at arteriolar inlets along the interlobular arteries (i.l.a.), depending on the C3M flow fraction, Ms size and i.l.a. diameter. If the observed fractional flow redistributions were solely due to variable Ms skimming, Ms 15 underestimated C3M flow by 53%, Ms 10 by 43%, during Ang as compared to Ach. Although Ms 10 and Ms 15 may correctly indicate the direction of fractional glomerular flow redistribution, at least Ms 15 overestimates this phenomenon quantitatively.

Acetylcholine↗
PubMed1981

Distribution of blood flow in the dog kidney. IV. Reversed net inward postglomerular capillary flow in the cortex after blocking interlobular arteries by 50 mum microspheres.

Simultaneous measurement of glomerular flow by 15 mum microspheres (Ms) and postglomerular capillary flow by 125I-iodoantipyrine (I-Ap) suggest that about 10% of total RBF flow inward through the entire cortex in the postglomerular capillaries of the dog kidney. This flow fraction might be variable (Clausen et al. 1978, 1980) and perhaps even reversible. To test this possibility we injected 50 mum Ms into the renal artery in order to obstruct interlobular arteries and produce a selective reduction of outer cortical glomerular blood flow and postglomerular pressure. The 50 mum Ms reduced total RBF by 50%. In the outer cortex, postglomerular flow measured by I-Ap was significantly less reduced than glomerular flow as measured by 15 mum Ms: Whereas the inward flow fraction from inner cortex to the medulla was maintained, about 5% of RBF now drained from midcortex to outer cortex. This observation support the theory of a variable net postglomerular capillary flow of radial direction in the cortex of the dog kidney.

Animals↗
PubMed1981

Skimming of microspheres in vitro: implications for measurement of intrarenal blood flow.

Skimming could result in erroneous estimation of renal cortical blood flow distribution as measured by microspheres. Skimming of microspheres with diameters 10, 12, and 15 micrometers and red blood cells was therefore studied in a model in which an interlobular artery and its first arteriolar branch were simulated by 80- and 30-micrometers-wide slits between glass prisms. The experiments were performed with citrated blood at a hematocrit (Hct) of 40, flow velocities of 3 and 6 cm/s, and branch flow varying from 2 to 25%. At a branch flow fraction comparable to that of a deep arteriole in the dog kidney (3%), Hct in branch blood was 24% lower than that of input blood, whereas 10-, 12-, and 15-micrometers microsphere concentrations were 75, 81, and 87% lower, respectively. The size-dependent skimming was probably caused by wall exclusion in the main channel. Differences in particle inertia did not affect skimming. The results suggest that the disparate local flow values obtained by use of microspheres of different sizes in dog and rat kidneys are due to a size-dependent skimming of the microspheres.

Animals↗
PubMed1981

Effect of exogenous angiotensin-II on local blood flow in kidneys with neoplasm. Experiments in the rat.

The effect of angiotensin-II on the local renal blood flow and arterial blood pressure was investigated in the rat with the H2 gas washout technique. Increasing intravenous infusion rates gave a decreasing blood flow and increasing blood pressure, renal vascular resistance being close to proportional to the log of infusion rate. In kidneys with experimental neoplasm, the flow reduction was proportionally less in the tumor than in intact renal tissue. The respective flow levels were maintained for 10 to 45 min without tendency to change.

Angiotensin II↗
PubMed1980

Distribution of blood flow in the dog kidney. II. Saturation rates of inert diffusible tracers versus uptake of 15 mu microspheres during vasodilation and vasoconstriction.

While 15 mu microspheres (Ms) in principle provide a measure of glomerular flow, uptake rate of inert diffusible tracers indicates "effective" or "nutrient" flow, i.e. essentially postglomerular capillary flow. Paired measurements of glomerular and postglomerular flow were made in tissue samples from outer, middle and inner cortex (C1, C2, C3) and medullary zones. After a control Ms injection, renal vascular conductance (RVC) was altered in one kidney whereupon a second Ms injection was made, immediately followed by infusion of the 125I-iodoantipyrine and tritiated water. RVC was increased maximally by i.a. infusion of acetylcholine with and without reduced renal arterial pressure, whereas moderate vasodilation was produced by lowering renal arterial or rising ureteral pressure. RVC was reduced by i.a. or i.v. infusion of angiotensin II. Within a mean RVC range of 50 to 180% of control the fractional distribution of zonal postglomerular flow remained unaltered, in agreement with previous results obtained from local H2 gas desaturation rate. Glomerular flow was about 20% higher in C1, equal in C2 and 40% lower in C3 as compared to postglomerular flow in control kidneys. This disparity nearly disappeared during maximal vasodilation and tended to increase during vasoconstriction. The results might suggest a variable net postglomerular effective flow in radial direction through the renal cortex. Alternatively, the fractional redistribution of Ms might reflect a variable degree of Ms skimming at the afferent arteriolar inlets along the interlobular arteries.

Acetylcholine↗
PubMed1979

Partition of 125I-iodoantipyrine among erythrocytes, plasma, and renal cortex in the dog.

The tissue/blood partition coefficient, lambda tb, defined as the amount of blood having the same tracer content as one unit of tissue at diffusion equilibrium, was determined for 125I-iodoantipyrine (I-Ap) and tritiated water (THO) in the dog kidney cortex. Measurements were made after in vivo equilibration for 75 to 300 s and with liver circulation excluded. In 18 kidneys, lambda tb for I-Ap averaged 1.38 (S.D. 0.13) w/w (weight/weight), without significant correlation to hematocrit (range: 23-43) or to urine pH (range 5.5-8.6). The lambda tb for THO averaged 0.97 (S.D. 0.06) v/w (volume/weight), close to the relative water contents. Erythrocyte/plasma partition for I-Ap was 0.82 w/w, compared to a water partition of 0.72. Thus, at diffusion equilibrium the apparent I-Ap concentration in renal cortical and red cell water exceeds that of plasma water by 14 and 60%, respectively. It follows that I-Ap cannot be used as a general indicator for total tissue water content. When used for measurement of local blood flow and modum Kety, lambda tb must be determined for each tissue and species.

Animals↗
PubMed1979

Distribution of blood flow in the dog kidney. I. Saturation rates for inert diffusible tracers, 125I-iodoantipyrine and tritiated water, versus uptake of microspheres under control conditions.

Disparate reports on intrarenal blood flow distribution prompted a direct comparison between microspheres (Ms) and inert diffusible tracers (DT). The "tissue sampling technique" for estimating local flow with DT (Kety) was adapted for the dog kidney, using 125I-iodoantipyrine (1-Ap) and tritiated water (THO). Ms (15 micron) were injected 2-3 min prior to 10-15 s DT infusion made during continuous 1 s arterial blood sampling. Tracers were measured in 7 to 20 samples from each of the following zones: Outer, middle and inner cortex (C1, C2, C3), outer and inner halves of outer medulla (OM1, OM2), and inner medulla (IM). I-Ap and THO gave closely similar flow distribution, and average total renal blood flow (RBF) of 3.90 and 3.78 as compared to 3.94 ml/min . g with Ms. Flow in C2 (ml/min . g) was similar with all tracers, and in per cent thereof average local flows were: C1 102, C3 70, OM1 34, OM2 12, and IM 2 with DT versus 117, 53, 12, 3, and 0 with Ms. Zonal flow fractions of total RBF obtained with DT were: C1 0.41, C2 0.33, and C3+medulla 0.26 versus 0.51, 0.33 and 0.16 with Ms. Thus, a Ms surplus in C1 relative to DT flow, representing 10% of total RBF, matched a Ms deficit in C3+medulla. This disparity might result from: (1) Failure of Ms to enter deep afferent arterioles in proportion to blood flow, (2) diffusion of DT from deep portions of the interlobular arteries, and/or (3) postglomerular inward flow of blood and DT.

Animals↗
PubMed1977

Intrarenal distribution of blood flow and glomerular filtration during chronic unilateral ureteral obstruction.

Paired hydronephrotic (HN) and hypertrophic (HT) rat kidneys were studied after 6 days with complete unilateral ureteral obstruction without exposing the kidneys. Total HN renal blood flow (RBF), estimated by total microsphere (MS) uptake and from local 125I-antipyrine (Ap) uptake, averaged about 3/4 of control. HN kidney GFR was reduced to about 1/2 of control level as estimated from inulin clearance of HT kidney times the HN to HT ratio for mean single nephron filtration rate, determined by 14C-ferrocyanide. Whereas blood flow (Ap) was proportionately reduced in outer and inner cortex (OC and IC), fractional flow to the outer medulla (OM) was doubled as compared to controls (p less than 0.01). Filtration was well preserved in deep as compared to superficial glomeruli with a smaller deep nonfiltering fraction (p less than 0.02). Thus the results oppose the current concept that HN is characterized by disproportionate circulatory damage to IC and OM with little or no filtration in deep nephrons. In HT kidneys average RBF (MS) and GFR rose by about 1/2. Whereas total blood flow (Ap) rose proportionately in OC and IC, it remained at control level in OM, indicating dissociation between the total RBF and GFR and the effective blood flow to the OM zone.

Animals↗