Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex

Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05–0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57± (S.D.) 1.73 ml/min g and 4.35±0.57 ml/min g, which is higher than found using 0.2–0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow.     

Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex.

Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05-0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57 +/- (S.D.) 1.73 ml/min.g, and 4.35 +/- 0.57 ml/min.g, which is higher than found using 0.2-0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow.     

Renal blood flow distribution during E. coli endotoxin shock in dog

The effect of endotoxin on renal blood flow distribution was studied in anesthetized dogs. Renal blood flow was measured as hydrogen clearance by platinum electrodes placed in outer and in inner halves of cortex and by electromagnetic flowmeter. Intravenous injection of E. coli endotoxin, 3–5 mg/kg b. wt., promptly reduced arterial blood pressure (AP) and renal blood flow. After a transient increase for 45 min AP and renal blood flow declined to about 50% of the control 2½-3 h after injection. The reduction in outer cortical blood flow (OCF) was not significantly different from the reduction in inner cortical blood flow (ICF). The hematocrit (Hct) increased from 40.1±3.8% to 54.6±8%, but mean renal vascular resistance did not change. Total plasma protein concentration was not significantly elevated. A marked local flow variability was observed in some periods during the phase of shock with declining AP and total renal blood flow at high Hct. Thus renal blood flow showed phasic changes, but the OCF/ICF ratio was not changed during endotoxin shock. Local blood flow instability was observed periodically at high Hct.     

Effect of vasoactive agents on the distribution of renal cortical blood flow in dogs.

The distribution of renal cortical blood flow was studied in 6 Nembutal anesthetized dogs during control periods and during infusions of adrenaline, noradrenaline, angiotensin and vasopressin. Local cortical blood flow was measured as H2 gas desaturation rate recorded polarographically by platinum electrodes in outer and inner cortex. The total renal blood flow (RBF) was measured by an electromagnetic flow meter. In the control period the outer cortical blood flow (OCF) and inner cortical blood flow (ICF) averaged 3.59 (+/- S.D. 0.85) ml/min - g and 3.23 (+/- S.D. 0.64) ml/min - g, respectively. Infusions of the various vasoactive agents caused essentially equal vascular responses. All agents caused increased local renal resistance and reduction of RBF whether given intravenously or intraarterially. The RBF could be lowered to 20-50% of initial control flow by increasing doses of vasoactive agents. OCF and ICF fell proportionately and almost to the same extent as RBF, or OCF fell slightly more than ICF. There was no evidence for patchy or zonal hypoperfusion in cortex caused by infusion of adrenaline, noradrenaline, angiotensin and vasopressin.     

Effects of steady-state plasma vasopressin levels on the distribution of intrarenal blood flow on electrolyte excretion.

1. In order to evaluate the effects of arginine vasopressin (AVP) on the distribution of intrarenal blood flow and on electrolyte excretion, steady-state plasma AVP levels (4-8, 19-1, 44-3, and 100-6 micro u./ml.) were produced in anaesthetized dogs, which were hydrated to minimize endogenous anti-diuretic hormone (ADH) release. 2. The urinary excretion of sodium and potassium increased without change in their filtered loads during AVP infusion. 3. Measurement by the 133xenon washout method revealed diphasic blood flow shifts, as a function of the plasma AVP level, between compartment 1 (outer cortex) and compartment 2 (inner cortex and outer medulla) without change in compartment 3 (inner medulla). 4. In a separate study, the radioactive microsphere (15 micronm) method was used with a plasma AVP levels of 19-8 micronu./ml. Blood flow (expressed as % flow/g tissue) decreased in the outer cortex and increased in the inner cortex. 5. Total renal blood flow did not change during infusion of AVP. However, the values measured by 133xenon were lower than those measured by the microsphere method. 6. There was agreement between these two independent methods that blood flow shifted from outer to inner cortex, with no change in total renal flow, at similar plasma AVP levels (19-1 and 19-8 micronu./ml.). The relationship of these intrarenal circulatory changes to the increased electrolyte excretion is discussed.     

The Effect of Indomethacin on Renal Blood Flow Distribution during Hemorrhagic Hypotension in Dog

The effect of indomethacin in hemorrhagic hypotension (HH) on total renal blood flow (RBF) and cortical flow distribution was studied in 9 pentobarbital anesthesized dogs. Local blood flow was measured as hydrogen clearance by 6 platinum electrodes in outer and inner cortex. RBF was recorded by electromagnetic flowmeter. Injection of indomethacin (3–5 mg/kg b.wt.) to inhibit prostaglandin synthesis, reduced renal blood flow only a few percent in control period. After the pretreatment with indomethacin, bleeding to mean arterial pressure 50 mmHg decreased RBF abruptly to 25% of control flow. Thus a renal vasoconstriction is observed both in early and late periods of bleeding in contrast to the initial vasodilation observed during the first half an hour of HH when prostaglandin formation was not blocked. Local blood flow in outer cortex decreased proportionally to flow in inner cortex during bleeding in both the indomethacin treated as in the untreated group, indicating an equal vasodilatory effect of prostaglandin in all parts of renal cortex during early periods of HH.     

Renal intracortical blood flow during hemorrhage: role of adrenergic mechanisms.

Hemorrhagic hypotensin in anesthetized dogs produced a redistribution of renal blood flow from the outer to the inner cortex. The role of adrenergic mechanisms in this redistribution was studied in anesthetized dogs using a radioactive microspheres to determine intrarenal blood flow. Neither renal denervation, nor pretreatment with reserpine altered the characteristic redistribution of renal cortical flow during hemorrhage. These observations suggest that neither intact renal nerves nor circulating catecholamines are necessary for the redistribution of renal intracortical blood flow during hemorrhagic hypotension, and the role of myogenic autoregulation is emphasized.     

Mechanism of intrarenal blood flow redistribution after carotid artery occlusion.

Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.     

Effect of Dehydration on Renal Blood Flow in Dog

The effect of dehydration on intrarenal blood flow was investigated in 11 dogs, using polarographic determination of H₂-gas desaturation for measuring local blood flow in inner cortex (ICF) and outer cortex (OCF). Dehydration was induced by 48 h water deprivation + 2–300 mg ethacrynic acid (EA) per os the day before the experiment. Compared to a control group (n = 9) ICF was markedly reduced to 2.40 ± 0.47 ml/min×g (control 3.23 ± 0.64) whereas OCF 3.29 ± 0.80 ml/min×g was nearly unchanged (control 3.59±0.85). The ratio OCF/ICF was increased to 1.37 (1.11). Further dehydration by hypertonic peritoneal dialysis for 3 h increased Hct to 60 ± 4 and further reduced OCF and ICF, without significant change of the OCF/ICF-ratio. At Hct above 55 sudden and intermittent changes in local cortical blood flow were recorded randomly at individual electrode sites, showing ischemic periods lasting for 1 to 60 min. Such flow changes were observed in 13 of 14 expts. and were not accompanied by changes in RBF. It is concluded that moderate dehydration causes a greater reduction of ICF than of OCF. Severe dehydration gives in addition rise to patchy, intermittent ischemia in both cortical layers.     

烫伤大鼠肾皮、髓质血流的变化

用ＬＤＦ－３型激光多普勒血流计分别测定重度皮肤烫伤大鼠肾皮、髓质烫伤前后血流变化。结果发现：伤后５ｍｉｎ，肾皮、髓质血流均严重下降。分别降至伤前的６０％和５２％；继而皮质血管呈现明显的节律运动。伤后３０ｍｉｎ，皮质血流随动脉血压代偿性回升呈明显增加趋势，而髓质血管节律性运动不明显，其血流也不随血压代偿性回升而增加，呈持续减少趋势。上述结果表明：重度皮肤烫伤大鼠肾皮、髓质血流均明显下降，但以髓质为著；髓质血管自律性运动较皮质差。在病理情况下，髓质血供具有更大的易损性。     

Renal vasoconstriction induced by arachidonic acid during burn shock in rats

Metabolites of arachidonic acid are possible mediators of local renal vasoconstriction in burn shock. The prostanoid precursor arachidonic acid (AA) therefore was infused in the control period and at 1 and 2 h after scalding in anaesthetized rats. To avoid systemic effects. AA was infused at low doses directly into the renal artery through a thin cannula introduced through the aortic wall. After control observations 40% of the body surface was scalded in 80 degrees C water. Renal arterial blood flow (RBF), measured by an electromagnetic probe, fell to 70% and 58% of the control level at 1 h and 2 h after scalding respectively. Arterial blood pressure was almost maintained. Infusion of AA (5, 15 and 25 nmol) in the renal artery over 15 s caused no effects in the control period, whereas a dose-dependent decrease in RBF was observed after scalding, and was most pronounced 2 h post-burn. The highest dose of AA reduced RBF by 37% at 1 h and by 80% of preinfusion flow at 2 h after scalding. The AA-induced decrease in RBF was abolished by blocking the thromboxane A2 receptors with AH23848. In contrast, inhibition of prostacyclin synthesis or blocking of serotonin S2 receptors did not significantly influence the response to AA during shock. Thus, infusion of AA into the renal artery caused a marked reduction of RBF after scalding, at doses that did not induce a change during the control period. The augmented effect of AA infusion may be due to an increased capacity for synthesis of thromboxane A2 (TxA2), and possibly PGH2 and PGF2 alpha, after scalding.     

Maturation of glomerular blood flow distribution in the new-born dog

1. Glomerular blood flow distribution was studied in seventy-eight new-born mongrel dogs aged 1-40 days by measuring the distribution of radioactive labelled microspheres within the kidney.2. The microsphere technique was found to be a valid indicator of glomerular blood flow distribution for the new-born dog since (a) the spheres were completely extracted by the kidney, (b) more than 95% of the spheres were trapped in glomerular capillaries, (c) the spheres were evenly distributed within any specific region of the kidney and, (d) the spheres did not interfere with renal haemodynamics.3. Plasma flow per gram tissue to inner cortical glomeruli, relative to that to outer cortical glomeruli, the IC/OC flow ratio, was high at birth, decreased over the first 2 weeks of life and remained relatively constant thereafter. Plasma flow per gram tissue to the outer cortex increased over the whole 40 day period while that to the inner cortex decreased slightly and then increased after 2 weeks.4. The IC/OC flow ratio decreased in a curvilinear fashion as blood pressure rose with maturation. Acute increases or decreases in blood pressure in any animal produced decreases or increases, respectively, in the IC/OC flow ratio.5. There was no correlation between the IC/OC flow ratio and renal extraction of p-amino-hippurate (E(PAH)).6. There was histological evidence that glomerular differentiation persists for 2 weeks during the post-natal period in the dog. This continuing post-natal glomerulogenesis takes place only in the outer cortex.7. These results are consistent with the hypothesis that an important factor in renal maturation is a redistribution of blood flow within the kidney. As the animal matures a greater fraction of the total glomerular blood flow goes to outer cortical glomeruli. This is due partly to the continuing glomerular differentiation taking place in the outer cortical region and partly to the increasing arterial blood pressure occurring with maturation.     

重型颅脑创伤并发大面积脑梗死的成因分析

目的探讨外伤性大面积脑梗死的形成原因及易发因素。方法对40例重型颅脑损伤患者临床资料进行回顾性研究,就梗死血管内外的可能因素,如血管外机械压迫因素（脑疝形成）,血管内血流因素（休克、术中低血压、血渗透压、血钠、血糖以及年龄）进行Logistic回归分析。结果有27例患者伤后出现大面积脑梗死,与脑疝形成血管外持续压迫及血管内因素（休克以及术中低血压）关系密切,而与渗透压、血钠、血糖、年龄相关度不高。结论严重颅脑伤后并发大面积脑梗死形成是梗死血管内外多种因素共同作用的结果,与脑疝形成后的机械压迫作用以及休克、低血压后血容量、脑灌注不足的关系密切。     

Role of focal adhesion kinase (FAK) in renal ischaemia and reperfusion

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays important roles in cell migration, cell proliferation and cell survival. Because these processes participate in the restoration of tubular integrity in renal ischaemia and reperfusion, FAK expression and phosphorylation at Tyr-397, the latter indicative of its activity, were examined in the different kidney zones by Western blot analysis and immunohistochemistry. Expression and phosphorylation of FAK were also studied in Madin-Darby canine kidney (MDCK) and medullary thick ascending limb (mTAL) cells after ATP depletion and repletion. In control rat kidneys, FAK expression in outer and inner medulla exceeded that in cortex, and phosphorylation of FAK at Tyr-397 was most pronounced in the inner medulla. Although this expression pattern was not affected by 20 (40, 60)-min ischaemia and 20 (40, 60)-min ischaemia followed by 60-min or 24-h reperfusion, FAK phosphorylation was significantly reduced in all kidney zones immediately after ischaemia, but increased during reperfusion, exceeding control values in the outer and inner medulla. ATP depletion and repletion of MDCK and mTAL cells were associated with a decrease in FAK phosphorylation during ATP depletion, followed by an increase during repletion. Rephosphorylation of FAK after ATP repletion was enhanced by N-acetylcysteine, a reactive oxygen species scavenger. ATP depletion disrupted focal adhesions in MDCK cells. Their reformation after ATP repletion paralleled the increase in FAK phosphorylation. These findings suggest an essential role for FAK-signalling during renal ischaemia and early reperfusion.     

高渗晶胶复合液静脉补液在犬烧伤早期防治休克疗效观察

目的研究应用高渗晶胶复合液快速静脉补液对35%TBSA烧伤犬伤后早期休克的防治作用及对血流动力学的影响。方法 Beagle犬12只,采用凝固汽油燃烧法制作Ⅲ度烧伤面积35%TBSA模型,随机分为常规补液组(A组)和高渗补液组(B组)。A组按照4ml/(kg.1%TBSA)输入乳酸钠林格氏液,在前8h输入总量的一半,B组采用高渗氯化钠羟乙基淀粉40注射液,按照8ml/kg快速补液后终止补液。分别于伤前、伤后1h、2h、4h、6h、8h进行血流动力学检测,测定各组犬的胸腔内血容量指数(ITBI)、血管外肺水量(EVLW)、血容量(PV)及血浆渗透压。结果烧伤后两组ITBI均呈逐步降低趋势,B组经高渗补液后,伤后1h其ITBI降低与A组相比差异无统计学意义(P0.05),至伤后2h开始明显降低,4h后显著低于A组,两组相比差异有统计学意义(P0.05);A组EVLW显示伤后渗出增多,而B组经高渗补液,EVLW显示伤后2们h内血管外渗出较伤前差异无统计学意义(P0.05),渗出量显著低于A组,两组相比差异有统计学意义(P0.05);伤后A组PV明显降低,B组经高渗补液,PV在伤后1、2、4h降低缓慢,且PV明显高于A组,两组相比差异有统计学意义(P0.05),伤后4h后PV迅速减少,并显著低于A组,两组相比差异有统计学意义(P0.05);伤后A组血浆渗透压有所降低,B组经高渗补液,血浆渗透压在伤后1、2h较伤前增高,且显著高于A组(P0.05),两组相比差异有统计学意义,伤后4h后逐步降低,至伤后8hB组显著低于A组,两组相比差异有统计学意义(P0.05)。结论烧伤早期快速静脉补充高渗晶胶复合液,在4h内能够有效维持血流动力学指标稳定,并减少组织渗出,从而起到大大减少补液量、节约医疗资源、降低并发症、提高复苏疗效的作用,适于危重烧伤早期院外现场急救。     

The pressure-flow relationship of different nephron populations in the rat.

The mechanisms behind the autoregulation of the total renal blood flow and the glomerular filtration rate are unclear. In this investigation a modified microsphere technique was applied to measure the blood flow at different depths in the renal cortex during normotensive and hypotensive conditions. No autoregulation was found in the outer cortex while it was well pronounced in the inner one. During similar conditions, glomerular capillary pressure, welling point pressure and intratubular pressure were recorded. By combining these results with the blood flow data, the preglomerular and postglomerular resistances were calculated. It was then found that the preglomerular resistance decreased and the postglomerular resistance increased when the blood pressure was lowered. The results indicate a redistribution of blood flow from the outer parts to the inner parts of the cortex when the blood pressure is decreased. The redistribution of the blood flow might explain the well known linear relationship between the arterial pressure and the urine flow. The single nephron filtration rate of the outermost glomeruli could be calculated and the results seem to indicate a non-equilibrium at the end of the glomerular capillaries.     

Renal Cortical Blood Redistribution after Bumetanide Related to Heterogenicity of Cortical Prostaglandin Metabolism in Dogs

Bumetanide is shown to increase renal blood flow and to augment the proportion of the cortical blood flow to middle cortex. This redistribution still takes place even when renal blood flow is maintained constant by renal artery clamping. Indomethacin pretreatment inhibits the increase of renal blood flow as well as the cortical blood redistribution. In vitro examinations of canine kidney tissue slices suggest that outer cortex and papilla are sites of prostaglandin synthesis. No differences in prostaglandin E degradation are observed within the cortex. This suggests a relative autonomy for prostaglandins in the outer cortex, whilst inner cortical areas are dependent on medullary/papillary prostaglandin E supply. The renal hemodynamic effect of bumetanide is therefore thought to be a result of a stimulation of mainly medullary/papillary prostaglandin synthesis.     

The effect of prostaglandin synthesis inhibitors on renal blood flow distribution in conscious rabbits.

1. We have studied the effects of two prostaglandin synthesis inhibitors on renal cortical blood flow distribution in conscious rabbits. 2. Renal blood flow distribution was estimated by means of radioactive microspheres injected into chronically implanted left atrial cannulae. Cardiac output was measured by a thermodilution technique. 3. Measurements were made in groups of animals treated with either indomethacin, meclofenamate or control injections of phosphate buffer. 4. A method of microtome slicing of the renal cortex was developed to standardize measurements. Microtome sections were grouped into inner, middle and outer zones. After both indomethacin and meclofenamate there was a reduction in total renal blood flow with a redistribution of flow from inner to outer cortex. 5. Estimated renal vascular resistance rose in all three cortical zones. 6. The data support the hypothesis that renal prostaglandin synthesis is necessary for maintaining flow to the deep cortex. It is suggested that renal prostaglandins may also influence flow in more superficial zones. 7. Estimated total systemic vascular resistance was increased both with meclofenamate and indomethacin, suggesting an inhibiting effect of prostaglandins on arteriolar tone throughout a major part of the systemic circulartion.     

Freeze-dissection analysis of 133Xe distribution to measure regional renal blood flow

To verify the freeze-dissection technique for measuring renal blood flow (RBF) distribution in anesthetized dogs we compared the sum of all compartment flow rates with total RBF, compared compartment flow distribution with intercepts, and determined recirculated 133Xe. By dissection, we found that the cortex, delineated by its granular brownish red appearance, comprised 69%, whereas the outer medulla (the reddish portion) was 18% of the total kidney weight. Average cortical flow was 3.77 ml X g-1 X min-1 and the y-intercept for 133Xe washout was 85% of the initial radioactivity distribution. Outer medullary flow was 2.01 ml X g-1 X min-1 with a y-intercept of 13%. In a 100-g kidney, total cortical flow would be 259.8 ml/min (3.77 ml X g-1 X min-1 X 68.9 g) and total outer medullary flow would be 36.0 ml/min. These calculations indicate that 86% of the total flow is distributed to the cortex and 13% to the outer medulla, as the intercept-calculated percentages indicated. Summing whole cortical and medullary flows results in a flow that agrees with the electromagnetically measured flow of 292 ml/min for a 100-g kidney.