Clinical Evaluation of a Disposable Artificial Kidney

The in-vivo performance of a new disposable parallel flow countercurrent type of artificial kidney has been compared with that of the modified four-layered Kiil dialyser. The dialysance of urea and endogenous creatinine in the former was significantly better than in the latter for similar blood flow rates, and, moreover, unlike the dialysance with the Kiil dialyser it continued to improve over 12 hours. Among 100 disposable artificial kidneys tested no failure occurred from blood leaks despite the use of high negative pressures in the dialysate compartment. No pyrogen reactions were observed.These new artificial kidneys were ready for use in less than one-seventh of the time taken to prepare the conventional Kiil dialyser. Other advantages are their low priming volumes, the lack of a pump in the blood line, and the reduced risk of infection.     

A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs

The endogenous peptides somatostatin and secretin are effective in the therapy of upper gastrointestinal tract bleeding and acute pancreatitis. The clinical effects may be partly brought about by changes in the regional blood flow. To evaluate the effects of somatostatin (50 and 100 μg/min over 6–8 min) and secretin (0.1 and 0.5 U · kg^?1 · min^?1 over 3–5 min) on tissue blood flow, particularly of the gastrointestinal tract, the tracer microsphere reference sample method was used in anesthetized dogs.Infusion of somatostatin significantly diminished gastric and pancreatic blood flow whereas no changes of duodenal and ileal blood flow could be obtained. Blood flow through spleen, kidneys and adrenal glands was increased but no changes were observed in the blood flow of other tissues. Cardiac hemodynamics remained unchanged.Secretin increased the blood flow of the duodenum, the kidneys and the adrenal glands and diminished gastric blood flow without changing pancreatic, ileal, hepatic, pulmonary and muscle blood flow. Cerebral, pituitary and myocardial blood flow was increased by a higher dose of secretin. It also evoked a slight but significant positive ino- and chronotropic effect. Since secretin and somatostatin differ in their respective effects on gastrointestinal blood flow it is suggested that the previously reported beneficial effects of both peptides on upper gastrointestinal bleeding cannot solely be attributed to changes in regional blood flow.     

Impaired blood flow autoregulation in nonfiltering kidneys: effects of theophylline administration

To investigate blood flow autoregulation in filtering and nonfiltering kidneys, renal blood flow was determined during graded reductions in renal perfusion pressure in seven anesthetized dogs containing both a filtering and nonfiltering kidney. In each dog, one kidney was made nonfiltering by the method of EH Blaine, JO Davis, and RT Witty (Circ Res 27:1081-1089, 1970). Renal perfusion pressure was decreased from 129 to 115, 99, and 83 mm Hg by stepwise constriction of the suprarenal aorta. In filtering kidneys, the maximum decrease in renal perfusion pressure reduced renal blood flow only 20.1% of control whereas renal blood flow of nonfiltering kidneys decreased by 41.0% of control. During aortic constriction, renal vascular resistance of nonfiltering kidneys remained unchanged or slightly increased. These hemodynamic changes were associated with significantly greater autoregulation indices in nonfiltering kidneys. In eight dogs with nonfiltering kidneys, competitive inhibition of adenosine with theophylline (9 mg/kg iv) restored autoregulation of renal blood flow as shown by significant decreases in renal vascular resistance. These data indicate that in the nonfiltering kidney model, autoregulation of renal blood flow is impaired. It is suggested that this impaired autoregulatory response may result from renal ischemia and the vasoconstrictor influence of elevated intrarenal adenosine concentration.     

Short term suppression of hyperacute renal allograft rejection in presensitised dogs with prostacyclin

One of the main features of hyperacute renal allograft rejection in presensitised dogs is platelet aggregation within the kidney as detected by light microscopy and renal arterio-venous platelet counts. Graft failure, as determined by reduction and ultimate cessation of renal blood flow and urine production, can be abrogated in the short term by prostacyclin which is the most potent inhibitor of platelet aggregation yet discovered. After 4 h of extracorporeal perfusion, by which time all control kidneys had been rejected, all prostacyclin treated kidneys had normal or above normal blood flow rates, were producing urine and were similar histologically (light microscopy) to 4-hour autografts.     

Urinary concentrating processes in vertebrates.

Avian and mammalian kidneys can produce a urine hyperosmotic to the blood by means of a renal countercurrent system. Birds are uricotelic; mammals are ureotelic. It is proposed that the inner medulla present in mammalian, but not in avian kidneys serves specifically to accumulate urea in the inner and outer medulla. Among mammalian kidneys the degree to which urea accumulates in the inner medulla is inversely related to the complexity of the vascular bundles (in the outer medulla) and the cortical urea recycling index. A model is proposed for urea recycling via the vascular bundles. The renal pelvis varies in size among mammals. Its relative size is unrelated to the type of vascular bundles, cortical recycling index; or urea accumulation in the inner medulla. Since urine refluxes into the renal pelvis during rising urine flow only, the function of the pelvis could be that of bringing the more dilute urine into contact with the outer medulla and underlying capillaries, thereby aiding in reducing the urea concentration in outer and inner medulla during rising urine flow. The size of the renal pelvis may be related to the volume of the inner medulla. Other factors may also be involved.     

Effect of synthetic neuromedin U-8 and U-25, novel peptides identified in porcine spinal cord, on splanchnic circulation in dogs

Two novel peptides which exert a potent stimulant effect on rat uterus smooth muscle have recently been identified in porcine spinal cord. These peptides designated neuromedin U-8 and U-25 have been reported to exert a hypertensive effect in rats. But further biological activities are not known. In the present study, the effect of these peptides on blood flow in portal vein, superior mesenteric artery and pancreatic tissue and on blood pressure were examined in dogs, utilizing recently developed ultrasonic transit time volume flow meter and laser Doppler flow meter. Neuromedin Us potently reduced blood flow in superior mesenteric artery. The minimum reductions could be observed even at very small doses of neuromedin U-25 (32 fmol/kg) and U-8 (90 fmol/kg), while the maximal reductions of 48.4 and 51.0% were attained at the doses of 320 pmol/kg (U-25) and 900 pmol/kg (U-8), respectively. These peptides also reduced portal vein blood flow, and the maximal reductions of 42.1 and 37.2% were attained at the doses of 32 pmol/kg (U-25) and 90 pmol/kg (U-8), respectively. On the other hand, blood flow in pancreatic tissue increased slightly with the maximal increases of 13.8% at 3.2 pmol/kg (U-25) and 11.8% at 9 pmol/kg (U-8), respectively. The maximal increases of blood pressure were 5.2% at 320 pmol/kg (U-25) and 4.3% at 90 pmol/kg (U-8). Furthermore, neither neuromedin U-25 nor U-8 influenced the axillary artery blood flow, suggesting their selective effect on splanchnic blood flow. Because of the potent and probably selective activity on splanchnic circulation, neuromedin U-25 and U-8 may well be recognized as physiologically significant novel neuropeptides or hormones.     

Novel polymeric solid-phase extraction material for complex biological matrices Portable and disposable artificial kidney

The replacement of conventional hemodialysis treatment for a patient with malfunctioning kidneys by providing him/her with a portable and disposable “artificial kidney” which is connected to implanted artery and vaneous cannulas on a patient's wrist is discussed. During a continuous flow of blood, plasma diffuses through a plasmapheretic membrane, passes through a bed of plasmacompatible sorbent Styrosorb, and arrives at an ultrafiltration membrane. Vacuum-operated ultrafiltration removes excess water together with dissolved urea and other small molecules, and Stryosorb removes medium-sized toxic substances. The hemocompability of the sorbent is improved by chemical modification of the surface.     

冠状动脉血流信号的计算机测量与分析

本文介绍在药效学研究的实验中，应用计算机技术测量，处理血流信号的新方法，通过分离实验运动左冠状动脉的旋支，接入电磁流量计探头，直接引出血流波形，经计算机采集，得到与左室压，动态压，心电图等同步的血流信号，再由计算机对血流信号的基本参数进行计算分析，为深入进行有关药效学研究提供了新手段。     

急性低氧与间断低氧适应对家兔局部血流分布的影响

本实验目的在于探讨急性低氧和间断低氧适应对局部血流分布的影响。我们将26只家兔分为急性低氧,低氧适应和常氧对照三组。在麻醉状态下用放射性标记的蟾蜍红细胞分别测定左心室、双侧肾、双侧肾上腺的血流量;并分区测定了大脑皮质、海马、丘脑下部、脑干的局部脑血流。吸入10％低氧混合气1小时后,急性低氧组脑局部、左心室、肾上腺的血流显著高于对照。经2周间断低氧适应后,低氧适应组脑局部(脑干除外)、左心室、肾上腺的血流下降。两组动物低氧时的肾血流变化不明显。结果提示,2周间断低氧适应能改变局部血流分布,血流的再分布有利于改善机体的抗低氧能力。     

Measurement of blood flow from an assist ventricle by computation of pneumatic driving parameters

The measurement of blood flow from an assist ventricle is important but sometimes difficult in artificial heart experiments. Along with the development of a pneumatic cylinder-piston driver coupled with a ventricular assist device, a simplified method for measuring pump flow was established. From driving parameters such as the piston (or cylinder) displacement and air pressure, the pump flow could be calculated by the use of the equation of state for an ideal gas. The results of this method are broadly in agreement with electromagnetic and Doppler measurements.     

Evidence for Na-retaining humoral agents and vasoconstrictor humoral agents in hypertension-prone Dahl 'S' rats. Prevention of NaCl-induced hypertension in Dahl 'S' rats with thiazide

Dahl 'S' rats become hypertensive when fed a high NaCl diet but remain normotensive on a low NaCl diet. Dahl 'R' rats are normotensive on either diet. For a given perfusion pressure, isolated 'S' kidneys excrete 50% less Na than 'R' kidneys. Therefore, we searched for a Na-retaining hormone in 'S' rats. Kidneys were isolated without ischemia from normal rats and were continuously perfused at 125 mm Hg with blood from Dahl 'S' and 'R' rats, all on low NaCl diets. Kidneys and adrenals had been extirpated from the perfusing rats. During 15 min of perfusion, the isolated 'normal' kidneys excreted a mean of 164 micronEq of Na/min/100 g during 26 perfusion experiments with blood from 'R' rats. The 'normal' kidneys excreted a mean of 84 micronEq Na during 24 perfusions with blood from 'S' rats. Thus, the normal kidneys excreted half as much Na when perfused with 'S' blood compared with 'R' blood (p less than 0.02). Seemingly, a Na-retaining humoral agent is present in the blood of 'S' rats on a low Na diet in the absence of renal and adrenal tissue. Moreover, in these normal kidneys, perfusion with 'S' blood induced a 16% higher renal vascular resistance than perfusion with 'R' blood (p less than 0.01), indicating vasoconstricting agents in 'S' blood. However, the Na-retaining humoral effect in 'S' blood could lead to Na retention by 'S' kidneys in vivo, which could partially account for the susceptibility of 'S' rats to NaCl hypertension. Hypertension in Dahl 'S' rats can be almost completely prevented by concomitant treatment with thiazide diuretics which act mainly on the kidney to facilitate Na excretion. This result is in agreement with the hypothesis that a shift in the pressure natriuresis curve, reducing Na excretion for a given arterial pressure, is partially responsible for the great sensitivity to NaCl hypertension in the 'S' rat. The Na-retaining hormone may contribute to this shift.     

Exercise causes a tissue-specific change of NO production in the kidney and lung.

Nitric oxide (NO) is produced in the vascular endothelium and is a potent vasodilator substance that participates in the regulation of local vascular tone. Exercise causes peculiar changes in systemic and regional blood flow, i.e., an increase of systemic blood flow and a redistribution of local tissue blood flow, by which the blood flow is greatly increased in the working muscles, whereas it is decreased in some organs such as the kidney and intestine. Thus we hypothesized that exercise causes a tissue-specific change of NO production in some internal organs. We studied whether exercise affects expression of NO synthase (NOS) mRNA and protein, NOS activity, and tissue level of nitrite/nitrate (stable end products of NO) in the kidneys (in which blood flow during exercise is decreased) and lungs (in which blood flow during exercise is increased with the increase of cardiac output) of rat. Rats ran on a treadmill for 45 min at a speed of 25 m/min. Immediately after this exercise, kidneys and lungs were quickly removed. Control rats remained at rest during this 45-min period. Expression of endothelial NOS (eNOS) mRNA in the kidneys was markedly lower in exercise rats than in control rats, whereas that in the lungs was significantly higher in exercise rats than in control rats. Western blot analysis confirmed down- and upregulation of eNOS protein in the kidney and lung, respectively, after exercise. On the other hand, neither expression of neuronal NOS (nNOS) mRNA and nNOS protein nor inducible NOS (iNOS) mRNA and iNOS protein in the kidneys and lungs differed between exercise and control rats. NOS activity in the kidney was significantly lower in exercise rats than in control rats, whereas that in the lung was significantly higher in exercise rats than in control rats. On the other hand, the iNOS activity in the kidneys and lungs did not differ between exercise rats and control rats. Tissue nitrite/nitrate level in the kidneys was markedly lower in exercise rats, whereas that in the lungs was significantly higher in exercise rats. The present results show that production of NO is markedly and tissue-specifically changed in the kidney and lung by exercise.     

Glutaraldehyde crosslinking of red blood cells by using a hemodialyzer

Summary Human red blood cells (RBC) were crosslinked with glutaraldehyde (GA) by using a hemodialyzer which is used as an artificial kidney. Human RBC, which was in a flow of 2 ml/min, was extensively crosslinked with 50 mM GA solution of 10 ml/min flow rate. The crosslinked RBC showed high stability against osmotic pressure. The oxygen transport activity of the crosslinked RBC was similar to unmodified RBC. This crosslinking method could be used for the development of an efficient reactor which produces a stable and active RBC.     

Exercise causes tissue-specific enhancement of endothelin-1 mRNA expression in internal organs

Endothelin-1 (ET-1) is a potent vasoconstrictorpeptide, which also potentiates contractions to norepinephrine in humaninternal mammary and coronary vessels. Exercise causes a redistribution of blood flow, i.e., the increase in working muscles that is partly attributable to a decrease in visceral blood flow. We hypothesized thatexercise causes a tissue-specific increase in ET-1 expression ininternal organs. We studied whether exercise affects expression ofpreproET-1 mRNA in the kidneys and lungs. The rats performed treadmillrunning (0% grade) for 45 min at a speed of 25 m/min. The plasmaconcentrations of ET-1, epinephrine, and norepinephrine were greater inthe exercise rats than in the sedentary control rats. The expression ofpreproET-1 mRNA in the kidneys was markedly higher in the exercise ratsthan in the sedentary control rats, whereas that in the lungs did notdiffer between the two groups. Therefore, the present study provides apossibility that the exercise-induced increase in production of ET-1 inthe kidneys causes vasoconstriction and hence decreases blood flow inthe kidneys through its direct vasoconstrictive action and/orits indirect effect of enhancing vasoconstrictions to norepinephrine.

     

Measurement of mucosal blood flow in the canine intestine with laser doppler velocimetry

Laser Doppler velocimetry is a technique for continuous estimation of changing blood flow in the surface of a tissue and does not require invasion of the circulation. This technique is based upon the Doppler principle that a shift in the frequency of an electromagnetic wave emitted or reflected from a moving object is proportional to the velocity of the object. The capacity of Laser Doppler velocimetry to estimate changes in intestinal mucosal blood flow was tested in a canine free flow preparation. In anesthetized dogs in which a segment of ileum was isolated, simultaneous measurements of instantaneous changes in total blood flow (measured with the electromagnetic blood flow meter) and instantaneous changes in presumed mucosal blood flow (using laser Doppler velocimetry) were obtained. Determinations were made during conditions of rest, prostacyclin induced vasodilation and norepinephrine induced vasoconstriction. Changes in laser Doppler velocimeter readings were qualitatively similar to and temporally related to changes in total blood flow to the gut segment during administration of the vasoactive drugs. The magnitude and direction of changes with the two measurements were significantly correlated. Stabilizing the laser probe on the mucosal surface to ensure reproducible readings proved technically difficult. Pharmacologically induced changes in laser Doppler velocimeter estimated changes in flow were more readily correlated with changes in electromagnetic flow meter readings than were control values obtained with the two methods.     

Training effects on regional blood flow response to maximal exercise in foxhounds

The effect of training on the regional blood flow response to maximal exercise was investigated in the foxhound. Training consisted of 8-12 wk of treadmill running at 80% of maximal heart rate 1 h/day for 5 days/wk and resulted in a 31% increase in maximal O2 consumption, a 28% increase in maximal cardiac output, and a 23% decrease in systemic vascular resistance during maximal exercise. Blood flow to the heart, diaphragm, brain, skin, and 9 of 10 muscles investigated was similar during maximal exercise pre- and posttraining; however, blood flow to the gastrocnemius muscle was greater posttraining than it was pretraining. Blood flow to the stomach, small intestine, and pancreas decreased during maximal exercise pre- and posttraining; however, blood flow to the large intestine, spleen, liver, adrenal glands, and kidneys decreased during maximal exercise only posttraining. In addition, a larger decrease in blood flow to the stomach during maximal exercise was found posttraining compared with pretraining. These results demonstrate that blood flow to skeletal muscle, the kidneys, and the splanchnic region of the foxhound during maximal exercise can be significantly altered by dynamic exercise training.     

树鼩血压和心率的无创测定

目的建立健康树鼩的心率、血压正常值参考范围,并探讨不同来源、不同性别、不同年龄树鼩心率、血压的差异。方法随机挑选实验树鼩180只,按来源分为野生成年组、F1代自繁成年组和青幼年组三个组,每组雌雄各半,共60只。采用智能无创血压计（鼠仪）逐只测定HR（心率）、SBP（收缩压）、DBP（舒张压）和MBP（平均动脉压）。结果野生成年树鼩、自繁成年树鼩和青幼年树鼩心率分别为394.33±37.74 BPM、351.61±72.76 BPM和378.19±69.04 BPM,野生和自繁成年树鼩组差异有显著性（P〈0.05）。自繁成年树鼩收缩压、舒张压和平均动脉压均明显低于青幼年树鼩,差异有极显著性（P〈0.01）。野生成年树鼩和自繁成年树鼩相比,收缩压、舒张压和平均动脉压差异均无显著性（P〉0.05）。结论大鼠无创血压计适合于树鼩的血压、心率的测量。通过测定,获得了野生成年树鼩、F1代自繁成年树鼩和青幼年树鼩的心率和血压参考值范围,丰富了树鼩基础生理数据,可为相关研究提供科学参考。     

Leukotriene D4 increases nasal blood flow in humans

The effect of leukotriene D4 on the nasal mucosal blood flow in humans was measured using a laser doppler flow meter. The leukotriene solution was applied topically to the nasal mucosa in 9 healthy subjects, and changes in blood flow were measured non-traumatically by the laser doppler instrument. The response showed a consistent increase in blood flow. A dose-response was found in the range of 0.063 - 4.0 nanomole. These results confirm an earlier study on the human skin, implicating leukotriene D4 as an important vasodilator in humans. No increase in nasal secretion was noted by the subjects tested.     

A comparative analysis of the persistence of capillary blood flow oscillations in the left and right rat kidneys

Several parameters of the nonlinear dynamics of blood flow oscillations were studied in the left and right rat kidneys in baseline conditions and a perturbed state. An intramuscular injection of aspirin in 0.9% saline (0.5 mg per 100 g body weight) was used as a perturbation factor. Capillary blood flow was measured at baseline and 50 min after the aspirin injection by laser Doppler flowmetry. The persistence of time series was estimated by the Hurst method. Baseline time series were persistent in the right kidney and nonpersistent in the left kidney. Aspirin-perturbed time series were persistent in both the right and left kidneys, but the Hurst index was significantly higher in the left kidney. The results showed that the microcirculatory bed of the right rat kidney is more stable to perturbation as compared with that of the left kidney.     

Effect of ACE inhibition on the fetal kidney: decreased renal blood flow.

The kidneys of nine fetuses whose mothers were chronically hypertensive were examined microscopically. Three of these mothers used antihypertensive agents throughout pregnancy including one who used an angiotensin-converting enzyme (ACE) inhibitor. The tubular defects found in these kidneys were compared to the kidneys of 20 normal controls, 13 fetuses with various multiple malformation syndromes and six cases of the twin to twin transfusion syndrome. Evidence from these cases as well as the literature suggest that the primary mechanism by which ACE inhibitors affect development of the fetal kidney is through decreased renal blood flow.