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At least 163 records · Page 9Linked to original sources
PubMed2002

Lung protection during total cardiopulmonary bypass by isolated lung perfusion: preliminary results of a novel perfusion strategy.

BACKGROUND: The present pilot study was conducted to evaluate the effect of isolated short-term lung perfusion during cardiopulmonary bypass (CPB) on inflammatory response and oxygenation. METHODS: A total of 24 patients undergoing elective cardiac surgery with routine CPB were prospectively assigned to three groups. Group I (n = 7), control subjects receiving neither lung perfusion nor ultrafiltration; group II (n = 9), patients undergoing lung perfusion; and group III (n = 8), patients undergoing lung perfusion plus ultrafiltration. Lung perfusion consisted of single-shot hypothermic pulmonary artery perfusion with oxygenated blood. Proteins indicative of leukocyte activation and lung injury were measured in plasma and bronchoalveolar lavage fluid (BALF). The alveolar-arterial oxygen gradient (A-aDO2) and the oxygenation index (PO2/FiO2) were also determined. RESULTS: Oxygenation values were best preserved in group III, followed by group II. After CPB, elastase-alpha1-proteinase inhibitor complex had increased in plasma in all groups; in BALF it increased in groups I and II, but not in group III. Alpha2-macroglobulin increased significantly in BALF in group I but not in groups II and III. CONCLUSIONS: These preliminary results provide some evidence that single-shot hypothermic lung perfusion with oxygenated blood at the beginning of CPB may have a protective effect on the lungs, especially when combined with ultrafiltration.

Adult↗
PubMed2003

Surgical repair of acute type A aortic dissection: continuous pulmonary perfusion during retrograde cerebral perfusion prevents lung injury in a pilot study.

OBJECTIVE: Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection operated on with deep systemic hypothermia. Interaction between neutrophils and pulmonary endothelium along with ischemic insult and reperfusion are the major determinants of lung injury. The aim of this prospective study was to evaluate the effect of continuous pulmonary perfusion during retrograde cerebral perfusion on lung function. METHODS: Twenty-two patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to one of 2 treatment groups. Pulmonary perfusion was performed during retrograde cerebral perfusion in group B (11 patients), whereas the conventional Ueda technique was applied in group A (11 patients). Lung function was evaluated on the basis of intubation time, scoring of chest radiographs at 12 hours after cardiopulmonary bypass, and Pao(2)/fraction of inspired oxygen ratio assessed from immediately before the operation to 72 hours after termination of cardiopulmonary bypass. RESULTS: Study groups were homogeneous for age, sex, interval between symptom onset and surgical operation, previous aortic surgery, preoperative ejection fraction and pulmonary gas exchange function, extent of aortic repair, and concomitant procedures. Cardiopulmonary bypass time, length of retrograde cerebral perfusion, operation time, need for blood substitutes, and surgical revision for bleeding did not differ between treatment groups. Postoperative Pao(2)/fraction of inspired oxygen ratios were higher in group B than in group A, and the difference remained statistically significant throughout the study period. The incidence of prolonged ventilator support (>72 hours) and the severity of the radiographic pulmonary infiltrate score were lower in the perfused group (18.2% vs 72.7% [P =.015] and 0.81 +/- 0.75 vs 1.8 +/- 0.78 [P =.028], respectively). CONCLUSIONS: Continuous pulmonary perfusion provided a better preservation of lung function in patients operated on with deep systemic hypothermia.

Acute Disease↗
PubMedDate not supplied

Recombinant antibody production by perfusion cultures of rCHO cells in a depth filter perfusion system.

Recombinant Chinese hamster ovary cells, producing recombinant antibody against the human platelet, were cultivated in a depth filter perfusion system (DFPS). When perfusion cultures with working volume of 1 L were operated at perfusion rates of 5/d and 6/d, volumetric antibody productivities reached values 28 and 34 times higher than that of batch suspension culture in Erlenmeyer flasks and 43 and 53 times higher than that of batch culture in a controlled stirred tank reactor, respectively. Perfusion cultures in the DFPS showed stable antibody production over the whole culture period of up to 20 days. In the DFPS, inoculated cells in suspension were entrapped in a few hours within the depth filter matrix by medium circulation and retained there until the void space of the filter matrix was saturated by the cultured cells. After cells in the depth filter matrix reached saturation, overgrown viable cells at a perfusion rate of 5/d or 6/d were continuously collected into waste medium at a density of 2-4 x 10(5) cells/mL, which resulted in stable operation at high perfusion rates, maintaining values of process parameters such as glucose/lactate concentration, pH, and dissolved oxygen concentration. Because the DFPS overcomes most drawbacks observed with conventional perfusion systems, it is preferable to be used as a key culture system to produce monoclonal antibody stably for a long culture period.

Animals↗
PubMed1984

Effect of in vivo plasma insulin levels on the relationship between perfusate free fatty acid concentration and triglyceride secretion by perfused rat livers.

Previous evidence has indicated that plasma concentrations of insulin and free fatty acid (FFA) play crucial roles in regulation of hepatic triglyceride (TG) secretion. To further define the relationship between these variables, we have assessed the effect of pre-existing ambient insulin levels on the ability of perfusate FFA concentrations to stimulate TG secretion by perfused livers from five groups of rats. The groups and their mean plasma in vivo insulin concentrations were as follows: sucrose-fed (49 microU/ml), control (35 microU/ml), moderate streptozotocin-induced insulin deficiency (24 microU/ml), semi-starved control (11 microU/ml), and severe streptozotocin-induced insulin deficiency (6 microU/ml). Hepatic TG secretion by perfused rat livers from all five groups was stimulated by increments in perfusate FFA concentration. However, the magnitude of the stimulation of hepatic TG secretion by any given perfusate FFA concentration varied considerably among the groups, and appeared to be directly related to the height of the in vivo insulin concentrations. These results indicate that TG secretion by perfused rat livers is related to perfusate FFA concentrations, but emphasize the importance that pre-existing ambient insulin levels have in modulating the quantitative nature of this relationship.

Animals↗
PubMed2005

Effect of x-ray tube current on the accuracy of cerebral perfusion parameters obtained by CT perfusion studies.

The purpose of this study was to investigate the effect of x-ray tube current on the accuracy of cerebral perfusion parameters obtained by CT perfusion studies using multi-detector row CT (MDCT). Following the standard CT perfusion study protocol, continuous (cine) scans (1 s/rotation x 60 s) consisting of four 5 mm thick contiguous slices were performed using an MDCT scanner with a tube voltage of 80 kVp and a tube current of 200 mA. We generated the simulated images with tube currents of 50 mA, 100 mA and 150 mA by adding the corresponding noise to the raw scan data of the original image acquired above using a noise simulation tool. From the original and simulated images, we generated the functional images of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in seven patients with cerebrovascular disease, and compared the correlation coefficients (CCs) between the perfusion parameter values obtained from the original and simulated images. The coefficients of variation (CVs) in the white matter were also compared. The CC values deteriorated with decreasing tube current. There was a significant difference between 50 mA and 100 mA for all perfusion parameters. The CV values increased with decreasing tube current. There were significant differences between 50 mA and 100 mA and between 100 mA and 150 mA for CBF. For CBV and MTT, there was also a significant difference between 150 mA and 200 mA. This study will be useful for understanding the effect of x-ray tube current on the accuracy of cerebral perfusion parameters obtained by CT perfusion studies using MDCT, and for selecting the tube current.

Aged↗
PubMedDate not supplied

A coronary active perfusion system for off-pump coronary artery bypass: advantage over passive perfusion regarding the physiology of the coronary artery.

To avoid myocardial ischemia during off-pump coronary artery bypass, we developed a coronary active perfusion system (CAPS) that perfuses arterial blood to the coronary artery at the diastolic phase of the cardiac cycle by a syringe pump system. We report herein the details and compare CAPS with a passive shunt circuit from the femoral artery (FA shunt), regarding the physiology of the coronary artery. Six pigs were used for this study. After CAPS or FA shunt perfusion was established, coronary flow and coronary pressure were measured. The coronary flows in the native coronary artery, FA shunt perfusion, and CAPS perfusion with syringe pump stroke volume settings ranging from 0.1 to 0.4 ml were 27.2+/-3.0, 4.1+/-1.5, 12.7+/-1.2, 24.8+/-1.9, 33.3+/-1.6, and 42.2+/-1.9 ml/min, respectively. Mean coronary pressures under FA shunt perfusion and CAPS perfusion with stroke settings from 0.1 to 0.4 ml were 23.7+/-4.6, 48.8+/-5.0, 61.3+/-7.5, 70.8+/-5.4, and 82.3+/-5.2 mm Hg, respectively. CAPS had an advantage over the FA shunt regarding coronary flow with safe coronary pressure. Using CAPS, an off-pump coronary artery bypass can be performed safely without myocardial ischemia.

Anastomosis, Surgical↗
PubMed1989

Combined cold storage-perfusion preservation with a new synthetic perfusate.

Based upon encouraging experimental results, we began employing a synthetic perfusate for cadaver kidney preservation. The new perfusate contains hydroxyethyl starch (HES) as the sole colloid for oncotic support; 107 cadaver kidneys were preserved and transplanted (93 primary, 14 nonprimary) using the HES solution and were compared with our previous experience of 180 cadaver kidneys (161 primary, 19 nonprimary) preserved and transplanted utilizing an albumin-based perfusate. All cadaver kidneys were locally harvested and preserved by machine perfusion. Donor and preservation characteristics in the HES (n = 61) and the albumin (n = 101) groups were comparable, with a mean preservation time of 30.9 hr. Cold storage in combination with hypothermic pulsatile perfusion (HPP) preservation was performed more often in the HES group (68.2% vs. 31.1%, P less than 0.001). Recipient characteristics were also comparable, and all received quadruple immunosuppressive therapy with sequential/Minnesota antilymphoblast globulin/(MALG)/cyclosporine. After primary transplantation, the incidence of immediate function (82.6% vs. 89.2%), preservation-related dialysis (14.9% vs. 8.6%), and primary nonfunction (2.5% vs. 0) were similar between the 2 groups, with trends favoring the latter HES data. One-month serum creatinine (1.8 vs. 1.7 mg/dl) and graft survival (95% vs. 97.8%) also were comparable. Similar trends were present in the retransplant group, including a significantly lower 1-month serum creatinine in the HES group (2.2 vs. 1.5 mg/dl; P less than 0.05). The preservation-related dialysis rate did not differ between primary and nonprimary transplants. Primary nonfunction has not occurred with our new perfusate. Combined cold-storage-HPP preservation with HES perfusate offers advantages over standard retrieval technology and provides excellent immediate allograft function.

Albumins↗
PubMed2001

Effects of hypothermic machine perfusion on rat liver function depending on the route of perfusion.

BACKGROUND AND METHODS: The aim of this study was to evaluate the efficacy of hypothermic machine perfusion (HMP) to preserve rat livers according to the route of perfusion, i.e., via portal vein, hepatic veins (retrograde), or hepatic artery. Livers were preserved for 24 or 48 hr by simple cold storage (SCS) or by HMP. Preservation solution was supplemented with (HMP) or without (SCS) hydroxyethyl starch. After preservation, grafts were reperfused for 2 hr with an oxygenated Krebs-Henseleit bicarbonate buffer. RESULTS: After 24 hr of preservation, total glutathione concentrations in HMP livers were similar (1287+/-37, 1418+/-118, and 1471+/-62 nmol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in the SCS (833+/-118 nmol/g, P<0.05) group. These higher total glutathione values were due to higher reduced glutathione concentrations. ATP concentrations in the liver tissue were similar in HMP groups (0.75+/-0.4, 0.64+/-0.1, and 0.77+/-0.1 micromol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in SCS (0.32+/-0.06 micromol/g, P<0.05). After 2 hr of normothermic reperfusion, bile production in the HMP portal and HMP retrograde groups were similar (391+/-29 ml and 372+/-25 ml) and higher than in the HMP artery or SCS groups (275+/-25 ml and 277+/-32 ml, respectively; P<0.05). Aspartate transaminase, alanine transaminase, lactate dehydrogenase, and purine nucleoside phosphorylase release into the perfusate of HMP portal and HMP retrograde perfused livers was similar and significantly lower compared to the HMP artery and SCS groups. At the end of reperfusion, no statistical differences were found for glutathione concentration and energetic reserves in the livers of each group. After 48 hr of preservation, livers from the HMP portal and HMP retrograde groups did significantly better than livers from the HMP artery or SCS groups. CONCLUSIONS: This study confirms the superiority of HMP over SCS to preserve the liver graft. It shows that retrograde perfusion is similar to PV perfusion and that perfusion by HA is less beneficial.

Animals↗
PubMed1993

Improvements in the technique of vascular perfusion-fixation employing a fluorocarbon-containing perfusate and a peristaltic pump controlled by pressure feedback.

A new improved technique for whole-body perfusion-fixation of rats and other small animals is described. The driving force is a peristaltic pump which is feedback regulated by a pressure transducer that monitors the blood-perfusion pressure in the left ventricle of the heart. The primary perfusate-fixative is composed of a blood substitute--13.3% oxygenated fluorocarbon FC-75--in 0.05 M cacodylate buffer (pH 7.4) with a 2% glutaraldehyde. The secondary perfusate-fixative is composed of 2% glutaraldehyde in 0.05 M cacodylate buffer (pH 7.4) with 20 mM CaCl2. A double-barrelled, self-holding cannula is used to cannulate the heart; the outer and inner barrels of the cannula are connected to the peristaltic pump and to the pressure transducer, respectively. The tissue oxygen tension in the rat is monitored by a subcutaneous oxygen electrode. Measurements showed that tissue hypoxia/anoxia did not develop before or during the perfusion-fixation. Thus, the technique permits study of specimens which do not exhibit fixation gradients and do not contain cells fixed in a state of asphyxia. This is substantiated by electron micrographs of cells from different organs, revealing new fine structural elements. By adding oxygenated fluorocarbon to glutaraldehyde perfusate-fixatives, enough oxygen is made accessible for cellular respiration as well as for the oxygen-consuming chemical reactions of glutaraldehyde with the tissue. Data on anaesthesia, operative manoeuvres, mechanical components of the system, preparation of fixatives and flow of the perfusate-fixatives are furnished and discussed.

Animals↗
PubMed1987

Phosphorus-31 nuclear-magnetic-resonance study of phosphorylated metabolites compartmentation, intracellular pH and phosphorylation state during normoxia, hypoxia and ethanol perfusion, in the perfused rat liver.

A quantitative analysis of the phosphorus-31 NMR spectra of excised perfused rat liver has been carried out at 80.9 MHz using a 30-mm sample cell. The results indicate that in liver from fed rats, all intracellular ATP is detected by NMR. In contrast, only the cytosolic fractions of Pi and ADP can be observed as indicated by careful analysis of spectra obtained from perchloric acid liver extracts and intact liver under valinomycin perfusion. In well-oxygenated perfused liver the ATP concentration is 7.4 mM. Values of 5.3 mM and 0.9 mM are found respectively for Pi and ADP concentrations in the cytosolic compartment. Cytosolic pH value (pHi) is 7.25 +/- 0.05 and free magnesium concentration 0.5 mM. Addition of 70 mM (0.4%) ethanol to the perfusate of a fed rat liver induces 25% and 38% reduction of ATP and Pi levels, respectively. A large amount of sn-glycerol 3-phosphate is synthesized (up to 11 mM) in the cytosol. After ethanol withdrawal, a large overshoot in cytosolic Pi is observed, which is indicative of a net uptake of Pi across the plasma membrane that occurred during ethanol oxidation. No significant pH variation is observed during ethanol infusion. In perfused liver of rats subjected to 48-h fasts, the concentrations of cytosolic phosphorylated metabolites are 5.3 mM, 0.8 mM and 11.5 mM for ATP, ADP and Pi, respectively. The perfusion of the liver with 70 mM ethanol does not change the adenine nucleotide levels, while the Pi content is decreased by 10%. During a 4-min hypoxia, induced by reducing the perfusion flow rate from 12 ml to 3 ml min-1 (100 g body weight)-1, ATP concentration decreases to 5.8 mM in the fed rat liver. Cytosolic Pi and ADP increase to 8.7 mM and 1.6 mM, respectively. The cytosolic pH evolves to more acidic values and reaches 7.02 +/- 0.05 at the end of the 4-min hypoxic period.

Animals↗
PubMed1977

A simplified kidney preservation system: the use of hyperosmolar perfusates for continuous perfusion preservation of canine kidneys.

Since the quality of renal preservation following simple ice storage is improved by the use of hyperosmolar washout solutions, hyperosmolar perfusates were evaluated for continuous perfusion preservation. Canine kidneys were preserved for 48 hours by continuous perfusion at 5 degrees C, using hyperosmolar cryoprecipitated plasma and 5% albumin perfusates of osmolalities 397 to 430 mOsm/kg H2O. Hyperosmolar plasma gave significantly better preservation than isosmolar plasma, but the results were only marginally superior to those already obtainable with isosmolar albumin solution. No further improvement in preservation by albumin perfusion was obtained with the hyperosmolar formulations. Because isosmolar albumin solution is easier to prepare than hyperosmolar cryoprecipitated plasma and gives comparable results, it remains our perfusate of choice for continuous perfusion preservation.

Animals↗
PubMed1973

Effects of potassium cyanide, strophanthin or sodium-free perfusion fluid on the electrical potential difference across the guinea-pig placenta perfused in situ.

1. The possible role of active transport of Na in generating the transplacental potential difference (p.d.) was studied in the guinea-pig placenta perfused in situ by testing the effects of strophanthin or KCN added to the perfusate or of Na-free perfusion fluid.2. The p.d. across the perfused placenta was about -20 mV, and was relatively steady during perfusion.3. Strophanthin (10(-5)M) slightly increased the p.d. In a concentration of 2 x 10(-6)M strophanthin was without significant effect.4. KCN (10(-3)M) decreased the p.d. When KCN was removed after a 30 min treatment the p.d. increased significantly exceeding the initial level. KCN (10(-4)M) slightly increased the p.d.5. Perfusion with Na-free fluid decreased the p.d. to a steady level of about 50-60% of the control values.6. Perfusion with Na-free fluid containing KCN (10(-3)M) for 30 min decreased the p.d. However, the effect did not seem different from the effect of KCN (10(-3)M) or Na-free fluid alone. When KCN was removed the p.d. significantly increased in spite of continued perfusion with Na-free fluid.7. Excepting the effect of KCN (10(-4)M), which could not be explained, the observations were found to be consistent with active transport of Na from foetal to maternal side of the placenta as a source of the p.d. The Na transport could account for about 40-50% of the p.d.

Animals↗
PubMed1994

Lithium reabsorption in perfused loops of Henle: effects of perfusion rate and bumetanide.

The contribution of the loop segments to lithium reabsorption in sodium-replete, anesthetized Sprague-Dawley rats was examined by perfusing superficial loops of Henle between late proximal convolutions and early distal tubules. Preliminary experiments in which lithium was initially present only inside or outside the perfused loop confirmed substantial permeability of one or more of the loop segments to lithium. In subsequent experiments, in which lithium was infused intravenously and included in the perfusate so that the perfusate-to-plasma lithium concentration ratio was close to that found in late proximal tubules during lithium clearance studies, lithium reabsorption was inversely related to the perfusion rate: values for fractional lithium reabsorption (FRLi) at perfusion rates of 10, 20, and 30 nl/min were 58 +/- 3, 17 +/- 2, and 2 +/- 2%, respectively. Bumetanide (10(-6) M) markedly inhibited FRLi but also reduced water reabsorption, suggesting an effect on the pars recta at this dose; 10(-7) M bumetanide, which was without effect on water reabsorption, had only a small effect on FRLi at a perfusion rate of 10 nl/min but reduced FRLi by approximately 70% at 20 nl/min. We argue that the remarkable flow dependency of lithium reabsorption, together with its bumetanide sensitivity, provides evidence for significant voltage-driven lithium reabsorption in the thick ascending limb of Henle.

Absorption↗
PubMed1998

Perfusion technique determines alveolar fluid resorption rate in the isolated perfused rat lung.

The isolated perfused lung (IPL) preparation is a well-established model for the study of alveolar epithelial sodium transport. We noted that preparations of normal fluid-filled rat lungs with recirculated perfusate reproducibly lost weight, whereas preparations in which the perfusate was discarded after a single pass through the lungs had a variable and lesser weight change. To confirm this, we performed IPL experiments by using male Sprague-Dawley specific-pathogen-free rats (175-225 g). In 10 IPLs, perfusate initially was discarded after passing through the lungs and then was recirculated continuously. During the single-pass period, the rate of weight change was +0.7 +/- 2.0 mg/min compared with -9.0 +/- 1.3 mg/min for the recirculating period. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulated during recirculation. The weight loss induced by recirculation was reproduced by perfusion with 8-bromoadenosine 3',5'-cyclic monophosphate or terbutaline in single-pass fashion and blocked when the kinase inhibitor H-8 or phosphodiesterase was present in the recirculating perfusate. In summary, perfusate recirculation in the IPL stimulates fluid resorption at least partially via cAMP. This should be factored into the design and interpretation of IPL experiments.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1980

The significance of pH variations in human albumin perfusion media during continuous hypothermic renal perfusion.

The variation of pH in perfusate during renal machine perfusion has been regarded exclusively as an effect of kidney metabolism. During preservation of 21 canine kidneys for 48 hours in a Gambro PF-2D machine the pH was measured in the human albumin perfusion medium used, and in control samples stored a 4 degrees C. An increase in pH from 7.21 (+/- 0.03) to 7.66 (+/- 0.10) was found in the machine perfusate. In the stored perfusion medium an increase from 7.21 (+/- 0.03) to 7.43 (+/- 0.20) was measured. We conclude that the pH change in perfusate is not a reliable parameter for the functional state of the kidney unless the spontaneous pH variation in the perfusion medium is simultaneously recorded and a correction made.

Albumins↗
PubMed1975

[Swelling and loss of potassium in perfused livers following the influence of the vapours of carbon tetrachloride, chloroform and halothane on the perfusion medium (author's transl)].

Erythrocyte free perfused rat livers were treated with vaporous carbon tetrachloride, chloroform and halothane by equilibration in the oxygenator system. The potassium loss, the amount of swelling and the alteration of the perfusion rates were measured during the experiments as criteria of acute toxicity. In contrast to the well known behaviour of perfused livers during the intoxication with phalloidin the amount of liver swelling did not marekdly depend on the perfusion rates in acute CCl(4) poisoning. The mechanism of swelling must be different in both intoxications. Exposure of perfused livers to high concentrations of CCl(4) for several minutes only produced a marked K-+-loss within a short time. This injury could not be fully compensated after finishing the exposure. Dose response diagrams are presented for carbon tetrachloride, chloroform and halothane by use of the following criteria: potassium loss, swelling (increase of wet weight) and perfusion rates (ml.min-1.g-1). As total doses the amounts of solutes vaporized during the exposition were listed. In these diagrams chloroform appears to be more toxic than halothane. CCl4 occupies a middle position between chloroform and halothane. The course of dose response diagrams of halothane is different from those of CCl(4) and CHCl(3). The halothane diagrams increase critically at high doses, whereas the courves for CCl(4) and CHCl(3) rise continuously. With respect to effects on the hepatic microcirculation halothane seems to be less toxic than CCl(4). The results are discussed on the basis of the periods of exposition and the maximal concentrations of the solutes in the perfusion medium. With respect to these data CCl(4) is much more toxic than CHCl(3) and halothane. On the other hand there is no marked difference in acute hepatotoxicity between CHCl(3) and halothane.

Acute Disease↗
PubMedDate not supplied

Effect of organ perfusion on renal drug transport. Application to furosemide in the isolated perfused rat kidney.

Angiotensin II was used as a probe to study the effect of changes in perfusate flow rate on the renal clearance parameters of furosemide in the isolated perfused rat kidney. Drug studies were performed in three rats with no angiotensin II present in the perfusate (treatment I) and in three rats with a 2.7 ng/min infusion of angiotensin II into the perfusate (treatment II). Furosemide was introduced into the recirculating perfusate at an initial concentration of 3.5 micrograms/ml and was assayed using HPLC. The protein binding of furosemide in perfusate was determined by equilibrium dialysis. Angiotensin II was found to have a dramatic effect on the renal hemodynamics, resulting in a 42% decrease in perfusate flow, a 27% decrease in GFR, and a 25% increase in filtration fraction. Values for the fractional excretion of glucose were very low and consistent, with or without angiotensin II (3.0-3.5%). Although the fraction unbound of furosemide was unchanged between treatments (0.770 for treatment I vs. 0.695% for treatment II), the renal and secretion clearances of furosemide were reduced by about 30% in the presence of angiotensin II. However, if the renal clearance (CLr) was corrected for free fraction (fu) and glomerular filtration rate (GFR) [ER = CLr/(fu.GFR)], there was no difference between the excretion ratio (ER) values of furosemide after the two treatments (29.0 for treatment I vs. 29.6 for treatment II). These results imply that the altered clearance parameters of furosemide are more likely the consequence of a reduction in functional nephron mass rather than a change in intrinsic secretory transport per unit mass of nephron.

Angiotensin II↗
PubMed1985

[Kallikrein secretion by the isolated perfused rat kidney. Role of perfusion pressure and the renin-angiotensin system].

The isolated perfused rat kidney (IPRK) releases kallikrein in urine and renin in perfusate. We have previously shown (Kidney Int 24: 58-65, 1983) and confirm here that kallikrein, as well as renin releases are influenced by changes in renal hemodynamics in this model: a rise in perfusion pressure (PP) from 80 to 98 mmHg increases renal perfusate flow (RPF) by 48 +/- 3 p. 100, inhibits renin release and stimulates kallikrein secretion to 234 +/- 84 p. 100 of control values (n = 8). Since the perfusate lacks angiotensinogen, we decided to study the effect on kallikrein of the reconstitution of the renin-angiotensin system in the IPRK by adding angiotensinogen + angiotensin converting enzyme (AG + ACE) to the perfusion medium. After AG + ACE, PP rose to 107 +/- 4 mmHg, RPF decreased by 82 +/- 3 p. 100 as a consequence of the vasoconstrictor effect of angiotensin II, and renin release was suppressed. Again kallikrein secretion was stimulated and increased to 333 +/- 153 p. 100 of control values (n = 4). It is concluded 1) that kallikrein release is influenced by changes in PP but not in RPF on the IPRK. 2) that reconstitution of the renin-angiotensin system by addition of AG + ACE to the perfusate leads to vasoconstriction, suppression of renin release and a marked increase in kallikrein secretion.

Animals↗