Renal vein outflow recording in rats and rabbits: alternative method of R.B.F. measurement

A method is described for continuous measurement of total renal blood flow in anesthetized rats and rabbits. It consists of recording time intervals in which a fixed volume of renal vein outflow enters into an extracorporeal renin vein - jugular vein shunt and is pumped back to animals' circulation. This technique yields absolute flow values of unequalled accuracy and requires virtually no calibration; however, it is not suitable for recording rapid flow transients. The RBF measured averaged 5.5 +/- (SE) 0.1 ml/min.g kidney weight in rats and 2.5 +/- 1.1 ml/min.g in rabbits; the flow was stable over at least 1.5-2 hrs. The rat kidneys tested showed usual capacity to autoregulate blood flow during graded reduction in renal perfusion pressure.     

A modified technique for the production of an arterio-venous shunt in sheep, allowing a comparison of biocompatibility of synthetic materials

Polytetrafluorethylene (PTFE) prostheses were implanted in 12 sheep as a shunt between the carotid artery and the jugular vein using an end-to-side anastomosis technique. This technique allows repeated tests of the pharmacological and toxicological safety of artificial kidney units after both single and multiple administration. Furthermore, it enables the investigation of detoxification of compounds via dialysis, thus contributing to drug safety. Implantation of the prosthesis was uncomplicated. Connection to the extracorporeal circulation was achieved via catheters and maintained using a pump with an output of up to 300 ml/min. This enabled maintenance of extracorporeal circulation for several hours without clinical impairment to the animals. The AV-shunts remained functional for between 8 and 253 days (mean 112.3 days).     

The rabbit as an animal model for haemoperfusion: surgical preparation and use

In this paper the authors describe the surgical procedure to prepare rabbits for haemoperfusion experiments. The carotid artery and jugular vein are cannulated and a simple shunt device inserted to maintain patency of the vessels over a period of time. The cannulas and shunt remain patent and free of infection for some months. Specially designed outflow and inflow extracorporeal tubing sets minimize blood volume outside the body of the rabbit. The authors also illustrate the efficacy of this system in haemoperfusion trials to remove specific antibodies. Recently a system was described to remove mercury from the bloodstream of poisoned animals. The rabbit is a useful experimental animal for this type of haemoperfusion trial.     

A respiratory venous chemoreceptor in the young puppy.

An extracorporeal venovenous shunt system utilizing a membrane oxygenator to alter venous blood gases was used to study the regulation of ventilation in 28 newborn and 4 adult dogs. There was no effect of the extracorporeal circuit per se (without the oxygenator in the system) on essential cardiovascular or respiratory function. When the puppies were placed on the extracorporeal circuit with the oxygenator in the system to effect changes in mixed venous blood gas composition there was a significant increase in venous P02 (Pv02), a decrease in venous Pco2 (Pvco2), a rise in venous pH (PHv), and a marked fall in minute ventilation (VE). There were no significant changes in cardiovascular function or arterial blood gases to account for the depression of ventilation. Acute changes in Pvo2 produced appropriate directional changes of VE under conditions where other arterial and venous blood gases were held constant. At a low Pvco2/Paco2 ratio, ventilation was depressed compared to those conditions with a high ratio. At any Pvc02/Paco2 ratio, ventilation could be depressed by raising the Pvo2. In adult animals ventilation could not be altered by changing venous blood gases. These experiments support the existence of a respiratory chemoreceptor sensitive to both PO2 and PCO2 in the prepulmonary or venous circulation of the newborn animal.     

Proteomics in extracorporeal blood purification and peritoneal dialysis

Extracorporeal blood purification and peritoneal dialysis are widely used in renal replacement therapy for patients with end-stage renal disease (ESRD) and acute kidney injury (AKI). Additionally, extracorporeal blood purification can be used also for treatment of non-renal disorders to remove endogenous or exogenous toxins from the blood circulation. Efforts have been made to characterize these toxins removed by diffusion (dialysis), convection (ultrafiltration), and/or adsorption (toxins are adsorbed onto the dialysis membrane and are thus removed) using different types of dialysis membrane. This review summarizes important findings obtained from recent proteomic studies applied to extracorporeal blood purification and peritoneal dialysis in settings of ESRD, AKI and hepatic failure.     

Computational model of the fluid dynamics in systemic-to-pulmonary shunts

A systemic-to-pulmonary shunt is a connection created between the systemic and pulmonary arterial circulations in order to improve pulmonary perfusion in children with congenital heart diseases. Knowledge of the relationship between pressure and flow in this new, surgically created, cardiovascular district may be helpful in the clinical management of these patients, whose survival is critically dependent on the blood flow distribution between the pulmonary and systemic circulations. In this study a group of three-dimensional computational models of the shunt have been investigated under steady-state and pulsatile conditions by means of a finite element analysis. The model is used to quantify the effects of shunt diameter (D), curvature, angle, and pulsatility on the pressure-flow (DeltaP-Q) relationship of the shunt. Size of the shunt is the main regulator of pressure-flow relationship. Innominate arterial diameter and angles of insertion have less influence. Curvature of the shunt results in lower pressure drops. Inertial effects can be neglected. The following simplified formulae are derived: DeltaP=(0. 097Q+0.521Q(2))/D(4) and DeltaP=(0.096Q+0.393Q(2))/D(4) for the different shunt geometries investigated (straight and curved shunts, respectively).     

Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy

Some lines of evidence have suggested that the challenge to antioxidants and biomolecules provoked by pro-oxidants such as ozone may be used to generate a controlled stress response of possible therapeutic relevance in some immune dysfunctions and chronic, degenerative conditions. Immune and endothelial cells have been proposed to be elective targets of the positive molecular effects of ozone and its derived species formed during blood ozonation. On the bases of these underlying principles and against often prejudicial scepticism and concerns about its toxicity, ozone has been used in autohemotherapy (AHT) for four decades with encouraging results. However, clinical application and validation of AHT have been so far largely insufficient. Latterly, a new and more effective therapeutic approach to ozone therapy has been established, namely extracorporeal blood oxygenation and ozonation (EBOO). This technique, first tested in vitro and then in vivo in sheep and humans (more than 1200 treatments performed in 82 patients), is performed with a high-efficiency apparatus that makes it possible to treat with a mixture of oxygen-ozone (0.5-1 microg/ml oxygen) in 1 h of extracorporeal circulation up to 4800 ml of heparinized blood without technical or clinical problems, whereas only 250 ml of blood can be treated with ozone by AHT. The EBOO technique can be easily adapted for use in hemodialysis also. The standard therapeutic cycle lasts for 7 weeks in which 14 treatment sessions of 1 h are performed. After a session of EBOO, the interaction of ozone with blood components results in 4-5-fold increased levels of thiobarbituric acid reactants and a proportional decrease in plasma protein thiols without any appreciable erythrocyte haemolysis. On the basis of preliminary in vitro evidence, these simple laboratory parameters may represent a useful complement in the routine monitoring of biological compliance to the treatment. The clinical experience gained so far confirms the great therapeutic potential of EBOO in patients with severe peripheral arterial disease, coronary disease, cholesterol embolism, severe dyslipidemia, Madelung disease, and sudden deafness of vascular origin. Extensive investigation on oxidative stress biomarkers and clinical trials are under way to validate this new technique further.     

The effect of cephalothin prophylaxis on postoperative ventriculoperitoneal shunt infections.

Postoperative infection is an important complication after insertion of a ventriculoperitoneal (VP) shunt in children with hydrocephalus. A randomized double-blind placebo-controlled study was performed to determine the efficacy of cephalothin in preventing postoperative shunt infection. Sixty-three children who presented for elective VP shunt insertion between January 1982 and December 1985 and who did not have a history of shunt infections were randomly assigned to receive four doses of prophylactic cephalothin, 25 mg/kg (32 patients), or of a multivitamin placebo (31 patients). Postoperative infection developed in 6% of the treatment group, compared with 10% of the placebo group, a difference that was not statistically significant, although a clinical significance may have been masked by the small sample size. A large multicentre trial is needed to determine the efficacy of antibiotic prophylaxis in reducing the incidence of postoperative VP shunt infections.     

Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs.

The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2-3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model.     

Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy

Abstract

Some lines of evidence have suggested that the challenge to antioxidants and biomolecules provoked by pro-oxidants such as ozone may be used to generate a controlled stress response of possible therapeutic relevance in some immune dysfunctions and chronic, degenerative conditions. Immune and endothelial cells have been proposed to be elective targets of the positive molecular effects of ozone and its derived species formed during blood ozonation. On the bases of these underlying principles and against often prejudicial scepticism and concerns about its toxicity, ozone has been used in autohemotherapy (AHT) for four decades with encouraging results. However, clinical application and validation of AHT have been so far largely insufficient. Latterly, a new and more effective therapeutic approach to ozone therapy has been established, namely extracorporeal blood oxygenation and ozonation (EBOO). This technique, first tested in vitro and then in vivo in sheep and humans (more than 1200 treatments performed in 82 patients), is performed with a high-efficiency apparatus that makes it possible to treat with a mixture of oxygen–ozone (0.5–1 μg/ml oxygen) in 1 h of extracorporeal circulation up to 4800 ml of heparinized blood without technical or clinical problems, whereas only 250 ml of blood can be treated with ozone by AHT. The EBOO technique can be easily adapted for use in hemodialysis also. The standard therapeutic cycle lasts for 7 weeks in which 14 treatment sessions of 1 h are performed. After a session of EBOO, the interaction of ozone with blood components results in 4–5-fold increased levels of thiobarbituric acid reactants and a proportional decrease in plasma protein thiols without any appreciable erythrocyte haemolysis. On the basis of preliminary in vitro evidence, these simple laboratory parameters may represent a useful complement in the routine monitoring of biological compliance to the treatment. The clinical experience gained so far confirms the great therapeutic potential of EBOO in patients with severe peripheral arterial disease, coronary disease, cholesterol embolism, severe dyslipidemia, Madelung disease, and sudden deafness of vascular origin. Extensive investigation on oxidative stress biomarkers and clinical trials are under way to validate this new technique further.     

Blood Vessels in the Hind Limb of the Mallard (Anas platyrhynchos): Anatomical Evidence for a Sphincteric Action of Shunt Vessels in Connection with the Arterio-venous Heat Exchange System

Midtgård, U. 1980. Blood vessels in the hind limb of the Mallard (Anas platyrhynchos): anatomical evidence for a sphincteric action of shunt vessels in connection with the arterio-venous heat exchange system. (Institute of Comparative Anatomy, University of Copenhagen, Denmark.) — Acta zool. (Stockh.) 61(1): 39–49. The rete tibiotarsale is the main arterio-venous heat exchange system in the hind limb of the Mallard. A large arterial shunt and a venous shunt allow the blood to by-pass the rete. These shunt vessels must be able to constrict so as to direct the blood to the rete when heat conservation is needed. Using ordinary histological methods and the technique of Falck and Hillarp for demonstration of biogenic monoamines, it was shown that the arterial shunt is more muscular and receives a more dense adrenergic innervation than adjacent segments of the same vessel. Perfusion with noradrenaline before fixation revealed that the arterial shunt was able to reduce its lumen to near closure. No structure, in the ordinary sense of a sphincter, was found in the shunt vein but adrenergic nerves were scattered throughout the tunica media at the base of venous valves, suggesting that a sphincteric action at these sites is possible.     

Cardiorespiratory changes during HCl infusion unrelated to decreases in circulating blood pH

To test the hypothesis that infusion of HCl changes blood pressure and respiration independent of decreases in circulating blood pH, an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and vein was installed in anesthetized cats. Into this loop, acid (0.25 M HCl) and, approximately 10 cm downstream, base (0.25 M NaOH) could be infused simultaneously. Likewise, either acid or base could be infused individually. Right ventricular (Prv) and arterial (Pa) blood pressure, tidal volume (VT), and respiratory frequency (fresp) were recorded as well as blood gases and pH in arterial, right ventricular, and shunt loop blood at the reentrance into the animal. When HCl and NaOH were infused simultaneously and at equimolar rates (0.2 mmol/min for 10 min), there was a large increase in Prv, with little change or decrease in Pa. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in VT. The rise in Prv and increase in fresp were transient in that they could only be evoked during the first HCl-NaOH infusion in a given animal. Repetitive infusions of HCl-NaOH into the same animal failed to elicit the response. Similar transient acid effects were evoked when HCl was infused without NaOH but not when NaOH was infused without HCl. During the second and third infusion of HCl, ventilatory responses were elicited that were explainable by stimulation of known chemoreceptors. The transient rise in Prv and fresp evoked by acid infusion might be explained by release of an agent from blood elements at the tip of the HCl infusion catheter, which in turn would constrict pulmonary vessels and influence breathing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of exact focusing of extracorporeal shock waves (ESWT) in therapy of tendinitis calcarea. A prospective randomized study]

A controlled randomized study was designed to analyse the effect of extracorporeal shockwave therapy (ESWT) focussed on either the calcified region or the insertion of the supraspinatus tendon. The study included 50 patients who were treated with a Storz Minilith SI-1 prototype shockwave generator. In the treated group, 4000 impulses (ED+ 0.78 ml/mm2) were applied, under local anaesthesia to the insertion of the supraspinatus in 2 treatment sessions. Control patients received ESWT focussed on the calcified region. Follow-up examinations were carried out 12 weeks after treatment by an independent observer. We found functional improvement and pain reduction in both groups. Statistical analyses showed significant superiority of ESWT focussed on the calcified region for the parameters constant-score (primary endpoint, p < 0.001) and pain intensity (p = 0.001). For the treatment of calcific tendinitis affecting the supraspinatus, we recommend accurate fluoroscopy-controlled focussing of ESWT on the calcification. Focussing on the calcification rather than on the insertion of the supraspinatus tendon is significantly more effective. On the basis of our results, ESWT requires the use of suitable shockwave generators that permit accurate focussing.     

Treatment of autoimmune disease with extracorporeal photochemotherapy: pemphigus vulgaris--preliminary report

Extracorporeal photochemotherapy is a new form of immunotherapy which involves the extracorporeal photoinactivation of peripheral blood cells by 8-methoxypsoralen in the presence of ultraviolet A irradiation, followed by readministration of the cells. To explore the efficacy of this therapy in the treatment of autoimmune disease, four patients with a lengthy history of corticosteroid and immunosuppressive drug-resistant pemphigus vulgaris were initiated on extracorporeal photochemotherapy. Three patients experienced a complete remission in cutaneous disease expression, permitting discontinuation of medications in two and a substantial decrease in the third. Significant reductions in serum antiepidermal cell antibody titers occurred in all four patients. The treatments were well tolerated without the occurrence of adverse events. These results in a small number of patients suggest that extracorporeal photochemotherapy may prove to be a useful tool in the treatment of aggressive autoimmune disease.     

Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs

Ventilatory responses to CO2 inhalation and CO2 infusion were compared in the awake dog. The CO2 was introduced directly into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow, QX, was maintained constant at one of two rates: low, 0.5 l/min; or high, 2.0 l/min. A total of 13 experiments was performed in four dogs comprising 50 control and 25 inhalation and infusion observations at each of the two flow rates. Comparison of CO2-response curve slopes, S = delta V E/delta PaCO2, between CO2 inhalation and infusion showed no significant difference either within or between flow rates. The mean value of S for all conditions was 1.88 l/min per Torr with a 95% confidence interval of 1.66 -2.14. An independent additive ventilatory drive amounting to 28% of low-flow control VE was found at the highflow rate. We conclude that at constant blood flow the responses to both CO2 inhalation and infusion are hypercapnic and not significantly different.     

Renal replacement therapy review: past, present and future

Support of renal function in modern times encompasses a wide array of methods and clinical scenarios, from the ambulatory patient to the critically ill. The ability to safely and routinely deliver ongoing organ support in the outpatient setting has until recently separated renal replacement therapy from other organ support. Renal replacement therapy (RRT) can be applied intermittently or continuously using extracorporeal (hemodialysis) or paracorporeal (peritoneal dialysis) methods. The purpose of this article is to familiarize the reader with the history, physiology, mode, dose, equipment and future of renal replacement therapy and not to detail the technical methods employed for blood purification.     

The distribution of ventilation-perfusion ratios in the lungs of newborn foals

The distributions of ventilation-perfusion ratios, and the effects of 100% oxygen administration on the distributions, were studied in 3 foals from 4h to 9 days of age, using the multiple inert gas elimination technique. The distributions were calculated from the pulmonary clearance of 6 inert gases following infusion into a peripheral vein of a solution containing the inert gases. The results from a total of 8 studies showed several consistent features. The major findings were (i) the absence of low ventilation-perfusion ratios, i.e. regions where blood flow was greatly in excess of ventilation; (ii) the presence of variable right to left shunt; (iii) a reduction in this shunt with increasing post-natal age; (iv) the presence of a separate high mode of ventilation-perfusion ratios where ventilation was greatly in excess of blood flow and; (v) the observation that breathing enriched oxygen mixtures for 40 min did not increase the right to left shunt in any foal at any age studied. These studies indicate that hypoxaemia in the neonatal foal is attributable to right to left shunt which may be intrapulmonary or intracardiac, or both, rather than overperfusion of poorly ventilated lungs.     

Hemodynamics and vascular sensitivity to circulating norepinephrine in normal skin and delayed and acute random skin flaps in the pig

Cutaneous circulation in 4 X 10 cm skin samples and delayed and acute random skin flaps constructed on the flanks of castrated Yorkshire pigs (13.3 +/- 0.7 kg; n = 12) were studied during intravenous infusion (0.5 ml per minute) of 5% dextrose solution (vehicle) and 5% dextrose containing norepinephrine (1 microgram/kg per minute). Total and capillary blood flow and A-V shunt flow were measured by the radioactive microsphere technique 6 hours after the raising of 4 X 10 cm single-pedicle acute and delayed random skin flaps using the technique and calculations published previously. Fluorescein dye test was also performed to assess vascular perfusion. It was observed that the capillary blood flow in the single-pedicle delayed skin flaps was similar to that in the normal skin, and the maintenance of this normal skin blood flow was not due to the closing of A-V shunt flow in the delayed skin flaps. Similarly, the significant (p less than 0.01) decrease in capillary blood flow and distal perfusion in the acute skin flaps compared with the delayed skin flaps was not due to the opening of A-V shunts in the acute skin flaps. There was no evidence to indicate that A-V shunt flow per se was the primary factor for the regulation of capillary blood flow in the acute and delayed skin flaps in the pig. Our data seemed to indicate that tissue ischemia in the distal portion of acute skin flaps was likely the result of vasoconstriction of the small random arteries which supplied blood to arterioles and A-V shunts, and locally released neurohumoral substances may play an important role in the pathogenesis of vascular resistance and ischemia in the acute skin flaps.     

Methods of Immobilization of Proteins to Polymethylmethacrylate

An extracorporeal hemoperfusion chamber for insertion into the peripheral circulatory system has previously been described. In 4 to 6 hours perfusion its aim is to exert a subtractive, selective effect on the blood and to stimulate immunocompetent cells. The chamber is made from polymethylmethacrylate (PMMA). Two general methods for immobilization are described here. The first is based on hydrazinolysis of the PMMA surface. Biologically active substances can be attached through diacylhydrazine bridges, amine bonds and amide groups to the PMMA surface. In the second method carboxyl groups are generated by hydrolysis of the PMMA methyl ester groups. The biologically active substance is immobilized using diamine or dialdehyde coupling agents. Methods are provided to attach the substances to the PMMA either via their carboxyl or via their amino groups.     

Methods of immobilization of proteins to polymethylmethacrylate

An extracorporeal hemoperfusion chamber for insertion into the peripheral circulatory system has previously been described. In 4 to 6 hours perfusion its aim is to exert a subtractive, selective effect on the blood and to stimulate immunocompetent cells. The chamber is made from polymethylmethacrylate (PMMA). Two general methods for immobilization are described here. The first is based on hydrazinolysis of the PMMA surface. Biologically active substances can be attached through diacylhydrazine bridges, amine bonds and amide groups to the PMMA surface. In the second method carboxyl groups are generated by hydrolysis of the PMMA methyl ester groups. The biologically active substance is immobilized using diamine or dialdehyde coupling agents. Methods are provided to attach the substances to the PMMA either via their carboxyl or via their amino groups.