Blood flow mechanical models

Matsuno et al. (1991) reports a method to induce thrombosis in the rat femoral artery by means of a photochemical reaction after injection of a fluorescent dye (rose Bengal, 10 mg/kg i.v.) and transillumination with a filtered xenon lamp (wave length 540 nm). Blood flow is monitored by a pulsed Doppler flow meter. Occlusion is achieved after approximately 5-6 min. Pretreatment with heparin dose-dependently prolongs the time required to interrupt the blood flow. The model also enables the study of thrombolytic mechanisms, which had been evaluated with t-PA. A comparative data for hirudin in various models was carried out by Just et al. (1991). 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Several models have been developed to simulate the absorption, distribution, metabolism and excretion of butadiene, some of its metabolites and its adducts to haemoglobin in mouse, rat and man. Critical aspects are discussed in Csanady et al. (1996) and in Himmelstein et al. (1997). Basically, the models consist of a number of compartments representing diverse tissues and organs, several of which are grouped together. These compartments are linked by blood flow. The main differences between models are the number of metabolizing and nonmetabolizing compartments, the mechanisms of metabolism, the metabolites taken into consideration, and the values of the biochemical. 

As demonstrated by the power spectra in Figs. 12.2a and 12.3b, regulation of the blood flow to the individual nephron involves several oscillatory modes. The two dominating time scales are associated with the period Tsiow 30—40 s of the slow TGF-mediated oscillations and the somewhat shorter time scale Tjast 5—10 s defined by the myogenic oscillations of the afferent arteriolar diameter. The two modes interact because they both involve activation of smooth muscle cells in the arteriolar wall. Our model describes these mechanisms and the coupling between the two modes, and it also reproduces the observed multi-mode dynamics. We can, therefore, use the model to examine some of the phenomena that can be expected to arise from the interaction between the two modes. 

Our insight into the development, evolution and the mechanisms of damage in cerebral ischemia is mainly based on animal studies. A large variety of experimental models have been developed that imitate conditions of stroke and cardiac arrest (Hossmann 1991). In the past, experiments had to be terminated at certain timepoints to obtain invasive measurements of lesion size, blood flow, metabolism or other markers of injury. Therefore, longitudinal observations required large animal numbers and the inter-individual differences complicated the analysis of results. The advent of MR techniques of imaging... 

The neuroprotective properties of mild hypothermia have been demonstrated in numerous experimental animal models. Research in this area has been conducted for many years, yet the mechanisms of cerebral protection by mild hypothermia remain unclear and continue to be the subject of intense investigation. The neuroprotective effects of mild hypothermia have been attributed to alterations in metabolic rate (24), neurotransmitter release (25-27), activity of protein kinases (28), resynthesis of cellular repair proteins (29), cerebral blood flow (30), preservation of the blood-brain barrier (BBB) (31), attenuation of inflammatory processes (32,33), and decreases in free radical production (34). Although these may all be components of a complex cascade leading to neurologic injury, it has become increasingly clear that the primary mechanism of action of hypothermia may be different at various temperatures as well as under different ischemic and traumatic conditions. 

Fig. 4. Technique for monitoring platelet aggregation in the partially obstructed left circumflex coronary artery of the dog. Electromagnetic flow probes measure blood flow. Partial obstruction of the coronary artery with a plastic Lexan cylinder results in episodic cyclical reductions in coronary blood flow that are due to platelet-dependent thrombus formation. Every 2-3 mm the thrombus must be mechanically shaken loose to restore blood. For detailed application of the Folts model, see Sullivan et al. (1992) Folts, Rowe (1974, 1988) and Folts et al. (1976, 1982).

Harbauer (1984) first described a venous model of thrombosis induced by mechanical injury and stenosis of the jugular vein. In a modification, both arterial and venous thrombosis is produced in rabbits by stenosis of the carotid artery and the jugular vein with simultaneous mechanical damage of the endothelium. This activates platelets and the coagulation system and leads to changes in the bloodstream pattern. As a consequence, occluding thrombi are formed as detected by blood flow measurement. The dominant role of platelets in this model is shown by the inhibitory effect of an antiplatelet serum in both types of vessels (Just 1986). The test is used to evaluate the antithrombotic capacity of compounds in an in vivo model of arterial and venous thrombosis where thrombus formation is highly dependent on platelet activation. 

Rote et al. (1993, 1994) used a carotid thrombosis model in dogs. A calibrated electromagnetic flow meter was placed on each common carotid artery proximal to both the point of insertion of an intravascular electrode and a mechanical constrictor. The external constrictor was adjusted with a screw until the pulsatile flow pattern decreased by 25 % without altering the mean blood flow. Electrolytic injury to the intimal surface was accomplished with the use of an intravascular electrode composed of a Teflon-insulated silver-coated copper wire connected to the positive pole of a 9-V nickel-cadmium battery in series with a 250000 ohm variable resistor. The cathode was connected to a subcutaneous site. Injury was initiated in the right carotid artery by application of a 150 xA continuous pulse anodal direct current to the intimal surface of the vessel for a maximum duration of 3 h or for 30 min beyond the time of complete vessel occlusion as determined by the blood flow recording. Upon completion of the study on the right carotid, the procedure for induction of vessel wall injury was repeated on the left carotid artery after administration of the test drug. 

There are three chapters in this volume, two of which address the microscale. Ploehn and Russel address the Interactions Between Colloidal Particles and Soluble Polymers, which is motivated by advances in statistical mechanics and scaling theories, as well as by the importance of numerous polymeric flocculants, dispersants, surfactants, and thickeners. How do polymers thicken ketchup Adler, Nadim, and Brenner address Rheological Models of Suspensions, a closely related subject through fluid mechanics, statistical physics, and continuum theory. Their work is also inspired by industrial processes such as paint, pulp and paper, and concrete and by natural systems such as blood flow and the transportation of sediment in oceans and rivers. Why did doctors in the Middle Ages induce bleeding in their patients in order to thin their blood ... 

Ischemic, nephrotoxic, and septic rodent models of acute renal injury were developed to study mechanisms of acute kidney injury. Decreasing renal blood flow is critical in the pathophysiology of AKI in humans. Ischemic and other animal models are used to reproduce the morphological features of human disease. 

Tafluprost significantly increases retinal blood flow and blood velocity in animal models. The improvement of ocular blood flow is thought to be relevant in glaucoma therapy, especially for normal-tension glaucoma patients since it is assumed that optic nerve damage is involved not only in mechanical compression caused by IOPbut also in impairment of ocular blood flow. 

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