[Nutritive skin circulation in partial ischemia: effect of various vasoactive substances].
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Biomedical subjects
Publications and source records attributed to K Messmer.
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UNLABELLED: Impaired right ventricular (RV) performance due to increased RV afterload in patients with sepsis or acute respiratory failure has been attributed to relative hypoperfusion and myocardial ischemia of the stressed free RV wall. There is evidence from experiments, however, that the normal RV is able to respond to a pressure load with adequate increases in myocardial blood flow. Whether or not ischemia of the free wall contributes to RV failure and whether restoration of RV perfusion can improve RV performance remains to be elucidated. The aim of this study was to compare local RV contractility to parameters of global RV contractility prior to and after induction of ischemia to its free wall. METHODS: Studies were performed in a total of 16 open-chest dogs using sonomicrometry to determine local contractility (velocity and percentage of fiber shortening) in the RV inflow tract (n = 8) prior to, 5, and 30 min after acute ligation of the right coronary artery (RCA). Parameters of global RV contractility (dP/dtmax, Vmax) were derived from intraventricular pressure measurements (tip-manometer). Regional myocardial blood flow (n = 6) was determined by the radioactive microsphere technique. Furthermore, the septal-lateral diameters of the RV (n = 8) and left ventricle (LV, n = 5), as well as the anterior-posterior diameter (n = 4) of the LV were measured simultaneously by use of sonomicrometers (Fig. 1); ventricular pressure-diameter diagrams were constructed in order to assess the dynamic geometry of the heart. RESULTS: Acute ligation of the RCA resulted in a reduction of myocardial blood flow (-39% to -72%), predominantly in the RV inflow tract (Table 1). The segment length of the RV free wall and diameter of the RV increased following RCA ligation (Fig. 3a) whereas the septal-lateral diameter of the LV decreased concomitantly. The LV anterior-posterior diameter remained unaffected (Table 2, Fig. 3b). While local RV contractility (percent shortening and velocity of fiber shortening) deteriorated (-40% and -32%, respectively), the parameters of global RV contractility (dP/dtmax, Vmax) remained unchanged (Fig. 4a). Heart rate, mean arterial pressure, RV systolic pressure, and LV filling pressure remained unchanged (Fig. 4b), whereas RV filling pressure increased (+52%) and cardiac output was reduced (-13%).(ABSTRACT TRUNCATED AT 400 WORDS)
Right ventricular (RV) epicardial tissue oxygen pressure (PtO2) was measured polarographically by means of a platinum multiwire surface electrode on the in situ beating heart of ten anesthetized dogs prior to and after moderate (Hct 28%) normovolemic hemodilution (HD) with dextran 60. In five dogs the effect of acute occlusion of the right coronary artery (RCA) on PtO2 was analyzed. The PtO2 histograms at baseline revealed a bell-shaped configuration and a mean PtO2 of 46.2 +/- 7.1 mm Hg which coincides with the PtO2 on the left ventricle (LV) reported by others. After HD mean PtO2 increased to 51.4 +/- 8.5 mm Hg (P = 0.02) without alterations of the histogram's configuration. Hemodynamics and blood gas analyses were unchanged after HD. RCA ligature was followed by non-uniform changes in the PtO2 pattern. Thus, despite marked differences in external work and O2 consumption, the PtO2 in both RV and LV myocardium are similar at rest. The increase of PtO2 in the RV at reduced Hct values, which is not seen in the LV myocardium, can be related to differences in functional capillary density between both ventricles.
The effect of the calcium-channel blocker nifedipine on the electromyographic activity of the small bowel and sphincter of Oddi was studied in conscious opossums. Electromyographic and arterial pressure recordings were started 7-10 days after implantation of seven pairs of electrodes along the small bowel and sphincter of Oddi. Continuous infusion of nifedipine caused a dose-dependent reduction of the frequency of spike bursts in the small bowel and sphincter of Oddi. Nifedipine at high doses abolished the migrating motor complex in the gastrointestinal tract. The frequency of slow waves was unchanged. This drug possibly inhibits the membrane influx of calcium into the smooth muscle cells of the gastrointestinal tract. We conclude that nifedipine causes an intense decrease in the motility of the small bowel and sphincter of Oddi.
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The effect of hemodilution on oxygen delivery to the tissue was investigated analytically by taking into consideration the oxygen loss that occurs along the arterial microvasculature due to diffusion into the tissue and shunting to parallel running venules. The theoretical findings were related to experimental data on microvascular oxygen distribution and the blood flow weighted by the oxygen-carrying capacity of plasma and red blood cells (Q) during hemodilution. It was found that at 30-33% hematocrit, the amount of oxygen brought to the tissues is increased by 5% when diffusion is the only mechanism of oxygen loss, and by 15% when the loss is due to arteriole-venule (A-V) shunting. These increases are relative to the conditions of normal hematocrit, and are in addition to the 10% increase due to the enhancement of Q caused by hemodilution. The analysis was extended to conditions of low oxygen tension and flow condition, characteristic of ischemia. In the case of severe ischemia the total increase in oxygen delivery at hematocrit 30-33% was 38% for tissues with diffusion losses only, and 66% when shunting losses are predominant. These results suggest that hemodilution is particularly effective in increasing oxygenation in ischemic tissue, while it has a comparatively small effect in normal conditions.
The effect of successive normovolemic hemodilution was studied in the microcirculation of the skeletal muscle (tenuissimus) of the rabbit. Normovolemic hemodilution was obtained by the progressive equal replacement of blood with a 6% solution of dextran 70 (MW = 70,000). Systemic parameters (mean arterial pressure, heart rate, and systemic hematocrit) were monitored throughout the procedure to ensure that normovolemia was maintained, and that the animal did not have adverse responses to the procedure. Microcirculatory hemodynamics were characterized by the measurements of capillary red blood cell (RBC) flux, RBC velocity, capillary hematocrit (Hcap), and flowmotion (the effect of arteriolar vasomotion on capillary flow velocity). The same capillaries were chosen throughout a given experiment and the measurements in the hemodiluted states were normalized to the control value. The changes of RBC flux up to 50% hemodilution were not statistically significant and flux remained essentially constant. Capillary RBC velocity increased significantly, where it was 45% higher than control at 50% hemodilution. Hcap was maintained at the control level up to 25% hemodilution.
Sodium nitroprusside (SNP)-induced hypotension is associated with tissue hypoxia in liver and skeletal muscle, suggesting a redistribution of nutritional capillary flow. To test this hypothesis, the effects of SNP and nitroglycerin (NTG) on striated muscle vessels were studied in 42 hamsters using intravital microscopy, quantitative video image analysis, a platinum multiwire electrode for local Po2 measurements, and a micropuncture system for the determination of microcirculatory pressure. A transparent chamber was implanted in a dorsal skin fold. When the mean arterial pressure was reduced to 70 or 40 mmHg by SNP, the precapillaries dilated and precapillary resistance decreased, but significant changes in venular diameter were not observed. However, SNP-induced hypotension was associated with a consistent increase in intravascular pressure within the venules. As a result, the arteriolar-venular pressure gradient was reduced by more than 50%. Furthermore, the functional capillary density was less, and tissue hypoxia was present during SNP hypotension. In contrast, NTG dilated both arterioles and venules in the microvascular network. Despite a lower blood cell velocity in all segments, the functional capillary density and local Po2 remained unchanged during NTG, principally because there was only a 10% reduction of the arteriolar-venular pressure gradient. These findings suggest that, in terms of tissue oxygenation, NTG may be preferable to SNP for deliberate hypotension.
Normovolemic hemodilution on a whole body basis is studied by means of a steady flow, hydraulic analogue simulation of the cardiovascular system, based on the Casson's model and current hemodynamic and rheological data. The vasculature is divided into serially connected compartments whose hydraulic resistance is characterized by the average diameter, length, number of vessels, and the corresponding rheological properties of blood formulated by Dintenfass (1971) and Lipowsky et al. (1980). This model computes the pressure distributions in all compartments, where the calculated venous pressure modulates the cardiac function according to the Starling mechanism for cardiac performance. The alterations of flow induced by the action of the heart are added to the effects due to changes in peripheral vascular resistance as a result of hematocrit variation. This model shows that when the response of heart to the changes of venous pressure is impaired, the maximum oxygen carrying capacity occurs at 40% hematocrit (H) where it is 1% higher than normal hematocrit (H = 44%). The normal cardiac response to the changes of venous pressure, causes the maximum oxygen carrying capacity to occur at 32% H where it is 12% greater than that at normal hematocrit. Mean arteriolar pressure and capillary pressure increase while venular pressure is slightly reduced during normovolemic hemodilution.
Specimens of syngeneic spleen, myocardium, and spongious bone as well as lyophilized dura were implanted into a dorsal skinfold chamber of hamsters. Using intravital microscopy and quantitative video-image analysis, the formation of the implants microcirculation was observed for 2 weeks. The steps of revascularization were similar for spleen, myocardium, and spongiosa: After initial bleeding into the implants (12-54 h), the specimens cleared up and revealed small channels devoid of blood cells (diameter 2-5 microns) 3-4 days after implantation. After 3-5 days blood flow could be observed throughout the specimens. Despite these similarities, the evolving angioarchitecture was specific for each tissue. In contrast, dura specimens were not vascularized. Histology of the implants revealed characteristic structures of the original organs 10-15 days after implantation. It is concluded that the hamster dorsal skinfold chamber provides a suitable host tissue for syngeneic implants. By this procedure, the study of the microcirculation of remote or unpredictably moving organs becomes possible over prolonged periods of time.
Continuous biliary pressure and electromyographic activity of the sphincter of Oddi and gastrointestinal tract were recorded in conscious opossums following administration of analgesic drugs. Morphine, meperidine, and pentazocin increased significantly the duration of the migrating motor complex (MMC) cycle. Periods of 1-2 minutes of intense burst of spike potentials were seen in the sphincter of Oddi and duodenum following administration of morphine (8 experiments), meperidine (6 experiments), and pentazocin (3 experiments). The biliary pressure in the control studies was similar to that following administration of all analgesics in the animals with gallbladder and following instillation of tramadol, metamizol, and acetylsalicylic acid in animals with no gallbladder. However, the biliary pressure was significantly higher following administration of morphine, meperidine, and pentazocin in the animals with no gallbladder. It is concluded from this study that morphine, meperidine, and pentazocin may cause important disturbances in the motility of the sphincter of Oddi and gastrointestinal tract. These myoelectric disturbances may cause an increase in the biliary pressure in animals that have been subjected to cholecystectomy, but not in animals with intact gallbladder. The gallbladder may accommodate the bile produced by the liver during periods of sphincter of Oddi dysfunction and thus impede an increase in the biliary pressure.
Preoperative intentional hemodilution is induced by isovolemic exchange of whole blood with colloid solutions in order to gain autologous blood while maintaining normovolemia. The basic mechanism that compensates for the fall of oxygen capacity of the diluted blood is the rise in cardiac output, and organ blood flow, factors that result from the improved fluidity of blood at lower hematocrits. Normal tissues maintain adequate oxygenation during hemodilution through the enhanced redistribution of blood. In ischemic tissues this effect is enhanced, and causes an increase in the oxygenation of ischemic tissues. Limited preoperative and intraoperative hemodilution are alternatives to donor blood transfusion in patients undergoing elective surgery. In shock patients the hemodilution achieved with red cell free primary volume substitutes is an effective treatment for shock-induced microcirculatory disorders; furthermore, intentional hemodilution is the most effectual hemorheological therapy for the treatment of ischemic disease.
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A prerequisite elucidating the pathomechanism of hemorrhagic shock are reproducible experimental models, leading to a predictable outcome. Two concepts have been reported to be a good predictor for the outcome both employing a fixed hypotension level: total oxygen deficit and shed blood volume uptake. To correlate these two models we subjected 31 dogs to a standardized hemorrhagic shock procedure. Besides determination of acid-base status, hematocrit, mean arterial pressure, and cardiac output, these two parameters were measured continuously. Seventeen dogs survived the shock procedure, 14 died within 24 h. During shock, neither oxygen deficit nor any other parameter mentioned above correlated with the final outcome of the shock state. The only significant difference between surviving and non-surviving animals during this period was the amount of uptake. The non-surviving dogs exhibited a higher uptake volume, indicating an incipient collapse of the microcirculation. Terminating the duration of hypotension at an uptake volume of 5% of the maximum shed blood, all animals survived, while after an uptake volume of 15% about 50% of the dogs died. Using uptake volumes of various degrees in a hemorrhagic shock model as the endpoint of the hypotensive stress, it seems possible to produce reliable survival rates.
Oxygen consumption, hemodynamics, and regional blood flow (with the radioactive microspheres technique) were determined in 12 anesthetized dogs subjected to hemorrhagic shock. The animals were kept in hypotension at 40 mmHg, until 15% of the maximum shed blood had been infused to keep arterial pressure stable, whereafter all the shed blood was retransfused. Cardiac output (CO) decreased to 33% and 25% of preshock values in survivors (S) and nonsurvivors (NS), respectively, and after retransfusion it was significantly higher in S. After retransfusion, NS showed a higher arterial pCO2 than S adding a respiratory component to the metabolic acidosis that occurred during and after hemorrhage. Blood flow to the brain was not impeded during shock, but as CO decreased the fraction delivered to the brain was increased 2.6-3.3-fold. Myocardial blood flow decreased to about 28% of preshock values immediately after hemorrhage, and increased to about 54% at the end of hemorrhage. After retransfusion S had a higher myocardial flow than NS. The flow to the gut paralleled the decrease in CO during hemorrhage and immediately after retransfusion NS exhibited an overperfusion in ileum and colon compared to the preshock values. Kidney blood flow fell progressively during the course of hypotension, similarly in S and NS. After retransfusion it was normalized in S but not in NS. The preshock flow to pancreas was significantly higher in S than in NS, but during and after shock the blood flow did not differ between S and NS.
This report provides fine structural evidence that, dependent upon the malignancy, tumor as well as mesenchymal cells may participate actively in the neovascularization of experimental tumors grown in transparent tissue chambers implanted into skinfolds of syrian hamsters. Such non-endothelial cells may help to promote angiogenesis in two different ways: (1) They are incorporated into capillary sprouts thereby accelerating the growth rate of the latter independent of endothelial cell proliferation. (2) Extravascular cells (tumor and mesenchymal elements) become integrated in varying numbers into the linings of comparatively large blood-perfused vessels. This facilitates the rapid establishment and functional remodelling of the microvascular bed to adapt the microcirculation to the varying local demands of the growing tumor. If these results can be confirmed for other tumors, and if they are independent of the tumor's environment and the experimental protocol, then we will have to reconsider the significance of tumor angiogenesis as a realistic biological model from which general conclusions with regard to neovascularization in non-tumorous tissues may be drawn.
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