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PubMed1985

Actions of prostaglandin E2 metabolites on skin microcirculation.

The actions of prostaglandin, E2 on skin microcirculation were compared with two of its metabolites. 2-10 ng prostaglandin E2, 2-10 micrograms 15-keto prostaglandin E2 and 5-10 micrograms 13,14-dihydro-15-keto prostaglandin E2 produced the following dose-related effects: increased area and intensity of erythema in human skin, increased vascular permeability in rat skin, potentiation of the increased vascular permeability elicited by either histamine or bradykinin, potentiation of carrageenan-induced oedema in the rat paw. The prostaglandin E2 metabolites are about 1000 times less active than the parent prostaglandin and are unlikely to account for the inflammatory actions of prostaglandin E2.

Animals↗

PubMed1995

Comparative effects of secretin (SEC) and cholecystokinin-octapeptide (CCK-8) on pancreatic microcirculation.

Using epifluorescent microscopy, we investigated the dynamic changes in pancreatic microcirculation in vivo after bolus administration of secretin (SEC) (0.1-10.0 micrograms/100 g body wt) and cholecystokinin-octapeptide (CCK-8) (0.005-1.2 micrograms/100 g body wt) in pentobarbital-anesthetized rats. Pancreatic capillary red cell velocity as a monitor for pancreatic capillary blood flow was measured in 1-min intervals from 2 min prior to 8 min following bolus infusion of SEC or CCK-8. Physiological concentrations of SEC did not increase pancreatic capillary blood flow. However, pharmacological SEC concentrations induced a dose-dependent increase in pancreatic capillary blood flow (to 162 +/- 19% of baseline; P < 0.05), due to an increase in blood flow velocity (to 153 +/- 18% of baseline; P < 0.05). In contrast, bolus administration of physiological CCK-8 concentrations, which have been proven to stimulate enzyme secretion, induced a transient and dose-dependent increase in pancreatic capillary blood flow (to 235 +/- 24% of baseline; P < 0.05), due to an increase in blood flow velocity (to 184 +/- 13% of baseline; P < 0.05) and capillary diameters (+0.63 +/- 0.15 micron; P < 0.05).

Analysis of Variance↗

PubMed1994

Effects of chronic normovolemic anemia on gastric microcirculation and ethanol-induced gastric damage in rats.

The effects of chronic normovolemic anemia on gastric microcirculation and gastric mucosal susceptibility to ethanol-induced gastric damage were investigated in anesthetized rats. Blood exchange by a plasma expander during four consecutive days rendered the animals anemic with a 34% decrease in the baseline hematocrit but without affecting blood volume. Chronic anemia induced a decrease in whole blood viscosity, an increase in gastric mucosal blood flow measured by hydrogen gas clearance, a decrease in gastric vascular resistance, and a decrease in gastric hemoglobin content without changes in the gastric oxygen content, the latter two parameters being measured by reflectance spectrophotometry. Gastric mucosal blood flow was lowered by intragastric administration of 100% ethanol in both anemic and control rats, but the final blood flow was significantly higher in anemic than in control animals. Macroscopic gastric damage induced by ethanol administration was significantly lower in anemic than in control rats. We conclude that chronic normovolemic anemia increases gastric mucosal blood flow and leads a protecting mechanism against gastric mucosal damage induced by absolute ethanol.

Anemia↗

PubMed1994

Preservation of cortical microcirculation after kidney ischemia-reperfusion: value of an iron chelator.

Treatment of suprarenal aneurysms and renal artery reconstructions are both responsible for normothermic ischemia of the kidney (during clamping) followed by reperfusion (declamping). During reflow through an organ undergoing ischemia the production of free radicals can be associated with cell injury and a no-reflow phenomenon characterized by perfusion defects after a period of transient hyperemia. The objectives of this study were to demonstrate the existence of this phenomenon in the kidney undergoing ischemia followed by reperfusion and to test the potential protection afforded by an iron chelator (desferrioxamine) since free radical reactions are catalyzed by iron. Adult New Zealand white rabbits were divided into the following three groups: group A, 15 minutes of ischemia plus 10 minutes of reperfusion; group B, 60 minutes of ischemia plus 10 minutes of reperfusion; and group C, 60 minutes of ischemia plus 10 minutes of reperfusion combined with infusion of desferrioxamine (50 mg/kg). Cortical microcirculation in the kidney was measured by laser Doppler flowmeter before ischemia and 1, 5, and 10 minutes after reperfusion. Vitamin E content was determined in the cortex of the left kidney after 10 minutes of reperfusion and compared with that of the right (control) kidney. After 1 minute of reperfusion the cortical microcirculatory flow was significantly increased in all three groups (reactive hyperemia). In groups A and C blood flow returned to preclamping values after 10 minutes of reperfusion; however, blood flow in group B remained significantly reduced (29.2% +/- 10.5%) after 5 minutes of reperfusion with a further reduction to 48.5% +/- 5.7% after 10 minutes. These findings were correlated with the dosage of vitamin E since the vitamin E content was greatly reduced by 46.7% +/- 7.8% in group B but did not change significantly in groups A and C. This study shows that 60 minutes of normothermic ischemia is followed by a significant reduction in cortical microcirculatory flow (no-reflow phenomenon). Infusion of an iron chelator (desferrioxamine), however, which decreases the intensity of lipid peroxidation induced by the free radicals, preserves the microcirculatory flow.

Animals↗

PubMed1986

Measurements of retinal microcirculation in retinal vessel occlusion before and after treatment.

Blood flow, arterial velocity, and vascular diameter were measured in patients with retinal vessel occlusion before and after treatment, especially after light coagulation. The mean values in the patient group showed significantly reduced blood flow and velocity compared to the normal group. The mean group difference before and after therapy revealed that while there is an increase in blood flow after treatment, the normal value is not reached. Individual patient values indicated both increased and decreased blood flow and velocity after treatment as compared with the values before therapy. There are various stages in microcirculatory disease and the microcirculation also behaves differently after treatment, which could be observed by measurement in vivo of the physiological flow parameters.

Adult↗

PubMed1990

[Reactive changes in the periodontal microcirculation under orthodontic forces].

The influence of intrusive forces on the periodontal microcirculation exerted as conventional through brackets on the teeth is demonstrated with laser Doppler flowmetry. This noninvasive method shows that forces of 0.1 N on the human upper incisor cause a decrease of the periodontal perfusion of 20% which shall regain its initial level after 50-80 seconds. With an intrusive force of 0.5 N the perfusion decreases 42% within two to three seconds, which however shall not even regain its original level after ten minutes. Immobilisation of the teeth and infiltrative anaesthesia with vasoconstrictor were carried out in order to specify these measurements.

Adult↗

PubMed1996

Reflexes of the cutaneous microcirculation in amitriptyline and in fluoxetine treated patients.

Cutaneous microcirculation was investigated in 30 major depressed inpatients receiving either 150 mg amitriptyline (n = 15) or 30 mg fluoxetine (n = 15) as monotherapy, and in 15 normal control subjects matched for age and sex. The laser Doppler flux (LDF) was recorded while resting and under the condition of a sudden deep breath ("inspiratory gasp response"). In normal subjects this autonomic function test caused a marked decrement of LDF signal, which rapidly returned to the baseline value. In both groups of drug treated patients the decrements of LDF signal after a sudden deep breath did not differ from those found in the normal control subjects. However, in the amitriptyline-treated patients the return of LDF-signal to the baseline values was significantly delayed (P = 0.0007), while patients treated with fluoxetine showed the same behaviour as normal subjects. With a discriminant analysis using the results of the inspiratory gasp responses, 100% of the amitriptyline treated patients were correctly classified. Since both groups of depressed patients revealed comparable depression scores, the differences found are probably due to the side effects of amitriptyline. Possible clinical implications of these findings are discussed.

Adult↗

PubMed1995

Direct observation of microcirculation of the basal region of rat gastric mucosa.

We modified and improved techniques for the intravital microscopic observation of the rat gastric microcirculation. The stomach of anesthetized rats was cut along the greater curvature, and the posterior wall of the glandular stomach was fixed in a chamber with the serosal side up and perfused with warmed Tyrode's solution. A portion of the muscularis externa was resected with the serosa to make an observation window. Vascular casts were studied histologically after the injection of Monastral blue B gelatin solution. Vascular casts revealed that most of the microvasculature observed in the window was not located in the submucosa, but in the basal part of the mucosa. Microscopic observation showed that the basal mucosal arterioles branched to form the mucosal capillaries, and the collecting venules from the mucosal surface were seen in cross-sections to drain into the venules located in the basal mucosa, without penetrating the muscularis mucosae. Topical application of acetylcholine (0.03-10 microM) to the window dilated the arterioles, and topical application of epinephrine (0.03-3 microM) constricted them dose-dependently without affecting the collecting venules and the venules. This method made possible the direct observation of the microvasculature in the basal mucosa of the stomach, in which common microvessel characteristics were shown.

Acetylcholine↗

PubMed1996

Single-fibre laser Doppler flowmetry and electromyography for evaluating microcirculation in forearm muscle during static and continuous handgrip contractions.

A technique is described for intramuscular measurement of muscle blood flow in the forearm, by using a 0.5-mm thin optical single-fibre for laser Doppler flowmetry (LDF) inserted percutaneously. Continuous recordings were performed of the brachioradial muscle during an 11-min series of alternating 1-min periods of increased static contraction and rest determined by an electronic handgrip forcemeter and surface electromyography (EMG) of the muscle. Stepwise increased handgrip contractions were performed at 10%, 20%, 30%, 40% and 50% maximal voluntary contraction (MVC). This was followed by a similar series of continuous contractions. Finally, an endurance test was performed with a handgrip force of 50% MVC maintained for as long as possible. A group of ten healthy men of different ages was studied. Signal processing was done on line by computer. Successive increases in rootmean square (rms)-EMG and a fall in the mean power frequency (MPF) of the EMG spectrum occurred during the series of static contractions, which evoked perceived local fatigue in the forearm. Muscle blood flow recorded simultaneously showed no change from resting level during contractions at 10%, 20% and 30% MVC, while at 40% and 50% MVC mean increases of 150% and 200% were recorded. Blood flows measured during the rest periods showed large variability with no significant changes. This was also found after continuous contractions of the same intensities. The endurance time was 1.2-3.5 min (mean 2.4 min). Muscle blood flow showed mean increases of 214%, 256% and 229% of resting level each minute of the maintained contraction. Nevertheless, EMG signs of local fatigue developed, such as a rise in rms-EMG and a fall in MPF, and the subject experienced local fatigue. To conclude, this technique of percutaneous, continuous LDF recorded, at high sensitivity, the microcirculation at different fluxes and EMG-defined muscle activity.

Adult↗

PubMedDate not supplied

Whitaker Lecture 1996: microcirculation, biomedical engineering, and artificial blood.

The development of artificial blood requires the understanding of how blood behaves at the level of the microcirculation. A number of measuring systems have recently become available that allow analysis of the transport properties of blood and the microvessels in terms of pressure, flow, the dynamics of their diameter changes, and the rate and manner of oxygen delivery. Findings from this technology have led to the development of an analytical framework with which to assess the consequences of altering the physical properties of blood and to verify quantitatively theoretical predictions. Results show that blood viscosity and oxygen-carrying capacity are directly related, and must be jointly modified in a prescribed manner to maintain tissue oxygen delivery. The use of optical techniques to assess flow and oxygen delivery in experimental animal models show that the consumption of oxygen by the microvessel wall is an important determinant of tissue oxygenation. Furthermore, the viscosity of blood and/or the mixture of blood and an artificial substitute must achieve a viscosity that is close to normal. Low blood viscosity is not necessarily beneficial, unless blood flow velocity rises to maintain the shear stress at the wall needed for the generation of local vasodilators. Manipulating physical properties of currently available modified hemoglobins by mixing them with conventional plasma expanders yield fluids that may provide optimal blood replacements.

Biomedical Engineering↗

PubMedDate not supplied

Simulation of intraluminal gas transport processes in the microcirculation.

Intraluminal resistance to gas transport between the microcirculation and tissue was neglected for a half-century following the early work of Krogh. In recent years it has come to be understood that this neglect is seriously in error. This paper reviews the background for the long period of misdirection, and progress in placing the simulation of gas transport processes on a more accurate, quantitative basis.

Acid-Base Equilibrium↗

PubMed1989

Effects of a newly synthesized pancreatic protease inhibitor (PATM) on pancreatic microcirculation in experimental acute pancreatitis.

Pancreatic inschemia, especially due to pancreatic microcirculation disturbance, has been considered to trigger and aggravate acute pancreatitis. In this work experimental acute pancreatitis was produced by autologous bile and trypsin in mongrel dogs to study the time-course changes in systemic and local hemodynamics in association with disease progress. In addition, the effects of a new synthetic pancreatic protease inhibitor (PATM, 3 mg/kg/hr, i.v.) on systemic and local circulation were examined. In animals with untreated pancreatitis the mean baseline pancreatic microflow was 55.6 +/- 17.0 ml/min/100g before the onset of pancreatitis and this decreased by 22% and 52% at 1 hr and 5 hr, respectively. The femoral arterial pressure and cardiac index also decreased during the 5 hr experiment at period in comparison with the respective preoperative levels. The portal venous flow showed a sharp reduction immediately after the onset of pancreatitis, staying at a low level thereafter. The pancreatic microflow was significantly improved by PATM treatment for the first 60 min and the portal venous flow for the first 120 min. PATM treatment prevented the decrease in femoral arterial pressure, although it failed to exert any appreciable effect upon the cardiac index. These findings suggest that intravenous administration of PATM might be of value for improving the pancreatic microflow and portal venous flow, at least in the early stage of experimental acute pancreatitis in dogs.

Acute Disease↗

PubMed1991

[Dopaminergic effect of anisodamine on the microcirculation of the hydronephrotic kidney of rats].

Anisodamine is an alkaloid extracted from the Tibetan plant "Anisodus tanguticus". Since 1965 it has been used in China for the treatment of shock but the mechanisms of its action are not fully known. The present study was performed to determine the effect of anisodamine on the renal microcirculation and to examine the underlying mechanism of its actions. The addition of anisodamine (10(-8) M to 10(-3) M) to the kidney bath resulted in a significant and dose dependent dilation of all preglomerular vessels. The maximal dilation (about 30% dilation) was found in the proximal interlobular artery. In contrast to preglomerular vessels anisodamine caused constriction of postglomerular vessels. The glomerular blood flow increased by about 50% at anisodamine concentration of 10(-3) M. Haloperidol, a dopamine receptor antagonist could abolish the renal vascular effect of anisodamine. It is suggested that anisodamine could improve renal function by the dilation of preglomerular vessels in combination with the constriction of postglomerular vessels, and the effect of anisodamine may be mediated by activation of the dopaminergic system.

Animals↗

PubMed1997

[Microcirculation and hemostasis in inflammatory processes. Modulation by administration of physiologic protease inhibitors as a therapeutic approach].

BACKGROUND: The course of an inflammatory process is based upon complex interactions between the vessel wall and the humoral or cellular compounds of the vascular content as a consequence of a defense reaction. There are no substantial differences between the pathophysiology of local or of whole body inflammation on the molecular and cellular level. Sepsis, which is clinically regarded as a systemic inflammatory process requires the broad therapeutical spectrum of nowaday intensive care medicine, but still has a high mortality. The pathophysiology and clinical examples for both systemic and local inflammatory reactions are presented in this paper. Thereby, similar interactions between the vascular endothelium, the mediator systems to which the hemostatic system has to be considered as a part of, and the microcirculation remain in the foreground at first. Based on that, the use of polyvalent protease inhibitors in the therapy of local or systemic inflammatory reactions of different origin will be discussed. The spotlight falls on physiological inhibitors of the hemostatic and complement system, antithrombin III and C1-esterase inhibitor, which may have a regulatory function within these systems because of their multiple targets. CONCLUSION: The possibility of an adjuvant therapy of local or generalized inflammatory processes with physiologic protease inhibitors seems to be very promising. Nevertheless, at yet the substantial mechanisms of action are not fully understood.

Antithrombin III↗

PubMed1998

[Microcirculation of kidney and skin during left ventricular assisted circulation--comparative studies of pulsatile and nonpulsatile assists].

We examined microcirculation of the kidney and skin over a six-hour period in an acute myocardial infarction model in pigs. The outflow cannula was placed in the ascending aorta, the inflow cannula was placed the in left atrium, and a pump was connected to each (pulsatile group, Zeon Medical pneumatic pump; nonpulsatile group, Nikkiso HPM-15). Items examined included the regional blood flow of the cortex and medulla in the kidney and skin, renal and carotid arterial flow, arterial ketone body ratio (AKBR), lactate/pyruvic acid (L/P), BUN, creatinine, and beta 2-microglobulin. After the experimental study, the major organs were removed and a pathological study was performed. The mean aortic pressure after the assist could be maintained at about 100 mmHg. There were no significant differences between the two groups in mean aortic pressure and total cardiac output. Under assisted circulation, the pulse pressure was maintained at about 15 mmHg in the nonpulsatile group and about 40 mmHg in the pulsatile group. After the assist, there were no significant differences in the carotid arterial blood flow between the two groups. However, there were significant differences between the two groups in the renal arterial, renal cortical, and regional skin blood flows. In the laboratory data, there were significant differences between the two groups in AKBR, L/P, and beta 2-microglobulin. Pathological findings on the kidney in the nonpulsatile group showed expansion of the proximal tubes, retention of red blood cells, and expansion of blood capillaries within the glomerulus. On the other hand, the pulsatile group showed almost normal formation. In the lungs, the nonpulsatile group showed edematous change in the air cells and the pulsatile group showed almost normal formation. The results of the previous and current study indicated that the pulsatile assist produced superior circulation in the kidney and peripheral organs and superior cellular metabolism in the early treatment of acute left cardiac failure. On the other hand, nonpulsatile assisted circulation was found to be ineffective in maintaining the circulation in the body, and to be potentially capable of causing irreversible damage of major organs if continuous for more than three hours. The results also indicated that pulsatility was necessary to maintain normal circulation in the peripheral organs and cellular metabolism in the early treatment of acute left cardiac failure.

Animals↗

PubMed2005

[Coronary microcirculation. Pathophysiology, clinical relevance, and importance for regenerative therapy after myocardial infarction].

The coronary microcirculation does not only control perfusion of the myocardium, but also plays an important role for the manifestation of ischemic heart disease throughout all stages of the disease. Risk factors for coronary artery disease are associated with a reduced endothelium-dependent blood flow regulation, which not only may aggravate myocardial ischemia but also determines blood flow-induced shear stress exposed to the vascular wall, modulating the vascular milieu (e. g., by controlling nitric oxide bioactivity) and thereby altering progression of atherosclerosis in conductance vessels. Furthermore, generally impaired microvascular function is predictive of cardiovascular events, e. g., after percutaneous coronary interventions or after an acute myocardial infarction. In the latter case, thrombotic embolism from ruptured plaques in the conductance vessels as well as inflammation and reperfusion injury are the essential components of the microvascular disorder. Interestingly, therapeutic strategies which improve microvascular dysfunction, such as statins in stable coronary artery disease or glycoprotein IIb/IIIa inhibitors during acute myocardial infarction, are associated with an improved long-term prognosis. These facts give promise for new therapeutic principles: experimental data demonstrate, that the therapeutic application of stem or progenitor cells after an acute myocardial infarction induces growth of new microvessels (neovascularization) and thereby improves microvascular perfusion, which may favorably alter infarct expansion and remodeling. First clinical data, demonstrating indeed an improved coronary blood flow regulation after progenitor cell therapy in patients with ischemic heart disease, have to be established by further clinical trials.

Coronary Circulation↗

PubMed2005

[Vasopressin and terlipressin in sepsis and systemic inflammatory response syndrome. Effects on microcirculation, oxygen transport, metabolism and organ function].

Vasopressin and terlipressin are increasingly used as alternative non-adrenergic vasopressors for hemodynamic support of septic patients with arterial hypotension. Despite excellent vasopressive effects, vasopressin analogues may potentially impair macro-hemodynamics, oxygen transport and microvascular blood flow. Due to those unwanted side-effects, vasopressin and terlipressin may potentially compromise organ function and possibly foster the development of multiple organ failure. This review article discusses the results of clinical and experimental studies to judge the effects of vasopressin and terlipressin on microcirculation, oxygen supply, metabolism and organ function in patients with sepsis or systemic inflammatory response syndrome (SIRS). Although vasopressin analogues are emerging as promising alternatives to treat catecholamine-refractory hypotension, there is no evidence that vasopressin receptor agonists improve outcome. To date, vasopressin and terlipressin can, therefore, not be recommended for routine clinical use.

Animals↗

PubMed1997

[Perfusion changes in hemodilution. The effect of extensive isovolemic hemodilution with gelatin and hydroxyethylstarch solutions on cerebral blood flow velocity and cutaneous microcirculation in humans].

OBJECTIVE: Quantifying the influence of extreme isovolemic hemodilution (NH) with different colloids on cerebral blood flow velocities (transcranial Doppler sonography) and cutaneous microcirculatory blood flow (laser Doppler flowmetry) in healthy, non-premedicated volunteers was the aim of this study. METHODS: In seven volunteers (randomized cross-over design) 20 ml/kg blood was withdrawn within 30 min and simultaneously replaced with 6% hydroxyethyl starch (200,000/0.5, HES) or 3% gelatin (GEL). Thirty minutes later, the autologous blood was retransfused (RT) within 30 min. Due to a severe allergic reaction to gelatin in one volunteer, only 6 GEL-NH were evaluated. Recorded parameters were: mean blood flow velocities (Vm-MCA) as well as the pulsatility index (PI) and the resistance index (RI) over the middle cerebral artery. In addition laser Doppler flux (FLUX), cell velocity (SPEED), mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb) and hematocrit (Hc) were monitored. RESULTS: NH resulted in a withdrawal volume of 1498 +/- 85 ml (HES) and 1493 +/- 95 ml (GEL), (mean +/- SD) and induced a decrease in hemoglobin from 40.9 to 29.0% (HES) and from 39.8 to 30.0% (GEL). RT increased Hc to 34.2% (HES) and 34.5% (GEL). MAP and HR showed no significant alterations in both groups. Following NH, Vm-MCA rose almost the same way in either case (26% HES), 21% (GEL), but decreased continuously again during RT. After completing RT, only in the HES group Vm-MCA still remained higher than baseline values (14% HES, only 3% GEL). Similar inverse regression lines were found for the two groups between Hc and Vm-MCA: [Vm-MCAHES (cm/s) = -1.27 x Hc + 110.9; r = 0.98, P < 0.001 and Vm-MCAGEL (cm/s) = -1.32 x Hc + 110.9; r = 0.91, P < 0.001]. Furthermore, as a result of NH, FLUX and SPEED increased about 61% and 38% in the HES group and remained on higher values in comparison with starting positions (21% FLUX, 13% SPEED). However, the results in the GEL group were of a different kind: FLUX and SPEED increased stupendously to 291% and 114% combined with NH, but both were reduced by RT on a large scale (39 and 27% below baseline values). Whereas RI showed no group differences, there was a remarkable drop in PI during RT (17% HES, 12% GEL). CONCLUSION: The two plasma expanders studied show a close inverse correlation between the alterations of blood flow velocities in the middle cerebral artery and systemic hemoglobin and hematocrit values. In both groups the change in blood flow velocities is comparable. For the first time the results of relative changes in blood flow velocities following hemodilution and retransfusion in healthy volunteers are described that correspond closely by relative cerebral blood flow alterations found in animal studies as well. Moreover, a non-linear correlation of cutaneous microcirculation was shown by means of HES, but also by GEL. Obviously, there was the GEL group to be responsible for pronounced differences in cutaneous circulation.

Adult↗