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PubMed1998

Intravital microscopic investigation of xenogeneic microcirculation and impact of complement depletion by cobra venom factor.

Discordant xenografts are hyperacutely rejected within minutes. Disturbances in the microcirculation are considered to be the central mechanisms of hyperacute xenogeneic rejection (HXR). In this study intravital fluorescence microscopy was applied to investigate the dynamics of microcirculatory alterations in a setting in which HXR was inhibited by complement (C) depletion. Blood flow was measured as rat livers were perfused with isogeneic rat or xenogeneic human blood to assess the pattern of either physiological isogeneic hemoperfusion or in the course of HXR. Next, the complement system of the perfusate was inactivated by cobra venom factor (CVF) in order to inhibit HXR. Liver sinusoids of the isogeneic group were homogeneously perfused (sinusoidal perfusion rate 93.6+/-0.3%), whereas in the xenogeneic group the sinusoidal perfusion rate dropped to 67.1+/-3%. The perfusion in the periportal zone of an acinus was significantly lower ( 59.0+/-3.3%) than in the pericentral zone (76.2+/-3.1%). Treatment with CVF improved the sinusoidal perfusion to a value of 85.6+/-2.3%, physiological perfusion, however could not be reached. In contrast to the isogeneic group, massive white blood cell (WBC) and platelet accumulation was found in the xenogeneic group, especially in the terminal portal vessels and in the periportal zone of liver acini. WBC and platelet counts show that the adherence of these cells appears rapidly in the first 5 min after reperfusion as firm adherence. CVF was not able to inhibit WBC and platelet accumulation, indicating that WBC endothelial interactions do not require an intact complement system. Bile flow, a parameter of liver function, decreased only slightly during isogeneic perfusion. The addition of CVF to the rat blood reduced the bile flow to one half of the untreated isogeneic flow, indicating a hepatotoxic side-effect of CVF. In xenogeneic perfusion the bile flow dropped to 62.6% and with the addition of CVF to 37.5% in the first 15 min after reperfusion. The bile flow of the CVF treated groups recovered during the perfusion but could not reach isogeneic values.

Acute Disease↗

PubMed1979

Effects of enflurane and halothane on the microcirculation.

Experiments have been carried out on the microvessels of the mesocaecum of Wistar rats exposed to equipotent doses of either halothane or enflurane. Parameters for evaluating microcirculation included venular flow, capillary flow, vasomotricity of precapillary sphincters and response to norepinephrine. Venular and capillary flow underwent relatively small modifications in both groups, but sensitivity to norepinephrine was increased in the halothane-treated rats and decreased in the enflurane-treated group. Although these variations were of a limited degree, the reduced sensitivity to norepinephrine in the enflurane group may express a certain degree of protection against tissue ischemia.

Anesthesia, Inhalation↗

PubMed1991

Effects of diltiazem on postischaemic renal cortical microcirculation in the pig.

Diltiazem--a calcium entry blocker--was tested in a porcine model under continuous chlormethiazole-pancuronium anaesthesia as protection against renal failure following 60 min of renal ischaemia. Fourteen pigs were randomly allocated to one experimental (diltiazem and ischaemia) and one control group (only ischaemia) (n = 7 in each). Diltiazem was administered as a continuous intravenous infusion started before the ischaemic insult. In two additional animals diltiazem was given but ischemia was not induced. The postischaemic renal cortical microcirculation was simultaneously investigated in four different regions in the left kidney during the first 4 h of reperfusion. Laser Doppler flowmetry (LDF) was performed in two different regions and measurement of tissue oxygenation was done in two other regions. In the two animals treated with diltiazem without ischaemia, only minor variations in central haemodynamic and renal microcirculatory parameters were evident. In the control group (ischaemia), superficial renal cortical blood flow (Qsrc) decreased from 49 +/- 11 (s.d.) arbitrary units at baseline to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1991

Postischaemic renal cortical microcirculation and tissue oxygenation in the pig.

Porcine and human renal physiology are similar in important aspects. Renal cortical microcirculation and its relation to inulin clearance (CIn) was therefore studied before and after renal ischaemia in 28 pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The anaesthesia used provided essential stability in central haemodynamics. The animals were studied for 90 min of reperfusion following 0, 30 or 60 min of renal ischaemia. Twelve of the animals (four were subjected to each duration of ischemia) were also studied 18 h after start of reperfusion. Regional blood flow in the superficial renal cortex was measured by laser Doppler flowmetry (LDF), and tissue oxygenation (PtO2) by surface microelectrode technique. These techniques allow continuous or repeated measurements. During the first 90 min of reperfusion, superficial renal cortical blood flow measured by LDF (Qsrc) underwent considerable temporal variation which followed a certain pattern. Thus, when the renal arterial blood flow was restored after ischaemia, we observed an instant peak in Qsrc followed by a decreasing flow until a minimum value (Qmin) was reached between 3 and 9 min after start of reperfusion (tQmin). Thereafter, Qsrc increased until a maximal value (Qmax) was reached between 11 and 64 min after start of reperfusion (tQmax). The parameters tQmin and tQmax were related to inulin clearance 18 h after start of reperfusion (P less than 0.05 and P less than 0.01, respectively). Thus, it might be possible soon after start of reperfusion--to evaluate the severity of ischaemic damage. This could be useful in the evaluation of different prophylactic strategies, since the full extent of the ischaemic damage, as assessed by clearance determinations, cannot be established until hours later.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

PubMed1997

In vivo effects of halothane, enflurane, and isoflurane on hepatic sinusoidal microcirculation.

BACKGROUND: It has been proposed that halogenated anaesthetics interfere with the endothelium-dependent circulatory control by attenuating the effects of endothelium-derived relaxing factor (EDRF/NO). This study was designed to determine whether or not volatile anaesthetics in vivo influence the microvascular tone in hepatic sinusoids. METHODS: Using epifluorescence videomicroscopy, we compared the effects of the volatile anaesthetics halothane, enflurane, and isoflurane on hepatic microcirculation halothane, enflurane, and Animals were initially anaesthetized with pentobarbitone (50 mg.kg-1 i.p.) to allow instrumentation and laparotomy and were randomly allocated to one of 4 groups (n = 5-6 each) to receive either a supplementary dose of i.v. pentobarbitone (25 mg.kg-1; control group) or 0.75 MAC halothane, enflurane or isoflurane (1.5 MAC.h). RESULTS: Halothane decreased significantly the volumetric blood flow as compared with isoflurane (P < 0.05) or pentobarbitone controls (P < 0.05). The decrease in sinusoidal blood flow caused by halothane was largely attributable to a decrease in sinusoidal diameter (P < 0.05), while red blood cells velocity remained unchanged. Isoflurane led to a significant decrease in sinusoidal width compared with controls (P < 0.05) but an increase in red cell velocity offset the effect of sinusoidal narrowing of volumetric blood flow, while enflurane had no significant effect on any of the measured parameters. CONCLUSION: This study provides the first direct evidence that the volatile anaesthetics halothane and isoflurane in vivo shift the hepatic microvascular tone toward a more constricted state; however, flow velocity is enhanced with isoflurane, offsetting this effect. As a result the volumetric flow is at least affected by isoflurane, then enflurane and most significantly by halothane. Furthermore, our data are consistent with the concept that volatile anaesthetics in clinically relevant concentrations may influence the balance between endothelium-derived vasoactive factors which control microvascular tone.

Anesthetics, Inhalation↗

PubMed2005

Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation.

BACKGROUND: Sufficient cardiac pre-load for maintaining adequate cardiac output is a major goal in the treatment of critically ill patients. We studied the effects of increasing cardiac output by fluid loading on the indocyanine green plasma disappearance rate (ICG-PDR) and gastric mucosal regional CO2 tension (PRco2) as an indicator of splanchnic microcirculation. METHODS: With approval by our ethics committee and written consent, we studied post-operatively 12 patients (1 female, 11 males; 66 +/- 13 years) with elective coronary artery bypass grafting (n = 10) or aortic valve replacement (n = 2). All patients had received pulmonary artery and left atrial catheterization previously for clinical indications. Cardiac output and filling pressures were measured immediately after intensive care unit (ICU) admission and 1 h after the beginning of fluid loading. RESULTS: Overall, 630 +/- 130 ml of 6% hydroxyethylstarch (130 kDa) was infused with the splanchnic perfusion pressure remaining constant. Norepinephrine and epinephrine dosages were unchanged. The cardiac index increased significantly from 2.8 +/- 0.7 to 3.5 +/- 0.6 l/min/m2 and the stroke volume index from 30 +/- 7 to 38 +/- 8 ml/m2. ICG-PDR showed no significant change, i.e. from 21.2 +/- 6.5 to 21.6 +/- 6.5%/min. Gastric mucosal PRco2 and the Pco2 gap (difference between regional and end-tidal CO2 tension) were constant, i.e. changed from 5.1 +/- 0.8 to 5.5 +/- 1.1 kPa and from 0.9 +/- 0.5 to 1.0 +/- 0.7 kPa, respectively. CONCLUSION: Increasing cardiac output to supranormal values by fluid loading is not associated with a significant change in ICG-PDR or gastric mucosal PRco2.

APACHE↗

PubMedDate not supplied

Disturbance of peripheral microcirculation by LHRH-agonists. II.

It could be demonstrated with the aid of a cheek pouch model of the hamster that the LHRH-agonist lutrelin (Wyeth, WY 40972) caused disturbances of microcirculation within minutes, for example constriction of the arterioles and venules, reduction in capillary density and increased permeability, effects which were not reversible within the observation period (1 h) and could not be antagonized by the cyclooxygenase inhibitor indomethacin. Likewise, the lutrelin-induced accumulation of leucocytes in the capillaries of the testes of the rat could not be prevented within 6 hours after administration of indomethacin, whereas the harmful effect of lutrelin on the germinal epithelium could be antagonized by indomethacin within 24 hours. A biphasal course is assumed, characterised by an acute non-prostaglandin-dependent phase and a second prostaglandin-dependent phase, which causes the definitive damage to the testis of the rat.

Animals↗

PubMed1992

Potassium channel activation improves blood flow pattern of conscious rats in cutaneous microcirculation.

1. A dose-dependent mean arterial blood pressure reduction (tailcuff method) to an intravenously administered potassium channel activator (22 or 24 micrograms/kg bw) was found in conscious rats. 2. Intravital microscopic analysis of skin microcirculation in conscious rats was performed with respect to erythrocyte flow velocity and diameters of capillaries. There was a dose-dependent increase of erythrocyte flow velocity; diameters of capillaries were dilated following a dosage of 6 and 12 micrograms/kg bw, but constricted following a dosage of 24 micrograms/kg bw. 3. Frequency distributions of velocity ranges in capillaries under observation (real time video recordings) proved that the increase of microvascular perfusion is manifested by a shift of maximal values to increasing velocity ranges. 4. It is concluded that potassium channel activation plays an important role in the local regulation of perfusion on the peripheral circulation.

Animals↗

PubMed1985

Ultrastructure of microcirculation in renal grafts in patients with acute or chronic rejections.

Using electron microscopy, we studied the renal microcirculation in 31 biopsied specimens from 24 transplants in patients with acute or chronic rejection. Endothelial damage was followed by extensive denudation and platelet attachment, fibrin deposition, focal or whole cytoplasmolysis, rarefaction necrosis of the medial smooth muscle cells, with or without the attachment of inflammatory cells. Medial smooth muscle cells modified by hyperplasia of ergastoplasm, appeared to migrate into the intima and to proliferate there. The endothelium was regenerated with time. Chronic rejection was characterized by "moth-eaten-like" atrophic changes of the medial smooth muscle cells in interlobular arteries with an increase in intercellular spaces with necrotic debris and basement membrane densities. Larger interlobular arteries showed additional mucoid lamellar thickening of the intima, with stenosis. Acute changes in glomerular capillaries included endothelial injury and denudation, thrombotic occlusion and enlargement of subendothelial spaces, apparently due to an increase in permeability. Extensive circumferential mesangial interposition was present in one case of a repeated rejection. Thus, chronicity with various rejections leads to severe luminal narrowing and obstruction in both interlobular arteries and the glomerulus of the grafts.

Endothelium↗

PubMed1986

Hepatic microcirculation of liver cirrhosis studied by corrosion cast/scanning electron microscope examination.

Changes of hepatic microcirculations in 22 autopsy cases of liver cirrhosis were analyzed by corrosion cast/scanning electron microscope (SEM) examination. By this method, the site of arterioportal (A-P) communication in liver cirrhosis was clearly demonstrated between proliferated portal venules and arterial capillaries. The communications were observed at the same site as in the normal liver and were not at larger arterial and portal vein branches. The findings indicate that the increase of A-P communication in liver cirrhosis may be called "capillary shunting". On the basis of the findings, it was postulated that the A-P shunt could not assist in the development of portal hypertension by the transmission of high arterial pressure to the portal vein but could only compensate for decreased portal flow and/or elevate the oxygen concentration in the sinusoids to improve the hypoxic state of the liver parenchyma. It was also demonstrated that the arterial capillarization of the interstitial septa in micronodular wide septal cirrhosis was more prominent than that in macronodular thin septal cirrhosis. A grade of portal vein reduction and compensatory arterialization in a fibrous septum have been regarded as an index to estimate the advancement of liver cirrhosis. Therefore, if alcoholic micronodular cirrhosis could change into macronodular, the process should have occurred at least before the establishment of micronodular wide septal cirrhosis.

Adult↗

PubMed2006

Inflammation-responsive focal constrictors in the mouse ear microcirculation.

In many capillary exchange beds, blood flow is locally regulated by precapillary sphincter-like activity. In this study, we used intravascular tracers and scanning electron microscopy to investigate precapillary blood flow regulation in the mouse ear. Gelatin ink injections of the normal mouse ear demonstrated 6.8 +/- 2.3 axial vessels with a cutoff of detectable tracer in the early branches: 19 +/- 11 focal constrictions were observed along the 1st to 5th order branches of the axial vessels. A perfusion tracer consisting of biotinylated anti-endothelial lectins (Ricinus Communis Agglutin, Lycopersicon Esculentum and Griffonia Simplicifolia) was circulated for 30 min under physiological conditions. Subsequent enzyme histochemistry demonstrated no significant change in distal perfusion or in the number of focal constrictions (P > 0.05). Furthermore, the focal constrictions were unresponsive to vasodilators such as organic nitrates and prostaglandin E1. By contrast, the presence of oxazolone-induced inflammation resulted in significant and sustained vasodilatation for more than 96 h (P > 0.001). Scanning electron microscopy demonstrated discrete constricting bands morphologically distinct from known precapillary sphincters. These results suggest that these previously unappreciated inflammation-responsive precapillary constrictors regulate capillary recruitment in the mouse ear microcirculation.

Animals↗

PubMed1989

Local skin pressure and its effects on skin microcirculation as evaluated by laser-Doppler fluxmetry.

The effect of prolonged local pressure on the skin microcirculation was investigated in the regions of the sacrum and gluteus maximus muscle to determine the aetiology of pressure sores. Thirty normal subjects (15 female, 15 male) were investigated. The subjects were divided into three age groups: group 1, less than or equal to 35 years; group 2, 36-64 years; and group 3, greater than or equal to 65 years. Local pressure was applied with a specially designed instrument according to the sequence 0----110----0----110----0----mmHg. Skin blood cell flux (SBF) was measured with a laser-Doppler technique and the local skin temperature measured with a thermistor. No significant differences were seen in SBF due to sex or age. However, differences between the two areas studied were observed. SBF was maximal over the sacrum at 12-50 mmHg (1.6-6.7 kPa) applied pressure. With further pressure increases, the SBF signal decreased successively, reaching minimum level at 110 mmHg (14.6 kPa), where it was approximately 43% below the initial value. The SBF in the gluteus region showed a more stable pattern, with a maximum SBF at 13-60 mmHg (1.7-8.0 kPa). At both locations, an increased SBF at zero pressure was seen when the pressure was decreased from 110 to 0 mmHg. The skin temperature (n = 7) increased by 2.7 degrees C (range 1.9-3.5 degrees C) over the gluteus and by 1.3 degrees C (range 0.8-2.5 degrees C) over the sacrum. This increase was more rapid over the gluteus region. Concomitantly a temperature-dependent increase of SBF could be seen. It is concluded that a cause for the greater frequency of pressure sores over the sacrum than over the gluteus region is the comparatively poorer regulation of microvascular flow in this area.

Adult↗

PubMed1976

Studies on the relative effects of prostaglandins, bradykinin, 5-hydroxytryptamine and histamine on the synovial microcirculation in dogs.

1 The relative effects of prostaglandins E1, E2, F1alpha, F2alpha, bradykinin, histamine and 5-hydroxytryptamine (5-HT) on the canine synovial microcirculation were investigated using the rate of clearance of radioactive xenon (133Xe) as an index of synovial perfusion. 2 All the compounds tested, except prostaglandin F1alpha, produced a vasodilator effect. The descending order of potency of the active compounds was (i) prostaglandin E1, (ii) prostaglandin E2 and bradykinin, (iii) histamine and 5-HT, (iv) prostaglandin F2alpha. The most potent compound tested, prostaglandin E1 produced an effect in nanogram amounts in each joint. 3 Prostaglandin F2alpha has been reported to have an anti-inflammatory action; however no evidence was found of antagonism of prostaglandin E1 by two dose levels of prostaglandin F2alpha. 4 Preliminary studies showed that threshold doses of prostaglandin E1 did not potentiate the vasodilator action of threshold or sub-threshold doses of bradykinin in the dog synovium.

Animals↗

PubMed1992

Endogenous nitric oxide and sensory neuropeptides interact in the modulation of the rat gastric microcirculation.

1. The effects of depletion of sensory neuropeptides from primary afferent neurones by capsaicin pretreatment, on the changes in resting gastric mucosal blood flow following administration of inhibitors of nitric oxide biosynthesis have been investigated in the pentobarbitone-anaesthetized rat. 2. Bolus administration of the NO-synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.8-12.5 mg kg-1 i.v.), induced a dose-dependent increase in systemic arterial blood pressure (BP) and a reduction in resting mucosal blood flow, as determined by laser Doppler flowmetry. 3. Concurrent administration of L-arginine (300 mg kg-1 i.v.) attenuated the effects of L-NAME (6.25 mg kg-1) on resting mucosal blood flow and BP. The enantiomer, D-NAME (50 mg kg-1 i.v.), which does not inhibit NO biosynthesis, had no effect on either parameter. 4. The fall in mucosal blood flow induced by submaximal doses of L-NAME (0.8-3.2 mg kg-1) was substantially augmented in rats pretreated 2 weeks earlier with capsaicin. 5. The fall in resting mucosal blood flow induced by the less potent NO-synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 1.6-25 mg kg-1 i.v.) was likewise significantly augmented in capsaicin-pretreated rats. 6. Pretreatment (15 min) with indomethacin (5 mg kg-1 i.v.) did not augment further the microvascular actions of L-NAME or L-NMMA in capsaicin-pretreated rats, suggesting the lack of interaction of endogenous prostanoids with these other mediators in regulating local blood flow. The effects of L-NAME on BP were not altered by capsaicin and indomethacin administration.7. These findings indicate that endogenous sensory neuropeptides and NO can interact in the regulation of the gastric microcirculation.

Animals↗

PubMed1993

Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the cat.

1. Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2. The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. 3. Sumatriptan at 5 and 50 micrograms kg-1 had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 micrograms kg-1 of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg-1, elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose. 4. Thus, while a high dose of sumatriptan (500 micrograms kg-1) exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.

Animals↗

PubMedDate not supplied

A new technique to map vulva microcirculation using laser Doppler perfusion imager.

The location of the vulva has had limited technologic progress in the assessment of the skin microcirculation and its application to clinical practice. Our group previously demonstrated increased perfusion in vulvar cancer compared to adjacent uninvolved skin with the laser Doppler flowmetry (LDF). The LDF is severely limited by its low spatial resolution ( approximately 1 mm(2)) and pressure involved in positioning of the probe, which may affect value of the underlying tissue perfusion. Topographic perfusion mapping of the whole vulvar skin using LDF is also time consuming and is not clinically practical. We describe for the first time the application of the novel laser Doppler perfusion imager (LDPI) to map vulvar skin blood flow and give example in two cases with well-defined vulvar pathology-psoriasis and lichen sclerosus with invasive neoplasia-and discuss the potential of LDPI to study vulvar skin blood flow.

Adult↗

PubMed1996

Comparison studies of major organ microcirculations under pulsatile- and nonpulsatile-assisted circulations.

In these comparison studies, we examined changes in major organ microcirculations during circulatory support using pulsatile and nonpulsatile pumps. Acute myocardial infarction was created by left anterior descending (LAD) branch ligation. After the animals in these studies fell into cardiogenic shock, they were supported by mechanical assist devices: a pulsatile ventricular assist device (VAD) in 4 pigs, a nonpulsatile VAD in 4 pigs, and an intraaortic balloon pumping (IABP) plus nonpulsatile VAD in 4 pigs. Each group was supported for 3 h with an identical mean aortic pressure being maintained. As for parameters, the stomach mucosa, liver regional blood flow, stomach mucosal pH, and arterial blood keton body ratio (AKBR) were measured. Both regional blood flow and AKBR increased in the pulsatile group as compared with the nonpulsatile group. There were no differences in the stomach mucosal pH among the 3 groups. These results suggest that pulsatile assist rather than the nonpulsatile assist plays a significant role in the recovery of deteriorated splanchnic organs due to cardiogenic shock.

Animals↗

PubMed1997

Tumor growth in a defined microcirculation.

The fate of human tumor cells deposited in rat uteri was investigated by light microscopy of histological sections, immunohistochemistry, and scanning electron microscopy of microvascular corrosion casts. The human colonic tumor cell line LS 174 T was used as graft since it can be detected by CEA immunohistochemistry, and spayed nude rats (PVG rnu/rnu) were used as hosts, subjected to different hormonal regimens (no exogenous hormones, medroxyprogesterone acetate, 17-beta-estradiol, or the last two regimens in combination). Intrauterine deposition of a suspension of 2 x 10(6) tumor cells resulted in tumor take in 72% (21/29) of the nude rats. Endometrial growth was verified in only three animals (14%, 3/21). Extraendometrial growth, however, was found in all animals with tumor take. These observations suggest that the endometrium is comparatively resistant to growth of xenografted human colonic tumor cells. The tumor microcirculation consisted of new vessels, giving morphological evidence that tumor growth is dependent on angiogenesis and not on invasion of preexisting vessels.

Adenocarcinoma↗