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Biomedical subjects

D W Slaaf

Publications and source records attributed to D W Slaaf.

At least 55 records · Page 3Linked to original sources
PubMed1995

Capillary diameter changes during low perfusion pressure and reactive hyperemia in rabbit skeletal muscle.

Capillary diameter changes were studied in the tenuissimus muscle of 29 urethan-anesthetized New Zealand White rabbits. Capillaries were visualized with transillumination bright-field microscopy (saltwater lens, x 50; resolution approximately 0.3 microns). Median capillary diameter during the control period was 4.4 microns (range 3.2-6.9 microns). Complete aortic occlusion resulted in a reduction of median femoral arterial pressure to 17 mmHg (range 4-22 mmHg). During 2 min of occlusion, capillary diameter decreased by 6%, with greater change on the arteriolar side of the capillary than on the venular side. During reactive hyperemia after release of the occluder, capillary diameter maximally increased by 12% compared with the control period, with a larger response at the arteriolar end of the capillary than at the venular end. Median capillary resistance was estimated to increase by 27% during occlusion and to decrease by 36% during peak reactive hyperemia. The observed diameter changes are compatible with the idea that capillaries change their diameter relative to changes in transmural pressure.

Animals↗
PubMed1994

Involvement of nitric oxide and cyclooxygenase products in photoactivation-induced microvascular occlusion.

Photoactivation of intravascular dyes with high doses of light is a technique used clinically to treat tumors. This procedure results in arteriolar constriction, mast cell degranulation, platelet thrombus formation, and, ultimately, microvascular stasis. In vivo microscopy was utilized in the current study to examine if the endothelial release of prostaglandins and nitric oxide could participate in the microvascular effects of photoactivation. Diameter changes and thrombus formation of arterioles and venules of the cremaster muscle of male Sprague-Dawley rats were quantitated during continuous light activation of intravascular fluorescein isothiocyanate conjugated to bovine serum albumin. Vasoconstriction and thrombus development were assessed separately, using the relationships between the width of the red blood cell column, the inner wall diameter, and the thickness of the plasma layer. Venular photoactivation resulted in thrombus growth which reached 30% of the maximum size by 16.8 +/- 3.71 min and a subsequent growth rate of 6.2 +/- 1.64 microns/min. In arterioles, 30% thrombus growth occurred at 14.0 +/- 2.02 min with a growth rate of 3.0 +/- 0.57 microns/min. Continuous arteriolar photoactivation led to a vasoconstriction of 34.4 +/- 6.87% of the initial vessel diameter. Thirty percent of the maximal constriction occurred after 10.6 +/- 1.26 min of photoactivation. Constriction proceeded at a rate of 3.8 +/- 1.32 microns/min. Topically applied mefenamic acid (a cyclooxygenase inhibitor) and Nw-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) each enhanced both the arteriolar and the venular thrombus growth due to photoactivation. Photoactivation-induced arteriolar constriction was augmented by L-NAME and inhibited by mefenamic acid. These data suggest that the photoactivation of intravascular dyes is accompanied both by the release of nitric oxide, which inhibits thrombus development and arteriolar constriction, and by the release of cyclooxygenase products, which inhibit thrombus growth and induce vasoconstriction. Rats treated with busulfan to induce thrombocytopenia exhibited a 90% decrease in circulating platelets. In these animals, photoactivation caused significantly delayed thrombus growth in arterioles and venules, while arteriolar constriction remained unaltered, suggesting that the vasoconstrictor prostanoid is not of platelet origin.

Amino Acid Oxidoreductases↗
PubMed1994

The effects of 7-hour local hyperglycaemia on forearm macro and microcirculatory blood flow and vascular reactivity in healthy man.

Animal studies suggest that hyperglycaemia directly affects local blood flow and vascular reactivity. We studied the effects of 7 h of local forearm hyperglycaemia, on forearm (muscle) and skin microcirculatory blood flow in 12 healthy men. Furthermore, the effects of this local hyperglycaemia on forearm vasoreactivity to noradrenaline were studied. Using the perfused forearm technique, a local hyperglycaemia of approximately 16 mmol/l was induced by continuous intraarterial infusion of 5% glucose. All subjects received both glucose and placebo (0.9% NaCl) infusions on two different occasions, in random order and blinded for the subjects. Forearm (muscle) blood flow and vascular reactivity to noradrenaline were measured using venous occlusion plethysmography. Skin microcirculatory blood flow was evaluated using intravital capillary microscopy (nutritive blood flow) and laser-Doppler fluxmetry (thermoregulatory blood flow). Measurements were performed at baseline, after 4 h, and after 7 h of intraarterial glucose or placebo infusion. During local glucose infusion there was a slight increase in the levels of insulin, C-peptide, systemic glucose, and blood pressure, compared to the placebo experiments. No differences were observed in forearm blood flow and laser-Doppler flux ratio (infused: contralateral arm), as well as in capillary blood cell velocity between glucose and placebo experiments. Noradrenaline produced similar reductions in forearm blood flow ratio during glucose and placebo experiments. We conclude that in contrast to animal studies, local hyperglycaemia (approximately 16 mmol/l) for 7 h does not affect forearm macro and microcirculatory blood flow or vascular reactivity to noradrenaline in man.

Adult↗
PubMed1994

Reflex sympathetic dystrophy: result of autonomic denervation?

1. To investigate the nature of sympathetic dysfunction in the pathogenesis of reflex sympathetic dystrophy, the microcirculatory vasoconstrictive responses to dependency were investigated in the skin of the hand of 76 reflex sympathetic dystrophy patients with unilateral disease by means of laser Doppler flowmetry (in perfusion units) and capillary microscopy. The patients were divided into three stages according to their perception of skin temperature (stage I in the case of a stationary warmth sensation, stage II in the case of an intermittent warmth and cold sensation, and stage III in the case of a stationary cold sensation). The vasoconstrictive responses were induced by lowering of the affected hand. 2. As compared to controls, the mainly sympathetically mediated vasoconstrictive response at thermoregulatory level of the skin microcirculation, as measured by laser Doppler flowmetry, was attenuated at stage I (1.82 versus 1.41, P < 0.05), stage II (1.82 versus 1.09, P < 0.0001) and stage III (1.82 versus 1.14, P < 0.01), suggesting the involvement of sympathetic denervation at all stages of the reflex sympathetic dystrophy syndrome. This sympathetic denervation may also account for the observed increase in thermoregulatory skin blood flow at stage I as compared to controls (152 versus 81, P < 0.01). 3. Since sympathetic denervation has been reported to cause increased sensitivity of vascular structures to catecholamines, the decrease in thermoregulatory skin blood flow at stages II (54 versus 81, P < 0.05) and III (31 versus 81, P < 0.05), both as compared to controls, may result from hypersensitivity to catecholamines of skin microvessels. 4. The sympathetically independent vasoconstrictive response at the nutritive level of skin microcirculation, as measured by capillary microscopy, was impaired only at stage III as compared to controls (1.04 versus 2.06, P < 0.05). This divergence in microvascular reactivity upon dependency of the nutritive and thermoregulatory subsystems also supports the hypothesis of sympathetic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Diurnal variations in total forearm and skin microcirculatory blood flow in man.

The aim of the present study was to determine diurnal variations in total forearm and skin microcirculatory blood flow in healthy man. At six time points between 08.00 and 18.00 hours was measured: blood pressure, forearm blood flow (FBF; strain gauge plethysmography), skin thermoregulatory blood flow (LDF; laser-Doppler fluxmetry), and skin nutritive blood flow (CBV: Capillary Blood Cell Velocity; intravital capillary microscopy) in 15 healthy, fasting, and resting men. FBF increased gradually from 2.8 in the morning to 4.3 ml 100 ml min-1 in the afternoon (p < 0.001). In contrast, LDF decreased, predominantly in the morning, from 18.3 at 09.00 hours to 13.1 at 12.00 hours and to 12.1 perfusion units at 17.30 hours (p < 0.001). However, performing the same protocol starting in the afternoon resulted in a similar initial decrease in LDF, suggesting an acclimatization phenomenon. Although not statistically significant, the decrease in CBV showed a similar pattern as compared to LDF. Blood pressure did not change. In conclusion, forearm blood flow increased during the day, probably due to diurnal variation in muscle flow. The initial decrease we observed in skin thermoregulatory blood flow is probably not related to diurnal variation but due to long-term acclimatization to the experimental conditions. These data suggest different regulatory mechanisms for the different vascular beds studied. Measurements of forearm blood flow should preferably be performed at the same time of day, and skin microcirculatory haemodynamic measurements should be performed after a standard period of acclimatization.

Adult↗
PubMed1993

Different roles of prostaglandins in thromboembolic processes in arterioles and venules in vivo.

The involvement of prostaglandins in thromboembolic processes, as induced by wall puncture, was studied in rabbit mesenteric arterioles and venules using intravital videomicroscopy. Inhibition of prostaglandin formation with aspirin (100 mg/kg, i.v.) significantly increased in arterioles duration of embolization (from 91 to 200 s) and number of emboli produced (from 4 to 8.5 per vessel), while rate of embolus production was not influenced. In venules, aspirin only influenced embolization rate (a significant decrease from one embolus/14 s to one/23 s). Specific blockade of TXA2-receptors by sulotroban (30 mg/kg, i.v.) only influenced the arteriolar reaction: it significantly decreased embolization duration (from 560 to 218 s) and number of emboli produced (from 23 to 10 emboli per vessel), without affecting embolization rate. These findings indicate that both platelet activating and inhibiting prostaglandins play a more important role in thromboembolism in arterioles than in venules; this suggests a difference in prostaglandin synthetic capacity between arteriolar and venular endothelium.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Influence of dextrans on platelet distribution in arterioles and venules.

Dextrans bind to the surface of platelets, red blood cells and endothelium. We investigated whether a low doses (30 mg/kg IV) of 40-kDa (Dx40), neutral, 500-kDa (Dx500) or sulphated, 500-kDa (Dx500S) dextrans influence platelet distribution in rabbit mesenteric arterioles and venules (diameter 17-33 microns). Intravital fluorescence videomicroscopy was used to visualize platelets labelled in vivo with acridine red. Their concentration distribution determined within a thin optical section about the median vessel plane was expressed relative to the mean concentration in that vessel. In arterioles, Dx500 and Dx500S increased the relative platelet concentration in the centre [radial position (R): 0.0-0.4 R] from 0.60 to 1.07 (P < 0.001) and 1.20 (P < 0.003), and reduced it near the wall (0.8-0.9 R) from 1.59 to 0.93 (P < 0.02) and 0.95 (P < 0.03) respectively. In venules a similar, but non-significant, effect was observed. Dx40 did not change platelet distribution in arterioles, but decreased their concentration in venules in the centre from 1.08 to 0.71 (P < 0.03) and increased it at the wall from 0.89 to 1.27 (P < 0.04). The deformability of red blood cells was unchanged, but their aggregation tendency increased approximately two-fold after Dx500 and Dx500S injection, while Dx40 had no influence. Leucocyte margination in venules did not affect platelet distribution. Dextran injection did not change microvascular flow velocity or plasma viscosity, suggesting that the observed changes in arteriolar platelet distribution were caused by binding of dextran to the surface of platelets and/or red blood cells.

Animals↗
PubMed1993

Peripheral macro- and microcirculation in short-term insulin-dependent diabetes mellitus: the role of prostaglandins in early haemodynamic changes.

To determine whether vasodilator prostaglandins are involved in the peripheral hyperperfusion observed in patients with short-term insulin-dependent diabetes mellitus (IDDM), forearm and skin blood flow were studied before and after cyclooxygenase inhibition. Skin nutritive (CBV: capillary blood-cell velocity) and thermoregulatory (LDF: laser-Doppler fluxmetry), and forearm (muscle) blood flow (FBF) were measured before and after 500 mg acetylsalicylic acid (ASA) infused intravenously in 14 short-term IDDM patients and 22 healthy control subjects. In the IDDM patients, baseline LDF (median: 27 (19-35); interquartile range) vs. 17 (15-23) pu) and FBF (3.4 (2.5-4.1) vs. 2.6 (2.2-2.9) ml 100 ml-1 min-1) were increased, while CBV (0.70 (0.40-1.33) vs. 0.69 (0.41-0.96) mm s-1) was unchanged compared to healthy controls. ASA infusion had similar effects on baseline CBV, LDF, and FBF in patients and controls. In eight of the control subjects the role of prostaglandins in the regulation of basal peripheral blood flow was studied before and after ASA and placebo infusion. The changes in baseline CBV, LDF, and FBF were similar after ASA and placebo infusion in healthy controls. In conclusion, in short-term IDDM patients, increased skin thermoregulatory and forearm (muscle) blood flow are probably not related to vasodilator prostaglandins. Furthermore, prostaglandins are not likely to be involved in regulating basal peripheral blood flow in healthy man.

Adult↗
PubMed1993

Effects of partial plasma exchange transfusion on blood flow velocity in large arteries of arm and leg, and in cerebral arteries in polycythaemic newborn infants.

Continuous wave Doppler velocimetry was performed in brachial, femoral and cerebral arteries in four preterm, four small-for-gestational-age (SGA) and eight appropriate-for-gestational age (AGA) polycythaemic newborns before and at 3 and 24 h after partial plasma exchange transfusion and in 18 matched controls at 3 and 24 h after birth. In peripheral arteries, end-diastolic flow velocity was zero in all eight AGA controls, but only in two of the other infants. Consequently, mean flow velocity and red cell transport in AGA controls were significantly lower than in the other five groups, which did not differ. Partial plasma exchange transfusion did not influence flow velocities and red cell transport in peripheral arteries, but normalized the flow velocities in cerebral arteries in all three subgroups of polycythaemic infants, which were lower than in control infants. Cerebral red cell transport in controls increased significantly between 3 and 24 h, and in polycythaemic infants between 0 and 3 h after partial plasma exchange transfusion. In conclusion, reduction in haematocrit had different effects on blood flow velocity and red cell transport of peripheral and cerebral vessels, suggesting that the increased cerebral blood flow velocity after partial plasma exchange transfusion is not simply due to a reduction in viscosity or oxygen content of the blood. The lower peripheral blood flow velocities in normocythaemic AGA infants as compared to all other groups, suggest that the level of maturity is an important determinant for the capacity to regulate blood flow.

Age Factors↗
PubMed1993

Evidence for a novel angiotensin II receptor involved in angiogenesis in chick embryo chorioallantoic membrane.

Angiotensin II acts as a growth factor in the cardiovascular system and has been implicated in angiogenesis. The existence of at least two types of angiotensin II receptors, the AT1 and the AT2 receptors, has been suggested by ligand binding studies. We used three different AT receptor antagonists to study the receptor mediating angiotensin II-induced angiogenesis in the chorioallantoic membrane (CAM) of the chick embryo. Angiotensin II caused pronounced angiogenesis of pre- and postcapillary vessels of 30-40%. This response could only be blocked by adding the peptidergic AT2 antagonist CGP-42112A. The nonpeptidergic AT2 antagonist PD123319 and AT1 antagonist losartan (DuP 753) were not effective. In addition, we used radioligand binding studies with a range of ligands to define the nature of the receptor. Our results show a high density of specific single class AT receptor with a total number of binding sites of 1,190 fmol/mg protein and an affinity constant for angiotensin II of 2.7 nM. The inhibitory concentrations (IC50) for CGP-42112A, PD 123319 and losartan were 724, > 100,000, and 59,000 nM, respectively. Our studies suggest that these binding sites act as receptors for angiotensin II-induced angiogenesis. Both functional and radioligand binding studies suggest that the receptor is different from the classical mammalian AT1 and AT2 receptors.

Allantois↗
PubMed1993

Long-term effects of recombinant human erythropoietin on macro- and microcirculation in chronic hemodialysis patients.

Recombinant human erythropoietin therapy (ReHuEpo) at short term leads to an increase in systemic vascular resistance and to a decrease in cardiac index and skin microcirculatory flow. Long-term adaptive changes might occur. We studied the effects of ReHuEpo therapy on macrocirculation and skin microcirculation in 8 normotensive and normovolemic hemodialysis patients before and after, respectively, 4 and 14 months of treatment. The reported macrocirculatory changes at short term were at long term not significantly different as compared with the initial values. The mean arterial pressure remained unaltered, as might be explained by the slow correction of the hematocrit and the decrease in cardiac output in all initially long-lasting normotensive patients who were maintained normovolemic. Left ventricular end-diastolic dimensions decreased, and also the left ventricular muscle mass decreased, depending on the initial left ventricular muscle mass. The skin oxygenation improved, whereas the maximal capillary flow decreased both at short- and long-term ReHuEpo treatment. The number of capillaries in the nail fold remained unchanged. However, the percentage of tortuosity decreased significantly during ReHuEpo therapy.

Adult↗
PubMed1992

Assessment of the microcirculation provides additional information in critical limb ischaemia.

Systolic ankle and toe pressure measurements are considered to be the best way of documenting arterial occlusive disease. In the European consensus, chronic critical limb ischaemia is defined as persistent pain with an ankle pressure lower than 50 mmHg. To investigate the possible adjunct value of microcirculatory assessment, capillary microscopy and transcutaneous oximetry were performed in 21 asymptomatic persons (F1), 89 claudicants (F2) and 54 patients with critical limb ischaemia (F3/4). Capillary morphology (diameter, density) and dynamics [red blood cell velocity (RBCV), peak RBCV and time to peak RBCV], as well as transcutaneous oximetry parameters were determined for each Fontaine group and compared with ankle and toe pressure measurements. Despite considerable overlap, ankle and toe pressures were significantly (p less than 0.001) different between F1, F2 and F3/4 patients. Capillary density (p less than 0.05), diameter (p less than 0.05), peak RBCV (p less than 0.05) and time to peak RBCV (p less than 0.01), as well as transcutaneous oximetry parameters (p less than 0.001) were significantly different between all groups and impaired with progression of ischaemia. However, a similar overlap between all groups was observed, except the supine TcpO2 parameter which separated F3/4 patients completely from the other groups. In all patients with critical limb ischaemia, dynamic parameters, such as peak RBCV (p less than 0.01) and time to peak RBCV (p less than 0.001), were significantly lower as compared to non-critically ischaemic patients, irrespective of an ankle pressure below or above a value of 50 mmHg, illustrating the additional value of microcirculatory assessment in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Microvascular reactivity differences between the two legs of patients with unilateral lower limb ischaemia.

Posturally induced microvascular constriction in the skin of the leg is disturbed in severe ischaemia. It is unknown whether this disturbance is of local or central origin and whether the stage of ischaemia at which this disturbance occurs differs when the nutritive and thermoregulatory flow levels are compared. We investigated the effect of posture on the skin microcirculation in 21 patients with unilateral severe ischaemia. The results were compared with those from the contralateral, asymptomatic leg and with results from 11 age-matched controls. Patients were investigated in supine and sitting positions, using capillary microscopy to measure nutritive flow, and laser Doppler fluxmetry (LDF) to measure thermoregulatory flow, of the big toes. In the supine position, capillary flow and LDF were lower in the diseased than in the asymptomatic and control legs. After changing from the supine to the sitting position, capillary perfusion decreased in all three groups, but was most pronounced in the controls. Laser Doppler flux decreased in the controls, but increased in the diseased legs, suggesting disturbed vasoconstriction mechanisms in the deeper skin microvessels. These findings indicate that in severe limb ischaemia, posturally induced microvascular reactivity is sustained at the nutritive level but not at the thermoregulatory level. This disturbed reactivity is considered a local phenomenon, as it is not observed in the contralateral leg.

Adult↗
PubMed1992

Skin blood cell flux in insulin-dependent diabetic subjects in relation to retinopathy or incipient nephropathy.

We studied the relationship of retinal and/or renal microvascular complications and duration of disease with altered finger skin microcirculation in insulin-dependent diabetic (IDDM) subjects. Short-term and long-term IDDM subjects without complications or with proliferative retinopathy or incipient nephropathy were investigated with laser-Doppler fluxmetry. An increased resting flux in skin microcirculation was found in short-term (median: 34 perfusion units, PU) and uncomplicated long-term IDDM subjects (25 PU) as compared with age-matched healthy controls (18 PU), which suggests a generalized dilatation of the microcirculation throughout the body. In long-term IDDM subjects with retinopathy we also observed an increased resting flux (37 PU), but in subjects with incipient nephropathy resting flux was decreased (17 PU) relative to the other diabetic subjects, to a level not different from the healthy control group. Post-occlusive hyperaemic peak flux was decreased in patients with incipient nephropathy relative to the other diabetic patients, which suggests a defect in maximal arteriolar vasodilatation. No differences were found between the groups in the venoarteriolar reflex during venous occlusion. In conclusion, IDDM patients demonstrated increased red blood cell flux. However, with the occurrence of incipient nephropathy the resting flux and the maximal post-occlusive vasodilatation decreased, which suggests that development of nephropathic changes in diabetes is representative of a more generalized alternation of microvascular flow regulation. Local neurogenic microvascular control appears to be unaffected in these patients.

Adult↗
PubMed1992

Concentration profile of blood platelets differs in arterioles and venules.

Platelet distribution was investigated in 21 venules (V) and 10 arterioles (A) of the rabbit mesentery (vessel diam 15-33 microns). Circulating platelets were labeled in vivo with the dye acridine red and observed with fluorescence video microscopy. Only platelets flowing in a thin (5-7 microns) optical section located about the median plane of the vessel were used. The relative position of each platelet, i.e., the distance of its centroid to the left vessel wall divided by the local vessel diameter, was determined. In addition, in 10 venules leukocyte margination was inhibited by intravenous injection of dextran sulfate (500,000 mol wt; 30 mg/kg body wt). The number of platelets per unit volume (i.e., platelet density) relative to the mean density was significantly higher in the vessel center of V (1.04) than of A (0.55; P less than 0.005). In contrast, near the wall this density was significantly higher in A compared with V. Mean values were as follows: at radial position (R) = 0.9-1.0, 0.30 in A and 0.11 in V (P greater than 0.05); at R = 0.8-0.9, 1.63 in A and 0.84 in V (P less than 0.002); at R = 0.7-0.8, 1.60 in A and 1.36 in V (P greater than 0.05); at R = 0.6-0.7, 1.16 in A and 1.60 in V (P less than 0.02); and at R = 0.5-0.6, 0.92 in A and 1.36 in V (P less than 0.02). These differences in platelet distribution between arterioles and venules are not caused by the presence of leukocyte margination in venules.

Animals↗
PubMed1992

Capillary recruitment and pain relief on leg dependency in patients with severe lower limb ischemia.

BACKGROUND: Patients suffering from severe lower limb ischemia may experience pain relief on leg dependency despite the fact that dependency normally results in arteriolar vasoconstriction. To clarify this possible paradox, skin microcirculation of the limb was investigated in 75 patients with different stages of lower limb ischemia and in 12 asymptomatic subjects. METHODS AND RESULTS: Using nailfold capillary video microscopy, red blood cell-perfused capillary density and diameter and red blood cell velocity were assessed in supine and sitting positions. Capillary density increased by changing from the supine to the sitting position, especially in patients with limb-threatening ischemia (showing a 4.5-fold increase versus a 1.5-fold increase in asymptomatic subjects). In subjects without or with mild ischemia, capillary perfusion was two to four times lower in the sitting than in the supine position. In patients with limb-threatening ischemia, perfusion was strongly reduced, being slightly higher in the sitting position. Patients with relief of pain while sitting did not always have a higher capillary perfusion but did have a higher capillary density in the sitting position. CONCLUSIONS: The arteriolar postural vasoconstrictive mechanism at the nutritive level is still intact in subjects without or with mild ischemia but not in patients with severe ischemia. Capillary recruitment rather than disturbed arteriolar vasoconstriction could explain why patients with severe leg ischemia prefer leg dependency.

Adult↗
PubMed1992

Influence of platelet-vessel wall interactions on leukocyte rolling in vivo.

The influence of platelet-vessel wall interactions on leukocyte rolling was investigated in rabbit mesenteric venules (diameter, 21-40 microns) using intravital videomicroscopy. Puncture of the wall with glass micropipettes (tip, 6-8 microns) evoked the formation of a thrombus in all venules. In most vessels, emboli were produced as well. The rolling of leukocytes (i.e., their movement along the vessel wall at a velocity clearly lower than that of the other blood cells) was quantitated simultaneously in vessel segments upstream and downstream from a thrombus up to 10 minutes after puncture. During embolization the number of rolling leukocytes decreased significantly from the upstream to the downstream vessel segment (median decrease, 45%; p less than or equal to 0.001). It was still decreased by approximately 50% after embolization had stopped, indicating that the decrease in leukocyte rolling was not caused by inclusion of leukocytes in the emboli. In venules without embolization, leukocyte rolling did not change systematically, indicating that fluid dynamic changes induced by the thrombus do not influence leukocyte rolling. Inhibition of prostaglandin formation with aspirin (100 mg/kg) almost completely abolished the influence of the thromboembolic reaction on leukocyte rolling, but blockade of thromboxane A2 receptors with sulotroban (30 mg/kg) had no effect. In conclusion, this is the first report on a functional interaction in vivo, at a site of vessel wall injury, between platelets, vascular cells, and leukocytes. The findings suggest that substances produced by activated platelets and/or damaged vascular cells diminish leukocyte rolling. The identity of these substances is not yet clear, but the present study indicates that prostaglandins other than thromboxane A2 are involved.

Animals↗