Microcirculation, endothelium, and lymphatics最新文献

The arterially-derived capillaries of the eel rete mirabile are heavily invested with highly arborized pericytes. By perfusing vasoactive agents through these capillaries, measuring changes in outflow volume and analyzing alterations in capillary and pericyte morphology a set of vasoactive agent-correlated changes were quantified. Morphometric analysis of the capillary ultrastructure revealed that alterations in flow and appearance were associated with changes in the extension of pericyte processes. These responses of the arterial pericytes to the vasoactive agents used in this study suggest that pericyte contraction alters the architecture of the arterially-derived capillaries of the rete in a manner which affects their permeability.

Cerebromicrovascular membrane fluidity was studied in two model systems: 1) hepatic encephalopathy and 2) cultured endothelium exposed to free arachidonic acid alone or with H2O2. The membrane fluidity was measured by fluorescence anisotropy using 1, 6-diphenyl-1,3,5-hexatriene as a fluorescent probe. In addition, the effect of arachidonic acid with or without H2O2 on cellular permeability to trypan blue-albumin was investigated in endothelial cultures. The findings indicate that the hepatic encephalopathy and the arachidonic acid treatment of endothelium causes an increase in membrane fluidity. This modulation of endothelial membrane fluidity is not associated with changes in cellular permeability to trypan blue-albumin complex. An increased cellular permeability to trypan blue-albumin complex was seen after endothelial exposure to arachidonic acid and H2O2.

The effects of Atrial Natriuretic Peptide (ANP) on microvascular hemodynamics and macromolecular permselectivity were studied in the hamster cheek pouch under resting conditions and during intravenous renin infusion. Fluorescent intravital microscopy was used to observe arteriolar diameters and to detect escape of fluorescent dextran of 150 K-Daltons (FITC-Dx-150). Microvascular plasma flow was estimated by clearance of 51Cr-EDTA and net macromolecular transport by clearance of FITC-Dx-150. At rest, topical ANP (2-250 ng/ml) had no effect on arteriolar diameter, 51Cr-EDTA clearance, relative vascular conductance (RVC) or FITC-Dx-150 clearance. Infusion of renin (10 mU/Kg/Hr, iv) elevated systemic arterial pressure by 30% and reduced cheek pouch RVC by 26%. During renin infusion, topical ANP (50 ng/ml) produced transient arteriolar vasodilation, and increased 51Cr-EDTA clearance (+35%), RVC (+58%) and FITC-Dx-150 clearance (+54%), without affecting systemic pressure. ANP did not induce venular leakage sites under any condition, but changes in FITC-Dx-150 clearance were highly correlated with changes in 51Cr-EDTA clearance, suggesting that the larger macromolecular escape was due to increases in microvascular blood flow and capillary/post-capillary hydrostatic pressure.

The relationship between blood flow (xenon washout method), edema formation (percent total water content), and the number of polymorphonuclear leukocytes (PMNLs), as measured by the level of the enzyme myeloperoxidase, has been investigated in post-ischemic skeletal muscle of rats. A tourniquet model of temporary, complete ischemia of one hindlimb for 3 or 4 hours was used. Biopsies were taken after 0.5, 5 and 12 hours of reperfusion (6 experimental groups) and from a control group that had received only anesthesia. After 4 hours, but not 3 hours of ischemia there was a restricted blood flow during the early reperfusion phase, the "no-reflow" phenomenon, indicating severe ischemia. There was no significant accumulation of PMNLs in the skeletal muscle nor was there a correlation between the number of PMNLs in the post-ischemic muscle and the restricted bloodflow. With 4 hours of ischemia and 0.5 hours of reperfusion there was a statistically significant, positive correlation between the number of PMNLs and the amount of edema; no such correlation was evident in either of the other groups. These results suggest that PMNLs are not the major cause of reduced bloodflow or of edema in the early reperfusion phase after total ischemia.

We evaluated the total red cell Ca2+ content and the macro- and microrheological determinants in a group of subjects with vascular atherosclerotic disease (VAD). From the results obtained it is evident that, compared to controls, the VAD group presents an alteration of the macro- and microrheological parameters. No difference is evident for the red cell Ca2+ content in normals and in VAD subjects. No relationship is present between total red cell Ca2+ content, VBC (volume blood cells), MEA (mean erythrocyte aggregation) and red cell membrane fluidity expressed as Iex/Im ratio. In contrast to the latter, are the correlation between the red cell Ca2+ content and the degree of polarization obtained with fatty acid probes.

Intra-arterial infusion of a racemic mixture of the beta 2-agonist terbutaline blocks histamine-mediated increases in lymph flow and protein concentration in the canine forelimb. In the current study we have assessed the relative anti-inflammatory potencies of the purified stereoisomers of terbutaline. Infusion of histamine (4 micrograms base/min) increased lymph flow, protein concentration and protein transport. The intra-arterial infusion of 1-terbutaline (1 microgram/min) significantly decreased forelimb arterial pressures and prevented any changes in lymph parameters due to subsequent histamine infusion. Intra-arterial infusion of d-terbutaline (1 microgram/min) did not significantly affect forelimb vascular pressures but subsequent to histamine administration, lymph parameters increased similar to that seen with histamine alone. Infusion of a high dose of d-terbutaline (100 micrograms/min) slightly decreased forelimb arterial pressures but failed to inhibit histamine-mediated increases in lymph parameters. Infusion of 1-terbutaline alone (1 microgram/min) significantly decreased forelimb arterial pressures, lymph flow and protein transport and slightly but significantly increased lymph protein concentration. These data indicate that the beta 2-agonistic and anti-inflammatory properties of terbutaline are confined solely to the levorotatory enantiomer.

Platelets hyperaggregability and hypersecretion fibronectin (Fn) are known to occur in peripheral vascular disease (PVD) and diabetes mellitus (DM) with microangiopathy. To determine whether an increase in platelet membrane bound Fn constitutes to hyperaggregability of platelets, washed platelets from normal subjects and from patients with peripheral vascular disease and patients with diabetes mellitus were examined for the presence of fibronectin (Fn) by means of fluorescein linked antibody to Fn. Platelets from peripheral vascular disease and diabetes mellitus patients tended to aggregate during preparation and apparently exhibited greater fluorescence in platelet "smears" than was observed in smears from controls. In contrast, when washed platelet "smears" were prepared from platelet preparations containing iloprost, an analogue of prostacyclin, platelet aggregates did not form and the 'excess' of fluorescence disappeared from all the three groups. When platelets were stained for Fn fluorescence in suspensions, no fluorescence was observed on the surface of platelets from peripheral vascular disease and diabetes mellitus patients or controls. On stimulation with thrombin washed platelet suspension showed fluorescence for Fn. Platelet activation leads to Fn appearing on platelet surface but this effect cannot be quantified by optical fluorescence microscopy.

The objective of this study was to determine if and to what extent a veno-arteriolar reflex is responsible for the adjustments in regional and capillary blood flows that occur in response to gravitational stress in the human finger. Nine male subjects 20 to 40 years of age consented to have regional cutaneous blood flow measured in the index finger via a laser Doppler flowmeter (LDF) and blood cell velocity (CBV) measured in individual nailfold capillaries via video microscopy while placing the hand 20 then 40 cm below the heart and while a pneumatic cuff placed around the wrist was inflated to pressures of 20, 40 than 60 mm Hg. Both lowering the hand and selective elevation of venous pressure elicited significant decreases in LDF and CBV (P less than 0.03). The flow reductions that occurred with lowering the hand 20 cm below the heart were significantly greater (P less than 0.05) for both LDF and CBV when compared to cuff pressure elevation of 27 cm H2O (20 mm Hg), and significantly greater (P less than 0.095) for LDF in matching the 40 cm below the heart position to data obtained at a cuff pressure of 57 cm H2O (40 mm Hg). Analyzing the flow responses relative to precapillary perfusion pressure (arterial pressure - estimated capillary pressure) indicated the reductions in LDF and CBV that occurred in response to cuff pressure elevation were a passive effect of the increase in venous pressure itself. These results indicate that the reductions in regional and capillary blood flow that occur in response to gravitational stress in the fingers are due to myogenic vasoconstriction of arterioles secondary to a rise in arterial pressure and that a veno-arteriolar reflex mechanism is not operative in this region of the cutaneous circulation.

In the present study we examined the microvascular actions of endothelin (ET-1) in rat cremaster arterioles. Pentobarbital (35 mg/kg) anesthetized, five to six week old rats were prepared for in vivo observation and measurement of microvascular control dimensions and changes in diameter, in response to the topical administration of ET-1 (1 x 10(-11) to 5 x 10(-10) M). The effects of ET-1 were determined before and after the administration, by suffusion upon the cremaster muscle, of either indomethacin (IND, 10 micrograms/ml) or methylene blue (MB, 5 microM). Third order arterioles; 13-25 microns in diameter, were selected for study. The administration of ET-1 evoked a biphasic response of cremaster arterioles, an initial small, fleeting increase in diameter (14 to 26%) followed by a dose-dependent, longer lasting decrease in diameter (20 to 77%). The administration of either MB or IND had no effect on the arteriolar dilator and constrictor responses to ET-1. These results suggest that ET-1 is more potent a constrictor than dilator agent in this vascular bed and that the dilator component of the response is not mediated by either prostaglandins or EDRF. By virtue of its actions and potency, we conclude that ET may be an important factor in the regulation of vascular tone and local blood flow.

Chicago sky blue, also known as Niagara sky blue, is a vital dye that can successfully be used as an intravascular energy absorbing target for the light from a helium-neon (HeNe) laser. The result of this light/dye interaction is endothelium damage which can be controlled by adjusting the duration of the laser exposure and the amount of dye injected intravenously. The endothelial damage probably is the result of the heat generated by the dyes absorption of energy at the interface between plasma and endothelium. The most minimal damage resulted in selective loss of the dilation normally produced by acetylcholine and bradykinin, two endothelium dependent dilators. The dilation produced by sodium nitroprusside, a dilator acting directly on vascular smooth muscle, was preserved. More severe injury (i.e. more prolonged exposure to light and/or more dye, resulted in local platelet aggregation at the site of laser impact.