Microcirculation flow demonstration

Techniques have been developed for study of the renal microcirculation. These techniques have distinct advantages over in vitro endothelial and vascular smooth muscle cell preparations. They allow study of important anatomic and physiologic relationships that are lost in isolated cell systems. For example, the effects of both pressure and flow can be determined and the spatial relahonship between the endothelium and smooth muscle is maintained. These techniques permit functional assessment of the resistance micro-vasculature without destroying vessel integrity while eliminating the confounding influence of undetected circulating, neural and parenchymal factors. The techniques are demonstrated in Table 8. 

Infusions of AmB, intravenously or into the renal artery, induce short-term reduction in renal blood flow (RBF) and GFR, and an increase in renal vascular resistance, in both rats and dogs [83-85]. The effects of short term infusions of AmB on the renal microcirculation in rats revealed that the single nephron GFR was decreased by 2 mechanisms (Table 1) 1) a decrease in single nephron plasma flow, due to vasoconstriction of the afferent and efferent arterioles, and 2) a reduction in the glomerular capillary ultrafiltration coefficient (Kf), an effect probably mediated by mesangial cell contraction [86]. Previous micropuncture studies demonstrated a similar vasoconstriction of the afferent arteriole but also an increased permeability of the tubular epithelium to inulin [75]. Thus, the reduction in GFR after acute AmB infusions can be attributed to contraction of afferent smooth muscle cells, efferent smooth muscle cells and glomerular mesangial cells, as well as increased tubular permeability with back-leak... 

One of the earlier studies demonstrating the role of blood flow on percutaneous absorption in humans used comparison dermal concentrations after topical application in vitro and in vivo (Schaefer and Stuttgen, 1978). Perfusion caused by cutaneous microcirculation also affected responses after the topical penetration of the vasodilator methyl nicotinate in humans (Guy et al., 1983). Altered transdermal drug absorption of the vasoactive nonsteroidal antiinflammatory drug (NSAID) methyl salicylate (MeSA) has also been attributed to changes in in vivo cutaneous perfusion. Exercise, heat exposure, or both increased MeSA absorption more than three times the control levels in six volunteers (Danon etal., 1986). A later case study reported that skin necrosis and other toxic symptoms occurred when a heating pad was used with a topical MeSA and menthol formulation meant to treat arthritic pain (Heng, 1987). 

The autoregulation response should ultimately arise from the action of multiple precapfllary sphincters and resistance arterioles in the microcirculation. The control of flow in a microvascular model was analyzed by Mayrovitz et al. [1978]. This model included muscular arterial and venous vasomotion, capillary filtration and reabsorption, and lymph flow. Tissue pressure was assumed to be regulated and was used to provide the control pathway for the activation of the precapiUary sphincter. Local flow was found to vary considerably with periodic sphincter activity. This model demonstrated that autoregulation of flow is likely to find its genesis at the microcirculatory level. 

Problems of leukocyte distribution in the microcirculation and their interaction with the microvascular endothelium have attracted considerable attention in recent years [17]. Leukocyte rolling along the walls of venules, but not arterioles, has been demonstrated. This effect results from differences in the microvascular endothelium, mainly attributed to the differential expression of adhesion molecules on the endothelial surface [24]. Platelet distribution in the lumen is important because of platelets role in blood coagulation. Detailed studies of platelet distribution in arterioles and venules show that the cross-sectional distribution of these disk-shaped blood elements is dependent on the blood flow rate and vessel hematocrit [25] molecular details of platelet-endothelium interactions are available [26]. Considerable progress has been made in computational modeling of leukocytes in microvessels and their interaction with red blood cells [27-29]. 

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