Abstract:Pressure within the microvascular bed of the frog mesentery has been recorded continuously with micropressure transducers which have tip diameters ranging between 0.5–5 µ. The mean values of pressure are in the range of those previously reported. The waveform of the pressure pulses in arterioles and metarterioles closely resembles that in the larger arteries. This observation signifies that the vascular walls are considerably stiffer than is generally believed. The stiffness is probably attributable to the con… Show more
“…Microvascular pressures were measured with the servo-nulling technique developed by Wiederhielm et al (31). In this method, the unknown intravascular pressure is compared with a known, controlled pressure generated by a voltage-to-pressure converter.…”
-A surface-modified polyethylene glycol-conjugated human hemoglobin (MP4) and ␣␣-cross-linked human hemoglobin (␣␣Hb) were used to restore oxygen carrying capacity in conditions of extreme hemodilution (hematocrit 11%) in the hamster window model preparation. Changes in microvascular function were analyzed in terms of effects on capillary pressure and functional capillary density (FCD). MP4, at 1.0 Ϯ 0.2 g/dl blood concentration, significantly lowered mean arterial pressure (MAP) below baseline (99.6 Ϯ 7.6 mmHg) to 82.4 Ϯ 6.9 mmHg (P Ͻ 0.05) and decreased of FCD to 70 Ϯ 9%. ␣␣Hb caused a greater recovery in MAP to 94.4 Ϯ 6.2 mmHg and lowered FCD to 62 Ϯ 8%. However, differences between ␣␣Hb and MP4 in FCD were not statistically significant. Capillary pressures were in the ranges of 17-21 mmHg for MP4 and 15-19 mmHg for ␣␣Hb, with both significantly lower than baseline (P Ͻ 0.05). Pressure in 80-mdiameter arterioles was significantly increased with ␣␣Hb relative to MP4 (P Ͻ 0.05). These results were compared with previous findings on the relation between capillary pressure and FCD; they supported the concept of a relationship between FCD and capillary pressure. Measurement of changes in arteriolar diameter, microvascular blood flow, and FCD show that there was no statistical difference between using ␣␣Hb and MP4 in extreme hemodilution. Microvascular resistance in arterioles with a diameter range of 70 -80 m showed an increase relative to control with ␣␣Hb, whereas MP4 caused a decrease. shear stress; perfusion; plasma expander; blood pressure; blood substitutes
“…Microvascular pressures were measured with the servo-nulling technique developed by Wiederhielm et al (31). In this method, the unknown intravascular pressure is compared with a known, controlled pressure generated by a voltage-to-pressure converter.…”
-A surface-modified polyethylene glycol-conjugated human hemoglobin (MP4) and ␣␣-cross-linked human hemoglobin (␣␣Hb) were used to restore oxygen carrying capacity in conditions of extreme hemodilution (hematocrit 11%) in the hamster window model preparation. Changes in microvascular function were analyzed in terms of effects on capillary pressure and functional capillary density (FCD). MP4, at 1.0 Ϯ 0.2 g/dl blood concentration, significantly lowered mean arterial pressure (MAP) below baseline (99.6 Ϯ 7.6 mmHg) to 82.4 Ϯ 6.9 mmHg (P Ͻ 0.05) and decreased of FCD to 70 Ϯ 9%. ␣␣Hb caused a greater recovery in MAP to 94.4 Ϯ 6.2 mmHg and lowered FCD to 62 Ϯ 8%. However, differences between ␣␣Hb and MP4 in FCD were not statistically significant. Capillary pressures were in the ranges of 17-21 mmHg for MP4 and 15-19 mmHg for ␣␣Hb, with both significantly lower than baseline (P Ͻ 0.05). Pressure in 80-mdiameter arterioles was significantly increased with ␣␣Hb relative to MP4 (P Ͻ 0.05). These results were compared with previous findings on the relation between capillary pressure and FCD; they supported the concept of a relationship between FCD and capillary pressure. Measurement of changes in arteriolar diameter, microvascular blood flow, and FCD show that there was no statistical difference between using ␣␣Hb and MP4 in extreme hemodilution. Microvascular resistance in arterioles with a diameter range of 70 -80 m showed an increase relative to control with ␣␣Hb, whereas MP4 caused a decrease. shear stress; perfusion; plasma expander; blood pressure; blood substitutes
“…Microvascular pressure was measured in subcutaneous tumours using micropipettes and a servo-controlled counter-pressure system (Wiederhielm et al, 1964). The counter-pressure was generated to balance the change in the electrical resistance in the micropipette.…”
Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome.
“…P if was measured with sharpened glass capillaries (tip diameter 4 -7 m) connected to a servo-controlled counterpressure system (41,42). The counterpressure generated by a servo-controlled pump (model 201, Ling Dynamic Systems, Royston, UK) was recorded with a pressure transducer (model 1280C, Hewlett-Packard).…”
Neurogenic inflammation is known to induce lowering of interstitial fluid pressure (P if) in mouse skin. This study examined the possible role of mast cell activation secondary to neuropeptide release in lowering of P if by using , and neurokinin A, from the capsaicin-sensitive nerve endings. Capsaicin releases neuropeptides through binding to the vanilloid receptor subtype 1 (VR1) (9), which in turn induces an inflammatory response in various tissues of both rodents and humans (2, 21). This response is characterized by increased arteriolar vasodilatation and protein extravasation due to increased permeability of the postcapillary venules resulting in fluid accumulation in the tissue. Previous reports from our research group have shown that the response in the initial phase of neurogenic inflammation involves lowering of interstitial fluid pressure (P if ) as observed both in rat trachea (16) and mouse skin (25). P if is important in tissue fluid homeostasis both in the regulation of fluid filtration across the capillary and as the filling pressure for the lymphatics (1). In contrast to the classic view of P if serving as an edema-preventing mechanism, P if has been shown to play an active part in the initial phase of edema in a number of inflammatory models with a lowering of P if to more negative values (16,31,34,35). According to Starling's hypothesis, this lowering of P if will increase net filtration pressure across the capillary and hence contribute to fluid accumulation in the interstitial space.Mast cells have been thought of as possible participants in the neurogenic inflammatory response because they contain numerous inflammatory mediators and are localized in close proximity to the capsaicin-sensitive nerve endings (37,39). Alterations in the number of SP-reactive fibers and mast cell-nerve contacts have been reported as parts of the pathology of several diseases (3,19,45). SP can activate mast cells both through binding of the neurokinin-1 receptor present on these cells (8) and through receptor-independent mechanisms (10). The significance of mast cell activation as a part of neurogenic inflammation has been questioned in a number of studies, and the results are yet not conclusive. Supporting the involvement of mast cells are the findings that stimulation of the rat saphenous nerve induces mast cell degranulation (27) and that SP in high concentrations (40) as well as topical application of capsaicin (7) induce cutaneous mast cell degranulation in human forearm. In contrast, Petersen et al. (32) detected no release of SP and histamine after capsaicin injection in the same area.In light of the knowledge that capsaicin-sensitive nerve endings are localized close to connective tissue mast cells (CTMCs) in mouse skin (6) and that mast cell activation by compound 48/80 (C48/80) induces a lowering of P if in skin of both rats and mice (20,25,36), the question arises as to whether mast cells are involved in the events leading to lowering of P if in neurogenic inflammation. In a recent study (25) we exami...
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