Swelling of Capillary Endothelial Cells Contributes to Traumatic Hemorrhagic Shock-Induced Microvascular Injury: A Morphologic and Morphometric Analysis

Kretschmar, K; Engelhardt, T.

doi:10.1159/000178205

Cited by 21 publications

(16 citation statements)

References 13 publications

(14 reference statements)

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“…lactacidosis; bovine aortic endothelial cells; pH regulation CAPILLARY DIAMETERS under pathophysiological conditions may be reduced below those of the traversing undeformed red and white blood cells (16) and, therefore, may jeopardize cell passage through the microcirculation as well as nutritive blood flow. The major cause of the reduction of capillary patency is endothelial swelling, as observed in hemorrhagic shock (14,16) or systemic blood acidosis, but not at low flow conditions per se (15). Swelling in these experiments could be prevented by amiloride analogs, as an indication that a Na ϩ /H ϩ exchanger (NHE) participates in the swelling process.…”

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confidence: 78%

Mechanisms of endothelial cell swelling from lactacidosis studied in vitro

Behmanesh

Kempski

2000

American Journal of Physiology-Heart and Circulatory Physiology

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One of the early sequelae of ischemia is an increase of circulating lactic acid that occurs in response to anaerobic metabolism. The purpose of the present study was to investigate whether lactic acidosis can induce endothelial swelling in vitro under closely controlled extracellular conditions. Cell volume of suspended cultured bovine aortic endothelial cells was measured by use of an advanced Coulter technique employing the “pulse area analysis” signal-processing technique (CASY1). The isosmotic reduction of pH from 7.4 to 6.8 had no effect on cell volume. Lowering of pH to 6.6, 6.4, or 6.0, however, led to significant, pH-dependent increases of cell volume. Swelling was more pronounced in bicarbonate-buffered media than in HEPES buffer. Specific inhibition of Na+/H+exchange by ethylisopropylamiloride completely prevented swelling in HEPES-buffered media. Pretreatment with ouabain to partially depolarize the cells did not affect the degree of acidosis-induced swelling. In bicarbonate-buffered media, the inhibition of transmembrane HCO3 − transport by DIDS reduced swelling to a level comparable with that seen in the absence of bicarbonate ions. Lactacidosis-induced endothelial swelling, therefore, is a result of intracellular pH regulatory mechanisms, namely, Na+/H+ exchange and bicarbonate-transporting carriers.

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confidence: 78%

Mechanisms of endothelial cell swelling from lactacidosis studied in vitro

Behmanesh

Kempski

2000

American Journal of Physiology-Heart and Circulatory Physiology

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“…Endothelial cell swelling is a phenomenon observed in ischemia 21,22 and lactacidosis. 23 It is based on the activation of the plasma membrane Na ϩ /H ϩ exchanger inhibited by amiloride analogues as ethylisopropylamiloride.…”

Section: Discussionmentioning

confidence: 99%

Human Endothelium: Target for Aldosterone

et al. 2004

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Abstract-Aldosterone has long been known to control water and electrolyte balance by acting on mineralocorticoid receptors in kidney. However, recent studies demonstrated the presence of these receptors in nonclassical locations, including the cardiovascular system. We tested the hypothesis whether endothelial cells respond to aldosterone with changes in cell volume, a measure for ion-mediated water movement across the cell membrane. By means of atomic force microscopy in fluid, we measured volume of adherent human umbilical venous endothelial cells exposed for 72 hours to 10 nmol/L aldosterone. Over this period of time, cells swell by Ϸ18%. Aldosterone-induced swelling is prevented by 100 nmol/L of the mineralocorticoid receptor antagonist spironolactone, added to the primary endothelial cell culture. Aldosterone-treated cells dramatically shrink when 1 mol/L of the diuretic amiloride is applied. Cells deprived of aldosterone do not respond to amiloride. Our conclusions are: (1) aldosterone leads to sustained cell swelling inhibited by administration of spironolactone or the sodium channel blocker amiloride; (2) cells respond to amiloride after aldosterone exposure; (3) renal diuretics act on endothelial cells; and (4) Key Words: endothelium Ⅲ mineralocorticoids T he kidney is known to be the major target for aldosterone, a mineralocorticoid hormone synthesized in the adrenal cortex that acts on electrolyte transport in the distal nephron. 1 However, there is strong evidence that this hormone is also synthesized in heart 2 and blood vessels. 3 At these locations, it is regulated by similar mechanisms comparable to the renin-angiotensin aldosterone system. 4,5 Because of the fact that aldosterone acts on cardiomyocytes, cardiac fibroblasts, and endothelial cells, this hormone plays a major role in the development of heart failure, myocardial fibrosis, and endothelial dysfunction. 6 Moreover, there is much interest in the possibility of the use of aldosterone receptor blockade in patients to diminish pathological effects that can be produced by this hormone. 7 A study applying atomic force microscopy (AFM) on living aortic endothelial cells showed transient cell swelling that occurred over minutes and that was prevented by a high dose of amiloride known to inhibit plasma membrane Na ϩ /H ϩ exchange. 8 Although the underlying mechanism and its physiological relevance were still unclear, attention was placed on data suggesting that endothelial cells not only synthesize aldosterone 3 but also express mineralocorticoid receptors 9 and the epithelial sodium channel. 10 In a recent article, we applied cariporide, a specific Na ϩ /H ϩ exchange inhibitor, to human umbilical venous endothelial cells (HUVECs). 11 To our surprise, we found that the specific Na ϩ /H ϩ exchange inhibitor did not prevent aldosterone-induced cell swelling, whereas, in contrast, a low dose of amiloride known to block plasma membrane sodium channels was most effective. Taken together, these observations indicated that aldosterone triggers the "c...

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“…Specifically, we have found that it is the acidotic nature of the blood, and not the reduction in blood flow per se, which is responsible for cell swelling in the models of low-flow ischemia we investigated ( fig. 2) [7], Swollen capillary endothelium has been demonstrated in skeletal muscle after complete ischemia [14] and in mesentery after a combined trauma and hemorrhagic shock insult [5], This latter study just published conclud ed that endothelial cells swell in capillaries with an open lumen (mean endothelial height increase of about 70%), but not in capillaries with the lumen blocked by blood cells (no perfusion). It seems unlikely, as the authors spec ulate, that rigid RBCs keep the lumen open.…”

Section: Discussionmentioning

confidence: 99%

“…Swelling of the endothelium with encroachment into the vessel lumen has been shown for capillaries in skeletal muscle [2][3][4] and mesentery [5] during hemorrhagic shock (global low-flow ischemia). The acute decrease in luminal diameter would increase hydraulic flow resistance, thereby hindering re flow efforts.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms and Implications of Capillary Endotheloal Swelling and Luminal Narrowing in Low-Flow Ischemias

et al. 1995

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Decreased functional capillary density (FCD) is a characteristic of low-flow ischemia which often persists on reperfusion of a tissue even though supply blood flow is reestablished. Capillary narrowing is a possible mechanism for the reduced blood reflow through an increase of the hydraulic resistance of the capillary network. We attribute the narrowing to swollen endothelial cells, a condition that could be observed directly and was found to develop with blood acidosis in both hemorrhagic shock and intentional acid infusion. A computer model of blood flow in skeletal muscle was used to predict the impact of a 21 % decrease in capillary luminal diameter on flow and leukocyte transit through the network. For hemorrhagic shock, reduction in blood flow due to capillary narrowing and lowered systemic pressure was offset by hemodilution causing a low-flow state. On reperfusion, flow could be restored if the narrowing was rectified by infusion of a hypertonic saline-dextran solution. Reinfusion with conventional Ringer’s lactate only partially restored flow because of a persistent capillary narrowing. The rheological contribution of passive leukocytes added only a few percent to network resistance even with shock-narrowed capillaries. With leukocyte activation increased cell cytoplasmic viscosity caused prolonged transit times for leukocytes in the network with a concomitant elevation in resistance. We conclude that capillary narrowing is a mechanism of FCD reduction in reperfusion after low-flow ischemia, either by a direct effect on flow or by enhancing the transient plugging of leukocytes. Therapeutic strategies should aim to ameliorate or prevent capillary endothelial cell swelling, and to minimize the level of activated circulating leukocytes.

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Swelling of Capillary Endothelial Cells Contributes to Traumatic Hemorrhagic Shock-Induced Microvascular Injury: A Morphologic and Morphometric Analysis

Cited by 21 publications

References 13 publications

Mechanisms of endothelial cell swelling from lactacidosis studied in vitro

Mechanisms of endothelial cell swelling from lactacidosis studied in vitro

Human Endothelium: Target for Aldosterone

Mechanisms and Implications of Capillary Endotheloal Swelling and Luminal Narrowing in Low-Flow Ischemias

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