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PubMed1999

Effect of latanoprost on regional blood flow and capillary permeability in the monkey eye.

OBJECTIVE: To evaluate the effects of latanoprost on regional blood flow and capillary permeability in the monkey eye. METHODS: Anesthetized cynomolgus monkeys were unilaterally treated with a single dose containing 6 pg of latanoprost; or 10 microg of PhXA34 (13,14-dihydro-15R, S-17-phenyl-18,19,20-trinor-prostaglandin F2alpha [PGF2alpha]-isopropyl ester), which contains about 50% latanoprost. Regional blood flow in the eye was measured with radioactively labeled microspheres; capillary permeability was measured by determining the extravascular plasma-equivalent albumin space using 125I-albumin, 131I-albumin, and 51Cr-labeled erythrocytes. RESULTS: Latanoprost or PhXA34 had no or only a slight effect on the regional blood flow when measured 1, 2 1/2, 3, 4 1/2, and 6 hours after dose administration, with the exception of the anterior sclera, in which a moderate increase in blood flow was detected. No effect on capillary permeability to albumin was detected when studied 30 minutes to 2 1/2 hours and 5 to 6 hours after dose administration. CONCLUSION: Latanoprost, a selective prostaglandin F receptor agonist, exerted no or only slight vascular effects for up to 6 hours after dose administration in the monkey eye, with the exception of the anterior sclera, in which a moderate increase in blood flow was detected. CLINICAL RELEVANCE: Naturally occurring prostaglandins may cause marked microcirculatory changes in the eye that could be of clinical concern. Latanoprost, a selective prostaglandin F receptor agonist, seems to be devoid of such effects.

Administration, Topical↗
PubMed1999

Capillary permeability is increased in normo- and microalbuminuric type 1 diabetic patients: amelioration by ACE-inhibition.

BACKGROUND: Capillary leakage of sodium-fluorescein (NaF) in the skin reflects capillary permeability and may be a marker of diabetes-associated microcirculatory abnormalities. DESIGN: We evaluated transcapillary skin NaF leakage by fluorescence videodensitometry in 10 normoalbuminuric, 10 microalbuminuric Type 1 diabetic men (diabetes duration > 10 years) and 10 healthy subjects. The microalbuminuric patients were restudied after 6 weeks treatment with the ACE-inhibitor enalapril, 10 mg once daily. All measurements were performed at a blood glucose level of 5 mmol L-1. RESULTS: Transcapillary NaF leakage was strongly increased in normoalbuminuric Type 1 diabetic patients compared to healthy subjects (P < 0.001) and was still further increased in microalbuminuric Type 1 diabetic patients (P < 0.01 compared to normoalbuminuric patients). Enalapril reduced NaF leakage (P < 0.05), mean arterial blood pressure (P < 0.05) and microalbuminuria (P < 0. 05). After treatment, NaF leakage was not different from that in normoalbuminuric patients. CONCLUSIONS: Capillary permeability, as determined by NaF leakage, is elevated in normoalbuminuric Type 1 diabetic patients with long-standing disease, and the excess elevation in microalbuminuric Type 1 diabetic patients is ameliorated by ACE-inhibition. Skin NaF videodensitometry seems a useful tool to document capillary permeability in intervention studies.

Albuminuria↗
PubMed1983

Increased capillary permeability in diabetes mellitus and its relationship to microvascular angiopathy.

Increased capillary permeability to large molecular weight plasma proteins is an early phenomenon in diabetes that affects the microvasculature of the kidney, eye, brain, and many other peripheral tissues such as skin and muscle. This widespread vascular leakiness is related to the metabolic disturbance of diabetes and associated changes in blood flow and intravascular pressure. Correction of hyperglycemia and increased blood flow reduces and often normalizes the excessive leakage. The relevance of increased small vessel permeability to eventual organ and tissue damage remains largely speculative. However, recent experimental evidence has suggested that certain levels of subclinical elevated urinary albumin excretion rate strongly predict the onset of Albustix-positive proteinuria, a certain precursor of renal failure. Hemodynamic factors in the genesis of diabetic microangiopathy are discussed, and a hypothetic sequence of events leading from increased capillary permeability to end stage organ or tissue failure is suggested.

Blood Proteins↗
PubMed2000

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates.

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.

Acute Disease↗
PubMed1982

Capillary permeability in skeletal muscle of normal subjects.

Capillary diffusion capacity (CDC) and muscle blood flow (MBF) were determined from the anterior tibial muscle in 25 normal subjects by measuring the simultaneous clearance of 133xenon and sodium131iodide. The subjects were divided into two groups: one with a mean age of 31 years and the other with a mean age of 51. The older group had a significantly lower MBF (54.6 +/- 9.0 vs. 64.2 +/- 9.5 ml/100 g/min; p less than 0.05) and a significantly greater CDC (7.6 +/- 1.2 vs. 6.1 +/- 1.3 mol/min; p less than 0.01) than the younger group. There was a significant correlation between the CDC increase and the age of the subjects (r = 0.61; p less than 0.01). Furthermore, MBF decreased with increasing age (r = 0.48; p less than 0.05). No differences were found in MBF or CDC between female and male subjects. The mechanisms of increased capillary permeability are discussed.

Adult↗
PubMed1984

Capillary permeability in septic patients.

It is suspected, but still unproven, that the increased capillary permeability which accompanies sepsis and contributes to the development of pulmonary edema (PE) involves systemic as well as pulmonary capillaries. We investigated the relationship between the colloid osmotic pressure of serum (COPS) and edema fluid (COPE) in 16 septic and 19 nonseptic patients with severe generalized edema. COPS values of septic and nonseptic patients were not significantly different (14.6 +/- 2.1 and 15.8 +/- 3.4 torr, respectively). However, the COPE of septic patients was 2.4 +/- 0.7 torr while the COPE of nonseptic patients was 1.3 +/- 0.7 torr. The COPE/COPS ratio was 0.165 in septic patients and 0.084 in nonseptic patients. Both of these differences are significant (p less than .001). It was also possible to discriminate septic from nonseptic patients on the basis of the COPE/COPS ratio. Thus, 16/17 determinations in septic patients had a ratio greater than .1, while 17/22 determinations in nonseptic patients showed a ratio less than .1. PE was present in 8/16 septic patients but in only 2/19 nonseptic patients. These data suggest that the increase in capillary permeability during sepsis is generalized.

Aged↗
PubMed1995

Bacterial translocation and intestinal capillary permeability following major liver resection in the rat.

Bacterial infections constitute a major cause of morbidity and mortality after major liver resection and mechanisms of this type of complication have been poorly understood. The present study evaluated the translocation of enteric bacteria to mesenteric lymph nodes, viscera, and the systemic circulation and gut capillary permeability of a fine ultrastructural tracer in rats subjected to sham hepatectomy or 70% hepatectomy. Furthermore, the preventive effects of water-soluble ethylhydroxyethyl cellulose (EHEC) were studied. Cultures of all samples from rats subjected to sham hepatectomy or 70% hepatectomy with preoperative intravenous administration of EHEC were bacteriologically negative. The incidence of bacterial translocation from the gut to the systemic circulation and mesenteric lymph nodes was 30 and 80%, respectively (P < 0.01), and to the liver and kidneys 50 and 40%, respectively (P < 0.05), 12 hr after 70% hepatectomy. Intestinal capillary permeability and endothelial cell membrane permeability increased with the development of bacterial translocation. Translocating bacteria appeared within the cytoplasm of capillary endothelial cells. EHEC restored the changes in gut capillary permeability induced by major liver resection. These results indicate that gut capillary permeability may play an important role in maintaining the integrity of the gut barrier function and that increased permeability may be associated with the development of gut barrier failure.

Animals↗
PubMed1988

A model of radiation myelopathy in the rat. Pathology, regional capillary permeability changes and treatment with dexamethasone.

In order to identify the effects of x-irradiation on spinal cord histology and capillary permeability, we irradiated the upper thoracic spinal cord of adult rats with 3500 cGy to a single lateral field. After 165 +/- 14 (SD) days the rats became paraplegic over 4 to 8 days. Quantitative autoradiography using 14C-amino-isobutyric acid demonstrated a biphasic curve of regional capillary permeability changes (K1). K1 first increased 70 to 85% in all regions of the cord at 30 days, then normalized at 60 days. From 60-151 +/- 8 days in asymptomatic animals there was an apparently exponential increase of K1 in all spinal cord regions progressing at varying rates among regions, most rapidly in the posterior columns and least rapidly in grey matter. K1 continued to rise when the animals became paraplegic. Morphologically, the asymptomatic period was characterized by myelin pallor and vacuolation evident at 30 days, maximal at 60 days, without progression until 151 +/- 8 days when microscopic foci of necrosis appeared in the posterior columns of some clinically normal ('preparetic') animals. The paretic period was characterized by extensive posterior and lateral column necrosis with preservation of grey matter. High dose dexamethasone or indomethacin had no preventative effect when administered just prior to irradiation. Dexamethasone transiently improved motor strength in symptomatic rats and reduced K1 in nonnecrotic portions of the cord. This study suggests that, after a transient peak of 'early delayed' changes in regional capillary permeability, there is progressive damage to the endothelium that may play a primary role in delayed radionecrosis.

Angiography↗
PubMed1979

Horseradish peroxidase as a tracer for capillary permeability studies.

The permeability of capillaries was investigated utilizing an in vivo injection of horseradish peroxidase (HRP) and an in situ perfusion of a balanced salt solution containing HRP and lanthanum chloride. In the continuous capillaries of heart and muscle, HRP diffuses mainly through intercellular junctions, while in testicular capillaries, the transport is via micropinocytotic vesicles. The diffusion and micropinocytotic transport of HRP was demonstrated in both directions, i.e. from the capillary lumen to the interstitium and vice versa. Lanthanum can be used as a bidirectional inhibitor of micropinocytosis. The transport of HRP is then almost completely hindered in testicular capillaries. In heart muscle, the effect on HRP transport is not significant, due to second transport pathway, i.e. intercellular cleft passage.

Animals↗
PubMed2003

Measurements of extracellular volume fraction and capillary permeability in tissues using dynamic spin-lattice relaxometry: studies in rabbit muscles.

Dynamic MR longitudinal R(1) relaxometry after administration of a gadolinium contrast bolus (Gd-DTPA) has been used for in vivo measurements of the extracellular volume fraction (v) and the capillary permeability (k min(-1)) in rabbit muscles to distinguish between red slow- and white fast-twitch muscle fiber types. For this purpose a protocol imaging sequence has been used which allows fast R(1) measurements during the contrast agent uptake. Physiological tissue parameters, k and v, were obtained by computing procedures assuming a simplified monoexponential plasma model. These were shown to be about twice as large in the slow-twitch semimembranosous proprius muscle (SP), containing 100% oxidative type-I fiber, that in the fast-twitch rectus femorus muscle (RF), containing only 6% type-I fiber type. The capillary permeability has been found to be 0.25 +/- 0.02 min(-1) for the (SP) and 0.10 +/- 0.01 min(-1) for the (RF). Similarly, the extracellular volume fractions were 0.189 +/- 0.015 and 0.082 +/- 0.006 respectively, in close agreement with literature data and experimental results obtained by invasive radionuclide measurements. For the pool of the 10 studied animals, no significant variation among animals was observed in the extracellular volume fraction and the capillary permeability for the different muscle fiber types. The dynamic relaxometry method used is easy to implement on conventional MR imagers and has potential applications in muscle diseases. The method has also potential applications for tissue characterization based on extracellular volume and capillary permeability quantification. In particular, the method can be used for the evaluation of tumors and their responses to therapies.

Animals↗
PubMed1992

Measures of capillary permeability in acute falciparum malaria: relation to severity of infection and treatment.

Capillary permeability was investigated in 32 Thai patients aged 14-49 years who had acute falciparum malaria with use of three distinct techniques: quantitation of the urinary albumin/creatinine ratio (ACR), estimation of the transcapillary escape rate of radiolabeled albumin (TER), and retinal photography/fluorescein angiography. Fourteen patients had uncomplicated infections and 18 were severe cases. The severely ill patients had significantly higher ACRs (median, 4.8 mg/mmol; 95% confidence limits, 2.4-19.9 mg/mmol) and TERs (median, 8.3%/h; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 1.0-8.8 mg/mmol; TER: median, 5.9%/h; 95% confidence limits, 3.8-10.6%/h; P = .014 and .042). Both variables were significantly associated with biochemical indices of disease severity including total serum bilirubin levels (rs greater than or equal to 0.398, P less than .025 in each case), but there were no significant differences between ACRs and TERs among comatose and noncomatose patients with severe infections (P greater than or equal to .08). Retinopathy (hemorrhages, cotton-wool spots, capillary nonperfusion, and/or extravasation of fluorescein) was found in eight severely ill patients and in two uncomplicated cases. Fluorescein leakage was evident in six patients. Although fluorescein leakage had the strongest parametric correlation with the presence of coma relative to both ACR and TER in the full patient series (r = 0.58, P less than .01), multiple linear regression analysis indicated that concentrations of plasma lactate (t = 2.998, P = .006) and serum creatinine (t = 2.200, P = .036) were the factors responsible for this association. These data do not support a role for tissue edema in the pathogenesis of cerebral malaria but reveal an association between markers of disease severity and a generalized increase in systemic capillary permeability.

Adolescent↗