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Effect of prior statin therapy on capillary permeability in the lungs after cardiac or vascular surgery.

Cholesterol-lowering statins can ameliorate severe forms of vascular hyperpermeability in experimental studies, and may thereby ameliorate acute lung injury and sepsis. It is unknown whether this also applies to humans. This study aimed to define whether or not prior statin therapy reduces mild post-operative increases in pulmonary capillary protein permeability associated with acute lung injury after cardiac or major vascular surgery. A prospective observational study was performed in an intensive care unit of a university hospital on 64 patients, 37 after elective cardiac and 27 after major vascular surgery, of whom 68 and 44%, respectively, had received prior statin therapy. A mobile probe system was used to measure the pulmonary leak index (PLI), i.e. the transvascular transport rate of gallium-67-radiolabelled transferrin. For all of the patients together, the mean PLI did not differ between the statin and control groups (22.9 versus 24.4 x 10(-3) min(-1)). The prevalence of an elevated PLI was 57% in the statin and 59% in the control group. Subgroup analysis did not reveal significant differences caused by statins in the PLI of these patients. Prior statin therapy neither has an adverse effect on mildly increased pulmonary capillary permeability in patients after cardiac or major vascular surgery nor does it ameliorate this increased capillary permeability.

Adult↗

Regional blood flow, capillary permeability, and compartmental volumes: measurement with dynamic CT--initial experience.

Sequential computed tomographic scanning was performed in patients with neck tumors after contrast material administration. For data analysis, a pharmacokinetic two-compartment model was employed that takes into account both capillary blood supply and bidirectional diffusion of the contrast agent across the capillary wall. This approach offers the possibility to quantitatively characterize tissue microcirculation with regional blood flow, capillary permeability, and relative compartmental volumes.

Blood Volume↗

Myocardial sodium extraction at varied coronary flows in the dog. Estimation of capillary permeability of residue and outflow detection.

Sudden injections of boluses containing both 131I-albumin and 24NaCl were made into the coronary artery inflow of isolated blood-perfused dog hearts. Indicator dilution curves were recorded using gamma emissions from both the intact heart and the coronary sinus outflow, with plasma flows, Fs, ranging from 0.3 to 1.8 ml/g min-1. Three measures of sodium extraction, E, during transcapillary passage were obtained from each site by comparison of the sodium and albumin curves. The most useful estimates of E were "instantaneous extractions" obtained from the later part of the upslope and the peak of the venous dilution curves (coronary sinus) or from the corresponding early phase of washout of the externally monitored curves (intact organ). Extractions were lower at higher flows. Permeability-surface area products, PS, were computed (1) by the formula PS equals -Fsloge(1 - E), (2) by fitting the observed dilution curves with a Krogh capillary-tissue cylinder model, and (3) by the approximating formula PS equals -Fsloge (1 - 1.14E). The two latter approaches provided a correction for back diffusion of tracer from tissue to blood. For sodium, the values of PS averaged 0.88 +/- 0.36 (SD) ml/g min-1, (n equals 52). At high flows, with Fs greater than 1.0 ml/g min-1, the values of PS averaged 1.01 +/- 0.38 ml/g min-1 (N equals 11). Assuming S equals 500 cm2/g and plasma to be 93% water, our findings suggest capillary permeabilities for sodium of about 3.1 times 10(-5) cm/sec.

Animals↗

Changes in capillary permeability during severe experimental acute pancreatitis in rats.

Abnormalities of microcirculation are thought to have an important role in the pathogenesis of severe acute pancreatitis (SAP) and in the associated multiple organic failure. We studied changes in capillary permeability during experimental SAP in rats. Necrotizing acute pancreatitis was induced by retrograde injection of sodium taurocholate in pancreatic ducts in rats (n = 30). The animals were distributed in three groups in which the spaces of compartmental distribution as well as the tissue distribution of labeled tracers were evaluated with the use of erythrocytes and albumin tagged with radioactive chromium, apart from determining the volume of total body water. All the studies were carried out four hours after the induction of acute pancreatitis and the administration of radioactive tracers.

Acute Disease↗

Measurement of cerebral blood flow, cerebral blood volume, and cerebral capillary permeability in glioma-bearing rats.

Effective chemotherapy and radiation therapy of brain tumors require knowledge of the cerebral circulatory dynamics involved. In this study, regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), and regional cerebral capillary permeability (rCP) were measured in Wistar King Aptekman rats bearing experimental KEG-1 gliomas. These parameters were assessed by autoradiography with 14C-iodoantipyrine, 14C-deoxyglucose-labeled red blood cells, and 14C-aminoisobutyric acid, respectively. rCBF within the tumor was approximately one third that in the contralateral cortex and was consistently higher in the periphery than in the center of the tumor. In the periphery of the tumor, rCBV was approximately twice that in the contralateral cortex, but it was very low in the center of the tumor. Throughout the tumor, rCP was sharply increased relative to that measured in the contralateral cortex, and the increase was especially pronounced in the central portion. Thus, rCBF, rCBV, and rCP each appeared to vary within the tumor, implying that the combined use of lipid- and water-soluble chemotherapeutic agents is reasonable. Measurement of these parameters may also provide indices of radiation sensitivity.

Animals↗

In vivo effect of alpha 1-acid glycoprotein on experimentally enhanced capillary permeability in guinea-pig skin.

Anesthetized guinea-pigs were intravenously injected with Evans blue. After intracutaneous injection of agonists (lys-plasminogen, histamine, platelet-activating factor, thrombin, bradykinin), the resulting wheals appeared blue in a dose-dependent manner, due to an enhanced capillary permeability, alpha 1-Acid glycoprotein, given i.v. in different doses (3.125-50 mg/kg) and at different times (30-180 min) before Evans blue administration, antagonized the effects of all agonists listed above. This was shown by a parallel shift of the agonist dose-response curves to the right. The effect was time-dependent (tmax: mainly 120 min) and dose-dependent. alpha 1-Acid glycoprotein antagonized the agonists in the following order: lys-plasminogen > histamine = platelet-activating factor > thrombin > bradykinin. As all agonist mentioned are suggested to play a major role in the shock-related increase in vascular permeability, a putatively beneficial role of alpha1-acid glycoprotein in shock is discussed.

Animals↗

[Hypovolaemic shock due to increased capillary permeability (author's transl)].

In a 69-year-old man admitted to hospital for shock with symptoms suggesting acute cor pulmonale, laboratory tests showed low proteinaemia associated with haemoconcentration. Vascular filling led to recovery, but the condition relapsed 6 months later, heralded by weight increase, swelling of the face and profuse swelling; the patient again recovered. On this last occasion, a monoclonal peak of IgG kappa thought to have antibody activity was discovered. These attacks of hypovolaemic shock seem to be due to sudden increases in capillary permeability.

Aged↗