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    HYPERDYNAMIC CIRCULATION IN A CHRONIC MURINE SCHISTOSOMIASIS MODEL OF PORTAL-HYPERTENSION

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    Chronic murine schistosomiasis is a natural disease model of portal hypertension closely mimicking the clinical and histological features of human hepatic schistosomiasis. We studied the splanchnic and systemic hemodynamics in the murine model of schistosomiasis by radioactive microsphere technique. Mice infected with 60 cercariae of Schistosoma mansoni (n = 8) were studied hemodynamically 11 wk age-matched infection and were compared with age-matched healthy controls (n = 11). Mean portal venous inflow in the infected mice (3.82 +/- 0.32 ml/min) was 61% higher than in the healthy animals (2.37 +/- 0.25 ml/min; p < 0.01). A twofold increase in hepatic arterial flow was also seen in mice with schistosomiasis (0.47 +/- 0.14 ml/min) as compared with controls (0.16 +/- 0.03 ml/min; p < 0.05), whereas splanchnic arteriolar resistance (60.91 +/- 7.64 vs. 101.21 +/- 11.06 mm Hg.min.ml-1. gm; p < 0.01) were reduced. There was a significant increase in cardiac index (752 +/- 99 vs. 453 +/- 55 ml.min-1. kg body weight-1; p < 0.05) and reduction in mean arterial pressure (81.37 +/- 3.09 vs. 101.45 +/- 5.85 mm Hg; p < 0.05) in the infected animals compared with controls. These observations clearly demonstrate the existence of a hyperdynamic circulatory state in this model of portal hypertension

    SPLANCHNIC AND SYSTEMIC HEMODYNAMICS IN MICE USING A RADIOACTIVE MICROSPHERE TECHNIQUE

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    Mice are commonly used for the study of human disease processes. However, techniques for measuring systemic and hepatic blood flow in mice have not been developed. We attempted the conventional technique of radiolabeled microsphere injection into the left ventricle, but difficulties were encountered, including unsuspected ventricular perforation and outflow obstruction in 68% of the animals. We therefore evaluated whether an injection into the carotid artery close to the aortic arch can fulfill the criteria (approximately or greater than 300 microspheres in femoral blood or tissues, adequate mixing of microspheres with blood, and no significant alteration of blood pressure during microsphere injection) required for accurate measurement of systemic and regional hemodynamics. Carotid artery injection resulted in adequate mixing and number of microspheres in tissues in 78 and 91% of the animals, respectively. Portal venous inflow was 1.8 +/- 0.3 ml.min-1.g liver tissue-1 and renal blood flow was 5.1 +/- 0.75 ml.min-1.g tissue-1. Compared per unit weight, these values are quite similar to those reported in rats. Cardiac output was 12.1 +/- 1.2 ml/min and cardiac index was 462 +/- 47 ml.min-1.kg body wt-1. The reliability of cardiac output determination is improved if whole body radioactivity is taken into account. Five of 22 animals had to be excluded because of either a low number of microspheres in tissues or inadequate mixing of microspheres with blood (shown by asymmetrical distribution of microspheres between left and right kidney). With modifications, the radioactive microsphere technique can be adapted to the hemodynamic study of mice. </jats:p

    INFLUENCE OF ANESTHESIA, POSTANESTHETIC STATE, AND RESTRAINT ON SUPERIOR MESENTERIC ARTERIAL FLOW IN NORMAL RATS

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    To exclude possible confounding effects of anesthesia on splanchnic hemodynamics, two different awake postanesthetic models (PAM), restrained and unrestrained, have been used. However critical analysis of the splanchnic hemodynamic state in these models is not available. We conducted experiments using chronically implanted pulsed-Doppler flow probes on the superior mesenteric artery (SMA) in ketamine-anesthetized and in postanesthetic restrained and unrestrained normal rats. Baseline values of mean SMA flow were compared with those under anesthesia (30 min), PAM (restrained or unrestrained at 90 and 150 min), and reanesthesia. Sham-anesthetized unrestrained animals provided control values. The same animals (n = 7) underwent the restrained, unrestrained, and control experiments at least 5 days apart. Ketamine anesthesia did not significantly alter mean SMA flow (89 +/- 9% of baseline) compared with sham-anesthetized controls (99 +/- 9%). Mean SMA flow in both PAM, restrained and unrestrained, had a significant (P < 0.05) decrease at 90 min (78 +/- 8 and 83 +/- 12%) and at 150 min (68 +/- 14 and 78 +/- 14%) when compared with baseline and control. Reanesthesia returned SMA flows to baseline values (91 +/- 16%). The variability of mean SMA flow was significantly increased in both PAM. Maximum variability was observed in the restrained model (69 +/- 32%). These results indicate 1) that ketamine anesthesia does not significantly alter SMA flow and 2) that both the restrained and unrestrained PAM exhibit significant alterations of the splanchnic circulation for at least 2 h after complete recovery from anesthesia. Thus, in the absence of critical evaluation, results of splanchnic hemodynamic studies with these models should be questioned. Ketamine anesthesia administered intra-muscularly may be preferred to the awake PAM for the study of the splanchnic circulation

    A RANDOMIZED STUDY OF PROPRANOLOL ON POSTPRANDIAL PORTAL HYPEREMIA IN CIRRHOTIC-PATIENTS

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    Propranolol, a nonselective beta-adrenergic blocker, has been shown to reduce portal pressure and the risk fo variceal bleeding. The portal pressure-reducing effect of propranolol is mediated by splanchnic arterial constriction, which decreases portal flow. A double-blind randomized control study (crossover on 2 consecutive days) was designed to compare the effects of propranolol vs. placebo on portal flow in cirrhotic patients during fasting and after a standardized meal. Portal flow was measured with an ATL Ultramark 8 echo-Doppler system (Advanced Technological Laboratories, Bothel, WA) in 23 cirrhotic patients. Fasting portal flow and heart rate were obtained at baseline and 2 hours after the administration of propranolol or placebo. A standard test meal was then given, and measurements were repeated 30 minutes later. Thirteen patients (group 1) received placebo on day 1 and propranolol on day 2, whereas 10 patients (group 2) received propranolol on day 1 and placebo on day 2. In group 1 patients, heart rate declined by 20% (P less than 0.0001) and portal flow decreased by 12% (P less than 0.05) after propranolol administration. Similar reductions were found in heart rate (-21%, P less than 0.0001) and portal flow (-17%, P less than 0.001) for group 2 patients. For all 23 patients, 2 hours after propranolol administration, heart rate declined by 21% (P less than 0.0001) and portal blood flow was reduced by 14% (P less than 0.0001). The 10 patients who received propranolol on day 1 (group 2) showed a carryover effect of propranolol on day 2. On day 2, baseline portal flow and heart rate values were significantly lower than baseline values on day 1. This long-lasting effect of a single dose of propranolol may be caused by the longer half-life of propranolol in cirrhotic patients. The postprandial portal blood flow percentage increase after the meal was similar for both placebo and propranolol. Propranolol did not blunt postprandial hyperemia. However, whereas the absolute value of blood flow after the meal increased significantly in comparison with baseline in placebo-treated patients (P less than 0.001), this did not occur with propranolol. Furthermore, in propranolol-treated patients the absolute value of blood flow after the meal was lower than in placebo-treated patients. This may constitute a protective effect of propranolol in portal hypertension
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