European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023
Micro-lightguide spectrophotometry assessment of hepatic and intestinal microcirculation in endotoxemic rats during intravenous treatment with angiotensin II.
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Schmidt Götz, Pitz Laurenz, Markmann Melanie, Schneck Emmanuel, Sander Michael, Koch Christian, Edinger Fabian
Аннотация
INTRODUCTION: During septic shock, impairment of microcirculation leads to enhanced permeability of intestinal mucosa triggered by generalized vasodilation and capillary leak. Intravenous angiotensin II (AT-II) has been approved for the treatment of septic shock; however, no in-vivo data exist on the influence of AT-II on hepatic and intestinal microcirculation.
MATERIAL AND METHODS: Sixty male Lewis rats were randomly assigned to six study groups (each n = 10): sham, lipopolysaccharide-induced septic shock, therapy with low- or high-dose AT-II (50 or 100 ng/kg/min, respectively), and septic shock treated with low- or high-dose AT-II. After median laparotomy, hepatic and intestinal microcirculation measures derived from micro-lightguide spectrophotometry were assessed for 3 h and included oxygen saturation (SO2), relative blood flow (relBF) and relative hemoglobin level (relHb). Hemodynamic measurements were performed using a left ventricular conductance catheter, and blood samples were taken hourly to analyze blood gasses and systemic cytokines.
RESULTS: AT-II increased mean arterial pressure in a dose-dependent manner in both septic and non-septic animals (p < 0.001). Lower hepatic and intestinal SO2 (both p < 0.001) were measured in animals without endotoxemia who received high-dose AT-II treatment, however, significantly impaired cardiac output was also reported in this group (p < 0.001). In endotoxemic rats, hepatic relBF and relHb were comparable among the treatment groups; however, hepatic SO2 was reduced during low- and high-dose AT-II treatment (p < 0.001). In contrast, intestinal SO2 remained unchanged despite treatment with AT-II. Intestinal relBF (p = 0.028) and interleukin (IL)-10 plasma levels (p < 0.001) were significantly elevated during treatment with high-dose AT-II compared with low-dose AT-II.
CONCLUSIONS: A dose-dependent decrease of hepatic and intestinal microcirculation during therapy with AT-II in non-septic rats was observed, which might have been influenced by a corresponding reduction in cardiac output due to elevated afterload. While hepatic microcirculation was reduced during endotoxemia, no evidence for a reduction in intestinal microcirculation facilitated by AT-II was found. In contrast, both intestinal relBF and anti-inflammatory IL-10 levels were increased during high-dose AT-II treatment.
MATERIAL AND METHODS: Sixty male Lewis rats were randomly assigned to six study groups (each n = 10): sham, lipopolysaccharide-induced septic shock, therapy with low- or high-dose AT-II (50 or 100 ng/kg/min, respectively), and septic shock treated with low- or high-dose AT-II. After median laparotomy, hepatic and intestinal microcirculation measures derived from micro-lightguide spectrophotometry were assessed for 3 h and included oxygen saturation (SO2), relative blood flow (relBF) and relative hemoglobin level (relHb). Hemodynamic measurements were performed using a left ventricular conductance catheter, and blood samples were taken hourly to analyze blood gasses and systemic cytokines.
RESULTS: AT-II increased mean arterial pressure in a dose-dependent manner in both septic and non-septic animals (p < 0.001). Lower hepatic and intestinal SO2 (both p < 0.001) were measured in animals without endotoxemia who received high-dose AT-II treatment, however, significantly impaired cardiac output was also reported in this group (p < 0.001). In endotoxemic rats, hepatic relBF and relHb were comparable among the treatment groups; however, hepatic SO2 was reduced during low- and high-dose AT-II treatment (p < 0.001). In contrast, intestinal SO2 remained unchanged despite treatment with AT-II. Intestinal relBF (p = 0.028) and interleukin (IL)-10 plasma levels (p < 0.001) were significantly elevated during treatment with high-dose AT-II compared with low-dose AT-II.
CONCLUSIONS: A dose-dependent decrease of hepatic and intestinal microcirculation during therapy with AT-II in non-septic rats was observed, which might have been influenced by a corresponding reduction in cardiac output due to elevated afterload. While hepatic microcirculation was reduced during endotoxemia, no evidence for a reduction in intestinal microcirculation facilitated by AT-II was found. In contrast, both intestinal relBF and anti-inflammatory IL-10 levels were increased during high-dose AT-II treatment.