RESUMO
INTRODUCTION: Supraceliac aortic clamping in major vascular procedures promotes splanchnic ischemia and reperfusion (I/R) injury that may induce endothelial dysfunction, widespread inflammation, multiorgan dysfunction, and death. We tested the hypothesis that local or remote ischemic preconditioning (IPC) may be protective against injury after supraceliac aortic clamping through the modulation of mesenteric leukocyte-endothelial interactions, as evaluated with intravital microscopy and expression of adhesion molecules. METHODS: Fifty-six male Wistar rats (weight, 190 to 250 g), were divided into four groups of 14 rats each: control-sham surgery without aortic occlusion; I/R through supraceliac aortic occlusion for 20 minutes, followed by 120 minutes of reperfusion; local IPC through supraceliac aortic occlusion for two cycles of 5 minutes of ischemia and 5 minutes of reperfusion, followed by the same protocol of the IR group; remote IPC through infrarenal aortic occlusion for two cycles of 10 minutes of ischemia and 10 minutes of reperfusion, followed by the same protocol of the IR group. Seven animals per group were used to evaluate in vivo leukocyte-endothelial interactions in postcapillary venules with intravital microscopy and another seven animals per group were used to collect mesentery samples for immunohistochemistry demonstration of adhesion molecules expression. RESULTS: Supraceliac aortic occlusion increased the number of rolling leukocytes with slower velocities and increased the number of adherent leukocytes to the venular surface and leukocyte migration to the interstitium. The expression of P-selectin, E-selectin, and intercellular adhesion molecule-1 was also increased significantly after I/R. Local or remote IPC reduced the leukocyte recruitment in vivo and normalized the expression of adhesion molecules. CONCLUSIONS: Local or remote IPC reduces endothelial dysfunction on mesenteric microcirculation caused by I/R injury after supraceliac aortic clamping.
Assuntos
Aorta/cirurgia , Moléculas de Adesão Celular/metabolismo , Células Endoteliais/imunologia , Precondicionamento Isquêmico/métodos , Migração e Rolagem de Leucócitos , Traumatismo por Reperfusão/prevenção & controle , Circulação Esplâncnica , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Animais , Constrição , Selectina E/metabolismo , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Leucócitos/imunologia , Masculino , Microcirculação , Microscopia de Vídeo , Selectina-P/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/fisiopatologia , Fatores de Tempo , Vênulas/imunologia , Vênulas/fisiopatologiaRESUMO
Microcirculatory dysfunction plays a pivotal role in the pathogenesis of severe sepsis and septic shock; hence, microcirculation blood flow monitoring has gained increasing attention. However, microcirculatory imaging is still investigational in human sepsis and has not yet been incorporated into routine clinical practice for several reasons, including the difficult interpretation of microcirculation imaging data, difficulty to draw a parallel between sublingual microcirculation imaging and organ microcirculation dysfunction, as well as the absence of microvessel dysfunction parameters defining sequential microcirculatory changes from the early to late stages of the disease, which could aid in the context of therapeutic approaches and of prognostic parameters. The purpose of this review was to bridge the experimental abdominal organ microvascular derangement kinetics and clinical aspects of microcirculatory findings in the early phase of severe sepsis/septic shock.
Assuntos
Microcirculação , Sepse/fisiopatologia , Animais , Arteríolas/fisiopatologia , Arteríolas/ultraestrutura , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Infecções por Escherichia coli/complicações , Humanos , Microscopia de Vídeo , Ratos , Sepse/etiologia , Circulação Esplâncnica , Vênulas/fisiopatologia , Vênulas/ultraestrutura , Vísceras/irrigação sanguíneaRESUMO
Understanding microvascular oxygen transport requires the knowledge of microvessel topology and geometry, blood flow and oxygen levels. Microvascular hemodynamic responses to hemorrhagic hypotension (HH) such as size-dependent vasoconstriction and blood flow reduction could lead to increased longitudinal oxygen partial pressure (PO(2)) gradients. However, the mesenteric microvascular PO(2) has never been evaluated during HH. Therefore, we studied hemodynamic variables and PO(2) distribution in 165 mesenteric microvessels from 39 anesthetized rats to investigate whether HH-induced vasoconstriction and blood flow reduction were associated with changes in longitudinal PO(2) gradients. Vessels were analyzed according to their position in the network, as well as a few interstitial PO(2) areas. We found that during baseline a small PO(2) gradient exists, but HH is accompanied by more pronounced microvascular longitudinal PO(2) gradients. Decreased blood flow did not seem to completely explain these findings, since blood flow was uniformly diminished in arterioles and venules, independent of diameter and position in the network. During HH, some microvessels presented higher PO(2) than during baseline despite blood flow reduction, possibly due to a combination of systemic hyperoxia and low oxygen consumption of mesentery. The data suggest that blood flow measurements may be a poor indicator of the oxygenation status in some regions of the mesentery. The enhanced mesenteric longitudinal PO(2) gradient may lead to regions with different levels of other physiologically active compounds.
Assuntos
Hemodinâmica , Hemorragia/complicações , Hipotensão/fisiopatologia , Mesentério/irrigação sanguínea , Oxigênio/sangue , Circulação Esplâncnica , Animais , Arteríolas/metabolismo , Arteríolas/fisiopatologia , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Hemorragia/metabolismo , Hemorragia/fisiopatologia , Hipotensão/etiologia , Hipotensão/metabolismo , Masculino , Consumo de Oxigênio , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional , Resistência Vascular , Vasoconstrição , Vênulas/metabolismo , Vênulas/fisiopatologiaRESUMO
Cyclo 3 Fort is used in the treatment of chronic venous insufficiency. In this study, the effects of Cyclo 3 Fort, 2, 10 and 50 mg/kg, were studied in cheek pouch preparations from diabetic hamsters. The mean arteriolar diameter in animals receiving Cyclo 3 Fort, 10 and 50 mg/kg, was significantly greater than in control animals (p < 0.05), and the mean venule diameter was significantly lower in animals receiving the 50 mg/kg dose than in the control group. This suggests that Cyclo 3 Fort, 50 mg/kg/day, has a venotonic effect in diabetic animals. The venoarteriolar reflex was studied by measuring the internal diameter of arterioles during venular occlusion. The reflex was impaired in animals treated with either placebo or 2 mg/kg, but this was reversed by treatment with Cyclo 3 Fort, 10 and 50 mg/kg.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Extratos Vegetais/administração & dosagem , Reflexo/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Administração Oral , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiopatologia , Constrição Patológica , Cricetinae , Angiopatias Diabéticas/fisiopatologia , Masculino , Microcirculação/efeitos dos fármacos , Microcirculação/fisiopatologia , Vênulas/efeitos dos fármacos , Vênulas/fisiopatologiaRESUMO
1. The constrictor response of microvessels to norepinephrine and tyramine, and the dilator response to acetylcholine and papaverine was equivalent in normal and alloxan-induced diabetic rats. 2. Acetylcholine and phentolamine were equally effective as antagonists of the vasoconstrictor action of norepinephrine in both groups of animals. 3. The minimum effective doses of histamine and PAF-acether to produce maximum dilation of microvessels, or to antagonize the response to norepinephrine in normal rats had to be increased 20-fold to evoke equivalent effects in diabetic animals.