Efeitos do orlistate sobre os parametros bioquimicos e cardiovasculares de animais normotensos e hipertensos submetidos à isquemia e reperfusão cardíaca
Data
2015-03-31
Autores
Rodrigues, Francisco Sandro Menezes 
Orientadores
Caricati Neto, Afonso
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O presente estudo teve como objetivo principal estudar os efeitos do orlistate (ORL) sobre os parâmetros bioquímicos e cardiovasculares de animais normotensos (NWR) e hipertensos (SHR) submetidos à isquemia e reperfusão (I/R) cardíaca. O protocolo de I/R consistiu no garroteamento com fio cirúrgico da artéria coronária descendente esquerda da retirada do fio após 10 min para permitir a recirculação coronariana (reperfusão) por 75 min. Os SHR apresentaram aumento significativo da pressão arterial sistólica (51%) e da massa cardíaca (19%) em relação aos seus controles normotensos NWR, confirmando o franco estado hipertensivo em SHR. O tratamento com ORL (16 mg por animal, V.O.) durante 2, 5 e 10 dias não alterou os valores de pressão arterial ou da massa cardíaca, em SHR e NWR. O procedimento de I/R cardíaca resultou na alta incidência de arritmias ventriculares (AV), bloqueios atrio-ventriculares (BAV) e letalidade (LET), em SHR e NWR. Todavia, a incidência de AV, BAV e a LET foi menor em SHR (58%, 46% e 21%) em relação aos controles NWR (85%, 79% e 70%). O tratamento com ORL não foi capaz de alterar a incidência de AV e BAV em SHR e NWR, mas aumentou a LET em SHR e reduziu em NWR. A I/R cardíaca não alterou a concentração plasmática de marcadores da função hepática (aspartato aminotransferase ou AST, alanina aminotransferase ou ALT, fosfatase alcalina ou FA) e renal (creatinina), assim como do metabolismo lipídico (triglicerídeos ou TG, VLDL, LDL, HDL), em SHR e NWR. Além disso, a I/R cardíaca também não alterou a concentração plasmática do marcador de lesão muscular lactato desidrogenase (LDH), em SHR e NWR. Todavia, a I/R cardíaca aumentou significativamente a concentração plasmática do marcador de lesão muscular creatina quinase total (CKT) em SHR e NWR. Por outro lado, a I/R cardíaca aumentou significativamente a concentração plasmática do marcador de lesão cardíaca creatina quinase fração MB (CK-MB) em NWR, mas não em SHR. O tratamento dos NWR com ORL reduziu a concentração plasmática de LDL e preveniu o aumento da CKT, mas não alterou os níveis de TG, VLDL, HDL, AST, ALT, FA, LDH e CK-MB. O tratamento dos SHR com ORL reduziu a concentração plasmática de CK-MB, mas não alterou os níveis de TG, VLDL, HDL, AST, ALT, FA, LDH e CKT. Estes resultados sugerem que a I/R cardíaca produziu uma elevada incidência de arritmias cardíacas, incluindo os bloqueios atrio-ventriculares, em animais normotensos e hipertensos. Estas alterações da função cardíaca causaram uma elevada mortalidade em normotensos e hipertensos, porém esta foi 3 vezes menor nos hipertensos, apesar dos valores elevados da concentração plasmática de CKT e CK-MB estarem elevada nestes animais. O tratamento com ORL reduziu a mortalidade produzida pela I/R cardíaca nos normotensos, apesar de não alterar a concentração plasmática de CK-MB. Em contraste, este tratamento aumentou a mortalidade produzida pela I/R cardíaca nos hipertensos, apesar de reduzir a concentração plasmática de CK-MB.
This study aimed to investigate the effects of orlistat (ORL) on the biochemical and cardiovascular parameters of normotensive animals (NWR) and hypertensive (SHR) submitted to ischemia and reperfusion (I/R) cardiac. The I/R protocol consisted of the suture snaring with the left descending coronary artery after withdrawal of the wire 10 min to allow coronary circulation (reperfusion) for 75 min. The SHR showed a significant increase in systolic blood pressure (51%) and cardiac mass (19%) compared to their normotensive controls NWR, confirming the hipertensive state in SHR. Treatment with ORL (16 mg per animal, VO) during 2, 5 and 10 days did not affect the blood pressure or cardiac mass values in SHR and NWR. The I/R cardiac procedure has resulted in a high incidence of ventricular arrhythmias (VA), atrio-ventricular blocks (AVB) and mortality (LET) in SHR and NWR. However, the incidence of AV, BAV and the LET was lower in SHR (58%, 46% and 21%) compared to NWR controls (85%, 79% and 70%). Treatment with ORL has not been able to alter the incidence of AV and BAV in SHR and NWR, but LET increased in SHR and reduced in NWR. I/R cardiac did not alter plasma markers of liver (aspartate aminotransferase or AST, alanine aminotransferase or ALT, alkaline phosphatase or AF) and renal (creatinine) function, as well as lipid metabolism (triglycerides or TG, VLDL, LDL, HDL) in SHR and NWR. Furthermore, I/R cardiac did not affect the plasma concentration of the muscle damage marker lactate dehydrogenase (LDH) in SHR and NWR. However, I/R cardiac significantly increased the plasma concentration of muscle damage marker total creatine kinase (CKT) in SHR and NWR. On the other hand, I/R significantly increased the plasma concentration of cardiac damage marker for cardiac fraction MB creatine kinase (CK-MB) in NWR, but not in SHR. The treatment of NWR with ORL reduced plasma concentrations of LDL and prevented the increase of CKT, but did not alter the levels of TG, VLDL, HDL, AST, ALT, AF, LDH and CK-MB. The treatment of SHR with ORL reduced the plasma concentrations of CK-MB, but did not alter the levels of TG, VLDL, HDL, AST, ALT, AF, LDH and CKT. These results suggest that I/R cardiac produced a high incidence of cardiac arrhythmias, including the atrio-ventricular block, in normotensive and hypertensive rats. These changes in cardiac function caused high mortality in normotensive and hypertensive animals, however this was 3 times lower in hypertensive despite the high values of plasma concentration of CK-MB and CKT are high in these animals. Treatment with ORL reduced mortality produced by I/R cardiac in normotensive, although not change the plasma concentration of CK-MB. In contrast, this treatment increased the mortality produced by I/R cardiac in hypertensive animals, despite reducing the plasma concentration of CK-MB.
This study aimed to investigate the effects of orlistat (ORL) on the biochemical and cardiovascular parameters of normotensive animals (NWR) and hypertensive (SHR) submitted to ischemia and reperfusion (I/R) cardiac. The I/R protocol consisted of the suture snaring with the left descending coronary artery after withdrawal of the wire 10 min to allow coronary circulation (reperfusion) for 75 min. The SHR showed a significant increase in systolic blood pressure (51%) and cardiac mass (19%) compared to their normotensive controls NWR, confirming the hipertensive state in SHR. Treatment with ORL (16 mg per animal, VO) during 2, 5 and 10 days did not affect the blood pressure or cardiac mass values in SHR and NWR. The I/R cardiac procedure has resulted in a high incidence of ventricular arrhythmias (VA), atrio-ventricular blocks (AVB) and mortality (LET) in SHR and NWR. However, the incidence of AV, BAV and the LET was lower in SHR (58%, 46% and 21%) compared to NWR controls (85%, 79% and 70%). Treatment with ORL has not been able to alter the incidence of AV and BAV in SHR and NWR, but LET increased in SHR and reduced in NWR. I/R cardiac did not alter plasma markers of liver (aspartate aminotransferase or AST, alanine aminotransferase or ALT, alkaline phosphatase or AF) and renal (creatinine) function, as well as lipid metabolism (triglycerides or TG, VLDL, LDL, HDL) in SHR and NWR. Furthermore, I/R cardiac did not affect the plasma concentration of the muscle damage marker lactate dehydrogenase (LDH) in SHR and NWR. However, I/R cardiac significantly increased the plasma concentration of muscle damage marker total creatine kinase (CKT) in SHR and NWR. On the other hand, I/R significantly increased the plasma concentration of cardiac damage marker for cardiac fraction MB creatine kinase (CK-MB) in NWR, but not in SHR. The treatment of NWR with ORL reduced plasma concentrations of LDL and prevented the increase of CKT, but did not alter the levels of TG, VLDL, HDL, AST, ALT, AF, LDH and CK-MB. The treatment of SHR with ORL reduced the plasma concentrations of CK-MB, but did not alter the levels of TG, VLDL, HDL, AST, ALT, AF, LDH and CKT. These results suggest that I/R cardiac produced a high incidence of cardiac arrhythmias, including the atrio-ventricular block, in normotensive and hypertensive rats. These changes in cardiac function caused high mortality in normotensive and hypertensive animals, however this was 3 times lower in hypertensive despite the high values of plasma concentration of CK-MB and CKT are high in these animals. Treatment with ORL reduced mortality produced by I/R cardiac in normotensive, although not change the plasma concentration of CK-MB. In contrast, this treatment increased the mortality produced by I/R cardiac in hypertensive animals, despite reducing the plasma concentration of CK-MB.
Descrição
Citação
RODRIGUES, Francisco Sandro Menezes. Efeitos do orlistate sobre os parametros bioquimicos e cardiovasculares de animais normotensos e hipertensos submetidos à isquemia e reperfusão cardíaca. São Paulo, 2015. Tese (Doutorado em Farmacologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.