RESUMO
The aim of this study was to investigate the protective mechanisms of delayed-phase morphine preconditioning on myocardial ischemia-reperfusion injury. Thirty healthy male New Zealand white rabbits were randomly divided into three groups: a sham operation group (C), ischemia-reperfusion group (I/R), and delayed-phase morphine preconditioning group (M) (N = 10/group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group received left artery blockage for 40 min and reperfusion for 120 min. Rabbits in the M group received 1.0 mg/kg intravenous morphine 24 h prior to the identical treatment as the rabbits in the I/R group. In each group, the interleukin (IL)-10 and tumor necrosis factor (TNF)-α levels were detected at five time points: 20 min before the left coronary artery blockage (T1), 20 and 40 min after the left coronary artery blockage (T2 and T3, respectively), and 1 and 2 h after the myocardial reperfusion (T4 and T5, respectively). After reperfusion, the infarction size was measured with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Compared with the C group, serum IL-10 and TNF-α concentrations increased in the I/R and M groups; the difference was significant (P < 0.05). When compared with the I/R group, the IL-10 concentrations in the M group were significantly increased (P < 0.05), but the infarction size and TNF-α concentrations were significantly decreased (P < 0.05). These results suggested that delayed-phase morphine preconditioning might achieve myocardial protection through the regulation and balance of inflammatory cytokines.
Assuntos
Precondicionamento Isquêmico/métodos , Morfina/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Interleucina-10/sangue , Masculino , Coelhos , Distribuição Aleatória , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/sangueRESUMO
This study aimed to investigate the protective effects of delayed morphine preconditioning on myocardial ischemia-reperfusion injury. We randomly divided 30 rabbits into three groups with 10 rab-bits in each group as follows: sham operation group (C group), isch-emia-reperfusion group (I/R group), and morphine pretreatment group (M group). Rabbits in C Group received left coronary without blocking for 160 min. The left descending artery of rabbits in the I/R group was blocked for 40 min and reperfused for 120 min. Rabbits in the M group received intravenous administration of 1.0 mg/kg morphine; after 24 h, rabbits in this group received the same treatment as that administered to the I/R group. We determined tumor necrosis factor alpha (TNF-α) levels in blood samples from the internal carotid artery of rabbits in each group 20 min before occlusion of the left descending coronary artery, 20 and 40 min after occlusion of the left descending coronary artery, and 1 and 2 h after myocardial reperfusion. After 120 min of reperfusion, immunoblotting was used to measure the activity levels of myocardial p38 mitogen-activated protein kinase (MAPK); in addition, the infarct size was measured. Compared to the I/R group, the M group showed a significant decrease in TNF-α levels, p38 MAPK activity, and the myocardial infarct size (I/R group 37.8% ± 1.7% vs 21.5% ± 2.4%; P < 0.05). Thus, morphine preconditioning in the delayed phase may exert protective effects on myocardial I/R injury by inhibiting myocar-dial p38 MAPK activity and decreasing TNF-α production.
Assuntos
Estenose Coronária/tratamento farmacológico , Precondicionamento Isquêmico Miocárdico/métodos , Morfina/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Entorpecentes/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Estenose Coronária/genética , Estenose Coronária/metabolismo , Estenose Coronária/patologia , Modelos Animais de Doenças , Expressão Gênica , Injeções Intravenosas , Masculino , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Coelhos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
This study aimed to investigate the protective effects and the mechanisms underlying these effects of isoflurane preconditioning in the delayed phase of myocardial ischemia-reperfusion injury. We randomly divided 30 healthy male New Zealand white rabbits into three groups with 10 rabbits in each group as follows: sham operation group (C group), ischemia-reperfusion group (I/R group), and 2.0% isoflurane preconditioning group (S group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group underwent left coronary artery occlusion for 40 min and reperfusion for 120 min. Rabbits in the S group received inhalation of 2.0% isoflurane and 100% oxygen for 2 h; after 24 h, rabbits in this group received the same treatment as that administered to rabbits in the I/R group. We examined the tumor necrosis factor alpha (TNF-α) levels in each group 20 min before occlusion of the left coronary, 20 and 40 min after occlusion of the left coronary artery, and 1 and 2 h after myocardial reperfusion. After reperfusion, immunoblotting was used to measure the myocardial caspase-3 expression levels, and the infarct size was measured using Evans blue and tetrazolium chloride staining. The levels of TNF-α and caspase-3 were lower in the S group than in the I/R group, and the myocardial infarct size decreased in the S group. Thus, isoflurane preconditioning in the delayed phase exerted protective effects by decreasing the myocardial caspase-3 expression and TNF-α production in a rabbit model of ischemia-reperfusion injury.
Assuntos
Caspase 3/metabolismo , Precondicionamento Isquêmico/métodos , Isoflurano/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo , Animais , Caspase 3/biossíntese , Masculino , Modelos Animais , Miocárdio/metabolismo , CoelhosRESUMO
We examined the protective effects of Ginkgo biloba extract (EGb761) postconditioning on myocardial ischemia reperfusion injury in rabbits. Four groups of 8 white rabbits were allocated to: pseudo surgery group: the left coronary was lined without blocking for 160 min after thoracotomy; ischemia and reperfusion group (IR): the left anterior descending coronary artery was blocked for 40 min and reperfused for 120 min; ischemic postconditioning group: the left anterior descending artery was ligated for 40 min, reopened for 30 s and ligated for 30 s, repeated three times, and then reperfused for 120 min; EGb761 postconditioning group (E): 100 mg/kg EGb761 was injected into a vein while the left coronary artery was opened for 1 min. The reperfusion took 120 min. Internal carotid arterial blood in each group was collected for cTnI measurement at five times: 20 min before occlusion of the left coronary artery, 20 min after left coronary artery occlusion, 40 min after left coronary artery occlusion, 1 h after myocardial reperfusion, and 2 h after myocardial reperfusion. Superoxide dismutase (SOD), malondialdehyde (MDA) in the centrifuged blood and myocardial infarction area were measured at the end of reperfusion. We found that the serum cTnI concentrations in the E group during reperfusion decreased significantly compared with those in the IR group. The infarction area was significantly lower in the E group than that in the IR group. The SOD activity in the E group was increased compared with that in the IR group; the MDA content decreased significantly in the E group compared with that in the IR group. We conclude that G. biloba extract postconditioning had myocardial protection effects by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of the myocardial cells.