The protective effects of metoprolol on rat myocardium at 3 400 m / 药学实践杂志

ABSTRACT

Objective To investigate the effects on myocardial mitochondria-related indexes in rats after rapid elevation to 3 400 m altitude and myocardial protection effects with metoprolol.Methods Male Wistar rats were randomly divided into three groups with 12 rats in each group as follows,group A(normal group,55 m above sea level),group B(hypoxia group, 3 400 m above sea level),group C(metoprolol group,3 400 m above sea level).Heart rate and blood pressure were measured during the rapid transfer from the plain(Shanghai 55 m)to plateau of 3 400 m.Then,the rats were anesthetized with chloral hydrate.The blood was collected from the abdominal aorta and blood gas indexes were measured.The heart tissue was homog-enized.The oxidativee stress related parameters,such as superoxide dismutase(SOD),malondialdehyde(MDA)and nitric ox-ide(NO)were assayed.The mitochondrial function related parameters,such as complexes-Ⅰ,Ⅱ,Ⅲ,Ⅳ,succinate dehydro-genase(SDH),malate dehydrogenase(MDH)and adenosine triphosphate(ATP)were measured.Results After the rats were exposed to high altitude,the blood oxygen tension and oxygen saturation in the metoprolol group were increased in com-parison with the hypoxia group.Compared with the normal group,the content of MDA in the hypoxia group was increased sig-nificantly,while the content of SOD and NO were decreased significantly(P<0.01),the mitochondrial complex Ⅰ,Ⅱ,Ⅲand Ⅳ were also decreased 44.49%,32.38%,34.43% and 20.16%.Compared with hypoxia group,the MDA was decreased by 13.72%,while SOD and NO were increased by 25.73% and 168.55%,the activity of mitochondrial complexes were also increased by 44.92%,33.73%,37.11% and 10.09% for metoprolol group.The respiratory chain SDH and MDH in hypoxic group were decreased by 29.51% and 42.79% and the activity of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and T-ATPase were decreased by 20.24%,27.56% and 33.32% in comparison with the normal group.After intervention with metoprolol,SDH and MDH were increased by 47.36% and 88.57% separately,the activities of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and T-ATPase were also increased by 31.92%,26.95%,44.93% in comparison with hypoxia group.Those results indicated that metoprolol can increase ATPase activity.Conclusion Under the condition of acute hypoxia at 3 400 m above sea level,myocar-dial injury is related to the changes of oxidative stress and mitochondrial-related enzyme activity.Metoprolol helps to normalize the related indicators and provides the protection for myocardial injury caused by hypoxia.