| Objective: In terrorism raid, natural disaster and bad man-made project accidents, people might be buried and threatened by blood loss, hypoxia, water and diet depletion, so the life tolerance and vital signs would be affected. Heart is one of the sensitive organs to hypoxia and ischemia, and changes of cardiac structure and function are the key factors deciding life tolerance. There are only few reports about cardiac effects of people under condition of blood loss combined with hypoxia, water and diet depletion. Based on the simulation of bury disaster, this study investigated the structural and functional characteristics of cardiac injury and its mechanism induced by blood loss combined with hypoxia, water and diet depletion. Our results would be important for curing buried people in time and manufacturing monitor device of life exploration.Materials and Methods: Normobaric hypoxia chamber designed and manufactured by our studying team was used to make the oxygen concentration to 10%. One hundred and sixty healthy adult Wistar rats (male : female = 1:1) were divided into 4 groups randomly: control group, blood loss group, hypoxia combined with water and diet depletion group (three lack group) and blood loss combined with hypoxia, water and diet depletion group (blood loss combined with three lack group) . The blood loss model was established by cutting tail. The experiment data were recorded at 1d, 3d, 5d and 7d. Physiological, biochemical, pathological and immunhistochemical methods were used to detect changes of cardiac structure and function, and study the mechanism of hormones, cytokines, factors related to cell apoptosis in the experiment.Results: (1) Changes of hemogram: The numbers of WBC in three lack group and blood loss combined with three lack group reduced in 3-7d ; That of RBC and Hb reduced first and then increased; It indicated hemoconcentration, expecially for males.(2)Changes of blood gas analysis index: The values of pCO2 and pO2 decreased progressively in three lack group and blood loss combined with three lack group. That of PH reduced after 3 days, espescially in males. (3)Changes of myocardial enzymes: The values of LDH and CK decreased obviously in blood loss group,and that of AST had no changes;In three lack group, that of AST,LDH and CK all decreased and then increased. Blood loss combined with three lack group aggravated the changes of LDH and CK.(4)Changes of serum electrolyte:The concentrations of Na+,K+ and Cl- in three lack group and blood loss combined with three lack group showed increased tendency.(5)Changes of cytokines: Serum TNFαincreased temporarily. Serum IL-1 had no obvious changes. Serum IL-6 first decreased then increased.(6)Changes of plasma hormones: Plasma ACTH increased at 1d and then decreased; Serum corticosteroid increased obviously at 7d. The above changes were more obvious in blood loss combined with three lack group.(7)Changes of myocardial structure in rats:Basic pathological changes of blood loss group and three lack group: myocardial cells, degeneration, apoptosis, even necrosis. Myocardial fibers were dearranged, breakage, even deliquescenced. Swelling, cristae disappear and homogenize of mitochondria. Dilatation and granule doffing of endoplasm. Glycogen granule reduced. Apoptosis of vescular endothelia cells. The structural changes aggravated during 1d-7d. The injury was more obvious when three lack combined with blood loss. The pathological changes had characteristics of acute, progressive, whole cardiac and position difference. (Left heart was more obvious than right, ventricle obvious than atrium, inside obvious than outside, myocardial cells obvious than Purkiner cells)(8)Changes of apoptosis index: The apoptosis index of myocardial cells was higher significantly in other three groups than control group(P<0.05,P<0.01). The blood loss combined with three lack group was more obvious than the other two groups at 1d; The increased range showed decrease tendency during 3d-7d. It is probably related to the increase of necrosis myocardial cells.(9)Changes of factors in apoptosis: The expression and MOD value of Bax and Caspase-3 increased 1d-7d. That of Bcl-2 and the value of MOD reduced, especially in 5d-7d. Above changes in blood loss combined three lock group were more obvious than that in three lock group and blood loss group in turn.(10)Changes of factors in ERK signalling pathway: The expressions of p-CREB and RKIP increased at all time, and the value of MOD increased, especially significantly at early time in three lack group and blood loss combined with three lack group. However, the expression of p-ERK and the value of MOD decreased, especially in 5d-7d.According to the results of above (9) and (10), abnormity of factors in apoptosis and in ERK signalling pathway took part in the process of development of myocardial apoptosis .Conclusions: Under the condition of blood loss combined with three lack group: (1) Cardiac function including myocardial enzymes showed obvious abnormality; (2) Cardiac structures were injured seriously, and the apoptosis index of myocardial cell increased. The pathological changes had characteristics of acute, progressive, whole cardiac and position difference. (3) The functional abnormality and structural injury were more serious in blood loss combined with three lack group than that in blood loss and three lack group. The abnormal serum cytokines and plasma hormones both participated in the pathophysiologic process. (4)The apoptosis of myocardial cells correlated with the increase of promoting apoptotic factor (Bax) and the decrease of anti-apoptotic factor (Bcl-2). Furthermore, it might release cytochrome C by mitochondria pathway, activate Caspase-3 and initiate apoptosis of myocardial cells. (5)The abnormal expression of factors in ERK signaling pathway (the increase of RKIP and p-CREB, the decrease of p-ERK) all took part in the process of apoptosis of myocardial cells.
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