[Analysis of death characteristics and its potential mechanisms in rats with endotoxin- induced cardiomyopathy].

Objective: To approach the changes in heart failure and dying regularity of rats with endotoxin-induced cardiomyopathy, and to offer some help for clinical diagnosing and further investigation.

Methods: Injecting refined endotoxin (10 mg/kg) via vein of Wistar rats. The first experiment: antidromic observing the endotoxic rats from death to the beginning to discover the performance of clinic heart function which could forecast death. The second experiment: setting 6 rats per group, respectively killing the rats at 4, 8, 16, 24, 32, 40, 48 and 72 hours after endotoxin injection, and killing 6 normal rats as control group, getting the tissue of left ventricle for biochemistry test, routine pathological examination, transmission electron microscope examination, expression level of α(1)-actin gene with reverse transcription-polymerase chain reaction (RT-PCR), and serum creatine kinase (CK) was test within 24 hours.

Results: The first experiment: heart rate (HR) and left ventricular end-systolic pressure (LVESP) of endotoxic rats began significant lower than normal at 4 hours before death (F(1)=22.032, P(1)=0.000; F(2)=29.420, P(2)=0.000), maximum rate of rise/drop of left ventricular pressure (±dp/dt max) began significant lower than normal at 8 hours before death (F(1)=17.272, P(1)=0.000; F(2)=19.685, P(2)=0.000), left ventricular end-diastolic pressure (LVEDP) showed no significant during the whole time (F=0.265, P=0.988). The heart function of all the rats showed no significant changes in the first 4 hours after injection. Mortality was 73.9% from injection to 24 hours later. Most of them died in 8-16 hours after injection. The one who had survived over 24 hours could have 2/3 probability to survive to 48 hours. The second experiment: CK in serum of different groups showed no significant difference (F=0.402, P=0.805), but showed obvious discreteness in each group except normal group. Electron microscopy and pathological examination showed obvious intracellular and intercellular damage since 8 hours later from injection. Pathology displayed that cells range disorder, mitochondria swelling, capillary hemorrhage, transverse striation disappearing, construction of myocardial cell loosing, and lateral dissociation phenomena. Electron microscopy discovered that the fiber direction and transverse striation became vague and disappeared, mitochondria got injury, the fiber became disordered, cell-cell junction were damaged seriously. Compared with the control group (0.637±0.160), the gene expression level of α(1)-actin decreased after endotoxin injection. The value dropped to the bottom at 8 hours (0.493±0.067) after injection and then rised slowly but dropped to the second wave trough again at 32 hours (0.875±0.128), but had no statistic significance; the expression of α(1)-actin gene eventually rised significantly at 40, 48, 72 hours after injection (2.231±0.545, 1.850±0.436, 2.062±0.340, all P<0.01).

Conclusions: Endotoxic myocardiopathy does not result from plasmalemma destroy. Damage of α(1)-actin is a significantly important factor for endotoxic myocardiopathy.