Short-term cardioprotective effects of trimetazidine on acute myocardial infarction in rats

AIM: To observe the myocardial protective effects of trimetazidine on myocardial infarction (MI) in Sprague-Dawley (SD) rats. METHODS: Ninety SD rats were randomly assigned to 3 groups (n=30 each): myocardial infarction group (MI group), MI+trimetazidine group (MT group) and sham group (S group). By permanently ligating the left anterior descending artery, the MI model was set up in the rats in MI group and MT group. Before and after setting up the MI model, normal saline was given to the rats in MI and S group by gavage. On the other hand, trimetazidine (3 mg/kg,twice per day) was given to the rats in MT group by gavage. At 8 h, 24 h and 48 h after applying trimetazidine, the serum level of cardiac troponin I (cTnI) was measured. At the 1st week, 2nd week and 4th week after treated with trimetazidine, the size of myocardial infarction, the maximum rising rate of the left ventricular systolic pressure (+dp/dt_max) and the maximum descending rate of the left ventricular diastolic pressure (-dp/dt_max) were measured. Also at the 1st week after applying trimetazidine, the cardiomyocyte apoptotic index was detected. RESULTS: Compared with MI group 2 weeks after applying trimetazidine, +dp/dt_max significantly increased in MT group , and -dp/dt_max also significantly increased in MT group . Four weeks after applying trimetazidine, +dp/dt_max significantly increased in MT group , and -dp/dt_max also significantly increased in MT group . At 8 h and 48 h after applying trimetazidine, no statistically significant difference (P＞0.05) of serum cTnI between MI group and MT group was observed. However, at 24 h after applying trimetazidine, the serum level of cTnI decreased in MT group as compared with MI group . Aditionally, trimetazidine significantly decreased the infarction size of myocardium in MT group (0.248±0.052) as compared with MI group (0.362±0.082, P<0.01). CONCLUSION: Trimetazidine has short-term cardioprotective effects on the rats with acute MI by improving myocardial systolic and diastolic functions, reducing infarct size and inhibiting apoptosis.     

Effects of non-excitatory electric stimulation on cardiac function in normal and infarcted heart rabbits and it's regional effect on myocardium

AIM: To investigate the influences of electric stimulation applied during the absolute refractory period (ARP) on the cardiac function of normal rabbits and rabbits after myocardial infarction (MI) and to observe the regional effects of this electric stimulation. METHODS: 64 rabbits were randomly assigned to normal and MI groups and each group was then divided into the anterior and posterior groups. A thoracotomy was performed 4 weeks after MI in rabbits. One set of electrodes was inserted into the anterior and posterior wall of left ventricle of the anterior and posterior groups, respectively. Current pulses were delivered during the ARP (called CCM) during sinus rhythm in rabbits. The left ventricular systolic pressure (LVSP) and the left ventricular end diastolic pressure(LVEDP) as well as maximum positive and negative left ventricular pressure change (±dp/dt_max) were observed. RESULTS: In the normal and MI groups, LVSP, +dp/dt_max significantly increased, and LVEDP, -dp/dt_max were reduced during CCM stimulation compared with the baseline (P<0.05). In the normal rabbits, electric stimulation in the anterior group improved the cardiac function more significantly than that in the posterior group (P<0.05). In the MI rabbits, there was no difference between the anterior and the posterior groups (P>0.05). CONCLUSION: Electric stimulation delivered during the ARP significantly enhances the contractility and the relaxation of myocardium in normal rabbits and rabbits after MI, and the effects of CCM stimulation on heart are regional.     

Role of bradykinin in the therapeutic effect of enalapril on left ventricular hypertrophy and cardiac function after myocardial infarction in rats

AIM:To investigate the influences of bradykinin(BK)on left ventricular hypertrophy and cardiac function in angiotensin-converting enzyme inhibitor(ACEI) therapy in rats after myocardial infarction.METHODS:The effects of enalapril (500 μg·kg^-1·d^-1), enalapril (500 μg·kg^-1·d^-1)with BKB₂ receptor antagonist (Hoe-140 500 μg·kg^-1·d^-1), losartan(3 mg·kg^-1·d^-1) on left ventricular end-diastolic pressure (LVEDP), maximum positive left ventricular pressure change (+dp/dt_max) and LVW/BW as well as V(m)n of noinfarcted area were examined after 4 weeks treatment in rats after myocardial infarction.RESULTS:The values of LVEDP, LVW/BW and V(m)n of three treatment groups were higher than that of untreated MI group (P＜0.05),but the +dp/dt_max of three treatment groups were not significantly different compared with the untreated MI group. In addition, no significant difference in MAP was observed among the three treatment groups, but the LVW/BW and V(m)n of enalapril+Hoe-140-treated group were higher than that of enalapril-treated group (P＜0.05) .CONCLUSION:Enalapril can prevent left ventricular hypertrophy and improve cardiac function independent of blood pressure after myocardial infarction, which is partly due to the inhibition of BK degradation.     

Xinshuaikang inhibits myocardial autophagy and MAPK/ERK1/2 signaling pathway in rats with chronic heart failure

AIM:To explore the effect of Xinshuaikang on myocardial autophagy in the rats with chronic heart failure and its relationship with the MAPK/ERK1/2 signaling pathway. METHODS:The rats were divided into sham group, model group (rat model of chronic heart failure was established by ligation of anterior descending branch of left coronary artery), low-, middle-, and high-dose Xinshuaikang treatment (TL, TM and TH) groups and captopril group (treated with captopril as positive control), with 12 in each group. Doppler echocardiography was used to evaluate the cardiac function. The morphological changes of the myocardium were observed by HE staining. TUNEL staining was used to detect cardiomyocyte apoptosis. The expression of microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) in the myocardium was detected by immunofluorescence labeling. The protein levels of p-ERK, p-p38 MAPK, LC3-Ⅱ, beclin-1 and p62 in the myocardium were determined by Western blot. RESULTS:Compared with sham group, left ventricular end-diastolic dia-meter (LVEDD) and left ventricular end-systolic diameter (LVESD) in model group were increased, while left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular ejection fraction (LVEF), cardiac output (CO), left ventricular diastolic pressure (LVDP), left ventricular systolic pressure (LVSP) and maximum rate of rise/decrease of left ventricular pressure (+dp/dt_max/-dp/dt_max) were decreased (P<0.05). The myocardial cells were deformed and necrotic, and the myocardial fibers were broken, with inflammatory cell infiltration. The apoptotic rate, the positive rate of LC3-Ⅱ, and the protein levels of p-ERK, p-p38 MAPK, LC3-Ⅱ/LC3-I and beclin-1 were increased, and the protein expression of p62 was decreased (P<0.05). Compared with model group, the levels of LVEDD and LVESD were decreased, LVPWTd, LVPWTs, LVEF, CO, LVSP, LVDP, +dp/dt_max and -dp/dt_max were increased in Xinshuaikang groups and captopril group (P<0.05). The morphological changes of myocardial cells were gradually returned to normal, and inflammatory cell infiltration, the apoptotic rate and the positive rate of LC3-Ⅱ were decreased. The protein levels of p-ERK, p-p38 MAPK, LC3-Ⅱ/LC3-I and beclin-1 were decreased, and the protein expression of p62 was increased (P<0.05). CONCLUSION:Xinshuaikang inhibits myocardial auto-phagy to play a role of cardiac protection in the rats with chronic heart failure, and its mechanism may be related to inhibition of MAPK/ERK1/2 signaling pathway.     

Effects of valsartan alone or in combination with benazepril on blood pressure and left ventricular hypertrophy in spontaneously hypertensive rats

AIM:To evaluate the effects of different doses of valsartan alone or with concomitant be-nazepril on blood pressure,left ventricular hypertrophy,RAASfunction and endoxi nlevel in spontaneously hy-pertensive rats(SHR).METHODS:Thirty SHR(fourteen-week-old,male)were divi ded into five groups(six rats in each group):SHR control group:fed with normal saline;benazepril group:fed with 1 mg·kg^-1·d^-1benazepril);low dose valsartan group:fed with 8 mg·kg^-1·d^-1valsartan;high dose valsartan group:fed with 24 mg·kg^-1·d^-1valsartan;combination drug therapy group:fed with valsartan(8 mg·kg^-1·d^-1)and benazepril(1 mg·kg^-1·d^-1),all for 8 weeks.WKY control group(n=6):fed with normal saline for 8 weeks.RESULTS:SBP,LVM/BW,TDMof SHR were remarkably lower than those of control after drug i n-tervene,and effect on SBP was most remarkable in high dose valsartan group and i nthe combi nation drug ther-apy group;effect on LVM/BW,TDM were most remarkable in combination drug therapy group.Renin activi-ties in plasma and myocardiumwere remarkably i ncreased in drug i ntervene groups.The levels of AngⅡi nplasma and myocardiumwere remarkably increased in two different dose of valsartan treati ng group,and thelarger dose of valsartan were,the higher levels of AngⅡin plasma and myocardium were;decreased in be-nazepril treati ng group and combination drug therapy group.Na⁺-K⁺-ATPase activities in myocardi umwere remarkably i ncreased and the level of endoxi n i n myocardium were remarkably decreased as SBP de-creased after drug intervene.CONCLUSION:Different dose of valsartan alone or combi ned with benazeprilcan decrease SBP of SHR,have the effect of inhibiti ng progression of ventricular hypertrophy.The effect ofcombination drug therapy group was most remarkable among five groups and can avoi d the si de effect of highAngⅡin plasma and myocardiumduri ng long-termuse of valsartan alone.     

Effects of different β-adrenergic receptors on cardiac systolic and diastolic functions in hypoxic stress rats

AIM:To explore the effects of different β-adrenergic receptors (β-AR) on the left and right ventricular systolic and diastolic functions in rats under acute hypoxic stress. METHODS:The healthy male SD rats were randomly divided into 4 groups (n=7):control group, non-selected β-AR blocker propranolol group, selected β₁-AR blocker atenolol group and selected β₂-AR blocker ICI 118,551 group, and then the rats were exposed to normoxia (20.9% O₂, 79.1% N₂) and hypoxia (15.0% O₂, 85.0% N₂) condition respectively at the altitude of 2 260 m (Xining, China). The heart rate (HR), the left ventricular systolic pressure (LVSP), the right ventricular systolic pressure (RVSP), and the maximum raise/decline rate of left and right ventricular pressure (±dp/dt_max) were monitored, and the arterial blood gas in normoxia and hypoxia condition were compared to explore the effect of β-AR on the left and right ventricular systolic and diastolic functions in acute hypoxic stress rats. RESULTS:Under normoxia condition, the LVSP, ±dp/dt_max of left ventricular were decreased in propranolol group, atenolol group and ICI 118,551 group, the RVSP and ±dp/dt_max of right ventricle were decreased in propranolol group and atenolol group (P<0.05). Under hypoxia condition, the PaO₂, LVSP, ±dp/dt_max of left ventricle were decreased in all groups compared with the normoxia group, and the ±dp/dt_max of right ventricle was increased in all groups (P<0.05), also the degree of index change in control group was more obvious than that in propranolol group and atenolol group. CONCLUSION:The activation of β₁-AR is an important compensatory regulation for heart function during hypoxic stress. However, the compensatory enhancement of right heart function under acute hypoxia condition which through tonogenic dilation is more significant for maintaining the normal circulating blood flow.     

Dendranthema morifolium attenuated the reduction of contraction of isolated heart and cardiomyocytes induced by ischemia/reperfusion

AIM: To investigate the effect of Dendranthema morifolium (Ramat) Tzvel (DM) on isolated rat heart and ventricular myocytes during ischemia/anoxia and reperfusion/reoxygenation.METHODS: The Langendorff perfused rat hearts were used to measure intraventricular pressure and coronary flow. The cell contraction and intracellular calcium transient in enzymatically isolated ventricular myocytes were determined. RESULTS: (1) DM (0.5 g/L) significantly attenuated the inhibitory effects induced by ischemia/reperfusion on left ventricular developed pressure (LVDP), ±dp/dt_max, coronary flow and LVDP×HR, meanwhile increased the content of SOD and decreased the content of MDA in the myocardium; (2) DM (0.5 g/L) attenuated the inhibitory effects of anoxia and reoxygenation on i transient and cell contraction in isolated ventricular myocytes. CONCLUSION: DM attenuated the effects on contractility and intracellular calcium induced by ischemia/anoxia and reperfusion/reoxygenation in the isolated rat heart and the ventricular myocytes. The mechanism might be related to increase in SOD activity and maintaining [Ca]i homeostasis.     

Activation of corticotrophin releasing hormone-containing neurons in hypothalamic paraventricular nucleus contributes to sympathoexcitation in rats with congestive heart failure

AIM:To observe the expression of corticotropin releasing hormone (CRH) within the paraventricular nucleus of hypothalamus (PVN) and to explore the relationship between the activated CRH-containing neurons and sympathetic activity in rats with heart failure (HF).METHODS:Healthy male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to induce HF,and chronic intracerebroventricular (ICV) infusion was performed by osmotic pump for 4 weeks.The rats in sham group and HF group were given vehicle (VEH;artificial cerebrospinal fluid 0.25 μL/h).The rats in HF plus treatment group were treated with CRH competitive inhibitor αh-CRH (15 mg/h).Meanwhile,the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery.After 4 weeks,left ventricular end-diastolic pressure (LVEDP) and maximum positive/negative change in pressure over time (±dp/dt_max) were determined.The right ventricular-to-body weight (RV/BW) and lung-to-body weight (lung/BW) ratios were calculated.The renal sympathetic nerve activity (RSNA) was recorded and the plasma norepinephrine (NE) level was measured.The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone (ACTH) levels were measured.RESULTS:Compared with the sham-SD rats,the HF-SD rats had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased),accompanied by decreased±dp/dt_max and increased RSNA,plasma NE,LVEDP,lung/BW and RV/BW.However,ICV treatment with αh-CRH attenuated these changes in the HF-SD rats (P<0.05).Compared with the sham-Fisher 344 rats,the HF-Fisher 344 rats also had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased).In addition,they had significantly increased RSNA and plasma NE level,higher LVEDP,RV/BW and lung/BW,and lower±dp/dt_max(P<0.05).Compared with the SHAM-Lewis rats,the HF-Lewis rats had not significantly changed in the above parameters.CONCLUSION:In CHF,the CRH-containing neurons in PVN are activated,thus aggravating cardiac function by increasing sympathoexcitation.     

Effect of adenosine infusion before ischemic preconditioning on immature myocardial reperfusion injury in neonatal rabbits

AIM and METHODS:To investigate the cardioprotective effect of adenosine infusion before ischemic preconditioning on immature myocardial reperfusion injury in rabbit heart. Isolated perfused working heart model were performed, all hearts were subjected to 2-hour global hypothermic ischemia and received intermittent cold cardioplegia perfusion.RESULTS:During reperfusion, the recovery of left ventricular systolic pressure, left ventricular end-diastolic pressure, +dp/dt_max, and -dp/dt_max of hearts received adenosine infusion before ischemic preconditioning were significantly improved, myocardial adenosine triphosphate and adenosine diphosphate content and superoxide dismutase activity were higher, the leakage of myocardial creatine kinase and the malondialdehyde content were lower, and myocardial water content was obviously less.CONCLUSION:These results suggest adenosine infusion before ischemic preconditioning enhances cardioprotection of ischemic preconditioning against immature myocardial reperfusion injury in the rabbit heart.     

Cellular mechanisms of losartan on reversing left ventricular hypertrophy in spontaneously hypertensive rats

AIM:To investigate the role of proliferation and apoptosis in hypertensive left ventricular hypertrophy (LVH) and the effect of AT₁ blockade with losartan. METHODS:Left ventricles (LV) from 12, 24-week-old SHR (SHR₁₂, SHR₂₄), 24-week-old SHR treated with losartan (15 mg·kg^-1·d^-1, SHR-L₂₄) during 12 weeks, and age-matched WKY rats (WKY₁₂, WKY₂₄) were studied. Expression of PCNA was examined by immunohistochemistry. Apoptotic cells in LV sections were assessed by TUNEL method. Levels of fas mRNA were quantitated by RT-PCR. RESULTS: Compared with age-matched WKY, SHR₁₂ and SHR₂₄ showed increased LV hypertrophied index (HI), increased apoptotic index (AI) of myocytes (P＜0.01), but decreased AI of fibroblasts (P＜0.05). Moreover, SHR₁₂ exhibited increased PCNA labeling of myocytes (P＜0.05) with similar positive rates of fibroblasts.It was also showed that losartan reversed HI, significantly reduced the AI of myocytes and significantly increased the AI of fibroblasts. RT-PCR disclosed that levels of fas mRNA positively correlated with the frequency of apoptosis in LV of either SHR or WKY (r=0.52, P＜0.05). CONCLUSION:The cellular changes of LVH in adult SHR manifest as the imbalance between proliferation and apoptosis of myocytes, and insufficient apoptosis of fibroblasts. The mechanisms of losartan on reversing LVH may be mediated through adjusting the abnormal amount of cells and the expression of fas gene.     

Long-term effects of TCV116 on left ventricular remodeling and heart function after myocardial infarction in rats

AIM: To investigate the effects of long-term TCV116 on left ventricular remodeling and heart function after myocardial infarction. METHODS: Myocardial infarction (MI) was caused by ligation of the left anterior descending coronary artery in rats. One week after the surgical performance, the surviving rats were randomly assigned to the following treatment protocols: (1) MI rats with no therapy; (2) MI rats treated with TCV116 2 mg/kg per day; (3) Sham-operated control; (4) Sham-operated rats, treated with TCV116 2 mg/kg per day. At 22 weeks, cardiac hemodynamic parameters such as MAP, LVSP, dp/dt_max and LVEDP, and histomorphometric parameters such as LVW/BW and LVCA/BW were measured, mRNA of cardiac genes such as βMHC, BNP, TGF-β₁, collagen I and III were quantified, and survival rates were calculated. RESULTS: Compared with sham-operated rats, MI rats without therapy showed significant increases in histomorphometric parameters as well as in mRAN expressions of cardiac genes (P<0.01); While their hemodynamic parameters were significantly impaired (P<0.01), and survival duration shortened (P<0.05). Compared with MI rats without therapy, MI rats treated with TCV116 showed significant attenuation of mRAN expression of cardiac genes (P<0.01); While their hemodynamic parameters were significantly improved (P<0.05 or P＜0.01), and survival duration extended (P<0.05). CONCLUSION: Treatment with long-term angiotensin II type 1 receptor antagonist may improve left ventricular remodeling and cardiac function after MI in rats.     

Characteristics of morphology and left ventricular function in the mouse with myocarditis

AIM:To determine the relationship between microhistology and cardiac contractility in myocarditis animal model. METHODS: Setting up myocarditis animal model by injecting Coxsackivevirus B₃ (CVB₃) into mice, then observed myocardial morphological changes and measured left ventricular function of mice at the time of first three days and two weeks after injecting CVB₃. RESULTS:Subcellular structure (mitochondria) changed at the first three days after injecting CVB₃. The left ventricular pressure (LVP) and the rate of intraventricular pressure development (dp/dt) which is the index of reflecting cardiac contractility depressed in this stage (14.2±0.8) kPa and (273.1±10.0)kPa/s, respectively. There were (17.1±0.7)kPa and (359.8±9.3)kPa/s in normal mice, respectively (P＜0.01). Myocardial lesions were more severe during immune response stage-two weeks after injecting CVB₃, including myocardial inflammation and necrosis. LVP was (11.8±0.2)kPa and dp/dt was (209.5±6.1)kPa/s in immune response stage. There was significant difference between mice with myocarditis at early stage and at immune response stage (P＜0.01).CONCLUSIONS:The factor of causing the depression of cardiac contractility in early stage (virus-induced damage) is mainly change of subcellular structure. Mitochondria cannot provide energy as normal. There were more severe myocardial lesions in later stage (cell-mediated autoimmune response)than in early stage. The depression of cardiac contractility is a consequence of multifactor.     

Effect of livin-modified BM-MSCs transplantation on cardiac function following acute myocardial infarction in a rat model

AIM: To study the effect of livin gene-modified bone marrow mesenchymal stem cells(BM-MSCs) transplantation on the cardiac function following acute myocardial infarction in a rat model and the expression of livin, caspase-3, caspase-7 and caspase-9 in the livin gene-modified BM-MSCs. METHODS: The MSCs were obtained by the whole bone marrow culture method, and the apoptosis of the MSCs after infection with adenovirus vector carrying enhanced green fluorescent protein(EGFP) gene and livin recombinant vector(rAd-livin) were detected by flow cytometry. The expression of livin, caspase-3, caspase-7 and caspase-9 was detected by Western blot. After permanent left anterior descending artery occlusion, the rats were randomized to receive intramyocardial injection of DMEM without cells(vehicle group), or containing MSCs(MSCs group), MSCs(EGFP)(rAd-control/MSCs group) or MSCs(livin)(rAd-livin/MSCs group). Left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVEDP), the maximum increased rate of left ventricular pressure(-dp/dt_max) and the maximum decline rate of left ventricular pressure(+dp/dt_max) were recorded for evaluating the cardiac functions. RESULTS: The apoptosis of rAd-livin/MSCs was significantly decreased as compared with MSCs and rAd-control/MSCs(P<0.05). Meanwhile, the expression of caspase-3, caspase-7 and caspase-9 was significantly downregulated as compared with the other 2 groups(P<0.05). The cardiac function in rAd-livin/MSCs group was significantly improved as compared with DMEM group, and those in the other 2 groups got the similar results, but the function in rAd-livin/MSCs group was better improved. Meanwhile, the number of surviving cells in rAd-livin/MSCs group was significantly improved as compared with the other 2 groups. CONCLUSION: The apoptosis of MSCs is decreased after rAd-livin transfection, and the expression of caspase-3, caspase-7 and caspase-9 is also significantly downregulated while the expression of livin is significantly upregulated. Transplantation of livin-modified BM-MSCs by lentiviral vector results in better prognosis for treating myocardial infarction by enhancing cell survival.     

Effects of atorvastatin on expression of cytochrome P450 hydroaylase in spontaneously hypertensive rats

AIM: To investigate the effects of atorvastatin on blood pressure and expression of cytochrome P450 hydroaylase (CYP) 4A1 in spontaneously hypertensive rats (SHR). METHODS: SHRs (n=18) were randomly divided into three groups: SHR control group, 50 mg atorvastatin (HATV) group and 10 mg (LATV) group. Six male Wistar-Kyoto rats were selected as normal control group (WKY group). All rats were given vehicle once a day by gavage for 10 weeks. Systolic blood pressure (SBP) was measured before and after treatment every 2 weeks. The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney, and aorta were detected by RT-PCR and Western blotting analysis, respectively. Plasma lipids were also measured.RESULTS: SBP in all SHR groups was much higher than that in WKY group before experiment (P<0.01). Compared with SHR control group, SBP significantly decreased in HATV group at 6, 8, 10 weeks and in LATV group merely at 10 weeks (P<0.01 or P<0.05). The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney and aorta tissues of SHR control group were significantly higher than those in WKY group (P<0.01 or P<0.05). After 10 weeks, the levels of CYP 4A1 mRNA, protein and plasma lipids in HATV and LATV groups were markedly lower than those in SHR control group (P<0.01 or P<0.05).CONCLUSION: Atorvastatin down-regulates the expressions of CYP 4A1 mRNA and protein in SHR, which may be the mechanism of the favorable effects of statins on regulation of hypertension.     

Comparison on left ventricular contractility between Tibetan antelope and Tibetan sheep

AIM: To investigate the characteristics of adaptation of the heart to high altitude in Tibetan antelope.METHODS: Both Tibetan antelope and Tibetan sheep were captured at altitude of 4 300 m and then transported to Gurmud (2,800 m), where the study was conducted immediately after arrival. The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and the maximum rate of change in left ventricular pressure (±dp/dt) were measured directly by cardiac catheterization. After the baselines of the parameters were obtained, the animals were inhaled hypoxic gas of 14.6% O₂ or 12.5% O₂, which was simulated to the altitudes of 5,300 m and 6,300 m, and then those measurements were repeated within 15 min. The ratios of heart weight to body weight (HW/BW) and right to left ventricular plus septum weights were determined.The Ultra-structural changes of the cardiac muscle were also observed under electron microscope.RESULTS: The HW/BW of Tibetan antelope was significantly greater than that of Tibetan sheep (P<0.01), and no difference of RV/(LV+IVS) was observed between both animals. At baselines, HR and SBP of Tibetan antelope were significantly lower than those of Tibetan sheep . The value of +dp/dt in Tibetan antelope was similar to that of Tibetan sheep . However, after inhaled 14.6% or 12.5% hypoxic-gas for simulating the altitudes of 5,300 m and 6,300 m, the +dp/dt of Tibetan antelope was significantly increased to 145.1% and 148.1% respectively, while the Tibetan sheep was decreased to 68.4% and 70.5% of those in normoxia condition, respectively. Ultra-structural changes of the cardiac muscle indicated that there were more abundant mitochondria in the myocardium of the Tibetan antelope than those in the Tibetan sheep.CONCLUSION: The heart functions of Tibetan antelope are well adapted to hypoxic environment in the high altitude by increasing myocardial weight and mitochondria. On the other hand, the cardiac contractility of Tibetan antelope is normal in the rest, but obviously increases under stress conditions.     

Expression of angiogenic factors in myocardial tissue of diabetic rats

AIM：To observe the expression of angiogenesis factors in the myocardial tissue of streptozotocin-induced diabetic rats. METHODS：The diabetic rat model was induced by intraperitoneal injection of streptozotocin. After 12 weeks, the cardiac function was measured by MPA cardiac function analysis system. The myocardial collagen volume fraction (CVF) was assessed by Masson staining. The capillary vessels was quantified as the ratio of capillary to myocyte (C/M) using CD31 immunostaining. The expression levels of vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1, endostatin and Ang-2 were observed by Western blotting. RESULTS：Compared with normal control group, the left ventricular end-diastolic pressure (LVEDP) was evidently increased (P<0.01), but left ventricular pressure rise maximum rate (+dp／dtmax), left ventricular pressure decrease maximum rate (-dp／dtmax) and the ratio of capillary/myocyte (C/M) were significantly decreased (P<0.05). The CVF and the expression level of endostatin were significantly increased, whereas the expression levels of VEGF and Ang-1 evidently decreased (both P<0.05) in diabetic rats. However, no marked difference in the expression of Ang-2 between the 2 groups was observed (P>0.05). CONCLUSION：Imbalances between the angiogenic factors (VEGF and Ang-1) and anti-angiogenic factors (endostatin) may play an important role in the pathogenesis of diabetic cardiomyopathy.     

Effect of atorvastatin on HMG-CoA reductase expression in spontaneously hypertensive rats

AIM: To evaluate the effect of atorvastatin on HMG-CoA reductase (HMGR) expression level in spontaneously hypertensive rats (SHR). METHODS: Twelve eight-week-old SHR was randomized into distilled water group (SHR_DW group, n=6) and atorvastatin-treated group (SHR_ATV group, n=6). The age-matched Wistar-Kyoto rats (WKY) were used as control (WKY group, n=6). RT-PCR and Western blotting were used to detect HMGR mRNA and protein expression levels, respectively. Meanwhile, systolic blood pressure (SBP) and serum lipid levels were examined. RESULTS: Ten weeks a treatment, SBP in SHR_ATV group was markedly decreased compared with before treatment and SHR_DW group (P<0.05). The levels of TC, TG, LDL-C and HDL-C in SHR_ATV group were also markedly lower than those in SHR_DW group and WKYgroup (P<0.05). 10 weeks later, HMGR mRNA levels decreased markedly in SHR_ATV group compared to WKY group and SHR_DW group (P<0.05). The similar results were found in HMGR protein expression levels. CONCLUSIONS: Atorvastatin downregulates mRNA and protein expression levels of HMGR in SHR, which not only decreases the serum lipids levels, but also impacts blood pressure to a certain extent.     

Protective role of carnosine on cardiac dysfunction in type 1 diabetes mellitus rat model

AIM:To explore the effects of carnosine (CAR) on cardiac dysfunction in type 1 diabetic mellitus rats and the underlying mechanism. METHODS:The SD rats were randomly divided into 4 groups:control (C) group, control+carnosine (C+CAR) group, diabetes mellitus (DM) group and diabetes mellitus+carnosine (DM+CAR) group (n=10). The rats were sacrificed after 12 weeks. The cardiac function was assessed by ventricular cannulation. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were assessed by ELISA. The mRNA levels of tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β) and IL-6 were measured by real-time PCR. The distribution of connexin 43 (Cx43) was examined by immunofluorescence. The protein levels of Cx43 and protein kinase C (PKC) were determined by Western blot. RESULTS:Compared with the C group, the left ventricular end diastolic pressure (LVEDP) was increased whereas the left ventricular pressure maximum rise/fall velocity (±dp/dt_max) was decreased in the DM group (P<0.01). The activity of SOD decreased while the MDA increased in the left ventricular tissues (P<0.01). The mRNA levels of TNF-α, IL-1β and IL-6 were increased (P<0.01). The Cx43 distribution was irregular. The protein levels of phosphorylated Cx43 and PKCε were elevated (P<0.01). Compared with the DM group, the cardiac function of LVEDP and ±dp/dt_max in DM+CAR group was ameliorated (P<0.01), with increased SOD activity and decreased MDA content (P<0.05). The mRNA levels of TNF-α, IL-1β and IL-6 were reduced (P<0.01). The Cx43 distribution was improved and the protein levels of phosphorylated Cx43 and PKCε were decreased (P<0.01). CONCLUSION:CAR treatment can improve the cardiac function by its anti-oxidative and anti-inflammation effects and suppression of Cx43 abnormalities through PKCε in DM rats.     

Role of benazepril on extracellular signal-regulated kinase activity and expression of B-type natriuretic peptide in spontaneously hypertensive rats

AIM：To investigate the role of benazepril on extracellular signal-regulated kinase (ERK) activity and expression of B-type natriuretic peptide in spontaneously hypertension rat (SHR).METHODS：Wistar Kyoto rats were used as control group.Twenty one 14-week-age SHR were randomized into 3 groups,7 rats each：benazepril group (10 mg·kg-1·d-1);hydralazine group (10 mg·kg-1·d-1) and sham group.In each group drugs or equal volume of vehicle (0.5% carboxymethyl cellulose) were administered respectively for 10 weeks by gavage.The ratio of left ventricle weight to body weight （LVW/BW） was measured to reflect myocardial hypertrophy.The caudal arterial pressure was measured by tail-cuff.Protein expression of p-ERK in myocardial tissue was detected by Western blotting,BNP mRNA in myocardial tissue was examined by RT-PCR,and protein expression of plasma BNP was detected by ELISA.RESULTS：1.Benazepril and hydralazine lowered the blood pressure after 10 weeks treatment (P<0.01).2.The ratio of LVW/BW in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).3.The protein expression of p-ERK in myocardial tissue in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).There was no significant difference of p-ERK expression between SHR hydralazine group and SHR sham group (P>0.05).4.The levels of plasma BNP and BNP mRNA in myocardial tissue in SHR benazepril group were significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).There was no significant difference of plasma BNP and BNP mRNA in myocardial tissue between SHR hydralazine group and SHR sham group (P>0.05).CONCLUSIONS：Benazepril inhibited ERK activation,resulting in regression of myocardial hypertrophy and accompanied by the reduction of BNP level.However,in spite of the effect of lowering blood pressure,hydralazine did not prevent or regress cardiac hypertrophy and did not decrease the level of p-ERK and BNP in SHR.BNP level might serve as a therapeutic index for reversal of myocardial hypertrophy.     

Effect of moxonidine hydrochloride on left ventricular hypertrophy in spontaneously hypertensive rats

AIM:To investate the effect of domestric moxonidine hydrochloride on myocardium fibrosis and coronary artery microvascular structure in left ventricular hypertrophy of spontaneously hypertensive rats(SHR).METHODS:30 male SHR, aged 20 weeks, were divided into group Mox+SHR, Cap+SHR and SHR randomly (10 in each group). 10 age and sex-mached sprauge-dawley rats were designed as normal control(NC). At the end of 13 weeks, left ventricular wight/body weight ratio(LVW/BW), collagen volume fraction(CVF) and standardized perivascular collagen area(PVCA) as well as intramyocardial arterial average medial thickness (AMT) were determined.RESULTS:LVW/BW, CVF, PVCA and AMT in group Mox+SHR were lower significantly than that in group SHR, respectively.CONCLUSION:Long-term antihypertensive treatment with moxonidine hydrochloride reduces myocardium fibrosis and improves impaired coronary artery microvascular structure in left ventricular hypertrophy.