Effect of hypoxia on persistent sodium current in ventricular myocytes from 3-week infarcted rat heart

AIM: To investigate the effect of hypoxia on persistent sodium current (INap) in single ventricular myocyte isolated from acute myocardial infarction (AMI) heart of rats and to study the mechanisms of cardiac arrhythmias that occur after AMI. METHODS: AMI model was induced by ligating the left anterior descending coronary artery in rats. The whole-cell patch clamp technique was used to record the current in epicardial myocytes in infarcted region from rats at 3 week after AMI. RESULTS: In normoxic conditions, the current density of INap in cardiomyocytes of fake operation (FO) and AMI hearts was 0.144±0.022 pA/pF (n=9), 0.121±0.013 pA/pF (n=9，P<0.01)， respectively, which was blocked by tetrodotoxin (TTX). The amplitude of INap was gradually increased with the prolongation of hypoxia time, but the increase in extent of INap in FO cells was significant bigger than that in AMI cells. The INap was blocked by 1 mmol/L glutathione. CONCLUSIONS: After AMI, the amplitude of INaP in infarcted and noninfarcted myocardium showed differences both in normoxic and hypoxic conditions, which increased dispersion of repolarization. This may be one of the reasons of reentrant ventricular arrhythmias that occur after AMI.     

Changes of plasma and myocardial calcitonin gene-related peptide in myocardial stunning rats

AIM: To investigate changes of calcitonin gene-related peptide(CGRP) in myocardial stunning rats. METHODS: Rat in vivo myocardial stunning model was used. CGRP content in plasma and myocardium were determined by radioimmunoassay. RESULTS: Plasma level of CGRP increased significantly (P＜0.01), but in left ventricular myocardium CGRP decreased obviously (P＜0.05) in myocardial stunning group compared with the control group. CONCLUSION: CGRP content in the left ventricular myocardium was negatively correlated with plasma CGRP.     

Impairment of left ventricular function and mechanism analysis after intermittent hypoxia

Intermittent hypoxia (IH) is a direct consequence of obstructive sleep apnea syndrome (OSAS), which results in left ventricular dysfunction, remodeling and myocardial cell injury. Understanding the mechanisms of OSAS is important for us to prevent and treat the cardiovascular complications in the clinical practices. We summarize the effects of IH on left ventricular function, and analyze the mechanisms at the cellular and molecular levels, including oxidative stress, ion exchangers and inflammation. In addition, the effects of endothelin-1 and hypercapnia on IH-induced cardiac injury are discussed.     

Effect of compound salvae-dropping-pill on intracellular free calcium concentration of cultured rat myocardial cells in case of hypoxia and reoxygenation

AIM:To examine the effect of compound salvae-dropping-pill (CSDP) on intracellular free calcium in cultured rat myocardial cells subjected to hypoxia and reoxygenation.METHODS:The Fluo- 3/AM was applied to probe intracellular calcium concentration and the fluorescent intensity was detected using laser confocal microscopy technique.RESULTS:Fluorescent intensity in hypoxia plus CSDP group was significantly lower (1 217.78±312.07) than that of hypoxia group (1 509±508.48), and the Fluorescent intensity of hypoxia/reoxygenation plus CSDP group was also markedly lower (1 567.91±577.61) than that of hypoxia/reoxygenation group (1 617.60±477.53).CONCLUSION:The cultured rat myocardial cells could be effectively protected by administration of CSDP in case of hypoxia and reoxygenation through decreasing the intracellular calcium concentration.     

Effects of nebulized nitroglycerin on acute hypoxic pulmonary hypertension and myocardial impairment in newborn piglets

AIM: To investigate the effects of nebulized nitroglycerin(NTG) on pulmonary, systemic hemodynamics and myocardial impairment during pulmonary hypertension induced by hypoxia in piglets. METHODS: Twenty-four piglets (5-7 days old) were randomly divided into four groups: ① sham group; ② model group;③ NTG1 group; ④ NTG2 group. Mean artery pressure (MAP) and mean pulmonary artery pressure (MPAP) were monitored continuously. Serum CK-MB and cTnI were measured intermittently. Apoptotic cells were detected with TUNEL method. Myoglobin (Mb) and connexin 43 (Cx43) staining were studied by immunohistochemistry. RESULTS: After nebulization, MPAP in NTG1 group and NTG2 group were significantly lower than that in model group (P<0.05 and P<0.01, respectively). Five hours after hypoxia, serum cTnI in NTG1 group and NTG2 group were both significantly lower than that in model group (P<0.01). The percentage of apoptotic cells in NTG2 group was significantly lower than that in model group (P<0.05). Immunohistochemistry method results showed that the expression of Mb and Cx43 in NTG1 group and NTG2 group were both significantly stronger than those in model group (P<0.01 and P<0.05, respectively). CONCLUSION: NTG nebulization produces a selective pulmonary vasodilation either during or after the exposure of hypoxia and improves myocardial impairment in acute hypoxic newborn piglets.     

Effect of Xin-Tong capsule on nitric oxide production and cGMP content of ventricular myocardium in rats with experimental myocardial ischemia

AIM:To study the effect of xin-tong capsule on nitric oxide production and cGMP content of ventricular myocardium in rats with experimental myocardial ischemia. METHODS:Rat model of acute myocardial ischemia induced by pituitrin was used in this study, and the lift of ST segment in ECG was used as the index of myocardial ischemia. The NO₂^-/NO₃^- and cGMP contents of ventricular myocardium in rats with myocardial ischemia were determined.RESULTS: NO₂^-/NO₃^- and cGMP contents in ventricular myocardium of myocardial ischemia were (486±59) nmol/g protein and (0.38±0.08) nmol/g protein, respectively, and markedly lower than those of control (P＜0.01). After administration of Xin-Tong capsule, contents of NO₂^-/NO₃^- and cGMP in ventricular myocardium of rats with myocardial ischemia were obviously elevated . In comparison with control, ST segment of ECG in rats with myocardial ischemia was lifted, and the lift peak of ST segment occur in 45 min after myocardial ischemia (P＜0.01). Pretreatment of Xin-Tong capsule can improve conditions of myocardial ischemia . CONCLUSION:Xin-Tong capsule can elevate the contents of nitric oxide and cGMP, and attenuate myocardial ischemia injury in rats.     

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.     

Effect of fluvastatin on left ventricular remodeling after myocardial infarction in rats

AIM: To clarify the protective effect of long-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on ventricular remodeling after myocardial infarction (MI) in rats and its mechanisms. METHODS: Myocardial infarction were established by ligated left coronary anterior artery in SD rats, 24 hours after the operation, the survival rats were treated by gavage fluvastatin (20 mg·kg^-1·d^-1) or distilled water for 8 weeks. Doppler echocardiography, homodynamic and cardiac histomorphometry were used to assess the ventricular remodeling and cardiac function. The plasma levels of total cholesterol (Tch), creatinine (Cr), glutamic-oxal (o) acetic transaminase (AST), lipid peroxidation (LPO), glutathione perioxidase (GSH-PX), nitrogen monoxide (NO₂^-/NO₃^-) were detected. RESULTS: The Tch, Cr and AST were not significant difference in groups. Left ventricular end-diastole pressure, right relative weight, left ventricular posterior wall thickness, collagen volume fraction and the lung weight were decreased in AMI+fluvastatin group compared to AMI group (P＜0.05, P<0.01); The levels of LPO, NO₂^-+NO₃^- in plasma and LPO in myocardium decreased, but plasma GSH-PX level increased in AMI+fluvastatin group (P＜0.05). CONCLUSION: Fluvastatin ameliorates the ventricular structural remodeling in a rat model of infarction, and delays the development of heart failure. The anti-oxidation mechanism of fluvastatin may take part in this process.     

Correlation between myocardial interstitial collagen remodeling and changes in hemodynamics in rats with myocardial infarction

AIM: To study the relationship between cardiac extracellular matrix remodeling and cardiac function after myocardial infarction. METHODS: We observed sequential changes in collagen contents and collagen Ⅰ/Ⅲ ratios in infarct zone (IZ) and non-infarct zone (NIZ) and their relationship to the parameters of left ventricular systolic and diastolic function in the rat model of myocardial infarction induced by ligation of left main coronary artery. RESULTS: Collagen conteants in IZ and NIZ after 3d of myocardial infarction were significantly higher than those in sham group at corresponding time (P<0.05, P<0.01). Collagen Ⅰ/Ⅲ ratio in IZ decreased on day 3, significantly increased after 7 d (P<0.01). Collagen Ⅰ/Ⅲ ratio in NIZ increased significantly afte14 d. Correlated analysis between collagen contents in IZ or NIZ and collagen type Ⅰ/Ⅲ ratio and maximal ascending velocity (+p'_max) or maximal descending velocity of the left ventricular pressure (-p'_max) was performed and the negative correlation between collagen contents in NIZ and +P'_max (r=-0.589, P>0.05) and -P'_max (r=-0.788, P<0.01) was found. Collagen content in IZ positively correlated to the +P'_max (r=0.70, P<0.50), but not to -P'_max (r=-0.29, P>0.05). Collagen type Ⅰ/Ⅲ ratios in NIZ correlated negatively to the +P'_max (r=-0.504, P>0.05) and -P'_max (r=-0.545, P>0.05), but there were no relationship between collagen type Ⅰ/Ⅲ ratios in IZ and +P'_max or -P'_max in IZ. CONCLUSION: Collagen deposition in IZ after myocardial infarction was of benefit to improvement of systolic function. Collagen deposition in NIZ was harmful to systolic and diastolic function.     

Effects of miR-124 over-expression on right ventricular remodeling in rats with pulmonary hypertension

AIM: To investigate the effect of microRNA-124 (miR-124) over-expression mediated by adeno-associated virus (AAV) on right ventricular remodeling in rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). METHODS: Male SD rats (n=32) were randomly divided into 4 groups:normal control (control) group, MCT+normal saline (NS) group, MCT+AAV-GFP (MCT+GFP) group and MCT+AAV-miR-124 (MCT+miR-124) group. The rats in the latter 3 groups were instilled slowly with 100 μL NS, AAV-GFP and AAV-miR-124 by orotracheal instillation after anesthesia, respectively. Three weeks later, MCT (60 mg/kg) was intraperitoneally injected to establish the PAH model. Right ventricular systolic blood pressure (RVSP) and mean arterial pressure of the rats were measured, and right ventricular hypertrophy index (RVHI) and right ventricular weight index (RVWI) were calculated. The pathological sections of the right heart were stained with Sirius red, and the pathological changes of myocardium were observed under a microscope. The expression of miR-124 in the lung tissues was detected by RT-qPCR. The protein levels of transforming growth factor-β₁(TGF-β₁) and p-Smad2 in right heart tissues were determined by Western blot. RESULTS: Compared with control group, RVSP, RVHI, RVWI and the protein levels of TGF-β₁ and p-Smad2 in MCT+NS group and MCT+GFP group were significantly increased (P<0.05), the right ventricular myocytes were significantly enlarged, and collagen deposition was significantly increased. However, compared with MCT+GFP group, RVSP, RVHI, RVWI and the protein levels of TGF-β₁ and p-Smad2 in MCT+miR-124 group were significantly decreased (P<0.05), the degree of right ventricular myocyte hypertrophy was significantly reduced, and collagen deposition was significantly reduced. CONCLUSION: Over-expression of miR-124 obviously reduces RVSP of rats induced by MCT and relieves myocardial remodeling, which may be related to the down-regulation of TGF-β₁ and p-Smad2.     

Effect of ischemic post-conditioning on myocardial mitochondrial function in isolated rat heart

AIM: To investigate the protective effect of ischemic post-conditioning on isolated rat myocardial mitochondrial function during ischemia/reperfusion, and to study the role of mitochondrial ATP-sensitive potassium channel (mitoK_ATP) in myocardial protection. METHODS: Sprague-Dawley male rats were randomized into 4 groups (n=8 in each group): control group (C), model group (M), ischemic post-conditioning group (IPO) and 5-hydroxydecanoate plus IPO group (5-HD+IPO). The hearts isolated from the SD rats were mounted on a Langendorff apparatus and started with a 20-minute perfusion for equilibration. In C group, the hearts went on perfusion for another 70 min after equilibration. In M group, 4 ℃ St. Thomas cardioplegic solution was administered prior to ischemia, followed by ischemia for 40-minute, and reperfusion for another 30 min. In IPO group, the hearts underwent 40-minute global ischemia after equilibration, then perfusion for 10 s and ischemia for another 10 s. The procedure was repeated 6 times before 28-minute reperfusion. In 5-HD+IPO group, the hearts were perfused with 5-HD (100 μmol/L in K-H solution) and treated as that in IPO group, then reperfusion for 23 min. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and respiratory function of myocardial mitochondria were measured at the ends of equilibration and reperfusion. RESULTS: (1) Compared with the data collected at the end of equilibrium, the MMP was obviously decreased at the end of reperfusion in all groups, The highest in C group. MMP in 5-HD+IPO group was markedly higher than that in IPO group and M group. MMP in IPO group was higher than that in M group. (2) In contrast to that at the end of equilibrium, ROS was obviously increased at the end of reperfusion in all groups. However, ROS was observably higher in M group than that in the other 3 groups, and ROS in 5-HD+IPO group was markedly higher than that in IPO group and C group. ROS in IPO group was higher than that in C group. (3) The respiratory function of mitochondria was obviously injured at the end of reperfusion in all groups. The arrangement of the mitochondrial respiratory function from the best to the worse was C group > IPO group > 5-HD+IPO group > M group. CONCLUSION: Ischemic post-conditioning attenuates myocardial reperfusion injury by maintaining the stability of MMP, decreasing the generation of ROS and preserving the respiratory chain function of mitochondria. The mitoK_ATP antagonist 5-HD can not completely block the myocardial protective effect of ischemic post-conditioning. Myocardial protective effect of ischemic post-conditioning may achieve by activating mitoK_ATP, meanwhile the other factors may also take part in the myocardial protective processes.     

Effects of Tongxinluo on connexin 43 remodeling and ventricular arrhythmia after myocardial infarction in rats

AIM: To determine the effects of Tongxinluo(TXL) on connexin 43(Cx43) remodeling and ventricular arrhythmia(VA) after myocardial infarction(MI) in rats. METHODS: Male SD rats were randomly divided into sham-operated(sham) group(n=25) and operation group(n=75). The left anterior descending(LAD) was ligated in operated group, while the rats in sham group only underwent pericardiotomy. The rats in operation group which survived for 3 d after operation were randomly assigned to TXL group and MI group. The rats in TXL group was administrated with TXL(2 g·kg^-1·d^-1, intragastric administration) for 4 weeks, while normal saline was applied to the rats in sham group and MI group. The levels of interleukin-1β(IL-1β) and endothelin-1(ET-1) in the tissue from the border zone were measured by ELISA after treatment. The distribution and the mRNA and protein expression of Cx43 were detected by immunohistochemical staining, RT-PCR and Western blotting, respectively. The burst pacing was used to induce ventricular arrhythmia(VA). RESULTS: Compared with sham group, the levels of IL-1β and ET-1 and the incidence of VA were significantly increased, while the mRNA and protein expression of Cx43 was markedly reduced with irregular distribution in MI group(P<0.05). Compared with MI group, the levels of IL-1β and ET-1 and the incidence of VA were significantly reduced, while the expression of Cx43 at mRNA and protein levels was markedly increased with augmented linear distribution in the myocardial cell intercalated disc in TXL group(P<0.05). CONCLUSION: TXL reduces the incidence of VA after MI via inhibiting the Cx43 remodeling.     

Effects of catestatin on calcium handling abnormalities and ventricular arrhythmia after myocardial infarction in rats

AIM: To determine the effects of catestatin (CST) on calcium handling abnormalities and ventri-cular arrhythmia (VA) after myocardial infarction (MI) in rats. METHODS: The adult male SD rats (n=85) were randomly divided into sham group (n=20) and operation group (n=65). MI was induced by ligation of the left anterior descending coronary artery in operation group. The rats in sham group underwent pericardiotomy but without ligating the artery. The rats survived for 1 week after operation were randomly assigned to MI group and CST group. The rats in CST group was treated with CST (30 mg·kg^-1·d^-1, intraperitoneal administration) for 4 weeks, while saline was applied to the rats in sham group and MI group. The calcium imaging study was performed by loading isolated ventricular cardiomyocytes with Fura-2 AM. In the whole Langendorff-perfused hearts, the programmed electrical stimulation was used to induce action potential duration (APD) alternans and VA. The protein levels of ryanodine receptor 2 (RyR2), phosphorylated RyR2 (p-RyR2), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII (p-CAMKII) were determined by Western blot. RESULTS: Compared with sham group, the protein levels of p-RyR2 and p-CaMKII, the diastolic intracellular Ca²⁺ concentrations and the inducibility of VA were significantly increased, whereas the thresholds of Ca²⁺ transient (CaT) and APD alternans and the CaT amplitude were markedly decreased in MI group (P<0.01). Compared with MI group, the protein levels of p-RyR2 and p-CaMKII, the diastolic intracellular Ca²⁺ concentration and the inducibility of VA were significantly decreased, while the thresholds of CaT and APD alternans and the CaT amplitude were markedly increased in CST group (P<0.01). No significant difference of the protein expression of RyR2 and CaMKII among the 3 groups was observed (P>0.05). CONCLUSION: CST reduces the susceptibility to VA after MI via preventing calcium handling abnormalities.     

Salvia miltiorrhiza antagonized the alterations of contraction and intracellular calcium of rat ventricular cardiomyocytes induced by anoxia and reoxygenation

AIM:To study the effect of salvia miltiorrhiza (SM) on cell contraction and intracellular calcium of enzymatically isolated rat ventricular myocytes during normoxia and anoxia/reoxygenation.METHODS:Contraction and intracel ular calcium were determined with video tracking system and spectrofluorometric method,and the chemical anoxic method was employed. RESULTS:The ±dL/dt_max, dL of cell contraction and the amplitude of [Ca²⁺]_i in the cardiomyocytes following SM treatment were decreased in a dose-dependent manner. During anoxia, the ±dL/dt_max, dL and amplitude of [Ca²⁺]_i were decreased, while the diastolic Ca²⁺ level was elevated compared with control group. All the contractile parameters and the diastolic Ca²⁺ level were back toward pretreatment values during reoxygenation, but could not return to control level. After the treatment with SM (3 g/L), ±dL/dt_max and dL of cell contraction and the amplitude of [Ca²⁺]_i were higher and the diastolic Ca²⁺ level was lower than those in anoxia/reoxygenation group. CONCLUSION:SM antagonized effects of anoxia and reoxygenation on cell contraction and intracellular calcium in isolated ventricular myocytes.     

新书推荐：《分子克隆实验指南》（第三版）

AIM: To study the effect of panax notoginseng sponins (PNS) on L-type Ca²⁺ current in isolated right ventricle myocytes from chronic hypoxic rats. METHODS: Using whole cell patch clamp recording technique,we measured I_Ca-L in isolated right ventricle myocytes which were divided into three group:control group, chronic hy-poxic group and chronic hypoxic group with PNS(100 mg·kg^-1·d^-1). RESULTS: The result showed I_Ca-L of cells from chronic hypoxic group were significantly larger than the other two groups(P＜0.05). CONCLUSION: PNS decreases L-type Ca²⁺ current of the right ventricle myocytes from chronic hypoxic rats.     

Effects of pentoxifylline on ventricular remodeling and cardiac function of dilated cardiomyopathy rats

AIM: To explore the effects of pentoxifylline (PTX) on ventricular remodeling and cardiac function in dilated cardiomyopathy (DCM) rats.METHODS: Lewis rats were randomly allocated to a myocin-induced dilated cardiomyopathy (DCM) group receiving saline (n=10), a DCM group receiving PTX (PTX group; 25 mg·kg^-1·d^-1, ip, for 30 days, n=10) or healthy control group (n=10). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in the blood plasma were analyzed by ELISA. The extent of fibrosis was estimated using Massons staining and immunohistochemistry analyses. Cardiac structure and function were measured by echocardiography.RESULTS: PTX decreased plasma levels of TNF-α and IL-6, and increased IL-10 level in DCM animals compared with DCM group ［TNF-α: (7.21±0.24) μg/L vs (19.30±1.31) μg/L, P<0.01; IL-6: (119.60±36.58) ng/L vs (189.50±13.25) ng/L, P<0.05; IL-10: (41.26±3.27) μg/L vs (32.45±4.32) μg/L, P<0.05］. Collagen volume fraction (CVF), perivascular collagen area (PVCA) and collagen Ⅰ/Ⅲ ratio were lower in PTX group than those in DCM group ［CVF: (16.45±3.01)% vs (23.33±4.43)%, P<0.05; PVCA: 4.58±2.10 vs 13.74±4.29, P<0.05; Ⅰ/Ⅲ ratio: 2.84±0.67 vs 4.22±0.54, P<0.01］. Left ventricular end-diastolic dimension reduced ［(6.11±0.51) mm vs (6.46±0.28) mm, P<0.05］ and left ventricular ejection fraction elevated ［(77.29±5.20)% vs (62.73±10.11)%, P<0.01］ by PTX compared with DCM.CONCLUSION: PTX modulates plasma levels of inflammatory cytokines, delays the ventricle remodeling and improves the heart function in DCM 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 ischemia or hypoxia on vascular endothelial growth factor production in rat myocardium and its significance

AIM:To determine the relationship between ischemia, hypoxia and the production of vascular endothelial growth factor in rat myocardium and its basic mechanism. METHODS:(1) 28 Wistar rats were randomly divided into 4 groups: group A, normal control;group B, 1 day's acute myocardial infarction;group C, 3 day's acute myocardial infarction;group D, 7 day's acute myocardial infarction. (2) Rat cardiac myocytes cultured were primarily divided into some groups, hypoxia incubated 24 hours; PMA groups, hypoxia incubated 24 hours with PKC activator (PMA), A 0 ng/mL; B 10 ng/mL; C 100 ng/mL; D 1 000 ng/mL; Chelerythrine groups, hypoxia incubated 24 hours with PKC inhibitor (chelerythrine), A 0 nmol/L; B 10 nmol/L. (3) By computer scanned and quantitated, vascular endothelial growth factor (VEGF) protein was detected with immunohistochemical technique. RESULTS:The longer time of ischemia and hypoxia was, the higher the VEGF production.The relat ionship was found between the time of ischemia or hypoxia and the production of VEGF.The product ion of VEGF protein was further promoted by PMA with different concentrat ion, decreased by chelerythrine.CONCLUSION: Ischemia or hypoxia strongly stimulated the production of VEGF in myocardium, which played an important role in autoprotecting of ischemic or hypoxic myocardium. Hypoxia-induced PKC activation is one kind of basic mechanisms in this course.     

Characteristics of energy metabolism in brain mitochondria of rats exposed to hypoxia

AIM:To explore the characteristics of energy metabolism in brain mitochondria of rats exposed to acute and chronic hypoxia. METHODS: Animal grouping: Wistar rats were randomized into acute hypoxic group (AH), chronic hypoxic group (CH) and the control. Respiratory function, F₀F₁-ATPase activity, mitochondrial ATP, ADP and AMP contents and ATP production rate were measured respectively. RESULTS: In AH, brain mitochondrial respiratory state IV (ST₄) was increased, while respiratory control rate (RCR), mitochondrial ATP content, ATP production rate and F₀F₁-ATPase activity were decreased respectively. In CH, ST₄, RCR, mitochondrial ATP content and F₀F₁-ATPase activity were reversed partially.CONCLUSION: Acute hypoxia may impair brain mitochondria energy metabolism by way of depressing mitochondrial oxidative phosphorylation and ATP production and these parameters gain partial reablement during chronic hypoxia.     

Influences of chronic hypoxia on the gene expression of Kv1.3,Kv2.1 and Kv3.1 induced by acute hypoxia in PASMC of rats

AIM and METHODS: Total RNA was extracted from 6th rat subcultured pulmonary artery smooth muscle cells(PASMC) exposed to continual chronic hypoxia or normoxia and the effects of chronic hypoxia on the changes of Kv1.3,Kv2.1,Kv3.1 mRNA in cultured PASMC induced by acute hypoxia were studied by semiquantitative RT-PCR in vitro. RESULTS:①Kv1.3,Kv2.1,Kv3.1 genes were found to be expressed in PASMC of rats exposed either to hypoxia or normxia.②The expression of Kv2.1 and Kv3.1 in 6th subcultured of PASMC in normaxia group could be upregulated by exposure to acute hypoxia,the levels of Kv2.1 and Kv3.1 mRNA were significantly increased from 0.646±0.092, 0.782±0.104 to 1.059±0.134, 0.985±0.116,respectively (P<0.01,n=5). ③PASMC cultured continuously in chronic hypoxia for 6 subcultures and then exposed to normoxia for 12 h,thereafter the expression of Kv2.1 and Kv3.1 were downregulated by acute hypoxia for 6 hours.The level of Kv2.1 mRNA was significantly decreased from 1.008±0.117 to 0.649±0.097 (P<0.01,n=5). CONCLUSION:Kv2.1,Kv3.1 genes might be oxygen sensitive genes.Chronic hypoxia might change the response of these Kv genes of PASMC to acute hypoxia and down-regulate its expression,which might probably decrease the role of Kv in HPV.