Effects of pioglitazone on myocardial energy metabolism and hemodynamics in rats with myocardial infarction

AIM: To observe the effects of pioglitazone on myocardial energy metabolism and hemodynamics in rats with heart failure after myocardial infarction (MI). METHODS: The model of MI was established by ligation of left anterior descending artery. The 20 surviving rats were randomly divided into MI group (n=10) and pioglitazone intervention group (P group,n=10, pioglitazone 3 mg·kg^-1·d^-1 orally). The sham-operated rats (SH, n=10) served as controls. Hemodynamic parameters were measured. The ratio of left ventricular weight to body weight (LVW/BW) and the ratio of right ventricular weight to body weight (RVW/BW) were calculated after 8-week treatment. The expression of PPARγ was examined by Western blotting. Mitochondrial respiratory function was determined by Clark oxygen electrodes. The size of adenine acid pool (ATP, ADP and AMP) in mitochondria was measured by HPLC. The adenine nucleotide translocator(ANT) activity was detected by the atractyloside-inhibitor stop technique. RESULTS: Compared with SH group, the protein expression of PPARγ was significantly decreased in MI group (P<0.01). The mitochondrial respiratory activity, the transport activity of ANT and the high-energy phosphate content were decreased in MI group (P<0.01), and the hemodynamic parameters were in disorder (P<0.01). Compared with MI group, the protein expression of PPARγ in P group was significantly increased. The mitochondrial respiratory activity, the high-energy phosphate content, the transport activity of ANT were improved (P<0.01). However, the hemodynamic parameters were not significantly changed.CONCLUSION: Pioglitazone increases the protein expression of PPARγ and improves myocardial energy metabolism in the development of heart failure in the rat model of myocardial infarction, but dose not change the hemodynamic parameters significantly.     

人参果皂苷对实验性心肌缺血的保护作用

通过异丙肾上腺素及垂体后叶素诱发急性心肌缺血模型，观察人参果皂苷(GFS)对实验性心肌缺血的保护作用。结果表明，GFS30、60mg／kg对皮下注射异丙肾上腺素缩短小鼠的常压缺氧状态下的存活时间均具有明显对抗作用，20、40mg／kg均可明显减轻静脉注射垂体后叶素诱发的大鼠急性心肌缺血心电图(ST段抬高及T波高耸)变化程序，表明GFS对实验性心肌缺血具有明显的保护作用。     

Changes in plasma neurotension level of patients with coronary heart disease and its clinical significance

AIM: To investigate the plasma neurotensin(NT) concentration in patients with coronary heart disease: acute myocardial infarction(AMI),unstable angina(UA),stable angina pectoris(SAP), old myocardial infarction (OMI), and to study the relationship between the plasma NT level and the myocardial ischemia . METHODS:The plasma NT concentration of 30 patients with AMI,32 pat ients with UA,35 patients with SAP,31 pat ients with OMI and 32 normal controls were determined by radioimmunoassay(RIA). RESULTS: The plasma NT level in patients with AMI(24 h),in patients with UA when angina attacked is significantly higher than that of healthy controls. The plasma NT level in patients with SAP, in patients with OMI is not significantly different from that of healthy controls. The NT level of patients with UA when angina attacked is significantly higher than that after 2 weeks treatment (P＜0.01). The NT level of AMI patients rose from early period and reached peak value at 24 h .It began to decline at 48h,and restored to normal level at 72h. CONCLUSION: When acute myocardial ischemia occured in patients with coronary heart disease, the plasma NT level was elevated. This suggests NT may have participated in the pathophysiological course of myocardial ischemia.     

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.     

Changes in action potential and the conduction time of ventricular cells in subendocardium and subepicardium during ischemia and early reperfusion

AIM:To investigate the electrophysiological characteristics of ventricular myocyte both in subendocardium and in subepicardium during ischemia. METHODS:Using modified Ferrier's method of ischemic and reperfusion injury in isolated guinea pig right ventricular wall. RESULTS: The transmembranal electric activities in subendocardium and in subepicardium were all significantly abnormal, and it was more significant in subendocardium. CONCLUSION: The alteration degree of ventricular myocyte in subendocardium and in subepicardium during ischemia and early reperfusion was different, and this might be the electrophysiological basis of the vulnerability of the subendocardium.     

Effects of Dryk1A,ASF and alternative splicing of CaMKⅡδ on myocardial hypertrophy in renovascular hypertensive rats

AIM: To investigate the role of dual-specificity tyrosine phosporylation-regulated kinase 1A (Dyrk1A)-alternative splicing factor (ASF)-calcium/calmodulin-dependent protein kinase Ⅱδ (CaMK Ⅱδ) pathway in the progression of myocardial hypertrophy in renovascular hypertensive rats. METHODS: The renovascular hypertension was induced by two-kidney one-clip (2K1C) method. The changes of blood pressure and myocardial hypertrophy were measured. The techniques of RT-PCR and Western blotting were used to detect CaMKⅡδ alternative splicing and the protein expression of Dyrk1A and ASF, respectively. RESULTS: Eight weeks after operation, systolic blood pressure (SBP) and diastolic blood pressure (DBP) in 2K1C rats increased (P<0.05). The increases in left ventricular weight (LVW), the ratio of LVW to body weight (BW) and the area of myocardial cells indicated that the hypertensive rats developed significant cardiac hypertrophy. The protein expression of Dyrk1A and mRNA expression of CaMKⅡδA and δB were significantly increased, while the protein expression of ASF and mRNA expression of CaMKⅡδC were decreased compared with sham-operated control rats (P<0.05). Treatment with Dryk1A inhibitor epigallocatechin gallate (EGCG) or harmine effectively attenuated cardiac hypertrophy and reversed the changes in the protein expression of Dyrk1A, ASF and alternative splicing of CaMKⅡδ (all P<0.05). CONCLUSION: Dyrk1A-ASF-CaMKⅡδ pathway plays a role in the development of myocardial hypertrophy in renovascular hypertensive rats.     

Dynamic expression of thioredoxin 2 in myocardial mitochondria in selenium-deficiency rats during myocardial injury

AIM: To investigate the dynamic expression of thioredoxin 2 (Trx2) protein in the myocardial mitochondria under the condition of selenium deficiency. METHODS: A model of selenium deficiency was made using two-week-old SD rats. When the rats were fed for 20 weeks, 30 weeks and 40 weeks, the cardiac functions were detected by carotid artery intubation. The myocardial mitochondria were also extracted, and the protein expression of mitochondrial Trx2 was measured by Western blotting. The method of immunohistochemistry was used to detect Fas-associated death domain protein (FADD,a death marker protein) for determining the apoptosis of myocardial cells. The correlation between Trx2 and left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure rise(+dp/dtmax) and apoptotic index of the myocardial cells was analyzed. RESULTS: Compared with the corresponding period of normal control group, the expression of Trx2 protein in the selenium-deficiency rats was reduced. The expression of Trx2 protein was continuously reduced as the time of selenium deficiency prolonged. As the time of low-selenium feeding was going on, the systolic and diastolic functions of the heart were impaired, and the number of apoptotic myocardial cells was increased. The correlation analysis indicated that Trx2 had positive correlations with LVSP and +dp/dtmax, and had a negative correlation with the apoptotic index of myocardial cells. CONCLUSION: Selenium deficiency affects the expression of Trx2 protein,and causes impaired cardiac functions and the apoptosis of myocardial cells. Trx2 has a protective effect on myocardial cells.     

Cardiac arrhythmias and serum cardiac troponins in Vipera palaestinae envenomation in dogs

BACKGROUND: Vipera palaestinae is responsible for most poisonous envenomations in people and animals in Israel. Cardiac arrhythmias were reported in a retrospective study of V. palaestinae envenomations in dogs. HYPOTHESIS: Cardiac arrhythmias in V. palaestinae-envenomed dogs are associated with myocardial injury reflected by increased serum concentrations of cardiac troponins (cTns). ANIMALS: Forty-eight client-owned dogs envenomed by V. palaestinae. METHODS: Blood sampling (serum biochemistry and cTns, CBC, and coagulation tests) and electrocardiography were performed periodically up to 72 hours postenvenomation. Cardiac rhythm strips were assessed blindly for the presence and type of arrhythmias. RESULTS: Serum cTn-T and cTn-I concentrations were increased in 25% (n = 12) and 65% (n = 31) of the dogs at least once during hospitalization, respectively. Arrhythmias were identified in 29% (n = 14) of the dogs. Dogs with increased cTn-T had a significantly higher occurrence of arrhythmias (58 versus 19%), and higher resting heart rate upon admission and within the following 24 hours. Dogs with increased serum cTn-T concentrations were hospitalized for a significantly (P= .001) longer period compared to those with normal serum cTn-T concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs envenomed by V. palaestinae appear to sustain some degree of myocardial injury, as reflected by increased serum cTn concentrations and by the occurrence of arrhythmias. The latter should alert clinicians to a potentially ongoing cardiac injury. An increase in cTn-T may be of clinical relevance and indicate a cardiac injury in V. palaestinae envenomations in dogs.