Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation.

Objective: In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods: Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results: At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion: Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.

JMJD5 attenuates oxygen-glucose deprivation and reperfusion-induced injury in cardiomyocytes through regulation of HIF-1α-BNIP3.

Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro-proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non-transfected H9C2 or H9C2 transfected with pcDNA-JMJD5 plasmid to induce cell cytotoxicity. Data from qRT-PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R-induced H9C2. Secondly, JMJD5 over-expression attenuated OGD/R-induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA-mediated over-expression of JMJD5 with enhanced protein expression of LC3-I, LC3-II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/R-induced decrease in hypoxia-inducible factor-1α (HIF-1α), whereas JMJD5 over-expression enhanced BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) through upregulation of HIF-1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over-expression against OGD/R-induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R-induced injury in cardiomyocytes through upregulation of HIF-1α-BNIP3.

Thawing Rate Predicts Acute Pulmonary Vein Isolation after Second-Generation Cryoballoon Ablation.

OBJECTIVE: To evaluate whether thawing rate could be a novel predictor of acute pulmonary vein isolation (PVI) and explore the predictive value of thawing rate as a factor ensuring long-term PVI (vagus reflex). METHODS: A total of 151 patients who underwent cryoballoon ablation for atrial fibrillation (AF) were enrolled in this retrospective study between January 2017 and June 2018. The thawing rate was calculated using the thawing phase of the cryoablation curve. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of the thawing rate for acute PVI and vagus reflex. RESULTS: ROC curve analyses revealed that the interval thawing rate at 15°C (ITR15) was the most valuable predictor of PVI, with the highest area under curve (AUC) value of the ROC curve. The best cut-off value of ITR15 for PVI was ≤2.14°C/S and its sensitivity and specificity were 88.62% and 67.18%, respectively. In addition, the ITR15 of the successful PVI group after cryoballoon ablation was significantly slower than the failed PVI group. ITR15 was a predictor of vagus reflex and the occurrence of vagus reflex group had a slower ITR15 compared to the non-occurrence group. CONCLUSIONS: Thawing rate was a novel predictor of acute PVI and the ITR15 was the most valuable predictor of acute PVI. In addition, ITR15 was a predictive factor ensuring long-term PVI (vagus reflex). Our study showed that thawing rate may serve in the early identification of useless cryoballoon ablation.

Thawing rate predicts acute pulmonary vein isolation after second-generation cryoballoon ablation

OBJECTIVE: To evaluate whether thawing rate could be a novel predictor of acute pulmonary vein isolation (PVI) and explore the predictive value of thawing rate as a factor ensuring long-term PVI (vagus reflex). METHODS: A total of 151 patients who underwent cryoballoon ablation for atrial fibrillation (AF) were enrolled in this retrospective study between January 2017 and June 2018. The thawing rate was calculated using the thawing phase of the cryoablation curve. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of the thawing rate for acute PVI and vagus reflex. RESULTS: ROC curve analyses revealed that the interval thawing rate at 15°C (ITR15) was the most valuable predictor of PVI, with the highest area under curve (AUC) value of the ROC curve. The best cut-off value of ITR15 for PVI was ≤2.14°C/S and its sensitivity and specificity were 88.62% and 67.18%, respectively. In addition, the ITR15 of the successful PVI group after cryoballoon ablation was significantly slower than the failed PVI group. ITR15 was a predictor of vagus reflex and the occurrence of vagus reflex group had a slower ITR15 compared to the non-occurrence group. CONCLUSIONS: Thawing rate was a novel predictor of acute PVI and the ITR15 was the most valuable predictor of acute PVI. In addition, ITR15 was a predictive factor ensuring long-term PVI (vagus reflex). Our study showed that thawing rate may serve in the early identification of useless cryoballoon ablation.

Value of cystatin C in predicting atrial fibrillation recurrence after radiofrequency catheter ablation.

BACKGROUD: Recent studies have demonstrated that cystatin C is a valuable risk marker for cardiovascular disease morbidity and mortality. Therefore, we hypothesized that the pre-ablation cystatin C level was associated with post-ablation atrial fibrillation (AF) recurrence. METHODS: 207 patients were enrolled and completed in this prospective observational study. Patients with AF scheduled for receive radiofrequency catheter ablation (RFCA) therapy were screened for the study. Before ablation therapy, electrocardiogram, 24 h holter monitor, transesophageal echocardiography, serum cystatin C, high-sensitivity C-reactive protein, creatinine levels, and routine blood examinations were examined. After ablation, patients were followed up every week for the first month, and then at 2, 3, 6, 9, and 12 months. Thereafter, patients came back to out-patient clinic every six months regularly. Electrocardiogram or 24 h holter monitor were repeated if the patient experienced palpitations or every six months. AF recurrence was defined as atrial fibrillation/atrial flutter or atrial tachycardia lasting ≥ 30 seconds within three months after therapy. RESULTS: Compared to patients with no AF recurrence, patients with recurrence had longer AF history (P = 0.007), more early recurrence (P = 0.000), a larger left atrium (P = 0.004), and higher pre-ablation cystatin C levels (P = 0.000). Multivariate regression analysis revealed that cystatin C and left atria (LA) diameter were risk factors for AF recurrence. After adjusting for LA diameter, the risk of AF recurrence increased 30% with every milligram cystatin C elevation (95% CI: 1.117-1.523). CONCLUSIONS: Pre-ablation cystatin C levels were associated with AF recurrence after RFCA therapy, an optimal cut-off value of 1.190 mg/L (sensitivity = 0.576; specificity = 0.851).

[Cardiac protection from myocardial ischemic postconditioning and remote postconditioning during myocardial ischemia/reperfusion injury in rabbits].

OBJECTIVE: To observe whether there are some differences between myocardial postconditioning and remote postconditioning, and whether there is additional cardiac protection when they are used combined during myocardial ischemia/reperfusion injury in rabbits. METHODS: Thirty healthy New Zealand rabbits which were randomly divided into 5 groups (n = 5): ischemic control group (CON), sham operation group (Sham), myocardial postconditioning group (MPostC), remote postconditioning group (RPostC), myocardial postconditioning plus remote postconditioning group (MPostC + RPostC). Acute myocardial infarction was induced by 45 minutes occlusion on left circumflex coronary artery (LCX) and 2 hours reperfusion in all anesthetized open-chest rabbits except the Sham, the coronary occlusion and reperfusion were determined by changes of ECG and cardiac color. Skeletal muscle ischemia model was induced by extrinsic iliac arteries occlusion and reperfusion with artery clamps. The condition that the extrinsic iliac arteries were occluded or reperfused could be tested by according to the distal arterial pulse. Plasma creatine kinase (CPK) activity and lactate dehydrogenase (LDH) activity were measured at baseline, the end of ischemia, after 1 hour and 2 hours of reperfusion respectively. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining and measured by area ratio of AN/AAR. RESULTS: Compared with the Con, myocardial infarct size was significantly reduced in MPostC and RpostC group (P < 0.05). But there was no significant difference between MPostC and RPostC group. Combined MPostC and RPostC markedly enhanced myocardial protection (P < 0.05). The trend of CPK and LDH release was similar to the trend of myocardial infarct size. CONCLUSION: Both MPostC and RPostC induced cardiac protection. There was no significant difference between MPostC and RPostC. Combined MPostC and RPostC induced markedly additive effect on myocardial protection.

[Effects of rabbit limbs ischemia/ reperfusion on myocardial necrosis and apoptosis].

OBJECTIVE: To investigate the effects of rabbit limbs ischemia/reperfusion on myocardial necrosis and apoptosis in vivo. METHODS: Thirty-six healthy new zealand rabbits were randomly divided into 3 groups: (1) Sham group; (2) I/R(Ischemia/reperfusion) group; (3) RPostC (remote postconditioning) group. The activity of blood serum creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at baseline, the end of ischemia after 60 min and 120 min of reperfusion respectively. The extent of myocardial ischemia and the scope of myocardial infarction were assessed by evans blue and Triphenyl tetrazolium chloride (TTC). The myocardial cell's apoptosis at the area of myocardial ischemia was estimated by Tunel. Protein expression of caspase-3, Bcl-2 and Bax in myocardial ischemic area were analyzed with the method of immunohistochemistry. RESULTS: Compared with I/R group, the myocardial infarct size and the CK activity were significantly reduced in RPostC group. The Tunel positive index of RPostC group in ischemic myocardium was significantly lower than that in I/R group (21.79% +/- 1.07% vs 35.81% +/- 1.10%, P < 0.05). Caspase-3 positive cells index was calculated with randomly selected five regions in each slide and then the positive cells in per hundred cells were calculated. The RPostC group of caspase-3 positive cells was significantly lower than that in I/ R group(25.03% +/- 1.16% as 39% +/- 2.43%, P < 0.05). Compared with the sham group, the Bax protein expression index and the Bcl-2 protein expression index of I/R group and RPostC group were increased. The Bax/Bcl-2 ratio of RPostC group decreased, while it was increased in I/R. Compared with the I/R group, the Bax protein expression and Bax/Bcl-2 ratio of RPostC group significantly reduced, but the expression index of Bcl-2 ratio was significantly increased, the differences were statistically significant. CONCLUSION: Limbs ischemia/postconditioning could significantly reduce necrosis and apoptosis of ischemia/reperfusion myocardium. The mechanism of reducing the myocardial cell apoptosis may have relation to inhibiting the activation of pro-apoptotic gene caspase-3 and increased expression of Bcl-2.

[Cardioprotective effects of limb ischemic postconditioning by different strength and time in rabbits].

OBJECTIVE: In this study, we try to find the better protocol of limb ischemia postconditioning by observing different protective effects of limb ischemic postconditioning (different strength and time windows in rabbits). METHODS: 42 healthy New Zealand rabbits were randomly divided into 7 groups (n = 6): Sham; Control (CON); Skeletal muscle postconditioning (SP); 6 min-delayed skeletal muscle postconditioning (6M-DSP); 1 min-delayed skeletal muscle postconditioning (1M-DSP); Strengthen skeletal muscle postconditioning (SSP); Weakened skeletal muscle postconditioning (WSP). Acute ischemia/reperfusion (I/R) model was induced by 45 minutes occlusion on left circumflex coronary artery (LCX) and 2 hours reperfusion in all anesthetized open-chest rabbits except the Sham. Limb ischemia was induced by external iliac arteries occlusion and reperfusion through artery clamps. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining. Blood serum creatine kinase (CK) activity and lactate dehydrogenase (LDH) activity were measured at baseline,the end of ischemia, after 1 hour and 2 hours of reperfusion respectively. RESULTS: Compared with the CON, the weight ratio and area ratio of myocardial infarction size were significantly decreased by 49.97% and 43.78% in SP, by 42.32% and 42.68% in 1M-DSP, by 48.36% and 48.86% in SSP (P < 0.05). But there was no significant difference between SP and 1M-DSP and SSP (P > 0.05). Otherwise, compared with the CON, myocardial infarct size was not significantly reduced in 6M-DSP or WSP (P > 0.05). The change of CK was similar to the trend of myocardial infarct size. CONCLUSION: The limb ischemia strength of 5 mini/1 minR x 1 cycle could significantly reduce the myocardial ischemia/ reperfusion injury in rabbits, if it was achieved before myocardial reperfusion.

Fractional systolic and diastolic pressures act as predictors of coronary artery disease.

AIMS: This study was designed to determine if fractional systolic/diastolic pressures act as predictors of the extent of coronary artery disease. PATIENTS AND METHODS: A total of 545 consecutive patients (305 men, 240 women, with mean age 54.2 years) were involved in the study. The patients were diagnosed with coronary and non-coronary artery disease confirmed by angiography. RESULTS: 353 patients were confirmed to have coronary artery disease, with 134 cases involving one vessel, 101 two vessels and 118 three vessels. There were significant differences between brachial and ascending aortic systolic blood pressures, fractional systolic blood pressures and fractional diastolic blood pressures in the patients with coronary artery disease compared with patients with non-coronary artery disease. Blood pressure measured in the brachial artery was higher than the pressure measured in the ascending artery. Ascending aortic fractional systolic/diastolic pressures were associated with coronary Gensini score, and were significantly related to the number of diseased vessels. CONCLUSIONS: Fractional systolic and diastolic pressures in the ascending aorta were strong predictive factors for the extent of coronary artery disease. Central pressures measured invasively in the ascending aorta were more predictive than peripheral pressures for the evaluation of coronary artery disease.

[The efficacy of antihypertensive treatment on diabetes mellitus or impaired glucose tolerance patients with blood pressure below 140/90 mm Hg: a meta-analysis].

OBJECTIVE: To investigate whether antihypertensive treatment is beneficial to patients with diabetes mellitus when their blood pressure (BP) is below 140/90 mm Hg (1 mm Hg = 0.133 kPa). METHODS: MEDLINE, EMBASE, IPA database and secondary resources were searched with terms including blood pressure, hypertension and anti-hypertension drug. INCLUSION CRITERIA: random control study; subjects were patients with diabetes mellitus or impaired glucose tolerance; endpoint BP ≤ 140/90 mm Hg; endpoint BP between two groups had significant differences. There were 16 studies meet inclusive criteria with a total of 51 470 patients. RR and 95%CI were used as index to judge the difference of clinical outcomes between aggressive antihypertensive treatment group and standard antihypertensive treatment group. RevMan5.0 software was used for statistical analysis. RESULTS: When BP of patients with diabetes mellitus were below 140/90 mm Hg, anti-hypertensive treatment could reduce incidence rate of cardiovascular event (RR 0.91, 95%CI 0.87 - 0.96, P = 0.0004) and stroke (RR 0.75, 95%CI 0.63 - 0.88, P = 0.0005), and increased incidence rate of symptomatic hypotension (RR 3.57, 95%CI 1.41 - 11.20, P = 0.03) and hyperpotassemia (RR 1.57, 95%CI 1.05 - 2.33, P = 0.03). There were no significant differences in all-cause mortality (RR 0.94, 95%CI 0.87 - 1.01, P = 0.08), cardiovascular mortality (RR 0.95, 95%CI 0.85 - 1.08, P = 0.05), myocardial infarction (RR 0.93, 95%CI 0.82 - 1.05, P = 0.26), heart failure (RR 0.90, 95%CI 0.76 - 1.06, P = 0.21) between the aggressive antihypertensive treatment group and standard antihypertensive treatment group. CONCLUSIONS: When blood pressure of patients with diabetes mellitus was below 140 mm Hg, there was little benefit from aggressive antihypertensive treatment, and the risk of serious adverse events even increased.

[Impact of application time of aspirin and clopidogrel on platelet aggregation in patients with acute coronary syndrome].

OBJECTIVE: To observe the impact of various application time of aspirin and clopidogrel on the circadian rhythm changes of platelet aggregation in patients with acute coronary syndrome. METHODS: Patients with acute coronary syndrome were divided into day-time (8:00) and night-time (20:00) medication group (n = 15 each). After plasma concentration reached steady state, platelet aggregation was assessed at 5 time points within 24 hours with a mobile four-channel whole blood impedance aggregometer. The platelet aggregation was induced by ADP and arachidonic acid. Thereafter, the two groups were exchanged and platelet aggregation was assessed in the same way post plasma steady state. RESULTS: Arachidonic acid-induced platelet aggregation was the highest at 10:00 Am [(7.96 +/- 3.64) ohm] and the lowest at 0:00 [(6.12 +/- 3.29) ohm, P > 0.05] in day-time group. Platelet aggregation was the highest at 20:00 [(9.40 +/- 5.39) ohm] and the lowest at 10:00 [(5.46 +/- 3.93) ohm], P < 0.05). ADP-induced platelet aggregation was the highest at 10:00 and the lowest at 16:00 in day-time group (P > 0.05) and was the highest at 20:00 and the lowest at 10:00 in night-time group (P > 0.05). Platelet aggregation induced by two inducers was significantly higher at 10:00 in day-time group compared to values in night-time group (all P < 0.05). CONCLUSION: Taking aspirin and clopidogrel at 20:00 was superior to taking the same medications at 8:00 for inhibiting peak platelet aggregation in the morning.

[Gene polymorphism of CYP450 2C9 and VKORC1 in Chinese population and their relationships to the maintaining dosage of warfarin].

OBJECTIVE: To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations. Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied. METHODS: The genotype and allele frequencies were calculated and compared with those in other populations. One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio (INR) of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage. RESULTS: CYP450 2C9*3 + 1075C/A allele frequencies were:AA in 449 cases (92.2%), AC in 36 cases (7.4%) and CC in 2 cases (0.4%), respectively. VKORC1 -1639A/G allele frequencies were AA in 415 cases (85.2%), GA in 72 cases (14.8%), but GG in no case (0.0%), respectively. When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose, the final equation was: ln (D) = 0.346 + 0.017 (weight) - 0.376 (CYP450 2C9*3 + 1075C/A) + 0.148 (VKORC1-1639A/G) - 0.002 (age) (r = 0.827, P = 0.02). CONCLUSION: There existed significant gene polymorphism CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population. Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

Statin therapy shortens QTc, QTcd, and improves cardiac function in patients with chronic heart failure.

Although some data suggest that statins can improve cardiac mechanical function in some patients with chronic heart failure (CHF), the effects of long-term statin therapy on cardiac electrical instability remain unclear. We performed a randomized perspective analysis of the effects of 10 mg/d (statin group 1, n=40), 20 mg/d (statin group 2, n=38) of atorvastatin and controls (control group, n=41) on corrected QT intervals (QTc), corrected QT dispersion (QTcd) and cardiac function in patients with CHF secondary to coronary artery disease (CAD) for one year. At 6 and 12 months, the statin groups displayed lower QTc and QTcd compared with controls. The changes were becoming more distinct in statin group 2, (P<0.05). In statin groups, the changes of QTc and QTcd were independent of changes of plasma low-density lipoprotein cholesterol and total cholesterol levels, and the decrease of QTcd was correlated with the increase of LVEF within 12 months. Atorvastatin shortens QTc, QTcd and improves cardiac function, and might thereby be parts of the mechanisms which atorvastatin benefited CHF patients secondary to CAD.

[Effects of remote preconditioning induced by skeletal muscle ischemia on myocardial cells apoptosis and roles of opioid receptors in pigs].

AIM: To investigate the effect on myocardial apoptosis and Bcl-2/Bax induced by remote preconditioning (RP) and to discuss the hypothesis from opioid receptors in pigs. METHODS: Skeletal muscle ischemia was performed in pigs by occlusion of the femoral artery (FAO) for 15 min followed by a 10 min of reperfusion. Infarction of the heart was induced by 40 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min reperfusion. In the RP model induced by FAO, the role of opioid receptors was investigated by using antagonist of the opioid receptors (naloxone). The signal transduction pathway of RP was investigated by using hexamethonium. Apoptosis of left ventricular samples from nonischemic and ischemic areas was detected in situ with end-labeling (TUNEL) method and measured by flow cytometry. Bcl-2 and Bax was also measured by flow cytometry. RESULTS: (1) The apoptosis rate in ischemic myocardium in RP group measured by flow cytometry was lower (4.43% +/- 0.74%) compared with that in CONT group (15.4% +/- 1.15%), but Bcl-2/Bax was higher (1.36 +/- 0.09, CONT group: 0.56 +/- 0.08). (2) The protective effect could be prevented by naloxone used before RP protocol (apoptosis rate: 13.0% +/- 0.56% and Bcl-2/Bax: 0.69 +/- 0.18, P < 0.05). (3) Naloxone had no effect on apoptosis rate in CONT group. (4) Hexamethonium used before RP protocol had no effect on apoptosis rate and bcl-2/bax. Apoptotic cardiomyocytes detected in TUNEL correspond to the above. CONCLUSION: RP induced by skeletal muscle ischemia could prevent myocardium from apoptosis, in which Bcl-2 and Bax might take part in regulation and control. Furthermore opioid receptors could take part in triggering the course and a neuronal signal transmission from the remote area to heart could be excluded.

Crosstalk between ERK1/2 and STAT3 in the modulation of cardiomyocyte hypertrophy induced by cardiotrophin-1.

BACKGROUND: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway are the two major independent signal transduction pathways. However, it has recently been found that STAT3 may be negatively regulated by ERK1/2 in gp130-dependent signaling. Cardiotrophin-1 (CT-1), a potent novel hypertrophic cytokine, depends on gp130 to induce signaling and depends on STAT3 to exert hypertrophic effect. In this study, we examined whether STAT3 activity was negatively regulated by ERK1/2 during CT-1-induced signaling in rat cardiomyocytes and, if so, whether such crosstalk interfered with the hypertrophic effect of CT-1 and, furthermore, whether the mechanism underlying the crosstalk involved phosphorylation of serine 727 (S727) in STAT3. METHODS: The activities of ERK1/2 and STAT3 were assessed by in-gel kinase assay and Western blot analysis, respectively. The role of S727 phosphorylation in the crosstalk between ERK1/2 and STAT3 was determined by a transient transfection study using a STAT3S727A mutant. Cardiomyocyte hypertrophy was evaluated by the cellular protein-to-DNA ratio and [(3)H]-leucine incorporation. RESULTS: CT-1 simultaneously activated both ERK1/2 and STAT3 in rat cardiomyocytes. Inhibition of ERK1/2 by U0126 resulted in an increase of CT-1-induced tyrosine phosphorylation of STAT3 and, consequently, the protein-to-DNA ratio and [(3)H]-leucine incorporation. Transient transfection of the cells with STAT3S727A had no significant effect on CT-1-induced tyrosine phosphorylation of STAT3. CONCLUSIONS: STAT3 is activated by CT-1 in rat cardiomyocytes, but full activation is mitigated by the simultaneous activation of ERK1/2. The inhibition of ERK1/2 increases the activity of STAT3, which, in turn, enhances the hypertrophic effect of CT-1. The crosstalk between ERK1/2 and STAT3 is independent of the phosphorylation of the S727 in STAT3. Such crosstalk may contribute to the development of adequate cardiac hypertrophy.

[Myocardial protection and mechanism of Puerarin Injection on patients of coronary heart disease with ischemia/reperfusion].

OBJECTIVE: To explore the protective effect and the mechanism of Puerarin Injection (PI) on myocardial ischemia reperfusion in patients with coronary heart disease (CHD) and angina pectoris (AP). METHODS: Seventy-eight patients with AP planned to receive the PTCA and stenting treatment were randomly divided and single-blindedly into the conventional group and the PI group. Based on the conventional treatment and pre-operational preparation, the PI group was given 200 ml of PI by intravenous dripping once a day, beginning from one week before operation, but to the conventional group, normal saline was given for instead. The condition of AP attack in balloon dilatatory stage of PTCA was observed and change of ST segment of ECG detected by a 12-lead ECG monitor. The blood levels of von Willebrand factor (vWF:Ag), nitric oxide (NO) and endothelin-1 (ET-1) were also observed before and after treatment. RESULTS: As compared with those in the conventional group, number of patients having AP attack and ST segment change in PTCA process was lessened in the PI group, with blood levels of vWF:Ag and ET-1 obviously lower, and NO content obviously higher than those in the conventional group, CONCLUSIONS: PI could protect the myocardium in 2-3 days after ischemia reperfusion, one of the possible reasons is that PI can simulate the late phase of ischemic preconditioning, which may be related to its effect in lowering plasma vWF:Ag and ET-1, and increasing the serum NO content.