Renal sympathetic denervation attenuates left ventricle hypertrophy in spontaneously hypertensive rats by suppressing the Raf/MEK/ERK signaling pathway.

OBJECTIVE: To explore the effect of renal sympathetic denervation (RSD) on left ventricle hypertrophy and the Raf/MEK/ERK signaling pathway in spontaneously hypertensive rats (SHRs). METHODS: SHRs were divided into SHR, SHR + Sham, SHR + RSD and SHR + U0126 groups, with WKY rats as the baseline controls. The blood pressure of rats was observed, while myocardial fibrosis was evaluated through Masson staining. Thereafter, real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to determine the levels of myocardial-hypertrophy-related markers, and Western blotting was used to measure the activity of the Raf/MEK/ERK signaling pathway. RESULTS: In comparison with the WKY group, significant increases were observed in the systolic pressure and diastolic pressure of rats from the other four groups at different time points after surgery. In addition, rats in these groups had obvious increases in LVMI, renal NE and IVSd and decreases in LVEDd, LVEF and LVFS. In addition, the CVF of myocardial tissues was increased, with the upregulation of ANP, BNP and ß-MHC and the downregulation of α-MHC. For the activity of the Raf/MEK/ERK signaling pathway, the levels of p-Raf/Raf, p-MEK/MEK and p-ERK1/2/ERK1/2 were all remarkably elevated (all P < .05). Further comparison with the SHR group showed that the above indexes in the rats were significantly improved in the RSD group and SHR + U0126 group (all P < .05). CONCLUSION: RSD may decrease blood pressure, mitigate hypertension-induced left ventricle hypertrophy and improve cardiac function efficiently in SHRs via the suppression of the Raf/MEK/ERK signaling pathway.

Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel.

How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial KATP (mitoKATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca(2+) overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3ß. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoKATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Inhibition of the STIM1/Orai1 Signaling Pathway by Glycine Betaine Mitigates Myocardial Hypertrophy in Spontaneous Hypertension Rats.

Background: Spontaneous hypertension is a leading risk factor for cardiovascular diseases morbidity and mortality. Glycine betaine (GB) is a natural vitamin that has the potential to lower blood pressure. This work attempted to investigate the role and mechanisms of GB in spontaneous hypertension. Methods: Spontaneously hypertensive rats (SHRs) were administrated with 100, 200, or 400 mg/kg of GB by gavage or combined with by injection of lentivirus-mediated STIM1 overexpression vector. The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart weight/body weight (HW/BW) of rats were monitored. The pathological changes in myocardium were examined by hematoxylin and eosin staining and Masson staining. The expression of genes and proteins was detected by quantitative real-time PCR, western blotting, and immunohistochemistry. Results: GB at 200 and 400 mg/kg reduced the HR, SBP, DBP and HW/BW in SHRs. GB decreased the cross-sectional area and fibrotic area in the myocardium and downregulated the expression of atrial natriuretic peptide (ANP) and ß-myosin heavy chain (ß-MHC) in the myocardium of SHRs. It indicated that GB treatment effectively alleviated myocardial hypertrophy in SHRs. Additionally, GB treatment repressed the expression of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1) in the myocardium of SHRs. STIM1 overexpression reversed GB treatment-mediated inhibition of myocardial hypertrophy in SHRs. Conclusions: In conclusion, GB repressed STIM1/Orai1 signaling pathway, which contributed to alleviating myocardial hypertrophy in SHRs. Thus, our study provides a theoretical basis for GB as an antihypertensive drug.

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.

Trimetazidine Effect on the Cardiac Autonomic Nerve System after Percutaneous Coronary Intervention in Coronary Heart Disease: A Propensity-score Matched Study.

OBJECTIVE: To assess the effects of trimetazidine (TMZ) added to conventional drug therapy on cardiac autonomic nervous CANS in patients with coronary heart disease (CHD) after the percutaneous coronary intervention (PCI). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY:  Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei, China, from May 2018 to September 2019. METHODOLOGY: The study included 50 patients with CHD after a successful PCI who received trimetazidine plus conventional therapy were included as cases (exposed group), and 50 matched patients were identified as controls (non-exposed group). Heart rate (HR) and heart rate variability (HRV) parameters including sympathetic activity (SDNN, LF), parasympathetic activity (RMSSD, pNN50, SDSD, HF), and sympathovagal balance (LF/HF ratio) were used to evaluate CANS function. RESULTS: There were no statistical differences in the HR and HRV parameters before and after PCI (p>0.05). In the non-exposed group, conventional therapy significantly improved the HRV parameters (all p<0.05), while not affecting HR (p>0.05). In the exposed group, all HRV parameters except HR were improved after 4 weeks of treatment. After 4 weeks of treatment, the exposed group had higher parasympathetic-nerve activity, lower sympathetic-nerve activity, and LF/HF ratio compared to the non-exposed group (all p<0.05). CONCLUSIONS: The application of TMZ based on conventional therapy effectively improved the CANS in CHD patients who underwent PCI. KEY WORDS: Coronary heart disease, Percutaneous coronary intervention, Trimetazidine, Cardiac autonomic nervous system, Heart rate variability.

Two Novel Mutations (G774A and A1685G) Causing Coagulation Factor XII Deficiency in a Patient with Acute Inferior Myocardial Infarction.

OBJECTIVE: To identify the gene mutation of the coagulation factor XII (FXII) in a patient with FXII deficiency and acute inferior myocardial infarction. METHODS: The proband was a 51-year-old Chinese man who was diagnosed with acute inferior myocardial infarction and had a history of FXII deficiency. The patient presented with a prolonged activated partial thromboplastin time (160 s) and decreased FXII activity (2.3%) and FXII antigen (1%). DNA sequence analysis of the FXII gene was performed by next generation sequencing. The mutant FXII cDNAs were constructed in an expression plasmid vector and transfected into 293T cells. The expression of FXII antigen was detected by western blot. RESULTS: Sequencing of the FXII gene revealed two novel heterozygous mutations, one at exon 8 (G774A; p: W258X) and the other at exon 14 (A1685G; p: D562G). Western blot showed that the FXII antigens were detected only in the supernatant and whole cell lysate of the wild-type and A1685G mutant type, but not in G774A or G774A plus the A1685G mutant type. In addition, the results showed that secretion but not synthesis of A1685G mutant protein was markedly reduced compared to the wild type. CONCLUSION: The present study indicated that the G774A mutation might impair the secretion and synthesis of FXII protein, while the A1685G mutation only influences the secretion of FXII protein. The definition of these new mutations could be useful tools for analyzing the intracellular protein transport and structure-function relationship of FXII protein transport in the future.

[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.

Additive beneficial effects of amlodipine and atorvastatin in reversing advanced cardiac hypertrophy in elderly spontaneously hypertensive rats.

1. Additive beneficial effects on cardiovascular disease have been reported for amlodipine and atorvastatin. However, it is still unclear whether the combination of amlodipine and atorvastatin has additive beneficial effects on the regression of advanced cardiac hypertrophy in hypertension. In the present study, the effects of the drug combination on advanced cardiac hypertrophy were investigated in elderly spontaneously hypertensive rats (SHR). 2. Elderly SHR (36 weeks old) were randomly allocated into four groups of 12: (i) a vehicle-treated control group; (ii) an amlodipine (10 mg/kg per day)-treated group; (iii) an atorvastatin (10 mg/kg per day)-treated group; and (iv) a group treated with a combination of amlodipine and atorvastatin (both at 10 mg/kg per day). Drugs were administered by oral gavage every morning for a period of 12 weeks before hearts were harvested for analysis. 3. Combined administration of amlodipine and atorvastatin significantly suppressed cardiomyocyte hypertrophy, interstitial fibrosis and upregulation of hypertrophic and profibrotic genes, and also improved left ventricular diastolic dysfunction to a greater extent than did amlodipine monotherapy. Further beneficial effects of combination therapy on advanced cardiac hypertrophy were associated with a greater reduction of NADPH oxidase-mediated increases in cardiac reactive oxygen species (ROS), rather than decreased blood pressure and serum cholesterol levels. 4. To elucidate the underlying molecular mechanisms, we examined cardiovascular NADPH oxidase subunits and found that amlodipine clearly attenuated the expression of p47(phox) and p40(phox) and slightly but significantly reduced p22(phox) and Rac-1 levels in heart tissue. Combination treatment with amlodipine plus atorvastatin led to a further reduction in p22(phox), p47(phox) and Rac-1 protein levels compared with amlodipine alone. 5. In conclusion, combined amlodipine and atorvastatin treatment has a greater beneficial effect on advanced cardiac hypertrophy compared with amlodipine monotherapy. The benefits are likely to be related to the additive effects of the drugs on the suppression of NADPH oxidase-mediated ROS generation.

Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) alleviates myocardial hypoxia-reoxygenation injury by inhibiting oxidative stress and ameliorating mitochondrial dysfunction.

Oxidative stress and mitochondrial dysfunction are considered to be activators of apoptosis and serve a pivotal role in the pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) is a multifunctional protein that processes the cellular response to DNA damage and oxidative stress. Little is known about the role of APE1 in the pathogenesis of MI/R injury. The aim of the present study was to investigate the effects of APE1 on hypoxia-reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and the underlying mechanism responsible. It was demonstrated that H/R decreased cell viability and increased lactic dehydrogenase (LDH) release, as well as reducing APE1 expression in H9c2 cells. However, APE1 overexpression induced by transfection with APE1-expressing lentivirus significantly increased H9c2 cell viability, decreased LDH release, decreased apoptosis and reduced caspase-3 activity in H/R-treated H9c2 cells. APE1 overexpression ameliorated the H/R-induced increases in reactive oxygen species and NAPDH oxidase expression, as well as the decreases in superoxide dismutase activity and glutathione expression. Furthermore, APE1 overexpression increased mitochondrial membrane potential and ATP production, stabilized electron transport chain activity (as illustrated by increased NADH-ubiquinone oxidoreductase, succinate dehydrogenase, coenzyme Q-cytochrome c oxidoreductase and cytochrome c oxidase activities) and decreased the ratio of B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 in H/R, improving mitochondrial dysfunction. In conclusion, the results of the present study suggest that APE1 alleviates H/R-induced injury in H9c2 cells by attenuating oxidative stress and ameliorating mitochondrial dysfunction. APE1 may therefore be used as an effective treatment for MI/R injury.

IGF-1 deletion affects renal sympathetic nerve activity, left ventricular dysfunction, and renal function in DOCA-salt hypertensive mice.

To determine the influence of IGF-1 deletion on renal sympathetic nerve activity (RSNA), left ventricular dysfunction, and renal function in deoxycorticosterone acetate (DOCA)-salt hypertensive mice. The DOCA-salt hypertensive mice models were constructed and the experiment was classified into WT (Wild-type mice) +sham, LID (Liver-specific IGF-1 deficient mice) + sham, WT + DOCA, and LID+ DOCA groups. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IGF-1 levels in mice. The plasma norepinephrine (NE), urine protein, urea nitrogen and creatinine, as well as RSNA were measured. Echocardiography was performed to assess left ventricular dysfunction, and HE staining to observe the pathological changes in renal tissue of mice. DOCA-salt induction time-dependently increased the systolic blood pressure (SBP) of mice, especially in DOCA-salt LID mice. Besides, the serum IGF-1 levels in WT mice were decreased after DOCA-salt induction. In addition, the plasma NE concentration and NE spillover, urinary protein, urea nitrogen, creatinine and RSNA were remarkably elevated with severe left ventricular dysfunction, but the creatinine clearance was reduced in DOCA-salt mice, and these similar changes were obvious in DOCA-salt mice with IGF-1 deletion. Moreover, the DOCA-salt mice had tubular ectasia, glomerular fibrosis, interstitial cell infiltration, and increased arterial wall thickness, and the DOCA-salt LID mice were more serious in those aspects. Deletion of IGF-1 may lead to enhanced RSNA in DOCA-salt hypertensive mice, thereby further aggravating left ventricular dysfunction and renal damage.

[Single plane Simpson's method for measurement of right ventricular volume by X-ray ventriculography].

OBJECTIVE: To study the validity of single plane Simpson's method with conventional X-ray ventriculography for estimation of right ventricular (RV) volume. METHODS: Fifteen human RV casts were obtained from 15 subjects who died from non-cardiac causes within 24 hours after death. These casts were photographed respectively and their volumes were calculated by using the single plane Simpson's method based on a new half-circle model. The actual RV cast volumes were determined by water displacement method. RESULTS: The actual RV volume was (64.23 +/- 24.51) ml and the calculated volume was (58.04 +/- 24.45) ml. The calculated RV volume underestimated the actual volume by (6.19 +/- 12.38) ml, but there was no significant difference between the actual and the calculated RV volume (P > 0.05). There was a significant correlation between the actual cast volume and the calculated volume (r = 0.983, P < 0.01). The regression equation was: RV actual volume = 1.074 x (RV calculated volume). CONCLUSION: RV volume calculated by single plane Simpson's method with conventional X-ray ventriculography is accurate and deserves further study.

[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.

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 pravastatin on the expression of endothelin induced by aldosterone in rat cardiac fibroblasts].

AIM: To investigate the effects of pravastatin on endothelin(ET) expression induced by aldosterone in cultured neonatal rat cardiac fibroblasts. METHODS: ET concentration in conditioned medium was measured by radioimmunoassay, intracellular ET-1 level was evaluated by flow cytometry, and the expression of preproendothelin-1 (ppET-1) was detected and quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) method. RESULTS: The cardiac fibroblasts, treated with aldosterone at 107 mol/L, significantly up-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release. Pravastatin (10(-5), 10(-4), 10(-3) mol/L) dose-dependently blocked these effects. In contrast, pravastatin-induced inhibitory effects were reversed in the presence of mevalonate. CONCLUSION: Pravastatin down-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release induced by aldosterone in a process specifically related to mevalonate in cardiac fibroblasts.