Effects of Long-term Ramipril on Ventricular Remodeling, Cardiac Function and Survival in Rat Congestive Heart Failure after Myocardial Infarction

Objectives The purpose ofthis study was to investigate the effects of long-termramipril on ventricular remodeling, cardiac functionand survival in rat congestive heart failure after my-ocardial infarction. Methods Myocardial infarction(MI) was caused by ligation of the left anterior de-scending coronary artery in rats. 7 days after thesurgery, the surviving rats were randomly assigned tothe following treatment protocols: 1) MI ras with notherapy, 2) MI rats treated with ramipril 3 mg/kg perday, 3) Sham-operated control rats, and 4) Sham-op-erated rats treated with ramipril 3 mg/kg per day. At22 weeks, cardiac hemodynamic parameters such asMAP, LVSP, ±dP/dtmax and LVEDP were measured,and cardiac morphometric parameters such as HW,LVW and LVCA were measured, mRNA of cardiacmolecule genes, such as βMHC, BNP, collagen Ⅰ andⅢ, and TGF-β_1, were quantified, and survival rateswere calculated. Results Compared with sham-operated rats, MI rats without therapy showed significantincreases in cardiac morpholog     

The Effect of Verapamil on Left Ventricular Remodelling and Diastolic Function after Acute Myocardial Infarction (The Verapamil Infarction Study on Remodelling and Relaxation—VISOR)

The VISOR is a double blind, randomized, placebo-controlled study aimed to assess the effects of early and prolonged administration of verapamil on the left ventricular geometry and diastolic function in patients with anterior acute myocardial infarction treated with thrombolysis. Patients with heart failure or ejection fraction < 45% were excluded. Within 12 hours from starting thrombolysis, 70 patients were given verapamil (5 mg/hour intravenously for the first 24 hours, followed by 120 mg t.i.d. perorally for 6 months) or equivalent placebo. Echocardiograms were performed on admittance, before discharge, after 3 months and 6 months. The following parameters were calculated: left ventricular volumes, ejection fraction, sphericity index, early (E) and late (A) transmitral peak flow velocities and time-velocity integrals with their ratios, deceleration time and half-time of E, isovolumic relaxation time (IVRT), and non-invasive time constant of ventricular relaxation (). The basal and the last available parameters were considered for statistical analysis. The effects of the treatment on the left ventricular volumes, ejection fraction, and sphericity index were not statistically relevant. Conversely, a reduction of E/A ratio (P < .05) and increases of A integral (P < .01), deceleration time and half-time E, IVRT and (P < .05) were found in the placebo group and not in the verapamil group. No significant changes in the blood pressure, heart rate, PQ interval, and biochemical parameters were observed in the two groups. In conclusion, in patients with a thrombolysed anterior acute myocardial infarction and preserved systolic function, verapamil can prevent alterations of the diastolic function in absence of effect on ventricular remodelling, and has a good safety profile.     

Dynamic changes of α-AR,β1-AR and β2-AR expression during hepatic fibrogenesis

Objective To investigate the dynamic changes of α-AR,β1-AR and β2-AR expression in hepatic fibrosis.Methotis Rat hepatic fibrosis model was established by bile duct ligation(BDL).HE and Masson staining were used to determine hepatic fibrosis levels.Immunohistochemistry was applied to detect α-sooth muscle actin(α-SMA),a marker of hepatic stellate cell(HSC)activation;Western blot and realtime RT-PCR were used to measure the dynamic changes of α-AR,β1-AR,β2-AR expression on protein and mRNA levels.respectively,during the development of hepatic fibrosis.Results(1)HE and Masson trichrome staining showed that the liver fibrosis modeIs were established successfully.(2)At 1,2,3,4 wk after BDL,α-SMA positive area density of the model group(10.58%±1.75%,24.1 4%±2.02%,29.74%±2.59%,34.28%±2.01%)was significantly higher than that of the sham operation group (4.12%±1.51%),P＜0.01.(3)The expression of α-AR,β1-AR,β2-AR protein and mRNA was increased with the development of the hepatic fibrosis(P＜0.05).(4)α-SMA expression Was positively associated with α-AR,β1-AR,β2-AR,r values were 0.564,0.753 and 0.606,respectively.Conclusions The expression of α-SMA is increased dramatically during the fibrosis,and is positively associated with the expression of α-AR,β1-AR and β2-AR.     

MINI Myocardial Infarction with Novastan and tPA

标题 MINI研究:一个关于对比阿加曲班或肝素作为组织型纤溶酶原激活剂(tPA)的附加剂应用于急性心肌梗死患者的 多中心、随机临床试验作者 Jang I-K,Brown DFM,Gingliano RP,et al     

Viable Myocardium Impact on Left Ventricular Function after Late Revascularization of Infarct-related Artery in Acute Myocardial Infarction

Objectives The long-term benefit of late reperfusion of infarct-related artery (IRA) after acute myocardial infarction (AMI) is controversial, and the benefit mechanisms remain uncertain. Low dose dobutamine stress echocardiography (LDSE) can identify viable myocardium and predict improvement of wall motion after revascularization. Methods Sixty-nine patients with first AMI who did not received early reperfusion therapy were studied by LDSE at 5 to 10 days after AMI. Wall motion abnormality and left ventricular size were measured at the same time. Successful PCI were done in all patients at 10 to 21 days after AMI onset. Patients were divided in two groups based on the presence or absence of viable myocardium. Echocardiography was repeated six months later. Results There were 157 motion abnormality segments. 89 segments (57%) were viable during LDSE. 26 patients (38%) with viability and 43 (62%) without. In viable group, left ventricular ejection fraction (LVEF) was increased (P < 0.05), and left ventricular end systolic volume index (LVESVI) and wall motion score (WMS) were decreased (P < 0.05 and P < 0.01) significantly at 6 months compared with baseline. But in patients without viability, LVEF was decreased (P < 0.01), and LVESVI and left ventricular end diastolic volume index (LVEDVI) were increased (P<0.05) significantly after 6 months, and the WMS did not changed (P > 0.05). LVEF increased (P< 0.05) and WMS decreased (P < 0.05) on LDSE during acute phase in patients with viability, but they were not changed in the nonviable group. Conclusions Late revascularization of IRA in patients with presence of viable myocardium after AMI is associated with long-term preservation left ventricular function and less ventricular remodeling. Improvement of left ventricular systolic function on LDSE indicates late phase recovery of left ventricular function after late revascularization.     

Effects of Aging and Drugs on Myocardial β-Adrenergic Receptors in M-SHRSP and SHRSP

Myocardial β-adrenergic receptors were measured in membrane fractions from malignant SHRSP (M-SHRSP), SHRSP and WKY at different ages using [3H]-dihydroalprenolol (DHA) as a radioligand. The effects of isoproterenol (ISP) and chemical sympathectomy (6-hydroxydopamine treatment) on myocardial β-receptors were also investigated in 10 and 24 week-old SHRS and WKY to examine the effects of hypertension and aging on receptor regulation. The number of myocardial β-receptors in M-SHRSP at 4 weeks of age (W) and 10 W were significantly lower than those in age-matched SHRSP and WKY. In addition, the values in SHRSP at 4 and 10 W were significantly lower than those in age-matched WKY, but the numbers in SHRSP at 1, 24 and 48–54 W were not significantly different from age-matched WKY. The dissociation constant and activity of 5′-nucleotidase, which is a marker enzyme of cell membrane, were not significantly different among the three groups. ISP treatment significantly reduced the numbers of myocardial β-receptors in 10 week-old SHRSP and 10 and 24 week-old WKY, but did not in 24 week-old SHRSP. The extent of this decrease of β-receptors was lower in 10 week-old SHRSP than in 10 week-old WKY, and it was also lower in 24 week-old WKY than 10 week-old WKY. 6-Hydroxydopamine treatment significantly increased the number of myocardial β-receptors in 10 and 24 week-old WKY, but did not in SHRSP. The extent of this increase of β-receptors was lower in 24 week-old WKY than in 10 week-old WKY. These results suggest that the decrease of myocardial β-receptor numbers in 4 and 10 week-old M-SHRSP and SHRSP does not appear to be genetically determined, but rather is caused by accelerated sympathetic activity, and that the regulation of myocardial β-receptor is impaired in young and aged SHRSP and in aged WKY.     

Ranolazine Treatment for Myocardial Infarction? Effects on the Development of Necrosis,Left Ventricular Function and Arrhythmias in Experimental Models

Ranolazine, an inhibitor of the late current of the cardiac action potential (late I_Na), is a well established clinical treatment for chronic angina. The late I_Na in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic target to ameliorate consequences of myocardial infarction. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size, improve left ventricular function, decrease ischemia/reperfusion-induced arrhythmias and improve outcome in heart failure. Here we focus specifically on data from in vivo animal studies of myocardial ischemia and reperfusion.     

Early Anti-inflammatory and Pro-angiogenic Myocardial Effects of Intravenous Serelaxin Infusion for 72 H in an Experimental Rat Model of Acute Myocardial Infarction

Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days. SRLX30 did not reduce early myocardial fibrosis but reduced myocardial levels of sST2 and galectin-3. No significant effects were observed with SRLX10 treatment. A significant correlation was observed between plasma levels of serelaxin and effect measures. The results suggest serelaxin has a protective effect in early processes of cardiac remodeling after AMI.     

Effects of α-tocopherol on platelets and the coagulation system

Vitamin E is one of the most widely used antioxidants in cryopreservation and preservation technology. The objective of this study is to examine the effect of vitamin E on platelets and the coagulation system. Vitamin E was added at different concentrations in the range between 0.25 and 5 mM to donor plasma. Using a STA/STA Compact coagulation analyzer the following clotting tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT). The control clotting times PT (13.80 - 0.4 s), APTT (27.4 - 2.4 s) and TT (17.6 - 0.4 s) remained unchanged in the presence of vitamin E. The effect of vitamin E on platelets was assessed by platelet-induced clot retraction (PICR) and aggregation by thrombin. PICR was unaffected by vitamin E. Platelet aggregation, however, was profoundly inhibited by vitamin E. We found that inhibition of platelet aggregation by vitamin E was concentration dependent: increasing with increasing vitamin E concentration. This inhibitory effect, however, was widely reversible upon dilution of vitamin E with autologus platelet-poor plasma.     

Does Longitudinal Strain Predict Left Ventricular Remodeling after Myocardial Infarction?

Background: One of the most prognostically significant consequences of acute myocardial infarction (AMI) is the development of an adverse left ventricular (LV) remodeling. Objectives: The purpose of our study was to evaluate a feasibility of speckle tracking imaging (STI), in particular, global longitudinal strain (Ls) in predicting LV remodeling after AMI. Methods: A total of 82 AMI patients (mean age 57.6 ± 9.4) were included in the study. Within 48–72 hours of the onset of AMI and at a 4‐month follow‐up, two‐dimensional echocardiography was performed. The apical two‐ and four‐chamber views of the heart were analyzed offline using Echo Pac software for the assessment of strain by the STI method. LV remodeling was defined as a 15% increase from the baseline in LV end‐diastolic volume. Results: Twenty‐eight patients (34.1%) with LV remodeling at 4‐month follow‐up had comparable baseline clinical and echocardiographic characteristics with 54 patients (without LV remodeling), except for a predominance of the anterior wall MI (P < 0.01), higher leukocyte count value at admission (P < 0.01), lower ejection fraction (P < 0.05), increased end‐systolic volume (P < 0.05), and reduced global systolic Ls (P < 0.05). Multivariable logistic regression analysis revealed the systolic Ls as an independent determinant of LV remodeling after AMI. A receiver operating characteristic curve analysis showed that a cutoff value of ?11.6% for the systolic Ls yielded a 78% sensitivity and a 73% specificity to predict LV remodeling in 4 months. Conclusions. Our study has shown that LV longitudinal strain assessed by STI is an independent predictor of LV remodeling after AMI. (Echocardiography 2012;29:419‐427)     

Lipids,Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke

Background

Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.

Long-Term Prognostic Implications of Previous Silent Myocardial Infarction in Patients Presenting With Acute Myocardial Infarction

Objectives

This study investigated the prevalence of silent myocardial infarction (MI) in patients presenting with first acute myocardial infarction (AMI), and its relation with mortality and major adverse cardiovascular events (MACE) at long-term follow-up.

CB1 – Cannabinoid Receptor Antagonist Effects on Cortisol in Cannabis-Dependent Men

Background: The endocannabinoid system modulates the hypothalamic–pituitary–adrenal (HPA) axis, but the effect of cannabinoid type 1 (CB1) receptor antagonism following chronic CB1 receptor stimulation in humans is unknown. Objectives: To evaluate effects of the CB1 receptor antagonist rimonabant on the HPA axis in cannabis-dependent individuals. Methods: Fourteen daily cannabis smokers received increasingly frequent 20 mg oral Δ9-tetrahydrocannabinol (THC) doses (60–120 mg/day) over 8 days to standardize cannabis tolerance. Concurrent with the last THC dose, double-blind placebo or rimonabant (20 or 40 mg) was administered. Cannabinoid, rimonabant, and cortisol plasma concentrations were measured 1.5 hours prior to rimonabant administration and 2.0, 5.5, and 12.5 hours post-dose. Results: Ten participants completed before premature study termination due to rimonabant’s withdrawal from development. Five participants received 20 mg, three received 40 mg, and two placebo. There was a significant positive association between rimonabant concentration and change in cortisol concentration from baseline (r = .53, p < .01). There also was a borderline significant association between rimonabant dose and cortisol concentrations when the dose-by-time interaction was included. Four of eight participants receiving rimonabant (none of two receiving placebo) had greater cortisol concentrations 2 hours after dosing (at 11:30) than at 08:00, while normal diurnal variation should have peak concentrations at 08:00. Conclusion: Rimonabant 20 or 40 mg did not significantly increase plasma cortisol concentrations, consistent with an absence of antagonist-elicited cannabis withdrawal. Scientific Significance: Rimonabant doses >40 mg might elicit cortisol changes, confirming a role for CB1 receptors in modulating the HPA axis in humans.