Cardiac Hemodynamic Parameters Research Articles

Carfilzomib Induces Acute Endothelial Dysfunction Which Correlates with the Occurrence of Cardiovascular Events

Carfilzomib Induces Acute Endothelial Dysfunction Which Correlates with the Occurrence of Cardiovascular Events

The role of minocycline in alleviating aluminum phosphide-induced cardiac hemodynamic and renal toxicity

Poisoning with aluminum phosphide (AlP) has been attributed to the high rate of mortality among many Asian countries. It affects several organs, mainly heart and kidney. Numerous literature demonstrated the valuable effect of minocycline in mitigating pathological symptoms of heart and kidney disease. The aim of the present study was to evaluate the probable protective effect of minocycline on cardiac hemodynamic parameters abnormalities and renal toxicity induced by AlP-poisoning in the rat model. AlP was administered by gavage at 12 mg/kg body weight followed by injection of minocycline for two interval times of 12 and 24 h, at 40, 80, 120 mg/kg body weight. Electrocardiographic (ECG) parameters were monitored, 30 min after AlP gavage for 6 h using an electronic cardiovascular monitoring device. Kidney tissue and serum were collected for the study of histology, mitochondrial complexes I, II, IV, lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity, ADP/ATP ratio, mitochondrial cytochrome c release, apoptosis, lactate, BUN, and Cr levels. The results demonstrated that AlP induces ECG abnormalities, and failure of heart rate and blood pressure, which improved significantly by minocycline. Minocycline treatment significantly improved complexes I, IV, MPO and LDH activities, and also reduced the ADP/ATP ratio, lactate level, release of cytochrome c, and apoptosis in the kidney following AlP-poisoning. Also, the histological results showed an improvement of kidney injury in minocycline treated groups. In conclusion, the findings of this study showed that minocycline could improve cardiac hemodynamic abnormalities and kidney injury following AlP-poisoning, suggesting minocycline might be a possible candidate for the treatment of AlP-poisoning.

Using Zebrafish for Investigating the Molecular Mechanisms of Drug-Induced Cardiotoxicity.

Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate the molecular mechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.

189. Non-invasive study of haemodynamic parameters in normotensive versus hypertensive pregnancies

Background/Objectives Major physiological cardiovascular system adaptations during pregnancy include decreased systemic vascular resistance (SVR) and increased cardiac output (CO). In hypertensive disorders of pregnancy, especially preeclampsia, these usual cardiovascular adaptations maybe deficient. This study aims to evaluate differences in cardiac function and haemodynamic parameters using point-of-care, non-invasive testing, in women with normotensive and hypertensive (chronic hypertension, CH, gestational hypertension, GH preeclampsia, PE) pregnancies. Methods Normotensive (NT, n = 70) and hypertensive (HT, n = 65; 23 CH, 22 GH, 20 PE) pregnant women aged 18–45 with a singleton pregnancy studied cross-sectionally from 20 weeks’ gestation in this ongoing prospective study. Haemodynamic parameters were obtained non-invasively via the Ultrasound Cardiac Output Monitor (USCOM) and liquid crystal sphygmomanometer. Women are followed prospectively and pregnancy outcomes, including preeclampsia development, ascertained. Results There was no statistically significant difference in average stroke volume (73 mL/NT, 69 mL/CH, 70 mL/GH, 73 mL/PE; p = 0.838), cardiac output (5.9/5.7/5.5 and 5.7L respectively; p = 0.802) and cardiac output index between groups (3.2/2.8/2.7/2.9L/min/m2; p = 0.16) between groups. Pre-eclamptic pregnancies had significantly higher SVR (1851 ± 1111 versus 1215 ± 396 dyne/se/cm−5; p ⩽ 0.001) and systematic vascular resistance index (3653 ± 2189 versus 2274 ± 912dyne/s/cm−5/m−2; p ⩽ 0.001) than NT pregnancies. As expected, HT participants had significantly higher mean arterial pressure, systolic (110 ± 12,129 ± 11, 129 ± 10, 138 ± 12; p ⩽ 0.001) and diastolic blood pressure (70 ± 9, 79 ± 9, 83 ± 8, 87 ± 12 mmHg respectively; p ⩽ 0.001) than NT. Conclusions In this pilot study of non-invasive (USCOM) haemodynamic measurements, significant differences in systemic vascular resistance, but not overall cardiac output, were seen between normotensive and hypertensive pregnancies. A larger sample size is needed for further investigation, including determining whether USCOM may be useful in predicting which pregnancies will progress from gestational hypertension and/or chronic hypertension, to preeclampsia.

Polymorphism of the second type angiotensin II receptor’s gene in women with essential hypertension and the corresponding features of structural and functional parameters of myocardium

Objective. To improve the diagnosis of predisposition to Essential arterial hypertension (EH) and Chronic heart failure (CHF) in postmenopausal age’s women by determining the polymorphic genotypes of the first type angiotensin II receptor’s gene (AT1-R) and the corresponding structural and functional state of myocardium. Materials and methods. The study involved 180 women of postmenopausal age, they were residents of Podillya Region of Ukraine. 80 women without signs of cardiovascular diseases were the control group, 100 women with EH included the main study’s group. Genotyping of AT1-R was carried out using the polymerase chain reaction. The distribution of the frequencies of genotypes AT1-R was checked in accordance with the Hardy–Weinberg equilibrium law. The structural and functional parameters of myocardium were evaluated using an echocardiography. The left ventricular’s systolic function was preserved in cases where the left ventricular’s ejection fraction was more than 40 %. Mathematical processing was performed using the standard statistic package Statistica 6.0. Results. In patients with EH genotype AC was detected most often (49 %), AA and AC genotypes weer determined in 40 % and 11 % of patients (Р АА-СС ≤ 0.05, Р АС-СС ≤ 0.05) respectively. Carrying allele C of the AT1-P gene was associated with a higher probability of future occurrence of CHF in patients with EH, more significant structural disorders of myocardium and disturbances of systolic and diastolic functions of left ventricle (LV) such as pseudonormal and restrictive types. Conclusions. Allele C associates with the presence of EH and a greater probability of occurrence of CHF in postmenopausal women, residents of Podillya Region, more pronounced disturbances in the structure of myocardium, with diastolic and systolic dysfunctions of LV. Developed mathematical models help to determine approximately the structure of AT1-R according to the parameters of cardiac hemodynamics in the case of impossibility of laboratory investigation.

Determinants of Improvement in Cardiopulmonary Exercise Testing After Left Ventricular Assist Device Implantation

Although improvement in cardiac output and hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs), improvement in exercise capacity is inconsistently seen. Our purpose was to determine whether native cardiac factors, LVAD factors, or comorbid factors were associated with lack of improvement. Review of all patients undergoing preimplant cardiopulmonary exercise testing (CPET) and CPET on LVAD therapy at one institution was performed between 2007 and 2014 (n = 49). Comprehensive assessment of echocardiographic parameters, right heart catheterization data, medications, and comorbid illness was undertaken. There was no mean improvement in peak oxygen consumption (VO2; 11.8-12.4 ml/kg/min; p = 0.26), although exercise time (5.1 [46% predicted] to 5.8 min [56% predicted]; p = 0.02) and nadir of the ratio of minute ventilation to carbon dioxide production slope (VE/VCO2; 39-36; p = 0.001) improved. Factors most strongly associated with improvement in VO2 were Heartmate II pulsatility index (PI; R = 0.48; p = 0.001), power (R = -0.40; p = 0.009), pump flow (R = -0.40; p = 0.008), and pump speed (R = -0.32; p = 0.04). Peak heart rate (HR) was also associated with improvement in VO2 (R = 0.41; p = 0.004). Left ventricular ejection fraction (LVEF; R = 0.004; p = 0.77), right ventricular (RV) function (R = 0.22; p = 0.28), and aortic valve opening (R = 0.20; p = 0.57) were not associated with improvement in VO2. Our data suggest that less reliance on LVAD support was modestly associated with improvement in exercise capacity. Further studies should seek to determine the optimal level of device support prospectively in relation to exercise capacity.

Direct evidence that hypoxia triggers the cardioprotective response of ischemic preconditioning in a dog double-circuit cardiopulmonary bypass model

AimsIt has been widely accepted that ischemic preconditioning (IPC) exhibits a promising and reproducible cardioprotective effect against ischemia/reperfusion (I/R) injury. However, the actual trigger that amplifies the molecular signaling and protects I/R heart is still unclear. Main methodsTo separate the factors involved in IPC, we established a dog double-circuit cardiopulmonary bypass (CPB) model, which consists of a systemic circuit and a coronary circuit. Forty-two male adult beagle dogs were randomly allocated into 7 groups: sham, I/R, IPC, hypoxia preconditioning (HPC), accumulated metabolite preconditioning (MPC), oxygenated or deoxygenated erythrocytes preconditioning (OxyEPC and DeoxyEPC). After pretreatment, dogs were subjected to 2 h-cardiac arrest and 2 h-reperfusion. Key findingsThere were no differences in the cardiac function and hemodynamic parameters at baseline among groups. Like IPC, the hypoxia-related pretreatments HPC and DeoxyEPC improved post-arrest left ventricular systolic/diastolic performance and reduced pulmonary vascular resistance. The cardiac oxygen (O2) utilization was also greatly elevated in these hypoxia-related pretreatment groups, as evidenced by increased cardiac O2 consumption (VO2) and O2 extraction index (O2EI) and suppressed lactate level. Besides, we did not observe improvement of these parameters in the MPC and OxyEPC groups. Further study indicated that these hypoxia-related pretreatments were associated with the attenuation of pro-inflammatory cytokines release and the elevation of complex I-supported mitochondrial respiration. SignificanceWith a dog double-circuit CPB model, we demonstrated that hypoxia is the actual trigger to initiate the cardioprotective effect of IPC in vivo, which was related to reduced cardiac inflammation and ameliorated complex-I supported mitochondrial function.

Development of Cardiac Output Monitoring Technology

Cardiovascular disease has become a serious disease that threatens the health of human beings, cardiac output is an important indicator of cardiovascular function, monitoring cardiac output and related hemodynamic parameters have significant clinical value. This article summarizes the development history, principle, method, advantages and disadvantages of various monitoring technologies from three aspects:invasive, minimally invasive and noninvasive, the development and application of cardiac output monitoring technology are prospected.

Selective abdominal venous congestion to investigate cardiorenal interactions in a rat model.

Abdominal congestion may play an important role in the cardiorenal syndrome and has been demonstrated to drive disease progression. An animal model for abdominal congestion, without other culprit mechanisms that are often present in patients such as low cardiac output or chronic kidney disease, might be interesting to allow a better study of the pathophysiology of the cardiorenal syndrome. The objective of this study was to develop a clinically relevant and valid rat model with abdominal venous congestion and without pre-existing heart and/or kidney dysfunction. To do so, a permanent surgical constriction (20 Gauge) of the thoracic inferior vena cava (IVC) was applied in male Sprague Dawley rats (IVCc, n = 7), which were compared to sham-operated rats (SHAM, n = 6). Twelve weeks after surgery, abdominal venous pressure (mean: 13.8 vs 4.9 mmHg, p < 0.01), plasma creatinine (p < 0.05), plasma cystatin c (p < 0.01), urinary albumin (p < 0.05), glomerular surface area (p < 0.01) and width of Bowman’s space (p < 0.05) of the IVCc group were significantly increased compared to the SHAM group for a comparable absolute body weight between groups (559 vs 530g, respectively, p = 0.73). Conventional cardiac echocardiographic and hemodynamic parameters did not differ significantly between both groups, indicating that cardiac function was not compromised by the surgery. In conclusion, we demonstrate that constriction of the thoracic IVC in adult rats is feasible and significantly increases the abdominal venous pressure to a clinically relevant level, thereby inducing abdominal venous congestion.

Pulse pressure amplification and cardiac autonomic dysfunction in patients with type 2 diabetes mellitus.

The main aim of this cross-sectional study was to investigate the association between pulse pressure amplification (PPA) and cardiac autonomic activity (baroreflex sensitivity (BRS) and heart rate variability (HRV)) in patients with type 2 diabetes mellitus (T2DM). In addition, we examined the association between cardiac autonomic activity and central hemodynamic parameters that may affect PPA such as augmentation index (AIx), aortic stiffness (pulse wave velocity (PWV)), and common carotid artery stiffness distensibility coefficient (DC). A total of 142 patients with T2DM were included in the study. In multivariate linear regression analysis-after controlling for age, diabetes duration, height, waist circumference, aortic PWV, use of β-blockers, and BRS-PPA was associated significantly and independently with male gender (standardized regression coefficient (β) = 0.156, p = 0.007), aortic systolic blood pressure (β = -0.221, p < 0.001), heart rate (β = 0.521, p < 0.001), AΙx (β = -0.443, p < 0.001), and parameters of HRV, such as total power of HRV (β = -0.157, p = 0.005). No significant associations were found between BRS or parameters of HRV with aortic PWV, AIx, or DC. In patients with T2DM, cardiac autonomic dysfunction was associated with enhanced PPA. This association was independent from the well-described effect of resting heart rate, as well as from traditional cardiovascular risk factors or diabetes-related factors. Moreover, it was not mediated by effects of the autonomic dysfunction on arterial stiffness or on pressure wave reflections. These findings suggest that cardiac autonomic dysfunction affects PPA by mechanisms other than resting tachycardia and arterial properties.

Latest Advances in Cardiac Output Monitoring from High-Definition Impedance Cardiography

Cardiac output (CO) and hemodynamic parameters, and specifically the noninvasive approach to their measurement, have been the subject of continuous technological developments and lengthy debates. The challenge remains to measure these parameters in a user friendly and cost-effective way, without compromising accuracy and with few limitations in the real clinical environment. The industry might have solved the issue with the latest development of thoracic bioimpedance, called high-definition impedance cardiography (HD-ICG) and based on the direct analysis of morphology of the heart impedance signals. It may offer improvements in accuracy, inter-operator reproducibility, sensitivity, and parameters management, and also simplifies the understanding of the etiology of cardiac dysfunctions. HD-ICG might have the potential to make hemodynamic measurements in anesthesia come of age and become a clinical standard.

Crocin attenuates cigarette smoke-induced lung injury and cardiac dysfunction by anti-oxidative effects: the role of Nrf2 antioxidant system in preventing oxidative stress

BackgroundChronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in world. Cigarette smoke is known to cause oxidative stress and deplete glutathione (GSH) levels. Nuclear erythroid-related factor 2 (Nrf2) is involved in transcriptional regulation of glutamate-cysteine ligase catalytic subunit (GCLc). Antioxidant compounds may be of therapeutic value in monitoring disease progression. Crocin demonstrates antioxidant and anti-inflammatory functions. The aim of this study was to investigate the protective role of crocin against CSE-mediated oxidative stress, inflammatory process, Nrf2 modifications and impairment of cardiac function in rats with COPD.MethodsEighty rats were divided into four groups: Control, Cigarette smoke exposure (CSE), Crocin, Crocin+CS. Each group was divided into the two parts: 1) to evaluate lung inflammatory and oxidative process, 2) to evaluate the effect of Cigarette smoke induced-lung injuries on cardiac electrocardiogram (such as heart rate and QRS complex) and hemodynamic parameters (such as perfusion pressure and left ventricular developed pressure).ResultsCSE rats showed a significant increase in cotinine concentration (17.24 ng/ml), and inflammatory parameters and a decrease in PO2 (75.87 mmHg) and expression of PKC (0.86 fold), PI3K (0.79 fold), MAPK (0.87 fold), Nrf2 (0.8 fold) and GCLc (0.75 fold) genes, antioxidant activity, and finally cardiac abnormalities in electrocardiogram and hemodynamic parameters. Co-treatment whit crocin could restore all these values to normal levels.ConclusionsCS induced-COPD in rat model provides evidence that chronic CS exposure leads to lung injury and mediated cardiac dysfunction. Crocin co-treatment by modulating of Nrf2 pathway protected lung injury caused by COPD and its related cardiac dysfunction. In this study, we showed the importance of Nrf2 activators as a therapeutic target for the development of novel therapy for lung oxidative injuries.

Development of a murine model of heart failure with preserved ejection fraction

Pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood today. One of the hypothesis is the role played by the endothelial dysfunction. To develop a murine model of HFpEF to study the role of EC dysfunction. We chose to develop a model that reproduce cardiovascular risk factors and co-morbidity seen in humans HFpEF by using aging, obese diabetic mice (db/db) perfused with Angiotensin II pump for one month (low grade inflammation). Males and females mice were studied at 1, 6 and 12 months by echocardiography, histology (parameters of EC dysfunction, fibrosis) and hemodynamic. At 1 and 6 months, we recorded no difference in cardiac functional, histologic and hemodynamic parameters in males db/db as compared to male db+. At 6 months females db/db displayed discrete echocardiographic and hemodynamic parameters of HFpEF as compared to female db+. Results at 12 months will be available for the meeting. Obese diabetic with low-grade inflammation mice do not develop clear markers of HFpEF within 6 months of life.

Toward a better noninvasive assessment of preejection period: A novel automatic algorithm for B-point detection and correction on thoracic impedance cardiogram.

Impedance cardiography is the most common clinically validated, noninvasive method for determining the timing of the opening of the aortic valve, an important event used for measuring preejection period, which reflects sympathetic beta-adrenergic influences on the heart. Automatic detection of the exact time of the opening of the aortic valve (B point on the impedance cardiogram) has proven to be challenging as its appearance varies between and within individuals and may manifest as a reversal, inflection, or rapid slope change of the thoracic impedance derivative's (dZ/dt) rapid rise. Here, a novel automatic algorithm is proposed for the detection of the B point by finding the main rapid rise of the dZ/dt signal, which is due to blood ejection. Several conditions based on zero crossings, minima, and maxima of the dZ/dt signal and its derivatives are considered to reject any unwanted noise and artifacts and select the true B-point location. The detected B-point locations are then corrected by modeling the B-point time data using forward and reverse autoregressive models. The proposed algorithm is validated against expert-detected B points and is compared with different conventional methods; it significantly outperforms them by at least 54% in mean error, 30% in mean absolute error, and 27% in standard deviation of error. This algorithm can be adopted in ambulatory studies requiring beat-to-beat evaluation of cardiac hemodynamic parameters over extended time periods where expert scoring is not feasible.

Changes in left ventricular systolic and diastolic function on serial echocardiography after out-of-hospital cardiac arrest

AimReversible myocardial dysfunction is common after out-of-hospital cardiac arrest (OHCA). The aim of this study was to determine if changes on serial transthoracic echocardiography (TTE) can predict long-term mortality in OHCA subjects. MethodsThis is a single-center historical cohort study of OHCA subjects undergoing targeted temperature management who received >1 TTE during hospitalization. Two-dimensional and Doppler parameters of systolic and diastolic function were compared between paired TTE. Univariate analysis was used to determine associations between TTE parameters and all-cause mortality. ResultsFifty-nine patients were included; mean age was 59.4 ± 11.2 years (75% male). Initial rhythm was shockable in 90%. Initial TTE was done a median of 10.4 h after admission and repeat TTE was done 5.7 ± 4.1 days later. Between TTE studies, there were significant increases in left ventricular ejection fraction (LVEF, from 32% to 43%), cardiac output, stroke volume, and other Doppler-derived hemodynamic parameters, while systemic vascular resistance decreased (all p < 0.001). Systolic function and hemodynamic parameters on initial TTE were not associated with follow-up mortality. Patients who died during follow-up (n = 16, 27%) had smaller increases in LVEF and cardiac output-derived hemodynamic parameters than long-term survivors (p < 0.05). ConclusionsSignificant changes in systolic function and hemodynamic parameters occur on serial Doppler TTE after OHCA, consistent with reversible post-arrest myocardial dysfunction. The magnitude of those changes is greater in long-term survivors, emphasizing that the degree of recovery from post-arrest myocardial dysfunction may be more important than its initial severity.

Acute sleep deprivation induces cardioprotection against ischemia/ reperfusion injury through reducing inflammatory responses: the role of central GABA-A receptors.

Sleep is considered as a physiological regulator in the body. Gamma-aminobutyric acid (GABA) is a neurotransmitter that modulates sleep and affects cardiac functions. We evaluated effects of acute sleep deprivation (SD) on cardiac hemodynamic parameters, expression of pro-inflammatory cytokines, and Heat shock protein (Hsp70), serum level of lactate dehydrogenase (LDH) and prooxidant/antioxidant balance (PAB). Male Wistar rats were bilaterally cannulated in the central nucleus of amygdala (CeA) and saline or bicuculline was injected 24 hours prior to induction of 30 minute ischemia following 120 minute reperfusion. Forty-eight animals were randomly divided into four groups: Control (CONT), bicuculline (BIC), acute SD and bicuculline + acute sleep deprivation (BIC+SD). Animals in SD and BIC+SD groups were put in an aquarium for inducing sleep deprivation. SD attenuated LDH, pro-inflammatory cytokines and PAB; improved cardiac hemodynamic parameters and increased Hsp70 in non-infarcted area as compared to CONT. Administration of bicuculline increased LDH, pro-inflammatory cytokines and PAB, reduced cardiac hemodynamic parameters and Hsp70 as compared to CONT. Furthermore, bicuculline administration prior to acute sleep induction decreased SD effects on LDH, PAB, Hsp70, cardiac hemodynamic parameters and pro-inflammatory cytokines. Induction of SD prior to ischemia/reperfusion induces cardioprotection through suppressing inflammatory responses.

Sex Characteristics of Hydrogen Sulfide Effect on Ischemia-Reperfusion in Rat Myocardium

The changes in cardiac hemodynamics against the background of ischemia-reperfusion in 40 male and female white rats and their relationship with the level of hydrogen sulfide (H2S) in the blood serum were studied. In a model of ischemia-reperfusion injury, we evaluated the parameters of cardiac hemodynamics (microcirculation rate, left ventricle oxygen saturation, right and left ventricular pressure) and hydrogen sulfide content in the blood serum. It has been found that in males background levels of microcirculation coefficient in the left ventricle and the content of H2S in the blood serum are significantly lower (by 9-18%) than those in females. Under experimental occlusion of the left coronary artery, H2S level decreases in the blood serum (in males by 64.5%, in females by 51.1%), which is accompanied by an inhibition of microcirculation and oxygen supply of the left ventricle cardiomyocytes (microcirculation coefficient and oxygen saturation are reduced), by weakening the contractive capacity and violation of intraventricular hemodynamics (pressure is reduced in left and right ventricles). These changes are more pronounced in males compared to females. Reperfusion of coronary vessels in animals of both sexes does not cause total recovery of H2S content in the serum and cardiac hemodynamics indicators to the background levels, indicating the formation of no-reflow coronary circulation syndrome. Infusion of NaHS not only prevents ischemia of the heart muscle, but also contributes to a more complete recanalization by improving effective perfusion in both males and females. Correlative analysis has shown that H2S level in the blood serum reveals direct links with microcirculation coefficient, left ventricle oxygen saturation, right and left ventricular pressure (in males, r = 0.54-0.62; in females, r = 0.60-0.70). These data suggest an important role of H2S system in the regulation of microcirculation and cardiac hemodynamics in male and female rats against the background of ischemia-reperfusion.

Palmatine attenuates isoproterenol-induced pathological hypertrophy via selectively inhibiting HDAC2 in rats.

This study aimed to exploit the potential therapeutic value of palmatine in treatment of cardiac hypertrophy and the underlying molecular mechanism. Rat hypertrophy model was established by intraperitoneal isoproterenol (ISO) injection. The hypertrophy was evaluated with cardiac hypertrophic parameters, hemodynamic parameters, lipid profile, and non-specific cardiac markers. The animals were intraperitoneally administrated with either palmatine or vehicle. The relative expressions of ANP, BNP, HDAC2, HDAC5, KLF4, and INPP5F transcripts were determined by real-time polymerase chain reaction (PCR). The relative protein levels of HDAC2, HDAC5, KLF4, and INPP5F were analyzed by immunoblotting. Palmatine treatment significantly attenuated ISO-induced hypertrophy in rats and elicited remarkable repressions in ANP, BNP, and HDAC2 transcriptions but not HDAC5. The downstream effector genes KLF4 and INPP5F were greatly restored in a dose-dependent manner in response to palmatine treatment. Our data demonstrated that palmatine possessed promising therapeutic potential against hypertrophy, which was mediated by modulation of HDAC2-KLF4/INPP5F pathway.

Magnesium valproate ameliorates type 1 diabetes and cardiomyopathy in diabetic rats through estrogen receptors

Estrogen is known to exhibit cardioprotective and antihyperlipidemic action. Valproic acid has been shown to upregulate estrogen receptors (ERs) in breast and prostate cancer tissues. No pharmacological evaluations for magnesium valproate (MgV) so far have been done for diabetic cadio-lipidemic complications. Based on the above context, current study was undertaken to evaluate the therapeutic effectiveness of MgV in cardiac complications associated with type-1 diabetes mellitus in rats wherein diabetes was induced by single tail vein injection of streptozotocin (STZ, 45mg/kg, IV) in female Sprague Dawley rats and treatment of MgV (210mg/kg, PO) was given for eight weeks to diabetic animals, after which, various biochemical and cardiac biomarkers, hypertrophic, hemodynamic and histological parameters along with immunohistochemistry of ERs in the left ventricle (LV) were estimated. MgV treatment significantly controlled hyperglycemia and dyslipidemia, reduced elevated cardiac biomarkers and C-reactive protein(CRP), significantly improved hemodynamic functions and increased the rate of pressure development and decay. MgV also significantly reduced left ventricular hypertrophy index and cardiac hypertrophy index, LV wall thickness, LV collagen, cardiomyocyte diameter and prevented the oxidative stress with significant increase in Na+-K+-ATPase activity in LV. Moreover, MgV reversed STZ-induced histological alterations and decreased glycogen content in LV and increased the ERβ expressions in LV as evidenced by immunohistochemistry. The result indicated that MgV prevented disease progression in the early stage of diabetic cardiomyopathy which seems to be mediated by upregulation of estrogen receptors in LV tissue.

Extreme levels of ambient air pollution adversely impact cardiac and central aortic hemodynamics: the AIRCMD-China study

Ambient air pollution is an independent risk factor for cardiovascular diseases. However, the underlying mechanisms have yet to be fully elucidated. We performed a panel study on 65 nonsmoking patients with metabolic syndrome, with four repeated clinical visits between 2012 and 2013 in Beijing, China. Cardiac and central aortic hemodynamic parameters were measured by pulse wave analyses as subendocardial viability ratio, ejection duration, and central aortic pressure. We also calculated rate-pressure product parameter and collected peripheral blood for analyses. High levels of ambient particulate matter with diameter ≤10 and 2.5 μm (PM10 and PM2.5), black carbon, sulfur dioxide, and nitrogen dioxide were 121.3, 99.5, 6.5, 24.5, and 59.2 μg/m3, respectively. Short- to medium-term exposures to high levels of ambient air pollution adversely impacted central hemodynamics-derived surrogates of myocardial perfusion and oxygen demand. Each 10 μg/m3 increase in PM2.5 was associated with significant decreases of 0.67% (95% confidence interval: −2.84, −0.22) in subendocardial viability ratio at moving average 35 days (MA35) and an increase of 0.31 in rate-pressure product (95% confidence interval: 0.03, 0.59) at MA5. In conclusion, our results suggest that impaired myocardial perfusion and increased myocardial oxygen demand may play importantly mechanistic roles in air pollution–attributed cardiovascular diseases.