The additive prognostic value of end-systolic pressure-volume relation by stress CMR in patients with known or suspected coronary artery disease.

PURPOSE: The difference between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an afterload-independent index of left ventricular (LV) contractility. We assessed the independent prognostic value of ΔESPVR index by dipyridamole stress-cardiovascular magnetic resonance (CMR) in patients with known/suspected coronary artery disease (CAD). METHODS: We considered 196 consecutive patients (62.74 ± 10.66 years, 49 females). Wall motion and perfusion abnormalities at rest and peak stress were analysed. Replacement myocardial fibrosis was detected by late gadolinium enhancement (LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson's method. RESULTS: A reduced ΔESPVR index (≤ 0.02 mmHg/mL/m2) was found in 88 (44.9%) patients and it was associated with a lower LV ejection fraction (EF) and with a higher frequency of abnormal stress CMR and myocardial fibrosis. During a mean follow-up of 53.17 ± 28.21 months, 50 (25.5%) cardiac events were recorded: 5 cardiac deaths, 17 revascularizations, one myocardial infarction, 23 hospitalisations for heart failure or unstable angina, and 4 ventricular arrhythmias. According to Cox regression analysis, diabetes, family history, LVEF, abnormal stress CMR, myocardial fibrosis, and reduced ΔESPVR were significant univariate prognosticators. In the multivariate analysis the independent predictors were ΔESPVR index ≤ 0.02 mmHg/mL/m2 (hazard ratio-HR = 2.58, P = 0.007), myocardial fibrosis (HR = 2.13, P = 0.036), and diabetes (HR = 2.33, P = 0.012). CONCLUSION: ΔESPVR index by stress-CMR was independently associated with cardiac outcomes in patients with known/suspected CAD, in addition to replacement myocardial fibrosis and diabetes. Thus, the assessment of ΔESPVR index may be included into the standard stress-CMR exam to further stratify the patients.

MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis.

BACKGROUND: MicroRNA-1 (miR1), encoded by the genes miR1-1 and miR1-2, is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling. METHODS: miR1-1 or miR1-2 knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD; miR1-1+/-:miR1-2-/- or miR1-1-/-:miR1-2+/-) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays. RESULTS: In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na+ current and transient outward potassium current, coupled with elevated L-type Ca2+ current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1's RNA interference-direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias. CONCLUSIONS: miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.

Evaluation of cardiac contractility of fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound

SUMMARY OBJECTIVE: This study aimed to evaluate cardiac contractility in fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode. METHODS: A retrospective cross-sectional study was performed on 40 fetuses from nondiabetic pregnancies and 28 pregestational diabetic pregnancies between 20 and 33 weeks and 6 days. Cardiac contractility was assessed by measuring the ventricular myocardial area in diastole subtracted from the ventricular myocardial area in systole. RESULTS: Pregestational diabetic pregnancies had a lower maternal age than nondiabetic pregnancies (26.7 vs. 39.9 years, p=0.019). Cardiac contractility in fetuses from diabetic and nondiabetic pregnancies was similar (p=0.293). A moderately positive and significant correlation was observed between gestational age and cardiac contractility (r=0.46, p=0.0004). A 1-week increase in gestational age was responsible for a 0.1386 cm2 increase in cardiac contractility. CONCLUSION: Cardiac contractility as evaluated by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode showed no significant differences across fetuses with and without pregestational diabetes.

Robust Arm Impedocardiography Signal Quality Enhancement Using Recursive Signal Averaging and Multi-Stage Wavelet Denoising Methods for Long-Term Cardiac Contractility Monitoring Armbands.

Impedance cardiography (ICG) is a low-cost, non-invasive technique that enables the clinical assessment of haemodynamic parameters, such as cardiac output and stroke volume (SV). Conventional ICG recordings are taken from the patient's thorax. However, access to ICG vital signs from the upper-arm brachial artery (as an associated surrogate) can enable user-convenient wearable armband sensor devices to provide an attractive option for gathering ICG trend-based indicators of general health, which offers particular advantages in ambulatory long-term monitoring settings. This study considered the upper arm ICG and control Thorax-ICG recordings data from 15 healthy subject cases. A prefiltering stage included a third-order Savitzky-Golay finite impulse response (FIR) filter, which was applied to the raw ICG signals. Then, a multi-stage wavelet-based denoising strategy on a beat-by-beat (BbyB) basis, which was supported by a recursive signal-averaging optimal thresholding adaptation algorithm for Arm-ICG signals, was investigated for robust signal quality enhancement. The performance of the BbyB ICG denoising was evaluated for each case using a 700 ms frame centred on the heartbeat ICG pulse. This frame was extracted from a 600-beat ensemble signal-averaged ICG and was used as the noiseless signal reference vector (gold standard frame). Furthermore, in each subject case, enhanced Arm-ICG and Thorax-ICG above a threshold of correlation of 0.95 with the noiseless vector enabled the analysis of beat inclusion rate (BIR%), yielding an average of 80.9% for Arm-ICG and 100% for Thorax-ICG, and BbyB values of the ICG waveform feature metrics A, B, C and VET accuracy and precision, yielding respective error rates (ER%) of 0.83%, 11.1%, 3.99% and 5.2% for Arm-IG, and 0.41%, 3.82%, 1.66% and 1.25% for Thorax-ICG, respectively. Hence, the functional relationship between ICG metrics within and between the arm and thorax recording modes could be characterised and the linear regression (Arm-ICG vs. Thorax-ICG) trends could be analysed. Overall, it was found in this study that recursive averaging, set with a 36 ICG beats buffer size, was the best Arm-ICG BbyB denoising process, with an average of less than 3.3% in the Arm-ICG time metrics error rate. It was also found that the arm SV versus thorax SV had a linear regression coefficient of determination (R2) of 0.84.

Intravenous administration of apeling-13 induces a depressor response by releasing an unidentified substance.

Apelin and APJ receptor play an important role in the regulating cardiovascular function; however, conflicting results have been reported regarding the effect of apelin on cardiovascular regulation. In this study, blood pressure and heart rate were measured by femoral arterial catheterization; and cardiac contractility was recorded by left ventricular catheterization through the right carotid artery in rats before and after intravenous administration of [pyr1]-apelin-13. The results show that intravenous administration of apelin-13 caused a dramatic reduction in BP but did not significantly alter heart rate and contractility. To study the mechanism of the apelin-induced depressor response, isometric tension was measured in isolated mesenteric arteries using a myograph approach. Surprisingly, treatment of the arteries with [pyr1]-apelin-13 did not cause relaxation of mesenteric arteries preconstricted with norepinephrine; however, treatment with plasma collected from rats that received intravenous administration of [pyr1]-apelin-13 caused pronounced relaxation of isolated arteries. Incubation with the guanylyl cyclase inhibitor, ODQ, blocked NO-induced relaxation, but did not significantly alter the relaxation response to the plasma from apelin-treated rats. Taken together, these findings demonstrate that intravenous injection of apelin causes a significant depressor response that is mediated by a NO-independent mechanism involving an unidentified substance released into the bloodstream leading to vasodilation.

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.

Novel Speckle Tracking Analysis Showed Excellent Reproducibility for Size and Shape of the Fetal Heart and Good Reproducibility for Strain and Fractional Shortening.

INTRODUCTION: This study aimed to evaluate reproducibility and agreement of fetal cardiac shape and deformation using FetalHQ. METHODS: Fifty normal fetuses at 20-38 weeks of gestation were evaluated. Two operators independently selected an optimal cardiac cycle using FetalHQ®™software for speckle tracking analysis. Intra- and interobserver correlation coefficient and limits of agreement for cardiac shape and deformation were estimated. RESULTS: Global cardiac markers: high correlation (r = 0.98) and agreement (mean difference, standard deviation [MD, SD] 5.07, 75.8) for ventricular area; moderate correlation (r = 0.78) and agreement (MD, SD: 0.016, 0.08) for global sphericity index (SI) and for left ventricle (LV) global strain (r = 0.65; MD, SD: -4.48, 11.9); and low but still significant correlation (r = 0.58) and agreement (MD, SD: -3.77, 12.27) for right ventricle (RV) global strain. For individual ventricular parameters: high correlation for LV ([median r; range] 0.98; 0.93-0.99) and RV (r = 0.98; 0.97-1.0) SI, and for LV (r = 0.92: 0.56-0.99) and RV (r = 0.96; 0.67-0.99) end diastolic diameters; moderate correlation for LV fractional shortening (r = 0.53; 0.87-0.98); and no significant correlation for RV fractional shortening (r = 0.36; 0.32-0.97). Inter- and intraobserver correlation and agreement were similar for all evaluated parameters. CONCLUSION: Speckle tracking analysis of the fetal heart provides reliable estimations of global and LV shape and deformation. Low correlation in the RV can be related to anatomical structures such as the moderator band.

[Modulation of cardiac contractility in patients with chronic heart failure and atrial fibrillation].

AIM: to evaluate the effectiveness of cardiac contractility modulation (MSS) in patients with chronic heart failure (CHF) and atrial fibrillation (AF). MATERIALS AND METHODS: The following studies were performed in 40 patients with CHF and AF before implantation of the MSS device and after 2 and 6 months of follow-up: 12-channel ECG, transthoracic EchoCG, 6-minute walk test, determination of the level of Pro-natriuretic N-terminal peptide (NT-proBNP), daily ECG monitoring, and a questionnaire based on the Minnesota quality of life questionnaire for patients with CHF (MHFLQ). All patients received long-term optimal drug therapy for CHF before surgery. RESULTS: The results obtained indicate a statistically significant positive effect of the use of MSS in patients with CHF and AF on LV FV, the functional class of CHF, and levels of NT-proBNP regardless of the etiology of CHF. CONCLUSION: The use of MSS may be promising for the treatment of heart failure in patients with CHF and AF.

Protective effect of nicotinamide and L-arginine against monocrotaline-induced pulmonary hypertension in rats: gender dependence.

BACKGROUND: The purpose of this paper was to examine the effects of nicotinamide (ND) and L-arginine (L-ARG) on pulmonary vascular and heart changes induced by pulmonary hypertension in rats in a gender-dependent way. METHODS: Experiments were performed on male (M) and female (F) rats. PAH was induced via monocrotaline injection (sc, 60/kg B.W.) on day one of the 23-day observational period. After that, the animals were sacrificed, hearts removed and weighed and the papillary muscles isolated to measure force of contraction (Fc). Morphological changes of pulmonary vessels were also examined. RESULTS: Mixed diet supplementation with L-ARG + ND prevented highly significant right ventricle enlargement induced by PAH in both, male and female rats. Weight ratios between the right ventricle (RV) on one side and the left ventricle with septum on the other (LV + S) decreased from 0.46 ± 0.016 g to 0.29 ± 0.006 g in males and from 0.63 ± 0.03 g to 0.24 ± 0.008 g in females, n = 6, p < 0.001. Additionally, PAH increased basal contractility in female groups, and each of the diet allocations (L-ARG, ND, and mixed) were found to restore contractility to control values. All diet protocols in male and female restored decreased responsiveness of the myocardium to norepinephrine in hearts obtained from rats with PAH and prevented vascular changes observed in pulmonary hypertension (thickness of blood vessels and cell infiltration). CONCLUSION: Our study suggests that L-arginine, nicotinamide or both play a positive role in right ventricle function or the process reducing pulmonary vascular remodeling especially in a gender-independent way.

Reduced Coronary Flow Reserve Is Associated with Impaired Ventricular-vascular Interaction in Patients with Obstructive Sleep Apnea.

Background and Objectives: Obstructive sleep apnea (OSA) is associated with cardiac and arterial damage and adverse cardiovascular outcomes. We aimed to determine whether coronary flow reserve (CFR), which represents microvascular dysfunction, might be associated with the ventricular-vascular coupling index (VVI), which represents the afterload-adjusted contractility in patients with OSA. Methods: We enrolled 281 patients (257 males; mean age, 43±11 years) with newly diagnosed OSA. Transthoracic echocardiography was performed, and adenosine-associated CFR was measured in the left anterior descending coronary artery. We evaluated the differences between the patients with normal CFR ≥2.5 and reduced CFR <2.5. VVI was calculated using the effective arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees) as follows: 10×Ea/Ees. Results: The normal CFR group (n=214) showed increased Ees (7.28±2.31 vs. 8.14±2.33 mmHg/mL, p=0.016) and preserved VVI (3.17±1.53 vs. 2.78±1.20, p=0.044) compared with the reduced CFR group (n=67). There were no differences in LV dimension, LV ejection fraction, left atrial-volume index, E/e', left atrial strain and LV global longitudinal strain between the 2 groups (all p>0.05). CFR was significantly correlated to Ees (r=0.139; p=0.023) and VVI (r=-0.137; p=0.025). Conclusions: Reduced CFR is associated with decreased Ees and impaired VVI in OSA patients. It suggests the necessity of more intensive observation in OSA patients with reduced CFR to improve cardiovascular outcomes.

The Influence of Bee Venom Melittin on the Functioning of the Immune System and the Contractile Activity of the Insect Heart-A Preliminary Study.

Melittin (MEL) is a basic polypeptide originally purified from honeybee venom. MEL exhibits a broad spectrum of biological activity. However, almost all studies on MEL activity have been carried out on vertebrate models or cell lines. Recently, due to cheap breeding and the possibility of extrapolating the results of the research to vertebrates, insects have been used for various bioassays and comparative physiological studies. For these reasons, it is valuable to examine the influence of melittin on insect physiology. Here, for the first time, we report the immunotropic and cardiotropic effects of melittin on the beetle Tenebrio molitor as a model insect. After melittin injection at 10-7 M and 10-3 M, the number of apoptotic cells in the haemolymph increased in a dose-dependent manner. The pro-apoptotic action of MEL was likely compensated by increasing the total number of haemocytes. However, the injection of MEL did not cause any changes in the percent of phagocytic haemocytes or in the phenoloxidase activity. In an in vitro bioassay with a semi-isolated Tenebrio heart, MEL induced a slight chronotropic-positive effect only at a higher concentration (10-4 M). Preliminary results indicated that melittin exerts pleiotropic effects on the functioning of the immune system and the endogenous contractile activity of the heart. Some of the induced responses in T. molitor resemble the reactions observed in vertebrate models. Therefore, the T. molitor beetle may be a convenient invertebrate model organism for comparative physiological studies and for the identification of new properties and mechanisms of action of melittin and related compounds.

A long-term perspective on cardiovascular job stress research.

This review provides perspectives on cardiovascular occupational stress research since the 1960s until now. The author argues for closer links between basic science and clinical follow-up examinations of patients. In an excellent way urinary excretion of adrenaline and noradrenaline during wake hours mirrors day to day or week to week variations in sympathomedullary activity which could be related to variations in the patient's and cardiovascular and psychosocial situation. Modern methods for following variations over time in heart contractility should also be related to the patients' psychosocial situation. In addition the author argues for more extensive use of the increasing knowledge regarding regeneration and vagal activity in relation to variations in job conditions and development or prevention of cardiovascular disease.

The Effect of Chemerin on Cardiac Parameters and Gene Expressions in Isolated Perfused Rat Heart

Background: Chemerin is a novel chemoattractant adipokine expressed in cardiovascular system, and its receptor has been detected in the epicardial adipose tissue. Aims: To determine the effects of chemerin on the cardiac parameters and gene expressions in the isolated perfused rat heart. Study Design: Animal experiment. Methods: The hearts were retrogradely perfused with Langendorff technique to measure the cardiac parameters. The experimental groups were acutely treated with 10, 100, and 1000 nM doses of chemerin. Another group was given 10 µM L-nitric oxide synthase inhibitor for 5 min before 1000 nM chemerin administration. The real-time polymerase chain reaction was performed for detecting the expression of target genes. Results: All doses of chemerin significantly decreased the left ventricular developed pressure (max 35.33 Δ%, p<0.001), and +dP/dtmax (max 31.3 Δ%, p<0.001), which are the indexes of cardiac contractile force. In addition, 1000 nM chemerin reduced the coronary flow (max 31 Δ%, p<0.001). N(W)-nitro-L-arginine methyl ester antagonized the negative inotropic effect of chemerin on contractility. Chemerin induced a 2.16-fold increase in endothelial nitric oxide synthase mRNA and increased the cyclic guanosine monophosphate levels (p<0.001) but decreased the PI3Kγ gene expression (1.8-fold, p<0.001). Furthermore, all doses of chemerin decreased the CaV1.2 gene expression (1.69-fold, p<0.001). Conclusion: Acute chemerin treatment induces a negative inotropic action with the involvement of nitric oxide pathway, CaV1.2, and PI3Kγ on isolated rat heart.

Choke Attack: Atypical Cardiomyopathy Subsequent to Postnasal Drip.

Midventricular ballooning syndrome, an atypical presentation of takotsubo cardiomyopathy (TCM), presents with transient wall motion abnormalities of the midsegment of the left ventricle with apical sparing. In midventricular TCM, apical contractility is unaffected or may be hyperkinetic in contrast to the typical form of TCM. We report a case of atypical TCM, wherein the patient presented with chest pain following choking and coughing spells due to a postnasal drip.

Overexpression of prostaglandin E2 EP4 receptor improves cardiac function after myocardial infarction.

BACKGROUND: Prostaglandin E2 (PGE2) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We recently reported that PGE2 via its EP3 receptor could reduce cardiac contractility of isolated myocytes and the working heart preparation. We thus hypothesized that there is an imbalance in the EP3/EP4 ratio towards EP3 in the failing heart and that overexpression of EP4 in a mouse model of heart failure would improve cardiac function. METHODS AND RESULTS: Our hypothesis was tested in a mouse model of myocardial infarction (MI) with the use of AAV9-EP4 driven by the myosin heavy chain promoter to overexpress EP4 in the cardiac myocytes. Echocardiography was performed to assess cardiac function. We found that overexpression of EP4 improved shortening fraction (p = 0.0025), ejection fraction (p = 0.0003), and reduced left ventricular dimension at systole (p = 0.0013). Overexpression of EP4 also significantly reduced indices of cardiac hypertrophy and interstitial collagen fraction. Animals treated with AAV9-EP4 also had a significant decrease in TNFα mRNA expression and in the number of macrophages and T cells migrated post MI coupled with a reduction in the expression of iNOS. CONCLUSION: Overexpression of EP4 improves cardiac function post MI. This may be mediated through reductions in adverse cardiac remodeling or via inhibition of cytokine/chemokine production.

Comparative Assessment of the Heart's Functioning by Using the Akabane Test and Classical Methods of Instrumental Examination.

Acupuncture physicians have studied the application of reflexotherapy to cardiology. However, no one has investigated the connection of ancient Chinese diagnostic methods with modern tools. A total of 102 patients (54 men and 48 women) with heart pathology, namely, sick-sinus syndrome, Wolff-Parkinson-White syndrome, and atrioventricular blockade, were studied using the usual instrumental methods (transesophageal electrophysiological study of the heart, echocardiography), after which they underwent Akabane thermopuncture testing as in traditional Chinese medicine. The results of cardio examination from one side of the Akabane test with that from the other side were compared by means of a multiple stepwise regression analysis. We revealed the effects on the characteristic pattern of acupuncture channel lesions inherent in a definite heart pathology, i.e., the most vulnerable acupuncture channel (AC), of such factors as disturbances of the contractile, conductive, or automatic heart functions, and changes in the chambers' size or circulation volume. Сhanges in the indices of the left and the right branches of these channels usually reflect the opposing natures of the changes in these indicators, which should be considered in reflexotherapy. The main value of the Akabane test along with the use of mathematical analysis lies in early, quick, and inexpensive detection of the above-mentioned heart disturbances.

The safety and efficacy of cardiac contractility modulation in heart failure : A meta-analysis of clinical trials.

BACKGROUND: Cardiac contractility modulation (CCM) has developed as a promising treatment device for heart failure (HF). This meta-analysis aimed at systematically reviewing the latest available published trials to provide evidence on the safety and efficacy of CCM in patients with HF. METHODS: We searched the Cochrane Central Resister of Controlled Trials, PubMed, and EMBASE in May 2016 to identify eligible clinical trials comparing CCM with sham treatment or with usual care. All-cause mortality, all-cause hospitalization, and serious cardiopulmonary adverse effects were considered to be the primary outcomes of interest in evaluating the safety of CCM for patients with HF. Peak oxygen consumption and 6­min walk tests were performed as the second outcomes of interest to assess efficacy. Risk ratio (RR), standard mean difference (SMD), and 95% confidence intervals (CIs) were calculated. RESULTS: Four studies enrolling 723 participants were included. Compared with the control arm, CCM did not significantly improve all-cause mortality or all-cause hospitalizations. No differences were observed for adverse effects of CCM, possibly due to the low number of studies. By contrast, CCM significantly improved peak oxygen consumption (standard mean difference 0.233, 95% CI, 0.065-0.401 ml/kg/min, p = 0.006) and the 6­min walk test distance (standard mean difference 0.924, 95% CI, 0.001-0.334 m, p = 0.049). CONCLUSION: In our meta-analysis of published clinic trials we found that CCM did not lower the risk of severe cardiovascular adverse events; however, it was associated with remarkable improvements in functional cardiopulmonary capacity. Therefore, CCM may serve as an alternative option for patients with advanced HF.

Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor.

BACKGROUND: Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously, we reported that cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with reduced ejection fraction. Thus, we hypothesized that PGE2 increases contractility via EP4 but decreases contractility via EP3. METHODS AND RESULTS: The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes. Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10(-6) M) or sulprostone (10(-6) M) and compared with vehicle. Both PGE2 and sulprostone decreased +dp/dt (P<0.01) and left ventricular developed pressure (P<0.001) with reversal by an EP3 antagonist. In contrast, the EP4 agonist had the opposite effect. Adult mouse cardiomyocytes contractility was also reduced after treatment with either PGE2 or sulprostone for 10 minutes. We then examined the acute effects of PGE2, sulprostone, and the EP4 agonist on expression of phosphorylated phospholamban and sarcoendoplasmic reticulum Ca(2+)-ATPase 2a in adult mouse cardiomyocytes using Western blot. Treatment with either PGE2 or sulprostone decreased expression of phosphorylated phospholamban corrected to total phospholamban, whereas treatment with the EP4 agonist had the opposite effect. Sarcoendoplasmic reticulum Ca(2+)-ATPase 2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure-volume loops. Both PGE2 and sulprostone decreased +dp/dt, whereas the EP4 agonist increased +dp/dt. CONCLUSIONS: Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation.