Inotropic Function Research Articles

358. Early Cardiac Marker of Mortality in COVID-19

BackgroundEpicardial adipose tissue (EAT) is a highly inflammatory depot of fat, with high concentrations of IL-6 and macrophages, which can directly reach the myo-pericardium via the vasa vasorum or paracrine pathways. TNF-α and IL-6 diminish cardiac inotropic function, making EAT inflammation a potential cause of cardiac dysfunction. MethodsA retrospective cohort study assessing EAT Thickness and Density from CT scans, without contrast, from adult patients during index admission for COVID-19 infection at Mount Sinai Medical Center from March 2020 to January 2021. A total of 1,644 patients were screened, of which 148 patients were included. Follow-up completed until death or discharge. The descriptive analysis was applied to the general population, parametric test of normality for comparisons between groups. Kaplan survival analysis was conducted after survival distribution was confirmed significant. It was followed by the assumption of normality by Q-Q Plot, prior to performing a multiple regression analysis in the vulnerable group using a K-Matrix input for cofounders. A log-rank test was conducted to determine differences in the survival distributions for the different ranges of EAT thickness.ResultsA total of 148 Participants were assigned to two groups based on epicardial adipose tissue in order to classify them as increased or decreased risk of cardiovascular risk: >5mm (n = 99), < 5mm (n = 49). The survival percentage was higher in the group with no EAT inflammation compared to the group with EAT inflammation (95.0% and 65%, respectively). Participants with EAT >5mm had a median day of hospital stay of 18 (95% CI, 16.86 to 29.92). The survival distributions for the two categories were statistically significantly different, χ2(2) = 6.9, p < 0.01. A Bonferroni correction was made with statistical significance accepted at the p < 0.025 level. There was a statistically significant difference in survival distributions for the EAT >5 mm vs EAT < 5 mm, χ2(1) =6.953, p = 0.008. EAT Thickness Survival Analysis 2020-2021 COVID-19 MSMC Scatter Plot Length of Stay by EAT Thickness ConclusionThere was an association with increased EAT thickness and increased mortality. These findings suggest that EAT thickness can be used as a prognostic factor and as a risk factor for increased mortality in patients with COVID-19Disclosures All Authors: No reported disclosures

Anti-ischemic effect and cardiodynamic changes under low-intensive laser irradiation compared to the obsidan effect in patients with angina pectoris

Purpose: to estimate the anti-anginal effect and to assess changes in hemodynamic parameters in patients with angina pectoris (AP) under low-intensive laser irradiation and to compare them with those under Obsidan preparation administration.Materials and methods. 70 males with AP of functional class I–IV were enrolled in the study and randomized into 2 equivalent groups: Group 1 – patients who took Obsidan; Group 2 — patients who were treated with infrared laser light. Patients were examined at the initial stage-one hour after 40 mg Obsidan take (Group 1), and one month after 10-day course of laser therapy (LT) (Group 2). All patients had echocardiography and cycle ergometric test.Results. The performed examinations showed a statistically significant increase in exercise tolerance in patients of LT group and Obsidan group by 35.0% and 34.1%, respectively. It should be noted that echocardiographic indicators had unidirectional, statistically significant shifts characterized by improvements in the myocardial inotropic function: decrease in the end-systolic volume by 17.9% and 18.8%, increase in the left ventricular ejection fraction from 50.3 ± 6.2 to 55.7 ± 5.8% and from 46.3 ± 4.3 to 50.1 ± 6.1 after LT and Obsidan , respectively. The optimal diastolic cardiac function was confirmed by the reduced time of myocardium isometric relaxation from 112.9 ± 24.3 to 94.3 ± 25.3 ms (p=0.012) under LT and from 110.3 ± 22.7 to 97.3 ± 19.3 ms under Obsidan (p=0.012). Results of the exercise tolerance test indicated the activation of cardiac economy mechanisms in both groups.Conclusion. Low-intensive LT had an impact at the cardiac activity similar to that of Obsidan. Moreover, it also has the equal anti-ischemic effect what may be explained by the decrease of energy expenditure during physical activity in patients with AP.

Comparative evaluation of echocardiographic characteristics of the heart left ventricle in female and male rats

The aim of the present study is a comparative assessment of the echocardiographic characteristics in female and male mongrel rats. In experiments on anesthetized rats (ketamine 100 mg / kg, iv), it was shown that in female rats, the size and volume of the left ventricle are smaller than in males, but compared with males, their left ventricular ejection fraction, which characterizes its inotropic function, is statistically significantly higher.

Left ventricular depression and pulmonary edema in rats after short-term normobaric hypoxia: effects of adrenergic blockade and reduced fluid load

Acute normobaric hypoxia may induce pulmonary injury with edema (PE) and inflammation. Hypoxia is accompanied by sympathetic activation. As both acute hypoxia and high plasma catecholamine levels may elicit PE, we had originally expected that adrenergic blockade may attenuate the severity of hypoxic pulmonary injury. In particular, we investigated whether administration of drugs with reduced fluid load would be beneficial with respect to both cardiocirculatory and pulmonary functions in acute hypoxia. Rats were exposed to normobaric hypoxia (10% O2) over 1.5 or 6 h and received 0.9% NaCl or adrenergic blockers either as infusion (1 ml/h, increased fluid load) or injection (0.5 ml, reduced fluid load). Control animals were kept in normoxia and received infusions or injections of 0.9% NaCl. After 6 h of hypoxia, LV inotropic function was maintained with NaCl injection but decreased significantly with NaCl infusion. Adrenergic blockade induced a similar LV depression when fluid load was low, but did not further deteriorate LV depression after 6 h of infusion. Reduced fluid load also attenuated pulmonary injury after 6 h of hypoxia. This might be due to an effective fluid drainage into the pleural space. Adrenergic blockade could not prevent PE. In general, increased fluid load and impaired LV inotropic function promote the development of PE in acute hypoxia. The main physiologic conclusion from this study is that fluid reduction under hypoxic conditions has a protective effect on cardiopulmonary function. Consequently, appropriate fluid management has particular importance to subjects in hypoxic conditions.

On the Mechanism of Cardioprotective Effect of Fabomotizole in Alcoholic Cardiomyopathy.

The molecular mechanisms underlying the cardioprotective effect of fabomotizole were studied using the translational rat model of alcoholic cardiomyopathy developed by us. It was shown that intraperitoneal administration of fabomotizole (15 mg/kg) for 28 days to animals with alcoholic cardiomyopathy contributes to normalization of the expression of mRNA of genes of regulatory proteins СаМ (p=0.00001), Ерас1 (p=0.021), and Ерас2 (p=0.018) and receptors RyR2 (p=0.0031) and IP3R2 (p=0.006) in the myocardium of the myocardium of the left ventricle that is enhanced in control animals (p<0.05). These changes were accompanied by echocardiographically documented decrease in the degree of left ventricle remodeling and improvement of its inotropic function.

Choice of Tactics for Experimental Therapy of Chronic Heart Failure with ALM-802 Compound.

The cardioprotective activity of ALM-802 compound was demonstrated in model experiments simulating postinfarction chronic heart failure in rats forming in 90 days after anterior transmural myocardial infarction. ALM-802 decreased the left ventricle and improved its inotropic function (p=0.038). This effect was observed in case of systematic administration of ALM-802 over 28 days (starting from day 91 after infarction modeling). This is apparently the minimum time for the cardioprotective effect of ALM-802 to prevent or treat the resulting heart failure, because short-term systematic therapy (15 days) produced no positive effect.

Effect of serotonin on myocardial contractility in newborn rats with excess and deficiency of serotonin in the embryonic period

Serotonin as a neurotransmitter (5-HT) plays a crucial role in the cardiovascular system. Serotonin is a humoral system of regulators and modulators of physiological processes. Under pathological conditions, these processes can turn into factors contributing to the development of diseases such as atherosclerosis, arterial hypertension, and pulmonary hypertension. The 5-HT4 and 5-HT2B receptors are found in cardiomyocytes. During the embryonic period, serotonin acts as a growth factor and plays an important regulatory role in the crucial period of embryonic development, in particular, a heart of an embryo. Therefore, any interference with this system in the womb can disrupt the normal development of the cardiovascular system. In the given study, there is some data provided to indicate that a change in the serotonin concentration created by the serotonin synthesis and the membrane serotonin transporter blocked in the embryonic period of ontogenesis, affects the inotropic function of the right ventricular myocardium in early postnatal ontogenesis, which is caused by a change in the contraction time in the groups under the experiment. Thus, statistically the response of cardiomyocytes to serotonin is significantly higher in the group with an excess of serotonin and significantly lower in the group with a deficiency of serotonin compared to the control group.

Cardioprotective effects of a new glutamic acid derivative in chronic alcohol intoxication.

Alcohol abuse is a risk factor for heart damage and deterioration of its inotropic function. Currently, there is no pathogenetic pharmacological treatment for alcohol-induced myocardial injury. Therefore, the study of drugs with cardioprotective action is of current interest. Our earlier studies of stress-induced heart damage showed that a new derivative of glutamic acid - glufimet - protects the myocardium's inotropic function and limits lipid peroxidation. Additionally, we found that it increases the activity of antioxidant enzymes and improves mitochondrial respiration. The purpose of our study was to assess the effect of glufimet on the heart after chronic alcohol intoxication (CAI). The comparison drug was mildronate, which possesses cardioprotective properties and is used to treat alcohol withdrawal. We conducted our study using female Wistar rats (10 months old, 280-320g). CAI was simulated by replacing drinking water with a 10% ethanol solution sweetened with sucrose (50g/L) over a period of 24 weeks. The day after the animals stopped ethanol solution drinking, the control group was injected intraperitoneally (i.p.) with a saline solution once a day for 14 days, while the experimental groups received glufimet (28.7mg/kg) and the drug of comparison mildronate (50mg/kg), respectively. After that, we studied the heart contractility by measuring volume load, adrenergic reactivity, and maximum isometric load. Under CAI, the control group showed significantly lower growth in left ventricular pressure (LVP), myocardium contraction rate, and relaxation rate during functional tests. Higher concentrations of LPO products (malondialdehyde) and low activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase), indicating a disturbance in mitochondrial respiration compared to the control group, were registered. While being treated with glufimet and mildronate, the animals demonstrated higher growth rates of myocardial contraction, myocardial relaxation, and LVP, compared to the control group. Mitochondrial functioning and activity of the antioxidant enzymes increased in the same group as well.

Effect of RGPU-260, a Novel GABA Derivative, on Functional Reserves of Rat Heart after Chronic Alcohol Intoxication.

The effect of a new derivative of GABA, the compound RGPU-260, on the heart contractility of rats exposed to chronic alcohol intoxication (10% ethanol solution for 24 weeks) was studied. In comparison with intact rats, the alcoholized ones were characterized with smaller increments in the rates of myocardial contraction (+dP/dtmax) and relaxation (-dP/dtmax), left ventricular pressure, and maximum intensity of functioning of structures during the load tests (volume load/preload, stimulation of the cardiac adrenergic receptors, and occlusion of the ascending aorta/afterload) attesting to degraded cardiac contractility function. In rats treated with RGPU-260 (daily, 25 mg/kg intragastrically during 14 days), these parameters were higher in comparison with control values indicating a positive action of the examined agent on inotropic function of the heart. Effectiveness of cardiotropic action of RGPU-260 was comparable to that of the reference drug mildronate.

Studies of Molecular Mechanisms Underlying Cardioprotective Action of the ALM-802 Compound.

The mechanisms underlying cardioprotective activity of compound ALM-802 were studied in experiments on rats with chronic post-infarction heart failure. Real-time PCR showed that compound ALM-802 (daily intraperitoneal injections in a dose of 2 mg/kg for 28 days starting from day 91 after myocardial infarction modeling) restored the expression of genes encoding β1- (p=0.00001) and β2-adrenoreceptors (p=0.01) and type 2 ryanodine receptors (p=0.008) in the myocardium that was reduced in control animals. These effects can serve as the basis for the ability of the compound to reduce the intensity of remodeling and increase the inotropic function of the left heart ventricle shown earlier in this model.

Modern Possibilities of Metabolic Therapy in Improving the Quality of Life in Patients with Postinfarction Cardiosclerosis

95 patients with postinfarction cardiosclerosis and angina pectoris II and III functional classes were examined. The study included patients who refused intervention revascularization. The main group included 48 patients who were added taurine (Dibikor 750 mg / day) to enhance the effect of basic therapy, and the comparison group included 47 patients who received standard therapy and placebo. The duration of treatment was 3 months. The study demonstrated positive effects of taurine that was confirmed by significant improvements in the following indicators: subjective status, indicators of the Seattle questionnaire, echocardiographic parameters, cardiac arrhythmias. There was a decrease in the severity of fatigue by 2 times, a decrease in the intensity of complaints of palpitations by 72.3%, a decrease in the severity of dyspnea by 30.0% and a severity of pain in the heart area by 50%. Indicators of most scales of the Seattle questionnaire in patients of the main group at the end of the study significantly exceeded (p &lt;0.05) the corresponding values in patients of the comparison group. In patients whose treatment was used taurine, a significant improvement in inotropic function was noted (the ejection fraction is significantly higher than in the comparison group, respectively 56.0 ± 1.8 and 53.5 ± 1.1%, p &lt;0,05), the bathmotropic and chronotropic myocardial functions improved, which was shown by a 45% decrease in the number of ventricular extrasystoles, a 57% decrease in the frequency of supraventricular heart rhythm disturbances, a decrease in the incidence rate of ST segment depression (in the main group the number of episodes was significantly lower than p &lt;0,05 than in the comparison group). The use of taurine in the complex treatment of patients with exertional angina, after suffering a myocardial infarction, is safe and not accompanied by side effects. Taurine is advisable to include in the complex treatment of patients with exertional angina pectoris, who have had a myocardial infarction in order to improve the myocardial inotropic function, enhance the antiarrhythmic and lipid-lowering effects of the basic therapy. The recommended dose of Taurine is 750 mg per day as a supplement to standard therapy with a duration of therapy of at least 3 months.

Confirmation of validity of the developed translational model of chronic heart failure in rats

The exprimants based on our translational model of chronic post-infarction heart failure within the use of echocardiography showed that in animals after 90 days after the reproduction of the myocardial infarction compared to the sham operated animals there is a significant increase in the endsystolic and end-diastolic sizes of the left ventricle (respectively, from 2.49 ± 0.09 to 3.91 ± 0.17 mm, p = 0.0002, and from 3.56 ± 0.12 to 5.20 ± 0.19 mm, p = 0.0002) and the decrease of its inotropic function that indicates a simulated pathology. 5 days after the echocardiographic study, the animals' exercise tolerance was assessed in the treadmill-run to failure test. It is proved in rats that 90 days after the coronary artery litigation the tolerance of physical activity decreases sharply – the value of the distance covered by them is 109.21 ± 11.61 m, which is 2.5 times less than the distance covered by sham operated animals ( p = 0.003) and 5.3 times less than the distance covered by intact rats ( p = 0.0001), – which is pathognomonic for chronic heart failure and complements the data of previously conducted morpho-histological, biochemical and molecular studies, indicating that the present model reproduces the main clinical and diagnostic signs of the simulated pathology.

Влияние положения Тренделенбурга и пневмоперитонеума на сердечно-сосудистую систему при робот-ассистированной радикальной простатэктомии.

Introduction. Prostate cancer remains one of the most common malignant neoplasms of the genitourinary system. Robot-assisted radical prostatectomy (RARP) is currently considered the most effective option for the treatment of this pathology. Special conditions of this operation, such as long-term stay of the patient in the Trendelenburg position and pneumoperitoneum, affect blood pressure, vascular resistance and inotropic function of the heart. The clinical significance of this effect remains poorly understood. The aim of the study was to systematize new information about hemodynamic disorders in patients with pneumoperitoneum in the Trendelenburg position in RARP. Materials and methods. The search for relevant studies published before may 2019 was conducted in the electronic databases PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar using the keywords: «prostatectomy», «robotic surgery», «robotic assisted», «robotic laparoscopic radical prostatectomy», «pneumoperitoneum», «Trendelenburg position», «hemodynamics», «hemodynamic changes», «cardiac function», «cardiovascular function» without restrictions on the publication language. Forty one studies were identified, of which 15 were selected according to pre-defined inclusion criteria. Results. Most studies revealed an increase in arterial and central venous pressure in patients with pneumoperitoneum in the Trendelenburg position. Changes in stroke volume and cardiac output were multidirectional. There was also an increase in pulmonary artery pressure and filling pressure, a decrease in the aortic diameter and an increase in vascular resistance, a deterioration in central hemodynamic parameters, and increased microcirculation. Eleven studies did not show a negative effect of the Trendelenburg position and pneumoperitoneum on the cardiovascular system. The developed changes were easily controlled during anesthesia, and in the postoperative period, the indicators of the cardiovascular system returned to normal. In 4 studies, the negative impact of these factors was noted: the development of mitral valve dysfunction, a significant prolongation of the QT interval and an increase in blood pressure, and hemodynamic instability. Conclusions. The position of the Trendelenburg and pneumoperitoneum and in RARP are accompanied by hemodynamic disorders, most of which are controlled and reversible. Further studies with a longer follow-up period are needed to determine their clinical safety.

EPAC Proteins and Their Role in the Physiological and Pathological Processes in the Cardiovascular System. Part II. The role of EPAC Proteins in the Physiology and Pathology of the Heart

The second part of the review presents modern ideas about vision of the role of Epac proteins in the regulation of inotropic and rhythmic functions of the heart, intercellular coupling of cardiomyocytes and their apoptosis. The contribution of Epac proteins to the development of hypertrophy, fibrosis, and myocardial remodeling, as well as their role in the genesis of acute ischemic damage to the heart muscle and cardiac arrhythmias, is examined in detail.

Normal autonomic neurophysiology of postural orthostatic tachycardia and recommended physiological assessments in postural orthostatic tachycardia syndrome.

The current surge of interest in postural orthostatic tachycardia syndrome commonly known as POTS requires good knowledge of the very complex physiology involved, but this is currently lacking. The often overlooked normal physiology of orthostasis is reviewed including the definition of normal postural orthostatic tachycardia. An illustrated functional anatomy that embeds orthostatic tachycardia within the learned and skilful motor functions in the human population is presented. The four physiological phases of orthostasis and the role of tachycardia are described in a laboratory‐controlled and progressive orthostatic stress in normal human volunteers. Standardized surrogate measures of autonomic control were used to quantify the trigger level for excessive tachycardia and the minimum autonomic control required to sustain viable arterial blood pressure during severe orthostatic stress in normal human volunteers. Tachycardia during orthostasis is part of a “democratic” contribution by four cardiovascular parameters of which the chronotropic function of the heart is just one of the parameters contributing toward cardiovascular compensation. It is adjusted during orthostasis in proportion to contributions from the other three parameters, namely inotropic function of the heart, windkessel vascular resistance and venous vascular capacitance. The physiological effects of the two stressors during orthostasis, gravity and isometric contraction of skeletal muscles are reviewed. A model of how the four cardiovascular parameters are regulated during orthostasis to achieve proportionate contributions is proposed emphasizing the necessity to quantify individual contributions from all these four parameters. Any one or more of these parameters may be compromised due to disease requiring disproportionate contribution of the prevailing magnitude of orthostatic tachycardia in an individual. It therefore requires neurophysiological assessment of the autonomic regulation of all the four cardiovascular parameters to assess the condition fully. We recommend here some current and novel neurophysiological methods that use modern medical technology to quantify laboratory standardized surrogate measures of some of these cardiovascular parameters including central parasympathetic regulation in postural orthostatic tachycardia syndrome.

Cardioprotective Effects of Metalloproteinase Inhibitor 1-({4-[(4-Chlorobenzoyl)amino]phenyl}sulfonyl-L-Proline in Modeled Acute Myocardial Infarction.

Cardioprotective effect of 1-({4 [(4 chlorobenzoyl)amino]phenyl}sulfonyl-L-proline (compound AL-828) was studied in rats with modeled acute myocardial infarction. The test compound was administered intragastrically in a dose of 30 mg/kg/day for 3 days prior to infarction modeling. Metalloproteinase inhibitor antibiotic doxycycline served as the reference drug and was administered in a dose of 40 mg/kg/day by the same schedule. It was shown that AL-828 similar to doxycycline significantly reduced the intensity of myocardial remodeling and maintained the inotropic function of the myocardium in the acute phase of myocardial infarction. By the 20th minute of ischemia, the end-systolic dimension of the left ventricle in control animals increased from 1.98±0.12 to 3.84±0.16 mm, while in animals treated with AL-828, this increase was significantly (p=0.007) less pronounced (from 1.84±0.07 and 2.87±0.21 mm, respectively). The ejection fraction characterizing the inotropic status of the left ventricle in animals treated with AL-828 was significantly higher (p=0.02). By its cardioprotective activity, AL-828 was not inferior to the reference drug doxycycline. It can be assumed that the cardioprotective activity of compound AL-828 is related to suppression of MMP-9 expression and/or inhibition of its activity as was previously demonstrated by us.

Expediency of сitoprotective treatment of patients with acute myocardial infarction, who were performed percutaneous coronary intervention

The aim of the study was to increase the efficiency of treatment of patients with Acute Miocardial Infarction by incorporating the protocol therapy for the course of parenteral use of L-arginine and L-carnitine.Material and methods.A total of 45 patients with acute coronary syndrome with ST segment elevation were investigated, who had undergone urgent balloon angioplasty and stenting of a heart attack-dependent coronary artery. The study selected patients aged on average (59,57 ± 8,07) years. The experimental group consisted of 30 patients, who received standard protocol treatment of ACS (MI) and additionally were prescribed 4.2 g L-arginine and 2.0 g L-carnitine in the 100 ml solution for infusion once daily for 5 days intravenously. The control group included 15 patients with ACS (MI) who also had percutaneous coronary intervention, but this group received only standard protocol treatment.In addition to general clinical, instrumental and laboratory methods (general blood test, MB Creatinephosphokinase fraction (CFC-MB), Troponin T, oxygen saturation of arterial blood (SpO2), ECG in 12 standard leads, etc.), performed an echocardiography in the B-mode with the definition of linear and volume indicators of the left ventricle, as well as the global (by the ejection fraction (EF) and local contractile activity of the myocardium by the Simpson method. The functional state of the vascular endothelium was determined by the concentration of endothelin-1 (ET-1) in the blood plasma and the content of stable NO metabolites [5]. The determination of endothelin-1 (ET-1) in serum was carried out using for determining the ultimate stable metabolites of NO in the blood. Results. It has been established that patients with ACS (MI) after percutaneous coronary intervention often develop reperfusion syndrome with manifestations of left ventricular insufficiency and rhythm disturbances. Substantial clinical and functional improvement was noted under the influence of standard medical treatment in patients of control group. At the same time postinfarction remodeling with systolic and diastolic function of the heart, with the development of heart failure syndrome and endothelial dysfunction of blood vessels, and also remained resistant to extrasystole therapy, progressed.Patients in the experimental group under the influence of complex medical treatment with the inclusion of L-arginine and L-carnitine marked a significant decrease in the frequency of violations of rhythm and conduction for the second day of observation, as well as a decrease in the manifestations of post-infarction remodeling of LV, which ultimately manifested a significant improvement in myocardial contractility (EF increased by 13%) and decreased diastolic dysfunction. Improvement of the inotropic function of the heart and a significant reduction in the frequency and severity of reperfusion arrhythmias was achieved precisely due to cardiometabolic effects of L-carnitine. In addition, in patients undergoing additional treatment with L-arginine and L-carnitine after 10 days of treatment, the activity of ET-1 was significantly lowered and the concentration of nitrogen oxide metabolites in the blood plasma increased and reach the level of healthy subjects (P&gt; 0,05). So, they recovered the endothelial function of the vessels.Conclusions: In the first day after percutaneous coronary intervention on the background of standard drug therapy was most often diagnosed with reperfusion syndrome with manifestations of acute left ventricular failure and arrhythmias and conduction.The use of complex drug therapy with the inclusion of L-arginine and L-carnitine on the background of an individualized cardiorehabilitation program led to a significant improvement in the parameters of central cardiohemodynamics and restoration of vascular endothelial function, was accompanied by a significant decrease in the frequency of development and severity of such complications of ACS (MI) as reperfusion arrhythmias and acute left ventricular failure.

Association of right atrial conduit phase with right ventricular lusitropic function in pulmonary hypertension.

Alterations of right atrial (RA) function have emerged as determinants of outcome in pulmonary hypertension (PH). We aimed to clarify the pathophysiological associations of impaired RA conduit function with right ventricular (RV) function in PH. In 51 patients with PH (48 with pulmonary arterial hypertension), RA conduit function was assessed as echocardiographic peak early diastolic strain rate (PEDSR). PEDSR and cardiac magnetic resonance parameters were measured within 24h of right heart catheterization and generation of pressure-volume loops to assess RV diastolic (RV end-diastolic pressure [EDP] and relaxation [Tau]) and systolic function. Spearman rho correlation and linear regression analysis were used to determine the association of PEDSR with RV function. The impact of PEDSR on time to clinical worsening was assessed using Kaplan-Meier and Cox regression analyses. Median (interquartile range) PEDSR was - 0.56s - 1 (- 1.08 to - 0.37). Impaired PEDSR was significantly correlated with RV diastolic stiffness [EDP (rho = 0.570; p < 0.001) and Tau (rho = 0.500; p < 0.001)] but not with RV contractility or coupling. In multivariate linear regression including parameters of RV lusitropic and inotropic function, EDP remained independently associated with impaired PEDSR. During a median follow-up of 9months, 23 patients deteriorated. After multivariate adjustment, PEDSR remained associated with clinical worsening (hazard ratio: 2.85; 95% confidence interval: 1.20-6.78). Altered RV lusitropy is associated with impaired RA conduit phase. PEDSR emerged as a promising, non-invasive, bedside-ready parameter to evaluate RV diastolic function and to predict prognosis in PH.

Выбор тактики экспериментальной терапии хронической сердечной недостаточности соединением АЛМ-802

The cardioprotective activity of ALM-802 compound was demonstrated in model experiments simulating postinfarction chronic heart failure in rats forming in 90 days after anterior transmural myocardial infarction. ALM-802 decreased the left ventricle and improved its inotropic function (p=0.038). This effect was observed in case of systematic administration of ALM-802 over 28 days (starting from day 91 after infarction modeling). This is apparently the minimum time for the cardioprotective effect of ALM-802 to prevent or treat the resulting heart failure, because short-term systematic therapy (15 days) produced no positive effect.

Andrographolide Protects Against Adverse Cardiac Remodeling After Myocardial Infarction through Enhancing Nrf2 Signaling Pathway.

Adverse cardiac remodeling after myocardial infarction (MI) is associated with extremely high mortality rates worldwide. Although optimized medical therapy, Preservation of lusitropic and inotropic function and protection against adverse remodeling in ventricular structure remain relatively frequent. This study demonstrated that Andrographolide (Andr) significantly ameliorated adverse cardiac remodeling induced by myocardial infarction and improves contractile function in mice with LAD ligation compared with the control group. Briefly, Andr markedly attenuated cardiac fibrosis and relieved inflammation after myocardial infarction. Specifically, Andr significantly blocked oxidative stress and the nuclear translocation of p-P65 following myocardial infarction. At the mechanistic level, antioxidant effect of Andr was achieved through strengthening antioxidative stress capacity and attributed to the activation of Nrf2/HO-1 Signaling. Consistently, H9C2 administrated with Andr showed a decreased oxidative stress caused by hypoxia precondition, but treatment with specific Nrf2 inhibitor (ML385) or the silence of Nrf2 blunted the activation of Nrf2/HO-1 Signaling and removed the protective effects of Andr in vitro. Thus, we suggest that Andr alleviates adverse cardiac remodeling following myocardial infarction through enhancing Nrf2 signaling pathway.