Inotropic Function Research Articles

Perioperative Modulation of Left Ventricular Systolic Performance: A Retrospective Study on Ionized Calcium and Vitamin D in Cardiac Surgery Patients.

Background: The perioperative impact of calcium and vitamin D on left ventricular (LV) performance during major cardiac surgery remains unexplored. We aimed to assess the relation of calcium and vitamin D measured at different time points with the LV ejection fraction (EF), and to investigate whether changes in EF correlate with postoperative outcomes. Methods: We enrolled 83 patients, in whom ionized calcium was measured before, during, and after surgery (until discharge), vitamin D preoperatively, and EF pre- and postoperatively at 24 h. The postoperative outcomes were cardiopulmonary bypass (CPB) time, aortic cross-clamp time, mechanical ventilation time, vasoactive inotropic score (VIS) (intraoperative, day 0, day 1), and ICU stay time. Results: The mean age was 64.9 ± 8.5 years, with 21 of the patients (25%) having an EF < 50%. The median change from preoperative to postoperative EF was -2.0 (-10.0-0.0) % (p < 0.001). At the baseline, the EF < 50% group had significantly lower preoperative vitamin D levels than the EF ≥ 50% group (p = 0.048). The calcium trend did not differ across the groups. Preoperative EF was significantly associated with CPB time (r = 0.22, p = 0.044) and aortic cross-clamp time (r = 0.24, p = 0.031). Postoperative EF was significantly and inversely associated with intraoperative VIS (r = -0.28, p = 0.009), VIS day 0 (r = -0.25, p = 0.020), VIS day 1 (r = -0.23, p = 0.036), and ICU length of stay (r = -0.22, p = 0.047). Finally, the change in ejection fraction was significantly and inversely associated with CPB time (r = -0.23, p = 0.037), aortic cross-clamp time (r = -0.22, p = 0.044), intraoperative VIS (r = -0.42, p < 0.001), VIS day 0 (r = -0.25, p = 0.024), mechanical ventilation time (r = -0.22, p = 0.047), and ICU length of stay (r = -0.23, p = 0.039). Conclusions: The fluctuations in perioperative ionized calcium levels were not associated with the evolution of LVEF, although preoperative vitamin D levels may affect those with low EF. Correspondingly, a reduced EF significantly impacted all the studied postoperative outcomes. Further investigation into biomarkers affecting cardiac inotropic function is warranted to better understand their significance.

Long-Term Continuous Terlipressin Infusion Improves Cardiac Reserve in Patients With Decompensated Cirrhosis

Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis. Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve, the change in cardiac output (CO) in response to stress. The median age was 61 years (interquartile range, 56-64 years), the median Model for End-Stage Liver Disease score was 15 (interquartile range, 12.3-17.0), and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0 L/min [↑57.8%]) as compared with baseline (↑1.8 L/min [21.3%]) (P= .0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (P= .02), driven primarily by improvement in inotropic function. Resting CO decreased significantly after terlipressin from 8.9 ± 2.2 L/min to 7.2 ± 1.8 L/min (normal range 5-6 L/min) (P < .001), due to a decrease in stroke volume from 108 to 86 mL/beat (P= .006). Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. Australian New Zealand Clinical Trials Registry, Number: ACTRN12619000891123.

Factors associated with deterioration of myocardial inotropic function in patients with coronary artery disease

Material and methods. One hundred patients with functional class III-IV CAD, stage I-IIa heart failure with LV ejection fraction (EF) &gt;40%, successful coronary artery bypass grafting, SYNTAX Score of 33. During hospitalization, echocardiography, matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), monocyte chemoattractant protein 1 (MCP-1) were studied, while systemic immune-inflammation index (SII) was estimated. After 6 months, echocardiography revealed a group of patients with a decrease in LVEF.Results. The following factors of decreased LVEF were identified: type 2 diabetes, chronic kidney disease (p&lt;0,001), &gt;4 comorbid diseases (r=-0,597, p&lt;0,001), increase in SII by 44,6% (p&lt;0,001), MMP-9 by 62% (p&lt;0,001), MCP-1 by 55,1% (p&lt;0,001), TIMP-1 by 45,8% (p&lt;0,001). An inverse relationship was found between LVEF and the level of SII (r=-0,626, p&lt;0,001), MCP-1 (r=-0,747, p&lt;0,001), MMP-9 (r=-0,718, p&lt;0,001). There were following threshold values for predicting a decrease in LVEF: SII — 356,43, MMP-9 — 318,7 ng/ml, MCP-1 — 459,6 pg/ml.Conclusion. There are following markers of decreased LVEF in patients with CAD 6 months after successful coronary artery bypass surgery: type 2 diabetes, chronic kidney disease, &gt;4 comorbid diseases, SII, MMP-9 and MCP-1 with a threshold value of 356,43, 318,7 ng/ml and 459,6 pg/ml, respectively.

Correlation of the Left Ventricular Systolic Dysfunction and Ventricular Depolarization in a Post-Infarction Model of Chronic Heart Failure.

The body surface potential mapping of the heart during the period of ventricular depolarization and the inotropic function of the ventricles were studied in rats under conditions of a translational model of post-infarction chronic heart failure developed by us. We revealed a statistically significant (p<0.001) correlation between the left-ventricular ejection fraction and the values of the maximum positive and negative extrema of the cardioelectric field on the body surface of rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction. The calculated linear regression equations have high predictive efficiency, which makes it possible to use the amplitude characteristics of the heart cardioelectric field as a marker of the development of chronic heart failure.

FEATURES OF THE MORPHO-FUNCTIONAL MYOCARDIUM STATE AND RELATIONSHIP WITH GALECTIN-3 IN PATIENTS WITH CHRONIC HEART FAILURE OF ISCHEMIC ORIGIN ON THE BACKGROUND OF METABOLIC PATHOLOGY

The aim. To evaluate the presence and nature of changes in the morpho-functional state of the myocardium in patients with coronary heart disease (CHD) with concomitant type 2 diabetes mellitus (T2DM) and obesity, depending on the functional class (FC) of chronic heart failure (CHF) and the relationship with the concentration of galectin-3 in blood serum.&#x0D; Materials and methods. The study involved 75 patients with CHD with concomitant metabolic diseases such as T2DM and obesity, who were treated in the cardiology department of the State Clinical Hospital No. 27. Patients were divided into groups according to the FC of CHF. Group 1 included 30 patients with CHF FC II, group 2 – 24 patients with CHF FC III, group 3 – 21 patients with CHF FC IV.&#x0D; Results. In patients with СHD and metabolic disorders with CHF FC III, the levels of end-systolic dimension (ESD) and end-diastolic dimension (EDD) were higher by 16.3 % and 17.9 %, respectively, compared with FC II, end-systolic volume (ESV) and end-diastolic volume (EDV) also increased significantly in patients of this cohort with FC III compared with CHF FC II by 35.8 % and 16.5 %, respectively. Significantly increased ESV, EDV by 42.9 % and 37.8 %, respectively, as well as the size of the left atrium by 14.3 % in patients of the study group who had CHF FC IV compared with FC III. The ejection fraction (EF) index decreased in patients of this cohort with CHF FC IV by 14.4 % compared with FC III. The size of the right ventricle was larger by 10.8 % in CHF FC IV than in FC III in patients with CHD on the background of comorbid metabolic pathology. Indicators of the thickness of the LV posterior wall, LV relative wall thickness and intraventricular septum were lower in patients with FC IV compared with FC II, left ventricle mass (LVM) and left ventricle mass index (LVMI) increased by 32 % and 33 %, respectively. Сomparing the levels of Ea/Es in patients with CHF FC II and IV in СHD with concomitant T2DM and obesity, a significant increase in this indicator was found in FC IV (p&lt;0.05). The level of galectin-3 in patients with CHF FC III and IV of ischemic origin against the background of concomitant metabolic disorders was higher than in patients with FC II. Сomparing the concentration of galectin-3 in patients with CHF FC III and IV in patients with CHD with comorbid metabolic pathology, significantly higher levels were found in FC IV (p&lt;0.05). The study of the relationship between the fibrosis factor galectin-3 and cardiohemodynamic parameters revealed probable links, namely direct links between galectinemia and ESV (r=0.52; p&lt;0.05), EDV (r=0.58; p&lt;0.05), Еа/Es (r=0.51; p&lt;0.05).&#x0D; Conclusions. The growth of the functional class of chronic heart failure is accompanied by dilatation of the left cavities of the heart, a decrease in the inotropic function of the left ventricle, an increase in myocardial-arterial stiffness, and an increase in the levels of the galectin-3 fibrosis factor in the studied patients.

Features of the compound ALM-802 antiarrhythmic action

Introduction. Cardiovascular diseases (CVD) remain one of the leading causes of death worldwide, claiming over 17 million lives annually. This highlights the urgent need to develop innovative drugs to combat CVD. One potential target for such drugs is type 2 ryanodine receptors (RyR2), as they play an important role in maintaining ion homeostasis in cardiomyocytes, and their abnormal activity plays a key role in the genesis of cardiac arrhythmias.Research objective is to study the mechanisms underlying the antiarrhythmic action of ALM-802.Methods. In the first stage, in vivo experiments were performed using models of aconitine, calcium chloride, barium chloride arrhythmia, and reperfusion arrhythmias to evaluate the antiarrhythmic effect of the compound ALM-802. The second stage of the study involved electrophysiological experiments performed on hippocampal cells of newborn rats to evaluate the effect of the compound on voltage-gated transmembrane Na+, K+, and Ca2+ ion channels, as well as its effect on intracellular ion concentration of Ca2+. Experiments performed on an isolated myocardial strip evaluated the effect of the compound ALM-802 on the activity of RyR2.Results. In in vivo experiments, the compound ALM-802 (2 mg/kg, iv) exhibits significant antiarrhythmic activity comparable/superior to that shown by the reference drugs procainamide, verapamil, and amiodarone on the models mentioned above. In in vitro experiments, it was shown that ALM-802 (69.8 µM) initiates the inactivation of K+ and Na+ ion channels and does not affect the activity of Ca2+ ion channels. The compound ALM-802 effectively prevents the increase of Ca2+ ion concentration in the cytosol during depolarization of contraction. In addition, experiments on isolated myocardial strips showed that the compound ALM-802 (5x10-5 M) blocks RyR2.Conclusion. Thus, based on the spectrum of its antiarrhythmic activity, the compound ALM-802 combines the properties of antiarrhythmic drugs of class IA or IC and class III according to the E.M. Vaughan Williams classification. In addition, the ALM-802 compound exhibits antagonistic activity towards RyR2. The latter is also considered significant, as it is known that under conditions of myocardial pathology, abnormal activity of RyR2 initiates diastolic leakage of Ca2+ ions from the sarcoplasmic reticulum cysterns, which leads to a decrease in the inotropic function of the left ventricle of the heart and significantly increases the risk of developing malignant cardiac arrhythmias.

Involvement of alpha-adrenergic receptors in the regulation of inotropy in the isolated rat heart

Background. Although activation of 1-adrenergic receptors is not required for myocardial contractility, 1-adrenergic receptors can provide significant support for myocardial inotropy in various heart diseases.&#x0D; Aim. To study the participation of 1A- and 1B-adrenergic receptors in the force contraction regulation of the left ventricle of an isolated rat heart.&#x0D; Material and methods. Isolated hearts of 20-week-old rats were perfused with KrebsHenseleit solution according to the Langendorff method. The most important indicator of the inotropic function of the heart, the pressure developed by the left ventricle, was recorded using a latex balloon placed in the cavity of the left ventricle. At the 1st stage of the work, the effects of blockers of 1-adrenergic receptor subtypes on the force of contractions of an isolated heart were evaluated. At the 2nd stage, the effect of non-selective stimulation of 1-adrenergic receptors by methoxamine was studied. At the 3rd stage, the effect of methoxamine was evaluated against the background of selective blockade of 1A- or 1B-adrenergic receptors. Statistical analysis of data was performed using Statistica 6.0 software. The significance of changes between dependent data was assessed using the Wilcoxon test. To assess the differences between two sets of independent data, the MannWhitney U-test was used. Changes were considered statistically significant at p 0.05.&#x0D; Results. Infusion of the 1A-adrenergic blocker WB4101 at a concentration of 106 mol/l led to an increase in the force of contraction of the isolated heart by 5.6% (p=0.048). Blocker of 1B-adrenergic receptors chloroethylclonidine dihydrochloride at a concentration of 108 mol/l caused a decrease in the force of contraction of the heart by 15% (p=0.046). Stimulation of 1A-adrenergic receptors with methoxamine (108 mol/l) led to a decrease in pressure developed by the left ventricle of an isolated heart by 47% (p=0.002). Preliminary blockade of 1A-adrenergic receptors significantly reduced the severity of the negative inotropic effect of methoxamine on the left ventricular myocardium. Preliminary blockade of 1B-adrenergic receptors changed the direction of the inotropic effect of methoxamine on the myocardium of the left ventricle of an isolated heart.&#x0D; Conclusion. Non-selective stimulation of 1-adrenergic receptors by methoxamine leads to a significant decrease in cardiac inotropy, while preliminary blockade of 1A- or 1B-adrenergic receptors reduces the severity of this effect.

Effect of the nitric oxide synthesis inhibitor L-NAME on the isolated rat heart after hypokinesia

The effects of a non-selective nitric oxide synthase inhibitor L-NAME on the functional parameters of the isolated rat heart after a 30-day period of hypokinesia were studied. Electron paramagnetic resonance spectroscopy was employed in the analysis of a role for L-NAME in the intensity of nitric oxide production in rat heart tissues. The intensity of nitric oxide synthesis was assessed by the intensity of the signal belonging to the (DETC)2-Fe2+-NO complex. It was found that L-NAME decreased nitric oxide production on average by 69%. The Langendorff isolated perfused heart was used to evaluate cardiac activity, and the following parameters were measured: pressure generated by the left ventricle, heart rate, and coronary flow. Addition of the nitric oxide synthesis inhibitor L-NAME induced an increase in inotropic function and normalization of heart rate.

Overweight and dysregulation of the autonomic nervous system in young persons

Background. More than 1 billion people worldwide are obese, and this number is growing. Obesity at an early age is accompanied by impaired carbohydrate tolerance and the development of type 2 diabetes, lipid metabolism pathology, obstructive apnea, hypercoagulability, chronic inflammation and the development of insulin resistance in the future. In modern literature, there is no single point of view regarding the role of the autonomic nervous system in the coordination of hormonal, nervous and metabolic factors in the body.Aim. The article presents the results of studying the functional state of the sympathetic and parasympathetic parts of the autonomic nervous system in overweight persons and presents an assessment of the central hemodynamic parameter depending on the type of autonomic reactivity of the cardiovascular system.Methods. The study involved measuring systolic and diastolic blood pressure, heart rate, and anthropometric measurements for calculating the corresponding indices. An active orthostatic test to determine the functional state of reflex mechanisms for regulating hemodynamics. Statistical methods were used for data analysis.Results. Based on anthropometric indicators and calculated indices, boys and girls with overweight differed from the control group in abdominal and total distribution of fat. However, there were no differences in terms of vegetative tone (sympathicotonic, vagotonic, eutonic). The distribution of eutonic and vagotonic types of the autonomic nervous system and sympathicotonia was similar in both groups. Most overweight individuals had insufficient reactivity of the parasympathetic autonomic nervous system. Paradoxical reactivity in both groups was observed with the same frequency. In the group of people with paradoxical autonomic reactivity among overweight people, a significantly lower increase in heart rate was found than in the control group. In persons with overweight and increased autonomic reactivity, minute blood volume and pulse pressure increased 1.5-fold, there was a tendency to increase stroke volume and inotropic function of the heart. The increase in this characteristic indicated a hyperkinetic type of hemodynamics in overweight persons in the group with normal autonomic reactivity. In groups with paradoxical and increased autonomic reactivity of the cardiovascular system, a normokinetic type of hemodynamics was observed.Conclusions. Signs of altered autonomic reactivity found in most overweight individuals indicate dysfunction of the parasympathetic autonomic nervous system and possible dysfunction of nonspecific regulatory (limbic-reticular) parts of the brain.

Changes in Microcirculation in the Brain, Heart, and Liver in Female Rats with Translational Model of Alcoholic Cardiomyopathy.

We studied some features of blood and lymph microcirculation in the brain, heart, and liver of female rats with developed alcoholic cardiomyopathy. In female rats after 24-week forced consumption of 10% ethanol solution, the size and inotropic function of the heart were measured by echocardiography. Microcirculation in the brain, myocardium, and liver was assessed by laser Doppler flowmetry using LAKK-OP2 and LAZMA-D computerized laser analyzers. Using spectral wavelet analysis, we determined the absolute and normalized to total perfusion amplitudes of microcirculation oscillations reflecting various regulatory mechanisms. Intact animals served as controls. In rats of the experimental group, alcoholic cardiomyopathy completely developed. Under these conditions, the index of microcirculation in the brain, myocardium, and liver significantly decreased. At the same time, there was a redistribution in the brain between shunting and nutritive blood flow in favor of the latter. In the myocardium and liver, this ratio did not change.

Effects of Normobaric Hypoxia and Adrenergic Blockade over 72 h on Cardiac Function in Rats.

In rats, acute normobaric hypoxia depressed left ventricular (LV) inotropic function. After 24 h of hypoxic exposure, a slight recovery of LV function occurred. We speculated that prolonged hypoxia (72 h) would induce acclimatization and, hence, recovery of LV function. Moreover, we investigated biomarkers of nitrosative stress and apoptosis as possible causes of hypoxic LV depression. To elucidate the role of hypoxic sympathetic activation, we studied whether adrenergic blockade would further deteriorate the general state of the animals and their cardiac function. Ninety-four rats were exposed over 72 h either to normal room air (N) or to normobaric hypoxia (H). The rodents received infusion (0.1 mL/h) with 0.9% NaCl or with different adrenergic blockers. Despite clear signs of acclimatization to hypoxia, the LV depression continued persistently after 72 h of hypoxia. Immunohistochemical analyses revealed significant increases in markers of nitrosative stress, adenosine triphosphate deficiency and apoptosis in the myocardium, which could provide a possible explanation for the absence of LV function recovery. Adrenergic blockade had a slightly deteriorative effect on the hypoxic LV function compared to the hypoxic group with maintained sympathetic efficacy. These findings show that hypoxic sympathetic activation compensates, at least partially, for the compromised function in hypoxic conditions, therefore emphasizing its importance for hypoxia adaptation.

Viddalena efektyvnist revaskuliaryzatsii miokarda u khvorykh pislia perenesenoho hostroho koronarnoho syndromu (literaturnyi ohliad; rezultaty vlasnykh doslidzhen)

Introduction. Acute coronary syndrome (ACS) is an urgent problem in the world. The vast majority of publications indicate the effectiveness of myocardial revascularization in this pathology. However, the effectiveness of this method of treatment in the remote period of GIMeST has not been sufficiently studied. The aim of the study. Analyze the long-term effectiveness of myocardial revascularization in patients after ACS based on literature publications and own results of conducted research. Materials and methods. 42 sources of published literature were used and the results of our own research on increasing the clinical effectiveness of coronary artery stenting by combining it with medical treatment in patients with post-STEMI with cardiovascular events were presented. Results. It has been proven that the 30-month survival rate of a patient with a hemodynamically significant lesion of the coronary artery trunk with drug therapy was 6.4 %, and with CABG – 80.0 %. The best results of myocardial revascularization were observed with CA p-value more than 70.0 % stenosis. It was found that primary coronary intervention in comparison with thrombolytic therapy contributes to a more complete restoration of epicardial impact (III degree according to the TIMI scale). Successful endovascular recanalization of infarct-induced KA helps to limit the area of necrosis and restore the reduced inotropic function of the hibernating myocardium up to 2 hours after the start of ACS. In the later periods of restoration of anterograde blood flow, the beneficial effect is manifested within a year. On the basis of our own research, positive dynamics of improvement in late LV remodeling and reduction of cardiac arrhythmias (SHE, AF, LVPH, and HF) are observed in patients with post-GIMeST after medical treatment. Conclusions. On the basis of the cited literary sources and our own research, it should be noted that in patients who underwent STEMI with cardiovascular events compared to those without cardiovascular events and underwent myocardial revascularization and outpatient drug treatment for two years, there was an increase in LVEF by 12.6 %, respectively, and a decrease in angina attacks by 6.6 %, CHF III and II FC – by 11.9 %, reduces SHE, AF and BLPNH and improves the quality of life. However, mortality 2 years after myocardial revascularization compared with medical treatment did not change significantly, and according to the literature, it decreased after CABG.

Predyktory prohnozuvannia sertsevo-sudynnykh podii ta inshykh uskladnen systemy krovoobihu u khvorykh iz hostrym koronarnym syndromom (ohliad literatury; rezultaty vlasnykh doslidzhen)

Introduction. More than 15 million cases of AMI are recorded annually in the world, and in Ukraine in 2017 – 41.786 cases. Undoubtedly, acute coronary syndrome (ACS) manifests various complications of blood flow. At the same time, in such patients, significantly fewer works are devoted to predictors of other complications of the cardiovascular system. The aim of the study. Write a literature review and include the results of own research on predictors of predicting cardiovascular events and other complications of the blood flow system in ACS. Materials and methods. We used 49 published articles and our own research results on the study of predictors of predicting cardiovascular events and other complications of the blood flow system after undergoing ACS. The results of our own research are presented in a complex algorithm for predicting SCD in cardiovascular pathology, and our own criteria for cardiovascular events are given. Results. It has been proven that an increase in the thickness of the LV wall in patients with hypertension can be associated with an almost 7-fold increase in the risk of death. In our opinion, LVH in STEMI in combination with hypertension has a negative impact on the development of cardiovascular events. The development of pathological remodeling of the LV leads to further dilatation, deformation of the walls and cavities of the heart, a progressive decrease in the inotropic function of the LV with the development of congestive heart failure. Some authors suggest prognostic predictors of the development of acute left ventricular failure. The prognostic role of endothelial dysfunction in cardiovascular events is poorly understood. Conclusions. In recent years, predictors of the development of cardiovascular events (death, non-fatal MI, stroke, UA), as well as such complications of the blood flow system as acute left ventricular failure, progression of heart failure, development of VE 3-5 grades according to Laun have been established in patients with a transferred STEMI and UA in recent years , severe heart blocks with the occurrence of syncopal states. According to our data, clinical, ECG, and echocardiographic diagnostic criteria are predictors of cardiovascular events. The specified predictors of cardiovascular events and various complications of the blood flow system after a STEMI and UA need to be taken into account by cardiologists, emergency physicians, and family physicians in their practice and to carry out therapeutic measures aimed at preventing their occurrence in patients.

Artificial Muscles and Soft Robotic Devices for Treatment of End-Stage Heart Failure.

Medical soft robotics constitutes a rapidly developing field in the treatment of cardiovascular diseases, with a promising future for millions of patients suffering from heart failure worldwide. Herein, the present state and future direction of artificial muscle-based soft robotic biomedical devices in supporting the inotropic function of the heart are reviewed, focusing on the emerging electrothermally artificial heart muscles (AHMs). Artificial muscle powered soft robotic devices can mimic the action of complex biological systems such as heart compression and twisting. These artificial muscles possess the ability to undergo complex deformations, aiding cardiac function while maintaining a limited weight and use of space. Two very promising candidates for artificial muscles are electrothermally actuated AHMs and biohybrid actuators using living cells or tissue embedded with artificial structures. Electrothermally actuated AHMs have demonstrated superior force generation while creating the prospect for fully soft robotic actuated ventricular assist devices. This review will critically analyze the limitations of currently available devices and discuss opportunities and directions for future research. Last, the properties of the cardiac muscle are reviewed and compared with those of different materials suitable for mechanical cardiac compression.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular(LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

Relaxin does not prevent development of hypoxia-induced pulmonary edema in rats

Acute hypoxia impairs left ventricular (LV) inotropic function and induces development of pulmonary edema (PE). Enhanced and uneven hypoxic pulmonary vasoconstriction is an important pathogenic factor of hypoxic PE. We hypothesized that the potent vasodilator relaxin might reduce hypoxic pulmonary vasoconstriction and prevent PE formation. Furthermore, as relaxin has shown beneficial effects in acute heart failure, we expected that relaxin might also improve LV inotropic function in hypoxia. Forty-two rats were exposed over 24 h to normoxia or hypoxia (10% N2 in O2). They were infused with either 0.9% NaCl solution (normoxic/hypoxic controls) or relaxin at two doses (15 and 75 μg kg−1 day−1). After 24 h, hemodynamic measurements and bronchoalveolar lavage were performed. Lung tissue was obtained for histological and immunohistochemical analyses. Hypoxic control rats presented significant depression of LV systolic pressure by 19% and of left and right ventricular contractility by about 40%. Relaxin did not prevent the hypoxic decrease in LV inotropic function, but re-increased right ventricular contractility. Moreover, hypoxia induced moderate interstitial PE and inflammation in the lung. Contrasting to our hypothesis, relaxin did not prevent hypoxia-induced pulmonary edema and inflammation. In hypoxic control rats, PE was similarly distributed in the apical and basal lung lobes. In relaxin-treated rats, PE index was 35–40% higher in the apical than in the basal lobe, which is probably due to gravity effects. We suggest that relaxin induced exaggerated vasodilation, and hence pulmonary overperfusion. In conclusion, the results show that relaxin does not prevent but rather may aggravate PE formation.

COMPARATIVE EFFICACY OF ANTIARRHYTHMIC MEDICATIONS FOR SINUS RHYTHM MAINTENANCE AFTER ELECTRICAL CARDIOVERSION FOR ATRIAL FIBRILLATION

Objective: Sinusa rhythm maintenance while using IC class medications is not practically studied. IC class medications aethacizinum is widely used, but has no large studies proving safety and efficacy. The aim of this study was to compare the efficacy of class IC antiarrhythmic medications, for sinus rhythm maintenance, after ECV (electrical cardioversion), in patients with atrial fibrillation (AF). Design and method: It is an open-label, one-center prospective study that held in the Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital from September 2019 to June 2020. Before hospitalisation patients have not received any antiarrhythmic drugs except of amiodarone and beta blockers. Patients with persistent form of AF received beta blockers (bisoprolol 5 mg daily), amiodarone (200 mg daily), propaphenone (300 mg daily) or aethacizinum (100 mg daily) for 6 months after conversion to sinus rhytm by ECV. Rest ECG, Holter monitoring, echocardiography, ergometer stress test, blood tests were performed. Results: The total number of patients finished study per protocol – n = 52. On echocardiographical study no significant changes in AFR (AF paroxysm group) and MSR (maintained sinus rhythm) groups were found. No safety parameters were significantly changed in this group. All patients were followed up for 6-month period. Reccurance rate of AF in aethacizinum group showed a statistically significant superiority compared to propafenone (55,6% vs 72,5%) (p = 0,05). Patients with higher atrial strain and strain rate appear to have a greater likelihood of staying in sinus rhythm. In our research, duration of AF was not predictive value of maintenance of SR at follow-up after 6 months from ECV. Conclusions: Antiarrhythmic medications of Ic class may be safe in patients with persistent form of atrial fibrillation and have no negative impact on inotropic function of myocardium. The most commonly used drug from Ic class ir etacizin. The observed efficacy provides the rationale for a larger, double-blind controlled study with different antiarrhythmic medications in different daily dosage.

Direct evidence of a sympathetically‐mediated cardio‐inotropic response to baroreceptor unloading in rats

RationaleThe baroreflex is a cardio‐autonomic reflex that is responsible for buffering acute oscillations in blood pressure. Contemporary evidence suggests that, when stimulated, baroreceptors activate a neural reflex arc via two efferent pathways: the vascular‐sympathetic arm to control peripheral resistance, and the cardio‐vagal arm to control heart rate. However, since sympathetic post‐ganglionic fibres innervate both the vasculature and left ventricle (LV) it follows that the heart may also contribute to hemodynamic regulation during baroreceptor unloading through alterations in cardiac inotropy, yet to our knowledge this has not been empirically tested using a load‐independent index of LV inotropy.Aim1) To determine whether there is an increase in LV inotropy in response to baroreceptor unloading, and 2) to parse out whether this response occurs via sympathetic activation, parasympathetic withdrawal, or a combination of the two.HypothesesThere will be an increase in LV inotropy in response to baroreceptor unloading, and this response will occur via activation of the sympathetic nervous system.Methods10 male Wistar rats were anesthetized (urethane) and instrumented with a LV pressure‐volume catheter to measure the maximal rate of pressure generation for a given end‐diastolic volume (dP/dtmax–EDV mmHg·s‐1·µl‐1) as a load‐independent metric of cardiac inotropic function. Each rat was then placed in a customized servo‐controlled lower‐body negative pressure (LBNP) chamber that was programmed to reduce mean arterial pressure (MAP) by 10% for 60s to mechanically unload baroreceptors. The protocol was repeated in the same animal following infusions of lactated ringers (control), esmolol (β1 adrenergic receptor antagonist; blocks cardiac sympathetic transmission), atropine (muscarinic receptor antagonist; blocks cardiac parasympathetic transmission), and esmolol+atropine (full cardiac autonomic blockade). Between‐condition differences in LV inotropy were assessed using mixed‐models with Bonferroni corrected post‐hoc pairwise comparisons.ResultsUnder control conditions, dP/dtmax–EDV increased significantly (25.8±4.9 vs 29.9±6.7 mmHg·s‐1·µl‐1; p=0.002) during unloading. Sympathetic and full cardiac blockade significantly reduced baseline dP/dtmax–EDV (10.8±2.1 and 13.5±3.0 mmHg·s‐1·µl‐1, respectively; p&lt;0.001 for both), and abolished the response to baroreceptor unloading (10.6±2.1 and 14.3±4.0 mmHg·s‐1·µl‐1, respectively; p=0.999 for both). Parasympathetic blockade had no effect on baseline dP/dtmax–EDV (26.1±5.5 mmHg·s‐1·µl‐1; p=0.999) and the increase in dP/dtmax–EDV during baroreceptor unloading was maintained (30.5±8.3 mmHg·s‐1·µl‐1; p&lt;0.001).ConclusionThese results provide direct evidence of a sympathetically‐mediated increase in cardiac inotropic function in response to baroreceptor unloading in rats.

Features of Physical Development of Schoolchildren in the Conditions of Specialized Training

The article presents a comparative analysis of physical development of 13-year-olds and cadet basic profile of teaching in urban schools in the parameters of somatometry and visiometry characterizing physical development, functional state, adaptation of the heart and body to current training loads. Coming of puberty is marked by intense growth of the body with heterochronous changes in the proportions and dimensions of its muscular skeletal system and the structure of internal organs. During this period, the role of mechanisms for self-regulation of heart activity and, in general, autonomous regulation of the functions of the cardiovascular system increases. At the initial stage in adolescents the manifestation of tachycardia and cardiac type of self-regulation of blood circulation increases. It is accompanied with deterioration in inotropic function of the myocardium against the background of a pronounced effect of sympatotonia and vagotonia on the systolic function of the myocardium.

Features of the effect of serotonin on the inotropic function of the right ventricular myocardium in the early postnatal period in infant rats with altered serotonin levels during their embryogenesis

Serotonin plays an important role in the cardiovascular system and is a humoral system of regulators and modulators of physiological processes. Under pathological conditions, it can result in developing some factors contributing to the development of diseases, such as atherosclerosis, arterial and pulmonary hypertension. The 5-HT4 and 5-HT2B receptors have been identified in cardiomyocytes, which are involved in the regulation of the inotropic function of the myocardium. The serotonergic system is an essential link in embryonic development. As a key signaling molecule in heart progenitor cells, serotonin is involved in the development and differentiation of myocardial cells as well as the separation of the heart chambers. Therefore, interfering with this system in the womb and changing its concentration can disrupt normal development of the heart. It has been established that any change in the concentration of serotonin created by the blockade of the synthesis of serotonin and the membrane serotonin transporter in the embryonic period of ontogenesis, leads to a decrease in the contraction strength of the right ventricular myocardium in 7-day-old infant rats. However, at the age of 14 days, intergroup differences are not manifested. At 7 days of age, the response of the contraction strength to the maximum concentration of serotonin is lower in infant rats with an excess of serotonin and higher in infant rats with its deficiency, as compared to those animals in the control group. At the age of 14 days, the response of the contraction strength in both experimental groups has been reduced in comparison with the animals in the control group.