Decrease In Left Ventricular Contractility Research Articles

The Anti-Inflammatory Mediator 17(R)-Resolvin D1 Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis.

Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear. Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis. 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue. 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.

Cardiovascular disorders in children with COVID-19

Background. The purpose of the work is to study the prevalence of cardiac disorders in hospitalized children with coronavirus disease (COVID-19). Materials and methods. A retrospective, cohort, monocenter study of the medical records of children who underwent inpatient treatment between September and December 2021 at the Kyiv City Children’s Clinical Infectious Disease Hospital was conducted. For our study, we selected the medical records of patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the presence of at least one result of cardiac activity examination by electrocardiography (ECG) and/or echocardiography. The first study of cardiac activity by ECG and/or echocardiography was carried out in the first three days of inpatient treatment. Standard methods of descriptive statistics were used for data processing. Non-parametric statistical methods (Mann-Whitney test, chi-square, Pearson’s exact test) were used for mathematical analysis. The research was carried out in accordance with the Declaration of Helsinki principles. The study was approved by the bioethics committee of the hospital. Results. Among 305 children hospitalized with a diagnosis of U07.1 (2019-nCoV acute respiratory disease), there were selected 195 medical histories of patients aged 15 days to 18 years (median of 5.37 years), who were examined for cardiac activity by ECG and/or echocardiography. The most common changes were rhythm disturbances in the form of sinus tachycardia (20.8 %), bradycardia (11.9 %) and sinus arrhythmia (7.9 %), ventricular conduction disorders (25.7 %), deviation of the electrical axis of the heart (10.9 %) and repolarization disorders (31.7 %). During echocardiographic examination, structural abnormalities in the form of myocardial hypertrophy were detected in 3.1 % of patients, dilated heart chambers in 2 %, and pericardial effusion in 9.2 %. Among the functional changes, we observed: a decrease in left ventricular contractility in 4.1 % of cases, in cardiac output in 28.6 %, and an increase in total peripheral resistance in 41.8 %. Heart rhythm disturbances in the form of sinus tachycardia, deviation of the electrical axis of the heart, a decrease in the amplitude of the ECG waves, repolarization disorders, and pericardial effusion were associated with an increased risk of death in children with COVID-19. Clinical cases of cardiovascular complications in the form of jugular vein thrombosis and infectious endocarditis illustrate the role of the cardiovascular system in the pathogenesis of coronavirus disease. Conclusions. SARS-CoV-2 infection is often associated with damage to the cardiovascular system. In most pediatric patients, this occurs in the form of subclinical changes registered during laboratory or instrumental studies, but the development of manifest forms such as myocarditis, endocarditis, pericarditis, heart attack, coronary disease, thrombotic complications, and heart failure is possible. Using simple non-invasive methods (ECG and echocardiography) during screening, it is possible to diagnose damage to the cardiovascular system, as well as to detect changes in the cardiovascular system, which are subclinical, but can have an important prognostic value regarding the adverse course of the disease in children, which are hospitalized with SARS-CoV-2 infection.

Left atrial strain: a sensitive whistleblower lost in translation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Netherlands Organisation for Scientific Research (NWO- ZonMw, VIDI grant 016.176.340 to J.L.) and the Dutch Heart Foundation (ERA-CVD JTC2018 grant 2018T094; Dr. Dekker Program grant 2015T082 to J.L.) Background Left atrial (LA) function measured by peak/reservoir strain (PLAS) has been shown to be of prognostic value in various cardiac pathologies, including heart failure (HF). However, the underlying mechanisms leading to reduced PLAS remain poorly understood. Purpose To investigate how various combinations of left ventricular (LV) systolic-, diastolic, and LA failure affect PLAS. Method The CircAdapt computational model of the human heart and circulation is used to simulate the abovementioned LV and LA substrates, starting from a healthy reference simulation. LV systolic failure was simulated by a 25% decrease of LV contractility and LV eccentric hypertrophy (simultaneous increase of LV wall mass and area by 30%). LV diastolic failure was simulated by increasing LV myocardial stiffness by 100%, impairing LV relaxation function (increasing relaxation time constant from 35ms to 60ms, and LV concentric remodeling (increasing LV wall mass by 30%). LA failure was simulated by a fully non-contractile LA myocardium. Results LV systolic failure was characterized by reduced LV GLS (21 to 12%) and LVEF (54 to 34%), with marginal increase in PLAS (42 to 46%; Figure top row, first vs second column). LV diastolic failure was characterized by reduced PLAS (42 to 23%; Figure first vs third and fourth columns) with LA dilation (i.e. peak LA volume: 50 to 80 ml). Furthermore, LV concentric remodeling increased LVEF (54 to 64%). LA failure led to LA dilation and reduction of PLAS, regardless of LV substrate. Lastly, LV diastolic dysfunction and LA failure did not affect LV GLS (Figure bottom row). Conclusion Simulations showed that acute LV systolic failure hardly affected PLAS, but predominantly decreased LV GLS and LVEF. On the contrary, both LV diastolic dysfunction and LA failure reduced PLAS, rather than LV GLS and LVEF. Hence, LA strain can be considered as a whistleblower sensitive to various LV and/or LA abnormalities, which may explain why it is a rather nonspecific diagnostic marker. Abstract Figure. LA and LV strain in various substrates

ВЛИЯНИЕ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ И ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ НА ЭФФЕКТИВНОСТЬ ВОССТАНОВЛЕНИЯ СИНУСОВОГО РИТМА У БОЛЬНЫХ С ТРЕПЕТАНИЕМ ПРЕДСЕРДИЙ

The use of overdrive transesophageal cardiac pacing (OTECP) in atrial flutter (AF) can reduce the number of external electrical cardioversion (EEC) in arrhythmia refractory to drug-induced cardioversion. The conversion of AF to atrial fibrillation (AFib) with subsequent spontaneous sinus rhythm (SR) restoration with the help of OTECP and accompanying antiarrhythmic therapy (AAT) was carried out in 59 patients with diseases of the cardiovascular system aged 40 to 77 years. The duration of AF before pacing was 35.93 ± 5.25 days. The efficiency of OTECP was 71.19%, and the time for spontaneous SR restoration was on average 16.92 ± 2.67 h. During pacing, the combined AAT has no advantages over monotherapy, despite its higher efficiency before OTECP. The obtained results indicate that the duration of AF prior to the OTECP procedure did not affect either the effectiveness of the procedure or the timing of spontaneous SR restoration. Inadequate control of blood pressure during treatment was a risk factor for reducing the effectiveness of OTECP, and contributed to the persistence or recurrence of arrhythmia. In patients with AF without AH, a decrease in left ventricular contractility and severe grade of CHF with an increase in left ventricular chamber dimension at end systole, a decrease in ejection fraction (EF) and fractional shortening (FS), reduces the likelihood of spontaneous SR restoration after OTECP, while additional administration of digoxin to increase myocardial contractility did not influence the effectiveness the therapy being carried out. The enlarged dimensions of the left atrium, which did not go beyond the critical dimensions, also had no influence on the effectiveness of the therapy. The efficiency of SR restoration against the background of AAT was 71.19%. Taking into account the EEC accompanied by the treatment performed corresponds to 83.05%. The effectiveness of OTECP when performed on the background of mono- or combined AAT did not differ significantly and amounted to 70.83 and 71.43%, as well as the terms of spontaneous SR restoration — 16.94 ± 2.86 and 16.89 ± 2, 48 hours respectively. The effectiveness of OTECP during mono- or combined AAT was 70.83% and 71.43%, respectively, and the time for spontaneous SR restoration was 16.94 ± 2.86 and 16.89 ± 2.48 hours. Medicamentous cardioversion of AF prior to the OTECP procedure is effective in 54.29% of cases and only with the combined AAT.

Comparative assessment of the diagnostic value of echocardiography and magnetic resonance imaging in determining myocardial viability

Aim. To compare myocardial imaging methods in patients with complicated coronary artery disease with significantly decreased myocardial contractility.Material and methods. This single-center retrospective study included 109 patients with complicated coronary artery disease who underwent surgical treatment between 2014 and 2020. All patients had indications for delayed contrast-enhanced cardiac magnetic resonance imaging (MRI) in order to determine myocardial viability due to a pronounced decrease in left ventricular contractility according to echocardiography (ejection fraction (EF) ≤30%).Results. Impairment of local contractility according to MRI and echocardiography significantly correlates with depth of contrast accumulation (p=0,0000000018 and p=0,0000034, respectively). Delayed contrast-enhanced cardiac MRI with cine sequences allows to determine higher number of impaired contractility cases compared with echocardiography (p=0,000006).Conclusion. MRI with cine sequence allowed to determine higher number of impaired contractility cases compared with echocardiography. Delayed contrastenhanced MRI is a reliably more sensitive method than electrocardiography in detecting left ventricular scarring. The depth of contrast agent accumulation correlates with local contractility impairment detected by echocardiography and delayed contrast-enhanced cardiac MRI.

Descending thoracic aorta\u2013abdominal aortic bypass and bilateral renal arterial blood circulation reconstruction are effective in atypical coarctation of the aorta with heart failure: a case report

BackgroundThere are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta.Case presentationA 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu’s arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%.ConclusionIn atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective.

Flecainide-induced QRS complex widening correlates with negative inotropy

The negative inotropic effect of Class IC antiarrhythmic drugs limits their use for acute cardioversion of atrial fibrillation (AF). The purpose of this study was to examine, in an intact porcine model, the effects of pulmonary and intravenous (IV) administration of flecainide on left ventricular (LV) contractility and QRS complex width at doses that are effective in converting new-onset AF to sinus rhythm. Flecainide (1.5 mg/kg bolus) was delivered by intratracheal administration and compared to 2.0 mg/kg 10-minute IV administration (European Society of Cardiology guideline) and to 0.5 and 1.0 mg/kg 2-minute IV doses in 40 closed-chest, anesthetized Yorkshire pigs. Catheters were fluoroscopically positioned in the LV to monitor QRS complex width and contractility and at the bifurcation of the main bronchi to deliver intratracheal flecainide. Peak flecainide plasma concentrations (Cmax) were similar, but the 30-minute area under the curve (AUC) of plasma levels was 1.4- to 2.8-fold greater for 2.0 mg/kg 10-minute IV infusion than for the lower, more rapidly delivered intratracheal and IV doses. AUC for LV contractility (ie, negative inotropic burden) was 2.2- to 3.6-fold greater for 2.0 mg/kg 10-minute IV dose than for the lower, more rapidly delivered doses. QRS complex widening by flecainide was highly correlated with the decrease in LV contractility (r2 = 0.890, P <.0001, for all IV doses; r2 = 0.812, P = .01, for intratracheal flecainide). QRS complex widening in response to flecainide is strongly correlated with decrease in LV contractility. Rapid pulmonary or IV flecainide delivery reduces the negative inotropic burden while quickly achieving Cmax levels associated with conversion of AF.

Ibudilast, a Phosphodiesterase Inhibitor and Toll-Like Receptor-4 Antagonist, Improves Hemorrhagic Shock and Reperfusion-Induced Left Ventricular Dysfunction by Reducing Myocardial Tumor Necrosis Factor α

ObjectivesRapid loss of blood volume causes ischemic injury to myocardial cells and impairs cardiac function. Subsequent reperfusion, although necessary to revitalize stunned tissues, can induce production of reactive oxygen species and inflammation, causing further tissue damages and weakening cardiac function. Ibudilast, a Toll-like receptor-4 (TLR4) antagonist and an inhibitor of phosphodiesterase-4, possesses antioxidative and anti-inflammatory capacities. In this study, we aim to examine the protective efficacy of ibudilast against hemorrhagic shock and reperfusion (HSR)-induced myocardial injury and cardiac dysfunction. MethodsStudies were conducted on male Sprague-Dawley rats in 3 groups: sham-operated, HSR with, and HSR without pretreatment of ibudilast. Hemorrhagic shock was induced by withdrawing blood from the femoral artery until the mean aortic pressure dropped to around 40 mm Hg; reperfusion was conducted by replenishing blood after 120 minutes of hemorrhagic shock, and the observation continued for another 240 minutes. The left ventricular (LV) contractility, diastolic suction capacity, and ventricular stiffness were evaluated using simultaneous LV pressure, and volume was recorded during a temporary inferior vena cava constriction at the end of reperfusion. Ibudilast (10 mg/kg) was administered intraperitoneally 3 days and 20 minutes prior to HSR. Serum creatine kinase myocardial band (CK-MB) was examined at the end of both HSR, and serum CK-MB, myocardial TLR4 protein expression, and malondialdehyde (MDA) and tumor necrosis factor (TNF)-α levels at the end of reperfusion. ResultsHSR induced an increase in serum CK-MB. Subsequent reperfusion further increased serum CK-MB, upregulated myocardial TLR4 protein expression, and increased tissue levels MDA and TNF-α vs the sham (P < .05). HSR reduced LV contractility, prolonged LV relaxation time, and increased LV diastolic stiffness. Ibudilast pretreatment attenuated HSR-induced TLR4 protein expression, reduced myocardial MDA and TNF-α levels, and protected against cardiac dysfunction. ConclusionsIbudilast pretreatment reduced myocardial TLR4 expression, decreased MDA and TNF-α levels, and protected against HSR-induced decrease in LV contractility, prolonged LV relaxation time, and increased diastolic stiffness.

The Clinical Value of no-Reflow Phenomenon in the Routing Operation of The Regional Vascular Center

Coronary no-reflow phenomenon (CNR) is a complication of primary percutaneous coronary intervention (PCI). According to different reports, CNR occurs in 10 to 60 % of cases. Despite the long history of studying this phenomenon many issues remain unsolved. This article presents a clinical case of electrocardiographically confirmed ST-segment elevation myocardial infarction. In this case, the CNR phenomenon occurred during PCI and was associated with heart rhythm disorders, left ventricular (LV) cavity dilatation with a decrease in LV contractility, and formation of intracavitary thrombus. The patient asked for medical care late, which could influence the development of CNR. This case demonstrates the clinical significance, diagnostic characteristics, and successful drug correction of the no-reflow phenomenon.

Случай успешной хирургической коррекции критического аортального стеноза у пациента с выраженным снижением сократительной способности левого желудочка (фракция выброса 20%) и узким фиброзным кольцом аортального клапана

Случай успешной хирургической коррекции критического аортального стеноза у пациента с выраженным снижением сократительной способности левого желудочка (фракция выброса 20%) и узким фиброзным кольцом аортального клапана

Cardiac toxicity of some echinocandin antifungals

Background: Unexplained cardiovascular decompensation has been observed during central venous administration of some echinocandins.Objective: The purpose of this study was to assess cardiac toxicity associated with the echinocandins.Methods: Isolated rat hearts (Langendorff model) were perfused with anidulafungin (ANID), caspofungin (CASP), or micafungin (MICA) at exposures of 1, 4, and 10 times therapeutic concentrations. Changes in left ventricular contractility with experimental exposure were compared to control, and histologic and transmission electron microscopy (TEM) examinations of tissue were performed.Results: Mean concentrations of ANID (10 – 80 µg/ml) and CASP (6 – 48 µg/ml) were associated with significant decreases in contractility (-77.1 ± 9.4% and -40.6 ± 15.6%, respectively; p < 0.05). MICA was associated with an increase in contractility (13.6 ± 2.8%, p = NS). On TEM, samples exposed to ANID and CASP had enlarged mitochondria and disintegrating myofibrils. Samples exposed to MICA showed some enlarged mitochondria.Conclusion: Mean concentrations of ANID and CASP were associated with statistically significant decreases in left ventricular contractility at concentrations that may be achievable in humans after peripheral administration, while MICA caused no change. TEM studies suggest this may be a result of mitochondrial damage. Caution may be warranted with central administration of these agents to patients with preexisting cardiac dysfunction.

214: Left ventricular Tachykinin 1 gene expression is increased in chronically anemic fetal sheep

increased in chronically anemic fetal sheep Juulia Junno, Juha Rasanen, Jennifer Farwell, Roger Hohimer, Olli Vuolteenaho, Lowell Davis, Sonnet Jonker University of Oulu, Physiology, Oulu, Finland, Oregon Health and Science University, Obstetrics and Gynecology, Portland, OR, Kuopio University Hospital, Obstetrics and Gynecology, Kuopio, Finland, Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland OBJECTIVE: Chronically anemic fetuses increase cardiac output by 50%. Anemia-induced cardiac remodeling is associated with diminished isovolumic contraction velocity acceleration (IVCVacc) and isovolumic relaxation velocity deceleration (IVRVdec) in the left ventricle indicating reduced ventricular contractility and relaxation. We therefore sought to determine if there were changes in genes that affect ventricular function in chronically anemic fetuses. STUDY DESIGN: 7 fetal sheep with twin gestations had catheters placed surgically and 1 randomly selected twin was made anemic by daily isovolumic hemorrhage for 8 days. At 126 days gestation echocardiographic studies were performed under anesthesia and tissues from the right (RV) and left (LV) ventricles were obtained. Agilent’s 8x15K Sheep Gene Expression array with greater than 2 fold changes were selected for qRT-PCR. RESULTS: Hematocrit was reduced in anemic fetuses as compared to controls 13.1 (2.5) vs 34.9 (5.2)% means (SD) as well as oxygen content 2.3 (0.4) vs 8.4 (1.7) ml/dl. LV and RV IVCVacc and IVRVdec, and MRNA expression/18s are shown below. All the data are presented as means (SD).* p 0.05. CONCLUSION: Neither changes in -adrenergic receptor 1, phospholamban, nor troponin C account for the decrease in left ventricular contractility and relaxation in anemic fetuses. Increased Tachykinin 1 gene expression through substance P and neurokinin A may be important in mediating decreased ionotropy and lusitropy in chronic fetal anemia.

Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats

We have previously reported that resistin induces hypertrophy and impairs contractility in isolated rat cardiomyocytes. To examine the long-term cardiovascular effects of resistin, we induced in vivo overexpression of resistin using adeno-associated virus serotype 9 injected by tail vein in rats and compared to control animals. Ten weeks after viral injection, overexpression of resistin was associated with increased ratio of left ventricular (LV) weight/body weight, increased end-systolic LV volume and significant decrease in LV contractility, measured by the end-systolic pressure volume relationship slope in LV pressure volume loops, compared to controls. At the molecular level, mRNA expression of ANF and β-MHC, and protein levels of phospholamban were increased in the resistin group without a change in the level of SERCA2a protein expression. Increased fibrosis by histology, associated with increased mRNA levels of collagen, fibronectin and connective tissue growth factor were observed in the resistin-overexpressing hearts. Resistin overexpression was also associated with increased apoptosis in vivo, along with an apoptotic molecular phenotype in vivo and in vitro. Resistin-overexpressing LV tissue had higher levels of TNF-α receptor 1 and iNOS, and reduced levels of eNOS. Cardiomyocytes overexpressing resistin in vitro produced larger amounts of TNFα in the medium, had increased phosphorylation of IκBα and displayed increased intracellular reactive oxygen species (ROS) content with increased expression and activity of ROS-producing NADPH oxidases compared to controls. Long-term resistin overexpression is associated with a complex phenotype of oxidative stress, inflammation, fibrosis, apoptosis and myocardial remodeling and dysfunction in rats. This phenotype recapitulates key features of diabetic cardiomyopathy.This article is part of Special Issue Item Group entitled "Possible Editorial".

Left Ventricular Hypercontractility Immediately after Tilting Triggers a Disregulated Cardioinhibitory Reaction in Vasovagal Syncope: Echocardiographic Evaluation during the Head-Up Tilt Test

Objectives: Vasovagal syncope (VVS) has been believed to occur when mechanoreceptors are discharged by vigorous ventricular contraction. However, previous investigators have reported divergent observations regarding the presence of left ventricular (LV) hypercontractility in VVS. Because the autonomic nervous system can be promptly activated after certain stimuli, we postulated that instantaneously increased LV contractility at the time of venous pooling may trigger the disregulated vasovagal reaction in VVS. Methods: Forty-seven patients (31 males, mean age 41 ± 18 years) with unexplained syncope were enrolled. Echocardiography was performed during the head-up tilt test (HUTT) as follows: baseline, passive tilting (0 and 20 min), and tilting with isoproterenol administration (5 and 10 min). Patients were divided into 2 groups according to the results of the HUTT; group 1 (n = 12) had a positive result and group 2 had a negative response. Results: LV ejection fraction (LVEF), determined immediately after tilting, increased in group 1, whereas LVEF decreased in group 2 (p = 0.032). Although left atrial and LV volumes decreased similarly during the test, group 1 showed a progressive reduction in LVEF, while LVEF progressively increased in group 2 (p = 0.007). Conclusion: Patients with HUTT-induced VVS presented LV hypercontractions immediately after tilting and a subsequent decrease in LV contractility. An instantaneous activation of the sympathetic nervous system at the time of venous pooling may trigger an early disregulated vasovagal reflex via an increase in LV contractility in VVS.

O pré-condicionamento isquêmico influencia a contratilidade ventricular na cirurgia sem extracorpórea

Ischemic preconditioning is a method that prepares and protects cells to tolerate a long period of ischemia with the least possible injury. Evaluate the influence of ischemic preconditioning over left ventricular function during off-pump myocardial revascularization. Forty patients with clinical indication for off-pump myocardial revascularization were randomized in two groups, with or without ischemic preconditioning. Ischemic preconditioning was carried out by performing coronary occlusion for two minutes and releasing blood flow for one minute; two cycles were performed. Left ventricular contractility was evaluated through transesophageal Doppler by measuring blood flow acceleration in the descending aorta - Hemosonic 100. The acceleration measurements were performed at the start of the surgery, after heart positioning and five and ten minutes after coronary occlusion. There was no significant difference in left ventricular contractility between the two groups. At the beginning of the procedure flow acceleration was 9.37 +/- 2.9m/s(2) in the preconditioning group and 12.5 +/- 3.1 m/s(2) in no-preconditioning group (p = 0.23); after positioning of heart, it was 8.47 +/- 3.3 and 8.31 +/- 3.6 m/s(2) (p = 0.96); after five minutes - 8.7 +/- 4.1 and 7.94 +/- 2.9 m/s(2) (p = 0.80); and after ten minutes - 9.2 +/- 4.5 and 7.98 +/- 3.4 m/s(2) (p = 0.71). However, contractility evolution was different throughout time in each group. The preconditioning group maintained left ventricular contractility during the entire procedure, since the beginning (0.52), while the group without ischemic preconditioning presented reduction in left ventricular contractility (p = 0.0034). Ischemic preconditioning prevented the decrease in left ventricular contractility during off-pump myocardial revascularization surgery.

Abstract 3361: Progressive Left Ventricle, Myocyte Dysfunction, and Heart Failure in the Lethality of Anthrax Toxin in Conscious Dogs

Background . Bacillus anthracis ( BA ) infection is a cause of human and animal disease and associated with biowarfare. Although circulatory shock related to anthrax lethal toxin (LeTx) may play a primary role in lethality due to BA infection, its mechanisms are unclear. Methods . Six chronically-instrumented conscious dogs were assigned to receive a bolus injection of LeTx (10 ml saline with equivalent doses PA/LF, about 0.265 mg/kg, iv, n = 2) or saline (10 ml, iv, n = 4). Hemodynamic, left ventricular (LV) systolic and diastolic responses were determined periodically until 96 hours (h) in both groups. LV biopsies were performed at about 98H (before death). Isolated myocyte contractile function and histopathological alterations were determined. Results . Compared with control, in LeTx-treated animals, there were progressive decreases in LV contractility and slowed LV relaxation during the transition from LV dysfunction to heart failure (HF) over 96–98H. The cardiac depression was apparent about 6 – 8H after LeTx, but progressed through the subsequent 72–98H. At 72H after LeTx, heart rate (LeTx:129vsControl:95 bpm), LV end-diastolic pressure (P) (21vs9 mmHg), and the time constant of relaxation (40.9vs29.7 ms) were increased with markedly reduced ejection fraction, stroke volume (SV, 8.4vs15.8 ml), and end-systolic P (92vs118 mmHg). Moreover, LV contractility was decreased 49% (E ES , 4.1vs8.2 mmHg/ml and M SW , 44.9vs88.9 mmHg) with rightward shifts of LV P-V loops. At 96H, M SW , SV, and EF were further decreased accompanied by the development of severe HF. Pathologic finding of LV dilatation was associated with significantly increased length of LV myocytes (201±11vs122±13 μm). In LeTx-treated myocytes, there were about 46% reductions in cell contraction (79.0±9.7vs146.2±11.4 μm/s) and relaxation, respectively. LeTx produced lethality in dogs 4 days after LeTx treatment with similar time courses to those previously reported in man. Conclusions . LeTx causes direct and time-dependent progressive decrease in LV contractility, slow relaxation, cardiomyocyte dysfunction, LV, and myocyte remodeling and leads to HF, which suggests that the heart could be the primary target for the action of LeTx and plays an important role in lethality due to BA infection.

The role and regulation of cardiac angiotensin-converting enzyme for noninvasive molecular imaging in heart failure

Congestive heart failure is a pathologic condition characterized by progressive decrease in left ventricular contractility and consequent decline of cardiac output. There is convincing clinical and experimental evidence that the renin-angiotensin system (RAS) and its primary effector peptide, angiotensin II, are linked to the pathophysiology of interstitial fibrosis, cardiac remodeling, and heart failure. In addition to the traditional endocrine or circulating RAS, an active tissue RAS has been characterized. Tissue angiotensin-converting enzyme and locally synthesized angiotensin II, for example, by chymase, exert local trophic effects that modulate gene expression, which regulates growth and proliferation in both myocytes and nonmyocytes. The existence of the tissue RAS offers an opportunity for targeted imaging, which may be of considerable value for guiding medical therapy.

Altered calcium handling is critically involved in the cardiotoxic effects of chronic beta-adrenergic stimulation.

Chronic adrenergic stimulation leads to cardiac hypertrophy and heart failure in experimental models and contributes to the progression of heart failure in humans. The pathways mediating the detrimental effects of chronic beta-adrenergic stimulation are only partly understood. We investigated whether genetic modification of calcium handling through deletion of phospholamban in mice would affect the development of heart failure in mice with transgenic overexpression of the beta1-adrenergic receptor. We crossed beta1-adrenergic receptor transgenic (beta1TG) mice with mice homozygous for a targeted deletion of the phospholamban gene (PLB-/-). Phospholamban ablation dramatically enhanced survival of beta1TG mice. The decrease of left ventricular contractility typically observed in beta1TG mice was reverted back to normal by phospholamban ablation. Cardiac hypertrophy and fibrosis were significantly inhibited in beta1TG/PLB-/- mice compared with beta1TG mice, and the heart failure-specific gene expression pattern was normalized. Analysis of intracellular calcium transients revealed increased diastolic calcium levels and decreased rate constants of diastolic calcium decline in beta1TG mice. In beta1TG/PLB-/- mice, diastolic calcium concentration was normal and rate constants of diastolic calcium decline were greater than in wild-type mice. We conclude that modification of abnormal calcium handling in beta1TG mice through ablation of phospholamban resulted in a rescue of functional, morphological, and molecular characteristics of heart failure in beta1-adrenergic receptor-transgenic mice. These results imply altered calcium handling as critical for the detrimental effects of beta1-adrenergic signaling.

Addition of angiotensin II receptor antagonist to an ACE inhibitor in heart failure improves cardiovascular function by a bradykinin-mediated mechanism.

Whether cardiovascular responses to bradykinin are augmented by additional treatment with angiotensin II receptor antagonism (ATRA) to angiotensin-converting enzyme inhibition (ACEI) in congestive heart failure (CHF) is unknown. To clarify the level and functional effects of endogenous bradykinin in CHF with combined ATRA and ACEI, 35 dogs were assigned to the following treatment protocols: 1). rapid ventricular pacing (240 bpm), 2). concomitant ATRA (TCV116, 1.5 mg x kg-1.day-1) and rapid pacing, 3). concomitant ACEI (enalapril 1.9 mg x kg-1.day-1) and rapid pacing, 4). concomitant combined ATRA (TCV116, 0.75 mg x kg-1.day-1) and ACEI (enalapril 0.95 mg x kg-1.day-1) and rapid pacing, and 5). sham-operated control. Plasma bradykinin levels were increased and B(2) receptors were synergistically upregulated in CHF groups treated with combined ATRA and ACEI compared with those treated with ATRA or ACEI alone. HOE-140 (0.3 mg/kg), a bradykinin B(2) receptor antagonist, produced an increase in total systemic resistance and a decrease in left ventricular contractility in CHF with combined therapy compared with either monotherapy. Thus, endogenous bradykinin partially contributes to the synergistic improvement of cardiovascular function in CHF with additional treatment with ATRA to ACEI.

Effects of changes in left ventricular contractility on indexes of contractility in mice.

Measurement of left ventricular (LV) function is often overlooked in murine studies, which have been used to analyze the effects of genetic manipulation on cardiac phenotype. The goal of this study was to address the effects of changes in LV contractility on indexes of contractility in mice. LV function was assessed in vivo in closed-chest mice by echocardiography and by LV catheterization using a conductance pressure-volume (P-V) catheter with three different interventions that alter contractility by 1) atrial pacing to increase inotropy by augmentation of the force-frequency relation (modest increment of inotropy), 2) dobutamine to maximize inotropy, and 3) esmolol infusion to decrease contractility. Load-independent parameters derived from P-V relations, such as slope of end-systolic P-V relations (ESPVR) and slope of the first maximal pressure derivative over time (dP/dt(max))-end-diastolic volume relation (dP/dt-EDV), and standard echocardiographic parameters were measured. The dP/dt-EDV changed the most among parameters after atrial pacing and dobutamine infusion (percent change, 162.8 +/- 95.9% and 271.0 +/- 44.0%, respectively). ESPVR was the most affected by a decrease in LV contractility during esmolol infusion (percent change, -49.8 +/- 8.3%). However, fractional shortening failed to detect changes in contractility during atrial pacing and esmolol infusion and its percent change was <20%. This study demonstrated that contractile parameters derived from P-V relations change the most during a change in LV contractility and should therefore best detect a small change in contractility in mice. Heart rate has a modest but significant effect on P-V relationship-derived indexes and must be considered in the evaluation of murine cardiac physiology.