Inotropic Action Research Articles

Serum Apelin Levels and Ascending Aortic Aneurysm in Adults

Apelin is a peptide isolated from bovine stomach and has vasodilator and inotropic activities. The aim of this study was to confirm the relationship between serum apelin levels and ascending aortic dilatation in adult patients. This study included 39 patients with ascending aortic aneurysm who applied to the cardiovascular surgery outpatient clinic between 1 June 2019 and 31 August 2019 and 50 healthy volunteers. Serum apelin and serum apelin receptor levels were measured with ELISA method. Serum apelin levels were lower in patients with aortic aneurysm compared to the control group, while serum apelin receptor levels were higher. These findings may show that serum apelin and apelin receptor levels may be a potential biomarker for aortic aneurysm.

Comprehensive Cardiac Safety Assessment using hiPS-cardiomyocytes (Consortium for Safety Assessment using Human iPS Cells: CSAHi).

Current cardiac safety assessment platforms (in vitro hERG-centric, APD, and/or in vivo animal QT assays) are not fully predictive of drug-induced Torsades de Pointes (TdP) and do not address other mechanism-based arrhythmia, including ventricular tachycardia or ventricular fibrillation, or cardiac safety liabilities such as contractile and structural cardiotoxicity which are another growing safety concerns. We organized the Consortium for Safety Assessment using Human iPS cells (CSAHi; http://csahi.org/en/) in 2013, based on the Japan Pharmaceutical Manufacturers Association (JPMA), to verify the application of human iPS/ES cell-derived cardiomyocytes for drug safety evaluation. The CSAHi HEART team focused on comprehensive screening strategies to predict a diverse range of cardiotoxicities using recently introduced platforms such as the Multi-Electrode Array (MEA), cellular impedance, Motion Field Imaging (MFI), and optical imaging of Ca transient to identify strengths and weaknesses of each platform. Our study showed that hiPS-CMs used in these platforms could detect pharmacological responses that were more relevant to humans compared to existing hERG, APD, or Langendorff (MAPD/contraction) assays. Further, MEA and other methods such as impedance, MFI, and Ca transient assays provided paradigm changes of platforms for predicting drug-induced QT risk and/or arrhythmia or contractile dysfunctions. In contrast, since discordances such as overestimation (false positive) of arrhythmogenicity, oversight, or opposite conclusions in positive inotropic and negative chronotropic activities to some compounds were also confirmed, possibly due to their functional immaturity of hiPS-CMs, hiPS-CMs should be used in these platforms for cardiac safety assessment based upon their advantages and disadvantages.

SAT-LB83 Amiodarone Induced Myxedema Coma

Introduction Amiodarone is widely used as a rhythm-conversion agent in atrial fibrillation. It’s low negative inotropic activity and low risk of ventricular arrhythmia makes it an advantageous agent for atrial arrhythmia. One of the major limiting factors in the use of amiodarone can be its thyroid toxicity leading to thyroid-dysfunction; ranging from thyrotoxicosis to myxedema coma. Myxedema coma, although rare, is a deadly complication of hypothyroidism with a mortality rate as high as 60%. It is considered an endocrinologic emergency that requires prompt attention and treatment. We present a case of myxedema coma in the setting of chronic amiodarone intake.Case Presentation A 75-year-old female with a past medical history significant for atrial fibrillation, hypothyroidism, end stage renal disease from diabetic nephropathy on hemodialysis, Hepatitis C, hypertension, and hyperlipidemia was admitted to the hospital for evaluation of generalized weakness. Her medications included amiodarone 200mg/day among others. The next day, the rapid response team was called when the patient became hypotensive, bradycardic and unresponsive. She was transferred to the ICU and intubated immediately. On exam, her skin was dry and cold. Her laboratory findings revealed a markedly elevated TSH level of 185uIU/mL. Her most recent TSH level was 9.044uIU/mL from a year back. Other laboratory tests revealed WBC count of 9.0k/mm cu, hemoglobin 13.7 g/dL, platelet count 48 k/mm cu. A diagnosis of myxedema coma was made based on her presentation and lab findings. The patient was started on intravenous levothyroxine 100mg daily with intravenous hydrocortisone 100mg every 8 hours. T4 levels were 0.38ng/dL, T3 levels were 1.83pg/mL and TPO antibodies were negative. A decision was made not to administer intravenous T3 because of the patient’s advanced age and underlying atrial fibrillation. Over the course of the hospitalization, the patient was showing signs of clinical improvement and attempts were being made to wean her off the ventilator. However, later she died due to hemorrhagic shock.Conclusion Myxedema coma may manifest nonspecifically as lethargy and altered mental status and can present without the more specific symptoms of skin changes or myxedematous soft tissue changes. It is therefore, very important for physicians to consider myxedema coma as one of the differential diagnoses in patients on amiodarone with underlying thyroid disease. Administering amiodarone for elderly patients with underlying thyroid problems warrants attention to polypharmacy. The treatment guidelines for myxedema coma are yet to be established. While intravenous levothyroxine with intravenous hydrocortisone remains the mainstay of therapy, there are no consensus on T3 administration.

The Elabela-APJ axis: a promising therapeutic target for heart failure.

Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin–APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA–APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA–APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA–APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA–APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA–apelin–APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.

Synthesis of two 7,8-dioxabicyclo[4.1.1]octan-3-yl)-steroid derivatives and evaluation of their inotropic activity in an animal model.

The aim of this study was synthesizing two 7,8-dioxabicyclo[4.1.1]octan-3-yl)-steroid derivatives (compounds 3 or 4) to evaluate their inotropic activity in vitro. The first stage was achieved by the preparation of two 7,8-dioxabicyclo[4.1.1]octan-3-yl)-steroid derivatives using some chemical strategies. Then, the inotropic activity of both steroid derivatives against left ventricular pressure (LVP) was evaluated in an isolated rat heart model using Bay-k-8644, nifedipine, aucubin, and L-NAME as controls. The results showed that compound 3 increased LVP in a dose-dependent manner and this effect was inhibited by nifedipine. Other results showed that compound 4 decreased LVP in a dose-dependent manner and this effect was blocked in the presence of L-NAME. All these data indicate that 1) the positive inotropic activity exerted by compound 3 was through type L calcium channel activation; 2) the negative inotropic effect of 4 was via nitric oxide synthase activation. These phenomena could be due to the different functional groups involved in the chemical structure of compounds 3 and 4.

HEMODYNAMIC EFFECTS OF NITROXYL DONOR BMS-986231 COMPARED TO NITROGLYCERIN OR PLACEBO IN PATIENTS WITH CHRONIC HEART FAILURE-A RANDOMIZED DOUBLE-BLIND CROSSOVER TRIAL

Nitroxyl (HNO) causes post-translational modification of thiol proteins. In animal models, the HNO donor BMS-986231 causes vasodilation and has inotropic and lusitropic actions. We compared the effects of BMS-986231 to nitroglycerin (NTG) or placebo on cardiac performance in patients with chronic

3-Aryl-4-nitrobenzothiochromans S,S-dioxide: From Calcium-Channel Modulators Properties to Multidrug-Resistance Reverting Activity.

Our research groups have been involved for many years in studies aimed at identifying new active organic compounds endowed with pharmacological properties. In this work, we focused our attention on the evaluation of cardiovascular and molecular drug resistance (MDR) reverting activities of some nitrosubstituted sulphur-containing heterocycles. Firstly, we have examined the effects of 4-nitro-3-(4-methylphenyl)-3,6-dihydro-2H-thiopyran S,S-dioxide 5, and have observed no activity. Then we have extended our investigation to the 3-aryl-4-nitrobenzothiochromans S,S-dioxide 6 and 7, and have observed an interesting biological profile. Cardiovascular activities were assessed for all compounds using ex vivo studies, while the MDR reverting effect was evaluated only for selected compounds using tumor cell lines. All compounds were shown to affect cardiovascular parameters. Compound 7i exerted the most effect on negative inotropic activity, while 6d and 6f could be interesting molecules for the development of more active ABCB1 inhibitors. Both 6 and 7 represent structures of large possible biological interest, providing a scaffold for the identification of new ABCB1 inhibitors.

Deleterious cardiovascular effect of exosome in digitalis-treated decompensated congestive heart failure.

Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.

Design and synthesis of new azetidine‐steroid derivative with inotropic activity in a heart failure model

AbstractSeveral steroid derivatives have prepared as inotropic drugs; however, there are few reports on azetidine‐steroid derivatives with inotropic activity. The aim of this study was to synthesize four azetidine‐steroid derivatives (compounds 3 to 6) to evaluate their biological activity on left ventricular pressure. The first stage was achieved by preparation of azetidine‐derivatives using reactions of etherification and addition. The second stage involves the evaluation of biological activity from azetidine derivatives on left ventricular pressure in a heart failure model using estrone as control. The results showed that only compound 3 increases left ventricular pressure compared with estrone, compounds 2 and 4 to 6. In conclusion, the positive inotropic effect exerted by compound 3 depends on the functional groups involved in their chemical structure.

Mecanism and inotropic actions of the water exracts of the leaves and seeds of Datura metel (solanaceae) on isolated frogs heart

Datura metel leaves are used by athletes to enhance their performances. The water extract of the leaves and seeds was tested for their cardiotonic effect. Langherdoff’s model for the measurement of the mechanical activity of isolated amphibian heart in ventricular perfusion was used to evaluate some parameters of cardiac contractility. The effect of the extracts was also compared to sympathetic agonist and antagonist. The leaves and seed extracts induced significant (p

Synthesis of new azaindeno-acetonitrile derivative with inotropic activity against heart failure model

Several steroid derivatives have prepared as inotropic drugs; however, there are few reports on azaindeno-steroid derivatives with inotropic activity. The objective of this investigation was to prepare some azaindeno-acetonitrile derivatives (compounds 3 to 7) to evaluate their biological activity on left ventricular pressure. The first step was achieved by preparation of azaindeno-steroid derivatives using reactions of etherification and addition. The second stage involves the evaluation of biological activity from azaindeno-steroid derivatives on left ventricular pressure in a heart failure model using either estrone or an enone-steroid derivative (compound 2) as controls. The results showed that only compound 6 increases left ventricular pressure compared with estrone, compounds 2-5 and 6. In conclusion, the positive inotropic effect exerted by compound 6 depends on the functional groups involved in its chemical structure.

Cardiovascular effects of DWORF (dwarf open reading frame) peptide in normal and ischaemia/reperfused isolated rat hearts

The novel peptide dwarf open reading frame (DWORF), highly conserved across species and expressed almost exclusively in cardiac ventricular muscle, may play a role in cardiac physiology and pathophysiology. The effect of direct administration of DWORF in the intact heart has not previously been examined. Accordingly, we investigated the cardiac effects of DWORF (1−30 nM) in normal isolated perfused rat hearts and hearts undergoing ischaemia/reperfusion (I/R) injury, and evaluated potential mechanisms of action. Exogenous DWORF at the top dose (30 nM) increased perfusion pressure (PP) in normal hearts, which indicates coronary vasoconstriction; and during post-ischaemic reperfusion, DWORF increased PP in a dose-dependent manner. In I/R hearts, DWORF at the top dose also increased left ventricular end-diastolic pressure and maximum and minimum derivatives of left ventricular pressure noted dP/dt(max) and dP/dt(min), respectively, without affecting developed pressure (DP). Co-infusion of DWORF with Diltiazem, an l-type Ca2+ channel blocker (1μM), in I/R hearts attenuated the falls in DP, dP/dt(max) and dP/dt(min) observed with Diltiazem alone. DWORF co-infusion with both Diltiazem and Y27632 (1μM) (a Rho-Kinase inhibitor) reversed the coronary vasodilator effect of the inhibitors administered alone. In conclusion, we provide the first evidence that DWORF has coronary vasoconstrictor actions in normal hearts and when administered during reperfusion in an ex-vivo model of cardiac I/R injury, and also exhibits positive cardiac inotropic activity in the latter setting. DWORF’s effect on ventricular contractile function appears to be dependent on the l-type Ca2+ channel, whereas Rho-Kinase activity may be related to the coronary vasoconstrictor effects of DWORF.

2019 AGS Beers Criteria for older adults

2019 AGS Beers Criteria for older adults

Effects of Prosopis farcta Root Extract in the Vascular Reactivity of Isolated Goat Coronary Artery

Prosopis species is a medicinal plant, well-known for its beneficial effects in treating various smooth muscles disorders, and its phytochemical analysis revealed the presence of different bioactive compounds in different parts of the plant, most of which show a great role in reducing cardiovascular risks. In the present study, the cardiovascular effect of Prosopis farcta Root Extract (PFRE) was investigated in vitro for possible mechanisms of the extract effect in the vascular reactivity of isolated goat coronary artery (CA) using Organ bath and PowerLab Data Acquisition system. The results of the recording and analyzing of the effect of the PFRE in isolated CA, showed the negative inotropic activity of the extract in CA rings with intact-endothelium, while in CA ring with hyperglycemic-induced endothelium dysfunction the extract tended to vasodilate the CA ring non-significantly, and the extract induced dose-dependent vasodilation in CA rings pre-constricted with high concentration of (30 mM)KCl and showed no effects on contractions induced by (1X10-3-1X10-5) Phenylephrine PE, which is an indicator for its blockade activity on L-type voltage-dependent Ca+2 channel and non-interfering of the extract with the receptor-operated Ca+2 channel. The mechanical recording of the CA ring activities, revealed different potassium (K+) channels including selective calcium-activated potassium channel, ATP-sensitive potassium channel, and different endothelium-derived relaxing factors (EDRF) including nitric oxide and Prostacyclin (PGI2 ) seems to have no role in the relaxation effects of the extract, while the endothelium derived-hyperpolarizing factor (EDHF); epoxy eicosatrienoic acid (EET) showed significant participation in the vasodilation effects of the extract. On the other hand, the extract tended to relax the CA rings through its antagonizing of Ca+2, reducing and inhibiting Ca+2 influx and release from internal stores and interfering with the voltage-operated Ca+2 channels through its alkaloid and flavonoid active compounds which suggested to be the most predicted mechanisms for the maintenance of vasodilating tone and coronary circulation of the PFRE in coronary artery.

Design and synthesis of methylthiododec-5-en-7-yn-6-yl-steroid derivativewith positive inotropic activity

There are several drugs for the treatment of heart failure; however, some of these drugs can produce several secondary effects such as hyperkalemia, arrhythmias, and others. Therefore, the aim of this study was synthesized a new methylthiododec-5-en-7-yn-6-yl-steroid derivative using some chemical strategies. In addition, the biological activity of the steroid derivative against heart failure was evaluated using an isolated heart model. Also, the effect produced by this steroid derivative on left ventricular pressure (LVP) was determinate using some positive inotropic drugs such as milrinone, digoxin, levosimedan and dobutamine as controls. The results showed that methylthiododec-5-en-7-yn-6-yl-steroid derivative increase LVP in a dose-dependent manner and this effect was like that produced by milrinone. In conclusion, the biological activity produced by steroid-derivative; 1) depends on the functional groups involved in their chemical structure; 2) could act as a positive inotropic agent similar to milrinone. All these data suggest that steroid-derivative may be a good candidate for the treatment of heart failure.

Initiation of ivabradine in cardiogenic shock.

AimsIvabradine is a selective sinus node inhibitor indicated in patients with symptomatic chronic heart failure on stable guideline‐recommended heart failure therapy including appropriate doses of beta‐blockers. The use in cardiogenic shock remains off label and has been considered a contraindication due to the theoretical risk of attenuating compensatory tachycardia. Tachycardia, especially in the context of inotropic therapy, may be deleterious, resulting in increased myocardial oxygen consumption and reduction in diastolic filling. As ivabradine does not have negative inotropic action, it may present a potential means to manage tachycardia in cardiogenic shock. We present a case series of four patients with cardiogenic shock started on ivabradine who were unable to tolerate beta‐blockers.Methods and resultsFive patients identified with cardiogenic shock defined as a severe reduction in cardiac index (<2.0 L/min/m2) and elevated filling pressures on inotropic therapy were started on ivabradine in patients with sinus tachycardia [heart rate (HR) >100] who were intolerant to beta‐blockers. Each patient had a cardiac magnetic resonance imaging, echocardiogram, and coronary angiogram for determination of aetiology. Invasive haemodynamics via pulmonary artery catheterization were measured during initiation and titration of ivabradine (baseline, 6, 12, 24, and 48 h after ivabradine administration) with continuous telemetry monitoring for any dysrhythmia or bradyarrhythmias. All patients tolerated ivabradine initiation, and at 24 h, an observed decrease in HR (106 ± 6.8 vs. 91.6 ± 6.4 b.p.m., P = 0.04), pulmonary arterial occlusion pressure (30.4 ± 4.8 vs. 24 ± 5.1 mmHg, P = 0.04), and right atrial pressure (16.8 ± 6.2 vs. 9 ± 4.3 mmHg, P = 0.0002). An improvement was observed in mixed venous oxygen saturation (SvO2) (51 ± 8.8 vs. 64.8 ± 5.3%, P < 0.04), stroke volume (37.2 ± 7.6 vs. 49.2 ± 12.9 mL, P < 0.04), and right and left ventricular stroke work index (Table 1). No significant changes were observed with mean arterial pressure (73.4 ± 7.5 vs. 75.8 ± 5.0 mmHg, P = 0.81) and thermodilution‐derived cardiac index (1.7 ± 0.2 vs. 2.5 ± 0.7 L/min/m2, P = 0.58). Inotropic support was weaned successfully in three of five patients (88 ± 30 h) with subsequent titration of beta‐blocker therapy. Two patients improved clinically but ultimately required left ventricular assist device implantation. All patients were discharged alive from hospital at 17 ± 7.9 days following ivabradine initiation.ConclusionsIn our small non‐randomized series of patients in cardiogenic shock, ivabradine was safely used to reduce HR in patients previously intolerant of beta‐blockade. There are limited data surrounding the use of ivabradine in cardiogenic shock, and future studies should be undertaken to determine the optimal HR in humans with cardiogenic shock and whether systematic limitation of peak HR may improve outcomes.

The sodium pump and digitalis drugs: Dogmas and fallacies.

The sodium pump (Na/K‐ATPase) is a plasma membrane enzyme that transports Na+ and K+ against their physiological gradients in most eukaryotic cells. Besides pumping ions, the enzyme may also interact with neighboring proteins to activate cell signaling pathways that regulate cell growth. Digitalis drugs, useful for the treatment of heart failure and atrial arrhythmias, inhibit the pumping function of Na/K‐ATPase and stimulate its signaling function. In the current field of research on the sodium pump and digitalis drugs, some issues that are commonly accepted to be well established are not so, and this may impede progress. Here, several such issues are identified, their histories are discussed, and their open discussions are urged. The covered unsettled questions consist of (a) the suggested hormonal role of endogenous digitalis compounds; (b) the specificity of Na/K‐ATPase as the receptor for digitalis compounds; (c) the relevance of the positive inotropic action of digitalis to its use for the treatment of heart failure; (d) the conflicting findings on digitalis–induced signaling function of Na/K‐ATPase; and (e) the uncertainties about the structure of Na/K‐ATPase in the native cell membrane.

ROLE OF NITRIC OXIDE IN CARDIAC PERFORMANCE DURING EXPERIMENTAL ISCHEMIC CARDIAC ARREST AND REPERFUSION

Background: Re-perfusion strategies are the current standard therapy for acute myocardial infarction, despite the spectrum of re-perfusionassociated pathologies that may contribute to irreversible myocardial injury. Aim of the work: The aim of present study is to clarify the alterations in intrinsic cardiac functions in response to cardiac ischemic arrest followed by re-perfusion in isolated hearts perfused with nitric oxide (NO) donor, Larginine, or NO inhibitor, Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), to shed light on the possible role of NO in re-perfusion process. Materials and Methods: Cardiac activities of hearts isolated from Adult albino rats of both sexes were studied on Langendorff preparation under basal conditions and during 30 min re-perfusion following 30 min of total global ischemia. Rats were randomly allocated into three groups; control and L-arginine or L-NAME infused heart groups. Both L-arginine and LNAMEwere infused over 20 min during the baseline activity before induction of total global ischemia. Thereafter, cardiac tissue levels of malondialdhyde, catalase and nitrite were assessed. Results: Compared to the control, both L arginine and L-NAME infused hearts showed increased basal chronotropy and myocardial flow rate. Significantly depressed basal inotropic state was only observed in L-arginine group. The three studied groups demonstrated significant deterioration in the inotropic activity and compromised myocardial flow rate during the whole period of reperfusion. L-arginine infused hearts demonstrated depressed inotropy and chronotropy, weak systolic and diastolic functions with compromised myocardial flow at early 5 min of reperfusion, yet with significantly higher myocardial flow rate % recovery by the end ofreperfusion (82.7% ±3.01 in L-arginine vs. 56.4% ± 2.32 in control and 62.6% ±2.17 in L-NAME). The chronotropic activity was maintained in both the control and L-NAME infused hearts. Cardiac tissue NO showed the highest level in L-arginine group and the lowest level in L-NAME one. Both catalase and MDA were insignificantly changed among the three studied groups. Conclusion: Reducing NO availability by L-NAME revealed mild impact on the ischemia re-perfusion induced contractile dysfunction. Excess NO worsens cardiac performance at early re-perfusion. However, it may have potentially protective effect by acquiring higher the myocardial flow rate during the reperfusion.

Mechanism and clinical characteristics in diagnosis and treatment of amniotic fluid embolism

Amniotic fluid embolism(AFE) is a fatal intrapartum complication. Typical AFE is characterized by respiratory and circulatory failure, followed by disseminated intravascular coagulation(DIC), while atypical AFE, which had a higher survival possibility, presents with unexplained DIC only. Recent findings support an anaphylactoid inflammatory mechanism underlying the pathophysiology of AFE. Milrinone is currently the first choice for AFE due to its several functions, such as reducing pulmonary artery pressure, and improving right ventricular function through lowering heart rate and positive inotropic action. A multidisciplinary team is required in the rescue of AFE and medical staff who are skilled in critical medicine (such as anesthesiologists) often play a pivotal role. Key words: Embolism, amniotic fluid; Mastocytosis; Hypersensitivity

Sugars make the difference – Glycosylation of cardiodepressant antibodies regulates their activity in dilated cardiomyopathy

BackgroundCardiodepressant antibodies contribute to cardiac dysfunction in dilated cardiomyopathy (DCM). Changes in immunoglobulin G (IgG) glycosylation modulate the activity of various autoimmune diseases and influence disease activity as well as severity of various autoimmune diseases. We hypothesized that alterations in IgG glycosylation are involved in the disease course of DCM. Methods and resultsIgG glycosylation was analyzed in plasma samples of 50 DCM patients using a lectin-based ELISA. Negative inotropic (cardiodepressant) activity (NIA) of antibodies was assessed by measuring the effect of purified DCM-IgG on the shortening of isolated rat cardiomyocytes by means of a video-edge detection system. IgG obtained from plasma of healthy blood donors served as control.DCM-IgG contained significantly less sialic acid (−25%) and galactose (−16%; both P < 0.001), but showed no significant differences in core-fucosylation compared to controls. Interestingly, IgG with NIA displayed a lower percentage of sialylation (−16%, P < 0.001) core-fucosylation (−15%, P = 0.015) and galactosylation (−10%, P = 0.129) than IgG without NIA. The extent of NIA was directly associated with IgG sialylation (r = 0.68; P < 0.001) and galactosylation (r = 0.37; P = 0.001). ConclusionReduced sialylation and galactosylation of IgGs enhances their cardiodepressant activity in DCM indicating that changes in IgG glycosylation may be involved in the pathogenesis of DCM.