Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies

1990 ◽  
Vol 68 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Peter James O'Brien ◽  
C. David Ianuzzo ◽  
Gordon W. Moe ◽  
Terry P. Stopps ◽  
Paul W. Armstrong
Keyword(s):  
Heart Failure ◽  
Glycolytic Enzyme ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Pacing ◽  
Ventricular Ejection Fraction ◽  
Biochemical Alterations ◽  
Rapid Ventricular Pacing

Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 ± 7.6 vs. 50.5 ± 5.1%) and cardiac index (81 ± 22 vs. 178 ± 48 mL∙min−1∙kg−1), 287% higher pulmonary capillary wedge pressure (27.5 ± 6.8 vs. 7.1 ± 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 ± 3.7 vs. 11.2 ± 1.3 cm2) (all p < 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 ± 139 vs. 747 ± 220 ng/g protein), (ii) 25–50% lower activities of myofibrillar Ca ATPase (0.188 ± 0.026 vs. 0.253 ± 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 ± 0.074 vs. 0.288 ± 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 ± 10.0 and 47.7 ± 15.8 U/g), (iii) 32% higher activity of the β-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 ± 1.48 vs. 8.67 ± 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 ± 0.77 vs. 1.81 ± 0.95 U/g) (all p < 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin. The pacing-induced alterations in left ventricular norepinephrine and sarcoplasmic reticular and myofibrillar Ca ATPase best correlated with in vivo physiological alterations. Biochemical alterations produced by rate overload were similar to those reported for volume or pressure overload.Key words: heart disease, chronic tachycardia, biochemical changes.

Abstract 165: The 18 kDa FGF-2 Prevents the Doxorubicin-induced Cardiac Damage and Amp-activated Kinase Activation, in vitro and in vivo

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Navid Koleini ◽  
Jon Jon Santiago ◽  
Barbara E Nickel ◽  
Robert Fandrich ◽  
Davinder S Jassal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Wild Type ◽  
Rat Cardiomyocytes ◽  
Ventricular Ejection Fraction ◽  
Compound C

Introduction: Protection of the heart from chemotherapeutic (Doxorubicin, DOX) drug-induced toxicity is a desirable goal, to limit side effects of cancer treatments. DOX toxicity has been linked to the activation (phosphorylation) of the AMP-activated kinase, AMPK. The 18 kDa low molecular weight isoform of fibroblast growth factor 2 (Lo-FGF-2) is a known cardioprotective and cytoprotective agent. In this study we have tested the ability of Lo-FGF-2 to protect from DOX-induced damage in rat cardiomyocytes in vitro, and in transgenic mouse models in vivo, in relation to AMPK activation. Methods: Rat neonatal cardiomyocytes in culture were exposed to DOX (0.5 μM) in the presence or absence of pre-treatment Lo-FGF-2 (10 ng/ml). Compound C was used to block phosphorylation (activity) of AMPK. Levels of cell viability/death (using Calcein-AM/Propidium iodide assay), phospho -and total AMPK, and apoptotic markers such as active caspase 3 were analyzed. In addition, transgenic mice expressing only Lo-FGF2, and wild type mice, expressing both high molecular weight (Hi-FGF2) as well as Lo-FGF2 were subjected to DOX injection (20 mg/kg, intraperitoneal); echocardiography was used to examine cardiac function at baseline and at 10 days post-DOX. Results: DOX-induced cell death of cardiomyocytes in culture was maximal at 24 hours post-DOX coinciding with significantly increased in activated (phosphorylated) AMPK. Compound C attenuated DOX-induced cardiomyocyte loss. Pre-incubation with Lo-FGF-2 decreased DOX induced cell death, and also attenuated the phosphorylation of AMPK post-DOX. Relative levels of phospho-AMPK were lower in the hearts of Lo-FGF2-expressing male mice compared to wild type. DOX-induced loss of contractile function (left ventricular ejection fraction and endocardial velocity) was negligible in Lo-FGF2-expressing mice but significant in wild type mice. Conclusion: Lo-FGF-2 protects the heart from DOX-induced damage in vitro and in vivo, by a mechanism likely involving an attenuation of AMPK activity.

Abstract 542: Chronic Doxorubicin Cardiotoxicity Assessed in Engineered Cardiac Tissues Generated in Biowire™ II Platform

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Roozbeh Aschar-sobbi ◽  
Julia E Napolitano ◽  
Danielle R Bogdanowicz ◽  
Michael P Graziano
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Resting Membrane Potential ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues

The anthracycline doxorubicin is an effective anti-tumor agent widely used in both adults and children. One major adverse effect of doxorubicin therapy is dose-dependent cardiotoxicity, ranging from asymptomatic reduction in left ventricular ejection fraction to more serious, potentially fatal symptoms including arrythmias and congestive heart failure. The exact mechanism of doxorubicin-induced cardiotoxicity remains unknown. Recently, human induced pluripotent stem cells (hiPSC) have emerged as a potential tool to model cardiac toxicity, but their fetal-like phenotype raises concerns about the translatability of in vitro data to in vivo cardiotoxicity. To overcome this limitation, Biowire™ II platform was used to generate 3D engineered cardiac tissues (ECTs) from hiPSC-derived cardiomyocytes and human cardiac fibroblasts. Using long-term electrical stimulation, ECTs with a phenotype approaching that of adult human myocardium were obtained. The ECTs were then exposed to 1 μM doxorubicin for 8 days followed by 7 days of washout. Measurements of contractile force amplitude at 1 Hz stimulation showed a transient increase in force within 24 hours of doxorubicin exposure followed by decrease in force after 2 days. Intracellular recordings of action potential (AP) showed a decrease in maximum upstroke velocity (dV/dt), AP amplitude (APA), and resting membrane potential (RMP) after 8 days of doxorubicin treatment. In addition, action potential duration (APD) at 30% (APD30) repolarization was increased in doxorubicin-treated ECTs, whereas APD50 and APD90 were decreased. Following 7 days of washout, no difference in force or AP parameters was found between doxorubicin and vehicle-treated ECTs with the exception of APD50 and APD90 which remained abbreviated. A global untargeted analysis of the conditioned media from doxorubicin-treated ECTs identified 204 analytes and revealed an upregulation of redox homeostasis, differential fatty acid metabolism, altered glycolysis and TCA cycle metabolites, and decreased nucleoside metabolism compared to vehicle-treated ECTs. These results show that doxorubicin not only increases oxidative stress, but also irreversibly affects action potential duration which may predispose to cardiac arrhythmias.

Intrinsic cardiac nervous system in tachycardia induced heart failure

2003 ◽  
Vol 285 (5) ◽  
pp. R1212-R1223 ◽  
Author(s):  
Rakesh C. Arora ◽  
René Cardinal ◽  
Frank M. Smith ◽  
Jeffrey L. Ardell ◽  
Louis J. Dell'Italia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Early Stage ◽  
Membrane Properties ◽  
Right Atrial ◽  
Ventricular Pacing ◽  
Chemosensory Transduction ◽  
Efferent Neurons ◽  
Rapid Ventricular Pacing

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered α-or β-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.

scholarly journals Transient Cell Cycle Induction in Cardiomyocytes to Treat Ischemic Heart Failure

2020 ◽  
Author(s):  
Riham Abouleisa ◽  
Qinghui Ou ◽  
Xian-Liang Tang ◽  
Mitesh Solanki ◽  
Yiru Guo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Cycle ◽  
Single Cell ◽  
Left Ventricular ◽  
Metabolic Reprogramming ◽  
Left Ventricular Ejection ◽  
Cardiomyocyte Proliferation ◽  
Ventricular Ejection Fraction ◽  
Control Virus

Abstract The regenerative capacity of the heart after myocardial infarction (MI) is limited. Our previous study showed that ectopic introduction of Cdk1/CyclinB1 and Cdk4/CyclinD1 complexes (4F) promotes cardiomyocyte proliferation in 15-20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after MI. Here, we aim to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. Also, we aim to start the first preclinical testing to introduce 4F gene therapy as a candidate for the treatment of ischemia-induced heart failure. Temporal bulk and single-cell RNAseq and further biochemical validations of mature hiPS-CMs treated with either LacZ or 4F adenoviruses revealed full cell cycle reprogramming in 15% of the cardiomyocyte population after 48 h post-infection with 4F, which was associated with sarcomere disassembly and metabolic reprogramming. Transient overexpression of 4F, specifically in cardiomyocytes, was achieved using a polycistronic non-integrating lentivirus (NIL) encoding the 4F; each is driven by a TNNT2 promoter (TNNT2-4F-NIL). TNNT2-4F-NIL or control virus was injected intramyocardially one week after MI in rats or pigs. TNNT2-4F-NIL treated animals showed significant improvement in left ventricular ejection fraction and scar size compared with the control virus treated animals four weeks post-injection. In conclusion, the present study provides a mechanistic demonstration of the process of forced cardiomyocyte proliferation and advances the clinical feasibility of this approach by minimizing the oncogenic potential of the cell cycle factors using a novel transient and cardiomyocyte-specific viral construct.

Exosomes secreted by hiPSC-derived cardiac cells improve recovery from myocardial infarction in swine

2020 ◽  
Vol 12 (561) ◽  
pp. eaay1318 ◽  
Author(s):  
Ling Gao ◽  
Lu Wang ◽  
Yuhua Wei ◽  
Prasanna Krishnamurthy ◽  
Gregory P. Walcott ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Therapeutic Option ◽  
Wall Stress ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Left Ventricular Ejection ◽  
Cell Group ◽  
Ventricular Ejection Fraction

Cell therapy treatment of myocardial infarction (MI) is mediated, in part, by exosomes secreted from transplanted cells. Thus, we compared the efficacy of treatment with a mixture of cardiomyocytes (CMs; 10 million), endothelial cells (ECs; 5 million), and smooth muscle cells (SMCs; 5 million) derived from human induced pluripotent stem cells (hiPSCs), or with exosomes extracted from the three cell types, in pigs after MI. Female pigs received sham surgery; infarction without treatment (MI group); or infarction and treatment with hiPSC-CMs, hiPSC-ECs, and hiPSC-SMCs (MI + Cell group); with homogenized fragments from the same dose of cells administered to the MI + Cell group (MI + Fra group); or with exosomes (7.5 mg) extracted from a 2:1:1 mixture of hiPSC-CMs:hiPSC-ECs:hiPSC-SMCs (MI + Exo group). Cells and exosomes were injected into the injured myocardium. In vitro, exosomes promoted EC tube formation and microvessel sprouting from mouse aortic rings and protected hiPSC-CMs by reducing apoptosis, maintaining intracellular calcium homeostasis, and increasing adenosine 5′-triphosphate. In vivo, measurements of left ventricular ejection fraction, wall stress, myocardial bioenergetics, cardiac hypertrophy, scar size, cell apoptosis, and angiogenesis in the infarcted region were better in the MI + Cell, MI + Fra, and MI + Exo groups than in the MI group 4 weeks after infarction. The frequencies of arrhythmic events in animals from the MI, MI + Cell, and MI + Exo groups were similar. Thus, exosomes secreted by hiPSC-derived cardiac cells improved myocardial recovery without increasing the frequency of arrhythmogenic complications and may provide an acellular therapeutic option for myocardial injury.

scholarly journals The pacemaker ventricular lead position and outcomes in patients upgrading to crt

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
BV Silva ◽  
J Brito ◽  
T Rodrigues ◽  
P Silverio Antonio ◽  
S Couto Pereira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Pacemaker Implantation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Pacing ◽  
Ventricular Ejection Fraction ◽  
Right Ventricular Pacing ◽  
Ventricular Lead

Abstract Funding Acknowledgements Type of funding sources: None. Introduction   Adverse hemodynamic effects of right ventricular pacing are known, and the optimal right ventricular lead position is still being a matter of debate. According to the guidelines, upgrade to cardiac resynchronization therapy (CRT) is recommended in patients with indication for pacemaker and left ventricular ejection fraction less than 50% or who need more than 40% of ventricular pacing. Purpose   To compare clinical outcomes and ejection fraction in patients with previous pacemaker (apical versus septal right ventricular pacing) who are upgrated to CRT.  Methods   Single-center retrospective study of 94 consecutive patients who had previous pacemaker and upgraded to CRT over a 4-year period. Of these patients, 64 had previous apical lead pacemaker and 30 had previous septal lead pacemaker. Data on comorbidities, New York Heart Association (NYHA), left ventricular ejection fraction and hospitalizations due to heart failure were collected. The results were obtained using Chi-square, Mann-Whitney and t-test. Results Patients with septal pacemaker had significantly more diabetes (p = 0.04) and chronic obstructive pulmonary disease (p = 0.01), tended to be more symptomatic (p = 0.198) and had more days of hospitalization before and after pacemaker implantation (12 ± 3 versus 7 ± 2 days and 8 ± 4 versus 3 ± 1 days, respectively), mostly due heart failure decompensation.  Although there were no significant differences in the initial ejection fraction in patients with apical or septal pacemaker implantation (31.2 ± 1.2% and 29.1 ± 1.5%, respectively, p = 0.323), the time to upgrade to CRT was significantly shorter in patients with septal pacemaker implantation (1999 ± 227 days versus 3005 ± 279 days, p = 0.005).  After upgrading to CRT, patients with apical lead had a significant increase in ejection fraction (8.2%, p = 0.011), while patients with septal lead had a non-significant improvement of ejection fraction (4.5%, p = 0.448). In both, apical and septal lead patients, there was a significant improvement in NYHA class after upgrade to CRT (p = 0.03 and p = 0.02, respectively). Conclusion   Although patients with septal lead had more comorbidities and hospitalizations due to heart failure, they do not benefit from the upgrade to CRT, unlike what happens in patients with apical lead. These findings can be explained by the fact that the septal lead minimizes ventricular desynchrony induced by right ventricular pacing.

scholarly journals Delayed management of atrial lead dislodgment after pacemaker implantation: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Fu Guan ◽  
Guangping Li ◽  
Yong Liu ◽  
Xing Gao ◽  
Rui Zhou
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Sick Sinus Syndrome ◽  
Symptom Relief ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Atrial Pacing ◽  
Ventricular Pacing ◽  
Ventricular Ejection Fraction ◽  
Lead Dislodgement

Abstract Background Pacemaker lead dislodgement may cause malfunction in the pacing system, which may lead to severe adverse events. For patients with sick sinus syndrome but normal atrioventricular conduction, atrial lead dislocation may cause excessive unnecessary ventricular pacing, resulting in nonphysiological pacing leading to heart failure. The longer the unwanted ventricular pacing continues, the greater the chances that irreversible heart failure may occur. Ironically, we admitted a patient who had been refusing dislodged lead relocation for 7 years. The symptoms of heart failure were significantly resolved after new atrial lead implantation. We reviewed her clinical data before and after the procedure and believed the case was worthy of reflection. Case presentation An 83-year-old Han Chinese woman presented with heart failure symptoms for 7 years due to the late macro-dislodgement of an atrial pacing lead. Her echocardiogram showed average left ventricular ejection fraction (LVEF) but reduced left ventricular end-diastolic volume (LVEDV) during right ventricular pacing, indicating heart failure with preserved ejection fraction (HFpEF). After 7 years of refusal, she finally agreed to implantation of a new atrial lead. She has been doing well since the operation. Conclusions For patients with sick sinus syndrome with dual-chamber pacemaker indication, atrial lead dislodgement should be appropriately managed if the atrioventricular function is normal. As the consequences are subtle and appear gradually, they might be overlooked by patients and even doctors. Implanting a new atrial lead is the right thing to do rather than just passively waiting or treating with symptom relief medications.

Efficacy of Vitamin D on Chronic Heart Failure Among Adults

2020 ◽  
Vol 90 (1-2) ◽  
pp. 49-58 ◽  
Author(s):  
Wang Chunbin ◽  
Wang Han ◽  
Cai Lin
Keyword(s):  
Heart Failure ◽  
Vitamin D ◽  
Chronic Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Confidence Interval ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Controlled Trials ◽  
Ventricular Ejection Fraction ◽  
Randomized Controlled

Abstract. Vitamin D deficiency commonly occurs in chronic heart failure. Whether additional vitamin D supplementation can be beneficial to adults with chronic heart failure remains unclear. We conducted a meta-analysis to derive a more precise estimation. PubMed, Embase, and Cochrane databases were searched on September 8, 2016. Seven randomized controlled trials that investigated the effects of vitamin D on cardiovascular outcomes in adults with chronic heart failure, and comprised 592 patients, were included in the analysis. Compared to placebo, vitamin D, at doses ranging from 2,000 IU/day to 50,000 IU/week, could not improve left ventricular ejection fraction (Weighted mean difference, WMD = 3.31, 95% confidence interval, CL = −0.93 to 7.55, P < 0.001, I2 = 92.1%); it also exerts no beneficial effects on the 6 minute walk distance (WMD = 18.84, 95% CL = −24.85 to 62.52, P = 0.276, I2 = 22.4%) and natriuretic peptide (Standardized mean difference, SMD = −0.39, 95% confidence interval CL = −0.48 to 0.69, P < 0.001, I2 = 92.4%). However, a dose-response analysis from two studies demonstrated an improved left ventricular ejection fraction with vitamin D at a dose of 4,000 IU/day (WMD = 6.58, 95% confidence interval CL = −4.04 to 9.13, P = 0.134, I2 = 55.4%). The results showed that high dose vitamin D treatment could potentially benefit adults with chronic heart failure, but more randomized controlled trials are required to confirm this result.

Emerging Cardiac Resynchronisation Therapy Indications

2011 ◽  
Vol 7 (1) ◽  
pp. 29
Author(s):  
Charlotte Eitel ◽  
Gerhard Hindricks ◽  
Christopher Piorkowski ◽  
◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Heart Failure ◽  
Cardiac Resynchronisation Therapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Current Evidence ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Cardiac Resynchronisation ◽  
Resynchronisation Therapy

Cardiac resynchronisation therapy (CRT) is an efficacious and cost-effective therapy in patients with highly symptomatic systolic heart failure and delayed ventricular conduction. Current guidelines recommend CRT as a class I indication for patients with sinus rhythm, New York Heart Association (NYHA) functional class III or ambulatory class IV, a QRS duration ≥120ms, and left ventricular ejection fraction (LVEF) ≤35%, despite optimal pharmacological therapy. Recent trials resulted in an extension of current recommendations to patients with mild heart failure, patients with atrial fibrillation, and patients with an indication for permanent right ventricular pacing with the aim of morbidity reduction. The effectiveness of CRT in patients with narrow QRS, patients with end-stage heart failure and cardiogenic shock, and patients with an LVEF >35% still needs to be proved. This article reviews current evidence and clinical applications of CRT in heart failure and provides an outlook on future developments.

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