scholarly journals Computational Investigation of Transmural Differences in Left Ventricular Contractility

2016 ◽  
Vol 138 (11) ◽  
Author(s):  
Hua Wang ◽  
Xiaoyan Zhang ◽  
Shauna M. Dorsey ◽  
Jeremy R. McGarvey ◽  
Kenneth S. Campbell ◽  
...  
Keyword(s):  
Myocardial Contractility ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Contractile Force ◽  
Left Ventricular ◽  
Lv Function ◽  
Fe Model ◽  
Myocardial Layers ◽  
Best Fit

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.

Abstract 57: Platelet Extracellular-signal-regulated Kinase 5 is a Redox Switch which Regulates Myocardial Infarct Expansion via Matrix Metalloproteinases

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Scott J Cameron ◽  
Sara K Ture ◽  
Deanne Mickelsen ◽  
Enakshi Chakrabarti ◽  
Kristina L Modjeski ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Ex Vivo ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Fluorescent Imaging ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Dependent Manner ◽  
Platelet Receptor

Background: Dysregulated platelet activation in an ischemic microvascular environment may play a role in myocardial infarction (MI). Platelet receptor signaling is well-characterized, but mechanisms of receptor-independent activation, such as by reactive oxygen species (ROS) generated in ischemic conditions, are less well understood. We discovered that ERK5, a nuclear protein which is ROS-activated in others cells, is abundantly present in platelets. We investigated whether ERK5 could regulate platelet activation and thrombosis in healthy and diseased states. Methods: Human and mouse platelets were stimulated with agonists including ADP, U46619, TRAP, convulxin, or ROS (H 2 O 2 or 5% O 2 ). ERK5 activity was assessed by immunoblotting. Platelet activation was assessed via fluorescent-activated cell sorting (FACS) for P-selectin or activated GPIIb/IIIa. Intravascular thrombus (pulmonary embolus) or mesenteric thrombus (oxidative injury) formation was assessed by ex vivo fluorescent imaging and in vivo intravital microscopy, respectively. MI was performed in wild-type (WT) and in platelet specific ERK5 deficient (ERK5 -/- ) mice by LAD coronary artery ligation. Left ventricular (LV) function was determined by echocardiography. Matrix metalloproteinase (MMP) activity was determined by in-gel zymography. Results: Human and platelet ERK5 was activated by ROS and via the thrombin and thromboxane receptors, but not via the purinergic or collagen receptors. Murine in vivo thrombosis was regulated by platelet ERK5 only if the injury involved oxidative stress. MI in mice promoted sustained platelet activation over one week in an ERK5-dependent manner. Following MI, platelet ERK5 -/- mice had less reactive platelets, less platelet MMP activity and thromboxane production, attenuated MMP activity in the LV, less remodeling with smaller infarcts, and enhanced myocardial systolic performance. Conclusions: ERK5 is an ischemic sensor in platelets which regulates ongoing platelet activation after MI as well as remodeling via myocardial microvasculature. These observations may explain ischemic microvascular aberrations like the no-reflow phenomenon following percutaneous coronary intervention, suggesting a novel pharmacologic target.

scholarly journals A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm

2009 ◽  
Vol 131 (11) ◽  
Author(s):  
Kay Sun ◽  
Nielen Stander ◽  
Choon-Sik Jhun ◽  
Zhihong Zhang ◽  
Takamaro Suzuki ◽  
...  
Keyword(s):  
Myocardial Contractility ◽  
Active Material ◽  
Left Ventricular ◽  
Left Ventricular Aneurysm ◽  
Fe Model ◽  
Mr Images ◽  
Material Parameters ◽  
Lv Volumes ◽  
Formal Optimization

A noninvasive method for estimating regional myocardial contractility in vivo would be of great value in the design and evaluation of new surgical and medical strategies to treat and/or prevent infarction-induced heart failure. As a first step toward developing such a method, an explicit finite element (FE) model-based formal optimization of regional myocardial contractility in a sheep with left ventricular (LV) aneurysm was performed using tagged magnetic resonance (MR) images and cardiac catheterization pressures. From the tagged MR images, three-dimensional (3D) myocardial strains, LV volumes, and geometry for the animal-specific 3D FE model of the LV were calculated, while the LV pressures provided physiological loading conditions. Active material parameters (Tmax_B and Tmax_R) in the noninfarcted myocardium adjacent to the aneurysm (borderzone) and in the myocardium remote from the aneurysm were estimated by minimizing the errors between FE model-predicted and measured systolic strains and LV volumes using the successive response surface method for optimization. The significant depression in optimized Tmax_B relative to Tmax_R was confirmed by direct ex vivo force measurements from skinned fiber preparations. The optimized values of Tmax_B and Tmax_R were not overly sensitive to the passive material parameters specified. The computation time of less than 5 h associated with our proposed method for estimating regional myocardial contractility in vivo makes it a potentially very useful clinical tool.

scholarly journals Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Nancy S. Saad ◽  
Steven J. Repas ◽  
Kyle Floyd ◽  
Paul M. L. Janssen ◽  
Mohammad T. Elnakish
Keyword(s):  
Cardiac Hypertrophy ◽  
Ex Vivo ◽  
Antithyroid Drug ◽  
Left Ventricular ◽  
Treatment Withdrawal ◽  
Cardiac Complications ◽  
Lv Function ◽  
Cardiovascular Pathology ◽  
Antithyroid Treatment

Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day), on thyroxine (T4; 500 µg/kg/day)-induced increase in blood pressure (BP), cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV) function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV) contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

scholarly journals Impaired left ventricular mechanical and energetic function in mice after cardiomyocyte-specific excision of Serca2

2014 ◽  
Vol 306 (7) ◽  
pp. H1018-H1024 ◽  
Author(s):  
N. T. Boardman ◽  
J. M. Aronsen ◽  
W. E. Louch ◽  
I. Sjaastad ◽  
F. Willoch ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Left Ventricular ◽  
Lv Function ◽  
Mechanical Function ◽  
Transport Mechanisms ◽  
Working Capacity ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Plasmic Reticulum ◽  
The Relationship

Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2 transports Ca2+ from the cytosol into the sarcoplasmic reticulum of cardiomyocytes and is essential for maintaining myocardial Ca2+ handling and thus the mechanical function of the heart. SERCA2 is a major ATP consumer in excitation-contraction coupling but is regarded to contribute to energetically efficient Ca2+ handling in the cardiomyocyte. Previous studies using cardiomyocyte-specific SERCA2 knockout (KO) mice have demonstrated that decreased SERCA2 activity reduces the Ca2+ transient amplitude and induces compensatory Ca2+ transport mechanisms that may lead to more inefficient Ca2+ transport. In this study, we examined the relationship between left ventricular (LV) function and myocardial O2 consumption (MV̇o2) in ex vivo hearts from SERCA2 KO mice to directly measure how SERCA2 elimination influences mechanical and energetic features of the heart. Ex vivo hearts from SERCA2 KO hearts developed mechanical dysfunction at 4 wk and demonstrated virtually no working capacity at 7 wk. In accordance with the reported reduction in Ca2+ transient amplitude in cardiomyocytes from SERCA2 KO mice, work-independent MV̇o2 was decreased due to a reduced energy cost of excitation-contraction coupling. As these hearts also showed a marked impairment in the efficiency of chemomechanical energy transduction (contractile efficiency, i.e, work-dependent MV̇o2), hearts from SERCA2 KO mice were found to be mechanically inefficient. This ex vivo evaluation of mechanical and energetic function in hearts from SERCA2 KO mice brings together findings from previous experimental and mathematical modeling-based studies and demonstrates that reduced SERCA2 activity not only leads to mechanical dysfunction but also to energetic dysfunction.

Abstract 27: ApoA-I Improves Lymphatic Function Through a Platelet-Dependent Mechanism in Atherosclerotic Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
François Dallaire ◽  
Gabriel Jean ◽  
Jean-Claude Tardif ◽  
Yahye Merhi ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymphatic Transport ◽  
Lv Function ◽  
Experimental Conditions ◽  
Lymphatic Function ◽  
Beneficial Effects ◽  
Dependent Mechanism

Rationale: Lymphatic vessels (LVs) are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and a particular attention has been brought on the role of the collecting LVs in early atherosclerosis-related lymphatic dysfunction. Whereas recent findings revealed that apoA-I restores the neovascularization capacity of the lymphatic system during tumor necrosis factor-induced inflammation, the effect of apoA-I on collecting LV function during atherosclerosis has not been tested. Objective: In the present study, we address whether and how apoA-I can enhance collecting LV function in atherosclerosis-associated lymphatic dysfunction. Methods and Results: A 6-week systemic treatment with lipid-free apoA-I enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr –/– mice when compared to control. As injection of apoA-I has been shown to protect wild-type mice against flow restriction-induced thrombosis, and that platelets are identified as key elements in the maintenance of lymphatic vessel integrity via their interaction with lymphatic endothelial cells (LECs), we have tested whether the effects of apoA-I could be mediated through a platelet-dependent mechanism. Our in vivo results show that apoA-I kinetics in lymph reflected that of blood. Ex vivo experiments performed with washed platelets isolated from mouse blood reveal that apoA-I decreased thrombin-induced but not podoplanin-induced platelet aggregation. Whereas this result suggests that apoA-I limits platelet thrombotic potential in blood but not in lymph, we demonstrate that treatment of human LECs with apoA-I increases the adhesion of bridge-like platelets on human LECs. Conclusions: Our results suggest that apoA-I can mediate beneficial effects on lymphatic function by promoting platelet adhesion to the lymphatic endothelium and consequently restore collecting LV integrity. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

Doppler measurement of myocardial thickening with a single epicardial transducer

1983 ◽  
Vol 245 (6) ◽  
pp. H1066-H1072 ◽  
Author(s):  
C. J. Hartley ◽  
L. A. Latson ◽  
L. H. Michael ◽  
C. L. Seidel ◽  
R. M. Lewis ◽  
...  
Keyword(s):  
Transit Time ◽  
Sample Volume ◽  
Left Ventricular ◽  
Segment Length ◽  
Lv Function ◽  
Wall Thickening ◽  
Doppler Measurement ◽  
Time Segment ◽  
Doppler Technique ◽  
Myocardial Layers

To eliminate the need for intramyocardial transducers in measuring regional left ventricular (LV) function we have developed a pulsed Doppler technique utilizing a single epicardial transducer. Wall thickening is evaluated by digitally integrating the velocity of myocardial layers passing through the sample volume located at a selected depth. Thickening fraction (TF) can then be estimated by dividing the systolic excursion by the sample volume depth. The Doppler method was compared with the transit-time method in three acute dogs by placing the 4-mm-diameter epicardial Doppler transducer over a 2-mm-diameter endocardial crystal tunneled through the LV wall. With the sample volume set to 1 mm less than the minimum LV thickness, simultaneous measurements of TF by the Doppler and transit-time methods showed good agreement (r = 0.95) during control, ischemia, volume overload, shock, and anoxia. In 28 chronically instrumented piglets signals were obtained for longer periods with Doppler transducers than with transit-time segment-length crystals. We conclude that the Doppler technique provides a high-fidelity wall thickening waveform and a good estimate of TF with minimal disturbance to the ventricle and that the technique is suitable for use in both acute and chronically instrumented animals.

scholarly journals A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies

2018 ◽  
Vol 44 (2) ◽  
pp. E13 ◽  
Author(s):  
Goutam Ghoshal ◽  
Lucy Gee ◽  
Tamas Heffter ◽  
Emery Williams ◽  
Corinne Bromfield ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Minimally Invasive ◽  
Focused Ultrasound ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Rodent Model ◽  
Therapeutic Interventions ◽  
Porcine Liver

OBJECTIVEMinimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator.METHODSUsing an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson’s disease to investigate the feasibility of its application in brain.RESULTSThermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson’s disease.CONCLUSIONSThe authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

scholarly journals Acute impact of changes to hemodynamic load on the left ventricular strain-volume relationship in young and older men

2020 ◽  
Vol 318 (4) ◽  
pp. R743-R750 ◽  
Author(s):  
Hugo G. Hulshof ◽  
Arie P. van Dijk ◽  
Maria T. E. Hopman ◽  
Chris F. van der Sluijs ◽  
Keith P. George ◽  
...  
Keyword(s):  
Older Men ◽  
Left Ventricular ◽  
Lv Function ◽  
Diastolic Phase ◽  
Early Diastole ◽  
Volume Relationship ◽  
Acute Increase ◽  
Dimensional Echocardiography ◽  
Two Dimensional Echocardiography

Chronic changes in left ventricular (LV) hemodynamics, such as those induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof of concept that 1) the LV longitudinal strain (ε)-volume loop is sensitive to detecting an acute increase in afterload, and 2) these effects differ between healthy young versus older men. Thirty-five healthy male volunteers were recruited, including 19 young (24 ± 2 yr) and 16 older participants (67 ± 5 yr). Tests were performed before, during, and after 10-min recovery from acute manipulation of afterload. Real-time hemodynamic data were obtained and LV longitudinal ε-volume loops were calculated from four-chamber images using two-dimensional echocardiography. Inflation of the anti-gravity (anti-G) suit resulted in an immediate increase in heart rate, blood pressure, and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). This was accompanied by a decrease in LV peak ε, slower slope of the ε-volume relationship during early diastole, and an increase in uncoupling (i.e., compared with systole; little change in ε per volume decline during early diastole and large changes in ε per volume decline during late diastole) (all P < 0.05). All values returned to baseline levels after recovery (all P > 0.05). Manipulation of cardiac hemodynamics caused comparable effects in young versus older men (all P > 0.05). Acute increases in afterload immediately change the diastolic phase of the LV longitudinal ε-volume loop in young and older men. This supports the potency of the LV longitudinal ε-volume loop to provide novel insights into dynamic cardiac function in humans in vivo.

scholarly journals Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3471
Author(s):  
Fatima Saqib ◽  
Muhammad Arif Aslam ◽  
Khizra Mujahid ◽  
Luigi Marceanu ◽  
Marius Moga ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Ex Vivo ◽  
Inflammatory Cells ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Sprague Dawley ◽  
Positive Effects ◽  
Creatine Kinase Mb

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases

Positive Inotropic and Lusitropic Effects of Triiodothyronine in Conscious Dogs with Pacing-induced Cardiomyopathy 

1997 ◽  
Vol 87 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Iyad N. Jamali ◽  
Paul S. Pagel ◽  
Douglas A. Hettrick ◽  
Dermot Lowe ◽  
Judy R. Kersten ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Contractility ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Segment Length ◽  
Lv Function ◽  
Baseline Heart Rate ◽  
Stroke Work ◽  
Lv Dysfunction

Background The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs. Methods Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated. Results T3 produced immediate and sustained (24 h) increases (P &lt; 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs. Conclusions The findings indicate that T3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious dogs with LV dysfunction produced by rapid LV pacing.

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