Intracellular calcium dynamics in mouse model of myocardial stunning

1998 ◽  
Vol 274 (5) ◽  
pp. H1821-H1827 ◽  
Author(s):  
Thomas G. Hampton ◽  
Ivo Amende ◽  
Kerry E. Travers ◽  
James P. Morgan
Keyword(s):  
Intracellular Calcium ◽  
Myocardial Stunning ◽  
Left Ventricular ◽  
Stunned Myocardium ◽  
Control Group ◽  
Lv Function ◽  
Mouse Heart ◽  
Calmodulin Antagonist ◽  
Myocardial Ischemia And Reperfusion ◽  
Ischemic Contracture

Intracellular calcium ([Formula: see text]) and left ventricular (LV) function were determined in the coronary-perfused mouse heart to study[Formula: see text]-related mechanisms of injury from myocardial ischemia and reperfusion. Specifics for loading of the photoprotein aequorin into isovolumically contracting mouse hearts under constant-flow conditions are provided. The method allows detection of changes in [Formula: see text] on a beat-to-beat basis in a model of myocardial stunning and permits correlation of interventions that regulate Ca2+exchange with functional alterations. Twenty-three coronary-perfused mouse hearts were subjected to 15 min of ischemia followed by 20 min of reperfusion. In 13 hearts, the perfusate included the calmodulin antagonist W7 (10 μM) to inhibit Ca2+-calmodulin-regulated mechanisms. Peak [Formula: see text] was 0.77 ± 0.03 μM in the control group and was unaffected by W7 at baseline. Ischemia was characterized by a rapid decline in LV function, followed by ischemic contracture, accompanied by a gradual rise in[Formula: see text]. Reperfusion was characterized by an initial burst of [Formula: see text] and a gradual recovery to nearly normal systolic[Formula: see text] while LV pressure recovered to 55% after 20 min of reperfusion (stunned myocardium). These results in the mouse heart confirm that stunning does not result from deficiency of [Formula: see text] but rather from a decreased myofilament responsiveness to [Formula: see text] due to changes in the myofilaments themselves. In hearts perfused with W7, the rise in [Formula: see text] during ischemia was significantly attenuated, as was the magnitude of mean[Formula: see text] during early reflow. Ischemic contracture was abolished or delayed. Hearts perfused with W7 showed significantly improved recovery of LV pressure, rate of contraction, and rate of relaxation. Diastolic [Formula: see text]was increased in control hearts during stunning but returned to baseline in hearts perfused with W7. Simultaneous assessment of[Formula: see text] and LV function demonstrates that calmodulin-regulated mechanisms may contribute to the pathogenesis of myocardial stunning in the mouse heart.

Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Endothelial Function ◽  
Training Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Lv Function ◽  
Ventricular Ejection Fraction

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.

Effects of hypoproteinemia-induced myocardial edema on left ventricular function

1998 ◽  
Vol 274 (3) ◽  
pp. H937-H944 ◽  
Author(s):  
M. Miyamoto ◽  
D. E. McClure ◽  
E. R. Schertel ◽  
P. J. Andrews ◽  
G. A. Jones ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Protein Concentration ◽  
Systolic Dysfunction ◽  
Myocardial Edema ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Stroke Work ◽  
Plasma Protein Concentration ◽  
Total Plasma Protein

In previous studies, we observed left ventricular (LV) systolic and diastolic dysfunction in association with interstitial myocardial edema (IME) induced by either coronary venous hypertension (CVH) or lymphatic obstruction. In the present study, we examined the effects of myocardial edema induced by acute hypoproteinemia (HP) on LV systolic and diastolic function. We also combined the methods of HP and CVH (HP-CVH) to determine their combined effects on LV function and myocardial water content (MWC). We used a cell-saving device to lower plasma protein concentration in HP and HP-CVH groups. CVH was induced by inflating the balloon in the coronary sinus. Six control dogs were treated to sham HP. Conductance and micromanometer catheters were used to assess LV function. Contractility, as measured by preload recruitable stroke work, did not change in control or HP groups but declined significantly (14.5%) in the HP-CVH group. The time constant of isovolumic LV pressure decline (τ) increased significantly from baseline by 3 h in the HP (24.8%) and HP-CVH (27.1%) groups. The end-diastolic pressure-volume relationship (stiffness) also increased significantly from baseline by 3 h in the HP (78.6%) and HP-CVH (42.6%) groups. Total plasma protein concentration decreased from 5.2 ± 0.2 g/dl at baseline to 2.5 ± 0.0 g/dl by 3 h in the HP and HP-CVH groups. MWC of the HP (79.8 ± 0.25%) and HP-CVH groups (79.8 ±0.2%) were significantly greater than that of the control group (77.8 ± 0.3%) but not different from one another. In conclusion, hypoproteinemia-induced myocardial edema was associated with diastolic LV dysfunction but not systolic dysfunction. The edema caused by hypoproteinemia was more than twice that produced by our previous models, yet it was not associated with systolic dysfunction. CVH had a negative inotropic effect and no significant influence on MWC. IME may not have the inverse causal relationship with LV contractility that has been previously postulated but appears to have a direct causal association with diastolic stiffness as has been previously demonstrated.

scholarly journals Contractile protein phosphorylation predicts human heart disease phenotypes

2013 ◽  
Vol 304 (12) ◽  
pp. H1644-H1650 ◽  
Author(s):  
Lori A. Walker ◽  
David A. Fullerton ◽  
Peter M. Buttrick
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Protein Phosphorylation ◽  
Protein Phosphatase ◽  
Human Heart ◽  
Troponin I ◽  
Systolic Function ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function

Human heart failure has been associated with a low level of thin-filament protein phosphorylation and an increase in calcium sensitivity of contraction relative to both “control” human heart tissue and tissue from small animal models. However, diverse strategies of human tissue procurement and the reliance on tissue obtained from subjects with end-stage heart failure suggest this may be an incomplete characterization. Therefore, we evaluated cardiac left ventricular (LV) biopsy samples from patients with aortic stenosis undergoing valve replacement who presented either with LV hypertrophy and preserved systolic function (Hyp) or with LV dilation and reduced ejection fraction (Dil). In Hyp, total troponin I (TnI) phosphorylation was markedly increased and myosin light chain 2 (MLC2) phosphorylation was unchanged relative to a control group of patients with normal LV function. Conversely, in Dil, total TnI phosphorylation was significantly reduced compared with control subjects and MLC2 phosphorylation was increased. Site-specific analysis of TnI phosphorylation revealed phenotype-specific differences such that Hyp samples demonstrated significant increases in phosphorylation at serine 22/23 and Dil samples had significant decreases at serine 43. The ratio of phosphorylation at the two sites was biased toward serine 22/23 in Hyp and toward serine 43/45 in Dil. Western blot analysis showed that protein phosphatase-1 was reduced in Hyp and protein phosphatase-2 was reduced in Dil. These data suggest that posttranslational modifications of sarcomeric proteins, both singly and in combination, are stage specific. Defining these changes in progressive heart disease may provide important diagnostic and treatment information.

Abstract P028: The Effect of Cotransplantation of Human Embryonic Stem Cell--Derived Cardiomyocytes and Mesenchymal Stem Cells on Ventricular Function and Remodeling After Myocardial Infarction in Nude Rats

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Wangde Dai ◽  
Mary Kearns-Jonker ◽  
Paul Gerczuk ◽  
Mirja Gunthart ◽  
Nandini Girish ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Saline Group ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Left Ventriculography ◽  
Nude Rats

We determined whether co-transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and mesenchymal stem cells (MSCs) had additive effects on left ventricular (LV) function and remodeling compared with hESC-CMs treatment alone in a rat myocardial infarction model. One week after myocardial infarction induced by left coronary ligation, nude rats received hESC-CMs (n=15), hESC-CMs + MSCs (n=16), hESC-CMs + MSCs transduced to over-express hemeoxygenase 1(HO-1) (n=14), or saline (n=19). At 4 weeks after treatment, LV function was assessed by left ventriculography, echocardiography and Millar catheter. Some hearts were processed for histology. The LV ejection fraction (LVEF) in sham noninfarcted hearts was 78.1±1.8% (n=5) in the nude rat model. LVEF in the 3 cell treated groups (hESC-CMs: 67.6±1.4%; hESC-CMs + MSCs: 67.2±1.6%; and hESC-CMs + MSCs with HO-1: 66.3±1.7%) were comparable, and significantly higher than in the saline group (60.6±1.2%, n=19; p=0.0022). There was a trend for less left ventricular akinesis and dyskinesis (expressed as % of LV circumference) assessed by left ventriculography at 8.96±1.9% in hESC-CMs group, 8.37±1.67% in hESC-CMs + MSCs group and 4.57±1% in hESC-CMs + MSCs with HO-1 group compared to 10.73±1.76% in the control group (p=0.056). There was a nonsignificant trend for LV fractional shortening assessed by echocardiography to be greater in the 3 cell groups (32.1±3.9% in hESC-CMs; 30.2±2% in hESC-CMs + MSCs; 31.0±1.9% in hESC-CMs + MSCs with HO-1) compared to 24.8±2.2% in the saline group (p=0.18). Expansion index reflecting thinning and dilatation of the infarct was significantly worse in the control group at 0.71±0.05 versus the other 3 groups at 0.32±0.05 (p=0.0039). Thus, cell therapy by hESC-CMs alone or combination transplantation of hESC-CMs and MSCs (with or without HO-1) significantly improved LV function assessed by left ventriculography and reduced expansion index. However, co-transplantation of hESC-CMs and MSCs did not provide better functional improvement compared with hESC-CMs treatment alone after left coronary artery occlusion in nude rats over a period of 4 weeks, suggesting that there may be a ceiling effect above which LV function can not further improve after cell therapy.

Excitation-contraction coupling in isolated myocardium from dogs with compensated left ventricular hypertrophy

1994 ◽  
Vol 266 (6) ◽  
pp. H2436-H2442 ◽  
Author(s):  
C. L. Perreault ◽  
R. P. Shannon ◽  
Y. T. Shen ◽  
S. F. Vatner ◽  
J. P. Morgan
Keyword(s):  
Intracellular Calcium ◽  
Pressure Overload ◽  
Phosphodiesterase Inhibitors ◽  
Experimental Models ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Lv Function ◽  
Calcium Modulation ◽  
Contraction Duration ◽  
Calcium Indicator

To examine the relationship between left ventricular (LV) function and intracellular calcium modulation in the presence of myocyte hypertrophy, we compared LV muscles from nine dogs with compensated LV hypertrophy (LVH) induced by chronic aortic banding with 11 controls. Mechanical properties were studied in LV muscles (control, n = 25; LVH, n = 23) stretched to the length at which maximal isometric tension developed at 30 degrees C and stimulated at 0.33 Hz; a subset of LVH muscles was loaded with the intracellular calcium indicator aequorin. In LV myocardium from dogs with compensated LVH, both the contraction duration and calcium transients were prolonged at baseline, and the response to phosphodiesterase inhibitors was impaired in keeping with findings in both human and experimental models of pressure-overload hypertrophy and failure. However, in contrast to findings in the failing myocardium, the positive inotropic response to increasing intracellular calcium was preserved in myocardium from dogs with compensated LVH.

Increases in myocardial cyclic GMP attenuate contractile delay in myocardial stunning

2002 ◽  
Vol 80 (8) ◽  
pp. 804-810 ◽  
Author(s):  
Mark W Huang ◽  
Peter M Scholz ◽  
Harvey R Weiss
Keyword(s):  
Cyclic Gmp ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Control Group ◽  
Wall Thickening ◽  
Maximal Rate ◽  
Myocardial Wall ◽  
New Zealand White Rabbits

We tested the hypothesis that the effects of myocardial stunning would be reduced by cyclic GMP in rabbit hearts. In three groups of anesthetized open-chest New Zealand white rabbits, myocardial stunning was produced by 15 min of occlusion of the left anterior descending coronary artery followed by 15 min of reperfusion repeated twice. Either control vehicle (saline plus 1% dimethyl sulfoxide) or 8-bromo-cyclic GMP (8-Br-cGMP (10–4 and 10–3 M)) was topically applied to the left ventricular surface. Hemodynamic (left ventricular and aortic pressures) and functional parameters (wall thickening, delay in onset of wall thickening, and rate of wall thickening) were determined. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine myocardial O2 consumption (VO2). Myocardial stunning was observed in the control group through an increased delay in onset of myocardial wall thickening (29 ± 7 versus 55 ± 16 ms) and decreased maximal rate of wall thickening (20 ± 8 versus 11 ± 3 mm·s–1). After treatment with 8-Br-cGMP 10–4 and 10–3 M, stunning did not increase the delay (37 ± 5 versus 39 ± 7 and 39 ± 7 versus 28 ± 8 ms). Myocardial stunning did not significantly alter V02. 8-Br-cGMP 10–3 M significantly decreased subepicardial V02 (6.2 ± 0.8 versus 3.7 ± 0.6 mL O2·min–1·100 g–1) and insignificantly decreased subendocardial V02 (8.6 ± 0.9 versus 6.3 ± 1.2 mL O2·min–1·100 g–1) when compared with the vehicle-treated rabbits. We conclude that increasing cyclic GMP reduced the effects of myocardial stunning in the rabbit heart by ameliorating the delay in onset of wall thickening and decreasing the local O2 costs in the stunned region. Key words: cyclic GMP, myocardial stunning, O2 consumption, ischemia, reperfusion, wall thickening, rabbit.

Central Adaptations in Aerobic Circuit Versus Walking/Jogging Trained Cardiac Patients

1995 ◽  
Vol 20 (2) ◽  
pp. 178-197 ◽  
Author(s):  
Leonard S. Goodman ◽  
Donald C. McKenzie ◽  
Colin R. Nath ◽  
Wolfgang Schamberger ◽  
Jack E. Taunton ◽  
...  
Keyword(s):  
Radionuclide Angiography ◽  
Peak Oxygen Uptake ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Circuit Training ◽  
End Diastolic Volume ◽  
Before And After ◽  
Artery Disease ◽  
Systolic And Diastolic Function

This study was done to determine (a) whether in coronary artery disease (CAD) left ventricular (LV) adaptations differed after 6 months of walking/jogging (legs-only, LO) versus aerobic circuit training (arms and legs, AL) versus a control group, and (b) whether a transfer of fitness to the untrained arms in the LO group was related to superior LV adaptations. Peak oxygen uptake for arm and leg ergometry and for cycle ergometry using radionuclide cardiac angiography were performed before and after training. Leg and arm [Formula: see text] peak increased significantly by 13% in the AL group, and by 13% and 7%, respectively, for the LO group. LV function was greater after training for the LO versus the AL group. Improvements in systolic and diastolic function and a speculated hypervolemia explain these LV adaptations. In CAD patients, walking/jogging produces greater LV function improvements versus circuit training, possibly due to differences in the exercised muscle mass. Key words: cardiac rehabilitation, arm and leg ergometry, end-diastolic volume, stroke volume, radionuclide angiography

scholarly journals Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

2020 ◽  
Author(s):  
Runfeng Zhang ◽  
Jiang Yu ◽  
Ningkun Zhang ◽  
Wensong Li ◽  
Jisheng Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
General Hospital ◽  
Myocardial Viability ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
St Segment Elevation ◽  
Lv Ejection Fraction

Abstract Objective: Our aimed to evaluate efficacy and safety of intracoronary autologous bone morrow mesenchymal stem cells (BM-MSCs) transplantation in patients with ST-segment elevation myocardial infarction（STEMI）. Methods: In this randomised, single-blind, controlled trial, patients with STEMI (aged 39-76 years) were enrolled at 6 centers in Beijing (the People's Liberation Army Navy General Hospital, Beijing Armed Police General Hospital, Chinese People's Liberation Army General Hospital, Beijing Huaxin Hospital, Beijing Tongren Hospital, Beijing Chaoyang Hospital West Hospital). Patients underwent optimum medical treatment and percutaneous coronary intervention,and were randomly assigned in a 1:1 ratio to BM-MSCs group or control group. The primary endpoint was change of myocardial viability at 6 months' follow-up and left-ventricular (LV) function at 12 months' follow-up.The secondary endpoints were incidence of cardiovascular event, total mortality and adverse event at 12 months' follow-up. The myocardial viability assessed by single- photon emission tomography (SPECT). The left ventricular ejection fraction was used to assess LV function. All patients underwent dynamic ECG and laboratory evaluations. This trial is registered with ClinicalTrails.gov, number NCT04421274. Results: Between March , 2008, and July , 2010, 43 patients were randomly assigned to BM-MSCs group (n=21)or control group(n=22) and followed up for 12 months. LV ejection fraction increased from baseline to 12 months in the BM-MSCs group and control group ( mean baseline-adjusted BM-MSCs treatment differences in LV ejection fraction 4.8% (SD 9.0) and mean baseline-adjusted control group treatment differences in LV ejection fraction 5.8% (SD 6.04) ). After 6 months of follow-up, there was no significant improvement in myocardial metabolic activity in the BM-MSCs group before and after transplantation. however,there was no statistically significant difference between the two groups in the change of LV ejection fraction (p=0.30) and myocardial metabolic activity(p>0.05). We noticed that ,after 12 months of follow-up, except for 1 death and 1 coronary microvascular embolism in the BM-MSCs group, no other events occurred and Alanine transaminase(ALT) and C-reactive protein(CRP) in BM-MSCs group were significantly lower than that in control group. Conclusions: It is unreasonable to speculate that intracoronary transfer of autologous bone marrow MSCs could augment recovery of LV function and myocardial viability after acute myocardial infarction.Trial registration: clinicaltrials,NCT04421274. Registered 06,08,2020- Retrospectively registered, https://register.clinicaltrials.gov/NCT04421274.

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