Parameters Of Left Ventricular Contractility Research Articles

Left ventricular mechanical dyssynchrony after chemotherapy in breast cancer patients with normal rest gated SPECT-MPI.

Early diagnosis of chemotherapy-induced cardiotoxicity plays an important role in preventing heart failure. The main aim of our study was to assess left ventricular (LV) dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) as an early sign of cardiotoxicity after breast cancer chemotherapy. This cross-sectional study was conducted on patients with stage ≤ 3 breast cancer and no history of cardiovascular disease or diabetes. After mastectomy, the patients underwent rest gated SPECT myocardial perfusion imaging (MPI). Sixty patients with normal gated SPECT-MPI were selected and the imaging was performed after chemotherapy with doxorubicin, cyclophosphamide and paclitaxel. LV function and contractility parameters were extracted by QGS software and the results were compared with the t test method. The abnormality of at least one of the three phase analysis indices was considered as left ventricular dyssynchrony (LVD). The average LV end-systolic volume and ejection fraction (LVEF) before and after chemotherapy were (16.2 ± 8.0ml and 21.6 ± 11.6ml) and (73.4 ± 7.9% and 67.5 ± 9.2%) respectively, which showed a significant decrease (P < 0.05). In 2 patients (3.3%), the LVEF decreased to less than 50% after chemotherapy. The average parameters of left ventricular contractility before and after chemotherapy were, respectively, as follows: PHB (24.1 ± 7.5 and 33.8 ± 16.4), PSD (9.4 ± 6.1 and 5.7 ± 1.9) and entropy (28.9 ± 7.1 and 35.6 ± 9.7), which showed a significant increase (P < 0.05). LVD was observed in 14 patients (23.4%) after chemotherapy and prevalence of LVD was significantly higher in patients who had received a cumulative dose of doxorubicin of more than 400mg/m2 (P = 0.005). There was no relationship between age and body mass index with the incidence of LVD after chemotherapy (P > 0.05). Using phase analysis of gated SPECT-MPI, chemotherapy-induced LVD was seen in a significant number of patients with breast cancer, especially with a high cumulative dose of doxorubicin. LVD might indicate chemotherapy-induced cardiotoxicity before LVEF becomes abnormal.

Is perfusion index a surrogate indicator of left ventricular contractility in neonates? A prospective study.

Noninvasive blood pressure monitoring may not accurately reflect cardiac contractility in neonates due to low vascular tone. The perfusion index (PI) is a noninvasive method of assessing the strength of peripheral pulses. It is shown to have a significant correlation with the left ventricular output. This prospective study estimates the correlation between PI and cardiac contractility in neonates. All hemodynamically stable neonates who were on substantial enteral feeds and not on any respiratory or inotropic support underwent measurement of PI and echocardiography examination. Various indices of left ventricular contractility were estimated, and the correlation coefficient between them and PI was determined. Fifty-six neonates were studied. The median (interquartile range [IQR]) PI was 1.5 (1.25-1.75). The median (IQR) PI in preterm neonates was 1.5 (1.2-1.8) and that in term neonates was 1.8 (1.25-2.7) (P = 0.064). PI had a correlation of 0.205 with fractional shortening (P = 0.129) and 0.13 with left ventricular ejection fraction (P = 0.821). The Spearman's correlation coefficient between PI and velocity of circumference fiber shortening was 0.009 (P = 0.945). The Spearman's correlation coefficient between PI and cardiac output was -0.115 (P = 0.400). The PI does not correlate with left ventricular contractility parameters in neonates.

P912 Echocardiographic analysis of acute effects after treatment of functional mitral regurgitation by percutaneous mitral annuloplasty

Abstract Background Secondary or functional mitral regurgitation (FMR) is associated with increased morbidity and mortality, especially in heart failure patients, patients with many comorbidities and/or in the elderly. Previous studies about percutaneous mitral annuloplasty have shown evidence for long-term reduction of degree of FMR severity and left ventricular (LV) remodeling. In comparison to previous studies the present study did focus on the echocardiographic analysis of acute effects after percutaneous mitral annuloplasty (PMA). Methods Transthoracic echocardiography (TTE) has been performed in 30 patients with moderate or severe FMR before and after (± 3.5 days) percutaneous mitral annuloplasty (Carillon®). LV volumes and LV ejection fraction and semi-quantitative parameters, e.g. tenting Area, vena contracta and velocity-time-integral ratios of transmitral inflow and LV outflow (VTIMV/VTILVOT) were assessed. The assessment of the regurgitant volume (RV), regurgitant fraction (RF) and effective regurgitant orifice area (EROA) was quantitatively performed by the PISA method. RV and RF was also estimated by subtracting the effective forward stroke volume (SVLVOT, SVRVOT) from the total stroke volume (SVLV planimetry). Further, parameters of left ventricular contractility, e.g. global longitudinal strain (GLS), cardiac efficiency, peak power index etc., were assessed. Results a postinterventional reduction of degree of FMR severity was achieved in 25/30 patients (83%). In average, RF was reduced from 49 ± 11% to 34 ± 13% (p &amp;lt; 0.001), RV from 33 ± 13ml to 25 ± 12ml (p &amp;lt; 0.001) and EROA from 0.24 ± 0.1cm2 to 0.19 ± 0.1cm2 (p &amp;lt; 0.05). Significant decreases were also noted for vena contracta and VTIMV/LVOT. DiamMV (long axis) was reduced from 3.6 ± 0.6cm to 3.4± 0.6cm (p &amp;lt; 0.001), DiamMV (4-chamber view) from 3.9 ± 0.5cm to 3.6 ± 0.6cm (p &amp;lt; 0 .05). In patients with sinus rhythm (SR) or pacemacer stimulation a considerably higher reduction of RF was observed (ΔRF 20 ± 12%) in comparison to patients with atrial fibrillation (ΔRF 10 ± 12%). No significant changes were obtained for parameters of LV remodeling and LV contractility, e.g. GLS, cardiac efficiency, peak power index. Conclusion A reduction of degree of FMR severity can be achieved by percutaneous mitral annuloplasty (PMA) and acute effects can be quantitatively assessed by echocardiography. Further data are necessary to evaluate whether these acute effects will maintain in follow-up investigations. Abstract P912 Figure. Fig1-Reduction of RF and VC after PMA

The Implementation of an Adjustable Afterload Module for Ex Situ Heart Perfusion.

Windkessel impedance analysis has proven to be an effective technique for instituting artificial afterload on ex situ hearts. Traditional fixed parameter afterload modules, however, are unable to handle the changing contractile conditions associated with prolonged ex situ heart perfusion. In this paper, an adjustable afterload module is described comprising of three fully adjustable sub-components: a systemic resistor, a proximal resistor and a compliance chamber. Using a centrifugal pump, the systemic resistor and compliance chamber were subjected to testing across their operating ranges, whereby the predictability of resistance and compliance values was evaluated. The components were then assembled, and the full module tested on three separate porcine hearts perfused for 6h with success defined by the ability to maintain physiological systolic and diastolic aortic pressures across flow rate variability. For both the systemic resistor and compliance chamber, experimental measurements agreed with their theoretical equivalents, with coefficients of determination of 0.99 and 0.97 for the systemic resistor and compliance chamber, respectively. During ex situ perfusion, overall 95% confidence intervals demonstrate that physiological systolic (95-96.21mmHg) and diastolic (26.8-28.8mmHg) pressures were successfully maintained, despite large variability in aortic flow. Left ventricular contractile parameters, were found to be in line with those in previous studies, suggesting the afterload module has no detrimental impact on functional preservation. We conclude that due to the demonstrable control of our afterload module, we can maintain physiological aortic pressures in a passive afterload working mode across prolonged perfusion periods, enabling effective perfusion regardless of contractile performance.

Myofilament Ca2+ sensitivity correlates with left ventricular contractility during the progression of pressure overload-induced left ventricular myocardial hypertrophy in rats

AimHere we aimed at investigating the relation between left ventricular (LV) contractility and myofilament function during the development and progression of pressure overload (PO)-induced LV myocardial hypertrophy (LVH). MethodsAbdominal aortic banding (AB) was performed to induce PO in rats for 6, 12 and 18 weeks. Sham operated animals served as controls. Structural and molecular alterations were investigated by serial echocardiography, histology, quantitative real-time PCR and western blot. LV function was assessed by pressure-volume analysis. Force measurement was carried out in permeabilized cardiomyocytes. ResultsAB resulted in the development of pathological LVH as indicated by increased heart weight-to-tibial length ratio, LV mass index, cardiomyocyte diameter and fetal gene expression. These alterations were already present at early stage of LVH (AB-week6). Furthermore, at more advanced stages (AB-week12, AB-week18), myocardial fibrosis and chamber dilatation were also observed. From a hemodynamic point of view, the AB-wk6 group was associated with increased LV contractility, maintained ventriculo-arterial coupling (VAC) and preserved systolic function. In the same experimental group, increased myofilament Ca2+ sensitivity (pCa50) and hyperphosphorylation of cardiac troponin-I (cTnI) at Threonine-144 was detected. In contrast, in the AB-wk12 and AB-wk18 groups, the initial augmentation of LV contractility, as well as the increased myofilament Ca2+ sensitivity and cTnI (Threonine-144) hyperphosphorylation diminished, leading to impaired VAC and reduced systolic performance. Strong correlation was found between LV contractility parameters and myofilament Ca2+-sensitivity among the study groups. ConclusionChanges in myofilament Ca2+ sensitivity might underlie the alterations in LV contractility during the development and progression of PO-induced LVH.

Use of the Speckle tracking method for determining global parameters of heart contractility in healthy individuals

The speckle tracking method allows one to quantify the temporal and spatial characteristics of myocardial contraction. Importantly, it does not depend on a scanning angle and allows one to record the movement of speckles in 2D mode in any direction, unlike tissue Doppler imaging. This examination is non-invasive, safe for patients, and economically more beneficial in comparison with other modern methods of assessing heart contractility: MRI and scintigraphy. Diagnostic thresholds are suggested for obtaining peak values of all types of global strains and strain rates by sampling a healthy group, which can reveal early signs of left ventricle contractility failure. Correlation relationships of deformation parameters between themselves and with left ventricular hemodynamic indices, as well as anthropometric parameters in healthy subjects highlight the features of heart contraction biomechanics. However, currently this method is scarcely studied because no generally accepted normal range of strain values exists.•It is necessary to have sufficient qualification and skills in dealing with the XStrain™ Esaote software to obtain optimal values ??of myocardial deformation.•The study results expand the database of this software for users and determine the normal range of the left ventricular contractility parameters.•The revealed interrelationships of strain values ??in healthy individuals are relevant for understanding how the contractility mechanisms are altered in patients, and open up the prospect of studying the heart’s compensatory possibilities.

Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart.

Previous results from our laboratory showed that phosphorylation of ryanodine receptor 2 (RyR2) by Ca(2+) calmodulin-dependent kinase II (CaMKII) was a critical but not the unique event responsible for the production of reperfusion-induced arrhythmogenesis, suggesting the existence of other mechanisms cooperating in an additive way to produce these rhythm alterations. Oxidative stress is a prominent feature of ischemia/reperfusion injury. Both CaMKII and RyR2 are proteins susceptible to alteration by redox modifications. This study was designed to elucidate whether CaMKII and RyR2 redox changes occur during reperfusion and whether these changes are involved in the genesis of arrhythmias. Langendorff-perfused hearts from rats or transgenic mice with genetic ablation of CaMKII phosphorylation site on RyR2 (S2814A) were subjected to ischemia-reperfusion in the presence or absence of a free radical scavenger (mercaptopropionylglycine, MPG) or inhibitors of NADPH oxidase and nitric oxide synthase. Left ventricular contractile parameters and monophasic action potentials were recorded. Oxidation and phosphorylation of CaMKII and RyR2 were assessed. Increased oxidation of CaMKII during reperfusion had no consequences on the level of RyR2 phosphorylation. Avoiding the reperfusion-induced thiol oxidation of RyR2 with MPG produced a reduction in the number of arrhythmias and did not modify the contractile recovery. Conversely, selective prevention of S-nitrosylation and S-glutathionylation of RyR2 was associated with higher numbers of arrhythmias and impaired contractility. In S2814A mice, treatment with MPG further reduced the incidence of arrhythmias. Taken together, the results suggest that redox modification of RyR2 synergistically with CaMKII phosphorylation modulates reperfusion arrhythmias.

Early Hemodynamic Improvement after Percutaneous Mitral Valve Repair Evaluated by Noninvasive Pressure-Volume Analysis

Mitral regurgitation represents a volume load on the left ventricle leading to congestion and symptoms of heart failure. The aim of this study was to characterize early hemodynamic adaptions after percutaneous mitral valve (MV) repair. Forty-six consecutive patients with symptomatic high-grade MV insufficiency (mean age, 72years; 54% men) were prospectively included in the study and examined before and after successful catheter-based clip implantation. Seventy percent of patients had secondary mitral regurgitation. Noninvasive pressure-volume loops were reconstructed from echocardiography with simultaneous blood pressure measurements. MV repair reduced left ventricular end-diastolic volume index from 87±41 to 80±40mL/m(2) (P<.0001). End-systolic volume index was 55±37mL/m(2) before versus 54±37mL/m(2) after repair (P=.52). Hence, total stroke volume decreased from 60±23 to 49±16mL (P<.0001), as did total ejection fraction (from 41±14% to 37±13%, P=.002) and global longitudinal strain (from -11±4.9% to -9.1±4.4%, P=.0001). Forward stroke volume, forward ejection fraction, and forward cardiac output remained constant (43±12mL vs 42±11mL, 33±17% vs 35±18%, and 3.2±0.9L/min vs 3.4±0.8L/min, respectively). Parameters of left ventricular contractility (end-systolic elastance and peak power index) and measurements of afterload (arterial elastance, end-systolic wall stress, and total peripheral resistance) were similar before and after MV repair. Forward ejectionfraction correlated more strongly with end-systolic elastance (r=0.61, P<.0001) than did total ejection fraction (r=0.35, P=.0007) or global longitudinal strain (r=-0.38, P=.0002). Total mechanical energy (pressure-volume area) decreased from10,903±4,410 to 9,124±2,968mmHg×mL (P=.0007) because of reduced stroke work (5,546±2,241mmHg×mL vs 4,414±1,412mmHg×mL, P<.0001). At 3months, symptom statushad improved (76% of patients in New York Heart Association classes I and II), and 97% of patients had mitral regurgitation grade ≤2+. Left ventricular contractility and forward cardiac output remained unchanged after percutaneous MV repair despite decreases in total ejection fraction and global longitudinal strain. The left ventricle was unloaded through reduced end-diastolic volume. Thus, MV repair is associated with an improved hemodynamic state in noninvasive pressure-volume analysis.

Hypothermic continuous machine perfusion enables preservation of energy charge and functional recovery of heart grafts in an ex vivo model of donation following circulatory death.

Cardiac transplantation using hearts from donors after circulatory death (DCD) is critically limited by the unavoidable warm ischaemia and its related unpredictable graft function. Inasmuch as hypothermic machine perfusion (MP) has been shown to improve heart preservation, we hypothesized that MP could enable the use of DCD hearts for transplantation. We recovered 16 pig hearts following anoxia-induced cardiac arrest and cardioplegia. Grafts were randomly assigned to two different groups of 4-h preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems©, Itasca, Il). After preservation, the grafts were reperfused ex vivo using the Langendorff method for 60 min. Energetic charge was quantified at baseline, post-preservation and post-reperfusion by measuring lactate and high-energy phosphate levels. Left ventricular contractility parameters were assessed both in vivo prior to ischaemia and ex vivo during reperfusion. Following preservation, the hearts that were preserved using CS exhibited higher lactate levels (57.1 ± 23.7 vs 21.4 ± 12.2 µmol/g; P < 0.001), increased adenosine monophosphate/adenosine triphosphate ratio (0.53 ± 0.25 vs 0.11 ± 0.11; P < 0.001) and lower phosphocreatine/creatine ratio (9.7 ± 5.3 vs 25.2 ± 11; P < 0.001) in comparison with the MP hearts. Coronary flow was similar in both groups during reperfusion (107 ± 9 vs 125 ± 9 ml/100 g/min heart; P = ns). Contractility decreased in the CS group, yet remained well preserved in the MP group. MP preservation of DCD hearts results in improved preservation of the energy and improved functional recovery of heart grafts compared with CS.

Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes.

We recently demonstrated that the pre-treatment of rats with zinc and acetylsalicylic acid complex in the form of bis(aspirinato)zinc(II) [Zn(ASA)2] is superior to acetylsalicylic acid in protecting the heart from acute myocardial ischemia. Herein, we hypothesized that Zn(ASA)2 treatment after the onset of an acute myocardial injury could protect the heart. The rats were treated with a vehicle or Zn(ASA)2 after an isoproterenol injection. Isoproterenol-induced cardiac damage [inflammatory infiltration into myocardial tissue, DNA-strand breakage evidenced by TUNEL-assay, increased 11-dehydro thromboxane (TX)B2-levels, elevated ST-segment, widened QRS complex and prolonged QT-interval] was prevented by the Zn(ASA)2 treatment. In isoproterenol-treated rats, load-independent left ventricular contractility parameters were significantly improved after Zn(ASA)2. Furthermore, Zn(ASA)2 significantly increased the myocardial mRNA-expression of superoxide dismutase-1, glutathione peroxidase-4 and decreased the level of Na(+)/K(+)/ATPase. Postconditioning with Zn(ASA)2 protects the heart from acute myocardial ischemia. Its mechanisms of action might involve inhibition of pro-inflammatory prostanoids and upregulation of antioxidant enzymes.

Effects of glucagon-like peptide-1 agents on left ventricular function: Systematic review and meta-analysis

Background. The cardiovascular safety of many glucagon-like peptide-1 agents (GLP-1 agents) is unclear. In this study, we assess the effects of the GLP-1 agents on left ventricular function in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD).Methods. PubMed, EMBASE, and the Cochrane Library were searched for the relevant publications up to May 2013 without restriction by language. All clinical controlled trials assessing left ventricular function and cardiovascular outcomes with the GLP-1 agents were selected for eligibility. Fourteen trials (415 patients) were identified as eligible between 1966 and 2013. Twelve of the studies were randomized controlled trials (RCT).Results. The results showed that GLP-1 agent treatment in patients with T2DM and/or CVD led to significantly improved regional left ventricular contractile parameters (including peak left systolic tissue velocity and strain) and global left ventricular performance (including stroke volume, ejection fraction, and left ventricular chambers) compared with patients receiving placebo.Conclusions. GLP-1 agent treatment in T2DM and/or CVD patients is associated with a modest but significant increase in the odds of left ventricular contractile parameters and left ventricular performance compared with patients having received placebo, which may be indicative of additional cardiovascular benefits for these patients.

Hyperbilirubinemia modulates myocardial function, aortic ejection, and ischemic stress resistance in the Gunn rat.

Mildly elevated circulating unconjugated bilirubin (UCB) is associated with protection against hypertension and ischemic heart disease. We assessed whether endogenously elevated bilirubin in Gunn rats modifies cardiovascular function and resistance to ischemic insult. Hearts were assessed ex vivo (Langendorff perfusion) and in vivo (Millar catheterization and echocardiography), and left ventricular myocardial gene expression was measured via quantitative real-time PCR. Ex vivo analysis revealed reduced intrinsic contractility in the Gunn myocardium (+dP/dt: 1,976 ± 622 vs. 2,907 ± 334 mmHg/s, P < 0.01; -dP/dt: -1,435 ± 372 vs. -2,234 ± 478 mmHg/s, P < 0.01), which correlated positively with myocardial UCB concentration (P < 0.05). In vivo analyses showed no changes in left ventricular contractile parameters and ejection (fractional shortening and ejection fraction). However, Gunn rats exhibited reductions in the rate of aortic pressure development (3,008 ± 461 vs. 4,452 ± 644 mmHg/s, P < 0.02), mean aortic velocity (439 ± 64 vs. 644 ± 62 mm/s, P < 0.01), and aortic volume time integral pressure gradient (2.32 ± 0.65 vs. 5.72 ± 0.74 mmHg, P < 0.01), in association with significant aortic dilatation (12-24% increase in aortic diameter, P < 0.05). Ex vivo Gunn hearts exhibited improved ventricular function after 35 min of ischemia and 90 min of reperfusion (63 ± 14 vs. 35 ± 12%, P < 0.01). These effects were accompanied by increased glutathione peroxidase and reduced superoxide dismutase and phospholamban gene expression in Gunn rat myocardium (P < 0.05). These data collectively indicate that hyperbilirubinemia in Gunn rats 1) reduces intrinsic cardiac contractility, which is compensated for in vivo; 2) induces aortic dilatation, which may beneficially influence aortic ejection velocities and pressures; and 3) may improve myocardial stress resistance in association with beneficial transcriptional changes. These effects may contribute to protection from cardiovascular disease with elevated bilirubin.

Tempol prevents cardiac oxidative damage and left ventricular dysfunction in the PPAR-α KO mouse

Peroxisome proliferator-activated receptor (PPAR)-α deletion induces a profound decrease in MnSOD activity, leading to oxidative stress and left ventricular (LV) dysfunction. We tested the hypothesis that treatment of PPAR-α knockout (KO) mice with the SOD mimetic tempol prevents the heart from pathological remodelling and preserves LV function. Twenty PPAR-α KO mice and 20 age-matched wild-type mice were randomly treated for 8 wk with vehicle or tempol in the drinking water. LV contractile parameters were determined both in vivo using echocardiography and ex vivo using papillary muscle mechanics. Translational and posttranslational modifications of myosin heavy chain protein as well as the expression and activity of major antioxidant enzymes were measured. Tempol treatment did not affect LV function in wild-type mice; however, in PPAR-α KO mice, tempol prevented the decrease in LV ejection fraction and restored the contractile parameters of papillary muscle, including maximum shortening velocity, maximum extent of shortening, and total tension. Moreover, compared with untreated PPAR-α KO mice, myosin heavy chain tyrosine nitration and anion superoxide production were markedly reduced in PPAR-α KO mice after treatment. Tempol also significantly increased glutathione peroxidase and glutathione reductase activities (~ 50%) in PPAR-α KO mice. In conclusion, these findings demonstrate that treatment with the SOD mimetic tempol can prevent cardiac dysfunction in PPAR-α KO mice by reducing the oxidation of contractile proteins. In addition, we show that the beneficial effects of tempol in PPAR-α KO mice involve activation of the glutathione peroxidase/glutathione reductase system.

Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

BackgroundUnder conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs). They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3)-induced myocarditis.Methodology/Principal FindingsTo evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR) and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression.ConclusionsWe conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

331 Effect of acute hypoxia on left ventricular twist assessed by speckle tracking imaging

The impact of hypoxia on left ventricular (LV) myocardial contractility remains debated. Objectives: We hypothesized that acute hypoxia in healthy people increases LV twist as a consequence of the cardiovascular adaptation to stress (increased sympathetic nerve activity). Because hypoxia increases heart rate, we aimed to control for this change by studying the same subjects under atropine during normoxia. We studied 21 subjects (mean age: 27 ± 7 years) without medical history. Echocardiography was performed in normoxia and after 30 minutes of hypoxia (12% FiO 2 ). Short axis basal and apical views were analyzed using speckle tracking software. LV twist was defined as the net difference between the apical and basal rotation. The effect of atropine on LV twist was tested in the same subjects under normoxia. As expected, hypoxic breathing decreased arterial saturation in oxygen below 80% (table). Peak LV twist increased, as did heart rate, LV ejection fraction (LVEF) and systolic mitral annular velocity. Despite a decrease in mitral E/A ratio, early diastolic LV untwisting (at 5%, 10% and 15% of diastole) was not significantly modified under hypoxia. Atropine did not alter peak systolic twist (8.9 ± 3.1° versus 10.1 ± 2.6°, p = 0.09, without and with atropine, respectively), despite an increase in heart rate (from 64 ± 11 to 77 ± 11 beats/min, p = 0.0001). Acute hypoxia increases LV twist as well as other parameters of LV contractility. This change in LV twist does not result from the chronotropic effect of hypoxia. Values are means (SD) Normoxia Hypoxia p value SaO 2 (%) 97 (1.3) 76 (7.8) 0.0001 Heart rate (beats/min) 64 (11) 70 (9) 0.008 LVEF (%) 65 (5) 68 (7) 0.011 Systolic mitral annular velocity (cm/s) 8.0 (1.1) 8.7 (1.4) 0.03 E/A 2.1 (0.6) 1.8 (0.4) 0.015 Peak LV twist ( ° ) 8.9 (3.1) 11.1(2.8) 0.003

The Initial Tangent of the Aortic Pressure Increase is an Estimate of Left Ventricular Contractility in Pigs

The aim was, to identify an estimate of left ventricular contractility derived from the aortic pressure wave without load changing manoeuvres. For this purpose, left ventricular contractility was assessed with several aortic pressure wave form derived parameters and was compared to standard parameters of left ventricular contractility (conductance technique) in an experimental study. Measurements were taken during baseline, after beta-stimulation and after injection of a beta-antagonist. The initial and the secondary tangent, the area under the aortic pressure, and the stroke volume were correlated with the endsystolic elastance, a mainly load independent measure of left ventricular contractility: The initial tangent of the aortic pressure increase correlated significantly with the endsystolic elastance (r = 0.54, P < 0.05). The initial tangent of the aortic pressure increase was significantly increased from baseline at beta-stimulation (from 20.2 +/- 4.7 to 36.4 +/- 6.8 mmHg s(-1), P < 0.05) and decreased after injection of a beta-antagonist (from 20.2 +/- 4.7 to 12.3 +/- 2.0, P < 0.05). Thus, we conclude that the initial tangent of the aortic pressure increase is a valid estimate of left ventricular contractility in piglets.

Hypoxic Preconditioning Preserves Cardiac Contractility and Reduces Infarct Size In Vivo

Background: Preconditioning is a powerful endogenous mechanism to protect the heart against ischemic dam- age. The second window of preconditioning (SWOP) is therapeutically the most attractive, but is hard to achieve by local cardiac ischemia 24 hrs before the index ischemia in the many mice models for cardiovascular pathology, because of ex- cessive mortality during the two procedures or the period in between. Hypoxic preconditioning is an attractive alternative preconditioning stimulus. To date, the SWOP after hypoxic preconditioning has not been studied in mice concerning in- farct size reduction and preservation of left ventricular contractility in vivo. Aim: To determine whether transient hypoxia can induce a SWOP in vivo in mice. Methods: Hypoxic preconditioning was induced by 5 cycles of 6 minutes of 6% oxygen in 24-week-old wild type mice. Twenty-four hours later, a 30 minutes coronary occlusion was performed. After 1 hour of reperfusion, in vivo cardiac pressure-conductance catheterization was performed with determination of the load-dependent and load-independent pa- rameters. Infarct size was determined by TTC-staining. Sham procedures were used to obtain non-preconditioned con- trols. Results: There was no mortality with the hypoxic preconditioning protocol. The left ventricular contractile parameters ejection fraction, end-systolic elastance and preload recruitable stroke work were significantly better preserved after ischemia in the preconditioned group. Diastolic relaxation (tau) was also significantly better preserved. Infarct size was reduced to half that of the non-preconditioned group. Conclusion: Hypoxic preconditioning is a feasible stimulus to induce in vivo a second window of preconditioning in mice. Infarct size is reduced and cardiac contractility better preserved after 30 min regional ischemia in vivo by hypoxic precon- ditioning 24 hrs earlier.

Computerized Acoustic Cardiographic Electromechanical Activation Time Correlates With Invasive and Echocardiographic Parameters of Left Ventricular Contractility

Background Electromechanical activation time (EMAT) is a systolic time interval defined as the time from Q-wave onset to the peak first heart sound. We assessed the correlation between systolic dysfunction and EMAT calculated using computerized acoustic cardiography. Methods A total of 25 patients with heart failure contemporaneously underwent echocardiography, left-sided heart catheterization, and acoustic cardiography. Invasive pressure–volume hemodynamics included peak isovolumetric left ventricular (LV) pressure at the end-diastolic volume, end-diastolic pressure, dyssynchrony, and maximal +dP/dT. An EMAT/(R to R interval) (%EMAT) interval ≥ 0.15 was prospectively defined as abnormal. Results An abnormal %EMAT correlated with a lower LV ejection fraction (50.9% ± 18.6% with normal EMAT vs 32.0% ± 10.9% with abnormal EMAT, P = .015), end-systolic elastance (3.07 ± 1.56 mm Hg/mL vs 1.43 ± 0.83 mm Hg/mL, P = .018), and peak isovolumetric LV pressure at the end-diastolic volume (317 ± 90 mm Hg vs 222 ± 67 mm Hg, P = .015). An abnormal %EMAT was associated with a higher end-systolic volume index (33.6 ± 29.3 mL/m 2 vs 71.0 ± 35.8 mL/m 2, P = .011), end-diastolic volume index (61.2 ± 29.8 mL/m 2 vs 100.3 ± 40.8 mL/m 2, P = .012), and dyssynchrony (26.1% ± 6.0% vs 31.5% ± 3.5%, P = .028). There was no difference in end-diastolic pressure (20.3 ± 7.9 mm Hg vs 21.4 ± 12.3 mm Hg, P = .78). Conclusions An abnormal %EMAT was strongly associated with impaired LV contractility but had no association with LV filling pressures. This noninvasive, simple, point-of-care diagnostic test has potential applications when echocardiography cannot be obtained in a timely fashion to assess systolic function.

Computerized acoustic cardiographic electromechanical activation time correlates with invasive and echocardiographic parameters of left ventricular contractility

Computerized acoustic cardiographic electromechanical activation time correlates with invasive and echocardiographic parameters of left ventricular contractility

POSITIVE END-EXPIRATORY PRESSURE DOES NOT COMPROMISE MYOCARDIAL CONTRACTILITY IN MYOCARDIAL ISCHEMIA/REPERFUSION

Therapy for severe myocardial ischemia/reperfusion sometimes necessitates intermittent positive pressure ventilation, which may impair left ventricular function by reduction of ventricular loading. It is unknown today whether positive airway pressure also affects contractile force after myocardial ischemia/reperfusion. The authors tested whether positive end-expiratory pressure (PEEP) impairs myocardial contractility in acute ischemic heart failure. In 11 anesthetized mechanically ventilated pigs (28 +/- 3 kg), cardiac output (CO, aortic flow probe), load-independent parameters of left ventricular contractility (conductance method: preload recruitable stroke work [PRSW] and end-systolic elastance [E(es)]) and preload (end-diastolic volume [EDV] conductance) were assessed before and after myocardial ischemia and reperfusion (left anterior descending artery occlusion, 60 min). Data were taken during PEEP 0, 5, and 10 cm H2O. Before myocardial ischemia, both PEEP 5 and 10 cm H2O reduced CO (P < 0.05) because of a reduction of EDV (P < 0.05, PEEP 10 cm H2O). The PRSW remained unchanged (not significant [NS]) and E(es) increased (P < 0.05, PEEP 10 cm H2O). After myocardial ischemia/reperfusion, CO and PRSW, but not E(es) (NS), deteriorated markedly. At the same time, PEEP 10 cm H2O reduced CO (P < 0.05) and, slightly, EDV (NS). Now, both PRSW (P < 0.05, PEEP 5 cm H2O) and E(es) (P < 0.05, PEEP 10 cm H2O) improved upon ventilation with PEEP. In our model, the administration of PEEP impaired global left ventricular function before and after myocardial ischemia/reperfusion. The observed impairment is not attributable to compromised contractility.