Index Of Left Ventricular Contractility Research Articles

Mild Hypothermia Attenuates Circulatory and Pulmonary Dysfunction During Experimental Endotoxemia*

We tested whether mild hypothermia impacts on circulatory and respiratory dysfunction during experimental endotoxemia. Randomized controlled prospective experimental study. Large animal facility, Medical University of Graz, Austria. Thirteen anesthetized and mechanically ventilated pigs. Lipopolysaccharide was administered for 4 hours. With the beginning of lipopolysaccharide infusion, animals were assigned to either normothermia (38°C, n = 7) or mild hypothermia (33°C, n = 6, intravascular cooling) and followed for 8 hours in total. At the end of the protocol, cardiac output was lower in mild hypothermia than in normothermia (4.5 ± 0.4 L/min vs 6.6 ± 0.4 L/min, p < 0.05), but systemic vascular resistance (885 ± 77 dyn·s/cm vs 531 ± 29 dyn·s/cm, p < 0.05) and (Equation is included in full-text article.)(77% ± 6% vs 54% ± 3%, p < 0.05) were higher. Indices of left ventricular contractility in vivo were not different between groups. The high-frequency band in spectral analysis of heart rate variability indicated a better preserved vagal autonomic modulation of sinuatrial node activity in mild hypothermia versus normothermia (87 ± 5 vs 47 ± 5, normalized units, p < 0.05). Plasma norepinephrine levels were elevated compared with baseline in normothermia (2.13 ± 0.27 log pg/mL vs 0.27 ± 0.17 log pg/mL, p < 0.05) but not in mild hypothermia (1.02 ± 0.31 vs 0.55 ± 0.26, p = not significant). At 38°C in vitro, left ventricular muscle strips isolated from the mild hypothermia group had a higher force response to isoproterenol. SaO2 (100% ± 0% vs 92% ± 3%, p < 0.05) and the oxygenation index (PO2/FIO2, 386 ± 52 mm Hg vs 132 ± 32 mm Hg, p < 0.05) were substantially higher in mild hypothermia versus normothermia. Plasma cytokine levels were not consistently different between groups (interleukin 10) or higher (tumor necrosis factor-α and interleukin 6 and 8) during mild hypothermia versus normothermia. The induction of mild hypothermia attenuates cardiac and respiratory dysfunction and counteracts sympathetic activation during experimental endotoxemia. This was not associated with lower plasma cytokine levels, indicating a reduction of cytokine responsiveness by mild hypothermia.

Hemodynamic adjustments during breath-holding in trained divers

Voluntary breath-holding (BH) elicits several hemodynamic changes, but little is known about maximal static immersed-body BH. We hypothesized that the diving reflex would be strengthened with body immersion and would spare more oxygen than maximal dry static BH, resulting in a longer BH duration. Eleven trained breath-hold divers (BHDs) performed a maximal dry-body BH and a maximal immersed-body BH. Cardiac output (CO), stroke volume (SV), heart rate (HR), left ventricular end-diastolic volume (LVEDV), contractility index (CTI), and ventricular ejection time (VET) were continuously recorded by bio-impedancemetry (PhysioFlow PF-05). Arterial oxygen saturation (SaO2) was assessed with a finger probe oximeter. In both conditions, BHDs presented a bi-phasic kinetic for CO and a tri-phasic kinetic for SV and HR. In the first phase of immersed-body BH and dry-body BH, results (mean±SD) expressed as percentage changes from starting values showed decreased CO (55.9±10.4 vs. 39.3±16.8%, respectively; p<0.01 between conditions), due to drops in both SV (24.9±16.2 vs. 9.0±8.5%, respectively; p<0.05 between conditions) and HR (39.7±16.7 vs. 33.6±17.0%, respectively; p<0.01 between conditions). The second phase was marked by an overall stabilization of hemodynamic variables. In the third one, CO kept stabilizing due to increased SV (17.0±20.2 vs. 10.9±13.8%, respectively; p<0.05 between conditions) associated with a second HR drop (14.0±10.0 vs. 12.7±8.9%, respectively; p<0.01 between conditions). This study highlights similar time-course patterns for cardiodynamic variables during dry-body and immersed-body BH, although the phenomenon was more pronounced in the latter condition.

Myocardial contractile dysfunction associated with increased 3-month and 1-year mortality in hospitalized patients with heart failure and preserved ejection fraction

There is a clinical need for a contractility index that reflects myocardial contractile dysfunction even when ejection fraction (EF) is preserved. We used novel relative load-independent global and regional contractility indices to compare left ventricular (LV) contractile function in three groups: heart failure (HF) with preserved ejection fraction (HFPEF), HF with reduced ejection fraction (HFREF) and normal subjects. Also, we determined the associations of these parameters with 3-month and 1-year mortality in HFPEF patients. 199 HFPEF patients [median age (IQR): 75 (67-80) years] and 327 HFREF patients [69 (59-76) years] were recruited following hospitalization for HF; 22 normal control subjects [65 (54-71) years] were recruited for comparison. All patients underwent standard two-dimensional Doppler and tissue Doppler echocardiography to characterize LV dimension, structure, global and regional contractile function. The median (IQR) global LV contractility index, dσ*/dtmax was 4.30s(-1) (3.51-4.57s(-1)) in normal subjects but reduced in HFPEF [2.57 (2.08-3.64)] and HFREF patients [1.77 (1.34-2.30)]. Similarly, median (IQR) regional LV contractility index was 99% (88-104%) in normal subjects and reduced in HFPEF [81% (66-96%)] and HFREF [56% (41-71%)] patients. Multi-variable logistic regression analysis on HFPEF identified sc-mFS <76% as the most consistent predictor of both 3-month (OR=7.15, p<0.05) and 1-year (OR=2.57, p<0.05) mortality after adjusting for medical conditions and other echocardiographic measurements. Patients with HFPEF exhibited decreased LV global and regional contractility. This population-based study demonstrated that depressed regional contractility index was associated with higher 3-month and 1-year mortality in HFPEF patients.

Association of Serum Myeloid Cells of Soluble Triggering Receptor-1 Level with Myocardial Dysfunction in Patients with Severe Sepsis

Objective. To investigate the association of serum sTREM-1 with myocardial dysfunction in patients with severe sepsis. Methods. A total of 85 patients with severe sepsis were divided into severe sepsis group (n = 40) and septic shock group (n = 45). Serum levels of sTREM-1, NT-proBNP, APACHE II score, SOFA score, cardiac index, cardiac function index, global ejection fraction, and left ventricular contractility index were measured on days 1, 3, and 7 after admission to ICU. Results. Serum sTREM-1 levels of patients with septic shock were significantly higher than those with severe sepsis on days 1, 3, and 7. Serum sTREM-1 was positively correlated with APACHE II scores, SOFA scores, and NT-proBNP. However, The sTREM-1 level was markedly negatively correlated with CI, CFI, GEF, and dP/dt max, respectively. Multiple logistic regression analysis showed that sTREM-1 was independent risk factor to NT-proBNP increasing. The optimal cut-off point of sTREM-1 for detecting patients with myocardial dysfunction was 468.05 ng/mL with sensitivity (80.6%) and specificity (75.7%). There is no difference in TREM-1-mRNA expression between the two groups. Conclusions. Serum sTREM-1 is significantly associated with myocardial dysfunction and may be a valuable tool for determining the presence of myocardial dysfunction in patients with severe sepsis.

Central versus peripheral control of cardiac output in humans: insight from atrial pacing

Central <i>versus</i> peripheral control of cardiac output in humans: insight from atrial pacing

Real Time 3D echocardiography (RT3D) for assessment of ventricular and vascular function in hypertensive and heart failure patients

BackgroundCardiac and systemic hemodynamics have been historically in the domain of invasive cardiology, but recent advances in real-time 3-Dimensional echocardiography (RT3D echo) provide a reliable measurement of ventricular volumes, allowing to measure a set of hemodynamic parameters previously difficult or impossible to obtain with standard 2D echo.AimTo assess the feasibility of a comprehensive hemodynamic study with RT-3D echo.MethodsWe enrolled 136 patients referred for routine echocardiography: 44 normal (N), 57 hypertensive (HYP), and 35 systolic heart failure patients (HF). All patients underwent standard 2D echo examination followed by RT3D echo examination, including measurement of left ventricular (LV) end-diastolic and end-systolic volumes and derived assessment of LV elastance (an index of LV contractility), arterial elastance (characterizing the distal impedance of the arterial system downstream of the aortic valve); ventricular-arterial coupling (a central determinant of net cardiovascular performance); systemic vascular resistances. Blood pressure was derived from cuff sphygmomanometer and heart rate from ECG.ResultsA complete 2D echo was performed in all 136 patients. 3D echo examination was obtained in 130 patients (feasibility = 95 %). Standard 2D echo examination was completed in 14.8 ± 2.2 min. Acquisition of 3D images required an average time of 5 ± 0.9 min (range 3.5-7.5 min) and image analysis was completed in 10.1 ± 2.8 min (range 6–12 min) per patient. Compared to N and HYP, HF patients showed reduced LV elastance (1.7 ± 1.5 mmHg mL-1 m-2, p <0.001 vs N = 3.8 ± 1.3 and HYP = 3.8 ± 1.3) and ventricular-arterial coupling (0.6 ± 0.5, p < 0.01 vs N = 1.4 ± 0.4 and HYP = 1.2 ± 0.4). Systemic vascular resistances were highest in HYP (2736 ± 720, p < .01 vs N = 1980 ± 432 and vs HF = 1855 ± 636 dyne*s/cm5). The LV elastance was related to EF (r = 0.73, p < 0.01) and arterial pressure was moderately related to vascular elastance (r = 0.54, p < 0.01). The ventricular-arterial coupling was unrelated to systemic vascular resistances (r = −0.04, p NS).ConclusionRT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables – such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients.

CB1 cannabinoid receptor deficiency promotes cardiac remodeling induced by pressure overload in mice

BackgroundThe endocannabinoid system is known to play a role in regulating myocardial contractility, but the influence of cannabinoid receptor 1 (CB1) deficiency on chronic heart failure (CHF) remains unclear. In this study we attempted to investigate the effect of CB1 deficiency on CHF induced by pressure overload and the possible mechanisms involved. Methods and resultsA CHF model was created by transverse aortic constriction (TAC) in both CB1 knockout mice and wild-type mice. CB1 knockout mice showed a marked increase of mortality due to CHF from 4 to 8weeks after TAC (p=0.021). Five weeks after TAC, in contrast to wild-type mice, CB1 knockout mice had a higher left ventricular (LV) end-diastolic pressure, lower rate of LV pressure change (±dp/dt max), lower LV contractility index, and a larger heart weight to body weight ratio and lung weight to body weight ratio compared with wild-type mice (all p<0.05–0.001). Phosphorylation of the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (P38 and ERK) was higher in CB1 knockout mice than that in wild-type mice. In cultured neonatal rat cardiomyocytes, a CB1 agonist reduced cAMP production stimulated by isoproterenol or forskolin, and suppressed phosphorylation of the EGFR, P38, and ERK, while the inhibitory effect of a CB1 agonist on EGFR phosphorylation was abrogated by CB1 knockdown. ConclusionThese findings indicate that cannabinoid receptor 1 inactivation promotes cardiac remodeling by enhancing the activity of the epidermal growth factor receptor and mitogen-activated protein kinases.

Peripheral vasodilatation determines cardiac output in exercising humans: insight from atrial pacing

In dogs, manipulation of heart rate has no effect on the exercise-induced increase in cardiac output. Whether these findings apply to humans remain uncertain, because of the large differences in cardiovascular anatomy and regulation. To investigate the role of heart rate and peripheral vasodilatation in the regulation of cardiac output during steady-state exercise, we measured central and peripheral haemodynamics in 10 healthy male subjects, with and without atrial pacing (100–150 beats min(−1)) during: (i) resting conditions, (ii) one-legged knee extensor exercise (24 W) and (iii) femoral arterial ATP infusion at rest. Exercise and ATP infusion increased cardiac output, leg blood flow and vascular conductance (P < 0.05), whereas cerebral perfusion remained unchanged. During atrial pacing increasing heart rate by up to 54 beats min(−1), cardiac output did not change in any of the three conditions, because of a parallel decrease in stroke volume (P < 0.01). Atrial pacing increased mean arterial pressure (MAP) at rest and during ATP infusion (P < 0.05), whereas MAP remained unchanged during exercise. Atrial pacing lowered central venous pressure (P < 0.05) and pulmonary capillary wedge pressure (P < 0.05) in all conditions, whereas it did not affect pulmonary mean arterial pressure. Atrial pacing lowered the left ventricular contractility index (dP/dt) (P < 0.05) in all conditions and plasma noradrenaline levels at rest (P < 0.05), but not during exercise and ATP infusion. These results demonstrate that the elevated cardiac output during steady-state exercise is regulated by the increase in skeletal muscle blood flow and venous return to the heart, whereas the increase in heart rate appears to be secondary to the regulation of cardiac output.

Tissue Doppler-Derived Measurement of Isovolumic Myocardial Contraction in the Pediatric Population

Multiple echocardiographic techniques have been utilized to quantify systolic function. The shortening and ejection fraction remain the most commonly used and accepted methods. However, these measures are affected by altered loading conditions, and are not applicable when ventricular geometry differs from the prolate ellipsoid typical of a left ventricle. Mitral valve annular acceleration during isovolumic contraction (IVA) has been proposed as a load independent index of left ventricular contractility. However, published values for IVA demonstrating normal function vary. In addition, the value of IVA which may discern impaired systolic function has not been established. The purpose of this study is to determine a threshold IVA value for abnormal left ventricular function in the pediatric population. Structurally/functionally normal control (n = 90) and dilated cardiomyopathy (study = 64) patients were compared for differences in left ventricular: wall stress (WS), velocity of circumferential fiber shortening (VCFc), ejection fraction (EF), ejection force, and pulsed wave-derived medial and lateral wall IVA. No difference in body surface area (p = 0.61) or gender (p = 0.53) was noted. Left ventricular ejection fraction, ejection force, VCFc, and IVA were significantly lower and WS was significantly higher in the study group (p < 0.01). The medial IVA was 1.71 ± 0.89 m/s(2) for an EF <40%, 1.74 ± 0.70 m/s(2) for an EF = 40-50%, 2.46 ± 0.89 m/s(2) for an EF >50%. The lateral IVA was 1.81 ± 1.03 m/s(2) for an EF <40%, 2.07 ± 0.78 m/s(2) for an EF = 40-50%, 2.54 ± 0.99 m/s(2) for an EF >50%. ROC analysis demonstrated a medial IVA of 1.97 m/s(2) as the cut-off for predicting an EF <50% with a 77% sensitivity of and specificity of 66% (AUC = 0.75, CI = 0.67-0.83, p < 0.01). ROC analysis demonstrated a lateral IVA of 2.31 m/s(2) as the cut-off for predicting an EF <50% with a 73% sensitivity of and specificity of 63% (AUC = 0.72, CI = 0.63-0.82, p < 0.01). IVA lateral of 1.93 m/s(2) or less was associated with heart transplant and death. ICC analysis demonstrated some interobserver variability in IVA measurement (0.57-0.65). The normal IVA of the medial and lateral mitral valve annulus measure over 1.97 m/s(2) and 2.31 m/s(2), respectively; values less than this cut-off are associated with EF <50%. Despite some problems with reproducibility IVA remains a promising method of screening for diminished ventricular contractility in the setting of abnormal geometry.

Influence of preload and afterload on stroke volume response to low-dose dobutamine stress in patients with non-ischemic heart failure: A cardiac MR study

BackgroundLack of increase in left ventricular (LV) stroke volume (SV) during low-dose dobutamine stress (LDD) is attributed to exhausted cardiac contractile reserve in failing heart. However, the role of the afterload and preload in SV changes is underestimated. The aim of the study was to investigate the effects of LDD on preload reserve and afterload in patients with non-ischemic heart failure. Methods58 patients (age 62years) underwent LDD (up to 20μg/kg/min) using cardiac magnetic resonance. ResultsLV-SV increased by 27% in 24 patients (p<0.001) (SV+), while decreased by 19% in 22 patients (p<0.001) (SV−). The LDD-to-rest reduction in preload, as defined by LV end-diastolic volume (EDV), was more pronounced in SV− than SV+ (24% and 8% respectively, p<0.05). The LLD-to-rest increase in systolic blood pressure to LV end systolic volume ratio, an index of LV contractility, was higher but not statistically different in SV+ in comparison to SV− (70% vs 48%, p=ns). Systemic vascular resistance during LDD tended to be higher in SV− (23%, p=ns), while it was significantly reduced in SV+ (9.5%, p<0.011), whereas arterial elastance (Ea) increased in SV− (30%, p<0.001) but decreased in SV+ (0.5%, p=0.04). At multivariable regression models LV-EF, LV-EDV and Ea significantly contributed to LV-SV changes in all patients. Also among SV+ and SV− LV-EDV and Ea revealed significant contribution to LV-SV change. ConclusionsAt similar contractile reserve response, the lack of LDD-induced increase in LV-SV, can be related to reduced preload reserve as well as to increased afterload.

Human Skeletal Muscle Cells With a Slow Adhesion Rate After Isolation and an Enhanced Stress Resistance Improve Function of Ischemic Hearts

Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs.

Relevance of the volume-axis intercept,V0, compared with the slope of end-systolic pressure-volume relationship in response to large variations in inotropy and afterload in rats

The end-systolic pressure-volume relationship (ESPVR) is proposed and used as a reliable index of left ventricular (LV) contractility despite the fact that its afterload independence has been challenged. Furthermore, the physiological relevance of its volume-axis intercept, V(0), remains unclear. Systemic haemodynamics and pressure-volume loops obtained by inferior vena cava occlusion were recorded in 21 rats anaesthetized by isoflurane inhalation and instrumented with a conductance pressure-volume catheter in response to incremental I.V. doses of adrenaline, dobutamine, phenylephrine, metoprolol, papaverine and isoflurane inhalation. In conditions with large variations (± 100%) of both inotropy and afterload, infusion of negative inotropic drugs was associated with a dose-dependent rightward shift of ESPVR accompanied by a decrease in its slope (end-systolic elastance, E(es)), whereas positive inotropic agents produced an isolated decrease in V(0). With the predominant vasoactive drugs, there was a dose-dependent change in E(es) without major horizontal shifts, demonstrating that this slope mainly represents LV afterload rather than inotropy. When contractility was altered, V(0) was negatively correlated to the preload-adjusted contractility index, PAdP/dt(max), demonstrating that a reduced V(0) provides a good reflection of increased LV contractility. From these results, we computed a logarithmically adjusted E(es)/V(0) ratio, which resulted in reasonably strong concordance with PAdP/dt(max), including all the investigated drugs and dosages [n = 288; bias, 0.8 ± 16.2% (SD)]. Concordance with E(es) (bias, 7.2 ± 58.7%) or V(0) (bias, -0.6 ± 33.4%), used alone or with other commonly used contractility indices, was far less significant. In contrast to E(es), V(0) provides a relatively good LV contractility index because it is much less sensitive to afterload.

Early Detection of Left Ventricular Dysfunction in Asymptomatic Type 2 Diabetic Patients

Subclinical left ventricular (LV) systolic and diastolic dysfunction has been reported to be prevalent in diabetic subjects, but this recognition could often be missed. Isovolumic contraction velocity (IVCv) and acceleration during isovolumic contraction (IVA) have been proposed as indexes of global LV contractility.

Association between cardiopulmonary exercise and dobutamine stress testing in ambulatory patients with idiopathic dilated cardiomyopathy: A comparison with peak VO2 and VE/VCO2 slope

BackgroundBoth peak VO2 and VE/VCO2 slope are considered to be useful predictors of cardiovascular events. The left ventricular (LV) response to dobutamine stress testing (DST) also provides useful prognostic information. However, the relationship between these variables has not been fully investigated. Therefore, the aim of this study is to investigate the association between myocardial contractile reserve measured by DST and cardiopulmonary exercise testing (CPX) variables in patients with idiopathic dilated cardiomyopathy (IDCM). MethodsThirty-eight patients were subjected to CPX as well as cardiac catheterization for measurement of LV pressure. The maximum first derivative of LV pressure (LV dP/dtmax) was measured at baseline and during dobutamine infusion at incremental doses of 5, 10, and 15μgkg−1min−1. LV dP/dtmax at baseline and the percentage increase in LV dP/dtmax (ΔLV dP/dtmax) induced by DST served as indices of LV contractility and myocardial contractile reserve, respectively. ResultsPeak VO2, and VE/VCO2 slope were 18.6mLkg−1min−1 and 32.3, respectively. Peak VO2 was not correlated with LV dP/dtmax at baseline. However, peak VO2 was significantly correlated with ΔLV dP/dtmax, and the correlation became more pronounced as the dose of dobutamine was increased. There was no correlation between VE/VCO2 slope and ΔLV dP/dtmax. Multivariate regression analysis revealed that ΔLV dP/dtmax was independently correlated with peak VO2 (p=0.011). ConclusionsPeak VO2, but not VE/VCO2 slope, may reflect myocardial contractile reserve in ambulatory patients with IDCM. This study population is small, and therefore large confirmatory studies are needed.

Attenuation of Stress-based Ventricular Contractility in Patients with Heart Failure and Normal Ejection Fraction

The maximal rate of change of pressure-normalised wall stress dσ*/dtmax has been proposed as cardiac index of left ventricular (LV) contractility. In this study, we assessed the capacity of dσ*/dtmax to diagnose heart failure with normal ejection fraction (HFNEF). One hundred healthy normal controls and 140 patients admitted with heart failure (100, HFREF and 40, HFNEF) underwent echocardiography for stress-based contractility dσ*/dtmax. Patients with signifi cant valvular heart disease were excluded. Tissue Doppler indices were also measured. dσ*/dtmax was 4.43 ± 1.27 s-1 in control subjects; reduced in HFNEF, 3.02 ± 0.98 s-1; and HFREF, 2.00 ± 0.67 s-1 (P <0.001). In comparison with age- and sex-matched groups (n = 26 each), we found similar trend on reduction of dσ*/dtmax (normal control; 3.91 ± 0.87 s-1; HFNEF, 2.90 ± 0.84 s-1; HFREF, 1.84 ± 0.59 s-1, P <0.001). On multivariate analysis, dσ*/dtmax was found to be the independent predictor of HFNEF and HFREF. The area under the curve of the receiver operating characteristics (ROC) in detecting HFNEF compared with normal controls (dσ*/dtmax>3.2 s-1) was 0.84 (P <0.0001), and in detecting HFREF compared with HFNEF (dσ*/dtmax>2.32 s-1) was 0.88 (P <0.0001). This data confi rms that dσ*/dtmax on echocardiography is a powerful independent predictor in patients with HFNEF. In a population with a high suspicion of HFNEF, dσ*/dtmax may significantly contribute to early diagnosis and hence be useful in the triage and management of HFNEF patients.

Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism.

Acute myocardial dysfunction is a typical manifestation of septic shock. Experimentally, the administration of endotoxin [lipopolysacharride (LPS)] to laboratory animals is frequently used to study such dysfunction. However, a majority of studies used load-dependent indexes of cardiac function [including ejection fraction (EF) and maximal systolic pressure increment (dP/dt(max))], which do not directly explore cardiac inotropism. Therefore, we evaluated the direct effects of LPS on myocardial contractility, using left ventricular (LV) pressure-volume catheters in mice. Male BALB/c mice received an intraperitoneal injection of E. coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6, or 20 h, cardiac function was analyzed in anesthetized, mechanically ventilated mice. All doses of LPS induced a significant drop in LV stroke volume and a trend toward reduced cardiac output after 6 h. Concomitantly, there was a significant decrease of LV preload (LV end-diastolic volume), with no apparent change in LV afterload (evaluated by effective arterial elastance and systemic vascular resistance). Load-dependent indexes of LV function were markedly reduced at 6 h, including EF, stroke work, and dP/dt(max). In contrast, there was no reduction of load-independent indexes of LV contractility, including end-systolic elastance (ejection phase measure of contractility) and the ratio dP/dt(max)/end-diastolic volume (isovolumic phase measure of contractility), the latter showing instead a significant increase after 6 h. All changes were transient, returning to baseline values after 20 h. Therefore, the alterations of cardiac function induced by LPS are entirely due to altered loading conditions, but not to reduced contractility, which may instead be slightly increased.

Effect of aging on cardiac function during cold stress in humans

To determine whether skin surface cooling increases left ventricular preload and contractility to a greater extent in older compared with young adults we studied 11 young (28 +/- 2 yr; means +/- SE) and 11 older (64 +/- 3 yr) adults during normothermia (35 degrees C water perfused through a tube-lined suit) and cooling (15 degrees C water perfused for 20 min) using standard and tissue Doppler echocardiography. Cooling significantly decreased skin surface temperature in young (Delta2.8 +/- 0.3 degrees C) and older (Delta3.0 +/- 0.3 degrees C) adults and increased rate-pressure product, an index of myocardial oxygen demand, in older (6,932 +/- 445 to 7,622 +/- 499 mmHg x beats/min for normothermia and cooling, respectively), but not young (7,085 +/- 438 to 7,297 +/- 438 mmHg x beats/min) adults. Increases in blood pressure (systolic and mean blood pressure) during cooling were greater (P < 0.05) in older than in young adults. Cooling increased preload in older (left ventricular end-diastolic volume from 106 +/- 7 to 126 +/- 9 ml and left ventricular internal diameter in diastole from 4.69 +/- 0.12 to 4.95 +/- 0.14 cm; both P < 0.01), but not young adults (left ventricular end-diastolic volume from 107 +/- 7 to 111 +/- 7 ml and left ventricular internal diameter in diastole from 4.70 +/- 0.10 to 4.78 +/- 0.10 cm). Indices of left ventricular contractility (ejection fraction, myocardial acceleration during isovolumic contraction, and peak systolic mitral annulus velocity) were unchanged during cooling in both young and older adults. Collectively, these data indicate that cooling increases left ventricular preload, without affecting left ventricular contractility in older but not young adults. Greater increases in preload and afterload during cooling in older adults contribute to greater increases in indices of myocardial oxygen demand and may help explain the increased risk of cardiovascular events in cold weather.

Comparison of left ventricular contraction profiles among small, medium, and large dogs by use of two-dimensional speckle-tracking echocardiography

To assess differences in left ventricular contractile indices among dogs of 3 body sizes via 2-D speckle-tracking echocardiography (STE) and to determine body weight-independent systolic variables. 37 clinically normal adult dogs. Dogs were allocated into 3 groups on the basis of body weight: small (<7kg), medium (7 to 20kg), and large (>20kg). Right parasternal short-axis echocardiographic views were acquired to measure conventional M-mode variables (left ventricular internal diameter at end diastole, left ventricular internal diameter at end systole, and fractional shortening [FS]) and STE indices (peak systolic strain, peak systolic strain rate, synchrony time index [STI], peak systolic apical rotation, peak systolic basal rotation, peak apical twisting rate, and peak systolic torsion). Values were compared among the 3 groups. STE indices, except for peak systolic radial strain (SRad), peak systolic basal rotation, and STI, were significantly decreased in large dogs, compared with values for small and medium dogs. No significant difference was detected in stroke index, peak systolic SRad, and peak systolic basal rotation among the 3 groups. The STI in large dogs was significantly increased, compared with that of medium dogs. Results revealed that decreased systolic indices in large dogs should not be interpreted as signs of decreased systolic function. Increased STI in large dogs may contribute to decreased FS. Because peak systolic SRad was not affected by body weight, peak systolic SRad might be a better variable than FS for assessing systolic function.

Peak systolic velocity of mitral annular longitudinal movement measured by pulsed tissue Doppler imaging as an index of global left ventricular contractility

We sought to test whether the peak systolic velocity of mitral annular longitudinal movement (S') measured by pulsed tissue Doppler imaging technique is useful to assess global left ventricular (LV) contractility under various LV inotropic conditions, including regional wall motion abnormality. In addition, the accuracy of S' relative to LV ejection fraction (EF), a conventional index of LV contractility, and its association with apical rotation, a new index of LV contractility, were also evaluated. We measured S' at the medial mitral annulus and apical rotation in 11 open-chest anesthetized dogs at eight inotropic stages before and after ligation of either the left anterior descending or circumflex coronary artery. Maximal positive dP/dt (dP/dt(peak)) was monitored using a high-fidelity pressure catheter and used as the standard measure of LV contractility. S' showed dose-dependent increases and decreases after dobutamine and esmolol infusion, respectively. There was a stronger association between dP/dt(peak) and S' (R(2) = 0.665, P < 0.001) than between dP/dt(peak) and EF (R(2) = 0.408, P < 0.001), and this trend was more apparent with coronary ligation, regardless of the ligation site. The strength of association between dP/dt(peak) and S' (R(2) = 0.665) was not different from that between dP/dt(peak) and apical rotation (R(2) = 0.726) (P = 0.350). The association between LV EF and S' was modest (R(2) = 0.472, P < 0.001), whereas a good association between S' and apical rotation was observed both with (R(2) = 0.552, P < 0.001) and without (R(2) = 0.674, P < 0.001) coronary ligation. S' is a more sensitive index of global LV contractility than is LV EF, reflecting both LV longitudinal shortening and torsional deformation.

Human umbilical cord blood cells in infarcted rats

Therapy with bone marrow-derived cells has been used in ischemic patients with reported success. The aim of this study was to determine the therapeutic efficacy of fresh and frozen human umbilical cord blood cells (hUCB) in Wistar rats submitted to permanent occlusion of the left coronary artery. Three hours after myocardial infarction, 2 x 10(7) hUCB cells or vehicle were administered by intramyocardial injection. The animals were divided into five groups: control (N = 10), sham operated (N = 10), infarcted that received vehicle (N = 9), infarcted treated with cryopreserved hUCB (N = 7), and infarcted treated with fresh hUCB (N = 5). Cardiac function was evaluated by electrocardiogram (ECG) and echocardiogram (ECHO) before cell therapy, and by ECG, ECHO, cardiopulmonary test, and left ventricular pressure measurements 3 weeks later. After 3 weeks, both groups treated with hUCB still had Q wave present in L1, âQRS >90 degrees and reduced shortening fraction (less than 50%). In addition, cardiac indexes of left ventricular contractility and relaxation were 5484 +/- 875 and -4032 +/- 643 mmHg (cryopreserved hUCB) and 4585 +/- 955 and -2862 +/- 590 mmHg (fresh hUCB), respectively. These values were not statistically different from those of saline-treated animals. Cardiopulmonary exercise test profile was typical of infarcted hearts; exercise time was about 14 min and maximal VO2 was 24.77 +/- 5.00 mL.kg-1.min-1. These data show that hUCB therapy did not improve the cardiac function of infarcted animals or prevent cardiac remodeling.