Index Of Left Ventricular Contractility Research Articles

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.

Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

IntroductionWe developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming.MethodsTwelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls.ResultsDuring progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased.ConclusionsProgressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments.

CARDIAC CONTRACTILITY MEASURES OF LEFT VENTRICULAR SYSTOLIC FUNCTIONAL ASSESSMENT OF NORMAL AND DISEASED HEARTS

Left ventricular (LV) contraction is the basis of LV systolic function, impairment of which underlies heart failure pathophysiology. Its accurate quantification in the form of LV contractility indices is imperative for diagnostic and follow-up assessment of LV systolic function in heart failure. Herein, we analyze LV contractile performance by focusing on LV contractility indices at different physiological organizational levels: from sarcomere dynamics to LV myocardial properties (such as elastic modulus and elastance), and from LV wall contractile stress development to the generation of intra-LV blood flow velocities and pressure distributions. Further, we present the development analyses of these indices and their medical applications. Using improved development of invasive and noninvasive techniques for measuring ventricular pressure, geometry, and volume, we show how these indices have become more amenable for clinical usage to obtain better patient assessment. The purpose of this paper is to present a comprehensive coverage of LV contraction physiology, indices to qualify LV contraction, formulation, and medical applications of some major intrinsic LV contractility indices, so as to provide the basis of functional assessment of normal versus diseased hearts.

Heritability of Hemodynamic Reactivity to Laboratory Stressors in a Homogenous Arab Population: ‘Oman Family Study’

Exaggerated cardiovascular reactivity to stressful stimuli may be a risk factor for the development of hypertension. The genetic influence on blood pressure (BP) reactivity to stress and its control mechanisms has been receiving considerable support. This study aims at examining the heritability of BP and its intermediate hemodynamic phenotypes to acute stress in a homogeneous Arab population. Parameters were computed from continuous BP, electrocardiography and impedance cardiography measurements, during rest, word conflict (WCT) and cold pressor (CPT) tests. Heritability estimates (h(2)) were obtained using the variance components-based approach implemented in the SOLAR software package. Reactivity scores for WCT and CPT increased significantly (P < .05) for systolic (SBP), diastolic (DBP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR). They decreased significantly (P < .05) for stroke volume (SV), left ventricular ejection time (LVET), end diastolic (EDI) and cardiac contractility (IC) indices. Univariate analysis detected heritability estimates that ranged from 0.19-0.35 for rest, 0.002-0.40 for WCT and 0.08-0.35 for CPT. In this unique cohort, resting as well as challenged cardiovascular phenotypes are significantly influenced by additive genetic effects. Heritability estimates for resting phenotypes are in a relatively narrow range, while h(2) for their reactivity is somewhat broader with lower estimates. Further analyses of this study may offer important opportunities for gene finding in hypertension. WHAT IS KNOWN ABOUT THE TOPIC: (1) cardiovascular reactivity to stress predicts cardiovascular disease; (2) genetic susceptibility plays an important role in stress reactivity. Family studies using the cold pressure test reported significant heritability for blood pressure. (1) this cohort is from five highly consanguineous isolated Arab pedigrees with genetically verified genealogical records and environmental homogeneity; (2) This is the first study to estimate heritability of detailed intermediate hemodynamic phenotypes that make up normal blood pressure.

Myocyte apoptosis occurs early during the development of pressure-overload hypertrophy in infant myocardium

Abnormal hemodynamic loading often accompanies congenital heart disease both before and after surgical repair. Adaptive and maladaptive myocardial responses to increased load are numerous. This study examined the hypothesis that myocyte loss occurs during compensatory hypertrophic growth in the developing infant myocardium subjected to progressive pressure overload. Pressure-overload left ventricular hypertrophy was induced in 7- to 10-day-old rabbits by banding the thoracic aorta. Left ventricular function and mechanics were quantified by serial echocardiography and noninvasive left ventricular wall stress analysis. Left ventricular tissue sections were examined for fibrosis by using Masson's trichrome stain and for myocyte apoptosis by using a myocyte-specific DNA fragmentation assay and caspase-3 activation (specific fluorescent substrate). Significant myocyte apoptosis (198 +/- 37/10(6) myocytes, P < .01 vs control) and caspase-3 activation were present in early hypertrophy when left ventricular contractility was preserved and compensatory hypertrophy had normalized wall stress. By 6 weeks, multiple indices of left ventricular contractility were reduced, and left ventricular wall stress was increased. Myocyte apoptosis was accelerated (361 +/- 56/10(6) myocytes), caspase-3 activity further increased, and the estimated total number of left ventricular myocytes was significantly reduced by 18% +/- 4%. In experimental infant left ventricular hypertrophy, myocyte apoptosis is initiated in the face of normalized wall stress and preserved contractility. The ongoing rate of apoptosis causes a measurable decrease in myocyte number that is coincident with the onset of ventricular dysfunction. It thus appears that pressure overload, even at its earliest stages, is not well tolerated by the developing ventricle.

Aprotinin Modifies Left Ventricular Contractility and Cytokine Release After Ischemia-Reperfusion in a Dose-Dependent Manner in a Murine Model

Periods of ischemia-reperfusion (I/R) during cardiac surgery are associated with transient left ventricular (LV) dysfunction and an inflammatory response. In this study, we examined the potential dose-dependent effects of aprotinin (APRO) on LV contractility and cytokine release in the setting of I/R. An index of LV contractility, LV maximal elastance (E(max)), was measured at baseline, 30 min of ischemia, and 60 min of reperfusion by microtransducer volumetry. Mice were randomized as follows: (a) APRO 20,000 kallikrein-inhibiting units (KIU)/kg (n = 11); (b) APRO 4 x 10(4) KIU/kg (n = 10); (c) APRO 8 x 10(4) KIU/kg (n = 10); and (d) vehicle (saline; n = 10). APRO doses were calculated to reflect half, full, and twice the clinical Hammersmith dosing schedule. After I/R, plasma was collected for cytokine measurements. After I/R, E(max) decreased from the baseline value by more than 40% in the vehicle group as well as in the APRO 4 x 10(4) KIU/kg and APRO 8 x 10(4) KIU/kg groups (P < 0.05). However, E(max) returned to near baseline values in the APRO 2 x 10(4) KIU/kg group. Tumor necrosis factor (TNF) increased 10-fold after I/R, but it was reduced with higher APRO doses. This study demonstrated that a low dose of APRO provided protective effects on LV contractility, whereas higher doses suppressed TNF release. These unique findings suggest that there are distinct and independent mechanisms of action of APRO in the context of I/R.

Apical Rotation Assessed by Speckle-Tracking Echocardiography as an Index of Global Left Ventricular Contractility

Left ventricular (LV) apical rotation and twist can be estimated noninvasively by speckle-tracking echocardiography (STE). In this study, we tested whether apical rotation is an accurate index of LV contractility. We measured LV basal and apical rotation by STE in 11 open-chest anesthetized mongrel dogs under 8 different inotropic stages before and after ligation of either left anterior descending (n=6) or circumflex coronary artery (n=5). We measured LV pressure simultaneously with a high-fidelity pressure catheter and calculated LV ejection fraction (EF) with the biplane Simpson method and 2D echocardiography. Maximal positive dP/dt (dP/dt(max)) was used as the gold standard measurement of LV contractility. We compared LV twist and apical rotation and EF against dP/dt(max) by linear mixed model. LV apical rotation and twist showed dose-dependent increases and decreases after dobutamine and esmolol infusion, respectively. However, basal rotation did not change significantly during different inotropic conditions. There was a stronger association between dP/dt(max) and LV twist (R(2)=0.747, P<0.001) and apical rotation (R(2)=0.726, P<0.001) than between dP/dt(max) and EF (R(2)=0.408, P<0.001), and this trend was more apparent with coronary ligation irrespective of the ligation site. There was also a high association between dP/dt(max) and apical rotation alone, both with (R(2)=0.805, P<0.001) and without (R(2)=0.748, P<0.001) coronary ligation. Apical rotation alone showed comparable accuracy to LV twist. Apical rotational velocity also showed a high association with dP/dt(max) (R(2)=0.669, P<0.001) and LV twist (R(2)=0.892, P<0.001). Apical rotation assessed by STE is an effective noninvasive index of global LV contractility and is more closely related to dP/dt(max) than LV EF.

Left ventricular myocardial function during the acute phase of a subarachnoid haemorrhage

Objectives. Previous reports suggest that left myocardial ventricular function changes during the course of a subarachnoid haemorrhage. The aim of this study was to evaluate left myocardial ventricular function with tissue Doppler echocardiography at two time points during the acute phase of a subarachnoid haemorrhage. Design. Eighteen consecutive patients (median 52 years, range 33–74) with spontaneous subarachnoid haemorrhage and no history of heart disease were examined at 1–5 days and at 6–11 days following ictus. Eighteen control subjects were included for comparison (52 years, 32–72). Results. Tissue Doppler indices of left ventricular contractility were higher in patients than in controls at both examinations (p<0.001). Indices of left ventricular stroke volume were elevated compared to controls at examination 1 (p<0.05), but not at examination 2. Early diastolic relaxation rate decreased from examination 1 to 2 (p=0.001). Three patients had increased troponin T (range 0.010–0.131µg/l). Conclusion. In patients with subarachnoid haemorrhage, systolic and diastolic function is increased compared to healthy controls, suggesting a hyperdynamic and hypervolemic circulation.

Effects of Surgical Ventricular Restoration on Left Ventricular Contractility Assessed by a Novel Contractility Index in Patients With Ischemic Cardiomyopathy

A pressure-normalized left ventricular (LV) wall stress (dsigma*/dt(max)) was recently reported as a load-independent index of LV contractility. We hypothesized that this novel contractility index might demonstrate improvement in LV contractile function after surgical ventricular restoration (SVR) using magnetic resonance imaging. A retrospective analysis of magnetic resonance imaging data of 40 patients with ischemic cardiomyopathy who had undergone coronary artery bypass grafting with SVR was performed. LV volumes, ejection fraction, global systolic and diastolic sphericity, and dsigma*/dt(max) were calculated. After SVR, a decrease was found in end-diastolic and end-systolic volume indexes, whereas LV ejection fraction increased from 26% +/- 7% to 31% +/- 10% (p <0.001). LV mass index and peak normalized wall stress were decreased, whereas the sphericity index (SI) at end-diastole increased, indicating that the left ventricle became more spherical after SVR. LV contractility index dsigma*/dt(max) improvement (from 2.69 +/- 0.74 to 3.23 +/- 0.73 s(-1), p <0.001) was associated with shape change as evaluated by the difference in SI between diastole and systole (r = 0.32, p <0.001, preoperative; r = 0.23, p <0.001, postoperative), but not with baseline LV SI. In conclusion, SVR excludes akinetic LV segments and decreases LV wall stress. Despite an increase in sphericity, LV contractility, as determined by dsigma*/dt(max), actually improves. A complex interaction of LV maximal flow rate and LV mass may explain the improvement in LV contractility after SVR. Because dsigma*/dt(max) can be estimated from simple noninvasive measurements, this underscores its clinical utility for assessment of contractile function with therapeutic intervention.

Abstract 718: Head-to-Head Comparison of Apical Rotation versus Mitral Annular Systolic Velocity for Estimation of Global Left Ventricular Contractility

We sought to test whether mitral annular systolic velocity by tissue Doppler (S′) and apical rotation by speckle tracking echocardiography (AR) can represent global left ventricular (LV) contractility. We measured AR and S′ in nine open chest anesthetized mongrel dogs under eight different inotropic stages before and after ligation of left anterior descending (LAD, n=6) or circumflex coronary artery (LCX, n=3). We measured LV pressure simultaneously with a high-fidelity pressure catheter and calculated LV ejection fraction (EF) with the biplane Simpson’s method. Maximal positive dP/dt (dP/dt max ) was used as the gold standard measurement of LV contractility. We compared AR and S′ and EF against dP/dt max by linear regression. Both S′ and AR showed dose-dependent increases and decreases following dobutamine and esmolol infusion, respectively. There was a stronger association between dP/dt max and AR (r=0.820, P &lt;0.001) and S′ (r=0.784, P &lt;0.001) than between dP/dt max and EF (r=0.567, P &lt;0.001), and this trend was more apparent with coronary ligation. There was also a good correlation between AR and S′ with (r=0.690, P &lt;0.001) and without (r=0.740, P &lt;0.001) coronary ligation. Both AR and S′ are effective noninvasive indices of global LV contractility irrespective of coronary ligation and have better accuracy than LV EF.

Diet with isolated soy protein reduces oxidative stress and preserves ventricular function in rats with myocardial infarction

We investigated the effects of an isolated soy protein (ISP) diet offered over a 9-week period to rats in whom myocardial infarction (MI) had been induced, and a casein diet given as a control. Male Wistar rats were assigned to six groups after infarct size determination ( n = 8/group): Sham Casein (SC); Infarct Casein < 25% (IC < 25%); Infarct Casein > 25% (IC > 25%); Sham Soy (SS); Infarct Soy < 25% (IS < 25%); and Infarct Soy > 25% (IS > 25%). MI surgery was performed at the fifth week, and one month later, the animals were hemodynamically assessed to evaluate left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), contractility and relaxation indexes (±d P/d t). Lung and liver specimens were also collected for the estimation of organ congestion. Oxidative stress was evaluated in heart homogenates through chemiluminescence (CL), carbonyl groups, and antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Infarcted groups treated with casein showed cardiac hypertrophy, lung and liver congestion, increased LVEDP and decreased LVSP and ±dP/dt, all typical signals of heart failure. Ventricular dysfunction was correlated with increased myocardial oxidative damage as seen by CL and carbonyl groups data in the groups IC < 25% and IC > 25% (3 and 10-fold increase, respectively). The ISP diet was able to improve ventricular systolic and diastolic function in the groups IS < 25% and IS > 25% (LVEDP was reduced by 44% and 24%, respectively) and to decrease myocardial oxidative stress. The overall results confirm the preventive role of soy-derived products in terms of post-MI myocardial dysfunction probably by an antioxidant action.

Relationship Between Ventricular Contractility and Early Diastolic Intraventricular Pressure Gradients: A Diastolic Link to Systolic Function

Early diastolic intraventricular pressure gradient (IVPG), as derived by color M-mode echocardiography, has been proposed to correlate with left ventricular (LV) elastic recoil. However, any relationship to quantifiable indices of LV contractility is poorly defined. To relate IVPG with invasive and noninvasive indices of contractility, 6 closed-chest dogs each had a high-fidelity conductance catheter placed into the LV for continuous determination of end-diastolic pressures, volumes, +dP/dt(max), and the time constant of LV relaxation (tau) under baseline conditions and 4 different stages of beta-receptor modulation. At each stage, IVPGs were determined from color M-mode echocardiography images. Doppler-derived strain rate (epsilon') and myocardial systolic myocardial velocities (S(m)) were also measured. E(max) was obtained from the slope of the end-systolic pressure-volume relationship during caval occlusion. Results of contractility indices were compared to IVPG with regression analysis. IVPG ranged from 0.72 to 3.95 mm Hg whereas E(max) ranged from 0.66 to 14.9 mm Hg/mL and end-systolic volume ranged from 1.9 to 59.7 mL. IVPG correlated with epsilon' (r = 0.71), S(m) (r = 0.67), end-systolic volume (r = 0.53), and invasive indices (+dP/dt(max), r = 0.71, and E(max), r = 0.82). Early diastolic IVPGs are associated with LV contractility. These findings may explain the proposed mechanism in which potential energy stored during systole is released during diastole to provide for adequate ventricular filling, even under low filling pressures.

Cardiovascular changes induced by cold water immersion during hyperbaric hyperoxic exposure

The present study was designed to assess the cardiac changes induced by cold water immersion compared with dry conditions during a prolonged hyperbaric and hyperoxic exposure (ambient pressure between 1.6 and 3 ATA and PiO(2) between 1.2 and 2.8 ATA). Ten healthy volunteers were studied during a 6 h compression in a hyperbaric chamber with immersion up to the neck in cold water while wearing wet suits. Results were compared with measurements obtained in dry conditions. Echocardiography and Doppler examinations were performed after 15 min and 5 h. Stroke volume, left atrial and left ventricular (LV) diameters remained unchanged during immersion, whereas they significantly fell during the dry session. As an index of LV contractility, percentage fractional shortening remained unchanged, in contrast to a decrease during dry experiment. Heart rate (HR) significantly decreased after 5 h, although it had not changed during the dry session. The changes in the total arterial compliance were similar during the immersed and dry sessions, with a significant decrease after 5 h. In immersed and dry conditions, cardiac output was unchanged after 15 min but decreased by almost 20% after 5 h. This decrease was related to a decrease in HR during immersion and to a decrease in stroke volume in dry conditions. The hydrostatic pressure exerted by water immersion on the systemic vessels could explain these differences. Indeed, the redistribution of blood volume towards the compliant thoracic bed may conceal a part of hypovolaemia that developed in the course of the session.

Single transpulmonary thermodilution in off‐pump coronary artery bypass grafting: haemodynamic changes and effects of different anaesthetic techniques

Off-pump coronary artery bypass grafting (OPCAB) can be associated with severe cardiovascular changes, thus requiring advanced haemodynamic monitoring. Our aim was to investigate the feasibility of transpulmonary single thermodilution (STD) combined with pulse-contour analysis, a newly introduced method for cardiovascular monitoring, for assessment of changes in haemodynamics during different anaesthetic techniques in OPCAB. Thirty-six patients scheduled for elective OPCAB were randomized to receive anaesthesia either with midazolam, propofol or isoflurane, in addition to fentanyl and pipecuronium. After catheterization of the femoral artery, haemodynamic parameters were assessed using STD and pulse-contour analysis. The measurements were performed after induction of anaesthesia, during surgery and at 2, 4 and 6 h post-operatively. At the end of surgery, the global ejection fraction decreased by 29% and 19% in the midazolam and the propofol groups, respectively, (P < 0.05) but remained unchanged in the isoflurane group. Moreover, in the isoflurane group, the left ventricular contractility index was higher and the mean arterial pressure (MAP) and the systemic vascular resistance index (SVRI) decreased in comparison with pre-operative values. Post-operatively, the cardiac index (CI) and the cardiac function index (CFI) increased in all groups (P < 0.05). The peri-operative requirement for ephedrine and nitroglycerin increased in the propofol and the midazolam groups, respectively (P < 0.05). During OPCAB, STD and pulse-contour analysis displayed changes in preload, myocardial function and afterload that gave valuable guidance for the conduct of anaesthesia, fluid management, and the administration of vasoactive agents. As assessed using STD, isoflurane within the present dose range appears to maintain myocardial performance and vascular tone better than midazolam or propofol.

Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?

End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.

Validation of a novel noninvasive cardiac index of left ventricular contractility in patients

Although there are several excellent indexes of myocardial contractility, they require accurate measurement of pressure via left ventricular (LV) catheterization. Here we validate a novel noninvasive contractility index that is dependent only on lumen and wall volume of the LV chamber in patients with normal and compromised LV ejection fraction (LVEF). By analysis of the myocardial chamber as a thick-walled sphere, LV contractility index can be expressed as maximum rate of change of pressure-normalized stress (d sigma*/dt(max), where sigma* = sigma/P and sigma and P are circumferential stress and pressure, respectively). To validate this parameter, d sigma*/dt(max) was determined from contrast cine-ventriculography-assessed LV cavity and myocardial volumes and compared with LVEF, dP/dt(max), maximum active elastance (E(a,max)), and single-beat end-systolic elastance [E(es(SB))] in 30 patients undergoing clinically indicated LV catheterization. Patients with different tertiles of LVEF exhibit statistically significant differences in d sigma*/dt(max). There was a significant correlation between d sigma*/dt(max) and dP/dt(max) (d sigma*/dt(max) = 0.0075 dP/dt(max) - 4.70, r=0.88, P<0.01), E(a,max) (d sigma*/dt(max) = 1.20E(a,max) + 1.40, r=0.89, P<0.01), and E(es(SB)) [d sigma*/dt(max)=1.60 E(es(SB)) + 1.20, r=0.88, P<0.01]. In 30 additional individuals, we determined sensitivity of the parameter to changes in preload (intravenous saline infusion, n = 10 subjects), afterload (sublingual glyceryl trinitrate, n = 10 subjects), and increased contractility (intravenous dobutamine, n=10 patients). We confirmed that the index is not dependent on load but is sensitive to changes in contractility. In conclusion, d sigma*/dt(max) is equivalent to dP/dt(max), E(a,max), and E(es(SB)) as an index of myocardial contractility and appears to be load independent. In contrast to other measures of contractility, d sigma*/dt(max) can be assessed with noninvasive cardiac imaging and, thereby, should have more routine clinical applicability.

Inhibition of Endogenous Nitric Oxide Synthase Augments Contractile Response to Adenylyl Cyclase Stimulation Without Altering Mechanical Efficiency in Patients With Idiopathic Dilated Cardiomyopathy

Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to beta-adrenergic receptor stimulation. However, the physiological effects of NO on the beta-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure. The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure-volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 micromol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency. These findings suggest endogenous NO may modulate beta-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC.

The effect of continuous light exposure of rats on cardiac response to ischemia-reperfusion and NO-synthase activity.

Factors modulating cardiac susceptibility to ischemia-reperfusion (I/R) are permanently attracting the attention of experimental cardiology research. We investigated, whether continuous 24 h/day light exposure of rats can modify cardiac response to I/R, NO-synthase (NOS) activity and the level of oxidative load represented by conjugated dienes (CD) concentration. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light for 4 weeks. Perfused isolated hearts (Langendorff technique) were exposed to 25 min global ischemia and subsequent 30 min reperfusion. The recovery of functional parameters (coronary flow, left ventricular developed pressure, contractility and relaxation index) during reperfusion as well as the incidence, severity and duration of arrhythmias during first 10 min of reperfusion were determined. The hearts from rats exposed to continuous light showed more rapid recovery of functional parameters but higher incidence, duration and severity of reperfusion arrhythmias compared to controls. In the left ventricle, the NOS activity was attenuated, but the CD concentration was not significantly changed. We conclude that the exposure of rats to continuous light modified cardiac response to I/R. This effect could be at least partially mediated by attenuated NO production.

Non-invasive assessment of the left ventricular contractility and cardiac index monitoring during the exercise stress-echo

Non-invasive assessment of the left ventricular contractility and cardiac index monitoring during the exercise stress-echo

Left ventricular shape-based contractility index

This study develops contractility indices in terms of the left ventricular (LV) ellipsoidal geometrical shape-factor. The contractility index (CONT1) is given by the maximum value d σ * / d t wherein σ * = σ / P , σ is the wall stress, and σ * is expressed in terms of the shape factor S (the ratio of the minor axis and major axis, B / A , of the instantaneous LV ellipsoidal model). Another contractility index (CONT2) is also developed based on how far apart the in vivo S at the start of ejection is from its optimized value, CONT 2 = ( S se - S se op ) / S se op , where S se refers to the value of S at the start of ejection, S se op is the derived optimal value of S se for which σ* is maximum. The values of S(= B/A) were calculated from cineventriculographically monitored LV volume, myocardial volume and wall-thickness. Then both the contractility indices were evaluated in normal subjects, as well as in patients with mild heart failure and in patients with severe heart failure. The normal values of CONT1 and CONT2 are 8.75±2.30 s −1 and 0.09±0.07, respectively. CONT1 decreased in patients with mild and severe heart failures to 5.78±1.30 and 3.90±1.30, respectively. CONT2 increased in patients with mild and severe heart failures to 0.11±0.09 and 0.23±0.12, respectively. This implies that a non-optimal and less ellipsoidal shape is associated with decreased contractility (and poor systolic function) of the LV. CONT1 and CONT2 are useful as non-invasively determinable quantitative indices of LV contractility, to distinguish between normal and pathologic LVs.