[Significance of calcium kinetics in the modulation of relaxation by load].
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Animals↗
Biomedical subjects
T C Gillebert
Publications and source records attributed to T C Gillebert.
Relaxation-systolic pressure relation. A load-independent assessment of left ventricular contractility.
This contribution reviews the regulation of left ventricular pressure (LVP) fall by load and relates this regulation to left ventricular contractility. Load regulation of LVP fall has to be distinguished from neurohumoral regulation, from effects induced by arterial reflected waves and from long-term load effects on contractility. The response of LVP fall to a moderate elevation of systolic LVP is highly variable. It depends on the ratio between the actual systolic pressure and peak isovolumetric pressure, defined as "relative load". Up to a relative load of 81% to 84%, LVP fall accelerates. Above this relative load, LVP fall decelerates. Depending on the level of relative load there is a wide variety of effects ranging from moderate acceleration of LVP fall to marked deceleration of LVP fall. Acceleration of LVP fall in response to a load elevation is associated with normal cardiac function, while slowing of LVP fall is associated with impaired cardiac function. Similar but opposite effects are observed with reductions of systolic LVP. Effects of changes in systolic LVP on time constant tau reveal a fair correlation with systolic elastance (Ees), peak dP/dtmax and regional fractional shortening (or ejection fraction). There is an excellent correlation with measured isovolumetric LVP, indicating that contraction-relaxation coupling is close when contractility is expressed in terms of peak isovolumetric pressure. Assessment of contractility with systolic LVP-relaxation relation is precise and load independent and can be performed with the sole use of a high-fidelity pressure gauge positioned in the left ventricular cavity.
Animals↗
Effects of calcium on left ventricular function early after cardiopulmonary bypass.
OBJECTIVES: Evaluation of the effects of intravenous CaCl2 on systolic and diastolic function early after separation from cardiopulmonary bypass (CPB) DESIGN: Prospective study SETTING: University hospital PARTICIPANTS: Twenty patients scheduled for elective coronary artery surgery INTERVENTIONS: Left ventricular (LV) pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the LV were simultaneously recorded on videotape. Measurements were obtained before the start of CPB, 10 minutes after termination of CPB, after intravenous administration of CaCl2, 5 mg/kg, and 10 minutes later. MEASUREMENTS AND MAIN RESULTS: Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relation. CaCl2 increased Ees from 2.62 +/- 0.46 to 5.58 +/- 0.61 (mean +/- SD), but induced diastolic dysfunction with an increase in Kc from 0.011 +/- 0.006 to 0.019 +/- 0.007. These changes were transient and had disappeared within 10 minutes after administration of CaCl2. CONCLUSIONS: CaCl2 early after CPB transiently improved systolic function at the expense of an increase in ventricular stiffness, suggesting temporary diastolic dysfunction.
Adult↗
Effects of lidoflazine on left ventricular function in patients.
OBJECTIVE: The present study evaluated the effects of the nucleoside transport inhibitor, lidoflazine, at a dose of 1 mg/kg, on left ventricular function. DESIGN: Patients were randomly assigned to receive either lidoflazine or saline in a double-blind manner. SETTING: A university hospital. PARTICIPANTS: The study was performed in 32 patients scheduled for elective coronary artery bypass surgery. INTERVENTIONS: Left ventricular pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relationship. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relationship. Cardiac function was assessed at baseline and after administration of either lidoflazine (group A [n = 16]) or placebo (group B [n = 16]). Data were compared using two-factor analysis of variance. MEASUREMENTS AND MAIN RESULTS: At baseline, diastolic and systolic function were comparable in both groups. Lidoflazine increased Kc from 0.079 +/- 0.015 to 0.125 +/- 0.017 mmHg/mL and decreased Ees from 2.481 +/- 0.213 to 1.217 +/- 0.211 mmHg/mL (p = 0.009 and p = 0.004, respectively). None of these changes occurred when placebo was administered. CONCLUSIONS: Administration of lidoflazine before the start of cardiopulmonary bypass impaired left ventricular systolic function but also increased diastolic stiffness.
Aged↗
The hemodynamic manifestation of normal myocardial relaxation. A framework for experimental and clinical evaluation.
Myocardial relaxation clinically manifests itself as left ventricular pressure (LVP) fall. The transition from contraction to relaxation is the precise moment at which 81-84% of peak isometric force has developed or the equivalent timing early during ejection. Defining the completion of relaxation and distinguishing relaxation from diastole appears merely semantic. Diastole is not a passive phase of the cardiac cycle. During diastole mechanical left ventricular properties still change due to incomplete relaxation, due to creep and stress relaxation, and due to autoregulation by preload and by nitric oxide. Description of timing and rate of LVP fall may provide useful information on underlying cardiac diseases such as ischaemia and hypertrophy. This information will however only be reliable if systolic cardiac function and systolic load are normal, and in the absence of a significant degree of nonuniformity, such as induced by conduction disturbances or by regional myocardial ischemia. The various effects of load and of nonuniformity on myocardial relaxation in the normal heart are reviewed. Coupling of timing and rate of LVP fall are explained in terms of cross-bridge mechanics. Specific effects of systolic pressure on LVP fall and their relation to systolic cardiac function are emphasized. These data constitute a conceptual framework for the analysis of myocardial relaxation in cardiovascular research and in the cardiac patient. Comparison of clinical and experimental data during manipulation of afterload should lead to an improved understanding of clinical relaxation disturbances and to a therapeutic approach, which is relevant from the physiopathological point of view. LVP fall may provide useful and quantitative information on systolic LV function if measurements are performed under different conditions of systolic load. This information is similar to systolic pressure-volume relations, but can be performed with the sole use of a micromanometer in the LV cavity.
Animals↗
Continuous total intravenous anesthesia, using propofol and fentanyl in an open-thorax rabbit model: evaluation of cardiac contractile function and biochemical assessment.
Effects are reported of an anesthetic protocol involving use of predetermined intravenous (i.v.)-administered drug doses during acute experimental procedures in vagotomized, New Zealand White rabbits with open thorax (n = 20) in a nonsurvival study. After induction of anesthesia by intramuscular (i.m.) administration of ketamine hydrochloride (25 mg/kg of body weight) and xylazine hydrochloride (15 mg/kg), continuous total intravenous anesthesia (TIVA) with propofol (0.6 mg.kg-1.min-1), fentanyl (0.48 micrograms.kg-1.min-1) and the neuromuscular agent vecuronium bromide (0.003 mg.kg-1.min-1) was maintained. Oxygenation conditions, acid-base balance, biochemical and hemodynamic variables, and cardiac contractile function were assessed. Measurements were made and blood analysis was done at the moment of ear vein catheterization (P1); before (P2) and after (P3) sternotomy; after complete instrumentation (P4); and at the beginning (T1), in the middle (T2), and at the end (T3) of the experimental protocol. From T1 to T3, heart rate was kept constant by use of atrial pacing at a rate of 235 +/- 15 beats/min. During surgical preparation and instrumentation, hemoglobin (Hb) concentration decreased from 12.5 +/- 0.9 g/dl (mean +/- SEM) to 7.7 +/- 0.7 g/dl and remained stable thereafter. Blood gas analysis (PO2, PCO2, pH, HCO3-, base excess, measured SaO2) and measurement of plasma lactate concentration revealed constant, adequate oxygenation. Plasma electrolyte values (Na+, Cl-, K+, Ca2+) remained within physiologic ranges throughout. Blood glucose concentration increased from 229 +/- 30 mg/dl at P1 to 382 +/- 34 mg/dl at P3. At T1, glycemia had returned to normal values and remained stable. Heart rate, blood pressure, ventricular elastance (Ees), and diastolic stiffness constant (Kc) remained stable throughout. Other indices of ventricular function (dP/dtmax, thickening, ejection duration, and maximal left ventricular pressure) remained unaltered as well. Left ventricular relaxation (dP/dtmin, tau) did not change. After anesthesia induction by i.m. administration of ketamine and xylazine, TIVA with predetermined drug dosages of propofol and fentanyl provided stable cardiovascular function for open-thorax long-term experimental observations in a nonsurvival setting.
Anesthetics, Intravenous↗
Inotropic effects of sodium nitroprusside: a clinical study on coronary surgery patients.
OBJECTIVE: Sodium nitroprusside (SNP) induces release of nitric oxide and is widely used as a vasoactive drug. Recent research analyzed effects of SNP on cardiac muscle and described variable inotropic effects. The present study evaluated effects of SNP on left ventricular (LV) function in patients undergoing coronary artery surgery. METHODS: The study was performed in 100 patients with a preoperative ejection fraction > 40%. LV pressures were measured with a fluid-filled catheter in the LV cavity. Hearts were placed in AV sequential mode at a rate of 90 beats/min. Measurements were obtained at end-expiration and consisted of a control tracing and a tracing obtained after a 5 min infusion of SNP 0.5 microgram.kg-1.min-1. These measurements were obtained before and after cardiopulmonary bypass (CPB). An average of 5 consecutive beats was obtained for analysis. Ventricular function was assessed with LV pressure and dP/dt. Data were analyzed using two factor analysis of variance for repeated measurements. RESULTS: 1. Baseline patient data (n = 80). Before CPB, a variable inotropic response to SNP was observed. The direction of the inotropic response was related to preoperative beta-blocking medication. LVP and dP/dtmax increased with SNP in patients without preoperative beta-blocking medication. In patients on preoperative beta-blocking medication, SNP did not alter LVP and dP/dtmax. After CPB, a positive inotropic response was not observed in any of the patients. 2. Postoperative patient data under dobutamine (n = 20). Data of these separate observations were similar to baseline data before CPB. After CPB and under dobutamine administration (5 micrograms.kg-1.min-1) all 20 patients developed a positive inotropic response to SNP. CONCLUSIONS: In coronary surgery patients, SNP induced variable inotropic effect. The direction of the inotropic response appeared to be modulated by the beta-adrenergic drive.
Adrenergic beta-Agonists↗
Personality as independent predictor of long-term mortality in patients with coronary heart disease.
BACKGROUND: Emotional distress has been related to mortality in patients with coronary heart disease (CHD), but little is known about the role of personality in long-term prognosis. We postulated that type-D personality (the tendency to suppress emotional distress) was a predictor of long-term mortality in CHD, independently of established biomedical risk factors. METHODS: We studied 268 men and 35 women with angiographically documented CHD, aged 31-79 years, who were taking part in an outpatient rehabilitation programme. All patients completed personality questionnaire at entry to the programme. We contacted them 6-10 years later (mean 7-9) to find out survival status. The main endpoint was death from all causes. FINDINGS: At follow-up, 38 patients had died; there were 24 cardiac deaths. The rate of death was higher for type-D patients than for those without type-D (23 [27%]/85 vs 15 [7%]/218; p < 0.00001). The association between type-D personality and mortality was still evident more than 5 years after the coronary event and was found in both men and women. Mortality was also associated with impaired left ventricular function, three-vessel disease, low exercise tolerance, and the lack of thrombolytic therapy after myocardial infarction. When we controlled for these biomedical predictors in multiple logistic regression analysis, the impact of type-D remained significant (odds ratio 4.1 [95% CI 1.9-8.8]; p = 0.0004). In this group of CHD patients, type-D was an independent predictor of both cardiac and non-cardiac mortality. Social alienation and depression were also related to mortality, but did not add to the predictive power of type-D. INTERPRETATION: We found that type-D personality was a significant predictor of long-term mortality in patients with established CHD, independently of biomedical risk factors. Personality traits should be taken into account in the association between emotional distress and mortality in CHD.
Adult↗
Recovery of systolic and diastolic left ventricular function early after cardiopulmonary bypass.
BACKGROUND: Impairment of left ventricular function after cardiopulmonary bypass (CPB) is well recognized, but little is known about the time course of recovery of cardiac function early after separation from CPB. Therefore, recovery of left ventricular function was evaluated early after separation from CPB in patients undergoing coronary artery surgery. The authors tried to determine whether this recovery might be attributed to autoregulation of function by preload. METHODS: Left ventricular pressure was measured with fluid-filled catheters. Data were digitally recorded during increased pressure induced by elevating the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/ml) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, ml-1) of the diastolic pressure-volume relation. Cardiac function was assessed before CPB, after termination of CPB, and 5, 10, and 15 min later. Two different separation procedures from CPB were compared: in protocol 1, left ventricular function was documented during the standard procedure (n = 24); in protocol 2, the heart was optimally filled 10 min before separation from CPB (n = 12). RESULTS: In protocol 1, Ees was 2.88 +/- 0.21 mmHg/ml (mean +/- SEM) and Kc was 0.012 +/- 0.001 ml-1 before CPB. Within 10 min after separation from CPB, Ees increased from 1.10 +/- 0.32 to 2.92 +/- 0.34 (P = 0.001) and Kc decreased from 0.022 +/- 0.002 to 0.011 +/- 0.001 (P = 0.001). The parameters remained stable thereafter. In protocol 2, Ees was 2.92 +/- 0.51 mmHg/ ml and Kc was 0.011 +/- 0.002 ml-1 before CPB. Depression of systolic and diastolic function was not observed in these patients. At time 0, Ees was 2.46 +/- 0.16 and Kc was 0.012 +/- 0.002. These values remained stable throughout the entire observation period. CONCLUSIONS: Significant functional recovery was observed early after separation from CPB, which was suggestive of time-dependent changes in both systolic and diastolic left ventricular function induced by preload restoration.
Anesthesia↗
Myocardial relaxation in regionally stunned left ventricle.
Load regulation of pressure fall was analyzed in regionally stunned left ventricles (LV) of anesthetized dogs. Stunning delayed and slowed pressure fall. When partial aortic occlusions elevated systolic pressure by 12.5 +/- 0.4 mmHg, the rate of pressure fall remained unchanged at baseline but slowed after stunning. This different response after stunning could be attributed entirely to decreased contractility and decreased development of peak isovolumetric pressure. Total aortic occlusions were then performed at various timings during ejection. With early occlusions and isovolumetric heartbeats, systolic pressure was lower after stunning, but pressure fall slowed to the same extent. With midocclusions the stunned LV developed relatively more systolic pressure, and pressure fall slowed more. This suggested a delayed transition from contraction to relaxation. With late occlusions pressure fall did not slow as with earlier occlusions, but initial pressure fall accelerated both at baseline and after stunning. The data suggested that load dependence was preserved with stunning and that, even if myocardial inactivation might be delayed, this delay did not contribute to the observed slowing of pressure fall.
Animals↗
European certification of clinical competence in adult echocardiography issued in Belgium. The Steering Committee of the Belgian Working Group on Echocardiography and Cardiac Doppler.
In accordance with the European proposals, adapted guidelines are proposed for a certification of clinical competence in adult echocardiography, with transoesophageal echocardiography as a special option. The conditions required to be candidate to the certification, the exemptions of practical training for long-term echocardiographers and the organisation of the training itself are successively considered. Standards for training, site accreditation, official logbook characteristics, minimal numbers of examinations and minimal stage duration are defined. Content of theoretical training, as well as organisation of formal and informal education and of final examination, are described.
Adult↗
Preload, length-tension relation, and isometric relaxation in cardiac muscle.
It is widely believed that preload does not influence isometric relaxation and left ventricular pressure fall. Preload, however, alters cross-bridge interaction and intracellular Ca2+ handling. We therefore evaluated the effects of preload reduction on peak length-tension relation and on physiologically sequences isometric force decline. 1) Acute preload reduction resulted in a shift to the left of the peak length-tension relation, an earlier onset of force decline, and an increased rate of initial force decline. 2) Prolonged preload reduction was compared with acute preload reduction and resulted in an unchanged peak length-tension relation, a delayed onset of force decline, and a decreased initial rate of force decline. 3) Prolonged preload reduction was compared with baseline and resulted in a shift to the left of the peak length-tension relation, without predictable effects on timing or rate of force decline. Our hypothesis is that the findings reflected both changes in troponin C affinity for Ca2+ and altered Ca2+ reuptake by the sarcoplasmic reticulum.
Animals↗
Nonuniform course of left ventricular pressure fall and its regulation by load and contractile state.
BACKGROUND: Effects of systolic left ventricular pressure (LVP) on rates of pressure fall remain incompletely understood. This study analyzed phase-plane dP/dt versus LVP plots to differentiate between accelerating and decelerating effects and to investigate the variability in reported load effects on rates of LVP fall. METHODS AND RESULTS: Abrupt aortic occlusions were performed by inflating a balloon positioned in the ascending aorta of anesthetized open-chest dogs (n = 17). The occlusions resulted in clamp elevations of systolic LVP. In protocol A, the elevations of systolic LVP induced by total aortic occlusions were timed at early, mid, and late ejection. The magnitude of the elevations was 36.0 +/- 3.6 mm Hg for early, 11.6 +/- 0.6 mm Hg for mid, and negligible for late occlusions. The course of LVP fall appeared to be more complex than previously appreciated. Pressure fall might be subdivided in an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. The initial phase accelerated with mid and late occlusions. The intermediate phase slowed down with early and to a lesser extent with mid occlusions. The terminal phase was never affected by aortic clamp occlusions. In protocol B, early elevations of systolic LVP were obtained with multiple graded aortic occlusions. The effects of matched LVP elevations of 12 mm Hg on rate of LVP fall were evaluated with the time constant of LVP fall (tau) and showed an interanimal variability ranging from acceleration and a 20% decrease in tau to deceleration and a 35% increase in tau. Changes in tau were moderately correlated with commonly used indexes of contractility (peak +dP/dt, r = -.78; regional fractional shortening, r = -.63). These changes in tau showed a close correlation with the systolic LVP of the test beat, expressed as a percentage of the peak isovolumetric LVP, obtained with total aortic occlusion (r = .984). This suggested that the contraction-relaxation coupling should be analyzed in terms of peak force development rather than contraction velocity or ejection fraction. CONCLUSIONS: LVP fall could be subdivided into an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. Effects of elevations in systolic LVP on rate of LVP fall could be predicted by knowing peak isovolumetric LVP. Nonuniformity of LVP fall and adequate interpretation of load effects should be taken into account when clinical situations or pharmacological interventions are considered. In congestive heart failure, slow LVP fall could mainly reflect working conditions close to isovolumetric rather than relaxation disturbances.
Animals↗
Mechanisms of endocardial endothelium modulation of myocardial performance.
The nature of modulation of myocardial performance by the endocardial endothelium (EE) is briefly described. Possible mechanisms of this modulation include a physical barrier effect, the release of various chemical messengers and a transendothelial physicochemical barrier.
Animals↗
Diastolic failure: pathophysiology and therapeutic implications.
Primary diastolic dysfunction or failure is a distinct pathophysiologic entity. It results from increased resistance to ventricular filling, which leads to an inappropriate upward shift of the diastolic pressure-volume relation, particularly during exercise (exercise intolerance). The causes of diastolic failure are inappropriate tachycardia, decreased diastolic compliance and impaired systolic relaxation. Impaired (incomplete or slowed) systolic relaxation must be conceptually distinguished from compensatory prolonged systolic contraction (delayed or retarded relaxation). Optimal therapy will depend on the type of disease, the phase during the course of a given disease and the coexistence and relative contribution of various (de)compensatory processes. Treatment may consist of bradycardic, remodeling and lusitropic drugs.
Diastole↗
Diastolic dysfunction in post-cardiac surgical management.
Although an appropriate definition of primary diastolic failure is still not at hand, primary diastolic failure is a distinct pathophysiologic syndrome. It is due to an increased resistance to ventricular filling and results in an inappropriate upward shift of the diastolic P-V relationship, especially during exercise. This leads to exercise intolerance with symptoms of congestion. The causes are known, ie, impaired systolic relaxation, decreased diastolic compliance, and inappropriate tachycardia. Pathophysiologically impaired (incomplete or slowed) systolic relaxation must be distinguished from physiologic, compensatory prolonged contraction (delayed or retarded relaxation). Treatment of diastolic failure is feasible, but necessitates a clear understanding of the etiology, pathogenesis, and pathophysiology of the underlying cardiac disease. Optimal therapy will depend on the type of disease, on the phase during the pathophysiologic evolution of a given disease, and on the coexistence and relative contribution of various compensatory or decompensatory mechanisms. This often requires a comprehensive analysis of hemodynamics, for example, with echo-doppler, completed, whenever necessary, by catheterization.
Cardiac Output, Low↗
Role of the endocardial endothelium in the regulation of myocardial function. Physiologic and pathophysiologic implications.
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Animals↗
Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha 1-adrenergic stimulation.
BACKGROUND: High-power intracavitary ultrasound abbreviates left ventricular (LV) ejection duration, thereby decreasing mechanical LV performance, presumably by selective impairment of endocardial endothelial function. METHODS AND RESULTS: Effects of ultrasound were evaluated in the ejecting LV of anesthetized, open-chest dogs under different conditions of LV volume and contractile state and after mild selective alpha 1-adrenergic stimulation. LV pressures, left atrial pressures, and regional segment lengths were measured in anterior and posterior midwall. A cylindrical ultrasound probe (0.9 MHz, 25 W) mounted on a catheter was inserted into the LV cavity through the apex and was activated for 4 minutes in each condition. In protocol A (n = 7), LV volume was altered with caval vein occlusion and intravenous dextran infusion. The ultrasound probe was activated at low (4.1 +/- 0.9 mm Hg), mid (10.6 +/- 1.5 mm Hg), and high (17.9 +/- 1.8 mm Hg) LV end-diastolic pressure (EDP). Effects of ultrasound were less pronounced at higher EDP. For example, the time interval from end-diastole to peak (-)dP/dt decreased by 7.5 +/- 2.3% at low, 4.4 +/- 2.2% at mid, and 1.9 +/- 1.6% at high LVEDP (p < 0.001). In protocol B (n = 7), LV inotropic state was altered by slow intravenous infusion of low-dose calcium. The ultrasound probe was activated before and after calcium. Effects of ultrasound were less pronounced after calcium. Time from end-diastole to peak (-)dP/dt decreased by 8.4 +/- 3.1% at baseline and by 3.5 +/- 2.1% after calcium (p < 0.001). In protocol C (n = 7), activation of the ultrasound probe was performed at baseline and after mild selective alpha 1-adrenergic stimulation (propranolol plus phenylephrine). Effects of ultrasound were similar at baseline and after propranolol but increased after phenylephrine. Time from end-diastole to peak (-)dP/dt decreased by 5.2 +/- 2.4% at baseline, by 5.3 +/- 1.9% after propranolol, and by 8.9 +/- 3.2% after phenylephrine (p < 0.05). CONCLUSIONS: Effects of intracavitary ultrasound, which are presumably mediated through modulation of endocardial endothelial function, were more important at low volume, lower calcium, and under mild selective alpha 1-adrenergic stimulation.
Animals↗