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Left atrial inflow propagation rate: a new transesophageal echocardiographic index of preload.

We postulated that the rate of blood propagating into the left atrium from the left upper pulmonic vein would be a useful measure of pulmonary capillary wedge pressure (PCWP). In 23 adult patients who were critically ill (ie, study group) and receiving mechanical ventilation, color M-mode multiplane transesophageal echocardiography was used to measure left atrial inflow propagation rate (LAIF-PR) as a potential index of PCWP measured by right heart catheterization. LAIF-PR was measured in systole and diastole as the slope of the color M-mode signal entering the left atrium from the left upper pulmonic vein. Correlation with PCWP was good for systolic (r = -0.847, P < .0001) and diastolic (r = -0.78, P < .0001) LAIF-PR. The reliability of univariate linear regression equations derived from the study group was tested in 29 subsequent patients (ie, testing group). Measured PCWP was accurately estimated within 5 mm Hg in 85% (22 of 26 patients) and 68% (17 of 25 patients) of the testing group by systolic and diastolic LAIF-PR, respectively. Color M-mode transesophageal echocardiography-derived LAIF-PR, particularly in systole, is a promising new index to estimate PCWP in patients who are critically ill.

Adolescent↗

Direct evidence that sustained dysfunction of left atrial appendage contributes to the occurrence of cardiogenic brain embolism in patients with paroxysmal atrial fibrillation.

OBJECTIVE: The goal of this study was to investigate transesophageal echocardiographic (TEE) findings after the termination of atrial fibrillation to clarify the direct evidence for occurrence of acute cardiogenic brain embolism (CBE) in patients with paroxysmal atrial fibrillation (PAF). PATIENTS AND METHODS: Among 98 consecutive patients with CBE, we investigated TEE in 16 patients with PAF (Group CBE, 72 +/- 10 years) within 7 days of the onset and 2 weeks after the first study, in comparison with 15 age-matched PAF patients without CBE (Group N). The duration from reversal to normal sinus rhythm to first TEE was 6 +/- 1 days in both groups. RESULTS: There were no significant differences in left atrial dimension and emptying flow velocity of the left atrial appendage (LAA-eV) between groups. Group CBE had significantly larger LAA area (4.3 +/- 1.3 cm2 vs. 3.1 +/- 1.0 cm2, p < 0.05), smaller LAA fractional area change (LAA-FAC) (43 +/- 25% vs. 80 +/- 22%, p < 0.001), and a higher incidence of left atrial spontaneous echo contrast (LAA-SEC) (25% vs. 7%, p < 0.05) than group N, and those abnormalities in group CBE were significantly improved at the second TEE (LAA area: to 3.2 +/- 0.9 cm2, p < 0.05; LAA-FAC: to 84 +/- 26%, p < 0.001; LAA-SEC: to 0%, p < 0.05), respectively. CONCLUSION: LAA-FAC is a more sensitive marker for LAA dysfunction than the widely used index, LAA-eV, and a sustained deterioration of LAA-FAC may be direct evidence for thrombus formation and occurrence of acute CBE in patients with PAF.

Aged↗

Assessment of left atrial pressure-area relation in humans by means of retrograde left atrial catheterization and echocardiographic automatic boundary detection: effects of dobutamine.

OBJECTIVES: This study sought to validate and apply a new method for obtaining the left atrial (LA) pressure-area relation. BACKGROUND: In physiologic investigations, the pressure-area relation is the most accurate and representative index of LA hemodynamic status. METHODS: We applied real-time two-dimensional echocardiographic imaging with automatic boundary detection to estimate LA area changes. To obtain LA pressure, a catheter-tipped micromanometer was introduced retrogradely into the left atrium using a steerable cardiac catheter developed at our institution. Twenty-five patients (11 normal subjects, 7 patients with an enlarged left atrium due to heart failure, 7 patients with atrial fibrillation) were studied before and after dobutamine administration. From the LA pressure-area relation, the area of the A loop (the first counterclockwise loop) and the V loop (the second clockwise loop), the pressure-minimal area relation and the LA passive elastic chamber stiffness constant were measured. RESULTS: Normalized pressure-minimal area relation was highly linear and sensitive to changes in inotropic state (normal subjects: from 0.96 to 1.27 mm Hg/cm2, p < 0.01; patients with heart failure: from 0.59 to 0.68 mm Hg/cm2, p = NS; patients with atrial fibrillation: from 0.80 to 1.06 mm Hg/cm2, p < 0.05). The LA stroke work index was accurately calculated, and a very good correlation was found with LA preload. LA stroke work index was lower in patients with heart failure (3.9 +/- 0.8 cm2 x mm Hg, p < 0.001), whereas the LA stiffness constant was increased in patients with heart failure (0.801 +/- 0.097 cm(-2), p < 0.01) and atrial fibrillation (0.796 +/- 0.091 cm(-2), p < 0.01) compared with normal subjects (stroke work index 7.3 +/- 1.9 cm2 x mm Hg, stiffness constant 0.623 +/- 0.107 cm(-2), respectively). In addition, increased inotropic state after dobutamine administration resulted in improved LA pump function (stroke work index) in normal subjects (from 10.2 +/- 0.9 to 13.8 +/- 1.9 cm2 x mm Hg, p < 0.001) and patients with heart failure (from 4.3 +/- 0.4 to 7.6 +/- 0.4 cm2 x mm Hg, p < 0.001), as well as in decreased stiffness constant in all groups of patients (normal subjects: from 0.712 +/- 0.141 to 0.473 +/- 0.089 cm(-2); patients with heart failure: from 0.896 +/- 0.181 to 0.494 +/- 0.093 cm(-2); patients with atrial fibrillation: from 0.779 +/- 0.145 to 0.467 +/- 0.086 cm(-2), p < 0.001). CONCLUSIONS: The method described here is both safe and reproducible for obtaining the LA pressure-area relation. LA function is impaired in patients with heart failure and in those with atrial fibrillation and may be acutely improved with inotropic agents in both normal and diseased atria.

Adrenergic beta-Agonists↗

Effect of age and pathology on left ventricular diastolic function: the diagnostic yield of Doppler echocardiography.

BACKGROUND: Doppler echocardiography has been proposed to detect left ventricular (LV) diastolic dysfunction in the elderly. However, the validity of this technique in differentiating the effects of pathology from those of normal aging has not been defined. METHODS: Doppler indices of LV diastolic function were obtained in 85 patients (34 hypertensive, 29 with coronary artery disease, 22 with both conditions) and in 56 healthy volunteers. RESULTS: A linear correlation with age was found for all parameters in controls, and for many parameters in patients. Also, in the presence of heart diseases, age exerted a powerful, independent effect on Doppler parameters. None of these differed between patients and controls in advanced age. CONCLUSION: Due to the prevailing age-related variations in Doppler indices of diastolic performance occurring beyond the age of 65, Doppler echocardiography cannot be employed to diagnose LV diastolic dysfunction in the elderly.

Adult↗

Isolated paced guinea pig left atrium: a new ouabain-induced arrhythmia model.

Ouabain (1.0 x 10(-6) M) produced a uniform, consistent and reproducible arrhythmia on paced guinea pig left atrium bathed in Ringer-Locke solution. A second spell of arrhythmia of similar intensity and pattern, which had the same latency to onset, was reproduced 60 min after the first spell of arrhythmia. Lignocaine (3.46 x 10(-5) M) and propranolol (1.69 x 10(-5) M) gave full protection against the second spell of arrhythmia, whereas lower doses of these drugs were able to delay the onset and reduce the duration. Clonidine (3.75 x 10(-5) M), however, was found to be ineffective. This model can be used for the detection and assessment of directly acting antiarrhythmics in very low concentrations, since this is a sensitive and reliable method.

Animals↗

Beta-adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats.

To determine whether beta-adrenergic agonist therapy increases alveolar liquid clearance during the resolution phase of hydrostatic pulmonary edema, we studied alveolar and lung liquid clearance in two animal models of hydrostatic pulmonary edema. Hydrostatic pulmonary edema was induced in sheep by acutely elevating left atrial pressure to 25 cmH(2)O and instilling 6 ml/kg body wt isotonic 5% albumin (prepared from bovine albumin) in normal saline into the distal air spaces of each lung. After 1 h, sheep were treated with a nebulized beta-agonist (salmeterol) or nebulized saline (controls), and left atrial pressure was then returned to normal. beta-Agonist therapy resulted in a 60% increase in alveolar liquid clearance over 3 h (P < 0.001). Because the rate of alveolar fluid clearance in rats is closer to human rates, we studied beta-agonist therapy in rats, with hydrostatic pulmonary edema induced by volume overload (40% body wt infusion of Ringer lactate). beta-Agonist therapy resulted in a significant decrease in excess lung water (P < 0.01) and significant improvement in arterial blood gases by 2 h (P < 0.03). These preclinical experimental studies support the need for controlled clinical trials to determine whether beta-adrenergic agonist therapy would be of value in accelerating the resolution of hydrostatic pulmonary edema in patients.

Adrenergic beta-Agonists↗

Regional differences of beta 1- and beta 2-adrenoceptor-mediated functions in feline heart. A beta 2-adrenoceptor-mediated positive inotropic effect possibly unrelated to cyclic AMP.

The effects of (-)-adrenaline and (-)-noradrenaline were studied on isolated preparations of kitten heart. To define the contribution of beta 1-adrenoceptors (beta 1AR) and beta 2-adrenoceptors (beta 2AR) we used as tools the highly beta 1AR-selective antagonist CGP 20,712 A and non-linear analysis of antagonism. The beta 2AR-mediated responses to the catecholamines, disclosed by CGP 20,712 A, were verified by blockade with the beta 2AR-selective ICI 118,551. The relative density and contribution of beta 1AR and beta 2AR to (-)-adrenaline- and (-)-noradrenaline-induced adenylyl cyclase stimulation was also estimated in right ventricular membranes. 1. In the sinoatrial pacemaker (-)-adrenaline caused positive chronotropic effects through both beta 1AR and beta 2AR while (-)-noradrenaline does so predominantly through beta 1AR. During beta 1AR blockade (-)-adrenaline did cause the same maximum effects through beta 2AR as (-)-noradrenaline did through beta 1AR. 2. In left atria (-)-adrenaline caused positive inotropic effects predominantly through beta 1AR. CGP 20,712 A also uncovered a beta 2AR component at high (-)-adrenaline concentrations comprising one third of the maximum beta 1AR-mediated response. 3. Receptor binding assays revealed that 80% of right ventricular beta AR were beta 1AR and 20% beta 2AR. Consistent with this finding, around 80% of the adenylyl cyclase stimulation by both (-)-noradrenaline and (-)-adrenaline was mediated through beta 1AR, around 20% through beta 2AR. The positive inotropic effects of (-)-noradrenaline appeared to be nearly exclusively mediated through beta 1AR in right ventricular papillary muscles. 4. The positive inotropic effects of (-)-adrenaline were quite variable with regard to beta 1AR and beta 2AR in right ventricular papillary muscles. Although beta 1AR-mediated effects are predominant in many muscles with only a small contribution of beta 2AR, in some muscles beta 2AR mediated around 50% of the maximum effect elicited through beta 1AR. In 3 out of 17 muscles beta 2AR mediated the same maximum effect of (-)-adrenaline as beta 1AR. 5. On occasion, we found marked beta AR heterogeneity amongst two muscles from the same right ventricle. One muscle only exhibited beta 1AR-mediated effects of (-)-adrenaline whereas in the other muscle maximal effects could be elicited through beta 2AR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗

Assessment of left ventricular filling pressures by Doppler in the presence of atrial fibrillation.

BACKGROUND: Although Doppler echocardiography can be used to estimate left ventricular filling pressures (LVFPs) in patients in sinus rhythm, its utility in atrial fibrillation is unknown. METHODS AND RESULTS: An initial training population of 30 patients (17 men, 13 women: mean age, 69 +/- 9 years; range, 48 to 87 years) was studied. Measurements of LVFP were obtained simultaneously with pulsed Doppler recordings of mitral and pulmonary venous flow velocities and color M-mode recording of the flow propagation velocity of the mitral inflow. Measurements were averaged over 10 cardiac cycles. In addition, left atrial volume was derived from the apical four-chamber view. Significant relations were observed between LVFP and several parameters derived from the transmitral and pulmonary venous velocity and left atrial volume. The best relations were observed with the peak acceleration (PkAcc) of the mitral velocity (r = .84), isovolumic relaxation time (IVRT) (r = .76), mean early (E) velocity (r = .6), and the ratio of peak E velocity to color M-mode flow propagation velocity (r = .65). The best model obtained by multilinear regression analysis (r = .88) included PkAcc and IVRT. The equation LVFP = 22+0.005 (PkAcc)-0.183(IVRT) was tested in 30 additional patients (12 women and 18 men: mean age, 65 +/- 10.6 years; range, 43 to 87 years) with similar results (r = .87). When all 60 patients were combined, the mean +/- ISD difference between predicted and observed pressure was -0.88 +/- 3.6 mm Hg. CONCLUSIONS: LVFPs can be estimated with Doppler echocardiography in patients with atrial fibrillation.

Aged↗

Determinant of left atrial dilation in patients with hypertrophic cardiomyopathy: a real-time 3-dimensional echocardiographic study.

To identify the determinants of left atrial (LA) dilation for patients with hypertrophic obstructive cardiomyopathy (HOCM), first we validated LA volume determination by real-time 3-dimensional echocardiography using magnetic resonance imaging in patients. Subsequently, real-time 3-dimensional echocardiography and 2-dimensional Doppler echocardiography were performed in 60 patients with HOCM and in 17 age-matched control subjects. LA volumes and left ventricular (LV) filling pressures were higher for patients with HOCM than in control subjects. By stepwise multilinear regression analysis, LV end-diastolic pressure, resting LV outflow tract pressure gradient, and LV wall thickness were significant determinants of LA dilation. However, tau, -dP/dt, LV stiffness, provokable pressure gradient, and mitral regurgitation did not have any independent relationship with LA volumes. Therefore, it is concluded that LA volume can be accurately determined by real-time 3-dimensional echocardiography; and LA dilation in patients with HOCM is related to LV filling pressure, LV outflow tract pressure gradient, and LV wall thickness.

Atrial Function, Left↗

Correlation of left atrial size with p-wave duration in interatrial block.

BACKGROUND: Interatrial block (IAB) [P-wave duration > or = 110 ms] is associated with left atrial (LA) enlargement (LAE) and pathophysiologic derangements that result in atrial tachyarrhythmias, LA electromechanical dysfunction, and embolism. However, there has been no study addressing the direct correlation of P-wave duration in IAB and LAE. METHODS: One hundred eighty-one consecutive patients who were admitted to a tertiary care teaching hospital over 5 consecutive days were screened for past transthoracic echocardiogram evaluations and were then matched with ECGs done within 10 days of these echocardiographic investigations. ECGs were evaluated for presence of IAB, and patients were subsequently classified into two groups: control patients and patients with IAB. Patients were also matched for common comorbidities. Mean, SD of age, Pearson correlation coefficient (r), p values, and multivariate and linear regression analyses were analyzed for the investigated variables of LA size, left ventricular hypertrophy (LVH), posterior wall thickness, septal thickness, and P-wave duration. RESULTS: From the sample (n = 66; mean age +/- SD, 71.3 +/- 13.7; female gender, 48.5%), the mean LA size in the control group was 36.7 +/- 4.01 mm and for the group of patients with IAB (n = 38) was 42.2 +/- 7.25 mm (p = 0.004). Linear regression analysis revealed that P-wave duration was significantly correlated with LA size (p = 0.0002, r = 0.606). CONCLUSIONS: Degree of conduction delay in IAB (P-wave duration) is an independent, direct correlate of LAE, and the regression equation (LA size [in millimeters] = 2.47 +/- 0.29 x P-wave duration [in milliseconds]) could be used to estimate LAE.

Aged↗

Mapping and ablation of left atrial flutters.

BACKGROUND: Typical right atrial isthmus-dependent flutters have been described in detail, but very little is known about left atrial (LA) flutters. METHODS AND RESULTS: We performed conventional and 3D mapping of the LA for 22 patients with atypical flutters. Complete maps in 17 patients demonstrated macroreentrant circuits (n=15) with 1 to 3 loops rotating around the mitral annulus, the pulmonary veins, and a zone of block or a silent area. In 2 patients, a small reentry circuit with a zone of markedly slow conduction was identified. Linear ablation performed across the most accessible part of the circuit cured 16 patients (73%) with a follow-up of 15+/-7 months. CONCLUSIONS: LA reentrant tachycardias are related to individually varying circuits and are amenable to mapping guided radiofrequency ablation.

Adult↗

Pulmonary artery occlusion pressure is not accurate immediately after cardiopulmonary bypass.

Elevated pulmonary vascular resistance (PVR), differential cardiac dynamics, and increased lung water following cardiopulmonary bypass (CPB) have been proposed as limitations to the accuracy of the pulmonary artery occlusion pressure (PAOP) in estimating left ventricular preload. A prospective study of 22 patients undergoing elective myocardial revascularization is described wherein PAOP was compared with directly measured left atrial pressure (LAP). The reliability of PAOP to estimate LAP in the hour immediately following CPB and at 1, 4, 8, and 12 hours post-CPB was examined with repeated measures analysis of variance. Relationships between the PAOP-LAP difference and PVR, core temperature, arterial CO2 tension, and right and left ventricular stroke work indices (RVSWI, LVSWI) were tested by linear regression analysis. There was greater variability in measurements at 15, 30, and 45 minutes immediately after CPB, demonstrated by a pooled correlation coefficient of 0.73 versus 0.90 in the postoperative period. The degree of discrepancy between PAOP and LAP lessened with time. There was no determinable relationship of the PAOP-LAP gradient to PVR, level of PCO2, temperature, RVSWI, or LVSWI. Potential sources of discrepancy include airway pressure effects, position of the measuring catheters, positive end-expiratory pressure, infusion of protamine sulfate, extremes of pulmonary artery pressures, and effects of an open pericardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Correlation of end-diastolic pressure and myocardial elasticity with the transit time of the left atrial pressure wave (A-Ar interval).

Contraction of the left atrium in diastole generates a pressure wave that moves along the postero-lateral wall of the left ventricle (LV), rebounds off the LV apex, and is then directed toward the outflow tract. The movement of this atrial pressure wave may be detected with pulsed Doppler echocardiography by placing a sample volume in the LV outflow tract. The resulting spectral profile shows the initial. A velocity wave and also the Ar velocity wave, which is caused by the atrial pressure wave rebounding off the LV apex. The transit time from the inflow tract to the outflow tract of the atrial pressure wave (A-Ar interval) may be determined from the time axis of the spectral profile by measuring the peak-to-peak separation of the A and Ar, velocity waves. It occurs in the range 25 to 80 milliseconds. The primary determinant of the A-Ar interval is the elasticity of the LV myocardium. We correlated ventricular elasticity with the A-Ar interval in 47 patients and found a significant negative linear correlation (r = -0.782, p < 0.001). Because the pressure in a viscoelastic conduit such as the LV is determined by the elasticity of the ventricular wall, we correlated end-diastolic pressure with the A-Ar interval and again showed a significant negative linear correlation (r = -0.701, p < 0.001). The A-Ar interval is an easily measured noninvasive index of the diastolic function of the LV that reflects its intrinsic elasticity and end-diastolic pressure. It is therefore a quantitative measurement of LV wall stiffness and end-diastolic pressure.

Adult↗

Mechanisms of hypotensive effects of a posture change from seated to supine in humans.

The hypothesis tested was that the hydrostatic stimulation of carotid baroreceptors is pivotal to decrease mean arterial pressure at heart level during a posture change from seated to supine. In eight males, the cardiovascular responses to a 15-min posture change from seated to supine were compared with those of water immersion to the xiphoid process and to the neck, respectively. Left atrial diameter and cardiac output (rebreathing) increased similarly during the posture change and water immersion to the xiphoid process and further so during neck immersion. Mean arterial pressure decreased by 12 +/- 2 mmHg during the posture change, by 5 +/- 1 mmHg during xiphoid immersion, and was unchanged during neck immersion. Arterial pulse pressure increased by 12 +/- 3 mmHg during the posture change (P < 0.05) and less during xiphoid and neck immersion by 7 +/- 3 mmHg (P < 0.05). Total peripheral vascular resistance decreased similarly during the posture change and neck immersion and slightly less during xiphoid immersion (P < 0.05). In conclusion, the hydrostatic stimulation of carotid baroreceptors combined with some additional increase in arterial pulse pressure, which also stimulates aortic baroreceptors, accounts for more than half of the hypotensive response at heart level to a posture change from seated to supine.

Adult↗

Left ventricular versus left atrial cannulation for the Thoratec ventricular assist device.

In a retrospective study of 28 patients (23 men, 5 women) supported with ventricular assist devices greater than 3 days, the effect of LV cannulation versus LA cannulation on device performance was compared. Patients ranged in age from 12 to 67 years (mean 46 years) and were supported for 3-81 days (mean 15 years). Fifteen patients were supported with left VADs (6 LV and 9 LA), and 13 patients were supported with BVADs (5 LV and 8 LA). The mode of operation 91% of the time was the fill-to-empty mode. Ten data points were taken for each patient. LV cannulation results in higher VAD flow index at decreased preload, lower VAD systolic and vacuum pressures, and shorter diastolic durations. Eleven of the 28 patients survived. Although survival was greater in patients with LV cannulation, survival was more dependent upon reversibility of myocardial damage, eligibility for transplantation, or the development of complications. These data indicate that LV cannulation provides better VAD performance than LA cannulation in the fill-to-empty mode.

Adolescent↗

Comparative efficacy of the maze procedure for restoration of atrial contraction in patients with and without giant left atrium associated with mitral valve disease.

OBJECTIVES: We sought to determine the effectiveness of the maze procedure for restoring atrial contraction in patients with and without giant left atrium (GLA). BACKGROUND: Although the maze procedure has been reported to be effective for refractory atrial fibrillation, it is unknown whether this procedure can restore effective atrial contraction in patients with GLA. METHODS: Nineteen patients with and 32 patients without GLA were studied with Doppler echocardiography before and after the maze procedure. Peak velocity and the time-velocity integral of the left ventricular diastolic filling wave during atrial contraction (A wave) and the atrial filling fraction calculated as the ratio of the time-velocity integral of the A wave to that of total diastolic filling were compared between patients with and without GLA. A peak A wave velocity > or =10 cm/s was considered to indicate echocardiographic evidence of effective atrial contraction. RESULTS: Regular rhythm with P waves was restored in 10 patients (53%) with and 26 (81%, p < 0.05) without GLA. Four patients (21%) with and 21 patients (66%, p < 0.01) without GLA showed effective atrial contraction by echocardiography. Once atrial contraction was resumed, the degree of atrial contraction was comparable between patients with and without GLA (17+/-5% vs. 17+/-4% for atrial filling fraction at 12 months, respectively). CONCLUSIONS: Although most patients without GLA had restored atrial contraction by the maze procedure, it was resumed in fewer patients with GLA. However, once atrial contraction was resumed, the degree of atrial contraction was comparable between patients with and without GLA. Therefore, the maze procedure may be an option in selected patients with GLA.

Aged↗

The cardiovascular response to digoxin in conscious dogs with left atrial obstruction.

In addition to positive inotropic and atrioventricular conduction-blocking properties, digoxin is capable of producing systemic and pulmonary vasoconstriction. However, whether chronic digoxin treatment exacerbates the pulmonary hypertension that results from left atrial (LA) outflow obstruction has not been specifically examined. This study assessed the vascular and inotropic responses to 5 days of digoxin treatment in six conscious dogs before and after filling a permanently implanted LA balloon. Dogs were also instrumented to measure left ventricular (LV) pressure, LV dP/dt, mean systemic arterial (MAP), right atrial (RAP), pulmonary arterial, and pulmonary capillary wedge pressures, as well as cardiac output (CO). Under normal conditions with the balloon empty, digoxin treatment (40 micrograms/kg loading dose and 12 micrograms/kg/d for 5 days) reduced CO (-17%) and increased systemic (SVR) and pulmonary (PVR) vascular resistances 27% and 37%, respectively; heart rate (HR) and LV dP/dt were not changed. Filling the balloon with enough saline to double PVR also increased SVR (52%), HR (42%), and RAP (92%), and reduced CO (-24%). During LA outflow obstruction, 5 days of digoxin reduced HR (-17%), SVR (-29%), and RAP (-23%), but did not alter PVR, CO, or LV dP/dt. This study demonstrates that although systemic and pulmonary vasoconstriction result from chronic digoxin treatment under normal conditions, the drug produces systemic vasodilation and no change in PVR during LA outflow obstruction.

Animals↗

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

Acetamides↗