Effects of volume loading on left atrial systolic time intervals.

The effects of volume loading on the left atrial preejection period (LAPEP) and left atrial ejection time (LAET) were examined in 24 patients with various heart diseases using pulsed Doppler echocardiography. In response to volume loading, the left atrial dimension before atrial contraction significantly increased from 30.6 mm +/- 5.8 mm to 32.4 mm +/- 5.4 mm and the change in the left atrial dimension during atrial contraction tended to increase. The peak velocity in the atrial contraction phase significantly increased from 58 cm/s +/- 14 cm/s to 63 cm/s +/- 13 cm/s, and the integral of the atrial contraction phase tended to increase. LAPEP significantly decreased from 114 ms +/- 16 ms to 104 ms +/- 14 ms and LAET significantly decreased from 128 ms +/- 15 ms to 124 +/- 12 ms. The relation between LAET and left ventricular end-diastolic pressure, and that between LAPEP and mean pulmonary capillary wedge pressure, shifted downward to the right after volume loading. Thus, left atrial ejection is augmented by volume loading according to the Frank-Starling mechanism, while LAPEP decreases due to an increase in preload and LAET decreases due to an increase in afterload.     

Normal fluctuations in pulmonary artery pressures and cardiac output in patients with severe left ventricular dysfunction.

BACKGROUND: One barrier to accurate interpretation of changes in hemodynamic pressures and cardiac output is lack of data about what constitutes a normal fluctuation. Few investigators have examined normal fluctuations in these parameters and none have done so in patients with left ventricular dysfunction. AIMS: To describe normal fluctuations in pulmonary artery pressures and cardiac output in patients with left ventricular dysfunction. METHODS: Hemodynamically stable advanced heart failure patients (N=39; 55+/-6 years old; 62% male) with left ventricular dysfunction (mean ejection fraction 22+/-5%) were studied. Cardiac output and pulmonary artery pressures were measured every 15 min for 2 h. RESULTS: Mean+/-standard deviation fluctuations were as follows: pulmonary artery systolic pressure=7+/-4 mmHg; pulmonary artery diastolic pressure=6+/-3 mmHg; pulmonary capillary wedge pressure=5+/-3 mmHg; cardiac output=0.7+/-0.3 l/min. The coefficient of variation for fluctuations in pulmonary artery systolic pressure was 6.7%, in pulmonary artery diastolic pressure was 9.3%, in pulmonary capillary wedge pressure was 9.2%, and in cardiac output was 7.2%. CONCLUSIONS: Values that vary <8% for pulmonary artery systolic pressure, <11% for pulmonary artery diastolic pressure, <12% for pulmonary capillary wedge pressure, and <9% for cardiac output from baseline represent normal fluctuations in these parameters in patients with left ventricular dysfunction.     

Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure

Fifteen elderly patients with normal left ventricular (LV) systolic function and New York Heart Association functional class II-III were studied. The effect of verapamil on LV diastolic function was assessed by congestive heart failure (CHF) score, treadmill exercise test, and Doppler echocardiography at baseline, and after each three-month treatment period (placebo or verapamil 120 mg once daily), separated by a one-week washout period before crossover. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. Verapamil treatment significantly improved CHF score at 3 months (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/- 0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05) and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF, three months treatment with verapamil can improve CHF, increase exercise tolerance and improve LV diastolic function.     

Reduced coronary flow reserve in patients with congestive heart failure assessed by transthoracic Doppler echocardiography.

BACKGROUND: Although coronary flow reserve (CFR) has been reported to be restricted in various conditions, there has been no report of CFR for patients with congestive heart failure (CHF). The purpose of this study was to assess coronary flow characteristics for patients with CHF. METHODS: We studied 15 patients with CHF: 8 with dilated myocardiopathy and 7 with hypertensive heart disease. Phasic coronary flow velocities were obtained in the left anterior descending coronary artery at rest and during hyperemia (0.15 mg/kg/min adenosine triphosphate infusion intravenously) by transthoracic echocardiography before and after treatment of CHF. CFR was obtained from the ratio of hyperemic/baseline diastolic mean velocity. RESULTS: CFR was significantly restricted in the condition of CHF compared with that after improvement of CHF (1.5 +/- 0.2 vs 2.0 +/- 0.3, P < .01). Baseline diastolic mean velocity in the condition with CHF was significantly greater than that after improvement of CHF (41 +/- 13 cm/s vs 33 +/- 13 cm/s, P = .04), although maximal hyperemic diastolic mean velocity was not significantly different before and after improvement of CHF (63 +/- 20 cm/s vs 61 +/- 19 cm/s, P = .68). After improvement of CHF, heart rate, along with left ventricular end-diastolic volume and dimension, were significantly decreased, and deceleration time of transmitral early filling flow was increased compared with before treatment of CHF. Blood pressure and ejection fraction were not significantly different before and after treatment of CHF. CONCLUSIONS: Restriction of CFR is demonstrated during CHF because of the elevation of baseline resting flow velocity, which might be related to increase in left ventricular preload and heart rate.     

Structural-functional alterations in the heart affecting dynamics of transmitral blood flow during a hemodialysis session

AIM: To study dynamics of transmitral circulation (TMC) during a hemodialysis (HD) session in patients with chronic renal failure (CRF) regarding structural-functional alterations of the heart and baseline condition of the diastolic function of left ventricular (LV) myocardium. MATERIAL AND METHODS: Sixty one patients (34 females and 27 males, mean age 47 +/- 11 years) on programmed HD free of heart valvular disease, ischemic heart disease, acute myocardial infarction, atrial fibrillation. Before and after HD session the patients underwent echocardiography, including Doppler regime. RESULTS: Normal LV geometry was detected in 3 (4.9%) patients, concentric remodeling - in 9 (14.8%), concentric LV hypertrophy (LVH) - in 37 (60.7%), excentric LVH - in 12 (19.7%) patients. The ejection fraction was under 45% in 5 (8.2%) patients. Diastolic dysfunction of LV myocardium was found in 42 (68.9%) patients, TMC characteristic of slow relaxation was registered most frequently (47.6%). A pseudonormal type of TMC was recorded in 16 (38.1%) patients. HD did not change TMC significantly in patients with normal diastolic function (before HD E peak velocity was 88.7 +/- 19.8 cm/s, after - 80.0 +/- 24.6 cm/s, p > 0.05). In patients with initially disturbed relaxation the velocity of early diastolic flow (Vp) (color M-mode Doppler) increased (before HD, Vp was 67.6 +/- 17.1 cm/s, after - 72.9 +/- 15.7 cm/s, p < 0.05), E/Vp reduced (before HDm E/Vp was 1.2 +/- 0.4, after 1.0 +/- 0.4, p < 0.05). The subgroup with initially pseudonormal TMC showed decreased velocity in the E peak (before HD - 103.4 +/- 13.5 cm/s, after - 76.8 +/- 24.0 cm/s, p < 0.001). In restrictive TMC this velocity also decreased - 129.0 +/- 17.8 cm/s and 108.8 +/- 14.7 cm/s, p < 0.05, respectively). CONCLUSION: TMC alteration during a HD session depends more on initial type of diastolic dysfunction than on LV geometry. A HD session improves intracardiac hemodynamics in patients with pseudonormal TMC.     

Diagnosis of left-ventricular diastolic dysfunction in patients with predialysis chronic renal failure

AIM: To specify effectiveness of different methods for assessment of diastolic function in patients with pre-dialysis chronic renal failure (CRF). MATERIAL AND METHODS: Forty non-diabetic pre-dialysis CRF patients (20 males and 20 females, mean age 51 +/- 11 years) were studied. Serum creatinine was 209.3 +/- 117.4 mcmol/l. 19 patients had chronic heart failure (CHF) of NYHA class I-III. M-mode echocardiography and Doppler echocardiography were performed. Transmitral and pulmonary venous flows were assessed by Doppler echocardiography and the flow propagation velocity (Vp) was estimated by color M-mode Doppler echocardiography. The ratio of peak E-wave velocity of transmitral flow to Vp (E/Vp) was calculated. All the patients had preserved systolic function (ejection fraction > 45%). RESULTS: Interpretation of transmitral flow was difficult in 16 (40.0%) patients. During Valsalva's manoeuvre the E-wave peak velocities, the A-wave velocities and the ratio E/A were decreasing. However, we did not reveal any correlation between E/A and NYHA class of heart failure (r = 0.18; p = 0.32). Interpretation of pulmonary venous flow was possible only in 24 (60.0%) patients. Vp estimation by color M-mode Doppler echocardiography improved evaluation of diastolic function in 15 of 16 patients with problems of transmitral flow assessment. A negative correlation was revealed between NYHA class and Vp (r = -0.39; p = 0.013) and a positive correlation was between NYHA class and E/Vp (r = 0.45; p = 0.004). CONCLUSION: Vp assessed by color M-mode Doppler echocardiography improves the diagnosis of diastolic dysfunction in patients with chronic renal insufficiency. This method has an advantage over pulmonary venous flow investigation. The Valsalva's manoeuvre is low-effective for differential diagnosis of transmitral flow types.     

Contrast-enhanced Doppler hemodynamics for noninvasive assessment of patients with chronic heart failure and left ventricular systolic dysfunction.

We sought to evaluate whether contrast-enhanced Doppler echocardiography can improve the noninvasive estimation of hemodynamic variables in left ventricular (LV) dysfunction. Right-heart catheterization and Doppler echocardiography were simultaneously performed in 45 patients with LV dysfunction (ejection fraction: 29 +/- 7%) in sinus rhythm. Noninvasive variables were estimated as follows: cardiac output by pulsed Doppler of LV outflow tract; pulmonary capillary wedge pressure by a regression equation including mitral and pulmonary venous flow variables; pulmonary artery mean pressure from the calculated systolic and diastolic pulmonary artery pressures; and pulmonary vascular resistance from the previous measurements according to hemodynamic definition. Contrast enhancement increased the feasibility of pulmonary capillary wedge pressure estimation from 60% to 100%; of pulmonary artery mean pressure from 42% to 91%; and of pulmonary vascular resistance from 42% to 91%. Strong correlations between invasive and noninvasive hemodynamic variables were found: r = 0.90, standard error of the estimate (SEE) 0.45 L/min for cardiac output; r = 0.90, SEE 3.1 mm Hg for pulmonary capillary wedge pressure; r = 0.93, SEE 3.7 mm Hg for pulmonary artery mean pressure; and r = 0.85 SEE 1.0 Wood units for pulmonary vascular resistance. Weaker correlations for PAMP (r = 0.82, SEE 5.6 mm Hg) and PVR (r = 0.66, SEE 1.7 Wood units) were apparent prior to contrast enhancement. When patients were separated according to PVR threshold values, the contrast allowed the correct placement of 88% of patients, whereas only 57% were correctly assigned without it. The contrast increased accuracy and reduced interobserver variability in the evaluation of hemodynamic variables. The contrast-enhanced study is capable of increasing the value of noninvasive hemodynamic assessment in LV dysfunction.     

Contrasting cardiac regional responses of A-type and B-type natriuretic peptide to experimental chronic heart failure

OBJECTIVE: The aim of this study was to examine the regional myocardial variation in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) synthesis during development of congestive heart failure (CHF). METHODS: Heart failure was induced by left atrial rapid pacing for 3 weeks in pigs. The gene expression of ANP and BNP was measured by northern blot analysis and the peptide concentration in myocardial tissue and plasma by radioimmunoassay (RIA). RESULTS: At the end of the pacing period pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) increased, and cardiac output (CO) decreased compared to sham-operated controls (PCWP: 17.6 +/- 1.9 vs. 3.1 +/- 0.9 mmHg) (RAP: 10.4 +/- 1.7 vs. 2.2 +/- 0.6 mmHg) (CO: 3.5 +/- 0.4 vs. 5.3 +/- 0.3 l/min), indicating a state of moderate to severe CHF. The gene expression and tissue concentration of BNP was low in sham pigs, but was strongly increased in all cardiac regions, and especially in the left ventricle, during CHF. In contrast, ANP was mainly produced in the atria both in normal and heart failure conditions. The relative increases in mRNA levels, tissue concentrations and circulating peptide concentrations were more profound for BNP than for ANP. CONCLUSIONS: In response to CHF induction, ANP and BNP respond differently across the cardiac regions. Strong expression of the BNP gene was only found in the heart failure state, while ANP was clearly expressed also in the normal state. These findings support the concept of BNP being superior to ANP as a biochemical marker of CHF.     

Preload dependence of color M-mode Doppler flow propagation velocity in controls and in patients with left ventricular dysfunction.

The purpose of this study was to assess the effects of preload alterations on color M-mode flow propagation velocity (Vp) in volunteers with normal left ventricular (LV) function and in patients with depressed LV function. Color M-mode Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after administration of nitroglycerin in 30 healthy volunteers and in 30 age- and sex-matched patients with previous myocardial infarction (MI). Mean Vp in controls was 74 +/- 15 cm/s at baseline and 46 +/- 15 cm/s in MI patients (P <.0005). In both groups, minor changes in Vp were seen during preload alterations; however, these were not significant (control P =.72, MI P =.31). In both groups, peak E-wave velocity (P <.0005), ratio of early-to-late peak velocities (P <.0005), and E-wave deceleration time (P <.0005) were found to change during preload alterations. In conclusion, we found that in controls and patients with previous MI, the color M-mode flow propagation velocity is not affected significantly by preload.     

Effects of electrical stimulation postcardiomyoplasty in a model of chronic heart failure: hemodynamic results after daily 12-hour cessation versus a nonstop regimen

The hemodynamic effects of cardiomyoplasty (CMP) have been investigated in many centers, but the question of whether it is necessary to stimulate the latissimus dorsi muscle (LDM) 24 hours a day has not been answered. The main goal of our investigation was to determine whether hemodynamic results after CMP were impaired when continuous electrical stimulation (ES) was off for 12 hours a day. A model of chronic heart failure was created in 12 sheep by performing an arteriovenous anastamosis and administering doxorubicin. Two weeks after the anastomosis, CMP was performed in eight sheep (experimental series); ES training was begun at 2 weeks after CMP. After completion of the initial ES conditioning (8 weeks after CMP), one group of sheep continued to receive ES 24 hours daily. Another group of sheep had only 12 hours of ES daily. Hemodynamic parameters were investigated 2 weeks later with the stimulator turned on and then off. With doxorubicin administration, arteriovenous anastamosis created a stable model of biventricular heart failure (right atrial pressure 20 +/- 3 mmHg vs 6 +/- 2 mmHg at baseline; pulmonary capillary wedge pressure 18 +/- 3 mmHg vs 9 +/- 2 mmHg; left ventricular end-diastolic area 15.2 +/- 1.2 cm2 vs 6.4 +/- 0.7 cm2; left ventricular ejection fraction 0.38 +/- 0.6 vs 0.65 +/- 0.7). Cardiomyoplasty improved hemodynamic status in all eight experimental sheep. However, when the investigation was performed with the stimulator off, this improvement was statistically insignificant. With stimulation on, there was decreased right atrial pressure, pulmonary capillary wedge pressure, left ventricular end-diastolic volume, and increased left ventricular ejection fraction. With the stimulator turned off for 12 hours daily, hemodynamic measurements did not differ from data with continuous ES for 24 hours daily. Because hemodynamic results do not seem to be impaired, we recommend daily, periodic cessation of stimulation to prevent damage to the LDM after CMP.     

Single-beat determination of Doppler-derived aortic flow measurement in patients with atrial fibrillation.

The clinical assessment of left ventricular systolic function in patients with atrial fibrillation is unreliable and difficult because of beat-to-beat variation. We initially evaluated an index that is on the basis of the ratio of preceding R-R (RR1) to pre-preceding R-R (RR2) intervals (RR1/RR2) for the measurement of Doppler aortic flow (peak flow velocity [Vp] and time-velocity integral [TVI] proportional to stroke volume) in 20 patients (aged 65 +/- 9.6 years) with atrial fibrillation. We obtained each parameter for >13 cardiac cycles, and the relationship between each parameter at a given cardiac beat and the RR1/RR2 ratio were evaluated by linear regression analysis. The value of each parameter at RR1/RR2 = 1 was calculated from the equation of linear regression line and compared with measured average value over all cardiac cycles. Both parameters showed a significant positive correlation with the RR1/RR2 ratio (Vp, r = 0.98, y = 1.01x + 0.61; TVI, r = 0.99, y = 1.01x + 0.26). The calculated value of each parameter at RR1/RR2 = 1 was quite similar to the average value (Vp, 97.4 +/- 30.8 vs 95.7 +/- 29.8 cm/s; TVI, 17.7 +/- 6.8 vs 17.3 +/- 6.7 cm, respectively). In the additional 20 patients (aged 77.4 +/- 15.2 years), Doppler aortic flow parameters of a single beat with identical RR1 and RR2 intervals were compared with measured average value over all cardiac cycles and showed similar results (Vp, r = 0.99, y = 0.99x + 3.4, P <.0001, bias -0.5 cm/s; TVI, r = 0.99, y = 0.92x + 1.5, P <.0001, bias 0.1 cm). In conclusion, the Doppler aortic flow at RR1/RR2 = 1 allows the left ventricular systolic parameters to be accurately evaluated during atrial fibrillation and obviates the less reliable process of averaging multiple irregular beats.     

Prognostic value of the atrial systolic mitral annular motion velocity in patients with left ventricular systolic dysfunction.

BACKGROUND: Transmitral flow velocity variables are powerful predictors of poor prognosis in patients with left ventricular (LV) systolic dysfunction. However, these variables may not accurately reflect the severity of pulmonary congestion. This study was designed to determine whether the peak atrial systolic mitral annular motion velocity (MA-Aw) measured by pulsed Doppler tissue imaging can predict cardiac death or hospitalization for worsening heart failure in patients with LV systolic dysfunction. METHODS: MA-Aw was recorded in 96 patients with LV systolic dysfunction who were followed up for 29 +/- 10 months. All patients underwent Doppler echocardiography on entry into the study, and cardiac catheterization was performed in 45 patients. Patients were divided into 3 groups on the basis of the ratio of early (E) to late (A) diastolic filling (E/A) of the transmitral flow velocity: group 1 (n=31; E/A < 1); group 2 (n=37; 1 < or = E/A < 2); and group 3 (n=28; E/A > or = 2). RESULTS: During follow-up, 36 patients (38%) died of cardiac causes and 34 (35%) were hospitalized for worsening heart failure. There were 2 cardiac deaths (6%) in group 1, 14 (39%) in group 2, and 20 (56%) in group 3. The MA-Aw correlated closely with the mean pulmonary capillary wedge pressure. Univariate Cox model analysis showed that MA-Aw < or = 5 cm/s was the most powerful predictor of cardiac death or hospitalization for worsening heart failure compared with clinical, hemodynamic, and the other echocardiographic variables. Furthermore, MA-Aw < or = 5 cm/s was clearly discernible as a good predictor of cardiac mortality on multivariate Cox model and as assessed by Kaplan-Meier method. CONCLUSION: The MA-Aw obtained by pulsed Doppler tissue imaging is a sensitive index of pulmonary congestion in patients with LV systolic dysfunction. It is a simple and noninvasive outcome measure and can be used to monitor treatment.     

Hemodynamic effects of positive end-expiratory pressure during high-frequency ventilation

We studied the intrapleural and hemodynamic effects of positive end-expiratory pressure (PEEP) during high-frequency ventilation (HFV) with a Venturi high-frequency ventilator (Bird). Ten healthy mongrel dogs were anesthetized with sodium pentobarbital, catheterized with intrapleural and thermodilution pulmonary artery lines, and subjected to oleic acid-induced pulmonary edema. A mean PEEP of 16 +/- 6 (SD) cm H2O restored venous admixture to baseline in nine animals. Both mean airway pressure (Paw) and mean intrapleural pressure (Ppl) increased significantly with each increment of PEEP during HFV. Approximately 50% of Paw was transmitted to the intrapleural space. Cardiac index (CI) decreased with increments of PEEP in spite of constant transmural central venous and pulmonary capillary wedge pressures, so that oxygen delivery decreased despite increased PaO2. Possible mechanisms of PEEP-induced depression of CI during HFV are discussed. We conclude that both hemodynamic and intrapleural effects of PEEP during HFV are similar to those during conventional mechanical ventilation.     

Influences of sildenafil on lung function and hemodynamics in patients with chronic heart failure

BACKGROUND: Chronic heart failure (CHF) may be associated with a disordered nitric oxide (NO)-mediated regulation of the pulmonary vessel tone and permeability and of the gas transfer across the alveolar-capillary membrane. Whether enhancement of NO availability is beneficial with regard to these functions has not been explored. Phosphodiesterase 5 inhibitors, such as sildenafil, may provide a tool with which to test this possibility. METHODS: In 10 patients with CHF and 10 normal subjects, before and at 60 minutes after sildenafil (50 mg) or placebo, we measured left ventricular ejection fraction, pulmonary hemodynamics, lung diffusion capacity for carbon monoxide and its alveolar-capillary membrane and blood capillary volume subcomponents, and flow-mediated brachial artery dilation (FMD) during reactive hyperemia to distal circulatory arrest (an indirect index of NO-mediated endothelial function). RESULTS: In patients with CHF, sildenafil caused no variations in ejection fraction, cardiac index, wedge pulmonary pressure, and blood capillary volume; it decreased pulmonary artery systolic (-21.6%) and diastolic (-31.8%) pressure and arteriolar resistance (-36.9%); and it increased lung diffusion capacity for carbon monoxide (+11.2%), diffusing capacity of the alveolar-capillary membrane (+10.6%), and FMD (from +8.3% to +13.4%). All changes were significant at P < .01. None of these effects was observed in healthy subjects. Placebo was ineffective in both patients and control subjects. CONCLUSION: This study provides the novel information that, in patients with CHF, phosphodiesterase 5 inhibition with sildenafil ameliorates the pulmonary hemodynamics and reduces the impedance of the alveolar-capillary interface, even if left ventricular filling pressure and function remain steady. The associated improvement in FMD at the periphery substantiates the possibility that an enhancement in NO release may underlie these effects.     

Effects of hetastarch resuscitation on extravascular lung water and cardiopulmonary parameters in a sheep model of hemorrhagic shock

Eight sheep, weighing 29-71 kg, were used to evaluate the cardiopulmonary response to Hespan infusion following shock. Before shock was induced, mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAP), cardiac output (CO), extravascular lung water (EVLW), colloid oncotic pressure (COP), and hemoglobin were measured and shunt, arteriovenous oxygen content difference (C[a - v]O2) and COP-PCWP gradient were calculated. The animals were bled to a MAP of 50 mmHg and that level was maintained for 30 min. At the end of that time, the data were collected again. The animals were resuscitated back to baseline values of PCWP, MAP, and CO with a 6% hydroxyethylstarch solution. With shock, PCWP, MAP, CO, and arterial pH decreased and C(a - v)O2 increased significantly (P less than 0.05). With resuscitation, PAP, PCWP and CO were significantly greater than baseline. Arterial pH was less than the baseline value but was within normal range. MAP did not return to preshock levels. EVLW and venous admixture did not change at any time. C(a - v)O2 returned to baseline with resuscitation. Volume of hetastarch infused was 29.1 +/- 10 cm3/kg. We conclude that hetastarch is an effective resuscitation solution in a model of hemorrhagic shock and appears to have no adverse cardiopulmonary effects.     

Evidence for direct estrogen regulation of the human gonadotropin-releasing hormone gene.

Atrial natriuretic factor (ANF) is a peptide hormone of cardiac origin elevated in acute congestive heart failure (CHF), which is degraded by the enzyme neutral endopeptidase 24.11 (NEP). This study was designed to investigate the pulmonary and urinary clearance of ANF before and after the initiation of acute experimental CHF in dogs, and to assess the contribution of enzymatic degradation to these clearances in CHF. This study demonstrated a significant clearance of plasma ANF across the pulmonary circulation at baseline, and a tendency for pulmonary clearance to decrease in CHF (1115 +/- 268 to 498 +/- 173 ml/min, NS). The pulmonary extraction of ANF present at baseline was not altered with acute CHF (36.0 +/- 7.8 to 34.9 +/- 12.1%, NS). NEP inhibition (NEPI) abolished both the clearance and extraction of plasma ANF across the lung in CHF. Similarly, significant urinary clearance of ANF was present at baseline, and in acute CHF the urinary clearance of ANF decreased (0.14 +/- 0.02 to 0.02 +/- 0.01 ml/min, P less than 0.05). NEPI prevented the decrease in the urinary clearance of ANF, and enhanced the renal response to endogenous ANF, independent of further increases in plasma ANF during CHF. This study supports an important role for NEP in the pulmonary and urinary metabolism of endogenous ANF during acute CHF.     

Acute effects of non-invasive ventilatory support on functional mitral regurgitation in patients with exacerbation of congestive heart failure

OBJECTIVE: The purpose of this study was to evaluate the acute effects of continuous positive airway pressure (CPAP) and bi-level airway pressure (BiPAP) on functional mitral regurgitation (MR) in patients with acute exacerbation of severe chronic congestive heart failure (CHF). DESIGN: A cross-over study. SETTING: A cardiopulmonary intensive care unit. PATIENTS AND INTERVENTIONS: Ten male patients affected by an acute exacerbation of congestive heart failure and hemodynamically significant MR were submitted to an echocardiograph color Doppler ultrasound evaluation during CPAP and BiPAP non-invasive ventilation. We analyzed left ventricle ejection fraction, area of MR and deceleration time (Dec-t). OUTCOME MEASURES: The primary end point was to evaluate whether CPAP and BiPAP were effective in reducing functional MR. RESULTS: After 30 min, the area of MR decreased from 10.0+/-2.7 to 8.0+/-2.9 cm(2) with CPAP and from 9.9+/-2.6 to 8.6+/-2.6 cm(2) with BiPAP ( p<0.01); Dec-t increased from 120.9+/-12.7 to 136.0+/-8.7 ms after CPAP and from 120.5+/-11.4 to 134.2+/-13.6 ms after BiPAP ( p<0.01). CONCLUSION: In patients with exacerbation of severe CHF and functional MR, both modalities of non-invasive ventilation (CPAP and BiPAP) significantly improved ejection fraction and were equally effective in reducing MR.     

Recruitment maneuver and high positive end-expiratory pressure improve hypoxemia in patients after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism

OBJECTIVES: To investigate the effects of a recruitment maneuver and high positive end-expiratory pressure (PEEP) on oxygenation and hemodynamics in hypoxemic patients with pulmonary hypertension after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. DESIGN: Prospective, observational, clinical study. SETTING: A surgical intensive care unit in a national heart institute. PATIENTS: Fourteen consecutively admitted patients who developed acute lung injury (Pa(O2) <300 torr at F(IO2) 1.0) and pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. INTERVENTIONS: The recruitment maneuver was an increase of PEEP to 30 cm H2O in one step for 1 min at F(IO2) 1.0. The level of pressure control ventilation during the recruitment maneuver was the same as before the maneuver. Subsequently, PEEP was decreased in 15-min intervals from 15 to 10, 5, and 0 cm H2O. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and respiratory variables were analyzed before and during the recruitment maneuver and at each PEEP level. At F(IO2) 1.0, Pa(O2) increased from 240 +/- 62 torr to 470 +/- 83 torr at 15 cm H2O of PEEP and 469 +/- 75 torr at 10 cm H2O of PEEP after the recruitment maneuver (p < .001). At 15 cm H2O of PEEP, cardiac index decreased (from 2.7 +/- 0.6 at baseline to 2.2 +/- 0.3 L.min(-1).m(-2), p < .01) and mean blood pressure decreased (from 86 +/- 8 at baseline to 74 +/- 11 mm Hg, p < .05), but they returned to the baseline levels at 10 cm H2O of PEEP (2.5 +/- 0.4 L.min(-1).m(-2) and 83 +/- 9 mm Hg). There were no differences in mean pulmonary artery pressure at different levels of PEEP. CONCLUSIONS: In hypoxemic patients with pulmonary hypertension after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism, oxygenation was improved by the recruitment maneuver followed by high PEEP. However, hemodynamics were transiently suppressed and overall oxygen delivery did not change.     

Pathophysiological roles of endogenous endothelin-1 in dogs with chronic heart failure produced by rapid right ventricular pacing.

This study was designed to analyze the pathophysiological role of the endogenous endothelin (ET) system and the therapeutic approach to congestive heart failure (CHF) with ET(A)/ET(B) receptor antagonists in a canine CHF model. After 3 weeks of rapid right ventricular pacing (240 beats/min), concentrations of immunoreactive ET-1 in dogs increased approximately 2-fold in plasma and in the left and right ventricles but not in the lung. There were no meaningful changes in the density and affinity of total ET receptors, or in the ratio of ET(A) to ET(B) receptors. To clarify the functional role of endogenous ET, we examined the effects of acute injection of J-104132 (1 and 3 mg/kg i.v.), an ET(A)/ET(B) receptor antagonist, on cardiovascular and renal function in dogs with CHF. Compared with vehicle, J-104132 at both doses significantly decreased pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure (MAP), and increased cardiac output (CO) and renal blood flow. J-104132 had no effects on heart rate and cardiac contractility. In addition, we examined whether J-104132 has an additive effect in the presence of enalaprilat. J-104132 (1 mg/kg i.v.) administered after enalaprilat (0.05 mg/kg i.v.) induced further decreases in MAP, PCWP and PAP, and further increases in CO, resulting in further decreases in total peripheral resistance. These results indicate that the endogenous ET system is exaggerated in CHF and has a detrimental effect on cardiac function. Therefore, J-104132 given alone or as combination therapy may play a beneficial role in the treatment of CHF in humans.     

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF.