natriuretic-peptide--brain and Hypercapnia

The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored.. We tested in a prospective, placebo-controlled, three-way cross-over, double-blind randomized study the effects of the recombinant form of the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise.. Eleven stable chronic HF patients were randomized to sessions of 6-min treadmill-walking tests during placebo, or levosimendan or R-BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R-BNP effects. BNP blood levels remained unchanged.. The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise.

Topics: Adult; Brazil; Cardiovascular Agents; Chemoreceptor Cells; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Hypercapnia; Hyperventilation; Hypoxia; Infusions, Intravenous; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyridazines; Recombinant Proteins; Respiratory Rate; Simendan; Time Factors; Treatment Outcome

The aim of the present study was to investigate the prognostic significance of chemosensitivity to hypercapnia in chronic heart failure (HF).. Increased chemosensitivity to hypoxia and hypercapnia has been observed in HF. The potential value of enhanced chemosensitivity to hypercapnia to risk prediction in systolic HF has not been specifically evaluated.. One hundred ten consecutive systolic HF patients (age 62 +/- 15 years, left ventricular ejection fraction [LVEF] 31 +/- 7%) underwent assessment of chemosensitivity to hypoxia and hypercapnia (rebreathing technique) and were followed up for a median period of 29 months (range 1 to 54 months). The end point was a composite of cardiac death and aborted cardiac death (ventricular tachyarrhythmia treated by cardioverter-defibrillator).. At baseline, 31 patients (28%) had enhanced chemosensitivity to both hypoxia and hypercapnia. Although they had the same LVEF as the 43 patients (39%) with normal chemosensitivity, they were more symptomatic (New York Heart Association functional class), had higher plasma brain natriuretic peptide and norepinephrine, steeper regression slope relating minute ventilation to carbon dioxide output (V(E)/V(CO2) slope), more Cheyne-Stokes respiration, and more ventricular arrhythmias (all p < 0.05). Four-year survival was only 49%, in marked contrast to 100% for patients with normal chemosensitivity (p < 0.001). On multivariate analysis, combined elevation in chemosensitivity was the strongest independent prognostic marker, even when adjusted for univariate predictors (V(E)/V(CO2) slope, Cheyne-Stokes respiration, LVEF, and brain natriuretic peptide, p < 0.05).. Increased chemosensitivity to both hypoxia and hypercapnia, eliciting neurohormonal derangement, ventilation instability, and ventricular arrhythmias, is a very serious adverse prognostic marker in HF.

Topics: Chemoreceptor Cells; Exercise Test; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Hypercapnia; Hypoxia; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Prognosis; Prospective Studies; Stroke Volume; Time Factors

Natriuretic peptides are considered as reliable indicators of left-heart failure (HF) and are useful for differential diagnosis of dyspnoea.. We evaluated the clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic hypercapnic respiratory failure (CHRF).. In 60 patients with CHRF, plasma concentrations of NT-proBNP were assessed at baseline and after treatment including non-invasive ventilation (NIV). The relationship of NT-proBNP to disease severity and its predictive value for survival were evaluated up to 4 years.. NT-proBNP levels were markedly elevated in patients with CHRF (n=60; geometric mean (SD) 546.4 (4.9) pg/mL; p<0.001) compared to healthy controls (n=182; 49.0 (2.2) pg/mL). After excluding patients with concomitant HF or renal impairment, levels were still increased (n=43; 393.2 (3.8) pg/mL; p<0.001). According to multivariate regression, hypoxia and exacerbation independently determined NT-proBNP levels (p<0.05 each). After initiation of NIV, blood gases and lung function improved and NT-proBNP decreased (-31.3 (0.3)%; p<0.001). During 22.5 (2.2) months follow-up, NT-proBNP was not significantly associated with survival in the total population, however, the subgroup of patients with levels >722 pg/mL (67th percentile) and no adherence to NIV displayed poor prognosis (hazard ratio=0.21; 95%-CI=0.022-0.580; p=0.0091).. NT-proBNP was highly elevated in patients with CHRF and correlated with the degree of respiratory impairment and exacerbation. Correspondingly, treatment including NIV led to reduction of NT-proBNP. These data indicate a potential role of NT-proBNP in assessing disease severity, treatment efficacy and prognosis in CHRF.

Topics: Aged; Biomarkers; Carbon Dioxide; Case-Control Studies; Chronic Disease; Female; Humans; Hypercapnia; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Partial Pressure; Peptide Fragments; Prognosis; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; Treatment Outcome

The aim of this study was to investigate the haemodynamic and endocrinological effects of noninvasive positive pressure ventilation (NIPPV). Eleven patients with oedema and recent hypercapnic and hypoxaemic worsening of a chronic respiratory insufficiency were included. Echocardiography, cardiac radionuclide assessment, blood catecholamines, salt and water handling hormones were measured at admission and discharge (long study (LS)). To discriminate between the action of NIPPV and other treatments, measurements were performed on the fourth day, for 4 h without NIPPV and 4 h with NIPPV (short study (SS)). NIPPV entailed a correction of P(a,CO2) and an increase of P(a,O2) in LS and SS. Oedema disappeared. Body weight decreased (from 85+/-42 to 81+/-40 kg) during LS. Systolic and mean pulmonary arterial pressure decreased in LS and SS. Right ventricular ejection fraction increased in LS. Left ventricular ejection fraction did not change. Cardiac index was normal on admission and then decreased. Natriuretic peptides and catecholamines were increased on admission, whereas plasma renin activity, aldosterone and vasopressin were normal. We suggest that in these patients, oedema can occur independently of renin-angiotensin-aldosterone-vasopressin and with a normal cardiac output. Noninvasive positive pressure ventilation allowed a correction of blood gases, associated with the resolution of oedema, a decrease in pulmonary arterial pressures and an increase in right ventricular ejection fraction.

Topics: Atrial Natriuretic Factor; Body Composition; Case-Control Studies; Edema; Female; Hemodynamics; Hormones; Humans; Hypercapnia; Intermittent Positive-Pressure Ventilation; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pulmonary Wedge Pressure; Respiratory Insufficiency; Ventricular Function, Right; Water-Electrolyte Balance