natriuretic-peptide--brain and Hyperventilation

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

B-type (brain) natriuretic peptide (BNP) forms a peptide family with A-type (atrial) natriuretic peptide (ANP), which is involved in the regulation of blood pressure and fluid volume. We have demonstrated that BNP is a novel cardiac hormone secreted predominantly from the ventricle and that plasma levels of BNP markedly increase in proportion to the severity of congestive heart failure. Spasm of a major coronary artery (coronary spasm) is the cause of variant angina and can be induced by hyperventilation. We examined whether BNP infusion suppresses coronary spasm in patients with variant angina. The effect of BNP infusion on anginal attacks induced by hyperventilation was studied in 11 patients with variant angina in whom the attacks were reproducibly induced by hyperventilation. This study was performed in the early morning on 3 consecutive days. Fourteen minutes after infusion of BNP was begun (day 2, 0.05 micrograms/kg/min) or saline (days 1 and 3), hyperventilation was started and continued for 6 minutes. Anginal attacks were induced in all 11 patients by hyperventilation on days 1 and 3, respectively. Anginal attacks were not induced in any patient on day 2 (BNP infusion). Fourteen minutes after BNP infusion was begun, plasma BNP levels increased from 23.7 +/- 6.7 pg/ml to peak levels of 2591 +/- 255 pg/ml (p < 0.01) and plasma ANP levels increased from 28.9 +/- 7.5 pg/ml to peak levels of 69.2 +/- 13.2 pg/ml. Five minutes after BNP infusion was finished, plasma levels of cyclic guanosine monophosphate (cGMP) increased from 20.3 +/- 7.4 pg/ml to peak levels of 63.5 +/- 13.7 pg/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angina Pectoris, Variant; Atrial Natriuretic Factor; Blood Gas Analysis; Coronary Angiography; Coronary Vasospasm; Female; Guanosine Monophosphate; Hemodynamics; Humans; Hyperventilation; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins