title: Effects of the recombinant form of the natural human B-type natriuretic peptide and levosimendan on pulmonary hyperventilation and chemosensivity in heart failure.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise.
authors: Laboratório de Insuficiência Cardíaca e Transplante do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP (InCor HC-FMUSP), São Paulo, Brazil. dcledimar@incor.usp.br
authors: Edimar Alcides
authors: EA
authors: Bocchi
authors: Lídia Zytynski
authors: LZ
authors: Moura
authors: Victor Sarli
authors: VS
authors: Issa
authors: Fátima
authors: F
authors: Cruz
authors: Vitor Oliveira
authors: VO
authors: Carvalho
authors: Guilherme Veiga
authors: GV
authors: Guimarães
mesh_terms: D000328:Adult; D001938:Brazil; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000627:therapeutic use*; D006935:Hypercapnia / Q000097:blood / Q000503:physiopathology; D006985:Hyperventilation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011724:Pyridazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D056152:Respiratory Rate / Q000187:drug effects; D000077464:Simendan; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D006835:Hydrazones; D011724:Pyridazines; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; D000077464:Simendan