Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function

N Engl J Med. 1989 May 18;320(20):1317-22. doi: 10.1056/NEJM198905183202005.


To elucidate the pathogenesis of bronchospasm in congestive heart failure, we studied 23 patients with chronic impairment of left ventricular function due to coronary artery disease or dilated cardiomyopathy. In 21 of them we found marked bronchial hyperresponsiveness to methacholine. The mean dose (+/- SD) of methacholine that elicited a 20 percent decrease in the forced expiratory volume in one second (FEV1) was 421 +/- 298 micrograms, nearly the same as in patients with symptomatic asthma. In contrast, there was no bronchial response to methacholine in 9 of 10 patients who had coronary artery disease but normal left ventricular function. Administration of the bronchodilator albuterol led to a partial (43 percent) reversal of the methacholine-induced bronchial obstruction. In 12 patients, pretreatment with the alpha-adrenergic agonist methoxamine (10 mg by inhalation), a potent vasoconstrictor, fully prevented the methacholine-induced decrease in FEV1. The protective effect of methoxamine was blocked by the alpha-adrenergic antagonist phentolamine in all six patients who received this agent. We conclude that bronchial hyperresponsiveness to cholinergic agonists is frequent in patients with impaired left ventricular function and may contribute to the wheezy dyspnea commonly observed in such patients. The bronchoconstriction may be mediated at least in part by dilatation of the bronchial vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuterol / pharmacology
  • Bronchi / drug effects*
  • Bronchi / physiopathology
  • Bronchial Provocation Tests
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / physiopathology*
  • Coronary Disease / complications
  • Coronary Disease / physiopathology*
  • Dyspnea, Paroxysmal / etiology
  • Female
  • Forced Expiratory Volume
  • Heart Failure / complications
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Methacholine Compounds / pharmacology*
  • Methoxamine / pharmacology
  • Middle Aged
  • Receptors, Adrenergic, alpha / drug effects


  • Methacholine Compounds
  • Receptors, Adrenergic, alpha
  • Methoxamine
  • Albuterol