title: Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats.
abstract: BACKGROUND
  The effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR) following a left ventricular dysfunction (LVD) induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension.
  
  
  METHODS
  Airway resistance (Raw) was identified from the respiratory system input impedance (Zrs) in four groups of rats. End-expiratory lung volume (EELV) was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 μg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I), or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE), or a calcium channel blocker (diltiazem, Group ID). The equivalent dose of methacholine causing a 100% increase in Raw (ED50) was determined in each group. Diastolic pulmonary arterial pressure (PapD) was assessed by introducing a catheter into the pulmonary artery.
  
  
  RESULTS
  The sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p=0.004), ID (p=0.013) and IE (p=0.006). A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 μg/kg/min (p=0.006). The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p=0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 μg/kg/min p=0.56, respectively).
  
  
  CONCLUSIONS
  These findings suggest that a LVD following coronary ischaemia consistently induces BHR. The more consistent efficacy of both treatment strategies in preventing BHR than in treating the adverse pulmonary vascular consequences suggests the benefit of both calcium channel blockade and ACE inhibition to counteract the airway susceptibility following a LVD.
authors.affiliation: Department of Medical Physics and Informatics, University of Szeged, 9 Koranyi fasor, H-6720, Szeged, Hungary. petak@dmi.szote.u-szeged.hu
authors.forename: Ferenc
authors.initials: F
authors.lastname: Petak
authors.forename: Gergely
authors.initials: G
authors.lastname: Albu
authors.forename: Eniko
authors.initials: E
authors.lastname: Lele
authors.forename: Maurice
authors.initials: M
authors.lastname: Beghetti
authors.forename: Walid
authors.initials: W
authors.lastname: Habre
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D016210:Methacholine Chloride / Q000009:adverse effects; D017202:Myocardial Ischemia / Q000150:complications; D010991:Plethysmography; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016085:Bronchoconstrictor Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D016210:Methacholine Chloride