title: Role of force--frequency relation during AV-block, sinus node block and beta-adrenoceptor block in conscious animals.
abstract: OBJECTIVE
  Myocardial contractility is regulated by adrenergic stimulation, the strength-length relationship and the force-frequency relationship or Bowditch effect. The latter mechanism was clearly demonstrated in muscle strips, in the isolated heart as well as in in-vivo experiments. The aim of this study was to further investigate the role of the force-frequency effect on the contractile response to exercise or isoproterenol infusion in conditions of restricted increases in heart rate i.e., AV-block, sinus node block and beta-adrenoceptor block.
  
  
  METHODS
  Nineteen dogs were instrumented with a left ventricular miniature pressure gauge, catheters in the aorta, pulmonary artery and left atrium and pacing leads on the left atrium and left ventricle. In order to control the chronotropic response during sympathetic stimulation, permanent AV-block was induced in nine dogs, sinus node block using UL-FS 49 and beta-adrenoceptor block using propranolol was studied in ten dogs.
  
  
  RESULTS
  Adrenergic stimulation (isoproterenol 0.4 micro g/kg or exercise) after total AV-block failed to increase LVdP/dt. However, increasing LV pacing rate (from 50 up to 200 bpm) prior to adrenergic stimulation elicited a significant increase in LVdP/dt (4762 +/- 166 mmHg/s vs. 6485 +/- 381 mmHg/s, p < 0.05). In dogs in sinus rhythm, heart rate and LVdP/dt response to isoproterenol and exercise following pre-treatment with UL-FS 49 is significantly reduced, with heart rate increasing from 103 +/- 7 up to 154 +/- 5 bpm and LV dP/dt(max) from 2925 +/- 171 mmHg/s to 6249 +/- 400 mmHg/s compared to the response in control conditions (HR 220 +/- 3 bpm and LV dP/dt(max) 7473 +/- 616 mmHg/s) (p < 0.05). When heart rate is matched using atrial pacing, the LVdP/dt(max) response reached comparable values as observed in control conditions (7310 +/- 550 mmHg/s). Similar responses were obtained during exercise. Beta-adrenoceptor blockade attenuates considerably the heart rate and LVdP/dt response to sympathetic stimulation. Adjusting heart rate with atrial pacing restores only partially LVdP/dt(max).
  
  
  CONCLUSIONS
  During sympathetic stimulation, the chronotropic response plays a major role for the concomitant full expression of the inotropic response. In conditions where increases in heart rate are absent or severely restricted such as in permanent AV-block, sinus node block and beta-adrenoceptor block, the inotropic response will also be impaired.
authors.affiliation: Department of Cardiology, University Hospital Ghent, De Pintelaan 184, 9000 Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: De Pauw
authors.forename: J-P
authors.initials: JP
authors.lastname: Vilaine
authors.forename: G R
authors.initials: GR
authors.lastname: Heyndrickx
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006327:Heart Block / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D011433:Propranolol / Q000494:pharmacology; D012848:Sinoatrial Block / Q000503:physiopathology*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002316:Cardiotonic Agents; D011433:Propranolol; D007545:Isoproterenol; C043636:zatebradine