Role of ancillary properties of beta-adrenoceptor antagonists in protecting the heart from anoxia.
The mechanism of the cardioprotective action of beta-blocking drugs against anoxia or ischemia is still not clear. We used beta-blockers (5 x 10(-7) M) of various pharmacodynamic profiles in a model of isolated, perfused working guinea pig heart subjected to 20 min of anoxia to study this. The cardioprotective effects were evaluated by measuring the recovery of the flow indices after 15 min of reoxygenation. There was a significant cardioprotective action (as measured by the effect on stroke volume recovery and on recovery of other flow and work indices) of the beta-blocking properties (nadolol, P less than 0.05), of the membrane-stabilizing property [+)-propranolol, P less than 0.05) and of a combination of these two properties with (+/-)-propranolol, which had a significantly greater effect than nadolol (P less than 0.05). The addition of weak (acebutolol) or strong (pindolol) intrinsic partial agonist activity had no clear unfavourable effect, as the degree of cardioprotection was comparable with that obtained with (+/-)-propranolol. The stroke volume recovery (percent recovery after anoxia) in the control hearts was 42.57 +/- 12.75 compared to 54.84 +/- 6.94 in hearts pretreated with nadolol, 62.99 +/- 11.41 with (+)-propranolol, 71.02 +/- 11.36 with (+/-)-propranolol, 72.63 +/- 13.08 with acebutolol and 68.01 +/- 15.42 with pindolol. In vitro heart protection from anoxia with beta-blockers would appear to be related to beta-blocking activity and/or membrane stabilizing property but not a function of partial agonist activity. These ancillary properties of beta-blockers should thus be taken into account in studies on cardioprotection.
Marie
P Y
PY
Laboratoire de Pharmacologie, CHRU, Nancy, France.
Zannad
F
F
Parisot
M
M
Royer
R J
RJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000517:prevention & control*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects
D000319:Adrenergic beta-Antagonists