Role of ancillary properties of β-adrenoceptor antagonists in protecting the heart from anoxia

Abstract

The mechanism of the cardioprotective action of β-blocking drugs against anoxia or ischemia is still not clear. We used β-blockers (5 × 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 affect on stroke volume recovery and on recovery of other flow and work indices) of the β-blocking properties (nadolol, P < 0.05), of the membrane-stabilizing property ((+)-propranolol, P < 0.05) and of a combination of these two properties with (±)-propranolol, which had a significantly greater effect than nadolol (P < 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 β-blockers would appear to be related to β-blocking activity and/or membrane stabilizing property but not a functio of partial agonist activity. These ancillary properties of β-blockers should thus be taken into account in studies on cardioprotection.