Comparative effects of intracoronary administration of propranolol with systemic administration on hypoxic canine...

Myocardial protective effects of intracoronary administration of relatively small doses of propranolol were examined and compared with systemic administration in 20 open-chest dogs. In group 1 (n = 6) rate-pressure-product (R X P) did not change during 5-minute left anterior descending artery (LAD) perfusion with deoxygenated Krebs-Henseleit solutions (KHS). However, R X P decreased by the same degree in group 2 (n = 7), which received perfusion with KHS containing 0.4 or 0.8 mg/dl of propranolol, and in group 3 (n = 7) given LAD perfusion with original KHS and systemic administration of 0.02 to 0.04 mg/kg of propranolol. Total administered doses of propranolol were the same for groups 2 and 3. Transmural biopsy after 5 minutes of perfusion revealed less severe metabolic deterioration of hypoxic myocardium in group 2 when compared with that in group 1, as evidenced by higher ATP (adenosine triphosphate) (2.81 +/- 0.35 versus 2.23 +/- 0.45 mumol/g, p less than 0.05) and lower lactate content (5.62 +/- 1.44 versus 9.01 +/- 2.62 mumol/g, p less than 0.05). On the other hand, significant metabolic preservation was not noted in group 3. Sequential changes in regional myocardial contraction did not differ among the three groups. In conclusion, intracoronary administration of propranolol showed myocardial protective effects that were not mediated by the changes in hemodynamics and myocardial contraction.