The role of propranolol’s negative chronotropic effect on protection of the ischemic myocardium

L. David Hillis, Shukri F. Khuri, Eugene Braunwald, Peter R. Maroko

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Propranolol exerts a salutary effect on the ischemic myocardium. This beneficial influence is believed due mainly to a reduction in myocardial oxygen requirements, which, in turn, is caused by a decrease in both heart rate (HR) and contractility. The present study was performed to assess the salutary effect of propranolol on the ischemic myocardium, both when HR was allowed to decrease as well as when it was maintained constant by electrical pacing of the atria, then to compare the magnitude of its effect under these conditions. In 30 open-chest, anesthetized dogs, 10-min coronary artery occlusions (CAO) were performed 45 min apart, and intramural carbon dioxide tension (PmCO2) in the ischemic area was measured continuously with a mass spectrometer. 7 dogs received no intervention during any of the occlusions and, therefore, served as controls; 7 received propranolol, 2 mg/kg i.v. 10 min before the last CAO; 7 received the same dose of propranolol and, in addition, were paced to a HR identical to that during the previous CAO. In another 9 animals, atrial pacing was performed during the last CAO at a HR of 35-40 beats/min greater than during the previous CAO. In the controls, the rise in PmC02 (ΔPmCO2) during the last CAO was similar to that during the previous CAO. In contrast, in the 7 dogs which received propranolol alone, HR fell significantly (from 138 ± 6 to 105 ± 5 beats/min. p <0.01), and ΔPmCO2 fell by an average of 43 ± 5%. In the 7 dogs which received propranolol and were paced. ΔPmCO2 declined by 36 ± 5% (NS compared to those which received propranolol alone). In the dogs in which HR was increased by atrial pacing ΔPmCO2 did not rise significantly. In conclusion: (1) propranolol exerts most of its beneficial effect on myocardial ischemia independently of its negative chronotropic influences; (2) in the open-chest, anesthetized dog. further modest increases in heart rate do not greatly accentuate the severity of ischemia.

Original languageEnglish (US)
Pages (from-to)202-208
Number of pages7
Issue number4
StatePublished - 1979
Externally publishedYes


  • Beta-adrenergic blockade
  • Myocardial ischemia
  • Propranolol

ASJC Scopus subject areas

  • Pharmacology


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