Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure

Cooper M. Warne, Salman I. Essajee, Selina M. Tucker, C. Alberto Figueroa, Daniel A. Beard, Gregory M. Dick, Johnathan D. Tune

Research output: Contribution to journalArticlepeer-review


The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. However, the mechanisms responsible for coronary autoregulation remain a fundamental and highly contested question. This study interrogated the local metabolic hypothesis of autoregulation by testing the hypothesis that hypoxemia-induced exaggeration of the metabolic error signal improves the autoregulatory response. Experiments were performed on open-chest anesthetized swine during stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg under normoxic (n = 15) and hypoxemic (n = 8) conditions, in the absence and presence of dobutamine-induced increases in myocardial oxygen consumption (MVO2) (n = 5–7). Hypoxemia (PaO2 < 40 mmHg) decreased coronary venous PO2 (CvPO2) ~ 30% (P < 0.001) and increased coronary blood flow ~ 100% (P < 0.001), sufficient to maintain myocardial oxygen delivery (P = 0.14) over a wide range of CPPs. Autoregulatory responsiveness during hypoxemia-induced reductions in CvPO2 were associated with increases of autoregulatory gain (Gc; P = 0.033) but not slope (P = 0.585) over a CPP range of 120 to 60 mmHg. Preservation of autoregulatory Gc (P = 0.069) and slope (P = 0.264) was observed during dobutamine administration ± hypoxemia. Reductions in coronary resistance in response to decreases in CPP predominantly occurred below CvPO2 values of ~ 25 mmHg, irrespective of underlying vasomotor reserve. These findings support the presence of an autoregulatory threshold under which oxygen-sensing pathway(s) act to preserve sufficient myocardial oxygen delivery as CPP is reduced during increases in MVO2 and/or reductions in arterial oxygen content.

Original languageEnglish
Article number12
JournalBasic Research in Cardiology
Issue number1
StatePublished - Dec 2023


  • Coronary circulation
  • Feedback
  • Homeostasis
  • Hypoxia
  • Oxygen consumption


Dive into the research topics of 'Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure'. Together they form a unique fingerprint.

Cite this