Interplay between metabolic and myogenic mechanisms in coronary pressure-flow autoregulation

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dc.contributor.advisorTune, Johnathan D.
dc.contributor.committeeMemberDick, Gregory M.
dc.contributor.committeeMemberMallet, Robert T.
dc.creatorWarne, Cooper M.
dc.date.accessioned2022-10-26T15:26:26Z
dc.date.available2022-10-26T15:26:26Z
dc.date.issued2022-05
dc.description.abstractThe local metabolic hypothesis proposes that myocardial oxygen tension, indexed by coronary venous PO2 (CvPO2), determines the degree of coronary pressure-flow autoregulation. Conversely, the myogenic hypothesis proposes that pressure-induced vascular tone, indexed by the pressure at which coronary flow is zero (Pzf), determines autoregulation. My working hypothesis posits that if metabolism predominates, then autoregulation will be directly related to CvPO2, irrespective of reductions in coronary vasomotor tone. Conversely, if a myogenic mechanism predominates, then autoregulation will be directly related to Pzf, regardless of underlying CvPO2. I tested these hypotheses by examining the extent to which exaggeration of the metabolic error signal and attenuation of myogenic tone influences coronary autoregulation. Experiments were performed in anesthetized, open-chest swine in which a coronary artery was cannulated and connected to a servo-controlled roller pump system. This allowed coronary perfusion pressure (CPP) to be incrementally reduced from 140 to 40 mmHg before and during hypoxemia (SO2 ~50%). CvPO2 decreased 13 mmHg and coronary blood flow fell 57% as CPP was reduced. Hypoxemia augmented myocardial oxygen consumption (P < 0.01), increased coronary blood flow (P < 0.0001), and reduced CvPO2 (P < 0.0001) over the same CPP range. Coronary blood flow during hypoxemia maintained myocardial oxygen delivery (P = 0.20). Hypoxemia increased closed-loop autoregulatory gain (Gc) over a CPP range of 120 to 60 mmHg (P = 0.02). Gc was inversely correlated to CvPO2 and Pzf, but the correlation was stronger for CvPO2. These findings support that coronary pressure-flow autoregulation is augmented by hypoxemia-induced increases in the local metabolic error signal, regardless of the myogenic tone.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31891
dc.language.isoen
dc.subjectautoregulation
dc.subjectcoronary
dc.subjecthypoxemia
dc.subjectswine
dc.subject.meshHypoxia
dc.subject.meshCoronary Circulation
dc.subject.meshMetabolism
dc.titleInterplay between metabolic and myogenic mechanisms in coronary pressure-flow autoregulation
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentSchool of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameMaster of Science

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