Relationship between myocardial oxygenation and blood pressure: Experimental validation using oxygenation-sensitive cardiovascular magnetic resonance

RESEARCH ARTICLE Relationship between myocardial oxygenation and blood pressure: Experimental validation using oxygenationsensitive cardiovascular magnetic resonance Dominik P. Guensch ID1,2*, Kady Fischer1,2,3, Christof Jung1, Samuel Hurni4, Bernhard M. Winkler4, Bernd Jung2, Andreas P. Vogt1, Balthasar Eberle1 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, 2 Institute for Diagnostic, Interventional and Paediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, 3 McGill University Health Centre, Montreal, QC, Canada, 4 Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland * Abstract OPEN ACCESS Citation: Guensch DP, Fischer K, Jung C, Hurni S, Winkler BM, Jung B, et al. (2019) Relationship between myocardial oxygenation and blood pressure: Experimental validation using oxygenation-sensitive cardiovascular magnetic resonance. PLoS ONE 14(1): e0210098. https:// doi.org/10.1371/journal.pone.0210098 Editor: Vincenzo Lionetti, Scuola Superiore Sant’Anna, ITALY Received: July 29, 2018 Accepted: December 16, 2018 Published: January 16, 2019 Copyright: © 2019 Guensch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by institutional funds of the Department of Anaesthesiology and Pain Medicine at the Bern University Hospital, Inselspital, University of Bern and the Foundation for Research in Anaesthesiology and Intensive Care Medicine in Bern, Switzerland. Background The relationship between mean arterial pressure (MAP) and coronary blood flow is well described. There is autoregulation within a MAP range of 60 to 140 mmHg providing near constant coronary blood flow. Outside these limits flow becomes pressure-dependent. So far, response of myocardial oxygenation to changes in pressure and flow has been more difficult to assess. While established techniques mostly require invasive approaches, Oxygenation-Sensitive (OS) Cardiovascular Magnetic Resonance (CMR) is a technique that can non-invasively assess changes in myocardial tissue oxygenation. The purpose of this study was to follow myocardial oxygenation over a wide range of blood pressure variation within and outside known coronary autoregulatory limits using OS-CMR, and to relate these data to coronary hemodynamics. Methods Ten anaesthetized swine (German Large White) underwent left-sided thoracotomy and attachment of a perivascular flow probe to the proximal left anterior descending (LAD) coronary artery for continuous measurement of blood flow (QLAD). Thereafter, animals were transferred into a 3T MRI scanner. Mean arterial pressure (MAP) was varied in 10–15 mmHg steps by administering alpha1-receptor agents phenylephrine or urapidil. For each MAP level, OS-CMR images as well as arterial and coronary sinus blood gas samples were obtained simultaneously during brief periods of apnea. Relative changes (Δ) of coronary sinus oxygen saturation (ScsO2), oxygen delivery (DO2) and demand (MVO2), extraction ratio (O2ER) and excess (Ω) from respective reference levels at a MAP of 70 mmHg were determined and were compared to %change in OS-signal intensity (OS-SI) in simultaneously acquired OS-CMR images. PLOS ONE | https://doi.org/10.1371/journal.pone.0210098 January 16, 2019 1 / 17 Relationship between blood pressure and myocardial oxygenation Competing interests: The authors have declared that no competing interests exist. Results QLAD response indicated autoregulation between MAP levels of 52 mmHg (lower limit) and127 mmHg (upper limit). OS-CMR revealed a global myocardial oxygenation deficit occurring below the lower autoregulation limit, with the nadir of OS-SI at -9.0%. With MAP values surpassing 70 mmHg, relative OS-SI increased to a maximum of +10.6%. Consistent with this, ΔScsO2, ΔDO2, ΔMVO2, ΔO2ER and ΔΩ responses indicated increasing mismatch of oxygenation balance outside the autoregulated zone. Changes in global OS-CMR were significantly correlated with all of these parameters (p�0.02) except with ΔMVO2. Conclusion OS-CMR offers a novel and non-invasive route to evaluate the effects of blood pressure variations, as well as of cardiovascular drugs and interventions, on global and regional myocardial oxygenation, as demonstrated in a porcine model. OS-CMR identified mismatch of O2 supply and demand below the lower limit of coronary autoregulation. Vasopressor induced acute hypertension did not compromise myocardial oxygenation in healthy hearts despite increased cardiac workload and O2 demand. The clinical usefulness of OS-CMR remains to be established. Introduction Coronary autoregulation Myocardial blood flow in humans delivers approximately 70-80ml/min/100g myocardial tissue at rest. Coronary flow reserve can increase myocardial blood flow up to 3-5-fold from resting conditions [1–3]. Vascular autoregulation is characteristic for vital organs such as heart and brain, ensuring adequate and near constant tissue blood flow over a wide range of blood pressure [4]. Thus, blood pressure variation within autoregulatory limits should not compromise delivery of O2 and nutrients. The main mechanism of blood pressure-dependent regulation of blood flow has been proposed in 1902 by Bayliss [5], and is known since as the Bayliss effect or myogenic control of vascular tone [6]. In healthy humans, coronary autoregulation has been reported to be effective within a range of mean arterial pressures (MAP) between approximately 60 and 140mmHg. Such limits may vary with different pathologies, and higher perfusion pressures may be required to maintain constant blood flow [7]. Especially in the presence of a fixed coronary stenosis or of overriding coronary vasodilation, blood flow becomes pressure dependent [8]. Coronary perfusion of the left ventricular myocardium mainly occurs during diastole. Hence, an increase in aortic diastolic pressure and a longer diastolic time will improve perfusion. When MAP increases beyond the upper autoregulatory limit, coronary blood flow is markedly increased and becomes pressure dependent. Arterial hypertension will also increase oxygen demand and may reduce subendocardial blood flow [9]. This can outweigh enhanced oxygen supply from coronary vasodilation. In fact such challenges have been shown to increase oxygen demand and myocardial oxygen extraction [2,7–10]. Thus, severe hypertension may uncouple oxygen demand from supply and may compromise myocardial oxygenation. This effect has traditionally been assessed by calculating o (...truncated)