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

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.
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.

背景
平均动脉压（mean arterial pressure, MAP）与冠状动脉血流量之间的关联已有充分研究。在60至140 mmHg的MAP范围内存在自身调节机制，可维持冠状动脉血流量近乎恒定。超出该范围时，血流量将转为压力依赖性。迄今为止，心肌氧合对压力与血流量变化的响应更难评估。现有主流技术多需采用有创手段，而氧敏感（Oxygenation-Sensitive, OS）心血管磁共振（cardiovascular magnetic resonance, CMR）是一种可无创评估心肌组织氧合变化的技术。本研究旨在利用OS-CMR，在已知冠状动脉自身调节极限内外的广泛血压变化范围内监测心肌氧合情况，并将这些数据与冠状动脉血流动力学相关联。

方法
10只麻醉的德国大白猪（German Large White）接受左侧开胸术，并在左前降支（left anterior descending, LAD）冠状动脉近端安装血管周流量探头，以持续测量血流量（Q_LAD）。随后将动物转移至3T磁共振扫描仪中。通过给予α1受体激动剂去氧肾上腺素（phenylephrine）或乌拉地尔（urapidil），以10–15 mmHg的步幅调整平均动脉压。对于每一级MAP水平，在短暂屏息期间同步获取OS-CMR图像以及动脉和冠状窦血气样本。以MAP为70 mmHg时的参考水平为基准，计算冠状窦氧饱和度（ScsO2）、氧输送（DO2）、氧需求（MVO2）、氧提取率（O2ER）与氧过剩量（Ω）的相对变化量（Δ），并将其与同步采集的OS-CMR图像中的OS信号强度（OS-SI）变化百分比进行比较。

结果
Q_LAD的响应表明，自身调节发生在52 mmHg（下限）至127 mmHg（上限）的MAP范围内。OS-CMR显示，在自身调节下限以下会出现全局性心肌氧合不足，OS-SI的最低点为-9.0%。当MAP值超过70 mmHg时，相对OS-SI升高至+10.6%的峰值。与此一致的是，ΔScsO2、ΔDO2、ΔMVO2、ΔO2ER和ΔΩ的响应均表明，在自身调节区域外，氧合平衡的失衡情况加剧。全局OS-CMR的变化与除ΔMVO2外的所有上述参数均存在显著相关性（p≤0.02）。

结论
OS-CMR提供了一种新颖且无创的途径，可评估血压变化、心血管药物及干预措施对全局和局部心肌氧合的影响，这一点在猪模型中已得到验证。OS-CMR可识别冠状动脉自身调节下限以下的氧供需失衡情况。血管加压素诱导的急性高血压虽会增加心脏做功和氧需求，但并未对健康心脏的心肌氧合造成损害。OS-CMR的临床应用价值仍有待进一步确立。