Impact of Intermittent Apnea on Myocardial Tissue Oxygenation—A Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance

Friedrich MG (2013) Impact of Intermittent Apnea on Myocardial Tissue Oxygenation-A Study Using Oxygenation- Sensitive Cardiovascular Magnetic Resonance. PLoS ONE 8(1): e53282. doi:10.1371/journal.pone.0053282 Impact of Intermittent Apnea on Myocardial Tissue Oxygenation-A Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance Dominik P. Guensch 0 Kady Fischer 0 Jacqueline A. Flewitt 0 Matthias G. Friedrich 0 Wolfgang Rudolf Bauer, University Hospital of Wu rzburg, Germany 0 1 Stephenson Cardiovascular MR Centre at the Libin Cardiovascular Institute of Alberta, Departments of Cardiac Sciences and Radiology, University of Calgary , Calgary, Alberta , Canada , 2 CMR Research Centre at the Montreal Heart Institute, Universite de Montre al , Montreal, Quebec , Canada Background: Carbon dioxide (CO2) is a recognized vasodilator of myocardial blood vessels that leads to changes in myocardial oxygenation through the recruitment of the coronary flow reserve. Yet, it is unknown whether changes of carbon dioxide induced by breathing maneuvers can be used to modify coronary blood flow and thus myocardial oxygenation. Oxygenation-sensitive cardiovascular magnetic resonance (CMR) using the blood oxygen level-dependent (BOLD) effect allows for non-invasive monitoring of changes of myocardial tissue oxygenation. We hypothesized that mild hypercapnia induced by long breath-holds leads to changes in myocardial oxygenation that can be detected by oxygenation-sensitive CMR. Methods and Results: In nine anaesthetized and ventilated pigs, 60s breath-holds were induced. Left ventricular myocardial and blood pool oxygenation changes, as monitored by oxygenation-sensitive CMR using a T2*-weighted steady-state-freeprecession (SSFP) sequence at 1.5T, were compared to changes of blood gas levels obtained immediately prior to and after the breath-hold. Long breath-holds resulted in an increase of paCO2, accompanied by a decrease of paO2 and pH. There was a significant decrease of blood pressure, while heart rate did not change. A decrease in the left ventricular blood pool oxygenation was observed, which was similar to drop in SaO2. Oxygenation in the myocardial tissue however, was maintained throughout the period. Changes in myocardial oxygenation were strongly correlated with the change in paCO2 during the breath-hold (r = 0.90, p = 0.010). Conclusion: Despite a drop in blood oxygen levels, myocardial oxygenation is maintained throughout long breath-holds and is linearly correlated with the parallel increase of arterial CO2, a known coronary vasodilator. Breathing maneuvers in combination with oxygenation-sensitive CMR may be useful as a diagnostic test for coronary artery function. - Funding: The Husky Energy Inc., as part of the Husky Energy Program for the Early Detection of Cardiovascular Disease, sponsored this investigation, yet did not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Matthias G. Friedrich is advisor and shareholder of Circle Cardiovascular Imaging Inc., Calgary, AB, Canada. There is a pending patent (US Patent Pending 61_680,981), which protects the use of breathing maneuvers to induce changes of myocardial oxygenation for diagnostic purposes. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. Carbon dioxide (CO2) is a potent vasodilator in the cerebrovascular system [1,2]. With perturbations as little as such caused by breath holding can induce changes in cerebral blood flow. Recent data from our group indicate that this is paralleled by an increase in myocardial blood flow [3,4]. However, there is little information on the utility of CO2 as a vasodilator for diagnostic testing. Oxygenation-sensitive CMR detects changes of haemoglobin oxygenation by making use of the fact that its magnetic properties change when transitioning from oxygenated to deoxygenated status: While oxygenated haemoglobin (oxyHb) is diamagnetic exhibiting a weak stabilization of the magnetic field surrounding the molecule, deoxygenated haemoglobin (de-oxyHb) is paramagnetic, de-stabilizing the surrounding field and thereby leading to a loss of magnetic field homogeneity. T2* weighted CMR protocols sensitive to this blood oxygen level-dependent (BOLD) effect may show a regional signal intensity (SI) drop of tissue with such a relative increase of de-oxyHb [5,6] or a shortening in T2* time, as seen in myocardial ischemia [7]. Vice versa, increasing blood flow without a matching increase of oxygen consumption leads to a decrease in de-oxyHb and thus to an increased SI. Ogawa et al. used this to detect small variations of regional blood flow due to activation of brain areas in functional magnetic resonance imaging (fMRI) of the brain [8]. Using adenosine-induced coronary vasodilation, we could recently show that the vasodilatory effect leads to a measurable SI increase, which was linearly related to coronary sinus blood oxygenation yet not to blood flow [9]. We hypothesized that long-breath-hold induced hypercapnia leads to changes of myocardial haemoglobin oxygenation, which can be detected by oxygenation-sensitive CMR. Materials and Methods Experimental Protocol Nine juvenile male pigs (24.360.2 kg) were pre-medicated with 600 mg Ketamine, 10 mg Midazolam and 2 mg Fentanyl i.m., then anaesthetized with 2025 mg/kg Thiopental to establish an appropriate anaesthesia depth. They were intubated with a standard cuffed endotracheal tube (ID 5.56 mm) and ventilated with a Harvard Ventilator. Anaesthesia was maintained with an intravenous drip (13 mg/h Midazolam, 1.64.8 mg/h Fentanyl) and a nitrous oxide/Isoflurane (0.61.5%) gas narcosis. To prevent arrhythmia, the animals received a continuous Lidocaine infusion (1 mg/min). The right carotid artery and the femoral artery were cannulated for invasive blood pressure and arterial blood gas measurements throughout the experiment. The left jugular and femoral vein were cannulated for intravenous infusions. Monitoring of anaesthesia and haemodynamics included EtCO2, FiO2/FiN2O, 3-lead ECG, invasive blood pressure and arterial blood gases. After preparation, the animals were transferred to a clinical 1.5T MRI system (AvantoH, Siemens Healthcare, Erlangen, Germany). Custom 12 m long ventilator tubing connected the ventilator from outside the MR suite. Blood gases were adjusted to a target paO2 of 100 mmHg and a paCO2 of 40 mmHg. Then, BOLD-sensitive steady-state-free-precession (SSFP) cine images were acquired in mid left-ventricular short axis views (slice thickness 10 mm, TE 2.78 ms, TR 5.56 ms, flip angle 90u, FOV 2806157.5, matrix 128672) [9,10]. Each cine was composed of 20 phases covering the entire cardiac cycle, obtained by retrospective ECG gating. BOLD-SSFP cines were acquired during a 1 min breath-hold. Immediately after resuming ventilation an arterial blood sample was taken to determine the ch (...truncated)