BackgroundBreathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR).Methods and FindingsIn 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75) of the left anterior descending coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001), when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point.ConclusionIn an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary artery stenosis. This maneuver may allow for detecting severe coronary artery stenosis and have a significant clinical potential as a non-pharmacological method for diagnostic testing in patients with suspected coronary artery disease.

Background-Current guidelines limit the use of high oxygen tension after return of spontaneous circulation after cardiac arrest, focusing on neurological outcome and mortality. Little is known about the impact of hyperoxia on the ischemic heart. Oxygen is frequently administered and is generally expected to be beneficial. This study seeks to assess the effects of hyperoxia on myocardia oxygenation in the presence of severe coronary artery stenosis in swine. Methods and Results-In 22 healthy pigs, we surgically attached a magnetic resonance compatible flow probe to the left anterior descending coronary artery (LAD). In 11 pigs, a hydraulic occluder was inflated distal to the flow probe. After increasing PaO 2 to >300 mm Hg, LAD flow decreased in all animals. In 8 stenosed animals with a mean fractional flow reserve of 0.64±0.02, hyperoxia resulted in a significant decrease of myocardial signal intensity in oxygenationsensitive cardiovascular magnetic resonance images of the midapical segments of the LAD territory. This was not seen in remote myocardium or in the other 8 healthy animals. The decreased signal intensity was accompanied by a decrease in circumferential strain in the same segments. Furthermore, ejection fraction, cardiac output, and oxygen extraction ratio declined in these animals. Changing PaCO 2 levels did not have a significant effect on any of the parameters; however, hypercapnia seemed to nonsignificantly attenuate the hyperoxia-induced changes. Conclusions-Ventilation-induced hyperoxia may decrease myocardial oxygenation and lead to ischemia in myocardium subject to severe coronary artery stenosis. (Circ Cardiovasc Interv. 2015;8:e002928.

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I − HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T 2 , T 1), hemorrhage (T 2 *), vasodilator function (T 2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre-and post-contrast T 1) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T 2 * values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia-alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T 2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia-alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high-risk patients progressing towards heart failure.

PurposeArterial blood gases change frequently during anesthesia and intensive care. Apnea can occur during diagnostic exams and airway and surgical interventions. While the impact of blood gas levels on coronary blood flow is established, their confounding effect on coronary vasoreactivity in response to an apneic stimulus, especially in coronary artery disease, is not known.MethodsSix anesthetized control swine and eleven swine with coronary artery stenosis were examined. Nine different blood gas levels from a combination of arterial partial pressure of oxygen (70, 100, and 300 mmHg) and carbon dioxide (30, 40, and 50 mmHg) were targeted. Apnea was induced by halting controlled positive pressure ventilation for 3–30s, while the left descending coronary artery flow was measured and reported relative to apnea duration, and at the adjusted mean (12s).ResultsAt normoxemic-normocapnic blood gas levels, apnea increased coronary blood flow in proportion to the duration of apnea in the control (r = 0.533, p &lt; 0.001) and stenosed groups (r = 0.566, p &lt; 0.001). This culminated in a 42% (95% CI: 27–58) increase in controls (p &lt; 0.001) and, to a lesser extent, 27% (15–40) in the presence of coronary artery stenosis (p &lt; 0.001). Vasoreactivity was augmented by mild-hypoxemic levels [81% (65–97), and 66% (53–79) increase in flow respectively, p &lt; 0.001 vs. normoxemia], but markedly reduced during hyperoxia (7.5% (−8.2–23) and 0.3% (−12–13), respectively, p &lt; 0.001 vs. normoxemia).ConclusionAlterations of blood oxygen and carbon dioxide affect coronary vascular reactivity induced by apnea in swine, which was attenuated further in the presence of coronary stenosis. Especially hyperoxia significantly reduces coronary blood flow and blunts coronary vascular reactivity.

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BACKGROUND: Assessing the coronary response to vasoactive stimuli is common in clinical cardiac exams; a short breathhold may be used to induce an increase in coronary blood flow. Arterial blood gases have a known profound effect on coronary flow. While hypercapnia increases myocardial blood flow, hypocapnia decreases it. There is little data about the effects of hyperoxia. The assessment of hyperoxic conditions is in particular importance to cardiac patients because of the common use of supplemental oxygen in clinical situations. This study investigates the impact of a vasodilating breathhold stimulus at different baseline blood oxygen and carbon dioxide levels. METHODS: In 16 swine, blood flow in the LAD was measured with a perivascular probe. In 10 of these animals an acute stenosis of the left anterior descending artery (LAD) was induced using a hydraulic occluder. Arterial blood gas levels were targeted to reach nine levels (O2/ CO2): combinations of paO2 of 70, 100 or >300mmHg and a paCO2 of 30, 40 or 50 mmHg. Ventilator breathholds were induced at each baseline ranging from 3-25s in duration and flow was expressed as a percent-change (D-%) over the breath-hold stimulus. This blood flow response was compared between the groups accounting for the breathhold duration and baseline gas levels and displayed in a heatmap. For the figure, data points were grouped into 5s blocks, and blocks without at least three data points are shown as beige. RESULTS: Ten animals with a significant LAD stenosis (FFR¼ 0.63AE0.02) underwent 432 breath-holds, while the six control animals had 279 breath-holds. For both groups, flow increased with breath-holds from all hypoxic and normoxic baselines (red), whereas only minimal responses to the breathholds were observed during hyperoxia. Accounting for breathhold duration, the response from the breath-hold was significantly stronger for the healthy than the stenotic animals at both hypoxia and normoxia, but this was not observed with