Establishment Of A Canine Model Of Fat Embolism Induced No/slow Flow Of Coronary Artery

BackgroundAtherosclerotic coronary heart disease is one of the main morbidities that affect people's health in today's society. The treatment of coronary heart disease have evolved from medication treatment to the widely application of percutaneous coronary intervention (PCI), which enabled fundamental breakthrough of the prognosis and outcome of CHD treatment. Albeit the significant improvement of CHD treatment by PCI, some complications occur from time to time and deeply annoy the cardiologists. One of the most frequent complications is the slow/no-reflow phenomenon, which greatly hampered the left ventricular function improvement after PCI and increased the re-hospitalization rate and the mortality. Some statistics show that the rate of no-reflow after PCI can be as high as 13-37%.In"Percutaneous coronary intervention Guideline 2009", the slow/no-reflow was defined as: Obvious distal forward flow reduction (Thrombolysis in myocardial infarction, TIMI grade 2, defined as slow-flow) or loss (TIMI grade 0-1, defined as no-reflow) after lifting of the coronary stenosis. Slow/no-reflow phenomenon reflects the partial or overall suboptimal perfusion of the target vessel related region. With regard to the mechanism of slow/no-reflow, there are currently multiple hypotheses. Generally, the mechanisms proposed can be attributed to 2 categories, i.e., no-reflow caused by reperfusion and no-reflow caused by intervention. The former is caused by fatty content of plaque that is squeezed out of the plaque through the erupted fibrous cap, which then blocks flow to the distal segment of the artery. This type of no-reflow more frequently occurs on the right coronary arteries. It is shown that, the no-reflow in acute myocardial infarction patients after PTCA or stenting was closely related with the morphological changes after vascular injury detected by IVUS. The fatty pool has similar morphology as the vulnerable plaque, and can be utilized to simulate the no-reflow phenomenon in the real setting. Based on the clinical problem of slow/no-reflow, the present study was designed to establish a practical animal model of slow/no-reflow, in which we firstly would investigate if manual injection of fat emboli (FE) could result in slow/no- reflow, and then explore the amount of emboli to be used and the severity and mechanism of microvascular injuries caused by this model.MethodsPart I1. Preparation of the fat emboli.Ten milliliter of sterile fat emboli were prepared according to the literature for the subsequent experiment.2. Establishment of the no-reflow animal model.Routine pre-operation preparation was performed. The electrocardiograph (ECG) was recorded and the blood sample was drawn. Dynamic ECG monitoring was performed throughout the imaging procedure. The left ventricle was firstly imaged and the left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were recorded. Then, coronary arteriography (CAG) of both the left and right coronary artery was performed. Fat emboli solution (0.5 ml) was slowly (5 seconds) infused into the dominant artery through the microcatheter. Coronary imaging was performed and LVEDP recorded after the injection. The corrected TIMI frame count (CTFC) was calculated to evaluate whether slow/no-reflow existed. If no signs of no-reflow appear, the emboli infusion was repeated after 5 minutes, until the success of the model. Finally, left ventricular imaging was performed again to record the LVSP and LVEDP.Part II1. Post-operational monitoringThe evolvement of ECG was monitored by recorded ECG every 30 minutes, and blood sample was taken every 1 hour from the femoral artery sheath catheter of the dog to measure the biochemical indices.2. Histopathological examination and electronic microscopic observationThe animals were sacrificed 10 hours after the procedure. The heart was excised, and stained. The target region was examined by histopathological examinations and electronic microscopy.Results1. The success rate of the model was 75%, with average injections of 1.5 times.2. Hemodynamic changes: Heart rate, blood pressure and LVSP all changed significantly after the model establishment. Changes of ECG can be observed as soon as the injection of the emboli. Dynamic evolvement of ECG was observed afterwards.3. Blood examinations: The plasma levels of CK and CK-MB increased significantly after the establishment of the model.4. Histopathology: Target region myocardial injuries were confirmed by both routine histopathology and electronic microscopy.Conclusion1. Fat emboli can be used to induce slow/no-reflow phenomenon that resembles the clinical setting.2. It is feasible to simulate slow/no-reflow phenomenon by injecting fat emboli into the canine coronary. The injuries were minor and animal survival rate was high.3. Fat embolism causes incomplete mechanical obstruction, showing dynamic evolvement, which was in concordance with the slow/no-reflow phenomenon observed on patients.4. Fat embolism activates additional local injury mechanisms besides the mechanical obstruction, demonstrating comprehensive myocardial injury effects.