Levente Tóth

Overview of large animal myocardial infarction models (review).

There are several experimental models for the in vivo investigation of myocardial infarction (MI) in small (mouse, rat) and large animals (dog, pig, sheep and baboons). The application of large animal models raises ethical concerns, the design of experiments needs longer follow-up times, requiring proper breeding and housing conditions, therefore resulting in higher cost, than in vitro or small animal studies. On the other hand, the relevance of large animal models is very important, since they mostly resemble to human physiological and pathophysiological processes. The first main difference among MI models is the method of induction (open or closed chest, e.g. surgical or catheter based); the second main difference is the presence or absence of reperfusion. The former (i.e. reperfused MI) allows the investigation of reperfusion injury and new catheter based techniques during percutaneous coronary interventions, while the latter (i.e. nonreperfused MI) serves as a traditional coronary occlusion model, to test the effects of new pharmacological agents and biological therapies, as cell therapy. The reperfused and nonreperfused myocardial infarction has different outcomes, regarding left ventricular function, remodelling, subsequent heart failure, aneurysm formation and mortality. Our aim was to review the literature and report our findings regarding experimental MI models, regarding the differences among species, methods, reproducibility and interpretation.

Differentiation of acute and four-week old myocardial infarct with Gd(ABE-DTTA)-enhanced CMR.

BackgroundStandard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older myocardial infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older myocardial infarct using myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent.Dogs (n = 6) were studied in a closed-chest, reperfused, double myocardial infarct model. Myocardial infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second myocardial infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABE-DTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Massons trichrome staining provided histologic evaluation of infarcts.ResultsGd(ABE-DTTA) or Gd(DTPA) highlighted the acute infarct, whereas the four-week old infarct was visualized by Gd(DTPA), but not by Gd(ABE-DTTA). With Gd(ABE-DTTA), the mean ± SD signal intensity enhancement (SIE) was 366 ± 166% and 24 ± 59% in the acute infarct and the four-week old infarct, respectively (P < 0.05). The latter did not differ significantly from signal intensity in healthy myocardium (P = NS). Gd(DTPA) produced signal intensity enhancements which were similar in acute (431 ± 124%) and four-week old infarcts (400 ± 124%, P = NS), and not statistically different from the Gd(ABE-DTTA)-induced SIE in acute infarct. The existence and localization of both infarcts were confirmed by triphenyltetrazolium chloride (TTC). Histologic evaluation demonstrated coagulation necrosis, inflammation, and multiple foci of calcification in the four day old infarct, while the late subacute infarct showed granulation tissue and early collagen deposition.ConclusionsLate enhancement CMR with separate administrations of standard extracellular contrast agent, Gd(DTPA), and the new low molecular weight contrast agent, Gd(ABE-DTTA), differentiates between acute and late subacute infarct in a reperfused, double infarct, canine model.

Percent infarct mapping for delayed contrast enhancement magnetic resonance imaging to quantify myocardial viability by Gd(DTPA).

To demonstrate the advantages of signal intensity percent‐infarct‐mapping (SI‐PIM) using the standard delayed enhancement (DE) acquisition in assessing viability following myocardial infarction (MI). SI‐PIM quantifies MI density with a voxel‐by‐voxel resolution in clinically used DE images.

Evaluation of experimental myocardial infarction models via electromechanical mapping and magnetic resonance imaging.

The diagnostic characteristics of electromechanical mapping (EMM) were evaluated in porcine myocardial infarction (MI) models with the parallel application of cardiac magnetic resonance imaging (cMRI) from the aspect of different pathophysiology and localization. Balloon occlusion in the left anterior descending coronary artery (LAD balloon group) or coil deployment in the LAD (LAD coil group) or circumflex artery (Cx coil group) was applied percutaneously in 16 domestic pigs. Regional left ventricular viability data were captured via cMRI and EMM. The unipolar voltage (UV) value was significantly decreased in segments containing transmural and subendocardial late enhancement compared with viable segments in the LAD balloon, LAD coil, and Cx coil groups. Receiver operating characteristic analysis revealed area under the curve values of 0.809 and 0.691 in the LAD infarct territory, and 0.864 and 0.855 in the Cx infarct territory for the UV compared with cMRI viability results as transmural late enhancement or viable tissue and subendocardial late enhancement or viable tissue, respectively. In conclusion, the UV value detected the presence of scar tissue with differential transmural extent and which represented proper diagnostic features both in the reperfused and nonreperfused models. This data could provide additional benefit in the clinical use of EMM for diagnostic purposes.

Chronic postinfarction pseudo-pseudoaneurysm diagnosed by cardiac MRI

Left ventricular pseudo‐pseudoaneurysm is an extremely rare complication of myocardial infarction. In this condition the postinfarction rupture of the myocardium is not transmural, but remains circumscribed within the ventricular muscle itself as a cavity joining to the left ventricle through a narrow neck. The differentiation between postinfarction pseudoaneurysms and pseudo‐pseudoaneurysms may be very difficult using conventional imaging techniques, such as transthoracic, or transesophageal echocardiography and left ventricular angiography. Cardiac MRI (CMR), however, is capable of distinguishing among anatomical structures such as pericardium, thrombus, and myocardium. In our report a chronic postinfarction pseudo‐pseudoaneurysm is described by CMR in a patient with an old myocardial infarction. J. Magn. Reson. Imaging 2007.

Age-independent myocardial infarct quantification by signal intensity percent infarct mapping in swine

To test whether signal intensity percent infarct mapping (SI‐PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age.

REINFARCTION-SPECIFIC MAGNETIC RESONANCE IMAGING CONTRAST AGENT

Methods: Dogs (n=6) were studied in closed-chest, reperfused, double MI model. MIs were generated by occluding the Left Anterior Descending coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumfex coronary artery. Inversion-recovery gradient-echo (IR-GRE) delayed enhancement (DE) images were obtained on day 3 and day 4 after second MI, using Gd(DTPA) and Gd(ABE-DTTA), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Masson’s trichrome staining provided histologic evaluation of infarcts.

Dobutamine stress cardiovascular magnetic resonance imaging in patients with peripheral artery disease

Patients with peripheral arterial disease often have coronary heart disease, as well. However, their assessment with classical noninvasive cardiology methods is often non-diagnostic or limited. The aim of this study was to analyze the feasibility and the risks of dobutamine stress cardiovascular MRI for cardiac evaluation of patients with peripheral arterial disease. 21 patients with peripheral artery disease (mean±SD age 64.3±7.7 years) were studied prospectively with dobutamine stress cardiovascular MRI. The protocol was completed by all of 21 patients. The target heart rate was attained in 95.2% of the studies. No serious adverse event occurred. The image quality scores (1-4) for all ventricular wall segments were high (median, interquartile range) (4 [4-4]). Five patients (23.8%) have inducible wall motion abnormality. Interobserver agreement was almost perfect for wall motion scores (κ = 0.87, p<0.0001). Dobutamine stress cardiovascular MRI is feasible with low risk for the cardiological assessment of patients with peripheral arterial disease.

[Pacemaker in MR: absolute contraindication?].

Due to developments in pacemaker technology, implanted pacemakers do not mean an absolute contraindication for MRI examination. However, there are several aspects of MRI examinations that should be considered for safety reasons in pacemaker patients. Based on literature data and own experiments, the safety protocol of MRI examination in pacemaker-implanted patients is described. The interaction of pacemakers--frequently implanted in Hungary--with MR scanners of 0,35 and 1,5 T was studied in vitro. In addition, the cardiac MRI examination of two pacemaker patients is presented. -ICD pacemakers showed strong interaction with static and changing magnetic field that affected pacemaker performance significantly. MRI examination can be safely performed in pacemaker-independent patients. Based on our in vitro and in vivo measurements, MRI examination is still contraindicated in pacemaker-dependent patients. In pacemaker-independent patients blood pressure, ECG monitoring and pulsoximetry are absolutely necessary, in addition, equipment for resuscitation should be available. Pacemaker should be specifically programmed before MRI examination and parameters and functionality should be checked in details afterwards.