semi-minimal-invasive-method-to-induce-myocardial-infarction-rats

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily ...

Previous studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest.

Argon preconditioning enhances postischaemic cardiac functional recovery following cardioplegic arrest and global cold ischaemia.

We demonstrate the technical aspects of a novel adjustable mitral ring. This new ring was implanted in a female landrace pig, for training and educational purposes. It can be adjusted independently in the P1, P2 and P3 segments, if required, to treat  recurrent mitral regurgitation, and this is a key difference to comparable devices. The first-in-man implantation is anticipated in the near future.

Mitral valve repair with adjustable ring annuloplasty.

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder characterized by accelerated cardiovascular disease with extensive fibrosis. It is caused by a mutation in LMNA leading to expression of truncated prelamin A (progerin) in the nucleus. To investigate the contribution of the endothelium to cardiovascular HGPS pathology, we generated an endothelium-specific HGPS mouse model with selective endothelial progerin expression. Transgenic mice develop interstitial myocardial and perivascular fibrosis and left ventricular hypertrophy associated with diastolic dysfunction and premature death. Endothelial cells show impaired shear stress response and reduced levels of endothelial nitric oxide synthase (eNOS) and NO. On the molecular level, progerin impairs nucleocytoskeletal coupling in endothelial cells through changes in mechanoresponsive components at the nuclear envelope, increased F-actin/G-actin ratios, and deregulation of mechanoresponsive myocardin-related transcription factor-A (MRTFA). MRTFA binds to the Nos3 promoter and reduces eNOS expression, thereby mediating a profibrotic paracrine response in fibroblasts. MRTFA inhibition rescues eNOS levels and ameliorates the profibrotic effect of endothelial cells in vitro. Although this murine model lacks the key anatomical feature of vascular smooth muscle cell loss seen in HGPS patients, our data show that progerin-induced impairment of mechanosignaling in endothelial cells contributes to excessive fibrosis and cardiovascular disease in HGPS patients.

Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse.

Remote ischemic conditioning (RIC) is considered a potential clinical approach to reduce myocardial infarct size and ameliorate adverse post-infarct left ventricular (LV) remodeling, however the mechanisms are unknown. The aim was to clarify the impact of RIC on Neuregulin-1 (NRG-1)/ErbBs expression, inflammation and LV hemodynamic function.

Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction.

Tenascin C (TN-C) is considered to play a pathophysiological role in maladaptive left ventricular remodeling. Yet, the mechanism underlying TN-C-dependent cardiac dysfunction remains elusive.

Epigenetic modulation of tenascin C in the heart: implications on myocardial ischemia, hypertrophy and metabolism.

Alternative approaches for mitral valve repair are being constantly developed. Even though the safety of these devices has been extensively assessed in healthy animals before approval for first-in-man studies, often the efficacy of these new devices has been hardly challenged in vivoin the setting of MR. Therefore, reliable and reproducible preclinical animal models of MR are crucial to allow not only the safety assessment but also the efficacy evaluation of these novel approaches.

Article	Year
Argon preconditioning enhances postischaemic cardiac functional recovery following cardioplegic arrest and global cold ischaemia. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery\| PubMed ID: 29547976	2018
Mitral valve repair with adjustable ring annuloplasty. Multimedia manual of cardiothoracic surgery : MMCTS\| PubMed ID: 29750407	2018
Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse. The Journal of clinical investigation\| PubMed ID: 30422822	2019
Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction. International journal of cardiology\| PubMed ID: 30904281	2019
Epigenetic modulation of tenascin C in the heart: implications on myocardial ischemia, hypertrophy and metabolism. Journal of hypertension\| PubMed ID: 30950975	2019
Characterization of a novel percutaneous closed chest swine model of ischemic mitral regurgitation guided by contrast echocardiography. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology\| PubMed ID: 31235459	2019

Ouafa Hamza

Biography

JoVE Journal Publications

Other Publications