Name: real-time pressure-volume analysis of acute myocardial infarction in mice
Uploaded: 2018-07-02T13:30:00
Description: Watch this Scientific Journal Video about Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice at JoVE.com

The authors acknowledge the following funding sources: Else Kr&#246;ner-Fresenius-Stiftung (Tienush Rassaf); Hans und Gertie Fischer Stiftung (Tienush Rassaf), grant from the medical faculty, University Duisburg-Essen, Germany (Tienush Rassaf, Lars Michel); Ernst- und Berta Grimmke-Stiftung (Christos Rammos).

All experiments were completed in accordance and compliance with all relevant regulations&#160;(&#8216;European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes&#8217; (Directive 2010/63/EU) and animal care was in accordance with institutional guidelines. All experiments have been performed with male C57BL/6JRj mice at the age of 6 months.
1. Preparation
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	<li>Prepare a surgical microscope and a heating pad as well as a rectal probe ...

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PV monitoring of LV hemodynamics in acute myocardial infarction serves as a novel method for real-time in vivo assessment of cardiogenic shock and impaired LV function in I/R injury. PV catheterization can provide a broad spectrum of parameters with regard to LV systolic and diastolic function. In addition to the LV volumetric parameters typically obtained by echocardiography or MRI (chamber volumes, EF, stroke volume, and cardiac output), PV analysis yields a more complete profile of LV function by simultaneous...

Cardiovascular disease is the most common cause of death in western civilization1. Acute myocardial infarction is a critical event, which is associated with high acute and chronic mortality2. Even if revascularization is achieved via emergency percutaneous coronary intervention (PCI), mortality remains high, particularly within the first 48 h after onset of symptoms in patients with acute myocardial infarction3. Cardiogenic shock caused by acute reduction in left ventricular (LV) function is a major cause for in-hospital mortality in these patients3. This early reduction in LV function is caused by myocardial damage following ischemia and reperfusion. This so-called ischemia/reperfusion (I/R) injury is mediated by changes in cellular metabolome such as exaggerated generation of reactive oxygen species4,5.
To explore possible protective mechanisms leading to a decrease in myocardial damage in a preclinical setting, reliable mouse models are essential including methods for evaluation of post-I/R LV function6. In this setting, transthoracic echocardiography7 and magnetic resonance imaging (MRI)6 are widely used for functional phenotyping8,9. However, these methods are not suitable for the assessment of severe LV dysfunction and cardiogenic shock in an ongoing acute myocardial infarction and cannot directly show data on LV pressure. The Langendorff apparatus using isolated heart in an ex vivo assay provides information about the underlying pathomechanisms of early-phase I/R injury10. This method is limited due to its inability to reproduce in vivo adaptive mechanisms such as regulation of the autonomous nervous system or hormonal regulation and acid-base homeostasis. There is currently no method available for a complete functional phenotyping of cardiogenic shock and left ventricular dysfunction during an ongoing myocardial I/R injury.
A synchronized approach with combination of pressure-volume (PV) catheterization and transient surgical left main coronary artery (LCA) occlusion could be beneficial but technically challenging. Stable extracardiac hemodynamics during I/R injury are essential for valid results since unstable anesthesia or blood loss could heavily influence the results. A novel approach for hemodynamic phenotyping of I/R injury via LV PV catheterization and transient LCA occlusion could bring new insights on cardiogenic shock and LV dysfunction in acute myocardial infarction and serve as a method for future analysis on cardioprotection.

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real-time pressure-volume analysis of acute myocardial infarction in mice

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any potential therapeutic approach directed against acute left ventricular (LV) dysfunction. Current imaging modalities (e.g., echocardiography and magnetic resonance imaging) have several limitations since data on LV pressure cannot directly be measured. LV catheterization in mice undergoing coronary artery occlusion could serve as a novel method for a real-time evaluation of LV function.
At the beginning of the procedure, mice were anesthetized followed by endotracheal intubation. For LV catheterization, the right carotid artery was exposed via middle-neck incision. The catheter was introduced and placed into the LV cavity. Left thoracotomy was conducted and the left main coronary artery (LCA) was ligated. To induce reperfusion, the suture was released after 45 min. Pressure-volume data was recorded at all times.
Ligation of the LCA caused a decrease in LV systolic function as evidenced by a 30% reduction in stroke volume, LV ejection fraction (EF), and cardiac output. Maximum dP/dt as a parameter for LV contractility was also significantly reduced and diastolic function was severely impaired (minimum dP/dt -40%). Reperfusion over a period of 20 min did not lead to a complete recovery of LV function.
Real-time pressure-volume analysis served as a valid procedure for monitoring cardiac function during acute myocardial infarction in mice. Maintaining stable anesthesia and a standardized surgical approach was crucial to ensure valid results. As the early phase of acute myocardial infarction is critical for morbidity and mortality, the delineated method could be beneficial for preclinical evaluation of new strategies for cardioprotection.

After LV catheterization, reversible LCA ligation was performed for 45 min followed by 10 min of reperfusion. PV data was recorded at all times (Figure 1).
Correct placement of the PV catheter was confirmed by obtaining the characteristic LV PV graph (Figure 2A). LV catheter placement showed the typical ventricular pressure range with a minimum of 0 - 20 mmHg whereas fa...

Watch this Scientific Journal Video about Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice at JoVE.com

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Acute myocardial infarction in mice induces acute but incompletely characterized changes in left ventricular (LV) function. LV catheterization in mice undergoing coronary artery occlusion serves as a novel method for a real-time evaluation of LV function.

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...

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