The authors gratefully acknowledge Marlijn Jansen, Joyce Visser, Grace Croft, Martijn van Nieuwburg, Danny Elbersen and Evelyn Velema for their excellent technical support during the animal experiments.

<ol>
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The authors have nothing to disclose.

שיפוץ הלב הוא הדבר תלוי ברובו על גודל האוטם בשריר הלב ואת איכות אוטם שריר הלב לתקן 6,26. כדי להעריך את לשעבר באופן סטנדרטי, את כתב היד הנוכחי מספק שיטה אלגנטית של עירוי in vivo של אוונס כחול בשילוב עם vivo לשעבר מכתים TTC, אשר קיבל תוקף בהרחבה בשימוש 8,16,27,28. ...

אי ספיקת לב עם מקטע פליטה מופחתת (HFrEF) מהווה כ -50% מכלל מקרי אי ספיקת לב, המשפיעים על 1 מוערך -% 2 אנשים בעולם המערבי 1. הגורם הנפוץ ביותר שלה הוא התקף לב חריף (AMI). כפי התמותה חריפה לאחר AMI ירדה באופן ניכר מחמת להגברת מודעות ואפשרויות טיפול טובות, הדגש עבר לקראת הסיבוכים הכרוניים שלה; ההוויה הבולטת HFrEF 2,3. יחד עם הגדלת הוצאות הבריאות 4, המגיפה גדל והולך של אי ספיקת לב מדגישה את הצורך דיאגנוסטיקה טיפולים חדשניים, אשר ניתן ללמוד במודל חזירי translational ביותר של שיפוץ לוואי לאחר AMI כפי שתואר לעיל 5. שניהם, הקובעים (למשל, גודל האוטם) והערכות תפקודית (למשל, אקו) של שיפוץ לוואי משמשים לעתים קרובות בדיקות יעילות של תרופה חדשה, וציין את הצורך relשיטות iable וזולות יחסית. מטרת המחקר הנוכחי היא לתת מענה לצורך זה על ידי החדרת אמצעי תוצאה חשובות ואמינים לבדיקות יעילות במודל חזיר באוטם שריר לב. אלה כוללים גודל אוטם (IS) ביחס לאזור בסיכון (AAR), אקו דרך ושט 3D (3D-TEE) ולחץ בנפח מבוסס קבלה מפורט (PV) רכישת לולאה. גודל האוטם הוא הקובע העיקרי של שיפוץ לוואי והישרדות לאחר AMI 6. למרות רה-פרפוזיה במועד של שריר הלב איסכמי עשוי להציל cardiomyocytes נפצעו הפיך ולהגביל גודל האוטם, reperfusion עצמו גורם נזק נוסף באמצעות הדור של סטרס חמצוני תגובה דלקתית מידתית (פציעה-reperfusion איסכמיה (IRI)) 7. לפיכך, IRI זוהה כמטרה טיפולית מבטיחה. היכולת של הרפוי הרומן כדי להקטין את גודל האוטם היא לכמת ידי גודל האוטם השומה ביחסלאזור בסיכון (AAR). כימות AAR היא חובה לתקן את השונות בין הפרט באנטומיה כלילית של מודלים של בעלי חיים, כמו AAR גדול מוביל בגודל האוטם מוחלט גדול יותר. מאז גודל אוטם קשור ישירות ביצועי לב ואת התכווצות שריר לב, וריאציות AAR יכולות להשפיע ללמוד מדדי תוצאה ללא קשר שיטות טיפול 8. תלת ממד אקוקרדיוגרפיה דרך הוושט (3D-TEE) הוא בטוחה, אמינה, והכי חשוב, קליני החלים שיטה זולה למדוד לב פונקציה הלא פולשני. בעוד אקוקרדיוגרפיה transthoracic (TTE) תמונות מוגבלים ארוך parasternal 2D ונוף קצר ציר בחזירים 9, 3D-TEE ניתן להשתמש כדי להשיג תמונות 3-ממדי שלם של החדר השמאלי. לכן, היא אינה דורשת קירובים מתמטיים של החדר השמאלי (LV) כרכים כגון הכלל של סימפסון שונה 10. הלה נופל קצר של קורectly הערכת כרכים LV לאחר שיפוץ LV בשל חוסר הגיאומטריה גלילי 11. יתר על כן, 3D-TEE עדיפה על אקו epicardial כפי שהוא אינו דורש התערבות כירורגית, אשר נצפו להשפעות על הלב במודל הנוכחי 12. למרות השימוש טרנדיים 2D עבור להערכת תפקוד שריר לב תואר לפני 13,14, מגבלות לגבי גיאומטריה חדרית דומות לאלו שנצפו 2D-TTE ותלוי במידה של שיפוץ LV. לפיכך, האוטם הגדול (וכך עולה הסבירות של אי ספיקת לב), מדידות 2D הסבירות יותר להיות פגומות על ידי הנחות גיאומטריות שגויות וככל צורך טכניקות 3D. עם זאת, שיטות ההדמיה ביותר מוגבלות ביכולתם להעריך תכונות פעילות פנימיות של שריר הלב. PV לולאות לספק מידע נוסף שרלוונטי כאלה רכישתם לכןתאר בפירוט בהמשך.

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			<td height="21" style="height:21px;width:397px;">3-dimensional transesophageal echocardiography</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
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			<td height="21" style="height:21px;width:397px;">iE33 ultrasound device</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">X7-2t transducer</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Aquasonic&#174; 100 ultrasound transmission gel</td>
			<td style="width:180px;">Parker Laboratories Inc.</td>
			<td style="width:108px;">01-34</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Battery handle type C (laryngoscope handle)</td>
			<td style="width:180px;">Riester</td>
			<td style="width:108px;">12303</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Ri-Standard Miller blade MIL 4 (laryngoscope blade)</td>
			<td style="width:180px;">Riester</td>
			<td style="width:108px;">12225</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Qlab 10.0 (3DQ Advanced) analysis software</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Pressure-volume loop acquisition</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Cardiac defibrillator</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">0.9% saline</td>
			<td style="width:180px;">Braun</td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">8F Percutaneous Sheath Introducer Set</td>
			<td style="width:180px;">Arrow</td>
			<td style="width:108px;">CP-08803</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">9F Radifocus&#174; Introducer II Standard Kit&#160;</td>
			<td style="width:180px;">Terumo</td>
			<td>RS*A90K10SQ</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">8F Fogarty catheter</td>
			<td style="width:180px;">Edward Life Sciences</td>
			<td>62080814F</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7F Criticath&#8482; SP5107H TD catheter (Swan-Ganz)</td>
			<td style="width:180px;">Becton Dickinson (BD)</td>
			<td>680078</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:397px;">Ultraview SL Patient Monitor and Invasive Command Module (external cardiac output device)</td>
			<td>Spacelabs Healthcare</td>
			<td>91387</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">ADVantage system&#8482;</td>
			<td>Transonic SciSense</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7F tetra-polar admittance catheter (7.0 VSL Pigtail / no lumen)</td>
			<td>Transonic SciSense</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Multi-channel acquisition system (Iworx 404)</td>
			<td>Iworx</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Labscribe V2.0 analysis software</td>
			<td style="width:180px;">Iworx</td>
			<td style="width:108px;">-</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Infarct size / area-at-risk quantification</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Diathermy</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Lebsch knife</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Hammer</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Bone marrow wax</td>
			<td style="width:180px;">Syneture</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Klinkenberg scissors</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Retractor</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Surgical scissors</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7F Percutaneous Sheath Introducer Set&#160;</td>
			<td style="width:180px;">Arrow</td>
			<td>CP-08703</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">8F Percutaneous Sheath Introducer Set&#160;</td>
			<td style="width:180px;">Arrow</td>
			<td style="width:108px;">CP-08803</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">7F JL4 guiding catheter&#160;</td>
			<td style="width:180px;">Boston Scientific</td>
			<td style="width:108px;">H749 34357-662</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">8F JL4 guiding catheter&#160;</td>
			<td style="width:180px;">Boston Scientific</td>
			<td>H749 34358-662&#160;</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">COPILOT Bleedback Control Valves&#160;</td>
			<td>Abbott Vascular</td>
			<td>1003331</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">BD Connecta&#8482;&#160;</td>
			<td style="width:180px;">Franklin Lakes</td>
			<td>394995</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Contrast agent</td>
			<td style="width:180px;">Telebrix</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:397px;">Persuader 9 Steerable Guidewire 9 (0.014&#34;, 180 cm, straight tip), hydrophilic coating</td>
			<td style="width:180px;">Medtronic Inc.</td>
			<td>9PSDR180HS</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:397px;">SAPPHIRE&#8482; Coronary Dilatation Catheter (PTCA balloon suitable for the size of the particular coronary artery (2.75 - 3.25 mm))</td>
			<td style="width:180px;">OrbusNeich</td>
			<td style="width:108px;">103-3015</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Evans Blue&#160;</td>
			<td style="width:180px;">Sigma-Aldrich</td>
			<td>E2129-100G</td>
			<td>Toxic. Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">2,3,5-triphenyl-tetrazolium chloride (TTC)</td>
			<td style="width:180px;">Sigma-Aldrich</td>
			<td>T8877-100G</td>
			<td>Irritant. Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">9V battery</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Ruler</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Photocamera</td>
			<td style="width:180px;">Sony</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:397px;">ImageJ</td>
			<td style="width:180px;">National Institutes of Health</td>
			<td style="width:108px;">-</td>
			<td>Alternative product can be used</td>
		</tr>
	</tbody>
</table>

primary outcome assessment in a pig model of acute myocardial infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

<html> 3D דרך הושט אקו 3D דרך הושט אקוקרדיוגרפיה (3D-TEE) יכול לשמש להערכת תפקוד הלב העולמית. לאחר AMI, תפקוד לב העולמי נבדל ערכי בסיס בריאים. בפרט, מקטע פליטה של ​​חדר שמאל (LVEF) יורדת מ 59 ± 4% ל -37 ± ...

Watch this Scientific Journal Video about Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction at JoVE.com

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

הערכת תוצאה אמינה ומדויקת היא המפתח לתרגום של טיפולים פרה-קליניים לתוך טיפול מרפאתי. המאמר הנוכחי מתאר כיצד להעריך שלושה פרמטרים התוצאה העיקרית רלוונטיות קלינית של ביצועי הלב ונזק במודל אוטם לבבי חריף חזיר.

הערכת התוצאה העיקרית במודל חזיר של באוטם שריר הלב

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

primary-outcome-assessment-pig-model-acute-myocardial

Research

JoVE Journal

Medicine

11.4K Views.  University Medical Center Utrecht.  הערכת תוצאה אמינה ומדויקת היא המפתח לתרגום של טיפולים פרה-קליניים לתוך טיפול מרפאתי. המאמר הנוכחי מתאר כיצד להעריך שלושה פרמטרים התוצאה העיקרית רלוונטיות קלינית של ביצועי הלב ונזק במודל אוטם לבבי חריף חזיר. 

Video: Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Acute Myocardial Infarction in Rats

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial infarction (AMI). This model is also referred to as an acute ischemic cardiomyopathy or ischemia followed by reperfusion (IR); which is induced by an acute 30-minute period of ischemia by ligation of the left anterior descending artery (LAD) followed by reperfusion of the tissue by releasing the LAD ligation (Vasilyev and McConnell). This protocol will focus on assessment of the infarct size and the area-at-risk (AAR) by Evan's blue dye and triphenyl tetrazolium chloride (TTC) following 4-hours of reperfusion; additional comments toward the evaluation of cardiac function and remodeling by modifying the duration of reperfusion, is also presented. Overall, this AMI rat animal model is useful for studying the consequence of a myocardial infarction on cardiac pathophysiological and physiological function.

The rat model of acute myocardial infarction (AMI) is useful to study the consequence of a MI on cardiac pathophysiological and physiological function.

באוטם שריר הלב אצל חולדות

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular ...

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.

We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

אוטם שריר לב והערכת תוצאה תפקודית בחזירים

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction.

This protocol describes a highly reproducible model of cardiac regeneration by surgical induction of myocardial infarction in the left ventricle of postnatal day 1 mice. The method involves induction of hypothermic anesthesia and ligation of the left anterior descending coronary artery.

אוטם שריר לב עכברים ילודים, מודל התחדשות לב

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

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.

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.

ניתוח בזמן אמת לחץ-נפח של אוטם אקוטי בעכברים

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

Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released from the cardiovascular cells into the circulation. Circulating miRNAs are highly stable and can be quantified. The quantitative expression of specific miRNAs can be linked to the pathology, and some miRNAs show high tissue and disease specificity. Finding novel biomarkers for cardiovascular diseases is of importance for medical research. Quite recently, digital polymerase chain reaction (dPCR) has been invented. dPCR, combined with fluorescent hydrolysis probes, enables specific direct absolute quantification. dPCR exhibits superior technical qualities, including a low variability, high linearity, and high sensitivity compared to the quantitative polymerase chain reaction (qPCR). Thus, dPCR is a more accurate and reproducible method for directly quantifying miRNAs, particularly for the use in large multi-center cardiovascular clinical trials. In this publication, we describe how to effectively perform digital PCR in order to assess the absolute copy number in serum samples.

Circulating microRNAs have shown promise as biomarkers for cardiovascular diseases and acute myocardial infarctions. In this study, we describe a protocol for miRNA extraction, reverse transcription, and digital PCR for the absolute quantification of miRNAs in the serum of patients with cardiovascular disease.

PCR דיגיטלי עבור לכימות מחזורי מיקרו Rna חריפה אוטם שריר הלב, מחלות לב וכלי דם

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released ...

Implantation of hiPSC-derived Cardiac-muscle Patches after Myocardial Injury in a Guinea Pig Model

Due to the limited regeneration capacity of the heart in adult mammals, myocardial infarction results in an irreversible loss of cardiomyocytes. This loss of relevant amounts of heart muscle mass can lead to the heart failure. Besides heart transplantation, there is no curative treatment option for the end-stage heart failure. In times of organ donor shortage, organ independent treatment modalities are needed. Left-ventricular assist devices are a promising therapy option, however, especially as destination therapy, limited by its side-effects like stroke, infections and bleedings. In recent years, several cardiac repair strategies including stem cell injection, cardiac progenitors or myocardial tissue engineering have been investigated. Recent improvements in cell biology allow for the differentiation of large amounts of cardiomyocytes derived from human induced pluripotent stem cells (iPSC). One of the cardiac repair strategies currently under evaluation is to transplant artificial heart tissue. Engineered heart tissue (EHT) is a three-dimensional in vitro created cardiomyocyte network, with functional properties of native heart tissue. We have created EHT-patches from hiPSC derived cardiomyocytes. Here we present a protocol for the induction of left ventricular myocardial cryoinjury in a guinea pig, followed by implantation of hiPSC derived EHT on the left ventricular wall.

Here we present a protocol for the induction of left ventricular cryoinjury followed by the implantation of a cardiac muscle patch, derived from human iPS-cell cardiomyocytes in a guinea pig model.

השרשת נגזר hiPSC תיקונים שריר הלב לאחר פציעה שריר הלב במודל שפן

Due to the limited regeneration capacity of the heart in adult mammals, myocardial infarction results in an irreversible loss of cardiomyocytes. This loss ...

A Cryoinjury Model to Study Myocardial Infarction in the Mouse

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we demonstrate a murine cryoinjury infarct model that generates precise infarct sizes with high reproducibility and replicability. In brief, after intubation and sternotomy of the animal, the heart is lifted from the thorax. The probe of a handheld liquid nitrogen delivery system is applied onto the myocardial wall to induce cryoinjury. Impaired ventricular function and electrical conduction can be monitored with echocardiography or optical mapping. Transmural myocardial remodeling of the infarcted area is characterized by collagen deposition and loss of cardiomyocytes. Compared to other models (e.g., LAD-ligation), this model utilizes a handheld liquid nitrogen delivery system to generate more uniform infarct sizes.

This article demonstrates a model to study cardiac remodeling after myocardial cryoinjury in mice.

מודל לפציעה בהקפאה לחקור אוטם שריר הלב בעכבר

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we ...

Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.

Stem cell-based therapy has emerged as an efficient strategy to repair injured cardiac tissues after myocardial infarction. We provide an optimal in vivo application for stem cell transplantation using gelatin hydrogels that are able to be enzymatically cross-linked.

השתלה תוך-שרירית של הידרוג'ל להזרקה בטעינת MSC לאחר אוטם שריר הלב במודל מורין

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of ...

Utilizing Percutaneous Ventricular Assist Devices in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Cardiogenic shock is defined as persistent hypotension, accompanied by evidence of end organ hypo-perfusion. Percutaneous ventricular assist devices (PVADs) are used for the treatment of cardiogenic shock in an effort to improve hemodynamics. Impella is currently the most common PVAD and actively pumps blood from the left ventricle into the aorta. PVADs unload the left ventricle, increase cardiac output and improve coronary perfusion. PVADs are typically placed in the cardiac catheterization laboratory under fluoroscopic guidance via the femoral artery when feasible. In cases of severe peripheral arterial disease, PVADs can be implanted through an alternative access. In this article, we summarize the mechanism of action of PVAD and the data supporting their use in the treatment of cardiogenic shock.

Percutaneous ventricular assist devices are increasingly being utilized in patients with acute myocardial infarction and cardiogenic shock. Herein, we discuss the mechanism of action and hemodynamic effects of such devices. We also review algorithms and best practices for the implantation, management and weaning of these complex devices.

שימוש במכשירי סיוע חדרית עורית באוטם שריר הלב חריף מסובך על ידי הלם קרדיוגני

Cardiogenic shock is defined as persistent hypotension, accompanied by evidence of end organ hypo-perfusion. Percutaneous ventricular assist devices ...