Name: primary outcome assessment in a pig model of acute myocardial infarction
Uploaded: 2016-10-14T15:00:00
Description: Watch this Scientific Journal Video about Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction at JoVE.com

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.

Alla djurförsök har godkänts av den etiska kommittén djurförsöks av University Medical Center Utrecht (Utrecht, Nederländerna) och överensstämmer med den &quot;Guide för skötsel och användning av försöksdjur&quot;. OBS: Protokollet för att utföra en sluten kista ballong ocklusion är inte en del av den aktuella manuskriptet och beskrivs i detalj på annat håll 5. Kort sagt, svin - är (60 70 kg) utsattes för 75 min transluminal ballong tilltäppning av mittdelen ...

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Hjärt ombyggnad är till stor del beroende på hjärtinfarkt storlek och kvaliteten på hjärtinfarkt reparera 6,26. För att bedöma den förra på ett standardiserat sätt, tillhandahåller föreliggande manuskript en elegant metod för in vivo infusion av Evans blå i kombination med ex vivo TTC färgning, som har validerats och används flitigt 8,16,27,28. Denna metod gör det möjligt för kvantifiering av riskområdet (AAR) och infarktstorleken i förhållande till AAR <sup...

Hjärtsvikt med reducerad ejektionsfraktion (HFrEF) svarar för omkring 50% av alla hjärtsvikt fall drabbar uppskattningsvis 1-2% av befolkningen i västvärlden en. Dess vanligaste orsaken är akut hjärtinfarkt (AMI). Som akut dödlighet efter AMI har minskat kraftigt på grund av ökad medvetenhet och förbättrade behandlingsalternativ, har tyngdpunkten förskjutits mot sin kroniska följdsjukdomar; den mest framträdande är HFrEF 2,3. Tillsammans med ökande vårdkostnader 4, den växande epidemi av hjärtsvikt betonar behovet av nya diagnoser och behandlingar, som kan studeras i en mycket translationella grismodell av negativ ombyggnad efter AMI som tidigare beskrivits 5. Både bestämningsfaktorer (t.ex. infarktstorlek) och funktionella bedömningar (t.ex. ekokardiografi) av negativ ombyggnad används ofta för undersökning av effekten av nya läkemedel, vilket indikerar behovet av reliable och relativt billiga metoder. Syftet med det nuvarande pappers är att tillgodose det behovet genom att införa viktiga och tillförlitliga utfallsmått vid undersökning av effekten i en grismodell av akut hjärtinfarkt. Dessa inkluderar infarktstorleken (IS) i förhållande till riskområdet (AAR), 3D-transesofageal ekokardiografi (3D-TEE) och detaljerad tillträde baserade tryck volym (PV) loop förvärv. Infarktstorlek är den viktigaste faktorn för negativa ombyggnad och överlevnad efter AMI 6. Även tid reperfusion av ischemisk myokardium kan rädda reversibelt skadade hjärtmuskelceller och begränsa infarktstorleken, reperfusion själv orsakar ytterligare skada genom generering av oxidativ stress och en oproportionerligt inflammatoriskt svar (ischemi-reperfusionsskada (IRI)) 7. Därför har IRI identifierats som en lovande terapeutiskt mål. Förmågan hos nya behandlingar för att minska infarktstorleken kvantifieras genom att bedöma infarktstorlek i förhållandetill området som löper risk (AAR). AAR kvantifiering är obligatoriskt att korrigera för interindividuell variabilitet i koronaranatomin djurmodeller, som en större AAR leder till en större absolut infarktstorleken. Eftersom infarktstorlek är direkt relaterad till hjärtprestanda och hjärtkontraktilitet, kan variationer i AAR påverka studera effektmått oberoende av behandlingsmetoder 8. Tredimensionell transesofageal ekokardiografi (3D-TEE) är en säker, pålitlig och, viktigast av allt, kliniskt tillämplig billig metod för att mäta hjärtfunktionen icke-invasivt. Medan transtorakal ekokardiografi (TTE) bilder är begränsade till 2D parasternal lång- och kortaxel vyer hos svin 9, kan 3D-TEE användas för att få hela tre-dimensionella bilder av vänster kammare. Därför kräver inte det matematiska approximationer av vänster kammare (LV) volymer som den modifierade Simpsons regel 10. Den senare understiger korrrekt uppskatta LV volymer efter LV ombyggnad på grund av bristande cylindriska geometri 11. Dessutom är 3D-TEE föredra framför epikardiella ekokardiografi eftersom det inte kräver kirurgiska ingrepp, som har observerats att utöva hjärtskyddande effekter i den nuvarande modellen 12. Även om användningen av 2D-TEE för bedömning av hjärtmuskelfunktion har beskrivits tidigare 13,14, begränsningar i kammargeometrin liknar de som observerats i 2D-TTE och beror på omfattningen av LV ombyggnad. Därför desto större infarkt (och därmed högre sannolikheten för hjärtsvikt), desto mer sannolikt mätningar 2D blir bristfällig av felaktiga geometriska antaganden och högre behovet av 3D-tekniker. Icke desto mindre är de flesta avbildningsmetoder begränsas i sin förmåga att bedöma inneboende funktionella egenskaperna hos myokardiet. PV loopar tillhandahålla sådan relevant ytterligare information och förvärvet är därförbeskrivs i detalj nedan.

<table border="0" cellpadding="0" cellspacing="0" width="875">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">3-dimensional transesophageal echocardiography</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
			<td style="width:191px;"></td>
		</tr>
		<tr height="21">
			<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 transesofageal ekokardiografi 3D transesofageal ekokardiografi (3D-TEE) kan användas för bedömning av global hjärtfunktion. Efter AMI skiljer global hjärtfunktion från friska utgångsvärden. Framför allt lämnade ejektionsfraktion (LVEF) minskar från 59 ± 4% till 37 ± 6% efter en vecka av reperfusion (n = 10) (GPJ van Hout, 2015). En ökning av slutsystoliska volymen (51 ± 7 till 82 ± 13 ...

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

Tillförlitlig och noggrann effektvariabeln är nyckeln för översättning av prekliniska terapier i klinisk behandling. Den nuvarande papper beskriver hur man bedömer tre kliniskt relevanta primära utfalls parametrar för hjärtprestanda och skador i en gris akut hjärtinfarkt modell.

Primära effektvariabeln i en grismodell av akut hjärtinfarkt

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

Research

JoVE Journal

Medicine

Acute Myocardial Infarction in Rats

Akut hjärtinfarkt hos råttor

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 ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Hjärtinfarkt och bedömning Funktionell Utfall i Grisar

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

Hjärtinfarkt i neonatala möss, en modell av 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 ...

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

Realtid tryck-volym analys av akut hjärtinfarkt hos möss

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

Digital PCR för kvantifiering av cirkulerande mikroRNA i akut hjärtinfarkt och hjärt-kärlsjukdom

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

Implantation av hiPSC-derived hjärtmuskulatur fläckar efter Myokardskada i marsvin modell

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

En Kryoskademodell för att studera hjärtinfarkt i mus

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

Intramyocardial Transplantation av MSC-loading injicerbara hydrogeler efter hjärtinfarkt i en Murine Modell

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

Använda perkutan ventrikulära hjälpanordningar vid akut hjärtinfarkt som kompliceras av kardiogen chock

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