Name: cell-based therapy for heart failure in rat: double thoracotomy for myocardial infarction and epicardial implantation of cells and biomatrix
Uploaded: 2014-09-22T13:00:00
Description: Watch this Scientific Journal Video about Cell-based Therapy for Heart Failure in Rat: Double Thoracotomy for Myocardial Infarction and Epicardial Implantation of Cells and Biomatrix at JoVE.com

The authors thank Prof Hendrik Tevaearai and the Department of Cardiovascular Surgery for financial support for the initial part of the study.

NOTE: Lewis Male and Female rats, 200-220 g were housed under standard laboratory conditions (12 hr light and dark cycle, ad libitum water and food, IVC cage). All animals were treated in compliance with the recommendations of the FELASA and the Swiss Law on animal protection.
1. Cell Preparation: Mesenchymal Stem Cell Isolation from Bone Marrow
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	<li>Anesthetize the rats with isoflurane 5% and O2 5 L/min in an induction chamber for 5 min. Place the animal&#8217;s sno...

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The permanent ligation of LAD causes irreversible myocardial injury. The first animal model was described in 19604. Since then, it has been considered as a standard and suitable model for chronic MI. Its stability and reproducibility allowed experimental evaluation of therapies for MI5. Improved procedures following the initial description reported an operative mortality rate of 35-13%6.
As expected, LAD ligation induced impaired heart function observed within ...

Since the end of the 19th century, cardiovascular disease has remained the number one serial killer in industrialized countries. Among them, coronary artery disease represents the main etiology. The acute phase results in myocardial infarction (MI) and is followed by maladaptive remodeling that progressively develops toward a chronic phase and severe heart failure. Despite recent significant technological and therapeutic advances, the morbidity and mortality due to the progression of heart failure is still growing1. In this context, cell therapy has gained increasing interest as a new therapeutic option to stop the progression of the disease toward heart failure and to stimulate the recently identified regenerative capacity of the myocardium. Experimental and clinical investigations have provided compelling evidence of the beneficial effects obtained after cardiac transplantation of various cell types. Major outcomes included improved cardiac contractile function, decreased left ventricular remodeling, reduced infarct size, and increased vascular density in the infarcted area. However, the low cell number retention after cell injection remained an important drawback. Association of cells with a biomatrix to improve of cell delivery2 have recently fostered researcher and clinical interests.
Ligation of the left anterior descending coronary artery (LAD) is a reference method for MI in small animal model that results in transmural infarction and a mature scar. Cell therapy applied in the chronic phase of MI requires a second surgical intervention. A median sternotomy is usually performed to allow intramyocardial injection of the cells or epicardial implantation of biografts. Such invasive surgical procedures increase the mortality rate, post-surgery recovery time, pain, and risk of infection. The minimally invasive approach presented here not only prevents such bias but also provides optimal accessibility of the heart for treatment application. MI and epicardial implantation of cells associated with a gel type biomatrix are performed on a beating heart via left intercostal thoracotomies.

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			<td height="42" style="height:42px;width:216px;">INSPIRA ADVANCED VOLUME CONTROLLED VENTILATOR</td>
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			<td style="width:119px;">557058</td>
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			<td height="21" style="height:21px;width:216px;">DUMONT #7 Forceps</td>
			<td style="width:104px;">FST Germany</td>
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			<td height="21" style="height:21px;width:216px;">Fibrin sealant</td>
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			<td>use as retractor for the ribs</td>
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			<td>Gibco</td>
			<td>15140</td>
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			<td height="21" style="height:21px;">FBS</td>
			<td>PAA Clone</td>
			<td>&#160;&#160;&#160;&#160;&#160; A15-101</td>
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			<td height="42" style="height:42px;">bone scissors</td>
			<td style="width:104px;">Fine Science Tols</td>
			<td style="width:119px;">16044-10</td>
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			<td height="21" style="height:21px;">Red Blood Cell Lysis Solution</td>
			<td>Gentra Systems</td>
			<td>D-50k1</td>
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			<td height="42" style="height:42px;width:216px;">Accutase cell detachment solution</td>
			<td style="width:104px;">Stem cell technology</td>
			<td style="width:119px;">7920</td>
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cell-based therapy for heart failure in rat: double thoracotomy for myocardial infarction and epicardial implantation of cells and biomatrix

Cardiac cell therapy has gained increasing interest and implantation of biomaterials associated with cells has become a major issue to optimize myocardial cell delivery. Rodent model of myocardial infarction (MI) consisting of Left Anterior Descending Artery (LAD) ligation has commonly been performed via a thoracotomy; a second open-heart surgery via a sternotomy has traditionally been performed for epicardial application of the treatment. Since the description of LAD ligation model, post-surgery mortality rate has dropped from 35-13%, however the second surgery has remained critical. In order to improve post-surgery recovery and reduce pain and infection, minimally invasive surgical procedures are presented.&#160;Two thoracotomies were performed, the initial one for LAD ligation and the second one for treatment epicardial administration. Biografts consisting of cells associated with solid or gel type matrices were applied onto the infarcted area.&#160;LAD ligation resulted in loss of heart function as confirmed by echocardiography performed after 2 and 6 weeks. Goldner trichrome staining performed on heart sections confirmed transmural scar formation. First and second surgeries resulted in less that 10%&#160;post-operative mortality.&#160;

All animals recovered within 1 hr&#160;after thoracotomies. The wound healing was rapid. No infection or edema was observed.
The double left thoracotomy allowed optimal access to the heart (Figure 1). Pain and post-surgery mortality were low. The animal recovered quickly from the surgery and gained weight (Figure 2). Kaplan Meir survival percent was 96% for the first thoracotomy. Four rats over 104 died within the 24 hr following treatment application via<...

Watch this Scientific Journal Video about Cell-based Therapy for Heart Failure in Rat: Double Thoracotomy for Myocardial Infarction and Epicardial Implantation of Cells and Biomatrix at JoVE.com

Cell-based Therapy for Heart Failure in Rat: Double Thoracotomy for Myocardial Infarction and Epicardial Implantation of Cells and Biomatrix

Implantation of a biograft to treat myocardial infarction induced by LAD ligation in a rodent model has conventionally required two open-heart surgeries. In order to reduce mortality and provide optimal conditions for fixation of solid and gelatinous biomatrices associated with cells, minimally invasive procedures have been developed.

Cardiac cell therapy has gained increasing interest and implantation of biomaterials associated with cells has become a major issue to optimize myocardial ...

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