This work was supported by the Laerdal Foundation for Acute Medicine (3374), Holger and Ruth Hesse&#39;s Memorial Foundation, S&#248;ster and Verner Lippert&#39;s Foundation, Novo Nordisk Foundation (NNF16OC0023244, NFF17CO0024868), and Alfred Benzon&#39;s Foundation.

<ol>
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G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ventriculo-arterial+coupling+detects+occult+RV+dysfunction+in+chronic+thromboembolic+pulmonary+vascular+disease.">Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.</a> Physiological Reports. 5 (7), 13227 (2017).</li><li>Houser, S. 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An official american thoracic society research statement.</a> American Journal of Respiratory and Critical Care Medicine. 198 (4), e15-e43 (2018).</li><li>Morimont, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effective+arterial+elastance+as+an+index+of+pulmonary+vascular+load.">Effective arterial elastance as an index of pulmonary vascular load.</a> American Journal of Physiology - Heart and Circulatory Physiology. 294 (6), 2736-2742 (2008).</li><li>Kutty, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validation+of+admittance+computed+left+ventricular+volumes+against+real-time+three-dimensional+echocardiography+in+the+porcine+heart.">Validation of admittance computed left ventricular volumes against real-time three-dimensional echocardiography in the porcine heart.</a> Experimental Physiology. 98 (6), 1092-1101 (2013).</li><li>Bove, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+and+chronic+effects+of+dysfunction+of+right+ventricular+outflow+tract+components+on+right+ventricular+performance+in+a+porcine+model:+Implications+for+primary+repair+of+tetralogy+of+fallot.">Acute and chronic effects of dysfunction of right ventricular outflow tract components on right ventricular performance in a porcine model: Implications for primary repair of tetralogy of fallot.</a> Journal of the American College of Cardiology. 60 (1), 64-71 (2012).</li><li>Townsend, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measuring+pressure+volume+loops+in+the+mouse.">Measuring pressure volume loops in the mouse.</a> Journal of Visualized Experiments. 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None of the authors has any conflicts of interest to declare.

This paper describes a reproducible minimally invasive closed chest approach for bi-ventricular pressure-volume loop recordings.
Advancement of the PV catheter from the RA into the RV is the most critical step in this protocol. The complex composition of the RV and the stiffness of the catheter complicate insertion into the easily distended and geometrically challenging RV. This difficulty may explain why open chest instrumentation is often preferred. During pilot studies, numerous accesses an...

Pressure-volume (PV) loops contain a large number of hemodynamic information, including end-systolic and end-diastolic pressures and volumes, ejection fraction, stroke volume, and stroke work1. Furthermore, transient preload reduction creates a family of loops from which load-independent variables can be derived2,3. This load-independent evaluation of ventricular function makes PV loop recordings state-of-the-art in hemodynamic evaluation. PV loop recording can be performed in humans but is primarily used and recommended in preclinical research4,5,6.
Pressure-volume loops can be obtained from both the right ventricle (RV) and the left ventricle (LV). Most research hypotheses are focused on a single ventricle, resulting in only univentricular PV loops being recorded7,8,9,10. However, the right and left ventricles exert systolic and diastolic interdependence due to their serial and parallel connections within the tight pericardium11. Changes in the output or the size of one ventricle will affect the size, loading conditions, or perfusion of the other ventricle. Thus, bi-ventricular PV loop recordings provide a more comprehensive evaluation of the total cardiac performance. Pharmacological interventions may also affect the two ventricles and their loading conditions differently, further emphasizing the importance of bi-ventricular evaluation.
PV catheters can be advanced into either ventricle by several approaches, including open chest approach with access from the apex of the heart or through the RV outflow tract7,10,12,13,14. However, the opening of the thorax will affect the physiological conditions and may introduce bias.
Based on our experience from previous studies15,16,17,18, we aim to present our closed chest approach to bi-ventricular PV loop recordings in a large animal model of acute RV failure having minimal influence on cardiopulmonary physiology (Figure 1).

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>12L-RS</td>
			<td>GE Healthcare Japan</td>
			<td>5141337</td>
			<td>Ultrasound probe</td>
		</tr>
		<tr>
			<td>Adhesive Aperature Drape (OneMed)</td>
			<td>evercare</td>
			<td>1515-01</td>
			<td>75 x 90 cm (hole: 6 x 8 cm)</td>
		</tr>
		<tr>
			<td>Alaris GP Guardrails plus</td>
			<td>CareFusion</td>
			<td>9002TIG01-G</td>
			<td>Infusion pump</td>
		</tr>
		<tr>
			<td>Alaris Infusion set</td>
			<td>BD Plastipak</td>
			<td>60593</td>
			<td></td>
		</tr>
		<tr>
			<td>Alkoholswap</td>
			<td>MEDIQ Danmark</td>
			<td>3340012</td>
			<td>82% ethanol, 0,5% chlorhexidin, skin disinfection</td>
		</tr>
		<tr>
			<td>Amplatz Support Wire Guide Extra-Stiff</td>
			<td>Cook Medical</td>
			<td>THSF-25-260-AES</td>
			<td>diameter: 0.025 inches, length: 260 cm</td>
		</tr>
		<tr>
			<td>BD Connecta</td>
			<td>BD</td>
			<td>394601</td>
			<td>Luer-Lock</td>
		</tr>
		<tr>
			<td>BD Emerald</td>
			<td>BD</td>
			<td>307736</td>
			<td>10 mL syringe</td>
		</tr>
		<tr>
			<td>BD Luer-Lock</td>
			<td>BD Plastipak</td>
			<td>300865</td>
			<td>BD = Becton Dickinson, 50 mL syringe</td>
		</tr>
		<tr>
			<td>BD Platipak</td>
			<td>BD</td>
			<td>300613</td>
			<td>20 mL syringe</td>
		</tr>
		<tr>
			<td>BD Venflon Pro</td>
			<td>Becton Dickinson Infusion Therapy</td>
			<td>393204</td>
			<td>20G</td>
		</tr>
		<tr>
			<td>BD Venflon Pro</td>
			<td>Becton Dickinson Infusion Therapy</td>
			<td>393208</td>
			<td>17G</td>
		</tr>
		<tr>
			<td>Butomidor Vet</td>
			<td>Richter Pharma AG</td>
			<td>531943</td>
			<td>10 mg/mL</td>
		</tr>
		<tr>
			<td>Check-Flo Performer Introducer</td>
			<td>Cook Medical</td>
			<td>RCFW-16.0P-38-30-RB</td>
			<td>16 F sheath, 30 cm long</td>
		</tr>
		<tr>
			<td>Cios Connect S/N 20015</td>
			<td>Siemens Healthineers</td>
			<td></td>
			<td>C-arm</td>
		</tr>
		<tr>
			<td>D-LCC12A-01</td>
			<td>GE Healthcare Finland</td>
			<td></td>
			<td>Pressure measurement monitor</td>
		</tr>
		<tr>
			<td>Durapore</td>
			<td>3M</td>
			<td>-</td>
			<td>Adhesive tape</td>
		</tr>
		<tr>
			<td>E-PRESTIN-00</td>
			<td>GE Healthcare Finland</td>
			<td>6152932</td>
			<td>Respirator tubes</td>
		</tr>
		<tr>
			<td>Exagon vet</td>
			<td>Richter Pharma AG</td>
			<td>427931</td>
			<td>400 mg/mL</td>
		</tr>
		<tr>
			<td>Fast-Cath Hemostasis Introducer 12F</td>
			<td>St. Jude Medical</td>
			<td>406128</td>
			<td>L: 12 cm</td>
		</tr>
		<tr>
			<td>Favorita II</td>
			<td>Aesculap</td>
			<td></td>
			<td>Type: GT104</td>
		</tr>
		<tr>
			<td>Fentanyl</td>
			<td>B. Braun</td>
			<td>71036</td>
			<td>50 mikrogram/mL</td>
		</tr>
		<tr>
			<td>Ketaminol Vet</td>
			<td>MSD/Intervet International B.V.</td>
			<td>511519</td>
			<td>100 mg/mL</td>
		</tr>
		<tr>
			<td>LabChart</td>
			<td>ADInstruments</td>
			<td></td>
			<td>Data aquisition software</td>
		</tr>
		<tr>
			<td>Lawton 85-0010 ZK1</td>
			<td>Lawton</td>
			<td></td>
			<td>Laryngoscope</td>
		</tr>
		<tr>
			<td>Lectospiral</td>
			<td>VYGON</td>
			<td>1159.90</td>
			<td>400 cm (Luer-LOCK)</td>
		</tr>
		<tr>
			<td>Lubrithal eye gel</td>
			<td>Dechra, Great Britain</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>MBH qufora</td>
			<td>MBH-International A/S</td>
			<td>13853401</td>
			<td>Urine bag</td>
		</tr>
		<tr>
			<td>Natriumklorid</td>
			<td>Fresenius Kabi</td>
			<td>7340022100528</td>
			<td>9 mg/ml Isotonic saline</td>
		</tr>
		<tr>
			<td>PICO50 Aterial Blood Sampler</td>
			<td>Radiometer</td>
			<td>956-552</td>
			<td>2 mL</td>
		</tr>
		<tr>
			<td>Portex Tracheal Tube</td>
			<td>Smiths Medical</td>
			<td>100/150/075</td>
			<td>&#34;Cuffed Clear Oral/Nasal Murphy Eye&#34;</td>
		</tr>
		<tr>
			<td>PowerLab 16/35</td>
			<td>ADInstruments</td>
			<td>PL3516</td>
			<td>Serial number: 3516-1841</td>
		</tr>
		<tr>
			<td>Pressure Extension set</td>
			<td>CODAN</td>
			<td>7,14,020</td>
			<td>Tube for anesthetics, 150 cm long, inner diameter 0.9 mm</td>
		</tr>
		<tr>
			<td>Propolipid</td>
			<td>Fresenius Kabi</td>
			<td>21636</td>
			<td>Propofol, 10 mg/mL</td>
		</tr>
		<tr>
			<td>PTS-X</td>
			<td>NuMED Canada Inc.</td>
			<td>PTSX253</td>
			<td>Inferior vena cava balloon</td>
		</tr>
		<tr>
			<td>Radiofocus Introducer II</td>
			<td>Radiofocus/Terumo</td>
			<td>RS+B80N10MQ</td>
			<td>6+7+8F sheaths</td>
		</tr>
		<tr>
			<td>Rompun Vet</td>
			<td>Beyer</td>
			<td>86450917</td>
			<td>Xylazin, 20 mg/mL</td>
		</tr>
		<tr>
			<td>R&#252;sch Brilliant AquaFlate Glycerine</td>
			<td>Teleflex</td>
			<td>178000</td>
			<td>Bladder catheter, size 14</td>
		</tr>
		<tr>
			<td>S/5 Avance</td>
			<td>Datex-Ohmeda</td>
			<td>-</td>
			<td>Mechanical ventilator</td>
		</tr>
		<tr>
			<td>Safersonic Conti Plus &#38; Safergel</td>
			<td>SECMA medical innovation</td>
			<td>SAF.612.18120.WG.SEC</td>
			<td>18 x 120 cm (Safersonic Sterile Transducer Cover with Adhesive Area and Safergel)</td>
		</tr>
		<tr>
			<td>Scisense Catheter</td>
			<td>Transonic Scisense</td>
			<td>FDH-5018B-E245B</td>
			<td>Serial number: 50-533. Pressure-volume catheter</td>
		</tr>
		<tr>
			<td>Scisense Pressure-Volume Measurement System</td>
			<td>Transonic Scisense</td>
			<td>ADV500</td>
			<td>Model: FY097B. Pressure-volume box</td>
		</tr>
		<tr>
			<td>Swan-Ganz CCOmbo</td>
			<td>Edwards Lifesciences</td>
			<td>744F75</td>
			<td>110 cm</td>
		</tr>
		<tr>
			<td>TruWave Pressure Monitoring Set</td>
			<td>Edwards Lifesciences</td>
			<td>T434303A</td>
			<td>210 cm</td>
		</tr>
		<tr>
			<td>Vivid iq</td>
			<td>GE Medical Systems China</td>
			<td>Vivid iq</td>
			<td></td>
		</tr>
		<tr>
			<td>Zoletil 50 Vet (tiletamin 125 mg and zolazepam 125 mg)</td>
			<td>Virbac</td>
			<td>83046805</td>
			<td>Zoletil Mix for pigs: 1 vial of Zoletil 50 Vet (dry matter); add 6.25 mL Xylozin (20 mg/mL), 1.25 mL ketamin (100 mg/mL) and 2.5 mL Butorphanol (10 mg/mL). Dose for pre-anesthesia: 10 mL/10 kg as intramuscular injection</td>
		</tr>
	</tbody>
</table>

closed chest biventricular pressure-volume loop recordings with admittance catheters in a porcine model

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. 
We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. 
The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

The present instructions describe an approach to achieve admittance-based PV recordings from both the RV and the LV in a large animal.
To compare our simultaneous PV recordings in the RV and LV, we performed a linear regression of the bi-ventricular CO measurements from our largest study18 with the highest number of simultaneous RV CO and LV CO measurements (n=379 recordings from 12 animals). We found that the slope was 1.03 (95%CI 0.90-1.15) with a Y-intercept of 695 (...

Watch this Scientific Journal Video about Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model at JoVE.com

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular ...

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3.5K Views.  Aarhus University Hospital. Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

Video: Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ischemia and reperfusion. Immune response includes cytokine expression and release or secretion of endogenous ligands of innate immune receptors. Activation of innate immunity can potentially modulate infarct size. We have modified an existing murine closed-chest model using hanging weights which could be useful for studying myocardial pre- and postconditioning and the role of innate immunity in myocardial ischemia and reperfusion. This model allows animals to recover from surgical trauma before onset of myocardial ischemia.
Volatile anesthetics have been intensely studied and their preconditioning effect for the ischemic heart is well known. However, this protective effect precludes its use in open chest models of coronary artery ligation. Thus, another advantage could be the use of the well controllable volatile anesthetics for instrumentation in a chronic closed-chest model, since their preconditioning effect lasts up to 72 hours. Chronic heart diseases with intermittent ischemia and multiple hit models are other possible applications of this model.
For the chronic closed-chest model, intubated and ventilated mice undergo a lateral blunt thoracotomy via the 4th intercostal space. Following identification of the left anterior descending a ligature is passed underneath the vessel and both suture ends are threaded through an occluder. Then, both suture ends are passed through the chest wall, knotted to form a loop and left in the subcutaneous tissue. After chest closure and recovery for 5 days, mice are anesthetized again, chest skin is reopened and hanging weights are hooked up to the loop under ECG control.
At the end of the ischemia/reperfusion protocol, hearts can be stained with TTC for infarct size assessment or undergo perfusion fixation to allow morphometric studies in addition to histology and immunohistochemistry.

Surgical trauma induces an inflammatory response. Cytokines and endogenous ligands are known to modulate myocardial infarct size following ischemia and reperfusion. We present a modified closed-chest model of murine ischemia and reperfusion using hanging weights to minimize effects of thoracotomy.

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ...

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential phenotypic changes are best assessed by measurement of the changes in lung elasticity. To best understand specific mechanisms underlying such pathologies in mice, it is essential to make functional measurements that can reflect the developing pathology. Although there are many ways to measure elasticity, the classical method is that of the total lung pressure-volume (PV) curve done over the whole range of lung volumes. This measurement has been made on adult lungs from nearly all mammalian species dating back almost 100 years, and such PV curves also played a major role in the discovery and understanding of the function of pulmonary surfactant in fetal lung development. Unfortunately, such total PV curves have not been widely reported in the mouse, despite the fact that they can provide useful information on the macroscopic effects of structural changes in the lung. Although partial PV curves measuring just the changes in lung volume are sometimes reported, without a measure of absolute volume, the nonlinear nature of the total PV curve makes these partial ones very difficult to interpret. In the present study, we describe a standardized way to measure the total PV curve. We have then tested the ability of these curves to detect changes in mouse lung structure in two common lung pathologies, emphysema and fibrosis. Results showed significant changes in several variables consistent with expected structural changes with these pathologies. This measurement of the lung PV curve in mice thus provides a straightforward means to monitor the progression of the pathophysiologic changes over time and the potential effect of therapeutic procedures.

Here we present a protocol to simply and reliably measure the lung pressure-volume curve in mice, showing that it is sufficiently sensitive to detect phenotypic parenchymal changes in two common lung pathologies, pulmonary fibrosis and emphysema. This metric provides a means to quantify the lung&#8217;s structural changes with developing pathology.

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes &#8211; but is not limited to &#8211; hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation.

This article describes a rat model of electrically-induced ventricular fibrillation and resuscitation by chest compression, ventilation, and delivery of electrical shocks that simulates an episode of sudden cardiac arrest and conventional cardiopulmonary resuscitation. The model enables gathering insights on the pathophysiology of cardiac arrest and exploration of new resuscitation strategies.

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

A Novel Microsurgical Model for Heterotopic, En Bloc Chest Wall, Thymus, and Heart Transplantation in Mice

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression must be pursued. Employing vascularized bone marrow transplantation and co-transplantation of the thymus have shown promise in this regard in various animal models.1-11 Vascularized bone marrow transplantation allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and the incorporation of thymus tissue with vascularized bone marrow transplantation has shown to increase T-cell chimerism ultimately playing a supportive role in the induction of immune regulation. The combination of solid organ and vascularized composite allotransplantation can uniquely combine these strategies in the form of a novel transplant model. Murine models serve as an excellent paradigm to explore the mechanisms of acute and chronic rejection, chimerism, and tolerance induction, thus providing the foundation to propagate superior allograft survival strategies for larger animal models and future clinical application. Herein, we developed a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique. The experience in syngeneic and allogeneic transplant settings is described for future broader immunological investigations via an instructional manuscript and video supplement.

To study combined solid organ and vascularized composite allotransplantation, we describe a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique.

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression ...

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved drug to prevent or reduce myocardial I/R injury. The study and understanding of the pathophysiological mechanisms of myocardial I/R injury is essential to develop successful treatments. Large animal experiments are an important step in translational methods. The porcine model of acute myocardial infarction has been established and described by ourselves and others. We aimed to further improve the value of the model by focusing in detail on the sampling techniques for use in future experiments. Furthermore, we emphasize small but important steps that can affect the quality of the final results. To mimic the clinical situation of myocardial I/R injury, a percutaneous coronary intervention (PCI) catheter was inserted into the left anterior descending coronary artery (LAD) of an anesthetized pig. &#176;&#176;&#176;This model mimics acute myocardial infarction and PCI treatment in humans with the possibility of accurately determining the area at risk as well as the necrotic- and viable ischemic tissue. Here the model was used to investigate the effect of a bicyclic peptide inhibitor of FXIIa. The model can also be modified to allow longer reperfusion times to study later effects of myocardial infarction.

Here we demonstrate a protocol to standardize sampling procedures of an established porcine model of acute myocardial infarction in order to increase its translational value in the understanding of the pathophysiology of myocardial ischemia/reperfusion injury and to test novel drug candidates.

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to perform a partial thoracotomy to visualize the transverse aortic arch. However, the surgical trauma caused by the thoracotomy in open-chest models changes the respiratory physiology as the ribs are dissected and left unattached after chest closure. To prevent this, we established a minimally invasive, closed chest approach via lateral thoracotomy. Herein we approach the aortic arch via the 2nd intercostal space without entering the chest cavities, leaving the mouse with a less traumatic injury to recover from. We perform this operation using standard laboratory settings for open chest TAC procedures with equal survival rates. Apart from maintaining physiological breathing patterns due to the closed chest approach, the mice seem to benefit by showing rapid recovery, as the less invasive technique appears to facilitate a fast healing process and to reduce immune response after trauma.

Here, we present a protocol of Transverse Aortic constriction (TAC) via a lateral thoracotomy. This technique is a minimally invasive, closed chest surgical procedure aiming to simulate pressure overload and heart failure in mice utilizing standard TAC laboratory settings.

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

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.

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

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) generated by recording both pressure and volume during cardiac catheterization are vital when assessing both systolic and diastolic cardiac function. Left and right heart function are closely related, reflected in ventricular interdependence. Thus, recording biventricular function in the same animal is important to get a complete assessment of cardiac function. In this protocol, a closed chest approach to cardiac catheterization consistent with the way catheterization is performed in patients is adopted in mice. While challenging, the closed chest strategy is a more physiological approach, because opening the chest results in major changes in preload and afterload that create artifacts, most notably a fall in systemic blood pressure. While high-resolution echocardiography is used to assess rodents, cardiac catheterization is invaluable, particularly when assessing diastolic pressures in both ventricles.
Described here is a procedure to perform invasive, closed chest, sequential left and right ventricular pressure-volume (PV) loops in the same animal. PV loops are acquired using&#160;admittance technology with a mouse pressure-volume catheter and pressure-volume system acquisition. The procedure is described, beginning with the neck dissection, which is required to access the right jugular vein and the right carotid artery, to the insertion and positioning of the catheter, and finally the data acquisition. Then, the criteria required to ensure the acquisition of high-quality PV loops are discussed. Finally, the analysis of the left and right ventricular PV loops and the different hemodynamic parameters available to quantify systolic and diastolic ventricular function are briefly described.

Presented here is a protocol to assess biventricular heart function in mice by generating pressure-volume (PV) loops from the right and left ventricle in the same animal using closed chest catheterization. The focus is on the technical aspect of surgery and data acquisition.

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.
Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult G&#246;ttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model.
MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in G&#246;ttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in G&#246;ttingen minipigs and at 2 months in Landrace pigs, respectively.
Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in G&#246;ttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, G&#246;ttingen minipigs showed a slight increase in LVED mass only at 6 months.
In summary, this is the first characterization of post-MI HF in G&#246;ttingen minipigs in comparison to Landrace pigs, showing that the G&#246;ttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the G&#246;ttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

The overall goal of the current study is to present the techniques of induction of myocardial infarction (MI) and post-myocardial infarction heart failure (post-MI HF) in closed-chest, adult G&#246;ttingen minipigs and the characterization of post-MI HF model in G&#246;ttingen minipigs as compared to Landrace pigs.

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

Cardiac Response to &#946;-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of specific treatments on the heart. Due to the feasibility of genetic manipulations the mouse has become the most common mammalian animal model to study cardiac function and to search for new potential therapeutic targets. Here we describe a protocol to determine cardiac function&#160;in vivo using pressure-volume loop measurements and analysis during basal conditions and under &#946;-adrenergic stimulation by intravenous infusion of increasing concentrations of isoproterenol. We provide a refined protocol including ventilation support taking into account the positive end-expiratory pressure to ameliorate negative effects during open-chest measurements, and potent analgesia (Buprenorphine) to avoid uncontrollable myocardial stress evoked by pain during the procedure. All together the detailed description of the procedure and discussion about possible pitfalls enables highly standardized and reproducible pressure-volume loop analysis, reducing the exclusion of animals from the experimental cohort by preventing possible methodological bias.

Here we describe a cardiac pressure-volume loop analysis under increasing doses of intravenously infused isoproterenol to determine the intrinsic cardiac function and the &#946;-adrenergic reserve in mice. We use a modified open-chest approach for the pressure-volume loop measurements, in which we include ventilation with positive end-expiratory pressure.

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of ...