<meta charset="utf8"></head><body>作業ラット心臓灌流モデルを用いたドナー心臓保存の最適化

<ol>
	<li>Kwan, J. C., Gao, L., Macdonald, P. S., Hicks, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardio-protective+signalling+by+glyceryl+trinitrate+and+cariporide+in+a+model+of+donor+heart+preservation.">Cardio-protective signalling by glyceryl trinitrate and cariporide in a model of donor heart preservation.</a> Heart Lung Circ. 24 (3), 306-318 (2015).</li><li>Watson, A. J., 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=Enhanced+preservation+of+the+rat+heart+after+prolonged+hypothermic+ischemia+with+erythropoietin-supplemented+Celsior+solution.">Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution.</a> J Heart Lung Transplant. 32 (6), 633-640 (2013).</li><li>Chew, H. C., 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=Outcomes+of+donation+after+circulatory+death+heart+transplantation+in+Australia.">Outcomes of donation after circulatory death heart transplantation in Australia.</a> J Am Coll Cardiol. 73 (12), 1447-1459 (2019).</li><li>Dhital, K. K., 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=Adult+heart+transplantation+with+distant+procurement+and+ex-vivo+preservation+of+donor+hearts+after+circulatory+death:+a+case+series.">Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.</a> Lancet. 385 (9987), 2585-2591 (2015).</li><li>Joshi, Y., 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=Heart+transplantation+from+DCD+donors+in+Australia:+Lessons+learned+from+the+first+74+cases.">Heart transplantation from DCD donors in Australia: Lessons learned from the first 74 cases.</a> Transplantation. 107 (2), 361-371 (2023).</li><li>Villanueva, J. E., 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=Functional+recovery+after+dantrolene-supplementation+of+cold+stored+hearts+using+an+ex+vivo+isolated+working+rat+heart+model.">Functional recovery after dantrolene-supplementation of cold stored hearts using an ex vivo isolated working rat heart model.</a> PLoS One. 13 (10), e205850 (2018).</li><li>Villanueva, J. E., 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=The+cardioprotective+potential+of+the+sodium-glucose+cotransporter+2+inhibitor+empagliflozin+in+donor+heart+preservation.">The cardioprotective potential of the sodium-glucose cotransporter 2 inhibitor empagliflozin in donor heart preservation.</a> J Heart Lung Transplant. 39 (10), 1151-1153 (2020).</li><li>Gao, L., 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=Critical+role+of+the+STAT3+pathway+in+the+cardioprotective+efficacy+of+zoniporide+in+a+model+of+myocardial+preservation+-+the+rat+isolated+working+heart.">Critical role of the STAT3 pathway in the cardioprotective efficacy of zoniporide in a model of myocardial preservation - the rat isolated working heart.</a> Br J Pharmacol. 162 (3), 633-647 (2011).</li><li>Cropper, J. R., Hicks, M., Ryan, J. B., Macdonald, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardioprotection+by+cariporide+after+prolonged+hypothermic+storage+of+the+isolated+working+rat+heart.">Cardioprotection by cariporide after prolonged hypothermic storage of the isolated working rat heart.</a> J Heart Lung Transplant. 22 (8), 929-936 (2003).</li><li>Gao, L., 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=Enhanced+functional+recovery+of+the+heart+donated+after+circulatory+death+determination+with+antemortem+heparin.">Enhanced functional recovery of the heart donated after circulatory death determination with antemortem heparin.</a> J Heart Lung Transplant. 39 (6), 607-609 (2020).</li><li>Villanueva, J. E., 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=The+effect+of+increasing+donor+age+on+myocardial+ischemic+tolerance+in+a+rodent+model+of+donation+after+circulatory+death.">The effect of increasing donor age on myocardial ischemic tolerance in a rodent model of donation after circulatory death.</a> Transplant Direct. 7 (6), e699 (2021).</li><li>Kumarasinghe, 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=Improved+heart+function+from+older+donors+using+pharmacologic+conditioning+strategies.">Improved heart function from older donors using pharmacologic conditioning strategies.</a> J Heart Lung Transplant. 35 (5), 636-646 (2016).</li></ol>

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			<td>1.5 mL colorless Eppendorff tube, 1000 per box</td>
			<td>Bio Strategy Pty Ltd</td>
			<td>0030.125.150</td>
			<td></td>
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			<td>15 mL cent/tubes (S) Sleeve/25 PP ctn/500</td>
			<td>Sigma-aldrich Pty Ltd</td>
			<td>CLS430791-500ea</td>
			<td></td>
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			<td>BP Transducer/Cable kit</td>
			<td>ADInstruments</td>
			<td>MLT1199</td>
			<td>Data Acquisition</td>
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			<td>Bridge Amp</td>
			<td>ADInstruments</td>
			<td>FE221</td>
			<td>Data Acquisition</td>
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			<td>Carbogen 555G2</td>
			<td>BOC</td>
			<td>BOC002</td>
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			<td>Checktemp1 thermometer</td>
			<td>Hanna Instruments</td>
			<td>HI98509</td>
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			<td>Clamp Pinch 1/4-7/16 PK 12</td>
			<td>Thomas Scientific</td>
			<td>2848Y40</td>
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			<td>Coherent Scientific</td>
			<td>14121</td>
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			<td>8847E25</td>
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			<td>Covidien Sofsilk 2-0 black precut 45 cm box of 24</td>
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			<td>S195</td>
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			<td>N/A</td>
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			<td>Custom Made 750 mL Reservoir</td>
			<td>Custom Blown Glassware Pty Ltd</td>
			<td>N/A</td>
			<td>Rig Construction</td>
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			<td>Sigma-aldrich Pty Ltd</td>
			<td>G7528-1Kg</td>
			<td>To make Krebs Buffer</td>
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			<td>ADInstruments</td>
			<td>TS402</td>
			<td>Data Acquisition</td>
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			<td>Erlenmyer flasks 2 L&#160;</td>
			<td></td>
			<td></td>
			<td></td>
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			<td>Filter Microfibre type GF/C glass fibre 47 mm, 100</td>
			<td>Bio-strategy Pty Ltd</td>
			<td>1822047</td>
			<td></td>
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			<td>Forceps, 15 cm, 0.3 mm, CRVD</td>
			<td>Coherent Scientific</td>
			<td>14114</td>
			<td>Surgical Equipment</td>
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			<td>Four Prong Clamps with 9 mm x 115 mm long arm for holding 2-70 mm diam objects. Vinyl coated</td>
			<td>Met-App Australia Pty Ltd</td>
			<td>1352</td>
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			<td>Clffird Hallam Healthcare Pty Ltd</td>
			<td>1258693</td>
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			<td>Cenvet Australia Pty Ltd</td>
			<td>X5010</td>
			<td>Anaesthetic</td>
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			<td>Coherent Scientific&#160;</td>
			<td>CS-WPI-14117</td>
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			<td>Provet (NSW) Pty Ltd</td>
			<td>KETAI1</td>
			<td>Anaesthetic</td>
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			<td>Bio Strategy Pty Ltd</td>
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			<td>To make Krebs Buffer</td>
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			<td>Thomas Scientific</td>
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			<td>Thomas Scientific</td>
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			<td>Rig Construction</td>
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			<td>Sigma-Aldrich</td>
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			<td>VWR Chemicals&#160;</td>
			<td>26764.26</td>
			<td>To make Krebs Buffer</td>
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			<td>Sigma-Aldrich Pty Ltd</td>
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			<td>To make Krebs Buffer</td>
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			<td>ADInstruments</td>
			<td>ML826</td>
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			<td>ADInstruments</td>
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			<td>BSN Medical (Aust) Pty Ltd</td>
			<td>73252-36</td>
			<td></td>
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			<td>Merck Millipore</td>
			<td>SX0004701</td>
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			<td>Merck Millipore</td>
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			<td>Thomas Scientific</td>
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			<td>Sigma-aldrich</td>
			<td>59277</td>
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			<td>Rig Construction</td>
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			<td>Sigma-Aldrich Pty Ltd</td>
			<td>S6297 - 250g</td>
			<td>To make Krebs Buffer</td>
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			<td>Merck Millipore</td>
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			<td>Rig Construction</td>
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			<td>Becton Dickinson Pty Ltd</td>
			<td>302100</td>
			<td></td>
		</tr>
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			<td>Three Prong Clamps with 9 mm diameter x 125 mm long arm and twin screw for holding 5-80 mm</td>
			<td>Met-App Australia Pty Ltd</td>
			<td>1356</td>
			<td>Rig Construction</td>
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			<td>ADInstruments</td>
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			<td>Thermo Fisher</td>
			<td>NAL 8701-0900</td>
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			<td>Thermo Fisher</td>
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			<td>Coherent Scientific</td>
			<td>WPI-500-086</td>
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			<td>Thermoline Scientific</td>
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</table>

using an isolated working rat heart model to test donor heart preservation strategies

The success of a heart transplant can be greatly influenced by the preservation method used for the donor heart. Donor hearts are subjected to ischemic insults throughout the organ retrieval, transport, and transplantation process. The degree of ischemic damage to the donor organ can be mitigated by selecting an appropriate donor heart preservation strategy. Cold static storage (CSS) remains the most feasible and common method for donor heart preservation; however, CSS may not necessarily be the best option for all heart donation pathways. For example, hearts procured via the donation after circulatory death (DCD) pathway are maintained and assessed for viability using normothermic machine perfusion, whereas hearts procured via the donation after brain death (DBD) pathway can be preserved using CSS or hypothermic machine perfusion. Another important determinant for the preservation strategy used is the amount of either warm ischemia (for DCD) or cold ischemia (for DBD) the heart is subjected to during organ procurement and transportation.
Many centers use additional pharmacological supplementation of the heart preservation solution to increase ischemic tolerance and improve post-transplant heart function. Rodent studies from our laboratory showed that supplementation of cardioplegia with erythropoietin and glyceryl trinitrate was able to significantly improve cardiac functional recovery after prolonged cold storage of the donor heart1,2. These studies then progressed to porcine studies of donor heart preservation and provided the pre-clinical groundwork that led to the incorporation of erythropoietin and glyceryl trinitrate into the cardioplegia solution of hearts procured via a DCD pathway utilizing normothermic machine perfusion3,4,5. Currently, supplementation with erythropoietin and glyceryl trinitrate is also used in Australian transplant units for clinical DBD heart retrievals incorporating CSS. The overall goal of the isolated working rat heart (IWRH) perfusion protocol outlined below is to test donor heart preservation strategies in a laboratory setting and test their efficacy for preserving donor heart function after reperfusion. The isolated working rat heart protocol described has been used for over two decades within our laboratory and has proven extremely useful in screening for potential supplements and/or strategies that can improve donor heart preservation2,7,8,9.

<meta charset="utf8"></head><body>著者スポットライト:孤立したラット心臓灌流研究によるドナーの心臓保存の強化

単離された作業用ラット心臓モデルを使用して、ドナーの心臓保存戦略をテストする

Our research uses an isolated rat heart perfusion circuit to test supplementation strategies for donor heart preservation. We aim to identify preservation strategies that can improve the functional recovery of donor hearts after either long periods of cold storage or long periods of warm ischemia following donation after circulatory death. The isolated work in rat heart protocol was used to initially test the current clinical donor heart preservation strategy of using glyceryl trinitrate and erythropoietin in the heart preservation solution.This provided the rationale for testing in a porcine heart transplant study before transitioning to the clinic. The advantage of using an isolated working rat heart perfusion protocol compared to Langendorff perfusion techniques is the ability to obtain functional measurements of the heart, such as aortic flow and cardiac output.

Optimization of donor heart preservation solutions has played a key role in reducing ischemia-reperfusion injury in donor hearts during organ retrieval, ...

using-an-isolated-working-rat-heart-model-to-test-donor-heart

Research

JoVE Journal

Medicine

Using an Isolated Working Rat Heart Model to Test Donor Heart Preservation Strategies

226 ビュー.  Victor Chang Cardiac Research Institute. 私たちの研究では、単離されたラットの心臓灌流回路を使用して、ドナーの心臓保存のためのサプリメント戦略をテストします。私たちは、長期の冷蔵保管後または循環器死後の提供後の長期間の温虚血のいずれか後に、ドナー心臓の機能回復を改善できる保存戦略を特定することを目指しています。ラット心臓プロトコルにおける単離された?...