{"created":"2023-06-19T07:18:28.337232+00:00","id":3841,"links":{},"metadata":{"_buckets":{"deposit":"f9360eff-32a0-4347-a47e-ffda5408bc19"},"_deposit":{"created_by":4,"id":"3841","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3841"},"status":"published"},"_oai":{"id":"oai:az.repo.nii.ac.jp:00003841","sets":["370:15:392"]},"author_link":["17730"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"1997-11-05"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"麻布大学"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(獣医学)"}]},"item_10006_description_22":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"In recent years, the diagnostic techniques of cardiovascular diseases in small animals has improved through the introduction of various diagnostic apparatuses such as the ultrasonic equipment. Consequently, the diagnosis of a number of heart diseases, both congenital and acquired, has become clinically feasible. As treatments for these diseases, it is hoped that life is prolonged by conservative therapy and that radical treatment using thoracotomy and cardiotomy could be performed.\n Surgically, mechanical heart and lung apparatuses are necessary for maintaining the cardioplegia in order to safely conduct the thoracotomy and cardiotomy. They are used widely in human medicine and require a large circuit and large volume of filling blood within the circuit. The cases of heart surgery with cardiac disease in small animals are predominantly medium-size breeds of dogs weighing between three and 10kg. It is, therefore, unfeasible to apply the human mechanical heart and lung apparatus for small animals since there are problems such as large volume of filling blood within the circuit, hemolysis of the blood or resistance to the flow rate. In this study, we attempted to develop a mechanical heart and lung apparatus that can be applied to small- and medium-size breeds of dogs. Moreover, the amount of filling fluid is reduced within the circuit and the blood is replaced by non-blood materials to verify the clinical applicability of the apparatus based upon the vital reflexes when performing thoracotomy and cardiotomy using both the hypothermia (cooling) and non-hypothermia (non-cooling) methods of treatment.\n\n1. Prototype of the MERA mechanical heart and lung system from the Animal Clinical Research Foundation\n\n Trials were conducted using the prototype of the MERA mechanical heart and lung system from Animal Clinical Research Foundation (Senko Ikakogyo Ltd.), with built-in roller pump, temperature controlled water bath, and a full array of temperature sensors. The roller pump in the mechanical heart and lung apparatus used in these trials had a maximum blood flow of 1,280ml/min. when using the L circuit, and a maximum blood flow of 500ml/min. when using the S circuit. The mechanical lung was of the hollow fibers with perfusion type, and was able to use three separate effective surface areas of 0.3m^2, 0.6m^2, and 1.0m^2. It was also possible to use the membranes in parallel. The extracorporeal circuit can absorb blood from the heart chamber and feed it into the circuit for reuse, and the circuit itself is of a semi-closed design which permits closure of the catheter, employing L and S circuits. The circuit specification has been reduced for the purpose of simplification, which can reduce the amount of filling fluid as far as possible. The heat converter is a Brown-Harrison model, and uses a perfusion fluid for nephrectomized kidney requiring little filling fluid. As a result, the minimum amount of circuit fluid was 169ml for the S circuit when combined with the 0.3m^2 mechanical lung, and 317ml for the L circuit when combined with the 0.6m^2 mechanical lung, thereby making extracorporeal circulation possible using non-blood fluid.\n\n2. Extracorporeal circulation using non-hypothermic procedure\n\n Using the same dogs on the mechanical heart and lung apparatus in these experiments, thoracotomy and cardiotomy were carried out using the non-hypothermic procedure to examine both the reflexes of the dogs and the capabilities of the prototype of apparatus. The five normal dogs used in this experiment were all fully grown and weighed between 3.8 and 10.9kg. Each of them had previously undergone extracorporeal circulation using non-blood fluid. Thoracotomy was conducted under controlled ventilation using a muscle relaxant and intravenous microdrip infusion with 0.1% ketamine hydrochloride. The fluid and blood were supplied through the aortas, and removed through both the superior and inferior venae cavae. The cannulae used for both supply and removal were those used normally in pediatrics. Using this, extracorporeal circulation was started. Next, the cardiotomy was conducted after the aortas were blocked off. Following examination of the heart chamber, the incisional cardiac muscle was sutured closed. Heparin sodium was used as an anticoagulant, and protamine sulfate was used to suppress the anticoagulant effect. Further, 7% sodium bicarbonate was used to maintain the acid-base balance. A combined solution of lactic Ringer solution, 5% glucose, 20% mannitol, 7% sodium bicarbonate and hepar in was used to fill the extracorporeal circulation circuit.\n As a result, the mean time for a complete extracorporeal circulation among the five dogs was 84.8 ± 10.4 min. with a mean aorta blocking time of 32.8 ± 2.6 min. Also, both blood gasses and acid-base balance were highly satisfactory while circulating extracorporeally. Although the mean blood pressure dropped, it did not go below 75.5 ± 6.3mmHg, and a satisfactory quantity of urine could also be obtained during extracorporeal circulation. Blood coagulation could be controlled well by administering heparin prior to beginning extracorporeal circulation as well as protamine sulfate when it had been completed. Considerable hemolysis and a slight rise in creatinine was detected by the blood tests conducted during extracorporeal circulation, but other examinations showed these values to be within tolerable range. The Ht values during extracorporeal circulation lowered to a mean of 22.8 ± 1.1% for each of the five dogs due to filling fluid, but these recovered upon awakening. Yong fluid was used for cardioplegia and GIK to protect the cardiac muscle, and the status of cardioplegia was comparatively good. Following cardioplegia, ice slush was infused into the pericardial tent, and the cardiac muscle protected locally prior to the cardiotomy. Following removal of the aorta block, recovery of the heart beat could be achieved either spontaneously or through cardiac massage, but temporary ventricular tachycardia was also in evidence in some cases, requiring the administration of lidocaine. However, post-operative recovery was good. \n\n3. Extracorporeal circulation with hypothermic procedure\n\n In the previous experiment, it proved to be effective to apply extracorporeal circulation with the non-hypothermic method for surgery using a MERA mechanical heart and lung system for small animal use. Therefore, it was thought that even safer extracorporeal circulation may be possible with even greater effectiveness upon recovery if the metabolism of the body could by suppressed by means of extracorporeal circulation employing a hypothermic procedure. In this case, the water bath for cooling the extracorporeal circuit in the prototype had been newly fitted, and following the additional improvement of upgrading the roller pump from one that was suited to being the artificial heart of a small-sized dog to one suitable for a medium-sized dog, extracorporeal circulation was implemented using the hypothermic method. The normal weights of all these dogs used in this experiments were between 4.8 to 11.8kg, and extracorporeal circulation using non-blood fluid was carried out in all cases. In three cases, fluid was supplied from the aorta, but in two cases the supply cannulae blocked the surgical field, so that the cannulae were instead inserted into the femoral artery to ensure a wide, clear field for the operation. The fluid and blood were removed as in all cases by using both the superior and inferior venae cavae, and the supply cannuale were changed to a simple straight type for insertion into the artery. Thoracotomy and cardiotomy were performed in exactly the same way as in the previous experiment. Consequently, because thoracotomy and cardiotomy were comparatively easier under hypothermic conditions than under non-hypothermic ones, extracorporeal circulation time for the five dogs was a mean 76.4 ± 27.2 min., and the blocking time for the femoral artery was 30.0 ± 6.7 min., which is only slightly shorter than with non-hypothermic method. However, based on monitoring of both patient reflexes and the state of the exposed heart, it was adjudged possible to extend both the extracorporeal circulation time and the period of exposure of the heart. Body temperature in this case was approximately 3 ℃ lower in the rectum than with the non- hypothermic procedure, and the mean arterial pressure considerably lower, but urine quantity was sufficiently obtained. Arterial blood oxygenation was good, and both blood gasses and acid-base balance proved to be more stable than non-hypothermic method. Control of blood coagulation was almost as good as before. Various blood tests identified the presence of considerable hemolysis, a reduction in serum potassium, and a rise in CPK. Although fluctuations in LDH were observed, there was no definite tendency identified. The other values examined were all within tolerable limits. Ht values during extracorporeal circulation were reduced to a mean 21.8 ± 6.2%, but these recovered after extracorporeal circulation had ended. Cardiac resuscitation required cardioversion (electrical defibrillation) in three cases, and heart massage in two cases, and all of the cases experienced temporary tachycardia. Also, in one case, the weaning of the extracorporeal circulation was barely prolonged when compared with the non-hypothermic method, but the post-operative prognosis has been extremely good.\n\n4. Practical applications of extracorporeal circulation in clinical cases\n\n From the results of the our experiments to date, it has been understood that extracorporeal circulation with the non-hypothermic method is effective for the metabolism of the body, carrying out cardiotomy and post-operative recovery. However, the practical benefits to actual clinical cases were also examined because it is predicted that clinically, there is high surgical risk which is not present in normal dogs. These clinical cases were as follows: One case of atrial septal defect (ASD), three cases of ventricular septal defect (VSD) (one case was complicated by pulmonary artery stenosis), and one case of patent ductus arteriosus (PDA), making a total of five cases, each weighing between 3.8 and 10.4kg. Excluding the PDA case, for the remaining four cases, the mechanical heart and lung apparatus was used to employ non-blood extracorporeal circulation with the hypothermic technique. The thoracotomy and cannulation were performed under controlled ventilation using continuous intravenous microdrip of 0.1% ketamine hydrochloride and a muscle relaxant. Fluid and blood was supplied from the femoral artery, and removed via both the superior and inferior venae cavae. Following cardioplegia, radical treatment of a defect through cardiotomy was performed. The PDA case underwent non-blood extracorporeal circulation with the non-hypothermic method. Fluid and blood supplies were from the femoral artery, and extraction from the right ventricle. Incision of the arterial duct was made following blockage of the aortas. The mean time for extracorporeal circulation in these clinical cases was 103.6 ± 38.6 min., and the aortas were blocked for a period of 58.8 ± 11.3 min. It was possible to prolong the period of both thoracotomy and cardiotomy, as well as the time required for treating the defect, due to the thoracotomy and cardiotomy being comparatively long. Both blood gasses and acid-base balance during the extracorporeal circulation with the hypothermic procedure were good. Also, the fall in arterial pressure during the extracorporeal circulation was within tolerable limits. Blood coagulation control was also quite good, and various blood tests confirmed a tendency towards a reduction in serum potassium, considerable hemolysis, and rises in ALT, AST, CPK, and LDH, but other test values were within tolerable limits. The Ht values during the extracorporeal circulation were 17.6 ± 1.9%, but post-operative recovery was comparatively rapid after administering diuretics.\n In cases of cardioplegia, excellent cardiac recovery could be obtained in all cases by employing electrical fibrillation, and weaning from extracorporeal circulation, awakening, and post-operative recovery were good. In the two cases where tachycardia was observed, recovery was good following administration of lidocaine. Since the single case of PDA required partial circulation, abnormalities in the acid-base balance were confirmed. However, blood gasses were good, and recovery following removal of the aortic block, as well as weaning from the extracorporeal circulation and post-operative recovery were also good.\n From the above, it was demonstrated that prototype trials using the MERA mechanical heart and lung system for small animals worked well for dogs weighing between three and 10kg. Moreover, it shows that using the same system, the extracorporeal circulation with the non-hypothermic procedure is feasible with non-blood filling fluid in the L and S circuits. Also, by cooling the blood through the addition of equipment upgrades, the metabolism of the body is suppressed, so that thoracotomy and cardiotomy can be carried out easily. Moreover, as a result of application of the MERA mechanical heart and lung system from the Animal Clinical Research Foundation to actual clinical cases, prolongation of time requiring thoracotomy and cardiotomy, weaning from the extracorporeal circulation, and awakening and recovery are all excellent. Therefore, it has been confirmed that the conventional extracorporeal circulation method can be used with safety and is effective in radical surgical treatment","subitem_description_type":"Other"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"近年、超音波診断装置などの各種診断機器の導入によって、小動物における循環器疾患の診断が向上し、多くの先天性または後天性の心疾患が臨床的に診断可能となった。これらの心疾患に対する治療法として、内科的には保存療法による延命治療が行われ、外科的には開胸・開心術による根治療法が要望されている。\n　外科的に、安全な開胸・開心術を実施するには、心停止の状態を保つために人工心肺装置が必要となる。人工心肺装置は、医学の臨床で多く応用されているが、いずれも循環回路が大きく、多量の回路内充填血液が必要である。小動物臨床における心疾患で、心臓手術の対象となる症例は、体重3～10Kg程度の小・中型犬種が圧倒的に多く、したがって、人用の人工心肺装置は、多量の回路充填血液、充填血液の溶血あるいは流速抵抗などの問題があり、小動物臨床には応用できない。本研究では小動物臨床で、小・中型犬種に適用できる人工心肺装置として、循環回路の充填容量が少なく、無血充填が可能な小動物用人工心肺装置の開発を試み、潅流血液非冷却法ならびに冷却法によって、開胸・開心術を実施し生体反応を観察したのち、実際の臨床例に応用して、その適応性を確認した。\n\n1.メラ小動物用人工心肺システム動臨研タイプの試作\n　ローラーポンプ、温水槽、各種温度センサーを一体化したメラ小動物用人工心肺システム動臨研タイプ（泉工医科工業社製）を試作した。試作した人工心肺装置のローラーポンプは、L回路使用時の最大流量が1,280ml/min、S回路使用時の最大流量が500ml/minであり、人工肺は中空糸内部潅流型で、有効膜面積が、0.3m^2、0.6m^2、1.0m^2の3種類が利用できると同時に、その並列使用も可能とした。体外循環回路は、心腔内血液を吸引し、回路内へ導入して再利用できる構造であり、導入路の閉鎖が可能なセミクローズド回路とし、L回路とS回路を作成した。回路は簡略化して短縮し、回路充填量も可能な限り少なくした。熱交換器はブラウン・ハリソン型で、充填量の少ない摘出腎潅流用を使用した。その結果、回路の最低充填量は0.3m^2の人工肺を組み合わせたS回路で169ml、0.6m^2の人工肺を組み合わせたL回路で317mlの充填で無血体外循環が可能となった。\n\n2.潅流血液非冷却法による体外循環\n　この試作した人工心肺装置を使用して供試犬を用い、潅流血液非冷却法による開胸・開心術を実施し、試作器の性能と供試犬の生体反応について検討した。正常な供試犬5頭の体重は3.8～10.9Kgの成犬で、いずれも無血体外循環を行った。0.1%塩酸ケタミン微量持続点滴麻酔と筋弛緩剤投与による調節呼吸下で開胸し送血は大動脈から、脱血は前・後大静脈から行った。送血カニューレと脱血カニューレは小児用のものを使用して体外循環を開始した。ついで大動脈を遮断して開心術を行い、心腔内を観察してから心筋切開創を縫合閉鎖した。血液凝固機能のコントロールには、ヘパリン・ナトリウムによって抗凝固、硫酸プロタミンによって抗凝固の解除を、酸塩基平衡の調節には、7%炭酸水素ナトリウムを使用した。体外循環回路の充填液には、乳酸リンゲル液、5%ブドウ糖液、20%マンニトール液、7%炭酸水素ナトリウム液ならびにヘパリン液の配合液を使用した。\n　その結果、体外循環時間は5頭の平均値で84.8±10.4分であり、大動脈遮断時間は平均32.8±2.6分であった。また、体外循環中の血液ガスおよび酸塩基平衡はほぼ良好に推移し、平均動脈圧は体外循環によってやや低下したが、75.5±6.3mmHgを下回ることなく、尿量も十分に確保できた。血液凝固は体外循環開始前にヘパリン投与、硫酸プロタミンは体外循環終了時に投与して良好にコントロールできた。体外循環中に実施した血液の諸検査で、若干の溶血およびクレアチンニンの軽度の上昇がみられたが、その他の検査値は許容範囲であった。体外循環中のHt値は充填液によって5頭の平均値が22.8±1.1%に低下したが、覚醒時には回復した。心停止液にはYnog液、心筋保護液にはGIK液を使用したが、心停止の状態は比較的良好だった。心停止後は心膜テント内にアイススラッシュを注いで、心筋を局所的に保護して開心術を行った。大動脈遮断解除後に、自発的あるいは用手心マッサージによって心拍動の回復がみられたが、回復期に一過性の心室性早期拍動がみられ、リドカインを投与した例もあった。しかし、術後の回復は良好であった。\n\n3.潅流血液冷却法による体外循環\n　前段の実験において、メラ小動物用人工心肺システム試作器を使用して、潅流血液非冷却法による体外循環の有用性が明らかとなったことから、体外循環の潅流血液を冷却することによって生体組織の代謝を抑制すれば、回復時に一層有利で安全な体外循環が可能であると考えた。そこで、試作器に体外循環回路を冷却するための冷却水槽を増設し、人工心臓を小型犬から中型犬まで対応できるローラーポンプに変更して改良を加え、潅流血液冷却法によって体外循環を行った。本実験に供試した5頭の正常な犬の体重は4.8～11.8Kgで、いずれも無血体外循環とし、3例は大動脈から送血したが、2例は送血カニューレが術野の妨げとなることから大腿動脈に設置して術野を広く確保した。脱血は全例で前・後大静脈から行い、送血カニューレは、動脈への挿入が容易なストレートタイプに変更した。開胸・開心術は前段の方法と全く同一の方法で行った。その結果、潅流血液冷却法では、非冷却法よりも開胸・開心操作が比較的容易であったことから体外循環時間は、5頭の平均値で76.4±27.2分であり、大動脈遮断時間は30.0±6.7分で、潅流血液非冷却法よりわずかに短縮されたが、生体反応ならびに露出心臓の状態を観察した結果では、体外循環時間ならびに開心時間の延長が可能な状態にあった。この場合の体温は潅流血液非冷却法よりも直腸温で約3℃低下し、平均動脈圧は潅流血液非冷却法よりもやや低下したが、尿量は十分に確保された。動脈血の酸素加は良好で血液ガスおよび酸塩基平衡も潅流血液非冷却法の場合より安定した値を示した。血液凝固機能のコントロールはほぼ良好であった。血液の諸検査では若干の溶血、血清Kの低下、CPKの上昇がみられ、LDHは変動がみられたが一定の傾向はみられず、その他の検査値は許容範囲であった。体外循環中のHt値は平均21.8±6.2%に低下したが、体外循環後には回復した。心蘇生は3例で電気的除細動を行い、2例で用手心マッサージを行ったが、心室性早期拍動はいずれも一過性であった。また、1例で潅流血液非冷却法に比較して体外循環の離脱がわずかに延長したが、術後の経過は極めて良好であった。\n\n4.臨床例に対する体外循環の応用\n　これまでの実験結果から、潅流血液非冷却法による体外循環法が生体組織の代謝抑制、開心術操作ならびに術後回復の点で有利であることが判った。しかし、臨床例では健康犬と異なりサージカルリスクの高いことが予想されることから、実際の臨床例に応用し実用的な有利性について検討した。この場合の臨床例は心房中隔欠損（ASD）1例、心室中隔欠損（VSD）3例（1例は肺動脈狭窄症を合併）、動脈管開存症（PDA）1例の5例であり、体重は3.8～10.4Kgであった。使用した人工心肺装置は、PDA以外の4例は潅流血液冷却法による無血体外循環で、0.1%塩酸ケタミン微量持続点滴麻酔と筋弛緩剤投与による調節呼吸下で開胸してカニューレを挿入し送血は大腿動脈から、脱血は前・後大静脈から行い、心停止後に開心術による欠損孔の根治療法を行った。PDAは潅流血液非冷却法による無血体外循環で、送血は大腿動脈から、脱血は右心室から行い、大動脈を遮断した後に動脈管を切断した。臨床例における体外循環時間は平均値で103.6±38.6分、大動脈遮断時間は58.8±11.3分で、開心術による欠損孔の補修に比較的長い時間を要したと同時に開胸・開心時間の延長が可能であった。潅流血液冷却法による体外循環中の血液ガスおよび酸塩基平衡は良好であった。体外循環中の動脈圧の低下は許容範囲であった。血液凝固機能のコントロールはほぼ良好で、血液の諸検査では血清Kの低下傾向、若干の溶血およびALT、AST、CPK，LDHの上昇がみられたが、その他の検査値は許容範囲であった。体外循環中のHt値は17.6±1.9%であったが、術後は利尿剤の投与によって比較的迅速に回復した。\n　心停止を行った例では電気的除細動によっていずれも良好な心蘇生が得られ、体外循環からの離脱、覚醒ならびに術後の回復も良好であった。心室性早期拍動がみられた2例では、リドカインの投与によって、その後の回復は良好であった。PDAの1例は部分循環であったことから、酸塩基平衡に異常がみられたが、血液ガスの状態は良好に経過し、大動脈遮断解除後の回復、体外循環からの離脱および術後の回復も良好であった。\n　以上のことから、メラ小動物用人工心肺システム動臨研タイプを試作し、体重3～10Kg程度の犬に対し、潅流血液非冷却法による体外循環で、L回路またはS回路による無血充填で体外循環が可能であることを明らかにした。また、試作器に改良を加えて潅流血液を冷却することにより、生体組織の代謝を抑制し、開胸・開心術操作を容易にすることができた。さらにメラ小動物用人工心肺システム動臨研タイプを用いて、実際の臨床例に応用した結果、開胸・開心時間の延長、体外循環からの離脱、覚醒ならびに回復が良好で、臨床的に安全で有利な外科的根治療法が行える体外循環法であることが確認された。","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"乙第363号"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"山形, 静夫"}],"nameIdentifiers":[{"nameIdentifier":"17730","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2014-04-16"}],"displaytype":"detail","filename":"diss_dv_otsu0363.pdf","filesize":[{"value":"12.4 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_dv_otsu0363","url":"https://az.repo.nii.ac.jp/record/3841/files/diss_dv_otsu0363.pdf"},"version_id":"0f07dcee-503c-49e5-adb6-64a2c60facd3"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"小動物用人工心肺装置の開発と臨床応用に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"小動物用人工心肺装置の開発と臨床応用に関する研究"},{"subitem_title":"Studies on the development and clinical applications of mechanical heart and lung apparatus for use in small animals","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"4","path":["392"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-01-10"},"publish_date":"2014-01-10","publish_status":"0","recid":"3841","relation_version_is_last":true,"title":["小動物用人工心肺装置の開発と臨床応用に関する研究"],"weko_creator_id":"4","weko_shared_id":4},"updated":"2023-06-19T08:24:25.861668+00:00"}