Pressure-Induced Ischemic Wound Healing with Bacterial Inoculation in the Rat

取得学位 : 博士（保健学）, 学位授与番号 : 医博甲第1722号, 学位授与年月日 : 平成17年9月30日, 学位授与大学 : 金沢大学, 主査 :稲垣 美智子 , 副査 :木村 留美子, 真田 弘

褥瘡治癒促進に向けた看護技術の開発: 動物モデルを用いたずれ力の実証

平成14年度診療報酬改定により、以前と比べ、仰臥位および側臥位時の圧迫が原因となる褥瘡発生は確実に減少し、また発生したとしても早期に治癒促進が図れるようになった。しかし、依然として難治性褥瘡は残っており、その中のひとつとして創縁の肥厚がある。この肥厚形成要因は、体位変換、臥床時のポジションニング、ベッド頭側挙上などの看護技術によって生じる力学的負荷(ずれ)であると考えられている。しかし臨床においてこの因果関係を解明することは、センサーがないこと、24時間の生活をモニタリングする必要があることなどの課題が多く、困難である。この現象解明と看護技術改善には、研究者らはモデルを作成することが適した方法と考えるが、未だその方法論は確立していない。本研究では、最初に動物モデルを用いたずれ負荷実験を行い、組織学的検討を行った。その結果ずれの負荷量が大きいと循環障害・膠原線維の走行の変化を著しくさせ、治癒を遷延させることが示唆された。次に、モデルに組み込む肉眼的所見の数量化情報として、発赤部位を近赤外線を用いて測定し、その後の治癒過程との関連を分析した。その結果、近赤外線透過度相対値は、壊死部を呈する部位において31〜71%、壊死を呈さない部位において90〜122%の値が得られ、2分化することができた。このことからそれぞれの治癒過程をたどる部位の相対値を2分する分離値を設定し、その予測妥当性を検討したところ、壊死を呈すると予測される部位において平均75.0%の一致度がみられた。近赤外線の情報は妥当性があると示唆された。さらに、外力が負荷された場合の応力解析モデルを検討するための基礎実験ならびに有限要素法を用いたシュミレーションモデルを試案した。本研究により看護技術開発のためのモデルをどのように構築していくかの方法論が提示できたと考える。Government introduced penalty system for failure to comply with the three tasks for pressure ulcer (PU) management in 2002. Owing to this system, the prevalence of PU successfully reduced and a healing time was also shortened. However, refractory Pus have remained to date. One of the delayed factors for PU healing is shear. Shear forces occur inevitably with nursing interventions such as positioning patients in head-elevated positions or position changes. In clinical settings, it is very difficult to monitor shear forces because of a limited sensor. Thus, researches try to develop a new animal model to elucidate effectiveness of shear to the wound healing. Firstly, we examined the relationship between the intensity of the shear force and PU healing using our original animal model Eight kg of pressure and 0.5, 1, 1.5 kg shear toward the caudal side were applied for 6 hours to the flank region. The higher group\u27s wound healing was delayed by the necrotic tissue and the shallow ulcer development. Papillary dermis was flat and extravasations of red blood cells and thrombosis were seen. Collagen fibers in the dermis paralleled skin surface and subcutaneous and muscle layer necrosis were seen up to Day 14. Secondarily, we tried to measure the intensity of redness resulting from pressure and shear loading. Using a near-infrared device and an imaging soft wear, we converted the intensity of the redness from subjective values to objective values. The relative values of permeability of near-infrared rays in the necrotic tissues were 31 -71%. While those in the wound without necrotic tissue were 90-122%. According to these results, the predictive validity was calculated and demonstrated good validity (agreement rate: 75%). Moreover, we tried to incorporate the animal model results into a finite element model. A prototyped model was completed under the simple loading.研究課題/領域番号:17592199, 研究期間(年度):2005-2007出典：「褥瘡治癒促進に向けた看護技術の開発: 動物モデルを用いたずれ力の実証」研究成果報告書　課題番号17592199 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

体位変換時に生じる応力が褥瘡治癒過程に及ぼす影響: 組織学的検討

研究の目的は、臨床で起こりやすい一方向のずれが褥瘡の治癒過程にどのような影響を及ぼすのかを明らかにすることとした。その方法として、ラット褥瘡モデルを用いて、発生の段階で圧迫のみを負荷した群と圧迫と一方向(尾側方向)のずれを1kgの重りを用いて負荷した群の治癒過程を肉眼的・組織学的に比較、検討した。その結果、肉眼的所見では、ずれと圧迫を負荷した群には局所の壊死が見られ、圧迫のみを負荷した群より治癒が1週間程度遷延した。組織学的所見では、ずれと圧迫を負荷した群で7日目、14日目ともに尾側の筋層の変性が顕著であった。また、頭側の真皮にうっ血、出血が見られた。圧迫のみを負荷した群では、7日目に中央部の筋層に変性が見られたが、14日目では再生していた。以上より、一方向のずれと圧迫を負荷した褥瘡では壊死が形成され、圧迫のみを負荷した褥瘡と比較して、治癒が遷延することが明らかとなった。その理由には、尾側の皮下組織から筋層にかけての変性とそれによって引き起こされる頭側の真皮のうっ血が挙げられた。Shear force injury occurs when the skin remains stationary and the underlying tissue shifts. This shift diminishes blood supply to the skin and soon results in ischemia and tissue damage. However, no satisfactory animal models of a shear force induced ischemic wound have been constructed, and the effects of shear force on the healing process of such wounds have yet to be clarified. The present study therefore aimed to prepare a shear force induced ischemic wound model and histologically clarify the effects of shear force on wound healing.Two incisions were made down to the peritoneal cavity in the flank region of 16 rats, and a metal plate was passed through one incision under the peritoneum and then exited from the other. From the exterior surface, 8 kg of pressure was applied for 6 hours to the flank skin and abdominal muscle to prepare an ischemic wound. The wound was observed for two weeks, and histological tissue sections were prepared on days 7 and 14. Wound healing was compared between two groups : a shear force group (1.0 kg shear force loading) and a control group (only pressure was applied to prepare an\u27ischemic wound).It took one week longer for a shear force induced ischemic wound to heal than a pressure induced ischemic wound. Histopathlogical findings of the shear force induced ischemic wound were the caudal muscle layer\u27s degeneration and the cranial dermis layer\u27s congestion and hemorrhage. Control group\u27s histopathlogical findings were muscle layer\u27s degeneration on Day 7, and tissue regeneration on Day 14.研究課題/領域番号:15592226, 研究期間(年度):2003-2004出典：「体位変換時に生じる応力が褥瘡治癒過程に及ぼす影響: 組織学的検討」研究成果報告書　課題番号15592226 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

褥創発生リスクの高い集中治療室入室患者における褥創発生予防

金沢大学医療技術短期大学部褥創発生を予測し、最も減圧効果があると示唆されたセル型圧切替式エア-マットレス使用しても褥創が発生する。その予防には減圧されながらも低下する個々の組織耐久性の変化をとらえて褥創発生を予測する必要があると考えた。今回、エア-マットレスで減圧しても褥創発生に至った集中治療室入室患者を対象に事例検討を行い、どのような要因が変化し、また各要因がどのように出現して発生に至ったかを明らかにし、発生を予測する方法を検討した。対象は金沢大学医学部附属病院集中治療室に1992年8月〜1994年12月に入室し、日本語版ブレ-デンスケール14点以下の褥創発生危険者でセル型圧切替式エア-マットレスを導入したにもかかわらず発生に至った患者5名であった。方法は、レトロスペクティブな事例検討を行った。褥創発生要因はブレ-デンらの褥創発生要因の概念を基に組織耐久性の側面から抽出した。その結果、1.組織耐久性の中で変化する要因として、38℃以上の発熱、10g/dl以下の低ヘモグロビン、100mmHg以下の収縮期血圧の低下、酸素投与下での100mmHg以下の低酸素分圧、手術または呼吸・循環停止などの全身への侵襲、下熱に伴う全身の発汗であった。2.発生要因の現れ方は、全身への侵襲後に発熱、低ヘモグロビン、収縮期血圧の低下、低酸素分圧が3〜5日以内に重なり褥創発生に至った。これらの要因は、組織における酸素の受容と供給バランスにかかわり、褥創好発部の組織に虚血をもたらすと考える。以上より、褥創発生予測には、発生リスクの査定と引き金となる要因を加えたものが重要であることが示唆された。今後は対象数を増やし、プロスペクティブな検討を行い褥創発生予測スケールの開発を行いたい。研究課題/領域番号:06772234, 研究期間(年度):1994出典：研究課題「褥創発生リスクの高い集中治療室入室患者における褥創発生予防」課題番号06772234（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-06772234/）を加工して作

A Comparison of Techniques for Collecting Skin Microbiome Samples: Swabbing Versus Tape-Stripping

The swabbing and tape-stripping methods have traditionally been used for collecting skin microbiome samples for skin bacterial analysis, although no reports have compared the outcome of these methods for collecting skin bacteria. Our purpose was to show the differences in microbial composition between samples collected using the swabbing and tape-stripping methods, by both the next generation sequencing and culture studies. The skin microbiome was collected by both methods, and the samples were processed for a sequence-based microbiome analysis and culture study. The next-generation sequencing results showed that skin bacteria collected using the tape-stripping method were comparable to those collected using the swabbing method. In the culture study, the tape-stripping method collected a greater number and wider variety of viable skin bacteria than the swabbing method. These results suggest that the tape-stripping method is comparable to the swabbing method for collecting viable skin bacteria, without losing fidelity to the composition of skin microbiome

Relationship between lymphangiogenesis and exudates during the wound-healing process of mouse skin full-thickness wound

金沢大学医薬保健研究域保健学系We considered the relationship among exudate, wound area, angiogenesis, lymphangiogenesis, and reepithelialization during wound healing. Full-thickness wounds were made on the dorsum of mice. The weight of exudate absorbed into the dressing as well as the wound area was determined daily. Sections of the wounds were stained with anti-LYVE-1 and CD31 antibodies. Indian ink was injected into the wound for observing the movement of the exudate on days 3, 5, and 7 after wounding. New epithelium completely covered the wound on day 11. The quantity of exudate peaked on day 1, and then rapidly decreased until it was undetectable on day 11. Most of the Indian ink injected into the wound was retained within the wound and did not flow into the surrounding tissue. New blood vessels showed a uniform distribution in the granulation tissue on day 5. New lymphatics appeared in the granulation tissue approximately 2 days later than the blood vessels and they were distributed toward the center of the granulation tissue on day 11. Thus, reduction of exudate from the wound appears to be related to blood vessels, not lymphatics. However, increasing lymphatics may play a role in the late phase of the wound-healing process. © 2009 by the Wound Healing Society

Effectiveness of Indonesian Honey on the Acceleration of Cutaneous Wound Healing: An Experimental Study in Mice

The purpose to investigate the effectiveness of Indonesian honey in wound healing in comparison with Tegaderm hydrocolloid dressing and Manuka honey. Three groups of male mice were treated to produce two circular full-thickness skin wounds on the dorsum. They were then randomly allocated to receive daily Indonesian honey, Manuka honey or hydrocolloid as a control for treatment application. Macroscopic findings were observed from day 0 to 14 after wounding. Microscopic findings on days 3, 7, 11 and 14 after wounding were obtained. The ratios of wound areas for honey groups on day 3 were smaller than those of the control group. Wound areas of honey groups gradually decreased to almost the same wound area as the control group on day 14, while the wound area of the control group peaked on day 5 and rapidly decreased until day 14. On day 3, myofibroblasts and new blood capillaries in wound tissue of honey groups were observed, but not in the control group. After day 7, microscopic findings were almost the same among all groups. These results indicate that Indonesian honey is almost as effective for wound healing as Manuka honey and Tegaderm hydrocolloid dressing

Influence of the timing of switching a protein-free to a protein-containing diet on the wound healing process in a rat all-layer skin defect

金沢大学医薬保健研究域保健学系We prepared full thickness skin defects in rats fed on a protein-free diet as a hypoproteinaemia model, then switched the animals to a diet containing a normal protein level 1, 6 or 12 days after wounding (inflammatory, granulation and rearrangement phases of the wound healing process) to examine whether improvement in the low-protein state promotes subsequent wound healing. The interval until wound healing in rats fed on a normal protein diet was significantly shorter, whereas that in rats continuously fed on a protein-free diet was significantly longer than those of other groups. Early correction tended to accelerate wound healing. Although wound contraction in groups receiving a protein-corrected or protein-free diet remained similar until 15 days after wounding, thereafter the duration of the rearrangement phase was significantly longer in the protein-free group than in the other groups. The collagen level per unit of granulation tissue area during wound healing was significantly lower in the protein-free group than in the other groups. These findings indicate that protein correction at any time after wounding accelerates wound healing, although early correction is more effective, and reduces the duration of the rearrangement phase more than those of the inflammatory and granulation phases because of the deposit of collagen