Pulmonary Artery Occlusion Research Articles

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension

BackgroundOur aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. Methods and ResultsWe used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation. The median duration of ARHF before sacrifice was 162 (135–189) minutes. Although ventriculoarterial coupling (measured with multibeat pressure-volume loops) and stroke volume decreased after iterative pulmonary embolism and improved with dobutamine, relative pulmonary to systemic pressure increased by 2-fold and remained similarly increased with dobutamine. Circulating high-sensitivity troponin I increased after hemodynamic restoration. We found an increase in right ventricular subendocardial and subepicardial focal ischemic lesions and in expression of autophagy-related protein LC3-II (Western blot) in the ARHF-cPH group compared with the cPH (n = 5) and control (n = 5) groups. ConclusionsWe developed and phenotyped a novel large animal model of ARHF on cPH in which right ventricular ischemic lesions were observed early after hemodynamic restoration.

Abstract 216: Causal Role of Oxidized Lipids in Pulmonary Hypertension Development

Pulmonary arterial hypertension (PAH) is a deadly disease characterized by increased pulmonary arterial pressure and pulmonary vascular occlusion. Recently, we and others demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15-HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). We hypothesized that diets rich in 15-HETE are sufficient to cause PH in wild type mice. We also examined whether 15-HETE or its metabolites are required to cause PH by comparing the effect of 15-HETE with 15-HETE methyl ester, which is a stable form of 15HETE that is not easily metabolized. C57BL/6 male mice were fed for 3 weeks with 15-HETE diet (5μg/day), 15-HETE methyl ester (15-HETE-ME, 5μg/day), or regular chow diet (n=8-21 mice/group). PH development was followed via weekly serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via direct heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&E and Oil red O staining. Echocardiography revealed the first sign of PH in mice on 15HETE diet as early as one week and a significant decrease in the pulmonary arterial acceleration time after 2 weeks of treatment (16.6±1.9 vs. 21.2±1.4 msec, p<0.05). Mice on 15HETE diet also had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p<0.05). Increase in RVSP was concomitant with significantly higher RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p<0.05). Pulmonary arteriolar thickness was also significantly increased in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p<0.05). Our new model of PH is not a model of atherosclerosis as there was no detectable plaque in aorta of the mice on 15-HETE diet. Finally, mice on 15-HETE-ME diet also developed PH as RVSP was significantly higher compared to control (31.3±1.1 vs. 39±3 mmHg, p<0.05). The severity of PH was similar in 15HETE-ME and 15HETE, confirming 15HETE itself and not its metabolites is sufficient to cause PH in wild type mice. We have developed a new and physiologically relevant animal model to study PH as a consequence of oxidized lipids overload as it occurs in humans with PAH.

Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia.

Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT) pulmonary angiography and ventilation/perfusion (V/Q) scintigraphy, chronic thromboembolic pulmonary hypertension (CTEPH) was initially considered the most plausible diagnosis. However, during an attempted pulmonary endarterectomy, loose fibrous tissues were observed in the mediastinum and cryosection of the right pulmonary artery showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot-derived dopamine agonists, which are known to cause cardiac valve fibrosis and less frequently, non-cardiac fibrotic changes. The underlying mechanism is attributed to their interactions with serotonin receptors. There is much evidence that serotonin, a potent vasoconstrictor and mitogen, is involved in the pathogenesis of pulmonary hypertension. In conclusion, as CT and V/Q scintigraphy findings can occasionally be deceptive, physicians should be particularly aware of differential diagnoses in patients without obvious history of venous thromboembolism that are suspected of having chronic thromboembolic pulmonary hypertension.

Pulmonary Infarction: In the Beginning: The Natural History of Pulmonary Infarction

Massive pulmonary emboli can cause an abrupt onset of symptoms simultaneous with large pulmonary artery occlusions. In contrast, the temporal relationship between pulmonary vascular occlusion by smaller emboli and the development of symptoms of pulmonary infarction is unknown. We describe the time interval between embolization and the onset of clinical symptoms and signs compatible with pulmonary infarction. We examined the records of 56 patients with hereditary hemorrhagic telangiectasia (HHT) who underwent therapeutic balloon embolization of pulmonary arteriovenous malformation (PAVM) in a single center after noting that some of them experienced symptoms and signs compatible with pulmonary infarction. Because both the times of embolization and the onset of clinical symptoms were documented in medical records, we were able to calculate the time interval between embolic occlusion of vessels and the onset of symptoms. The records of 56 patients who underwent therapeutic embolization for HHT were examined. Five patients experienced a single episode of pleuritic pain postembolization, and one patient experienced episodes of pleuritic pain after each of two separate embolization procedures. Four of these pleuritic pain events evolved into a complex compatible with pulmonary infarction. The time intervals between embolization and the onset of pleuritic pain in those experiencing the infarction symptoms and signs were 24 hours, 48 ± 4 hours, 65 hours, and 67 hours, respectively. The clinically silent time interval between embolization of a pulmonary artery and the onset of symptoms and signs compatible with lung infarction is 24 hours or greater.

Catheter directed thrombolytic therapy and percutaneous thrombectomy

Abstract 40% of DVTs occur in the femoral and iliac veins and have a high risk of pulmonary thromboembolism and Post Thrombotic Syndrome (PTS), which can be avoided by timely interventional management. Catheter Directed Thrombolytic Therapy (CDTT) and Pharmacomechanical Catheter-Directed Thrombolysis (PCDT), (combination of CDTT with percutaneous mechanical thrombectomy) techniques enhance the efficiency and rate of thrombus removal. It also uncovers the May Thurner syndrome in many cases. Massive Pulmonary Embolism (PE) is associated with high morbidity and mortality due to thrombotic occlusion of main pulmonary artery and/or both major pulmonary arteries leading to severe hypoxemia, pulmonary artery hypertension and cardiogenic shock. Till now, open surgical pulmonary endarterectomy was the only option for prompt restoration of flow in major pulmonary arteries but carried a high mortality in hemodynamically unstable patients. Catheter based pulmonary thromboaspiration and intrapulmonary thrombolysis can be used. We present our experience in 45 consecutive patients of massive PE presenting with cardiogenic shock.

156 Inducers of pulmonary arterial hypertension upregulate the expression of plasma membrane calcium atpase 1 in pulmonary artery smooth muscle cells

Pulmonary arterial hypertension (PAH) is a chronic and life-threatening disease with high morbidity and mortality in adult and paediatric patients. PAH is characterised by a progressive narrowing and occlusion of small pulmonary arteries leading to increased pulmonary resistance, right ventricular hypertrophy, and, finally, right ventricular failure. A large body of data has shown that proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) represent key events in the vascular remodelling of pulmonary arteries that occurs during PAH. Levels of cytoplasmic calcium are an important determinant of PASMC proliferation and migration, and failure in maintaining appropriate levels of intracellular calcium are associated with PAH. The plasma membrane calcium ATPase (PMCA) proteins extrude calcium from the cytosol to the extracellular medium, and in doing so, play a critical role in the modulation of intracellular calcium levels. In this work, we have investigated whether inducers of PAH trigger any changes in the expression of PMCA proteins in PASMCs. Analysis of RNA expression levels for PMCA genes has revealed that treatment of PASMCs with PDGF results in a significant increase in the level of the RNA encoding for the protein PMCA1. Interestingly, PMCA1 RNA levels were also elevated in lungs of rats with monocrotaline-induced PAH. No changes were observed in the RNA levels for PMCA4, the other major PMCA isoform expressed in PASMCs. Although previous studies on the regulation of PMCA1 gene expression have identified functional binding sites for the transcription factors NFAT in the PMCA1 promoter region, we show here that PDGF-mediated upregulation of PMCA1 transcriptional expression is independent of activation of the calcineurin/NFAT signalling pathway. Our results suggest the involvement of PMCA1 in PASMC deregulation during PAH, although determination of the link between increased expression of PMCA1 and PAH requires further investigation.

経皮的心肺補助装置装着後に合併した線溶亢進型播種性血管内凝固のため，抗凝固療法を回避して救命した肺血栓塞栓症の1例(A case of massive pulmonary embolism successfully resuscitated with veno–arterial extracorporeal membrane oxygenation without anticoagulation management due to complication of fibrinolytic phenotype disseminated intravascular coagulation)

75歳の女性。突然発症した呼吸困難を主訴に，当院に救急搬送された。来院時，循環虚脱および低酸素血症を認め，心臓超音波検査で左室の圧排を伴う右室の著しい拡大を認めた。来院15分後に，心肺停止状態となったため，心肺蘇生術を開始した。約2分後に自己心拍が再開したが，循環虚脱が継続したため，経皮的心肺補助装置（veno–arterial extracorporeal membrane oxygenation: VA–ECMO）を導入した。その後に行った肺動脈造影検査で，肺動脈の塞栓像を認め，肺血栓塞栓症と診断した。しかし，線溶亢進型の播種性血管内凝固（disseminated intravascular coagulation: DIC）を合併し，出血傾向を認めたため，抗凝固療法，血栓溶解療法は施行せず，輸血療法およびVA–ECMOを用いた循環呼吸管理を行った。第2病日に，出血傾向，循環呼吸動態が改善したため，VA–ECMOから離脱した。抗凝固療法は，VA–ECMO抜去部の止血が完了した第3病日から開始した。その後の経過は良好であり，第29病日に，神経学的後遺症もなく独歩退院した。心肺停止に至った重症肺血栓塞栓症に，線溶亢進型DICが合併し，急性期に抗凝固療法や血栓溶解療法が施行できない場合でも，出血傾向が改善するまでVA–ECMOによる循環呼吸管理を継続することで救命できる可能性がある。 A 75–year–old woman was admitted to our hospital because of sudden–onset dyspnea. She was in a state of obstructive shock and hypoxia and echocardiography showed right ventricular dilatation. Approximately 15min after arriving at the hospital, she experienced a cardiac arrest; we performed cardiopulmonary resuscitation, and spontaneous circulation restored in 2min. However, as obstructive shock was not resolved, we performed veno–arterial extracorporeal membrane oxygenation (VA–ECMO). Pulmonary angiography revealed pulmonary artery occlusions. Disseminated intravascular coagulation (DIC) was of the fibrinolytic phenotype; it was complicated with pulmonary embolism, and a bleeding tendency was noted. Therefore, blood transfusions were performed and hemodynamic support was provided with VA–ECMO and catecholamines, without anticoagulation and thrombolysis. The following day, her coagulopathy resolved and hemodynamic status recovered; VA–ECMO support was successfully removed. Anticoagulation was started on the 3rd hospital day, when bleeding at the VA–ECMO puncture site was confirmed to have stopped. The patient recovered and was discharged from the hospital on the 29th hospital day. DIC is sometimes complicated with pulmonary embolism in post–cardiac arrest patients. This case shows the possibility that continued hemodynamic and respiratory support with VA–ECMO until bleeding tendency resolves might aid in recovery of patients for whom anticoagulation and thrombolysis are contraindicated. 心肺停止（cardiopulmonary arrest: CPA）蘇生後は，播種性血管内凝固（disseminated intravascular coagulation: DIC）や 1, 2，胸骨圧迫による胸部外傷など 3, 4，出血性合併症を来す場合がある。今回我々は，線溶亢進型DICを合併した肺血栓塞栓症（pulmonary embolism: PE）症例を経験した。出血傾向のため，急性期に抗凝固療法や血栓溶解療法が施行できなかったが，DICが改善するまで経皮的心肺補助装置（veno–arterial extracorporeal membrane oxygenation: VA–ECMO）による循環呼吸管理を継続することで，救命できたため報告する。本症例報告の作成にあたり，個人情報保護法に基づき匿名化し，患者本人の同意を得た。 患 者：75歳の女性，身長145cm，体重42.7kg，body mass index 20.3 現病歴：未治療の下肢静脈瘤の既往はあるが，他の特記すべき既往歴，家族歴，常用薬はない。また，長期臥床や，安静を強いられる長距離移動などの病歴もない。来院当日の起床後，屋外で散歩中に突然，呼吸困難を自覚した後に転倒し，顔面を打撲した。その後，独歩で帰宅したが，患者が呼吸困難を訴えたため，家族が救急要請し当院に搬送された。 来院後経過：来院時，JCS 3–R，血圧94/60mmHg，心拍数104/分，呼吸数30/分，体温35.8℃，SpO2 92%（酸素リザーバーマスク10L/分 投与下）であった。胸部レントゲン写真では肺野に明らかな異常は認めなかったが，12誘導心電図検査ではV1–3誘導で，陰性T波を伴う完全右脚ブロックを（Fig. 1），心臓超音波検査では左室の圧排を伴う右室の著しい拡大を認めた。身体所見上は，呼吸音，心音に明らかな異常を認めなかったが，頸静脈の怒張を認めた。また，転倒時に受傷したと考えられる非活動性の出血を伴う口唇，口腔内の挫創，鼻出血を認めた。両側下肢には網目状静脈瘤を認めた。来院時の血液検査結果は，WBC 8,900/μL，Hb 9.6g/dL，PLT 8.2×104/μL，CK 48U/L，CKMB 18U/L，トロポニンI 0.090ng/mL，BNP 31.3pg/mL，APTT 62sec，PT–INR 1.43，fibrinogen 81mg/dL，D–dimer 114.9μg/mL，AT III 82%であった。 Electrocardiogram on admission. Electrocardiogram showing complete right branch block and a negative T wave in leads V1–3. 来院後，徐々に血圧が低下し，来院15分後にCPA状態（無脈性電気活動）となったため，心肺蘇生術を開始した。気管挿管し，アドレナリン1mgを投与したところ，約2分後に自己心拍が再開したが，循環虚脱が継続した。広範型PEを疑い，来院から43分後に透視下に右大腿動静脈からVA–ECMOを導入した（カテーテルサイズは脱血19.5Fr，送血13.5Fr，テルモ社キャピオックス®システムを使用，2,000回転で駆動開始）。その後，左大腿静脈アプローチで肺動脈造影を施行すると，右上葉動脈，中葉動脈，左肺尖動脈，肺舌動脈などが閉塞しており，PEと診断した（Fig. 2）。左右の肺動脈主幹部には血栓を認めず，VA–ECMO挿入後，循環動態が安定したため，直視下肺動脈血栓摘出術や，カテーテル的治療は不要と判断し，右内頸静脈から肺動脈カテーテルを留置し手技を終了した。しかし，来院から約2時間後より，顔面外傷部およびVA–ECMO，肺動脈カテーテル刺入部から止血困難な出血を認めるようになった。血液検査を再検したところ，Hb 5.6g/dLと貧血の進行およびD–dimer 264.5μg/dL，fibrinogen 50mg/dL未満，PT–INR 2.44，PLT 11.3×104/μLと凝固障害の悪化を認めた。線溶亢進型DICと診断し，顔面外傷部の縫合，鼻腔内へのガーゼタンポン挿入，カテーテル刺入部の圧迫および輸血療法を開始した。経過中，出血性合併症のため，VA–ECMO導入時を含め，抗凝固薬や血栓溶解薬は使用しなかった。VA–ECMO導入後に撮影したCT検査では，肋骨骨折，気胸，胸腹腔内出血などの胸骨圧迫による合併症は認めなかった。 Pulmonary artery angiography. Right upper lobe, middle segmental, left apical segmental, and lingular pulmonary artery branches are occluded with thrombi (arrowheads). Fig. 3aにD–dimer，fibrinogen，PLTの経時的変化および輸血療法の時間経過を示す。来院後16時間までに，赤血球濃厚液14単位，新鮮凍結血漿30単位，濃厚血小板20単位の輸血を行い，凝固障害は改善し，Hbは9.2g/dLまで上昇した。Fig. 3bにVA–ECMOの血液流量，肺動脈カテーテルで測定した心拍出量の経時的推移を示す。最大量ドブタミン5μg/kg/min，ノルアドレナリン0.1μg/kg/minを使用したが，抗凝固療法や血栓溶解療法を施行しなかったにも関わらず，心拍出量は徐々に上昇し，導入23時間後にVA–ECMOを離脱した。集中治療室に入室後に施行した超音波検査で，両側下肢深部静脈内に浮遊血栓を多数認めたため，下肢深部静脈血栓症がPEの原因と考え，VA–ECMO抜去後，回収可能型下大静脈フィルターを留置した。抗凝固療法は，出血傾向が消失し，VA–ECMO抜去部の止血が完了した第3病日から，未分画ヘパリンの持続投与を500単位/hrで開始し，APTTがコントロール値の1.5～2.5倍になるように調節した。 Clinical course of the patient. Fig. 3a shows the results of blood tests. Two–way arrow indicates the duration of blood transfusions. –●– D–dimer, –▲– Fibrinogen, –■– PLT Fig. 3b shows the hemodynamic status, and the two–way arrow shows the duration of catecholamine use. –●– CO, –▲– ECMO flow PLT: platelet count, CO: cardiac output, VA–ECMO: veno–arterial extracorporeal membrane oxygenation 第5病日に，人工呼吸器から離脱した。食事摂取量が安定した後，第12病日よりワルファリンの内服を3mg/日で開始した。下肢静脈血栓の消失した第14病日に，下大静脈フィルターを抜去した。未分画ヘパリンは，ワルファリンによる抗凝固効果が得られた第20病日まで継続した。その後の経過は良好であり，第29病日に独歩退院した。退院時のワルファリン服用量は3.5mg/日であり，PT–INRは1.61だった。 後日測定した，プロテインC活性はワルファリン3.5mg服用下で95%，プロテインS活性は90%，ループスアンチコアグラントは蛇毒法で1.29，抗カルジオリピン抗体（IgG）8U/mL以下，抗カルジオリピンβ2グリコプロテインI複合体抗体1.2U/mL以下，と正常範囲であり，先天的な血液凝固能亢進素因は認めなかった。本症例における下肢深部静脈血栓症の原因は，下肢静脈瘤による下肢血流停滞が原因と考え，永続的な抗凝固療法の継続を指示した。 「肺血栓塞栓症および深部静脈血栓症の診断，治療，予防に関するガイドライン」 5では，心肺蘇生を要する，あるいは高度なショックが遷延する広範型PEには，VA–ECMOによる循環呼吸補助を行ったうえで，血栓溶解療法，カテーテル的治療，外科的血栓摘出術などを行うことを推奨している。血栓溶解療法は，迅速な血栓溶解作用や血行動態改善作用に優れており，循環破綻を伴う重症PEの予後改善につながるとの報告 6があるが，出血性合併症のリスクがある 5, 6。 CPA蘇生後症例は，その心停止原因に関わらず，線溶亢進型DIC 1, 2や，胸骨圧迫による肋骨骨折，気胸，内胸動脈損傷などの合併報告 3, 4があり，出血性合併症のリスクが高い。とくに，extracorporeal cardiopulmonary resuscitation（ECPR）症例での出血性合併症の報告は多く，Iwashitaら 7は未分画ヘパリン3,000単位を投与したECPR 32症例のうち，3例（9%）に外科的処置や血管塞栓術を要する出血が合併したと報告している。また，Hashibaら 8は，ECPRを施行したPEによるCPA症例12例のうち，5例に血栓溶解療法を行ったところ，6例（50%）に出血性合併症を認めたと報告している。 CPA蘇生後症例に合併する線溶亢進型DICは，組織低灌流や虚血に伴い産生される内因性線溶物質が引き起こすと考えられており 1，心停止時間が長いほどその合併頻度は高くなる 2。本症例は心停止時間が約2分間と短時間であったにも関わらず，DICを合併した。広範型PEは心停止の有無に関わらず消耗性の凝固障害を合併することが知られている 9。本症例の来院時血液検査から算出した急性期DICスコアは6点であり，本症例は，来院時すでに，PEに伴う組織低灌流や虚血，あるいは凝固因子の消耗により，線溶亢進型DICが合併しており，VA–ECMO導入後も遷延したと考えた。 出血を伴う線溶亢進型DICに対しては，未分画ヘパリンの投与は禁忌であり，濃厚血小板，新鮮凍結血漿の補充が必要となる 10。しかしながら，DIC治療の根幹は基礎疾患，本症例でいえばPEの治療である 10。本症例は，出血性合併症のため抗凝固療法や血栓溶解療法などのPEの特異的治療が施行できず，VA–ECMOを用いた循環呼吸補助および合併したDICに対する輸血療法のみを施行したにも関わらず，入院翌日にはVA–ECMOから離脱できた。野村ら 11は，肺動脈近位部の血栓は，胸骨圧迫により破砕される可能性を報告している。本症例でも，肺動脈造影時に，肺動脈主幹部には血栓を認めず，上記機序による有効肺血管床の回復が血行動態の改善につながった可能性が考えられた。また，線溶亢進型DIC合併の過程で産生された内因性線溶物質が，自ら肺動脈内の血栓溶解に働きかけた可能性も示唆された。 VA–ECMO使用時には，ACTを180–200sec前後に維持するように抗凝固を行うことが推奨されている 12。本症例では，抗凝固薬を使用せずVA–ECMOを使用したが，回路トラブルは起こらなかった。今回用いたECMOは，テルモ社のキャピオックス®であり，血液流路面には，血液適合性ポリマーコーティングが施されている。同コーティングおよび患者が線溶亢進状態であったため，回路トラブルが起こらなかったと考えた。 なお，本症例では測定していないが，凝固活性化の指標となるTATや，線溶活性化の指標となるPICの測定は，DICの病態把握に有用であり 10，測定を考慮すべきであった。 線溶亢進型DICを合併した重症PE症例を経験した。CPAを合併したPEの診療の際には，胸骨圧迫に伴う胸部外傷や，線溶亢進型DICなどの出血性合併症に注意し，抗凝固療法や抗凝固療法の適応は，慎重に評価する必要がある。 本論文における利益相反はない。

Predictors to Intravenous Fluid Responsiveness.

Management with intravenous fluids can improve cardiac output in some surgical patients. Management with static preload indicators, such as central venous pressure and pulmonary artery occlusion pressure, has not demonstrated a suitable relationship with changes in the cardiac output induced by intravenous fluid therapy. Dynamic indicators, such as the variability of arterial pulse pressure or stroke volume variation, have demonstrated a suitable relationship. Since improvement in cardiac output does not guarantee an adequate perfusion pressure, in patients with hypotension, it is also necessary to know whether arterial pressure will also increase with intravenous fluid therapy. In this regard, the functional assessment of arterial load by dynamic arterial elastance could help to determine which patients will improve not only their cardiac output but also their mean arterial pressure.

Microwave Ablation of the Lung in a Porcine Model: Vessel Diameter Predicts Pulmonary Artery Occlusion.

To determine the size of pulmonary artery (PA) at risk for occlusion during percutaneous microwave ablation and to assess the effect of vessel diameter, number, and patency, on ablation zone volume. Computed tomography (CT) fluoroscopy-guided percutaneous microwave ablations were performed in 8 pigs under general anesthesia. All ablations were performed at 65W for 5min with a single 17-gauge antenna positioned in the central third of the lungs. A CT pulmonary angiogram was performed immediately after the ablations. The maximum diameter, number and patency of PA branches within each ablation zone were recorded. Ablation volumes were measured at gross dissection and with CT. Student's t test was used to compare ablation zone volumes among groups. Twenty-one pulmonary ablations were performed. Six of the ablation zones (29%) contained at least 1 occluded PA branch. The mean diameter of the occluded PA branches in the ablation zones (2.4mm; range, 2.0-2.8mm) was significantly smaller than non-occluded PA branches (3.7mm; range: 2.1-6.9mm; p=0.009). No PA branches ≥3mm in size were occluded. There was no significant difference in volume of gross ablation zones that contained occluded versus non-occluded PAs (p=0.42), one versus multiple PAs (p=0.71), or PAs <3mm versus ≥3mm in diameter (p=0.44). PAs ≥3mm in size have a low risk for iatrogenic occlusion during percutaneous microwave ablation. The presence of multiple adjacent PA branches, an occluded PA branch, and a vessel diameter ≥3mm within the ablation zone had no observed effect on ablation zone volume.

Surgical embolectomy for high-risk acute pulmonary embolism is standard therapy.

Acute massive pulmonary embolism (AMPE) is a life-threatening condition that often induces rapid haemodynamic deterioration. The mortality of surgical embolectomy is still poor in patients with preoperative cardiopulmonary arrest (CPA). We analysed the outcome of surgical pulmonary embolectomy for haemodynamically unstable patients. Thirty-one patients underwent surgical embolectomy for haemodynamically unstable AMPE. The indications for surgical embolectomy were (i) <7 days from onset, (ii) haemodynamically unstable, (iii) massive clots in bilateral pulmonary arteries or unilateral pulmonary artery occlusion with a floating clot in the main pulmonary artery or right atrium and (iv) right ventricular dilatation in transthoracic echocardiography. Eight (25.8%) patients had cardiopulmonary arrest. Nine (29.0%) patients received preoperative percutaneous cardiopulmonary support (PCPS). The mean original Pulmonary Embolism Severity Index (PESI) and simplified PESI scores were 158 ± 51 and 2.4 ± 0.9, respectively. The hospital mortality rate was 12.9% (n = 4). Two patients died of hypoxia. Multiorgan failure occurred by sepsis and by right ventricular failure in 1 patient each. No hospital deaths occurred in patients with preoperative PCPS (n = 9). The mean follow-up period was 47.7 ± 35.9 months (range, 3 - 134 months) and the 5-year survival rate was 83.2 ± 6.9%. Postoperative pulmonary artery pressure significantly decreased from 52.7 to 25.8 mmHg. Surgical embolectomy for high-risk AMPE patients has an excellent operative mortality and long-term outcome. Preoperative PCPS may lead to an immediate stable haemodynamic state and improve surgical embolectomy results, especially in high-risk patients (e.g. those with preoperative CPA). Surgical embolectomy for AMPE is an established operation and considered as the first-line therapy.

Development of a Model of Pediatric Lung Failure Pathophysiology.

A pediatric artificial lung (PAL) is under development as a bridge to transplantation or lung remodeling for children with end-stage lung failure (ESLF). To evaluate the efficiency of a PAL, a disease model mimicking the physiologic derangements of pediatric ESLF is needed. Our previous right pulmonary artery (rPA) ligation model (rPA-LM) achieved that goal, but caused immediate mortality in nearly half of the animals. In this study, we evaluated a new technique of gradual postoperative right pulmonary artery occlusion using a Rummel tourniquet (rPA-RT) in seven (25-40 kg) sheep. This technique created a stable model of ESLF pathophysiology, characterized by high alveolar dead space (58.0% ± 3.8%), pulmonary hypertension (38.4 ± 2.2 mm Hg), tachypnea (79 ± 20 breaths per minute), and intermittent supplemental oxygen requirement. This improvement to our technique provides the necessary physiologic derangements for testing a PAL, whereas avoiding the problem of high immediate perioperative mortality.

Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload.

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.

Noninvasive stroke volume variation using electrical velocimetry for predicting fluid responsiveness in dogs undergoing cardiac surgery

ObjectiveTo evaluate the ability of a noninvasive cardiac output monitoring system with electrical velocimetry (EV) for predicting fluid responsiveness in dogs undergoing cardiac surgery. Study designProspective experimental trial. AnimalsA total of 30 adult Beagle dogs. MethodsStroke volume (SV), stroke volume variation (SVV) and cardiac index were measured using the EV device in sevoflurane-anaesthetized, mechanically ventilated dogs undergoing thoracotomies for experimental creation of right ventricular failure. The dogs were considered fluid responsive if stroke volume (SVI; indexed to body weight), measured using pulmonary artery thermodilution, increased by 10% or more after volume loading (10 mL kg–1). Relationships of SVV, central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) with SVI were analysed to estimate fluid responsiveness. ResultsBetter prediction of fluid responsiveness, with a significant area under the receiver operating characteristic curve, was observed for SVV (0.85±0.07; p=0.0016) in comparison with CVP (0.65±0.11; p=0.17) or PAOP (0.60±0.12; p=0.35), with a cut-off value of 13.5% (84% specificity and 73% sensitivity). Conclusions and clinical relevanceSVV derived from EV is useful for identification of dogs that are likely to respond to fluids, providing valuable information on volume status under cardiothoracic anaesthesia.

Surgical Embolectomy for Acute Pulmonary Thromboembolism.

Acute pulmonary thromboembolism is a catastrophic event, especially for hospitalized patients. The prognosis of pulmonary thromboembolism depends on the degree of pulmonary arterial occlusion. The mortality of massive pulmonary embolism is reportedly as high as 25% without cardiopulmonary arrest and 65% with cardiopulmonary arrest. In patients with unstable hemodynamics due to pulmonary thromboembolism, surgical pulmonary embolectomy is indicated for patients with a contraindication to thrombolysis, failed catheter therapy, or failed thrombolysis. Thrombolytic therapy adds an additional burden on patients who are at risk of potential hemorrhagic complications. It is also indicated if patients are already on a veno-arterial extra-corporate membrane oxygenator for circulatory collapse or cardiopulmonary arrest. The outcome for patients who require cardiopulmonary resuscitation for longer than 30 minutes is poor. Therefore, early triage for massive and sub-massive pulmonary embolism is crucial. A team approach including a cardiovascular surgeon may be effective to save critically ill patients. Prompt removal of emboli reduces the right ventricular load with quick recovery of cardiopulmonary function in the early postoperative period. A recent series reported excellent results, with in-hospital mortality of less than 10%. Surgical pulmonary embolectomy is an effective, safe, and easy procedure to save critical patients due to pulmonary thromboembolism.

From thrombosis to fibrosis in chronic thromboembolic pulmonary hypertension

The pathomechanisms underlying the development of thrombofibrotic pulmonary artery occlusions in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) are largely unknown. The aim of this study was to allocate distinct cellular processes playing a role in thrombus resolution, such as inflammation, hypoxia, proliferation, apoptosis and angiogenesis, to different stages of thrombofibrotic remodelling. A total of 182 pulmonary endarterectomy (PEA) specimens were collected from 31 CTEPH patients. To facilitate co-localisation, Tissue MicroArrays were prepared and processed for (immuno)-histochemistry and confocal fluorescence microscopy. Murine venous thrombus formation and resolution was examined after inferior vena cava ligation. PEA tissues exhibited five morphologically distinct regions predominantly consisting of either fibrin-, erythrocyte- or extracellular matrix-rich thrombus, myofibroblasts, vessels or fibrotic tissue, and were found to resemble chronological stages of thrombus resolution in mice. Cellularity was highest in vessel-rich regions, and numerous cells were strongly positive for HIF1α or HIF2α as well as markers of activated VEGF signalling, including endothelial nitric oxide synthase. On the other hand, negative regulators of angiogenic growth factor signalling and reactive oxygen species were also highly expressed. Immune cells, primarily macrophages of the M2 subtype and CD117 haematopoietic progenitors were detected and highest in vascularised regions. Our findings demonstrate the simultaneous presence of different stages of thrombus organisation and suggest that hypoxia-induced endothelial, mesenchymal and immune cell activation may contribute to thrombofibrosis in CTEPH. This systematic histological characterisation of the material obstructing pulmonary vessels in CTEPH may provide a valuable basis for further studies aimed at determining causal factors underlying this disease.

The Harmful Effects of Hypertonic Sodium Lactate Administration in Hyperdynamic Septic Shock.

Hypertonic sodium lactate (HTL) expands intravascular volume and may provide an alternative substrate for cellular metabolism in sepsis. We compared the effects of HTL, hypertonic saline (HTS), 0.9% ("normal") saline (NS) and Ringer's lactate (RL) on hemodynamics, sublingual and renal microcirculation, renal, mesenteric and brain perfusion, renal and cerebral metabolism, and survival in anesthetized, mechanically ventilated, adult female sheep. Animals (7 in each group) were randomized to receive a bolus (over 15-min) of 3 mL/kg 0.5 M HTL, 3 mL/kg 3% HTS, 10.8 mL/kg NS, or 10.8 mL/kg RL at 2, 6, and 10 h after induction of fecal peritonitis, followed by 2-h infusions of 1 mL/kg/h (HTL/HTS groups) or 3.6 mL/kg/h (NS/RL groups). Animals also received RL and hydroxyethyl starch (ratio 1:1) titrated to maintain pulmonary artery occlusion pressure at baseline levels throughout the experiment. Animals were observed until their spontaneous death. Fluid balance was lower in the HTL and HTS groups than in the other groups from 4 h. Hemodynamic variables were similar among groups during the first 12 h, but thereafter the HTL group had more pronounced decreases in blood pressure and cardiac function. Sublingual and renal microcirculatory abnormalities occurred earlier in the HTL group. Kidney and brain perfusion decreased more rapidly in the HTL group. Median survival times were significantly shorter in the HTL (17 h) and NS (16 h) groups than in the HTS (22 h) or RL (20 h) groups (P = 0.0029). In conclusion, in an ovine model of septic shock, administration of HTL was associated with earlier onset impaired tissue perfusion and shorter survival time. These observations raise concerns about use of HTL in septic shock.

Cyanoacrylate Glue and Central Venous Access Device Insertion

Patients with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals (TOF/PA/MAPCAs) undergoing unifocalization surgery are at risk for prolonged postoperative respiratory failure. We sought to understand whether patients undergoing reconstruction and incorporation of occluded pulmonary arterial branches were at risk for worse postoperative outcomes.We performed a retrospective chart review to identify patients who underwent unifocalization or unifocalization revision with incorporation of occluded pulmonary artery branches. Patients with and without occluded branches were compared, with a focus on clinical outcomes.We studied 92 patients who underwent unifocalization procedures between 2010 and 2014, 17 (18%) of whom underwent reconstruction of occluded pulmonary artery branches. Patients with occluded vessels were more likely to require staged unifocalization procedures, although more than two thirds of this cohort eventually underwent complete intracardiac repair. Durations of mechanical ventilation, intensive care, hospital stay, and the need for early reoperation were similar between the two groups.Occluded pulmonary arterial branches can be safely recruited into the pulmonary vasculature in patients with TOF/PA/MAPCAs without a significant difference in postoperative outcomes compared with patients who did not have an occluded branch. Incorporation of occluded branches may also facilitate ultimate complete intracardiac repair in this complex population of patients.

Optimal transducer levels for central venous pressure and pulmonary artery occlusion pressure monitoring in supine and prone positions in pediatric patients

Background: This study was performed to investigate optimal central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) transducer levels in supine and prone positions in pediatric patients. Methods: Chest tomography images of 213 children aged ≤ 10 years were reviewed. Distances from the back to the uppermost blood level of both atria and their ratios to the largest anteroposterior (AP) diameter of the thorax were calculated for the supine position. For the prone position, same distances and ratios were calculated from the anterior chest. Subgroup analysis was performed to evaluate if there were significant differences in each ratio according to age. Results: In the supine position, the ratio of the uppermost blood level of the right atrium (RA) and left atrium (LA) to the largest AP diameter of the thorax was 80-85% and 60-65%, respectively. The ratio of the most posterior blood level of the RA and LA to largest AP diameter of thorax was 45-50% and 55-60%, respectively, from the anterior chest in the prone position. Subgroup differences in each ratio were within the range of 5%. Conclusions: In pediatric patients, CVP and PAOP transducers should be differently placed according to supine and prone positions. The influence of age was minimal on the level of each transducer. Keywords: Central venous pressure; Position; Transducer

Clinical analysis of 25 cases of Behçet′s disease complicated with pulmonary hypertension

Objective To understand the clinical features of Behcet′s Disease(BD) with pulmonary hypertension(PH). Methods The etiology, clinical features, treatment and prognosis of 25 patients with Bahcet′s disease (BD) complicated with pulmonary hypertension (PH) admitted in Peking Union Medical College Hospital from January 2000 to August 2015 were retrospectively reviewed. Results Total 912 BD patients were hospitalized during the same period, among whom 25 cases were complicated with PH accounting for 3%. There were 15 males (60%) and 10 females (40%), with the mean age of (33±12) years (range 19 to 66 years). The median interval from the diagnosis of BD to the onset of PH was 1 year (range 0 to 40 years). The most common cause of PH was heart valve disease (n=10, 40%), followed by pulmonary arterial stenosis or occlusion (n=6, 24%), pulmonary arterial aneurysm with thrombus (n=1, 4%), pulmonary thrombosis (n=1, 4%), cardiomyopathy (n=1, 4%); there were no causes identified in 6 cases (24%). Pulmonary arterial pressures estimated by echocardiography were 40 to 117 mmHg(1 mmHg=0.133 kPa) with a mean pressure of (60±22) mmHg. When the PH developed, elevated erythrocyte sedimentation rate (ESR) and increased hypersensitive C-reactive protein (hs-CRP) were founded in 48% (11/23) and 82% (14/17) of patients, respectively. After treated with glucocorticoid(96%, 24/25), immunosuppressive agents(92%, 23/25), anticoagulation or thrombolysis(36%, 9/25)and specific targeted vasodilator(32%, 8/25), the levels of ESR and hs-CRP declined in 91% (10/11) and 71% (10/14) of patients, respectively; and pulmonary arterial systolic pressure declined in 50% of cases (8/16). Among 9 patients followed for 2 to 96 months, 4 died, 1 aggravated, 2 kept stable and 1 improved. Conclusion PH is an uncommon complication in disease.Heart valve disease, pulmonary artery involvement are the major causes of PH. The therapeutic effect and prognosis are poor. Key words: Behcet′s disease; Pulmonary hypertension

The effect of dexmedetomidine on left ventricular synchronization in patients undergoing coronary artery bypass grafting

Objective This study was designed to investigate the role of dexmedetomidin(Dex) on left ventricular synchronization in patients undergoing coronary artery bypass grafting(CABG) with CPB. Methods Twenty-one patients were selected using a random number table. These patients were classified as New York Heart Association(NYHA) class Ⅱ, Ⅲ and ASA physical statusⅡ,Ⅲ with age of 45-74 y and weight of 52-85 kg. They were further divided into Dex group(group D, n=10) and control group(group C, n=11). After stopping CPB for 15 min, a loading dose of Dex at 0.5 μg/kg was injected intravenously 10 min after stopping CPB for 15 min followed by infusion at 0.5 μg·kg-1·h-1 until the end of operation in group D, while equal volume of normal saline was given in group C. At the time of before sternotomy(T0), stopping CPB for 15 min(T1), injection of Dex for 30 min(T2) and for 1 h (T3), the MAP, HR, CVP, pulmonary artery occlusion pressure(PAOP) and transesophageal echocardiography(TEE) monitoring indicators including left ventricular ejection fraction (LVEF) and cardiac output(CO), stroke volume(SV), standard deviation of time to maximum systolic velocity of the 17 left ventricular segments of longitudinal strain(Tssl-17-SD) and standard deviation of time to maximum systolic velocity of the 16 left ventricular segments of circumferential strain(Tssc-16-SD) were recorded. Results The HR were statistically lower in group D[(71.0±5.4), (69.3±2.8) bpm] than those in group C[(89.5±14.7), (89.4±14.0) bpm] at T2, T3(P<0.05). CO in group D[(4.4±1.2) L/min] was statistically lower than that in group C[(5.8±1.5) L/min] at T2(P<0.05). Compared with group C, Tssl-17-SD was statistically increased at T2 in group D(P<0.01). Conclusions In patients undergoing CABG with CPB, the injection of Dex after CPB may inhibit the synchronized movement of the left ventricular longitudinal strain. Key words: Dexmedetomidine; Coronary artery bypass grafting; Left ventricle; Systolic synchrony; Standard deviation of time to maximum systolic velocity