Using hemoglobin vesicles to treat operative hemorrhagic shock after pneu- monectomy in dog models: an experimental study.

Hemoglobin vesicles (HbVs), considered as red blood cell substitutes, are liposomes encapsulating purified hemoglobin, with a phospholipid bilayer membrane (diameter: 250 nm; P50, 28 Torr). In this study, we aimed to investigate HbV function during hemorrhagic shock in lung resection and analyze the details of oxygen delivery. Left pneumonectomy was performed in dogs under mechanical ventilation, followed by rapid exsanguination of approximately 30% of the total circulating blood volume, which led to shock, reducing the mean arterial pressure (MAP) by approximately 60% of baseline. Subsequently, either 5% human serum albumin (HSA) or HbVs suspended in 5% HSA were infused for resuscitation. The MAP only recovered to 75% of baseline after HSA administration, but fully recovered (100%) after HbV administration, with significant differences between the groups (P < 0.005). Oxygen delivery was restored in the HbV group and was significantly higher than that in the HSA group (P < 0.0001). The infusion of HbVs dispersed in a 5% HSA solution compensated for the rapid loss of approximately 30% of the total circulating blood volume in a dog pneumonectomy model, even with impaired lung function. Thus, HbVs can be used for resuscitation from hemorrhagic shock during thoracic surgery.

Early reperfusion with hemoglobin vesicles into tracheal subepithelial capillaries in a mouse tracheal transplant model.

Hemoglobin vesicles (HbVs), liposomes containing concentrated hemoglobin extracted from outdated human red blood cells (RBC), are artificial oxygen carriers with a small particle size. To evaluate the reperfusion of capillaries with HbVs in a tracheal transplant model and compare it with that of RBC. Isogenic mice were used as donors and recipients in a parallel trachea transplant model. Both ends of the donor trachea were anastomosed end-laterally to the recipient trachea to form in parallel. After transplantation, 0.3 mL of HbV solution (Hb concentration, 10 g/dL) was administered via the tail vein. The recipients were euthanized 1, 4, 6, and 8 h after surgery (n = 5 in each group). The tracheas were harvested, and tracheal subepithelial capillaries (SEC) reperfusion was histologically evaluated. A significant number of particles defined as HbV by electron microscopy were observed in the SEC of the grafted tracheas 4 h after the transplant surgery and HbV administration when no RBC were found in the SECs. The number increased 6 and 8 h later. Our findings suggest that HbVs, which are smaller than RBC, can reperfuse the capillaries of grafts earlier than RBCs after transplantation and contribute to the oxygenation of transplanted tissues.

Unilateral versus bilateral cerebral perfusion during aortic surgery for acute type A aortic dissection: a multicentre study.

OBJECTIVES: The aim of this retrospective multicentre study was to investigate and compare clinical outcomes of unilateral and bilateral antegrade cerebral perfusion (ACP) strategies on cerebral protection during surgery for type A aortic dissection. METHODS: Data from 646 patients who underwent surgical repair of thoracic type A aortic dissection using unilateral and bilateral ACP with moderate hypothermic circulatory arrest in 3 cardiac surgical institutions between 2008 and 2018 were analysed. Propensity matching was performed to assess which technique ensured better outcomes. RESULTS: Unilateral and bilateral ACP techniques were performed in 250 (39%) and in 396 (61%) patients, respectively. Propensity score analysis identified 189 matched pairs. In the matched cohort, the lowest core temperature was 27.5°C and 28°C in the bilateral and unilateral groups, respectively (P < 0.001). The unilateral technique required significantly shorter aortic cross-clamp and cardiopulmonary bypass times than bilateral technique [82 min vs 100 min (P < 0.001); 170 min vs 195 min (P < 0.001)]. The 30-day mortality was comparable (P = 0.325). The bilateral group reported a significantly higher incidence of permanent neurologic deficits (P < 0.001), left brain hemisphere stroke (P = 0.007) and all-combined complications (P < 0.001). Ten-year survival was comparable (P = 0.45). CONCLUSIONS: Unilateral and bilateral ACP are both valid brain protection strategies in the landscape of aortic arch surgery. While admitting all the study limitations, unilateral technique could offer some clinical advantages. CLINICAL REGISTRATION NUMBER: 76049.

[Metastatic Cardiac Tumor in the Left Atrium from Esophageal Cancer].

Metastatic cardiac lesions are clinically silent and are usually found a necropsy. The most common primary tumor resulting in cardiac metastases is carcinoma of the lung, with there being only a few reports of metastases from esophageal cancer. We report two cases of metastatic cardiac tumors in the left atrium from esophageal cancer and perform a review of the literature. Case 1:A 62-year-old woman underwent esophagectomy and adjuvant chemotherapy. No other metastases were observed. Case 2:A 49-year-old man also underwent esophagectomy and adjuvant chemotherapy for lymph node and liver metastases. In both patients, the left atrial tumors were detected on recent follow-up computed tomography. Left atrial tumors often cause cerebral emboli with neurological sequelae. Therefore, surgical resection and cryo-ablation for the prevention of local recurrence were performed on the metastatic tumors. Local recurrence was not observed after the surgery in both patients. Although chemotherapy is usu-ally the most beneficial treatment for metastatic cardiac lesions, left atrial tumor should be treated with surgical resection because of the high risk of cerebral emboli. We suggest that surgical resection with cryo-ablation may prevent local recurrence.

Immediate effects of systemic administration of normal and high O2-affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model.

BACKGROUND: Haemoglobin vesicles (HbVs) are red blood cell (RBC) substitutes with a phospholipid bilayer membrane and a polyethylene modified surface (diameter=250 nm; P50=28 Torr). They can be preserved for years and can be used in patients of all blood types without the risk of infection. Their oxygen affinity can be modified by changing the allosteric effectors. METHODS: Left pneumonectomy was performed under mechanical ventilation on rats, followed by rapid exsanguination of ~30% of the total circulating blood volume. Rat RBCs shed in 5% human serum albumin (HSA) solution (rat RBC), HbV with high oxygen affinity in 5% albumin solution (low-P50 HbV, P50=9 Torr), normal HbV suspended in 5% albumin (HbV, P50=28 Torr) or 5% HSA was infused for resuscitation. Haemodynamics and oxygenation were evaluated. RESULTS: Systemic arterial blood pressure significantly decreased after exsanguination and increased after each infusion. In the HbV, low-P50 HbV and rat RBC groups, all rats were liberated from mechanical ventilation and blood pressure was stabilised, whereas 50% of the rats in the HSA group died within 1 hour after weaning from mechanical ventilation. The PaO2 in arterial blood for 1 hour after liberation from mechanical ventilation in the rat RBC, HbV and low-P50 HbV groups was 59.4±12.5, 58.3±10.1 and 70.5±14.5 mm Hg, respectively. The PaO2 in the low-P50 HbV group was significantly higher than those in the rat RBC and HbV groups (p=0.05 for both). Serum lactate elevations due to hypoxic damage were minimised by HbV, low-P50 HbV as well as rat RBCs. CONCLUSIONS: The oxygen-carrying ability of HbV was comparable to that of rat RBCs, even under impaired lung function after pneumonectomy. HbVs with high oxygen affinity may have more beneficial effects on oxygenation in pulmonary resection.

Association between false lumen segmental arteries and spinal cord ischemia in type A acute aortic dissection.

BACKGROUND: Spinal cord ischemia (SCI) and paraplegia are complications of surgery for type A acute aortic dissection (TAAAD). Since the segmental arteries play a key role in SCI, this study evaluated the association between SCI and false lumen segmental arteries (FLSAs: segmental arteries originating from the false lumen). METHODS: The study included 101 consecutive TAAAD patients (mean age, 66±13; range, 34-89 years) who underwent surgery from January 2011 to April 2017. The diagnosis of TAAAD and the number of FSLAs were determined by preoperative computed tomography (CT). Patients were divided into two groups according to the number of FLSAs at the Th9-L2 level: Group A (N.=13), ≥8 FLSAs; and group B (N.=88), ≤7 FLSAs. Preoperative, perioperative, and postoperative findings were compared between the groups, and risk factors for SCI were evaluated. RESULTS: The frequency of preoperative paralysis was significantly higher in Group A than Group B (P=.0070). The overall incidence of postoperative SCI was 8% (8/101) and significantly higher in Group A than Group B (5/13 [45%] vs. 3/88 (4%), P<0.0001). Hospital mortality was 8% (8/101) and significantly higher in Group A than Group B (3/13 [23%] vs. 5/88 [6%], P=.0302). Multivariate analysis showed that the independent risk factors for SCI were ≥8 FLSAs at Th9-L2 (odds ratio [OR], 20.4; 95% confidence interval [95% CI], 3.34-124.9, P=0.0011) and diabetes mellitus (OR, 22.3; 95% CI, 1.69-294.5; P=0.0184). CONCLUSIONS: In patients who underwent surgery for TAAAD, ≥8 FLSAs at the Th9-L2 levels on preoperative CT was a risk factor for SCI.

Abdominal aortic aneurysm with occlusion of three primary mesenteric vessels treated by surgery with perfusion of the left iliac artery†.

A 64-year-old woman who underwent thoraco-abdominal aortic replacement for a Crawford type II aneurysm 11 years ago was referred to our hospital because of a residual juxtarenal abdominal aortic aneurysm. The coeliac, superior mesenteric and inferior mesenteric arteries were occluded. Collateral vessels from the left internal iliac artery to these 3 mesenteric arteries had developed. We performed open aneurysm repair using an extracorporeal circuit to maintain collateral flow to these mesenteric arteries.

[Redo Valve Replacement of Wada-Cutter Prosthetic Valve at Tricuspid Valve Position 47 Years After Implantation;Report of a Case].

We experienced an explantation of Wada-Cutter prosthetic tilting disk valve of 47 years after implantation. The patient was 53 years old female who underwent the 1st operation for Ebstein's anomaly, which included tricuspid valve replacement (TVR), closure of atrial septal defect (ASD) and posterior annulorrhaphy when she was 6 years old. She was doing well after the 1st operation without symptom,but dyspnea and systemic edema worsened recently though increased admission of diuretics. Echocardiography revealed severe tricuspid valve stenosis, severe tricuspid valve insufficiency, and increased right atrium volume. The tilting disk of the valve was almost fixed. The patient underwent repeat TVR. The explanted Wada-Cutter valve was covered by pannus the whole casing and disk. The structure of the valve was preserved but the occlusion disk was almost fixed by pannus formation, not distorted or dislodged.

Comparison of Transcarotid vs. Transfemoral Transcatheter Aortic Valve Implantation.

BACKGROUND: Recently, the carotid artery has been used as an alternative approach for transcatheter aortic valve implantation (TAVI). The aim of this study was to prove the safety and feasibility of transcarotid (TC) vs. transfemoral (TF) TAVI. Methods and Results: This retrospective study enrolled 726 consecutive patients with severe symptomatic aortic stenosis. All patients underwent TC-TAVI or TF-TAVI at Hôpital Haut-Lévèque, Bordeaux Heart University Hospital between September 2012 and October 2017. The TC-TAVI (n=83) and TF-TAVI (n=643) groups were compared statistically. The EuroSCORE II was significantly higher (8.2±6.7 vs. 6.4±5.5; P=0.007) and rates of current smoking, dyslipidemia and peripheral arterial disease were higher in the TC-TAVI than TF-TAVI group. All TC-TAVIs and 9.3% of TF-TAVIs were performed under general anesthesia. Radiation time was significantly shorter in the TC-TAVI than TF-TAVI group (14.5±6.0 vs. 23.0±10.8 min; P<0.001). Postimplant balloon valvuloplasty was performed more frequently in the TF-TAVI than TC-TAVI group (7.2% vs. 19.4%; P=0.006). Postoperative echocardiographic data were similar between the 2 groups, and there were no significant differences in 30-day mortality (8.4% vs. 5.0%; P=0.189) or stroke rate (1.2% vs. 2.6%; P=0.428) between the TF-TAVI and TC-TAVI groups. CONCLUSIONS: The feasibility and 30-day safety of TC-TAVI and TF-TAVI are similar. When TF-TAVI is not suitable anatomically for a particular patient, TC-TAVI is a preferable alternative.

The long-term outcomes of partial arch repair using the frozen elephant trunk technique for distal arch aortic aneurysm.

PURPOSE: The purpose of this study was to evaluate the long-term results of partial arch repair using the frozen elephant trunk (FET) technique for distal arch aortic aneurysm and to examine the late complications. METHODS: Thirty-eight patients with true distal arch aortic aneurysms were repaired with FET introduced through an incision in the proximal arch aorta. Follow-up computed tomography was performed every 6 or 12 months in 36 surviving patients. The maximum dimension of the excluded aneurysmal space was measured to determine whether the aneurysmal space had decreased or disappeared. Late complications were also evaluated during the long-term follow-up. RESULTS: There was 1 hospital death (2.6%) and 1 (2.6%) case of paraplegia. There were 2 late sudden deaths (5.2%) thought to be due to aneurysm rupture and arrhythmia. Postoperative serial-computed tomography showed shrinkage of the excluded aneurysmal space in 33 of 36 patients. Late aneurysmal formation occurred in the anastomotic site in three patients. One patient underwent thoracic endovascular stent grafting 10 years after surgery, 1 patient had total arch replacement 9 years after surgery, and 1 died due to rupture. CONCLUSION: Frozen elephant trunk was found to be a useful alternative for treating true distal arch aortic aneurysm. However, we must be alert for late aneurysmal formation at the incision site.

Ventricular tachycardia storm originating from interventricular septum successfully treated with surgical cryoablation with electroanatomic and electrophysiological mapping before dual valve replacement.

A 58-year-old man with dilated cardiomyopathy was admitted with heart failure. He had a history of two catheter ablation procedures for ventricular tachycardia (VT) originating from the intraventricular septum (IVS). Before dual valve replacement (DVR), he suffered a VT storm. An electrophysiological study revealed an extended low-voltage area at the IVS with the exit of the induced VT at the anterior side. Radiofrequency application was performed at the VT exit as a landmark for surgical cryoablation (SA). During the DVR, SA was performed at the IVS using this landmark. After SA, the patient had no ventricular tachyarrhythmia.

Abdominal organ protection strategy for aortic arch aneurysm surgery.

INTRODUCTION: Body temperature maintained during open distal anastomosis in patients who undergo aortic surgery has been showing an upward trend; however, a higher temperature may increase visceral organ and spinal cord injury. Distal perfusion may reduce abdominal organ injury, especially acute kidney injury (AKI). METHODS: From 2009 to 2016, 56 patients who underwent ascending aortic and/or aortic arch surgery were enrolled. Open distal anastomosis was performed using one of three protection strategies: 1) systemic temperature of 25°C followed by selective cerebral perfusion (SCP) with lower body circulatory arrest (Group CA25, n=27); 2) systemic temperature of 28°C followed by SCP with lower body circulatory arrest (Group CA28, n=4); and 3) systemic temperature of 28°C followed by SCP with distal aortic perfusion (Group DP, n=25). RESULTS: During the postoperative course, levels of blood urea nitrogen, creatinine, liver enzymes, lactate dehydrogenase and lactate in Groups CA28 and CA25 were significantly higher than those in Group DP. AKI defined by the AKI Network occurred in 28 cases (50%) and 3 cases required permanent hemodialysis. AKI was significantly higher in Groups CA25 and CA28 than in Group DP (p=0.026). Mid-term follow-up showed that patients who developed postoperative AKI were more likely to suffer from cardiovascular events. CONCLUSIONS: Distal perfusion during open distal anastomosis reduced kidney and liver injury after thoracic aortic surgery despite an increased body temperature of up to 28°C. This strategy may be useful to prevent AKI, liver dysfunction, the need for hemodialysis and multiple organ failure and could improve mid-term results.

Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model.

OBJECTIVES: Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. METHODS: Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. RESULTS: In the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. CONCLUSIONS: The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.

Experimental Study of Intraparenchymal Fibrinogen and Topical Thrombin to Seal Pleural Defects.

OBJECTIVE: Fibrin sealants are used to close surgical pleural defects, but may detach, causing a postoperative air-leak. We investigated a new means of applying fibrin glue for closing pleural defects. METHODS: Pleural defects (10-mm and 4-mm diameters, respectively) were created in swine and rats via thoracotomy. They were sealed by a) injection of a fibrinogen solution into the lung parenchyma after instillation of a thrombin solution onto the pleural defect (group A), b) fibrinogen and thrombin spray (group B), c) fibrinogen instillation and a thrombin-dipped polyglycolic acid sheet (group C), or d) fibrin glue-coated collagen fleece (group D). Resistance to airway pressure was compared and the sealed areas were histologically examined. RESULTS: In group A, the minimum seal-breaking airway pressure was consistently > 40 cmH2O, versus 37.2 ± 3.6 cmH2O in group B, 37.2 ± 4.0 cmH2O in group C, and 39.0 ± 1.7 cmH2O in group D, which was statistically significant. Histologically, the fibrin layer infiltrated the lung parenchyma and covered the defect in group A, but not in the other groups. CONCLUSIONS: The intraparenchymal injection of fibrinogen combined with instillation of thrombin created an effective fibrin layer associated with early pleural regeneration that reliably prevented pleural air leaks.

Mid-term results of mitral valve palsty in patients with mitral sclerotic lesion.

BACKGROUND: Mitral valve repair is preferred over prosthetic replacement. We surgically repaired mitral valve with degenerated sclerotic lesion and demonstrated mid-term results. METHODS: Mitral valve plasty (MVP) was performed with several procedures including ring annuloplasty, leaflet slicing and decalcification. RESULTS: There were 19 males and 19 females with a mean age of 67 ± 12 y.o (n = 38). All patients were successfully treated MVP except one case with unrepairable injuries of the thin leaflet. In patients underwent MVP (n = 37), MVP included ring annuloplasty with a rigid full ring of 32 ± 2 mm (n = 37), leaflet slicing (n = 37), decalcification (n = 15) and artificial chordae (n = 14). Mitral valve area was statistically enlarged by MVP (1.65 ± 0.57 vs 2.51 ± 0.58 cm(2), p < 0.001). Left atrial diameter was statistically reduced after the operation (55 ± 10 vs 46 ± 9 mm, p < 0.001). Severity of MR and right ventricular systolic pressure (RVSP) were statistically decreased after the operation (MR; 1.8 ± 1.0 vs 0.7 ± 0.9, p < 0.001, RVSP; 38 ± 15 vs 30 ± 9 mm Hg, p < 0.001). There were 4 cases with residual MR (Grade II, n = 3; Grade III, n = 1). The 30-days mortality was 0 %. There was one late death due to non-cardiogenic cause (the 3-year survival rate of 97 %) and no redo case due to deterioration of the mitral valve during follow-up period of 21 ± 13 months. CONCLUSIONS: Successful mid-term survival and freedom from reoperation might expect to the durability of MVP in patients with mitral sclerotic lesion.

Preoperative Tissue Doppler Imaging-Derived Atrial Conduction Time Predicts Postoperative Atrial Fibrillation in Patients Undergoing Mitral Valve Surgery for Mitral Valve Regurgitation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and may result in stroke, heart failure and poor prognosis. This study evaluated a novel index of total atrial conduction time derived from the P-wave onset (lead II) to the peak A' wave on tissue Doppler imaging (PA-TDI duration) in patients undergoing mitral valve surgery (MVS) for mitral valve regurgitation. METHODS AND RESULTS: Seventy-three patients undergoing MVS had transthoracic echocardiography with tissue Doppler imaging preoperatively and were monitored postoperatively with continuous electrocardiographic telemetry for 14 days. Preoperative characteristics, echocardiographic data, operative data and postoperative findings were compared between patients with (n=44) and without (n=29) POAF. Postoperative cardiac events were higher in patients with than without POAF (12/44, 27% vs. 3/29, 10%; P=0.0798) and cerebral events occurred in only 2 POAF patients. On multivariate analysis the independent predictors of POAF were degenerative disease etiology (OR, 4.61; 95% CI: 1.41-15.0; P=0.0112) and PA-TDI duration (OR, 1.04; 95% CI: 1.01-1.07; P=0.0048). On ROC curve analysis a PA-TDI cut-off of 159.4 ms was optimal for predicting POAF. CONCLUSIONS: PA-TDI duration was an independent predictor of POAF after MVS. Patients with PA-TDI duration >159.4 ms should be considered high risk and treated appropriately to improve outcome.

Subvalvular Pannus Overgrowth after Mosaic Bioprosthesis Implantation in the Aortic Position.

PURPOSE: Although pannus overgrowth by itself was not the pathology of structural valve deterioration (SVD), it might be related to reoperation for SVD of the bioprostheses. METHODS: We retrospectively reviewed patients undergoing reoperation for SVD after implantation of the third-generation Mosaic aortic bioprosthesis and macroscopic appearance of the explanted valves was examined to detect the presence of pannus. RESULTS: There were 10 patients and the age for the initial aortic valve replacement was 72 ± 10 years old. The duration of durability was 9.9 ± 2.0 years. Deteriorated valve presented stenosis (valvular area of 0.96 ± 0.20 cm(2); pressure gradient of 60 ± 23 mmHg). Coexisting regurgitant flow was detected in two cases. Macroscopically, subvalvular pannus overgrowth was detected in 8 cases (80%). The proportion of overgrowth from the annulus was almost even and pannus overgrowth created subvalvular membrane, which restricted the area especially for each commissure. In contrast, opening and mobility of each leaflet was not severely limited and pannus overgrowth would restrict the area, especially for each commissure. In other two cases with regurgitation, tear of the leaflet on the stent strut was detected and mild calcification of each leaflet restricted opening. CONCLUSION: In patients with the Mosaic aortic bioprosthesis, pannus overgrowth was the major cause for reoperation.