Perfusion Time Research Articles

Simulation of Acute Pulmonary Hypertension in Beagle Dogs.

Acoustic cardiography (AC) combined with heart sound (HS) recording and electrocardiogram (ECG) provides a noninvasive and inexpensive way to understand the electrical mechanical activity of the heart. Pulmonary artery stenosis can cause hemodynamic abnormalities that might lead to pulmonary hypertension (PH). In this paper, we examined the relationships between the acoustic characteristics of the AC and hemodynamic changes in a beagle dog model of PH.Four healthy beagle dogs were injected with the prostaglandin endoperoxide receptor agonist U-44069 to induce acute PH states. AC was employed to analyze the process of pre-PH, intra-PH, and post-PH. Right ventricular blood pressure (RVBP) was measured via right cardiac catheterization, an invasive method performed in parallel for comparative hemodynamic evaluation. As RVBP increased or decreased, the HS features changed accordingly during acute PH occurrence and development. Right ventricular systolic blood pressure (RVSBP) significantly correlated with the minimum of the first HS (S1) amplitude (correlation coefficient (CC) = -0.82), energy of the S1 (CC = 0.86), energy of the second HS (S2) (CC = 0.67), entropy of the S1 (CC = -0.94), and ratio of electromechanical systolic time (EMST) to the cardiac cycle time (CC = 0.81). The two techniques (AC [HSs and ECG] versus right cardiac catheterization [RVBP]) were significantly correlated. Especially, the diastolic filling time (DFT) had a significant relationship with the right ventricular diastolic time (RVDT) (CC = 0.97), perfusion time (PT) (CC = 0.96), and cardiac cycle time (RR) (CC = 0.96). The CCs between the RVDT and the max dp/dt to min dp/dt, the EMST and the Q to min dp/dt, and the electromechanical activation time and the Q to max dp/dt were 0.95, 0.99, and 0.86, respectively. Furthermore, the logistic regression model with different combinations was used to identify the effective features for monitoring hemodynamic and pathophysiologic conditions.AC provided significant insight into mechanical dysfunction in a rapid and noninvasive way that could be used for early screening of PH.

Application of retrograde cerebral perfusion in aortic root replacement combined with right half aortic arch replacement.

After cardiac surgery involving the aortic arch, the incidence of neurological complications remains high, therefore it is very important to take measures to protect brain. This study is to investigate the safety and effectiveness of deep hypothermic circulatory arrest and retrograde cerebral perfusion for aortic root combined with right half aortic arch replacement. Clinical data of 31 patients, who underwent aortic root and right half aortic arch replacement with deep hypothermic circulatory arrest and retrograde cerebral perfusion in Xiangya Hospital, Central South University, were retrospectively analyzed. This cohort included 23 aortic aneurysms and 8 aortic dissections. Aortic root replacement was conducted in 26 patients by Bentall procedures, and 5 patients by David procedures. Time of deep hypothermic circulatory arrest and retrograde cerebral perfusion in surgery was (21.9±5.2) min. The in-hospital mortality, postoperative neurological dysfunction and other major adverse complications were observed and recorded. No in-hospital death and permanent neurological dysfunction occurred. Two patients had transient neurological dysfunction and 2 patients with aortic dissection requiring long-time ventilation due to hypoxemia, 1 patient underwent resternotomy. During 6-36 months of follow-up, all patients recovered satisfactorily. Deep hypothermic circulatory arrest and retrograde cerebral perfusion can be safely and effectively applied in aortic root and right half aortic arch replacement, and which can simplify the surgical procedures and be worth of clinical promotion.

Optimizing transcardial perfusion of small molecules and biologics for brain penetration and biodistribution studies in rodents.

Efficiently removing blood from the brain vasculature is critical to evaluate accurately the brain penetration and biodistribution of drug candidates, especially for biologics as their blood concentrations are substantially higher than the brain concentrations. Transcardial perfusion has been used widely to remove residual blood in the brain; however, the perfusion conditions (such as the perfusion rate and time) reported in the literature are quite varied, and the performance of these methods on blood removal has not been investigated thoroughly. In this study, the effectiveness of the perfusion conditions was assessed by measuring brain hemoglobin levels. Sodium nitrite (NaNO2 ) as an additive in the perfusate was evaluated at different concentrations. Blood removal was significantly improved with 2% NaNO2 over a 20 min perfusion in mouse without disrupting the integrity of the blood-brain barrier (BBB). In mice, the optimized perfusion method significantly lowered the measured brain-to-plasma ratio (Kp,brain ) for monoclonal antibodies due to the removal of blood contamination and small molecules with a moderate-to-high BBB permeability and with a high brain-unbound-fraction (fu,brain ) presumably due to flux out of the brain during perfusion. Perfusion with or without NaNO2 clearly removed the residual blood in rat brain but with no difference observed in Kp,brain between the perfusion groups with or without 2% NaNO2 . In conclusion, a perfusion method was successfully developed to evaluate the brain penetration of small molecules and biologics in rodents for the first time. The transcardial perfusion with 2% NaNO2 effectively removed the residual blood in the brain and significantly improved the assessment of brain penetration of biologics. For small molecules, however, transcardial perfusion may not be performed, as small molecule compounds could be washed away from the brain by the perfusion procedure.

MO662: Effects of Blood Contact with Haemodialysis Membrane on the Kidney in a Rat Extracorporeal Perfusion Model

Abstract BACKGROUND AND AIMS A microcirculatory disturbance was found to occur during hemodialysis in an organ such as the brain or heart, which was recently considered to lead to functional impairment of these organs. Decrease in blood volume due to water removal during hemodialysis and the reaction of blood vessels with activated leukocytes and platelets that have come in contact with the dialysis membrane may cause the microcirculatory disturbance of the organs. Residual renal function decline after initiation of hemodialysis is well-known, but the mechanism has not yet been fully understood. In the present study, we focused on the effects of leucocytes and platelets activated by contact with the dialysis membrane and aimed to clarify the effects of blood contact with the dialysis membrane on the kidney. METHOD Male Sprague–Dawley rats weighing 397.4 ± 38.6 g were used for the experiment. We compared three experimental groups; the sham group, in which only puncture and infusion of Ringer's lactate solution were performed; the extracorporeal perfusion alone group, in which extracorporeal perfusion was performed only through a blood circuit; and the dialyzer group, in which extracorporeal perfusion was performed through a blood circuit and dialyzer. Blood was withdrawn from the femoral artery and returned to the femoral vein. The blood flow rate was 0.5–1.0 mL/min, the perfusion time was 4-h and no water removal was performed. During the perfusion experiment, arterial pressure and percutaneous arterial oxygen saturation (SpO2) were measured and at the end of perfusion, serum interleukin-6 (IL-6), a marker of inflammation and urinary kidney injury molecule-1 (KIM-1), a marker of kidney injury, were measured. After completing the perfusion experiment, kidneys were removed and morphology was evaluated by a hematoxylin and eosin (HE) staining. RESULTS AND DISCUSSION Arterial pressure during perfusion showed a significant upward trend during the first 2-h in the extracorporeal alone and dialyzer groups, while SpO2 showed a significant downward trend in these groups. Serum IL-6 levels were significantly higher in the extracorporeal perfusion alone group (P < .05, n = 8) and the dialyzer group (P < .01, n = 6) than in the sham group (n = 7). Urinary KIM-1 level in the dialyzer group was significantly higher than that in normal rats (P < .01, n = 7). Glomerular congestion was observed in the kidney only in the dialyzer group from the HE staining. There was a significant correlation between the increase in arterial pressure and the decrease in SpO2, suggesting that peripheral circulatory disturbance due to peripheral vasoconstriction occurred in the extracorporeal perfusion alone and the dialyzer groups. In addition, extracorporeal perfusion through the dialyzer caused high levels of IL-6 in serum and KIM-1 in urine, suggesting that systemic inflammatory and kidney injury have occurred. These reactions may contribute to the progression of residual renal dysfunction due to dialysis treatment, especially for the patients after the initiation of hemodialysis. CONCLUSION Extracorporeal perfusion and blood contact with a dialyzer caused systemic inflammation and the microcirculatory disturbance of kidneys, resulting in glomerular congestion and kidney injury in a rat extracorporeal perfusion model.

Effects of Hyperoxia on Coronary Circulation in Patients with Peripheral Artery Diseases (PAD)

It is well‐known that hyperoxia evokes different effects in patients with different dieaseas conditions. Studies from this lab and others have shown that hyperoxia is a potent coronary vasoconstrictor. Recently, we found that hyperoxia exaggerates systolic blood pressure (BP) response in patients with PAD. The aim of this study is to characterize the coronary circulatory effects of hyperoxia in PAD patients and healthy controls. We recruited 20 PAD patients (14M, 6F, 66 ± 6yrs), and 16 age‐matched control subjects (10M, 6F, 65 ± 8yrs). The ankle‐brachial pressure index (ABI) in the most affected limbs of the patients was 0.58 ± 0.15, compared to the controls ABI of 1.04 ± 0.09. For the hyperoxia procedure the subjects breathed room air for three minutes and 100% oxygen for five minutes. BP and heart rate (HR) were monitored during baseline and hyperoxia. The rate pressure product (RPP), an index of myocardial oxygen consumption, was calculated as the product of systolic BP and HR. Transthoracic Coronary Echocardiography was used to record early and late peak coronary blood flow velocities (CBV1 and CBV2) in the left anterior descending artery. Early and late coronary vascular conductances (peak coronary blood velocity/diastolic blood pressure, CVC1 and CVC2) and coronary perfusion time fraction (CPTF, coronary perfusion time/R‐R interval) were calculated. All data was compared across time and between groups using Repeated Measures Analyses of Variance (RMANOVA).ResultsAt the baseline, RPP and coronary parameters (CBV2, CVC1, and CVC2) were higher in the PAD group compared to controls, also the PAD group showed significantly shorter CPTF. During hyperoxia, CBV1, CBV2, CVC1, and CVC2 decreased to varying degrees in both groups. However, no significant interactions were observed for RPP and all coronary parameters during hyperoxia between the groups (Table). Our findings suggest that the effect of hyperoxia on coronary circulation was not significantly different between PAD and healthy controls.

Perfusate Metabolomics Content and Expression of Tubular Transporters During Human Kidney Graft Preservation by Hypothermic Machine Perfusion.

Ischemia-related injury during the preimplantation period impacts kidney graft outcome. Evaluating these lesions by a noninvasive approach before transplantation could help us to understand graft injury mechanisms and identify potential biomarkers predictive of graft outcomes. This study aims to determine the metabolomic content of graft perfusion fluids and its dependence on preservation time and to explore whether tubular transporters are possibly involved in metabolomics variations. Kidneys were stored on hypothermic perfusion machines. We evaluated the metabolomic profiles of perfusion fluids (n = 35) using liquid chromatography coupled with tandem mass spectrometry and studied the transcriptional expression of tubular transporters on preimplantation biopsies (n = 26), both collected at the end of graft perfusion. We used univariate and multivariate analyses to assess the impact of perfusion time on these parameters and their relationship with graft outcome. Seventy-two metabolites were found in preservation fluids at the end of perfusion, of which 40% were already present in the native conservation solution. We observed an increase of 23 metabolites with a longer perfusion time and a decrease of 8. The predictive model for time-dependent variation of metabolomics content showed good performance (R 2 = 76%, Q 2 = 54%, accuracy = 41%, and permutation test significant). Perfusion time did not affect the mRNA expression of transporters. We found no correlation between metabolomics and transporters expression. Neither the metabolomics content nor transporter expression was predictive of graft outcome. Our results call for further studies, focusing on both intra- and extratissue metabolome, to investigate whether transporter alterations can explain the variations observed in the preimplantation period.

Results of post-infarction left ventricular aneurysms surgical planning using magnetic resonance imaging and three-dimensional modeling

Aim. To evaluate the results of surgical intervention planning using three-dimensional models based on magnetic resonance imaging in patients with postinfarction left ventricular aneurysms.Material and Methods. Two groups of patients with postinfarction left ventricular aneurysm (PLVA) were included in the study, totaling 41 patients. The first (experimental) group included 17 patients diagnosed with PLVA by magnetic resonance imaging (MRI), and surgical intervention planning was performed using a 3D model of the heart. The control group comprised 24 patients in whom PLVA was diagnosed by echocardiography (TTE) or ventriculography, and surgical intervention planning was performed using traditional two-dimensional slice images.Results. Comparison of full perfusion under cardiopulmonary bypass (CPB) showed statistically significant differences between the groups: this parameter was 60 [56; 68] min in group 1 vs. 71 [61; 84] min in group 2, which was significantly higher (p = 0.043). There were no significant differences in total operation time (280 [265; 320] min in group 1 vs. 263 [248; 283] min in group 2, p = 0.055), overall CPB time (93 [86; 109] min in group 1 vs. 104 [83; 109] min in group 2, p = 0.653), and partial CPB time (31 [26; 39] min in group 1 vs. 27 [21; 32] min in group 2, p = 0.127).Conclusion. The use of 3D models to support surgeons for PLVA correction makes it possible to determine the type of reconstructive surgery, practice the main stages of the upcoming intervention, and reduce the time of full perfusion under CPB during its implementation.

Use of Indocyanine green (ICG) angiography to minimize anastomotic leak in the neck after esophagectomy

Introduction: Anastomotic leak after esophagectomy for cancer of mid and lower esophagus and gastroesophageal junction (GEJ) still remains a major challenge. Poor perfusion of the gastric conduit remains the main factor for leak. Intra-operative assessment of the gastric conduit with indocyanine green (ICG) angiography helps to select a properly perfused site for anastomosis, thus minimizing the leak. Methods: Patients undergoing surgery for cancer of esophagus and GEJ either through open or minimally approach were taken up for this study. Stomach was used for reconstruction and anastomosis was made in neck. A 0.1ml of test dose of ICG was given intra-dermally to look for any reaction. After that a dose of 5-10 milligrams was injected intravenously. Perfusion was assessed with infrared light using laparoscopic telescope. The timing of perfusion of the conduit was recorded. Well perfused segment was used for gastroesophageal anastomosis. Different parameters including leak were compared with non-ICG group. Results: We studied 474 patients. Among these patients 67 were in ICG group and 407 were in non-ICG group. Mean age, mean weight loss and co-morbidities were similar in both groups. 72% of patients in ICG group and 50% of patient in non-ICG groups had multimodality treatment. 67% of patients in ICG group and 46% of patients in non-ICG group underwent minimally invasive surgery (p<0.001). Post-operative complications like pneumonia, recurrent laryngeal nerve palsy and surgical site infection were similar in both groups. Post-operative mortality was seen in 1.5% and 3.7% in ICG group and non-ICG group respectively (p=0.4). Overall leak in ICG group was 9% and 16.5% in non-ICG group (p=0.06). In ICG group with the perfusion time of more than 60 seconds, the leak rate was only 3.5% in comparison to 16.5% in non ICG group (p=0.009). Conclusion: ICG angiography provides an objective assessment about the perfusion of gastric conduit during the time of anastomosis. Anastomosis at area of gastric conduit with perfusion time less than 60 seconds, minimizes leak rate in neck.

Novel Portable Hypothermic Cardiac Preservation Device Extends Cardiac Viability and Function Beyond the Standard of Care Using Isolated Porcine Hearts

<h3>Purpose</h3> The standard of care: cold static storage (CSS), limits the time a heart can be preserved to 4-6 hours. Machine perfusion preservation has been shown to improve organ viability. However, current machine perfusion technology is complex and requires the use of blood or blood products. The purpose of this study was to test the efficacy of a portable hypothermic oxygenated and acellular perfusion machine device, in preserving cardiac viability and function in comparison to CSS for 4 hours at different perfusion times using an isolated heart porcine model. <h3>Methods</h3> Isolated porcine hearts (N=17) were recovered under anesthesia and by inducing cardiac arrest through cardioplegia administration. Experimental hearts were perfused using a novel cardiac preservation device with an acellular perfusate at 4-8°C for 4 hours(n=3), 8 hours(n=4), and 24 hours(n=3). In addition, 3 hearts were perfused for 2 hours and then kept inside the perfusor at 4-8°C for an additional 4 hours without perfusion (extended mode), to determine efficacy during inoperable conditions. Controls (n=4) were hearts kept in CSS for 4 hours. Hourly flow, pressure, temperature, and blood gas measurements were taken from perfused hearts. After preservation, the hearts were placed in a Langendorff for functional recovery determined by +/- dP/dT and maximum pressure. Biopsy samples were taken before and at the end of either preservation method for histological and gene expression analyses. <h3>Results</h3> Control hearts weight gain (%) was -3.4 ± 4.9 and perfused hearts was 1.52 ± 7.6. Venous and arterial lactate concentrations were less than 2.5 mmol/L across all experiments. Perfused hearts at 4 hours, 8 hours, and extended mode had significantly increased contractility (p<0.05) than CSS demonstrated by +dP/dT and peak pressure. Gene expression showed a significant reduction (p<0.005) of inflammation (IL-6, IL-8, TNFα) and cell death markers (p53,cTnI) in perfused hearts compared to control hearts. Furthermore, histological assessment confirmed greater myocardium damage in CSS hearts. <h3>Conclusion</h3> This novel cardiac preservation device enhances cardiac viability and function compared to CSS. Furthermore, it allows for 4 hours of CSS after 2 hours of perfusion in case of cessation of perfusion. Animal transplant studies will be conducted to verify these results.

Ischemia Minimization Reduces Cardiac Xenograft Injury

<h3>Purpose</h3> Previous work has shown the benefit of ischemia minimization (IM) to reduce initial xenograft dysfunction. We examined cardiac injury in an <i>ex vivo</i> xenoperfusion model comparing IM with cold storage (CS). <h3>Methods</h3> Hearts from pigs expressing TKO.GHRKO (QKO) were compared to wild-type (WT) using an <i>ex vivo</i> model. Three QKO and 1 WT hearts were treated with IM for 2.5 hours following procurement. IM consisted of continuous cold cardioplegia. Two QKO and 2 WT hearts were placed in iced saline for the same time period. Following IM or CS hearts were Langendorff perfused with warm human blood then converted to working heart mode (WHM) if able. Total perfusion time was 4 hours. Troponin levels and physiologic function were periodically observed. <h3>Results</h3> Release of troponin was significantly reduced in the WT IM group (IM 185, CS>1000; p=0.02). A similar yet non-significant observation was noted in the QKO IM hearts (IM 750, CS>1000; p=0.37) (Fig.1). Two WT hearts (1 CS and 1 IM) were physiologically unable to reach WHM. One WT CS heart achieved WHM though failed at 3 hours (Fig.2F). Physiologic function was maintained in 2 of 3 QKO IM hearts (Fig 2A, B), and 1 of 2 QKO CS hearts (Fig. 2E). All WT hearts (2 CS and 1 IM (Fig. 2F)) and 2 of 5 QKO hearts (1 CS (Fig. 2D) and 1 IM (Fig. 2C)) failed within 4 hours. The 4 hour survival rate was not significantly improved by IM. <h3>Conclusion</h3> IM was shown to reduce cardiac injury in WT hearts and promote an increase in functional outcomes. This was a limited pilot study, however, the results were consistent with prior reported observations showing that IM reduced heart xenograft injury and dysfunction and support further evaluation of IM in <i>ex vivo</i> and <i>in vivo</i> models.

New Methods to Extend Perfusion Duration of Rat Cardiac Grafts

<h3>Purpose</h3> Cardiac transplant is an established treatment for end-stage heart disease; however, there is a shortage of viable organs. Extending preservation time or reviving marginal grafts would greatly reduce the current shortage. Machine perfusion holds promise to overcome these challenges. Murine models are used due to their low cost, and availability of transgenic lines; however, perfusion are limited to ∼2 hours. Most rat retrograde perfusions apply aortic root pressures of 75-90 mmHg, and flows between 5-25 ml/min. As perfusion time extends, valvular injury, hypertrophy, edema, and graft disfunction can be observed. Methods to avoid these issues include a left ventricular apical drain and increasing oncotic pressure/oxygen delivery using packed red blood cells (pRBCs). Our research tests the effect of lower pressures/flow rates, 30-35 mmHg, 3.5-5 mL/min during a 4-hour normothermic perfusion. <h3>Methods</h3> Hearts from Sprague Dawley rats were retrogradely perfused for 4 hours, under varying flow, pressure, and perfusate parameters (Table 1). <h3>Results</h3> Group 3 (G3) had stable perfusion parameters over 4 hours with high oxygen uptake (average 22.53 mmHg•min•mL⁻¹/gram tissue) and low resistance (average 3.34 mmHg•min•mL⁻¹/gram tissue). Weight was significantly different at 4 hours comparing G3 with no weight gain, to the Controls that had 23% weight gain. Lactate rose in both G3 and Control but was not significant. Finally, G3 sustained full ventricular contraction (>150 bpm), with no arrhythmia, or tachycardia; whereas Control heart rate decreased throughout perfusion, and arrhythmia and tachycardia was noted within 2 hours. <h3>Conclusion</h3> We demonstrate the ability to prolong murine heart perfusion for up to 4 hours. With prolonged function and viability in a murine heart model, this opens a greater potential of low-cost mammalian heart perfusions for research.

Heart Transplantation Utilizing Organs Following Donation After Circulatory Death (DCD)

<h3>Purpose</h3> Donation after circulatory death (DCD) is gaining momentum for heart transplantation worldwide. Central to the process is a detailed assessment of the donor heart following the circulatory arrest and unpredictable warm ischemia time. Our team used the Organ Care System as the principal means of assessment and preservation of the DCD hearts. Here we describe our single centre experience with DCD heart transplantation. <h3>Methods</h3> Between 2015 and 2021, 36 donor hearts were procured via the DCD pathway. Donor management involved the withdrawal of treatment (WoT) in the donor, stand-down time of 5 minutes following circulatory arrest (asystole), transfer of the patient to the operating theatre, collection of 1.2L donor blood from right atrium for Organ Care System (OCS) prime, delivery of cardioplegia and its procurement. The organs were assessed utilizing OCS and 25 suitable hearts that met the criteria of suitability were transplanted. <h3>Results</h3> The mean age of donors was 30.6±10.7 years (12% females) with intracranial haemorrhage and hypoxic brain damage as main causes of WoT. 52% of the donors suffered cardiac arrest before hospital admission, 25% had a history of cocaine abuse and 48% were current smokers. Mean WoT to asystole time was 11.8±4.1 min, mean WoT to cardioplegia time was 23.1±4.6 min and a mean functional warm ischemia time was 16.3±3.5 min. The mean OCS perfusion time was 245 ±81min.The mean recipient age was 42.6±13.2 years (12% females) with dilated (64%) and ischemic (24%) cardiomyopathy as an aetiology of heart failure in the majority. 6 (24%) patients had long term LVAD while 2(8%) were supported on short-term mechanical support per-operatively.9 (36%) patients required mechanical circulatory support postoperatively with ECMO and IABP and 20 (80%) required continuous renal replacement therapy. The mean ICU stay was 17.8±16.5 days and the mean hospital stay was 45±40 days. Postoperative survival at 30-days was 88%. <h3>Conclusion</h3> Donor hearts procured following donation after circulatory death were transplanted with acceptable short-term survival especially given the high proportion of preoperative mechanical circulatory support and urgency of transplantation in our cohort. ‘Direct procurement and perfusion' method of procurement in DCD offers an opportunity to assess the donor heart for the suitability of transplantation.

Partial upper sternotomy for extensive arch repair in older acute type A aortic dissection patients

ObjectivesThe partial upper sternotomy (PUS) approach is acceptable for aortic valve replacement, and even aortic root operation. However, the efficiency of PUS for extensive arch repair of acute type A aortic dissection (AAAD) in older adult patients has not been well investigated.MethodsBetween January 2014 and December 2019, 222 older adult patients (≥ 65 years) diagnosed with AAAD went through extensive arch repair, among which 127 received PUS, and 95 underwent full sternotomy (FS). Logistic regression analysis was used to identify risk factors for early death, and negative binomial regression analysis was applied to explore risk factors related to post-operative ventilator-supporting time and intensive care unit stay time.ResultsTotal early mortality was 8.1% (18/222 patients). The PUS group had shorter Cardiopulmonary bypass time (133.0 vs.155.0 min, P < 0.001), cross-clamp time (44.0 vs. 61.0 min, P < 0.001) and shorter selective cerebral perfusion time (11.0 vs. 21.0 min, P < 0.001) than the FS group. Left ventricle ejection fraction < 50% (odds ratio [OR] 17.05; 95% confidence interval [CI] 1.87–155.63; P = 0.012) and malperfusion syndromes (OR 65.83; 95% CI 11.53–375.86; P < 0.001) were related to early death. In the multivariate model, the PUS approach contributed to shorter ventilator-supporting time (incidence rate ratio [IRR] 0.76; 95% CI 0.64–0.91; P = 0.003), when compared with the FS group.ConclusionsThe early results of emergency extensive arch repair of AAAD via PUS in older adult patients were satisfactory. However, the long-term results remain to be investigated.

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy.

Evaluation of an ex vivo model of the blood-perfused equine uterus

Uterine pathologies are the most common causes of infertility in mares. This study aimed to establish an ex vivo blood-perfused model for equine uteri and investigate the possible effects of different cycle stages (estrus, diestrus and anestrus) on the applicability of the model. Uteri (n = 13) were collected at an abattoir, flushed with preservation solution, transported to the laboratory on ice, and isolated perfused with autologous blood for 6 h (n = 12). For negative control, one uterus was handled as described but left without perfusion for 6 h. The cycle stage was determined by examination of the ovaries for the presence of Graafian follicles or corpora lutea and analysis of plasma progesterone concentration (estrus: n = 4; diestrus: n = 4; anestrus: n = 4). Sonomicrometry crystals were implanted into the myometrium to record spontaneous contractions and the response to 0.5 IU oxytocin after 6 h of perfusion. Analyses of the arterial and venous perfusate were performed every hour to determine glucose consumption, lactate production, pH, lactate dehydrogenase activity (LDH), and potassium concentration (K+). Biopsy samples were obtained directly after slaughter, after transportation, after equilibration, after 4, 5, and 6 h of perfusion, and immediately after removal from the perfusion system. The uteri's glucose consumption and lactate production increased over time (p < 0.05), but no differences among cycle stages were detected. pH (arterial and venous) increased over time (p < 0.05). No changes for LDH were observed. K+ increased after 4 h of perfusion (p < 0.05), but was unaffected by the cycle stage. Spontaneous contractions were present in all perfused uteri, but myometrial activity in the negative control was limited to the 2nd hour of perfusion. No effects of cycle stage on contraction amplitude and duration after oxytocin administration were detected. The cycle stage did not affect frequency (except after 5 h of perfusion), amplitude, duration of contractions, or edema formation. Histology revealed congestion of endometrial capillaries after 4, 5, and 6 h perfusion time. In conclusion, the ex vivo model was capable of supporting the functionality of equine uteri for 6 h. However, viability and histomorphology of the endometrium appeared to be impaired after 4 h of perfusion. Effects of the cycle stage on the applicability of the model were absent.

Contrast-enhanced ultrasound of adrenal hemorrhage: a helpful problem solving tool.

A focal lesion in the region of the adrenal gland in a newborn often requires further assessment. Ultrasound (US) is the initial imaging method of choice in young children as it does not use radiation or require sedation and it has excellent spatial resolution. In this case series, we present contrast-enhanced ultrasound (CEUS) as a problem-solving tool in the evaluation of neonatal adrenal lesions. The imaging and medical records of five patients with adrenal lesions were retrospectively reviewed. All patients underwent US as an initial examination and all had US follow-up. Additionally, two patients had MRI examinations. CEUS was performed in all patients as a follow up examination. The enhancement characteristics of the adrenal masses on CEUS were analyzed with the use of VueBox software. In addition, qualitative analysis of the cine loops for the presence of vascularization within the lesions was performed by consensus between two radiologists. The presence of an adrenal hematoma was correctly detected and characterized by CEUS in all five cases using VueBox perfusion analysis. Adrenal hematomas had no internal perfusion and flat time intensity curves. The quantitative and qualitative CEUS assessment of the mass can distinguish hemorrhage from a malignant lesion. Based on our findings, CEUS could serve as an alternative diagnostic tool to magnetic resonance imaging in the diagnosis of slowly resolving NAH lesions.

Safety Time and Optimal Temperature of Unilateral Antegrade Cerebral Perfusion in Acute Type A Aortic Dissection: A Single-Center 15-Year Experience.

The optimal level of hypothermia and safe time of unilateral antegrade cerebral perfusion (uACP) in acute type A aortic dissection (ATAAD) repair remain controversial. To analyze the association of uACP time and circulatory arrest temperature with surgical outcomes of ATAAD. We retrospectively analyzed 263 patients who had undergone ATAAD repair between 2006 and 2020 using uACP. The patients were stratified by three chronologically equivalent periods (period 1, 2006 to 2010; period 2, 2011 to 2015; period 3, 2016 to 2020) to demonstrate the decade-long evolution of surgical strategy and outcomes. The mean age of the patients was 59.4 ± 12.5 years, and 68.8% were male. The hospital mortality rates were 15.1%, 12.9%, and 11.0% from period 1 to 3 (p = 0.740). The median circulatory arrest temperatures were 20, 23, and 25 °C (p < 0.001), respectively, and the median uACP times were 72, 59, and 41 minutes (p < 0.001). The incidence rates of postoperative permanent neurologic deficits were 13.2%, 10.9%, and 18.3% (p = 0.312), and those of transient neurologic deficits were 9.4%, 10.9%, and 11.9% (p = 0.936), respectively. Multivariate logistic regression analysis showed that uACP time ≥ 60 minutes was an independent predictor of hospital mortality rather than postoperative stroke. ROC curve analysis estimated an optimal cutoff value of 52 minutes of uACP time when the circulatory arrest temperature was ≥ 25 °C to predict hospital mortality (area under the curve: 0.72). Unilateral antegrade cerebral perfusion time was associated with hospital mortality after ATAAD surgery. A safe threshold of 50 to 60 minutes of uACP should be considered.

Predicting 90-day Functional Dependency and Death after Endovascular Thrombectomy for Stroke: The BET Score

ObjectivesDespite being the current standard of care, outcomes after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) remain highly variable. Though several scoring systems exist to predict outcomes in AIS, they were mainly developed to direct patient selection for treatment. Recognizing the integral role peri-procedural metrics play on outcome, our study aimed to develop a post-EVT prognostic score to predict 90-day functional dependency and death. Materials and MethodsWe included all eligible adult AIS patients treated with EVT at our institution from June 2016 to January 2020. Data was systematically collected via chart review including pre-, intra- and post-procedural variables. The outcome was modified Rankin score (mRS) at 90 days post-EVT where a poor outcome was defined as mRS 3-6: 3-5 for functional dependency and 6 for death. Model selection methods including stepwise and Lasso were evaluated via cross-validation where the final multivariable logistic regression model was chosen by optimizing the Area Under the Receiver Operating Characteristic Curve (ROC AUC). ResultsWe included 224 patients (mean age: 65 years old, male: 55%, 90-day poor outcome: 60%). The final model achieved a median AUC of 0.84, IQR: (0.80, 0.87). A 7-point score, called Bronx Endovascular Thrombectomy (BET) score, was developed with more points indicating higher likelihood of 90-day poor outcome (0 point: ≤21% risk; 1-2: 24%; 3: 61%; 4: 86%; 5: 96%; 6-7: ≥99%). One point was awarded for the following variables: current smoker, diabetic, general anesthesia received, puncture to perfusion time ≥45 minutes, and Thrombolysis in Cerebral Infarction (TICI) score <3. Two points were awarded for a post-EVT National Institute of Health Stroke scale (NIHSS) of ≥10. ConclusionIncorporating peri-procedural data we developed the competitive BET score predicting 90-day functional dependency and death, which may help providers, patients and caregivers manage expectations and organize early rehabilitative services.

Effect on surgery outcomes owing to the interval between onset of symptoms and surgery of patients with acute type A aortic dissection

Abstract Background: This study aimed to identify whether the interval from onset of symptoms to surgery affects the outcomes of surgery in patients with acute type A aortic dissection (AAAD). Methods: This study retrospectively examined 249 patients with AAAD who underwent Sun's procedure. All patients were divided into 2 groups, hyperacute and acute, according to the interval from onset of symptoms to surgery. The primary endpoint was all-cause early mortality, and the secondary endpoint was early reoperation. Results: The surgery time, cardiopulmonary bypass time, clamp time, and selective cerebral perfusion time were not significantly different between the 2 groups. The intensive care unit length of stay and duration of mechanical ventilation of the 2 groups were 185.50 hours versus 185.00 hours (P = 0.970) and 41.50 hours versus 44.00 hours (P = 0.678), respectively. There were 52 early deaths: 29 in the hyperacute group and 23 in the acute group (21.6% vs. 20.0%, P = 0.751). The incidence of reoperation was 0.7% and 0.9% (P &gt; 0.999), respectively. The incidence rates of postoperative acute heart failure (AHF), acute respiratory failure (ARF), nervous dysfunction, and acute kidney injury were 37.3% versus 25.2% (P = 0.041), 51.5% versus 51.3% (P = 0.976), 13.4% versus 7.0% (P = 0.096), and 37.3% versus 37.4% (P = 0.990), respectively. Multivariable analysis indicated that surgery in the hyperacute phase might be an independent risk factor for AHF (OR: 1.765; 95% CI: 1.021–3.052; P = 0.042). Conclusion: Surgery in the hyperacute phase of AAAD was associated with postoperative AHF. Therefore, early medical management or interventional therapy for complications before surgery performed by experienced surgeons is recommended, especially in the hyperacute phase.

HEPCR.hTBM.hCD47.hHO-1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood.

Platelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti-pig antibody binding (α-1,3-galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO-1]), and a self-recognition receptor (integrin-associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena. Livers from GaltKO.hCD46 pigs ("2-gene," n=3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO-1 ("6-gene," n=4) were perfused ex vivo with whole human blood. Six-gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively. The average perfusion times increased from 304 (±148) min in the 2-gene group to 856(±61) min in the 6-gene group (p=.010). The average heparin administration was decreased from 8837 U/h in the 2-gene to 1354 U/h in the 6-gene group (p=.047). Platelet sequestration tended to be delayed in the 6-gene group (p=.070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p=.044) (401±124vs. 2048±712 at 60min). Thrombin production as measured by F1+2 levels tended to be lower in the 6-gene group (p=.058). The combination of the hEPCR.hTBM.hCD47.hHO-1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.