Pulmonary Shunt Research Articles

Effects of nebulized adipose-derived mesenchymal stem cells on acute lung injury following smoke inhalation in sheep

IntroductionTreatment of ARDS caused by smoke inhalation is challenging with no specific therapies available. The aim of this study was to test the efficacy of nebulized adipose-derived mesenchymal stem cells (ASCs) in a well-characterized, clinically relevant ovine model of smoke inhalation injury. Material and MethodsFourteen female Merino sheep were surgically instrumented 5–7 days prior to study. After induction of acute lung injury (ALI) by cooled cotton smoke insufflation into the lungs (under anesthesia and analgesia), sheep were placed on a mechanical ventilator for 48 hrs and monitored for cardiopulmonary hemodynamics in a conscious state. ASCs were isolated from ovine adipose tissue. Sheep were randomly allocated to two groups after smoke injury: 1) ASCs group (n = 6): 10 million ASCs were nebulized into the airway at 1 hr post-injury; and 2) Control group (n = 8): Nebulized with saline into the airways at 1 hr post-injury. ASCs were labeled with green fluorescent protein (GFP) to trace cells within the lung. ASCs viability was determined in bronchoalveolar lavage fluid (BALF). ResultsPaO2/FiO2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO2/PaO2) was significantly lower in the ASCs group at 36 hr (p = 0.003). Pulmonary shunt fraction tended to be lower in the ASCs group as compared to the control group. GFP-labelled ASCs were found on the surface of trachea epithelium 48 hrs after injury. The viability of ASCs in BALF was significantly lower than those exposed to the control vehicle solution. ConclusionNebulized ASCs moderately improved pulmonary function and delayed the onset of ARDS.

Bedside electrical impedance tomography (EIT) for early assessment of lung function in liver transplantation.

Early extubation after liver transplantation is recommended by the Enhanced Recovery After Surgery Society (ERAS guideline 2022) as the benefit to avoid prolonged mechanical ventilation and associated complications. The timing of extubation is challenged by early postoperative hypoxia due to both preoperative and surgical status. Timely identifying the cause of hypoxia, typically including hepatopulmonary syndrome (HPS), pulmonary edema, atelectasis, and effusion is critical to prevent delayed extubation, especially in cases with HPS. As a radiation-free bedside approach, electrical impedance tomography (EIT) facilitates real-time lung ventilation and perfusion(V/Q) monitoring, however, the applicability of EIT V/Q monitoring for the assessment of HPS and its value for the management of hypoxia after liver transplantation has never been reported. Under this context, we took the lead in monitoring V/Q with EIT for a 12-year-old girl diagnosed with HPS who suffered intra and post liver transplantation hypoxia at the bedside. Our image raises key points for physicians that: 1) V/Q measurement of intrapulmonary shunts with bedside EIT holds the potential to identify HPS, a novel application that requires clinical validation. 2) EIT helps timely identify hypoxia after liver transplantation to support early individualized respiratory interventions. To our knowledge, V/Q monitoring by EIT is increasingly used in respiratory therapy, especially for ARDS PEEP titration, pulmonary embolism detection and lung transplantation assessment. However, The potential of EIT in liver transplant patients has been rarely studied. Our images might provide a novel and convenient approach to diagnosis HPS at bedside and offer new clinical applications for EIT imaging techniques.

Effect of Balloon Pulmonary Valvuloplasty on Growth of Pulmonary Annulus in Infants with Tetralogy of Fallot.

Percutaneous balloon pulmonary valvuloplasty (PBPV) is an alternative intervention in infants with Tetralogy of Fallot (TOF). It can not only improve hypoxia but also promote pulmonary annulus (PA) growth. In this study, we evaluated the effect of PBPV on PA growth in infants with TOF. To eliminate the effect of the systemic to pulmonary shunt (SPS) that may promote PA growth, we divided TOF infants into 2 groups: group A, patients who underwent PBPV with or without other SPS, and group B, patients who attempted SPS but without PBPV. Sixty patients were included, 28 patients in group A and 32 patients in group B. Age at the time of intervention in group A (range, 0.4-5.4; median 1.4months) was lower than that in group B (range, 2.3-7.7; median 4.8months), p-value 0.02. The body weight in group A (range, 3-5.5; median 3.7kg) was also lower than that in group B (range 4.1-6.4; median 5.9kg), p-value 0.02. Echocardiographic data at the mean follow-up period of 37.2months (3-88months) in group A and 39.6months (6-95months) in group B demonstrated an increase in mean PA diameter from 5.0 ± 1.3mm to 10.2 ± 2.9mm, p-value < 0.001 in group A; and from 6.2 ± 2mm to 9.5 ± 2.9mm, p-value < 0.001 in group B. The median PA z-score increased from -3.4SD (-3.9 to -2.6SD) to -1.8SD (-2.5 to -0.8SD), with the p-value of 0.002 in group A; and increased from -2.9SD (-4.5 to -1.3SD) to -2.7SD (-3.6 to -1.4SD), with the p-value of 0.73 in group B. By using the PA z-score as the absolute value, there was a statistically significant increase in the PA z-score during follow-up in group A, but not in group B. Balloon pulmonary valvuloplasty in infants with TOF can facilitate the growth of the pulmonic annulus even after eliminating the effect of the systemic to pulmonary shunt.

HPC+ in the medical field: Overview and current examples.

To say data is revolutionising the medical sector would be a vast understatement. The amount of medical data available today is unprecedented and has the potential to enable to date unseen forms of healthcare. To process this huge amount of data, an equally huge amount of computing power is required, which cannot be provided by regular desktop computers. These areas can be (and already are) supported by High-Performance-Computing (HPC), High-Performance Data Analytics (HPDA), and AI (together "HPC+"). This overview article aims to show state-of-the-art examples of studies supported by the National Competence Centres (NCCs) in HPC+ within the EuroCC project, employing HPC, HPDA and AI for medical applications. The included studies on different applications of HPC in the medical sector were sourced from the National Competence Centres in HPC and compiled into an overview article. Methods include the application of HPC+ for medical image processing, high-performance medical and pharmaceutical data analytics, an application for pediatric dosimetry, and a cloud-based HPC platform to support systemic pulmonary shunting procedures. This article showcases state-of-the-art applications and large-scale data analytics in the medical sector employing HPC+ within surgery, medical image processing in diagnostics, nutritional support of patients in hospitals, treating congenital heart diseases in children, and within basic research. HPC+ support scientific fields from research to industrial applications in the medical area, enabling researchers to run faster and more complex calculations, simulations and data analyses for the direct benefit of patients, doctors, clinicians and as an accelerator for medical research.

Hypoxia Associated With Dihydropyridine Calcium Channel Inhibitors: A Pharmacovigilance Study in VigiBase.

Due to their negative effects on hypoxic pulmonary vasoconstriction, dihydropyridine calcium channel inhibitors (DCCIs) can lead to hypoxia in patients with a pulmonary shunt. To date, only preclinical studies and case reports have focused on this potential adverse drug reaction. We aimed to assess the reporting association between DCCIs and hypoxia using the World Health Organization pharmacovigilance database (VigiBase). We performed a disproportionality analysis to evaluate the strength of the reporting association between i.v. clevidipine and nicardipine, thought to be a surrogate of patients in the intensive care unit, and hypoxia. The information component and the lower end of its 95% credibility interval were used to evaluate disproportionality. A description of the cases was made. Secondary outcomes included the association between all DCCIs and hypoxia compared with other treatments with similar indications, urapidil and labetalol, regardless of the route of administration. Association between oral nicardipine and hypoxia was also searched. A statistically significant signal of hypoxia was found for intravenous clevidipine and nicardipine. The time to onset was reported with a median of 2 days (interquartile range 1.5-4.5). Four dechallenges were performed with intravenous nicardipine, leading to the resolution of the symptoms. Regardless of the route of administration, a signal of hypoxia was also found for nimodipine but not for other drugs, including comparators. For nicardipine no signal of hypoxia was found with the oral route of administration. Our pharmacovigilance database analysis showed a significant association between the use of intravenous DCCIs and hypoxia.

Propofol Versus Remimazolam on Cognitive Function, Hemodynamics, and Oxygenation During One-Lung Ventilation in Older Patients Undergoing Pulmonary Lobectomy: A Randomized Controlled Trial

To investigate the effects of remimazolam on postoperative cognitive function, intraoperative hemodynamics, and oxygenation in older patients undergoing lobectomy. A prospective, double-blind, randomized, controlled study. A university hospital. Eighty-four older patients with lung cancer who underwent lobectomy, aged ≥65 years. Patients were divided randomly into the remimazolam (group R) and propofol (group P) groups. Group R underwent remimazolam anesthesia induction and maintenance, whereas group P underwent propofol anesthesia induction and maintenance. Cognitive function was assessed with neuropsychological tests 1 day before surgery and 7 days after surgery. The Clock Drawing Test, Verbal Fluency Test (VFT), Digit Symbol Switching Test (DSST), and Auditory Verbal Learning Test-Huashan (AVLT-H) assessed visuospatial ability, language function, attention, and memory, respectively. The systolic blood pressure (SBP), heart rate, mean arterial pressure (MAP), and cardiac index were recorded 5 minutes before induction of anesthesia (T0), 2 minutes after sedation (T1), 5 minutes after intubation with two-lung ventilation (T2), 30 minutes after one-lung ventilation (OLV) (T3), 60 minutes after OLV (T4), and at the end of surgery (T5), and the incidences of hypotension and bradycardia were recorded. The PaO2, oxygenation index (OI), and intrapulmonary shunt (Qs/Qt) were assessed at T0, T2, T3, T4, and T5. The levels of S-100β and interleukin 6 were measured by enzyme-linked immunosorbent assay at T0, T5, 24 hours after surgery (T6), and on day 7 after surgery (T7). The VFT, DSST, immediate recall AVLT-H, and short-delayed recall AVLT-H scores were significantly higher in group R than in group P on day 7 after surgery (p < 0.05). The SBP and MAP at T2 to T5 were significantly higher in group R than in group P, the incidence of hypotension was significantly lower in group R (9.5%) than in group P (35.7%) (p=0.004), and remimazolam significantly reduced the dose of phenylephrine used (p < 0.05). The PaO2 and OI at T4 were significantly higher in group R than in group P, and Qs/Qt was significantly lower in group R than in group P. The levels of S-100β at T5 were significantly lower in group R than in group P (p < 0.05). The results showed that remimazolam (versus propofol) may lessen the degree of short-term postoperative cognitive dysfunction measured by standard neuropsychological tests, better optimize intraoperative hemodynamics, and lead to improved oxygenation during OLV.

Retraction Note: Influence of nimodipine and nifedipine on intrapulmonary shunting - a comparison to other vasoactive drugs.

Retraction Note: Influence of nimodipine and nifedipine on intrapulmonary shunting - a comparison to other vasoactive drugs.

Comparison of the efficacy of high-flow oxygen insufflations and continuous positive airway pressure during one-lung ventilation undergoing video-assisted thoracoscopic surgery

Isolation of one-lung leads to ventilation-perfusion mismatch and increases intrapulmonary shunt, which in some cases may lead to clinically significant hypoxemia.The objective was to compare the efficacy of hypoxemia correction and the convenience of surgical work during one-lung ventilation with the use of high-flow oxygen insufflation (HFI) and continuous positive airway pressure (CPAP) in the non-ventilated lung during video-assisted thoracoscopic surgery (VATS).Materials and methods. The study included 60 patients who underwent surgical intervention in the form of VATS lobectomy. All studied patients were randomly divided into two groups: group 1 included patients who received HFI into non-ventilated lung to correct hypoxemia, and group 2 – CPAP into non-ventilated lung. The study was divided into four stages. Stage I – two-lung ventilation. Stage II – one-lung ventilation. At stage III, HFI of 60 L/min (FiO2 = 0,5) into non-ventilated lung was used to correct hypoxemia in group 1, and CPAP of 5 cm H2O into non-ventilated lung was used in group 2. At stage IV, HFI of 30 L/min (FiO2 = 0,5) into non-ventilated lung was used to correct hypoxemia in group 1, and CPAP of 2 cm H2O into non-ventilated lung was used in group 2. The following parameters were recorded during the stages of the study: PaO2, PaCO2, SpO2, Qs/Qt, and surgical team satisfaction with lung collapse by 10-point visual analogue scale (VAS).Results. At stages I and II, there was no statistically significant difference between groups in such parameters as PaO2, PaCO2, SaO2, and SpO2 (p &gt; 0.05). Starting from stage III, a statistically significant difference between the two groups was found for a parameter PaO2 (U 26.0; Z = –6.27; p &lt; 0.001). For group 1, it was equal to 134.5 (126.0; 141.75) and for group 2 – 108.5 (104.0; 114.5) correspondingly. At stage IV, the values of PaO2 were higher in group 1: 118.5 (113.0; 122.25) vs 92.5 (89.0; 98.25) in group 2 (U 0.0; Z = –6.66; p &lt; 0.001). When comparing PaCO2 between the two groups, there were no statistically significant differences at all stages (p &gt; 0.35). When comparing SaO2 at stages I (U 450.0; Z = 0.0; p = 1.0), II (U 422.5; Z = –0.4; p = 0.69), III (U 339.0; Z = –1.8; p = 0.69), no statistically significant differences were indicated between the two groups. However, at stage IV, the value of SaO2 was higher (97 (96; 97)) in group 1 than in group 2 (94 (94; 95)), U 69.5; Z = –5.75; p &lt; 0.001. When comparing SpO2 between the two groups, there was no statistical difference at all stages (p &gt; 0.69). Comparing the two groups by such indicator as Qs/Qt, no statistically significant differences were found at the first three stages (p &gt; 0.4). A comparison of Qs/Qt at stage IV revealed statistically significant differences (U 69.0; Z = –5.6; p &lt; 0.001). This parameter was equal to 10.7% (9.5; 15.7) in group 1 and 21.3% (18.4; 23.9) in group 2 correspondingly. When assessing surgical team satisfaction levels with surgical field visualization by VAS, there were statistically significant differences between group 1 and group 2 at stage III (p &lt; 0.001) and stage IV (p &lt; 0.001). The satisfaction level was significantly higher in group 1.Conclusions. The usage of high-flow oxygen insufflation during one-lung ventilation undergoing VATS allows to effectively correcting hypoxemia similar to the CPAP method, but as opposed to CPAP, it can provide comfortable conditions for carrying out the surgical procedures.

Reverse Platypnea–Orthodeoxia with Atrial Septal Defect and Diffuse Pulmonary Arteriovenous Fistulae in Hepatopulmonary Syndrome

A 69-year-old male with a long-standing diagnosis of interstitial lung disease and on domiciliary oxygen therapy was evaluated by echocardiography. His supine oxygen saturation ranged between 77% and 86% and upright oxygen saturation was 93%–94%. Two-dimensional transthoracic echocardiography showed a secundum atrial septal defect of 15 mm diameter with left-to-right shunting but without dilatation of right-sided chambers. Air bubble contrast echocardiography showed no air bubbles crossing the atrial septum but bubbles appeared in left-sided chambers through pulmonary veins after five cardiac cycles indicating intra-pulmonary shunting. Computed tomography of the chest demonstrated a mosaic pattern of the lung parenchyma, characterized by the presence of alternating geographic areas of low attenuation with regions of relatively increased attenuation typical of diffuse pulmonary arteriovenous fistulae. This is a rare case of reverse platypnea-orthodexia with possible contribution of two different pathophysiologic mechanisms but precise mechanism remains elusive.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Patent Foramen Ovale Closure in a Nonagenarian With Platypnoea-Orthodeoxia Syndrome

Patent foramen ovale (PFO) is a common congenital cardiac abnormality that affects one-quarter of the general population. Hypoxaemia, because of large right-to-left shunt, is a rare complication of PFO and occurs under exceptional physiological conditions. Case: This 90-year-old lady presented with progressive dyspnoea over several months. At presentation to hospital, she was hypoxaemic with pO2 of 53 mmHg and oxygen saturation of 89% despite 15L of oxygen via a mask. While lying supine for a computed tomography pulmonary angiogram (CTPA), it was noted that her oxygen saturation normalised. The CTPA excluded pulmonary embolus and intrapulmonary vascular anomaly. Intermittent intracardiac shunt was suspected and confirmed on formal shunt testing with a shunt fraction calculated at 32%. Transthoracic echocardiogram and cardiac CT failed to demonstrate an intracardiac shunt. Transoesophageal echocardiogram confirmed a PFO with dynamic right-to-left shunting on colour Doppler and with agitated saline. She underwent percutaneous closure with a 25-mm Amplatzer PFO Occluder, with a good procedural result and resolution of her symptoms. At the 2-month follow-up she remained well with no breathlessness and no device-related complications. This case illustrates an unusual cause of platypnoea-orthodeoxia syndrome due to PFO in a nonagenarian. It was hypothesised that a prominent Eustachian valve, and anatomical factors including enlarged tortuous aorta and pectus excavatum, had gradually progressed over time, distorting the cardiac anatomy, and contributing to significant shunting. Percutaneous PFO closure resulted in immediate symptomatic benefit.

C32 CONSTRICTIVE PERICARDITIS WITH PLATYPNEA ORTHODEOXIA

Abstract A 56–year–old woman is admitted to our centre for biventricular heart failure. In anamnesis she reports a submandibular phlegmon complicated by pleuropericarditis at the age of 13 years requiring repeated pericardiocentesis. In the last three years she has been hospitalised twice for ascites and discharged with a diagnosis of idiopathic liver cirrhosis. On admission she presented with peripheral oedema, ascites and hippocratic fingers; oxygen saturation is 80% in room air. On blood tests creatinine, transaminases, albumin, coagulation and NT–proBNP are normal, bilirubin is elevated. An echocardiography is performed showing a calcific spicola impinging the free wall of the right ventricle producing endocavitary obstruction; diffusely thickened pericardium, septal bounce, annulus reversus and expiratory reflux in the suprahepatic veins. Biventricular contractile function is normal and no significant valvulopathy is present. CT scan confirms the presence of diffuse pericardial calcifications, small liver and irregular profile with large ascitic effusion. Decongestive therapy is started with weight loss of 22 kg and regression of oedema but severe hypoxia persists with evidence of platypnea–orthodeoxia syndrome. An echocardiography is repeated showing passage of microbubbles in the left atrium from the sixth beat onwards, compatible with intrapulmonary shunt. A large arteriovenous malformation (AVM) of the right lower pulmonary branch is found at CT angiography, which is also revealed by targeted invasive angiography. Cardiac catheterisation and cardiac MRI confirmed the diagnosis of constrictive pericarditis. Percutaneous closure of the AVM with complete resolution of the hypoxia and subsequent pericardiectomy is performed. The patient is discharged on day XXVII with normal saturation on room air, in good haemodynamic compensation and with normal liver stasis parameters. In conclusion, constrictive pericarditis is a rare cause of heart failure and to our knowledge this is the second case described reporting a pulmonary AVM secondary to constrictive pericarditis.

Effect of Deferasirox on Shunt Fraction During Thoracic Surgery With One-Lung Ventilation: A Randomized Controlled Study.

Context Deferasirox, an iron chelator, can potentially reduce intraoperative right-to-left shunt and improve oxygenation in patients undergoing thoracic surgery requiring one-lung ventilation (OLV) by potentiating hypoxic pulmonary vasoconstriction (HPV). Aim The aim was to determine the effect of deferasirox on the intraoperative shunt fraction (SF) of patients undergoing thoracic surgery using OLV. Study design andsettings This was a prospective, single-blind, randomized, controlled study. The study was conducted at a tertiary-care hospital. Methods Before surgery, 64 patients were allocated to two groups comprising 32 patients each. Group D patients were administered deferasirox, while those in group C were given a placebo. We included patients with the American Society of Anesthesiologistsphysical status III or IV, aged 18-60 years, undergoing elective thoracic surgery needing OLV. SFwas the primary outcome variable. Secondary outcome variables were arterial oxygen tension (PaO2), peripheral oxygen saturation (SpO2), the ratio of PaO2 and inspired oxygen concentration (P/F), and complications such as desaturation episodes, hypotension, and tachycardia. Results Baseline and postoperative values of outcome variables were statistically similar in both groups. Intraoperative values of SF were lower and PaO2, SpO2, and P/F were higher in group D. The incidence of intraoperative desaturationwas lower in group D. Conclusion We conclude that pre-treatment with deferasirox reduces intraoperative SF and improves oxygenation during thoracic surgery using OLV.

Repurposing Inhaled Ibuprofenate, a Non Steroidal Anti‐Inflammatory Drug, as a Potential Adjuvant Treatment for Pneumonia, CARDS and its Aetiological Agent SARS‐CoV‐2

AbstractIn this manuscript, we will describe and highlight the most important potential underlying mechanisms of action of the inhaled sodium ibuprofenate in hypertonic saline formulation‐NaIHS aerosolisable, as a probable adjuvant treatment for moderate and severe pneumonia and coronavirus disease 2019 (COVID‐19)‐associated acute respiratory distress syndrome in COVID‐19. In both pathological entities, we will refer exclusively to the pulmonary vasoplegic type and we will describe the following therapeutic effects of NaIHS: anti‐inflammatory, immunomodulatory and antiangiogenic. The synergistic action of these therapeutic effects anti‐inflammatory and immunomodulatory together may exert their action at the pulmonary level through the possible reversal of pulmonary vasoplegia and may thereby restore hypoxic pulmonary vasoconstriction, correcting the uncoupling of the ventilation/perfusion ratio and vasoplegic intrapulmonary shunting and, above all, it may reverse severe hypoxaemia and acute respiratory failure. We will also mention the potential virucidal effects of NaIHS on severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2).There are available three retrospective observational studies in moderate and severe COVID‐19 pneumonia, carried out in Argentina, with all three studies concluding that there was a significant reduction in mortality. The most important of these was conducted with the approval of the Institutional Review Board of the National Bureau of Economic Research of Harvard and Columbia Universities, which analysed data from 5146 patients and concluded that NaIHS reduced mortality by 48.7%, although randomized clinical trials are still needed to confirm these emerging data and enable the rise of NaIHS as a new adjuvant treatment.Conclusively, we deem essential to reuse known drugs, such as ibuprofen, in COVID‐19, due to the constant emergence of variants and subvariants of concern secondary to mutations and immune escape mechanisms of (SARS‐CoV‐2), since effective medical treatments are currently scarce and many of them are controversial or not available worldwide.

Impact of cardiac output and alveolar ventilation in estimating ventilation/perfusion mismatch in ARDS using electrical impedance tomography

IntroductionElectrical impedance tomography (EIT) can be used to assess ventilation/perfusion (V/Q) mismatch within the lungs. Several methods have been proposed, some of them neglecting the absolute value of alveolar ventilation (VA) and cardiac output (QC). Whether this omission results in acceptable bias is unknown.MethodsPixel-level V/Q maps of 25 ARDS patients were computed once considering (absolute V/Q map) and once neglecting (relative V/Q map) the value of QC and VA. Previously published indices of V/Q mismatch were computed using absolute V/Q maps and relative V/Q maps. Indices computed with relative V/Q maps were compared to their counterparts computed using absolute V/Q maps.ResultsAmong 21 patients with ratio of alveolar ventilation to cardiac output (VA/QC) > 1, relative shunt fraction was significantly higher than absolute shunt fraction [37% (24–66) vs 19% (11–46), respectively, p < 0.001], while relative dead space fraction was significantly lower than absolute dead space fraction [40% (22–49) vs 58% (46–84), respectively, p < 0.001]. Relative wasted ventilation was significantly lower than the absolute wasted ventilation [16% (11–27) vs 29% (19–35), respectively, p < 0.001], while relative wasted perfusion was significantly higher than absolute wasted perfusion [18% (11–23) vs 11% (7–19), respectively, p < 0.001]. The opposite findings were retrieved in the four patients with VA/QC < 1.ConclusionNeglecting cardiac output and alveolar ventilation when assessing V/Q mismatch indices using EIT in ARDS patients results in significant bias, whose direction depends on the VA/QC ratio value.

Support for Postinfarction Ventricular Septal Rupture: Keep it Simple, Swift, and Safe.

To the Editor: I read with much interest the case series by Ruiz Duque et al.1 on four patients with surgical repair of postinfarction ventricular septal rupture (PIVSR) treated with Impella. The authors propose to use Impella in patients with Qp/Qs >2.5. They also raise possible concerns related to the strategy. Several issues repetitively emerge when discussing the use of Impella in PIVSR patients. First, PIVSR patients differ to much degree. We recently treated a 61 year old male patient with 16 mm inferobasal PIVSR, invasively measured Qp/Qs of 3.3, occluded distal right coronary artery and small segmental akinesia of inferior left ventricular wall. To much of our surprise, complete hemodynamic stabilization was achieved with intra-aortic balloon pump only. There was no need for mechanical ventilation, shock resolved within 1 h, lactate levels normalized, renal function recovered completely and minimal analgesia with no sedation was needed. Patient underwent successful surgical repair after 10 days of support with no need for postoperative mechanical circulatory support (MCS). Such shunt usually advocates MCS upgrade, however, in this case it was not required. It would be interesting to hear the authors explanation for the proposed Qp/Qs threshold. I wonder what other patient features would promote (or demote) upgrade in MCS treatment? Systolic function of both ventricles, stage of the shock, severity of multiorgan failure, further extension of PIVSR, are among potential candidates. Second, two issues frequently emerge when considering Impella usage for PIVSR. One is the possibility of necrotic debris systemic embolization. Given the current data, Impella is optimal MCS for reducing shunt fraction.2 By such action sheer forces delivered at the necrotic edges of PIVSR are minimized, thus lowering the risk of embolization. On the other hand, MCS or no MCS, the risk of embolization is still present. Implementing MCS strategies that increase shunting, such as veno-arterial extracorporeal membrane oxygenation, could even provoke such embolic events, although we can argue that due to higher left-to-right shunting these events would be pulmonic, not systemic. Direct severing of the debris by the impeller is highly unlikely. Nevertheless, the outcome would be either pump obstruction or debris fragmentation, resulting in reduced intensity of embolic event. The other issue is the possibility of producing right-to-left shunting.3 However, this should occur only in case of high Impella flow levels.4 Despite Impella, left ventricular pressure created by the systole should prevent or even reverse the shunt throughout a significant fraction of cardiac cycle. Indeed, Sato et al.5 reported conversion of the shunt to right-to-left direction only at flow level P6 and systemic deoxygenation at P8. By adjusting the flow under echocardiogram, the authors successfully prevented further deoxygenation. So, despite the likelihood of systemic deoxygenation, meticulous guiding of the level of the support should prevent this issue. The optimal MCS strategy for such hemodynamically fragile patients as PIVSR patients should be simple, swift, and safe. Impella is swift and simple. There is no extensive evidence it is not safe. It should be our first choice in PIVSR.

Does the presence of systemic artery–pulmonary circulation shunt during bronchial arterial embolization increase the recurrence of noncancer-related hemoptysis? A retrospective cohort study

BackgroundThe presence of systemic artery–pulmonary circulation shunt (SPS) during the bronchial arterial embolization (BAE) procedure, has been inferred to be a potential risk factor for recurrence. The aim of this study is to reveal the impact of SPS on the recurrence of noncancer-related hemoptysis after BAE.MethodsIn this study, 134 patients with SPS (SPS-present group) and 192 patients without SPS (SPS-absent group) who underwent BAE for noncancer-related hemoptysis from January 2015 to December 2020 were compared. Four different Cox proportional hazards regression models were used to clarify the impact of SPSs on hemoptysis recurrence after BAE.ResultsDuring the median follow-up time of 39.8 months, recurrence occurred in 75 (23.0%) patients, including 51 (38.1%) in the SPS-present group and 24 (12.5%) in the SPS-absent group. The 1-month, 1-year, 2-year, 3-year and 5-year hemoptysis-free survival rates in the SPS-present and SPS-absent groups were 91.8%, 79.7%, 70.6%, 62.3%, and 52.6% and 97.9%, 94.7%, 89.0%, 87.1%, and 82.3%, respectively (P < 0.001). The adjusted hazard ratios of SPSs in the four models were 3.37 [95% confidence intervals (CI), 2.07–5.47, P < 0.001 in model 1], 1.96 (95% CI, 1.11–3.49, P = 0.021 in model 2), 2.29 (95% CI, 1.34–3.92, P = 0.002 in model 3), and 2.39 (95% CI, 1.44–3.97, P = 0.001 in model 4).ConclusionsThe presence of SPS during BAE increases the recurrence probability of noncancer-related hemoptysis after BAE.

Pulmonary bypass shunt is turned off during walking in the American alligator (Alligator mississippiensis)

In non-avian reptiles, the pulmonary bypass (right-to-left) shunt directs blood away from lungs via the left aorta (LAo). At times of elevated oxygen demand, such as exercise or digestion, animals can boost systemic oxygen delivery by either increasing pulmonary bypass shunting to augment cardiac output or reducing the shunt to maximise arterial oxygen content. Previous studies on squamates and turtles showed the shunt is reduced when oxygen demand rises. In contrast, a recent study showed increased shunting during digestion in the American alligator, but whether a similar response occurs during exercise has not been reported to date. We investigated the effects of terrestrial locomotion on blood flow and shunting pattern in female juveniles of the American alligator (n=6; body mass 700-1100g). Perivascular probes were chronically implanted on the major vessels of the outflow tract: the left aorta (LAo), the left pulmonary artery (LPA), the common carotid artery (CCA), and the right aortic arch jointly with the right subclavian artery (RAo+SCA). Shunt fraction was calculated as LAo flow relative to the right ventricular output (= LAo + 2✕LPA). Experiments were performed in a walk-in environmental chamber on animals fasted for a week and equilibrated to 30°C. Upon instrumentation and recovery from surgery, animals were exercised on a level treadmill (0.5 km/h) until exhaustion. Blood flows were recorded continuously before, during and after (10+ min) exercise. Systolic blood flow in the LAo was in the forward direction (shunt on) in alligators at rest, became retrograde (shunt off) immediately upon onset of exercise, and turned anterograde (shunt on again) during recovery. Compared with flow rate values obtained at rest (1.64±0.30 ml/kg/min), average (systolic and diastolic) flow in the LAo decreased significantly during exercise (0.65±0.46 ml/kg/min), and gradually increased with time during recovery (to 1.52±0.28 ml/kg/min in the 10 th min post-exercise). In contrast, blood flow in other instrumented vessels increased during exercise, and gradually decreased during recovery. Shunt fraction was highly variable in resting animals (0.4 – 11.5%), decreased significantly during exercise, remained depressed in the 1 st min post-exercise and increased gradually during recovery to (p&lt;0.05, mixed model ANOVA, post-hoc Dunnett’s test with rest as control). This suggests that alligators turn the pulmonary bypass shunt off during acute bouts of terrestrial exercise. According to the Fick Principle, crocodilians favour increasing arterial oxygen content, by reducing admixture of oxygenated and deoxygenated bloodstreams, over augmenting cardiac output with shunt flow. Thus, despite profound differences in their heart morphology, crocodilian and non-crocodilian “reptiles” exhibit the same response – turning the shunt off – at times of elevated oxygen demand. Whether this is modulated by exercise-induced sympathetic stimulation remains to be tested. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Non-Iatrogenic Cerebral Air Embolism: A Case Report of an Extremely Rare Cause of Ischemic Stroke (P6-5.031)

<h3>Objective:</h3> NA <h3>Background:</h3> Air embolism is an uncommon but potentially catastrophic event due to air entry into the vasculature resulting in ischemic strokes. Cerebral air embolism (CAE) can be a complication of medical procedures, although non-iatrogenic sources have rarely been reported. Nonetheless, it is a life-threatening emergency with high mortality and disability. We present a patient with an acute infarct due to a CAE during air travel. <h3>Design/Methods:</h3> NA <h3>Results:</h3> <h3>Case Report:</h3> A 67-year-old woman presents with two episodes of impaired consciousness during flights while in Europe. Both happened shortly after ascent. Her symptoms quickly resolved after an emergent landing on her first trip. During the second trip, however, symptoms recurred, and she remained unconscious. She was evaluated at a local hospital where a head computed tomography (CT) showed multiple cortical air locules, predominantly in the right hemisphere, consistent with cerebral air embolism. CT chest revealed a large left bulla with surrounding neovascularization, likely the cause of the embolism. A magnetic resonance imaging (MRI) brain confirmed numerous subacute infarcts across multiple vascular territories and diffuse white matter signal abnormality, consistent with the sequela of cerebral air embolism. She was transported to the US by sea for further management at a tertiary hospital, where she had successful resection of left lung bulla. She was subsequently discharged home with very mild left ataxia. <h3>Conclusions:</h3> Non-iatrogenic CAE is an extremely rare cause of ischemic stroke. Previously described cases relate to barometric pressure changes: during diving and ascent. We describe a patient presenting with CAE secondary to pulmonary shunt from a large lung bulla under barometric pressure changes during aircraft ascent. While literature suggests CAE as a life-threatening emergency with poor prognosis, this patient had an excellent outcome after surgical resection of the lung bulla, indicating possibly different outcomes between non-iatrogenic vs. iatrogenic CAE. <b>Disclosure:</b> Dr. Su has nothing to disclose. Dr. Pandya has nothing to disclose. Dr. Reyes has nothing to disclose. Dr. Shastry has nothing to disclose. Dr. Varade has nothing to disclose.

Oxygenation performance assessment of an artificial lung in different central anatomic configurations

Aim of this work was to characterize possible central anatomical configurations in which a future artificial lung (AL) could be connected, in terms of oxygenation performance. Pulmonary and systemic circulations were simulated using a numerical and an in vitro approach. The in vitro simulation was carried out in a mock loop in three phases: (1) normal lung, (2) pulmonary shunt (50% and 100%), and (3) oxygenator support in three anatomical configurations: right atrium-pulmonary artery (RA-PA), pulmonary artery-left atrium (PA-LA), and aorta-left atrium (Ao-LA). The numerical simulation was performed for the oxygenator support phase. The oxygen saturation (SO2) of the arterial blood was plotted over time for two percentages of pulmonary shunt and three blood flow rates through the oxygenator. During the pulmonary shunt phase, SO2 reached a steady state value (of 68% for a 50% shunt and of nearly 0% for a 100% shunt) 20 min after the shunt was set. During the oxygenator support phase, physiological values of SO2 were reached for RA-PA and PA-LA, in case of a 50% pulmonary shunt. For the same conditions, Ao-LA could reach a maximum SO2 of nearly 60%. Numerical results were congruous to the in vitro simulation ones. Both in vitro and numerical simulations were able to properly characterize oxygenation properties of a future AL depending on its placement. Different anatomical configurations perform differently in terms of oxygenation. Right to right and right to left connections perform better than left to left ones.