Systemic Perfusion Research Articles

Impact of extracorporeal cardiopulmonary resuscitation with ECPELLA on improvement of short-term survival in patients with refractory cardiac arrest

Abstract Background Extracorporeal cardiopulmonary resuscitation (E-CPR) is considered for cardiac arrest (CA) patients when conventional CPR is ineffective. While veno-arterial extracorporeal membrane oxygenation (VA-ECMO) robustly maintains systemic perfusion, it also increases left ventricular (LV) afterload. Recently, the transcatheter LV assist device Impella has been introduced, and the potential benefits of its combined use with VA-ECMO (ECPELLA) are anticipated. However, the utility and effective management of ECPELLA remain unclear. Purpose This single-site cohort study aimed to assess the impact of ECPELLA compared to VA-ECMO with or without intra-aortic balloon pump (IABP) in patients with refractory CA who received E-CPR. Methods We retrospectively reviewed 207 consecutive patients who underwent E-CPR between January 2012 and September 2023 at our institute. The patients were divided into two groups, ECEPLLA (n = 65) and VA-ECMO with or without IABP (n = 141). A propensity score analysis was conducted, utilizing 1:1 score matching based on variables including age, the rate of male gender, acute coronary syndrome, out-of-hospital CA (OHCA), in-hospital CA, shockable rhythm, and the time from collapse to VA-ECMO initiation, known as low flow time (LFT). We evaluated 180-day survival rates, hemodynamic data, and safety profiles. Result After propensity score matching, 57 ECPELLA patients and 57 VA-ECMO patients were included for analysis. No significant differences in the adjusted factors and comorbidities were found between the two groups. In the VA-ECMO group, 42 patients (74%) received concomitant use of IABP. During the first 72 hours following the initiation of VA-ECMO, the ECPELLA group received significantly higher total mechanical circulatory support flow compared to the VA-ECMO group, correspondingly received less catecholamine administration, and had more patients started on vasodilators and cardioprotective medications. There were no statistical differences in safety profiles, except for hemolysis and embolic cerebral infarction, between the two groups. Kaplan-Meier analysis demonstrated that the 180-day survival rates were significantly higher in the ECPELLA group than in the VA-ECMO group. In a multivariate Cox proportional hazard analysis that included age, shockable rhythm, OHCA, initial lactate levels, LFT, and ECPELLA, it was found that age (hazard ratio [HR], 1.28 [for 10-year increase]; 95% confidence interval [CI], 1.09–1.51; p = 0.002), initial lactate level (HR, 1.06; 95% CI, 1.01-1.11; p = 0.04), and ECPELLA (HR, 0.55; 95% CI, 0.36–0.85; p = 0.007) were significantly associated with 180-day mortality. Conclusion ECPELLA was associated with improvement of 180-day mortality in patient who received E-CPR. The results suggest that not only the choice of ECPELLA but also sufficient circulatory support during the acute phase, along with modulating catecholamines and vasodilators, may have influenced the prognosis.

STATE OF HAEMODYNAMICS AND OXYGEN BUDGET IN THE PERIOPERATIVE PERIOD IN PATIENTS WITH OSTEOARTHRITIS AND CONCOMITANT CARDIAC PATHOLOGY DURING TOTAL HIP ARTHROPLASTY SURGERY DEPENDING ON THE TYPE OF SURGICAL ACCESS

Summary. Aim. To compare the hemodynamic status and oxygen budget in patients with osteoarthritis and comorbid cardiac pathology during total hip arthroplasty, based on the type of surgical approach used. Materials and Methods. The study analyzed the treatment outcomes of 90 patients with stage 3-4 osteoarthritis of the hip who underwent total cemented hip arthroplasty. All patients were divided into two groups according to the surgical approach (traditional posterior or modified posterior). The study was conducted at the following stages: before surgery, immediately after surgery, 24 hours post-surgery, and one week after surgery. The following parameters were recorded: hemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and central venous pressure) and oxygen budget parameters (hemoglobin (Hb), lactate, hematocrit (Ht), oxygen saturation of hemoglobin in arterial and venous blood (SaO2 and SvO2), partial pressure of oxygen in arterial and venous blood (paO2 and pvO2)). Based on these data, the following indices were calculated: left ventricular ejection fraction (LVEF), cardiac index (CI); oxygen content in arterial and venous blood (CaO2 and CvO2), arteriovenous oxygen content difference (C(a-v)O2), oxygen transport (TO2), oxygen consumption (VO2); systemic perfusion pressure (SPP), blood flow power (BFP), oxygen reserve (OR), and circulatory reserve (CR). Results. The use of the modified posterior approach positively influenced hemodynamic parameters. After the surgery and on the 7th day post-surgery, SPP was significantly lower with the modified posterior approach. The CI was also significantly affected by the modified posterior approach. Throughout the study, except for the first stage, CI was significantly higher when using the modified posterior approach. LVEF increased significantly with both approaches, but on the 7th day post-surgery, it was significantly higher in the second group. BFP did not statistically differ between the two groups throughout the study, but its energy efficiency was lower, primarily due to the arteriovenous oxygen content difference (C(a-v)O2). C(a-v)O2 was the same before surgery for both approaches. At subsequent stages of the study, the differences between the groups increased, and on the 7th day, they were the most significant, with C(a-v)O2 being lower after using the modified posterior approach. The energy efficiency of blood flow was assessed by calculating OR and CR. Both indicators were significantly higher during the study, except at the preoperative stage, when using the modified posterior approach. Conclusions. Our study clearly demonstrates the benefits of implementing the modified posterior approach in total hip arthroplasty for patients with osteoarthritis and comorbid cardiac pathology. This approach improves hemodynamic and oxygen budget parameters compared to the traditional approach, which can significantly impact treatment outcomes for patients with cardiac comorbidity and reduce the number of postoperative complications.

The hearts of large mammals generate higher pressures, are less efficient and use more energy than those of small mammals.

A prevailing assumption in the cardiovascular field is that the metabolic rate of the heart is a constant proportion of a mammal's whole-body aerobic metabolic rate. In this Commentary, we assemble previously published cardiovascular, metabolic and body mass data from matched terrestrial mammalian species, at rest and during heavy exercise, and reveal scaling relationships that challenge this assumption. Our analyses indicate that the fractional metabolic cost of systemic perfusion compared with whole-body metabolic rate increases significantly with body size among resting mammals, from ∼2.5% in a mouse to ∼10% in an elephant. We propose that two significant body size-dependent effects contribute to this conclusion; namely, that larger species generate higher mean systemic arterial blood pressure and that their myocardium operates with lower external mechanical efficiencies compared with those of smaller species. We discuss potential physiological and mechanical explanations, including the additional energy needed to support the arterial blood column above the heart in larger species, especially those with long necks, as well as the possible sources of greater internal energy losses from the heart of larger species. Thus, we present an updated view of how increasing blood pressure and decreasing efficiency of the myocardium result in an increasing fractional metabolic cost of perfusion as body size increases among resting mammals.

Effects of Transjugular Intrahepatic Portosystemic Shunt on Renal and Pulmonary Function in Hepatic Decompensation with and without Hepatorenal and Hepatopulmonary Syndromes: A Review.

Cirrhosis is often characterized by decreased liver function, ranging from a compensated, typically asymptomatic phase to a decompensated phase characterized by the appearance of ascites or variceal bleeding, and ultimately hepatorenal syndrome (HRS) or hepatopulmonary syndrome (HPS). The latter two complications are associated with a poor prognosis and limited treatment efficacy. In cases of ascites or variceal bleeding resistant to medical therapy, transjugular intrahepatic portosystemic shunt (TIPS) is effective and safe. Shunting blood by TIPS diverts portal blood to the systemic circulation, potentially increasing systemic blood volume and benefiting renal function. However, TIPS could also divert nitric oxide to the systemic circulation, potentially worsening systemic hypotension and perfusion, which could be detrimental to renal function. Available evidence indicates that TIPS often improves renal function in patients with portal hypertension, with or without HRS. No studies have shown persistently decreased renal function after TIPS. However, these data are insufficient to support a recommendation for the use of TIPS specifically for HRS. In patients without pre-existing HPS, TIPS does not appear to significantly affect pulmonary gas exchange. Results of TIPS in HPS have been inconsistent; some studies have shown improvement, but effects were transient. No studies have shown a persistent decline in pulmonary function after TIPS. The evidence supports the need for large randomized controlled trials to investigate the beneficial effects of TIPS for HRS. Similar pulmonary function data are less clear regarding TIPS for HPS. The aim of the current report was to review the literature regarding the effects of TIPS on renal and pulmonary function in hepatic decompensation, with or without the development of HRS or HPS.

Effect of the dose, timing, and route of administration of mesenchymal stem cells on their regenerative capacity after myocardial infarction: A systematic review

Background The global rise in cases of acute myocardial infarction (AMI) poses a significant health challenge, which is why adult stem cells have gained great importance in recent years, due to their potential to promote the regeneration of the flowcardiac tissue, among which multipotent mesenchymal stromal cells (MSCs) stand out, thanks to their clinical usefulness. Objectives To evaluate the effect of the dose, timing, and route of administration of MSCs on their regenerative capacity after MI. Methods We searched for randomized clinical trials and experimental studies published up to April 25, 2024, in Medline (PubMed) and Scopus. Results Nine clinical studies were included in the qualitative assessment. The main routes of application were coronary, intramyocardially, epicardial topical and systemic venous perfusion, which could have clinical effectiveness with doses of 1x106 MSC/Kg,1 to 3 x 106, 4x106 and those greater than 0.5x106, respectively. The median number of viable cells administered was 2.4x106 (IQR: 1.6-2.4) in the PCI group versus 1.6x106 in the RCVI group (p=0.167). Median ex vivo retention was 2.55% in the RCVI group, 30 days after AMI, and 39.40% in the PCI group. At 4 and 12 months of follow-up, a better left ventricular end-to-end (LVEF) was observed in the group treated with ADSCs, at 4 (51.8% ±5.4% vs. 35.5% ±1.9%) and 8 weeks (52.1%± 3.4% versus 34.2% ±4.7%, p = 0.048). Conclusions The dosing, timing of administration, and routes of administration were important factors to assess the efficacy of the MSC.

Prognostic value of novel cardiovascular magnetic resonance transit times beyond the pulmonary circulation in patients with ventricular dysfunction.

To evaluate the prognostic value of transit time (TT) assessment in the systemic circulation and organ perfusion in patients with ventricular dysfunction (VD). The primary endpoint was defined as death, heart failure admission, or ventricular arrhythmias, and the secondary endpoint was worsening renal function. A retrospective study on 139 patients who underwent cardiac magnetic resonance for VD evaluation and 50 controls. TT was measured as peak-to-peak time in signal intensity over time curves obtained at different stages of circulation (right cavities, left cavities, aorta, and peripheral organs) from first-pass perfusion images. Outcomes were monitored over a median follow-up of 15 months. A total of 139 patients were included (84% male, age 63 [57-70] years). Patients exhibited significantly prolonged TT compared to controls, with in-patients showing longer times than outpatients. Among the 29 patients reaching the primary endpoint, both PTT and STT were significantly prolonged (PTT: 9.75 s vs 13.4 s, p < 0.01; STT: 4.77 s vs 7.00 s, p < 0.01). Concurrent prolongation of PTT (> 10 s) and STT (> 5 s) was associated with a higher event probability (42.3%), compared to isolated abnormalities (6.3% for PTT, 6.7% for STT). Multivariate analysis revealed that combined PTT and STT alteration independently predicted the combined endpoint (HR IC 95%: 8.685 (2.415-31.236), p = 0.001). Prolonged RPT was independently associated with renal function deterioration (OR IC 95%: 1.129 (1.015-1.256), p = 0.024). Evaluation of TT beyond pulmonary circulation provides prognostic insights into VD. Simultaneous assessment of PTT and STT enhances specificity compared to isolated PTT evaluation, predicting combined adverse events. RPT is independently associated with renal impairment. For the first time, it is described that transit time can be evaluated in systemic circulation and in peripheral organs and that this assessment can be easily made from conventional CMR perfusion images and holds significant prognostic value. Pulmonary transit time is a valuable hemodynamic parameter; systemic transit time may also be valuable. Transit time can be measured in the systemic circulation, and is longer in patients with ventricular dysfunction. Systemic transit time assessed by magnetic resonance imaging identifies patients with ventricular dysfunction who will experience events during follow-up.

The Relevance of the Endothelium in Cardiopulmonary Disorders.

The endothelium is a cell monolayer that lines vessels and separates tissues from blood flow. Endothelial cells (ECs) have a multitude of functions, including regulating blood flow and systemic perfusion through changes in vessel diameter. When an injury occurs, the endothelium is affected by altering its functions and structure, which leads to endothelial dysfunction, a characteristic of many vascular diseases. Understanding the role that the endothelium plays in pulmonary vascular and cardiopulmonary diseases, and exploring new therapeutic strategies is of utmost importance to advance clinically. Currently, there are several treatments able to improve patients' quality of life, however, none are effective nor curative. This review examines the critical role of the endothelium in the pulmonary vasculature, investigating the alterations that occur in ECs and their consequences for blood vessels and potential molecular targets to regulate its alterations. Additionally, we delve into promising non-pharmacological therapeutic strategies, such as exercise and diet. The significance of the endothelium in cardiopulmonary disorders is increasingly being recognized, making ECs a relevant target for novel therapies aimed at preserving their functional and structural integrity.

Factors influencing the prognosis of patients with cardiogenic shock treated with extracorporeal membrane oxygenation: A protocol for systematic review and meta-analysis.

Cardiogenic shock is a clinical syndrome caused by primary heart disease that results in decreased cardiac output and insufficient systemic perfusion. A study was conducted to determine what factors affect survival in patients with cardiogenic shock treated with extracorporeal membrane oxygenation (ECMO). A systematic search was conducted across various databases, including CKNI, VIP, Wan Fang, CBM, Embase, PubMed, Cochrane Library, and Web of Science databases, to gather factors linked to the prognosis of patients with cardiogenic shock who underwent ECMO treatment. The search period for each database was set to conclude on April 30, 2024. The findings suggest that, in comparison to the death group, the lactic acid levels of the survival group after treatment were significantly lower (95% confidence interval [CI]: -0.79, -0.58). In addition, the creatinine levels of the survival group after treatment were also significantly lower than those of the death group (95% CI: -0.39, -0.14). Furthermore, the troponin levels in the survival group after treatment were lower than those in the death group (95% CI: -0.32, 0.04), and the total bilirubin levels in the survival group after treatment were also lower than those in the death group (95% CI: -0.62, -0.23). According to the study, total bilirubin, creatinine, and lactic acid levels were lower in the survival group than in the death group when ECMO was used to treat cardiogenic patients, suggesting a better prognosis for patients with cardiogenic shock. Therefore, total bilirubin, creatinine, and lactic acid could be influential factors in the prognosis of survival in patients with cardiogenic shock.

Microaxial flow pump (Impella CP®) in patients with ST-elevation myocardial infarction complicated by cardiogenic shock.

Cardiogenic shock due to ST-elevation myocardial infarction remains a critical condition with a high mortality rate, even with current revascularization techniques. The use of mechanical circulatory support, such as the microaxial flow pump device (Impella CP®), presents a promising approach to enhance cardiac output and systemic perfusion. The DanGer Shock trial explored the efficacy of Impella CP® in addition to standard care compared to standard care alone in improving survival outcomes for these patients. Despite the potential for increased adverse events, the Impella CP® device significantly reduces mortality in patients with ST-elevation myocardial infarction complicated by cardiogenic shock. Future research should focus on refining patient selection criteria and minimizing device-related complications to maximize the therapeutic benefits of mechanical circulatory support in this critical population.

Crystalloid volume versus catecholamines for management of hemorrhagic shock during esophagectomy - assessment of microcirculatory tissue oxygenation of the gastric conduit in a porcine model using hyperspectral imaging - an experimental study.

Oncologic esophagectomy is a two-cavity procedure with considerable morbidity and mortality. Complex anatomy and the proximity to major vessels constitute a risk for massive intraoperative hemorrhage. Currently, there is no conclusive consensus on the ideal anesthesiologic countermeasure in case of such immense blood loss. The objective of this work was to identify the most promising anesthesiologic management in case of intraoperative hemorrhage with regards to tissue perfusion of the gastric conduit during esophagectomy using hyperspectral imaging (HSI). An established live porcine model (n=32) for esophagectomy was used with gastric conduit formation and simulation of a linear stapled side-to-side esophagogastrostomy. After a standardized procedure of controlled blood loss of about 1 L per pig, the four experimental groups (n=8 each) differed in anesthesiologic intervention i.e. (I) permissive hypotension, (II) catecholamine therapy using noradrenaline, (III) crystalloid volume supplementation and (IV) combined crystalloid volume supplementation with noradrenaline therapy. HSI tissue oxygenation (StO2) of the gastric conduit was evaluated and correlated with systemic perfusion parameters. Measurements were conducted before (T0) and after (T1) laparotomy, after hemorrhage (T2) and 60 minutes (T3) and 120 minutes (T4) after anesthesiologic intervention. StO2 values of the gastric conduit showed significantly different results between the four experimental groups with 63.3% (±7.6%) after permissive hypotension (I), 45.9% (±6.4%) after catecholamine therapy (II), 70.5% (±6.1%) after crystalloid volume supplementation (III) and 69.0% (±3.7%) after combined therapy (IV). StO2 values correlated strongly with systemic lactate values (r=-0.67; CI -0.77 to -0.54), which is an established prognostic factor. Crystalloid volume supplementation (III) yields the highest StO2 values and lowest systemic lactate values and therefore appears to be the superior primary treatment strategy after hemorrhage during esophagectomy with regards to microcirculatory tissue oxygenation of the gastric conduit.

Ketamine induced synaptic plasticity operates independently of long-term potentiation

Synaptic plasticity occurs via multiple mechanisms to regulate synaptic efficacy. Homeostatic and Hebbian plasticity are two such mechanisms by which neuronal synapses can be altered. Although these two processes are mechanistically distinct, they converge on downstream regulation of AMPA receptor activity to modify glutamatergic neurotransmission. However, much remains to be explored regarding how these two prominent forms of plasticity interact. Ketamine, a rapidly acting antidepressant, increases glutamatergic transmission via pharmacologically-induced homeostatic plasticity. Here, we demonstrate that Hebbian plasticity mechanisms are still intact in synapses that have undergone homeostatic scaling by ketamine after either systemic injection or perfusion onto hippocampal brain slices. We also investigated this relationship in the context of stress induced by chronic exposure to corticosterone (CORT) to better model the circumstances under which ketamine may be used as an antidepressant. We found that CORT induced an anhedonia-like behavioral phenotype in mice but did not impair long-term potentiation (LTP) induction. Furthermore, corticosterone exposure does not impact the intersection of homeostatic and Hebbian plasticity mechanisms, as synapses from CORT-exposed mice also demonstrated intact ketamine-induced plasticity and LTP in succession. These results provide a mechanistic explanation for how ketamine used for the treatment of depression does not impair the integrity of learning and memory processes encoded by mechanisms such as LTP.

Physiology-Guided Resuscitation: Monitoring and Augmenting Perfusion during Cardiopulmonary Arrest.

Given the high morbidity and mortality associated with cardiopulmonary arrest, there have been multiple trials aimed at better monitoring and augmenting coronary, cerebral, and systemic perfusion. This article aims to elucidate these interventions, first by detailing the physiology of cardiopulmonary resuscitation and the available tools for managing cardiopulmonary arrest, followed by an in-depth examination of the newest advances in the monitoring and delivery of advanced cardiac life support.

Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period.

Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.

Heat-related changes in the velocity and kinetic energy of flowing blood influence the human heart's output during hyperthermia.

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3h control (normothermic condition); (2) 3h of single-leg heating; (3) 3h of two-leg heating; and (4) 2.5h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2≥0.803; P<0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.

Development of novel technology for the visualization and quantitation of microvascular progenitor-driven adaptive angiogenesis during chronic lung disease

Introduction: Adaptive angiogenesis can drive repair or underlie the pathogenesis of tissue remodeling. Pulmonary vascular dysfunction is a major manifestation of chronic lung disease (CLD) but the role of angiogenesis in CLD is not well defined. Microvascular capillaries are the vessels most affected by pruning and remodeling in the lung resulting in reduced capillary length and density. Our lab has previously demonstrated that microvascular progenitors (ABCG2+ MVPCs) drive adaptive angiogenesis or loss of tissue structure downstream of the Wnt or mTOR signaling pathways. Therefore, we hypothesize that visualization of the pulmonary microvasculature and MVPC-driven adaptive angiogenesis in three-dimensions is essential to define the role of MVPC-driven adaptive angiogenesis during repair or the pathogenesis of CLD. Methods: To evaluate the contribution of Wnt activated MVPCs to angiogenesis in three-dimensions during injury repair, we crossed ABCG2-CreERT2 mice to a BOE strain (flΔex3) with stabilized β-catenin expression and a fluorescent membrane eGFP reporter strain to facilitate lineage tracing. The development and resolution of fibrosis were induced in vivo via aspiration of bleomycin sulfate (0.05U). Mice were retro-orbitally perfused with fluorescently conjugated tomato lectin. Lung tissue was inflated with agarose and up to 500μm thickness precision cut lung slices (PCLS) were mounted for imaging. PCLS were imaged on the Zeiss LSM900 and Z-stacks were obtained. Imaris software (Oxford Instruments) was used for three-dimensional reconstruction and FIJI and Wimasis Image Analysis (Onimagin Technologies) were utilized to segment vessels, quantitate vessel density, volume, diameter, and length. Results: Following perfusion, vascular staining of both the lung and kidney was observed, suggesting successful systemic perfusion and labeling. The pulmonary microvasculature was visualized to a diameter of 1-3μm in high fidelity. We observed a significant reduction in vessel density in mice treated with bleomycin compared to mice treated with a vehicle control. In our three-dimensional reconstructions we observed increased density of ABCG2+ MVPC-derived de novo angiogenic structures in areas of fibrosis. Conclusion: De novo angiogenesis driven by ABCG2+ MVPCs likely plays a role in tissue repair following bleomycin induced lung injury. In addition, we have developed a simple and reliable perfusion technique allowing for the visualization and quantitation of the pulmonary microvasculature in three-dimensions. This tool will allow the quantitation of microvessel remodeling underlying pathogenesis and repair in multiple lung injury models. Thus, this methodology will further support the study and understanding of angiogenesis during CLD and repair following injury. This approach may be utilized in various organ systems to visualize microvasculature structure and its role in disease. NIA RAG073317 NHLBI 1R35HL161238. This is the full abstract presented at the American Physiology Summit 2024 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.

The Effects of Dobutamine in Septic Shock: An Updated Narrative Review of Clinical and Experimental Studies.

The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.

Temporal changes in toe-brachial index results in haemodialysis patients.

Toe brachial index (TBI), the ratio of toe pressure to systolic blood pressure (SBP), helps predict peripheral arterial disease. In patients with kidney failure this may be performed during haemodialysis for convenience. Until recently there has been little evaluation of the impact of haemodialysis in limb and systemic perfusion on these values. We aimed to determine if the values of TBI would change during and after dialysis compared to pre-dialysis assessments. Using a repeated measures study, TBIs and toe pressures were measured using the Hadeco Smartop Vascular Ultrasound Doppler in 31 patients undergoing haemodialysis. TBI assessments were completed pre-dialysis and compared to values obtained at 1 hour, 2 hours, 3 hours, and post-dialysis to monitor change in TBI results. Comparison of values for each patient were tested for differences using paired t-tests. Linear mixed-effects models were used to test for the effect of patient and clinical factors on change in outcome measures. Mean TBI decreased from pre-dialysis at 1 hour (0.72 to 0.63, p = 0.01) and remained lower at 2 hours and 3 hours, before returning to pre-dialysis levels at post-dialysis. Mean systolic blood pressure also declined during dialysis. Mean TBI results were lower in those with a history of lower limb ulceration and in females. Sixteen patients (51.6%) had a normal TBI at baseline, 14 (45.2%) had a mildly low TBI, and one (3.2%) had a severely low TBI. Between baseline and 1 h, five patient's results moved from normal to mildly abnormal and one from mildly abnormal to severely abnormal. As haemodialysis concluded (post-dialysis) there were 17 (56.7%) 'normal' TBIs, with no severely abnormal TBIs (p = 0.73). 0.30). TBI and toe pressures are impacted significantly by dialysis. TBI and toe pressure assessments should be conducted before haemodialysis begins, or between dialysis sessions to avoid variability.

Haemodynamic implications of VA-ECMO vs. VA-ECMO plus Impella CP for cardiogenic shock in a large animal model.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS). Land-race pigs (weight 70kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2<30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4h. CS was induced in 15 pigs (VA-ECMO n=7, ECMELLA n=8). At time of CS MAP was <45mmHg in both groups, with no difference at 4h (VA-ECMO 64mmHg±11 vs. ECMELLA 55mmHg±21, P=0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239mL/min±97 vs. 213mL/min±133 (P=0.6) and 5.2±3.3 vs. 4.2±2.9mmol/ (P=0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567±1733 vs. 6921±5036mmHg×mL/min×10-3, P=0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248mL (179-930) vs. 506mL (418-2190); P=0.005]. In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion.

A Parameter Identification Approach towards Hemodynamics based on Capnography

Research question Pulse detection decisions during cardiopulmonary resuscitation (CPR) are commonly augmented by end-tidal CO2-concentration (etCO2) levels and trend as etCO2 is a surrogate measure of systemic blood flow during (CPR)1. However, ventilatory and circulatory parameters influence the interpretability of etCO2 heavily. Recently developed methods of continuous cardiac output measurement based on capnography are not applicable during CPR due to the required controlled ventilation settings2. In this study, a parameter identification for a model of CO2 transport during resuscitation is used to estimate cardiac output based on capnography and tidal flow. Methodology After development of a compartmental ordinary differential equation (ODE) model to represent CO2 transport during CPR, parameters such as airway dead space and the level of systemic perfusion are estimated by a multishooting parameter identification approach3. To evaluate the method, tests are conducted on experimental data from a porcine model (approved by an ethics committee vote of the Austrian Federal Ministry of Education, Science and Research (GZ: 2021-0.895.386)). The estimated level of systemic perfusion is compared visually to invasively measured mean arterial pressure due to a lack of continuous cardiac output measurements as a ground truth. Results For exemplary data from a female pig (weight 50.4 kg), airway resistance was estimated to 20.8 hPa s /L, compliance: 25.2 mL/hPa, and dead space: 109 mL. Changes in cardiac output can be identified qualitatively as shown in Fig. 1. Conclusion A validated, simple ODE model for CO2 extraction during CPR could contribute quantifying the impact of ventilatory parameters on etCO2 and elucidate CO2 production, storage and transport during cardiac arrest. Assumptions on CO2 production during cardiac arrest and redistribution in the body, and the lacking cardiac output measurements complicate the analysis. Conflicts of Interest All authors have no conflict of interest to declare.

Quantifying cardiac dysfunction and valvular heart disease associated with subretinal drusenoid deposits in age-related macular degeneration.

Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI). Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test. 82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs (p = 0.0040). All cases of aortic regurgitation (6/6, p = 0.0370) and mitral regurgitation (13/13, p = 0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, p = 0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95 ± 0.60 L/min/m2, non-SDD 2.71 ± 0.73 L/min/m2, p = 0.0004). Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.