Search Results (565)

Hemorrhagic shock is a leading cause of preventable death following multiple trauma, driven by a cascade of interacting cellular and molecular disturbances that extend well beyond simple volume loss. Acute blood loss initiates tissue hypoperfusion and cellular hypoxia, setting in motion the lethal triad of hypothermia, acidosis, and coagulopathy through several converging pathways: complement activation with excessive C3a and C5a production; neutrophil-mediated tissue injury; NADPH-oxidase-driven reactive oxygen species (ROS) overproduction that overwhelms superoxide dismutase defenses; mitochondrial respiratory chain impairment; dysregulation of the pro-inflammatory cytokine network; and endothelial apoptosis with degradation of the endothelial glycocalyx and disruption of interendothelial junctions, with consequent vascular hyperpermeability. These mechanisms provide the biological rationale for the resuscitation strategy. Each class of fluid acts on these pathways in a distinct way: crystalloids modulate acid–base homeostasis, chloride-mediated renal vasoconstriction, and coagulation factor activity; colloids influence oncotic pressure, endothelial integrity, and microvascular perfusion; and blood products, particularly plasma and whole blood, actively modulate mitochondrial metabolism, endothelial permeability, and pro-apoptotic signaling beyond their volume-expanding role. Translating this biology to the bedside requires a multimodal monitoring framework that converts molecular endpoints into real-time therapeutic targets, integrating lactate and base excess as markers of cellular oxygen debt, dynamic preload indices such as pulse pressure and stroke volume variation, advanced hemodynamic platforms, point-of-care ultrasonography, viscoelastic coagulation testing, and near-infrared spectroscopy of tissue oxygenation. This review synthesizes the biological basis of hemorrhagic shock and its translation into an individualized, goal-directed resuscitation strategy for the critically ill polytrauma patient. Full article

Cerebrovascular computational fluid dynamics (CFD) models often rely on generic boundary conditions, which may limit their ability to represent subject-specific hemodynamics and cerebral autoregulation (CA). We propose a multimodal data-driven boundary calibration (MDBC) framework integrating transcranial color-coded Doppler and continuous blood pressure monitoring to optimize individualized outlet resistances. As a proof-of-concept, we evaluated the MDBC framework in a single healthy volunteer at resting baseline and enhanced external counterpulsation (EECP)—a hemodynamic perturbation potentially triggering CA. Compared with conventional open boundary (OB) and static Murray allocation boundary (SMAB) strategies, MDBC achieved closer agreement with in vivo middle cerebral artery (MCA) velocity waveforms under both states. At rest, MDBC’s left MCA relative root mean square error (rRMSE) was 7.19%, versus 22.85% (OB) and 30.89% (SMAB). During EECP, conventional models yielded rRMSEs > 32%, whereas MDBC maintained 11.24%. Meanwhile, MDBC reproduced inter-hemispheric perfusion imbalance, an EECP-induced flow surge in the right MCA, and pronounced wall shear stress increases that were masked by generic boundary strategies. Moreover, MDBC estimated a 25.8% increase in global cerebrovascular resistance during EECP, suggesting the capability of the framework to characterize subject-specific impedance adaptations potentially associated with CA during intervention. These single-subject findings support the technical feasibility of integrating multimodal physiological measurements into cerebrovascular CFD boundary calibration and warrant further validation in larger cohorts and patient populations. Full article

Background and Objectives: Hemodynamic instability during anesthesia induction and endotracheal intubation remains a clinically important concern. Low-dose ketamine and intravenous lidocaine may provide complementary effects that improve cardiovascular stability and peripheral perfusion. This pilot study evaluated effects of adding ketamine and lidocaine to a propofol-based induction regimen using mean arterial pressure (MAP) and perfusion index (PI) as monitoring parameters. Materials and Methods: In this prospective observational pilot study, 30 adult patients undergoing elective surgery requiring general anesthesia and endotracheal intubation were allocated to either a standard induction regimen (Group 1: propofol 2 mg/kg and fentanyl 2 μg/kg) or an adjunctive regimen (Group 2: propofol 2 mg/kg, ketamine 0.4 mg/kg, lidocaine 1 mg/kg, and fentanyl 1 μg/kg). Hemodynamic variables and PI were recorded at baseline, after induction, and after intubation. Postoperative sore throat and cough-reflex responses were also assessed. Results: No significant differences between-groups were observed in heart rate, systolic blood pressure, diastolic blood pressure, MAP, or oxygen saturation at any time point. However, MAP decreased significantly within Group 1 after induction (94.9 ± 10.1 vs. 76.9 ± 13.8 mmHg, p < 0.001) and remained lower after intubation (p = 0.001), whereas no significant MAP changes occurred within Group 2. PI increased in both groups but was significantly higher in Group 2 after induction (5.35 ± 2.34 vs. 3.46 ± 2.90, p = 0.043) and after intubation (7.02 ± 2.89 vs. 4.71 ± 2.22, p = 0.020). Postoperative sore throat scores were lower in Group 2 (0.53 ± 0.91 vs. 1.67 ± 1.76, p = 0.035), and cough-reflex scores were also reduced (p = 0.024). Conclusions: The addition of low-dose ketamine and intravenous lidocaine to propofol-based induction was associated with higher perfusion index values and reduced airway-related adverse effects. No statistically significant between-group difference in mean arterial pressure (MAP) was detected. These findings are hypothesis-generating and warrant confirmation in larger randomized trials. Full article

While colonoscopies are generally benign procedures, rare complications such as colonic perforation may result in life-threatening consequences. A 15-year-old neutered male British Shorthair cat underwent colonoscopy for investigation of chronic gastrointestinal signs and persistent tenesmus. During endoscopic evaluation of a distal colonic stricture, the cat developed sudden tachycardia, severe hypoxaemia, and a dramatic decline in end-tidal carbon dioxide (EtCO₂), accompanied by diffuse subcutaneous emphysema. Intestinal perforation was suspected, and venous blood gas analysis revealed a markedly enlarged EtCO₂–PvCO₂ gradient, consistent with severe ventilation–perfusion mismatch and contributing to a presumptive diagnosis of pulmonary air embolism. Anaesthetic management focused on ventilatory adjustments, including an increased respiratory rate and initially high, then moderate peak inspiratory pressures, aimed at reducing EtCO₂ and improving oxygenation. However, improvements in oxygen saturation were limited and the cat was euthanised. Contrast-enhanced post-mortem computed tomography confirmed a distal colonic perforation with extensive air dissemination, including pneumoretroperitoneum, pneumomediastinum, pneumothorax, and subcutaneous emphysema. Full article

Background/Objectives: Intraoperative hypotension (IOHs) affects up to 87% of patients under general anesthesia and is consistently associated with acute kidney injury, myocardial damage, stroke, and mortality. The intermittent unavailability of ephedrine across healthcare systems underscores the need for evidence-based alternatives. This review critically evaluates pharmacological options for IOH when ephedrine is unavailable, focusing on receptor pharmacodynamics, population-specific evidence, and clinical consequences of inadequately managed hypotension. Methods: A narrative, evidence-based review was conducted examining mechanisms of action, dosing strategies, adverse effect profiles, and clinical applicability of key vasoactive agents: ephedrine, phenylephrine, norepinephrine, and epinephrine. Population-specific evidence across obstetric, pediatric, and elderly cohorts was synthesized from randomized controlled trials, meta-analyses, and observational studies. The clinical impact of IOH on neurological, cardiovascular, and renal outcomes was reviewed. Results: Each vasopressor exhibits a distinct receptor-selectivity profile that determines its hemodynamic effect and optimal clinical context. Norepinephrine’s favorable α1/β1 balance tends to preserve cardiac output better than pure α1-agonists and has emerged as a promising alternative in obstetric and elderly populations, although the optimal agent ultimately depends on the underlying mechanism of hypotension and individual patient characteristics. Epinephrine provides combined vasopressor and inotropic support for hypotension with myocardial depression. IOH is associated with a greater than twofold increase in postoperative AKI and significantly elevated risks of myocardial infarction and stroke, with outcomes driven by cumulative hypotensive exposure rather than isolated pressure nadirs. Conclusions: Effective management of IOH requires individualized vasopressor selection guided by underlying pathophysiology, cardiovascular profile, and surgical context. A physiology-based strategy—rather than protocol-driven drug substitution—enables anesthesiologists to achieve precise hemodynamic control and preserve end-organ perfusion even when ephedrine is unavailable. Full article

Postoperative complications following colorectal surgery—including anastomotic leak (AL), surgical site infection (SSI), perioperative haemorrhage and colovesical fistula—represent major causes of patient morbidity and mortality, prolonged hospitalisation, and healthcare expenditure. This review summarises contemporary evidence across two key domains of complication management—prevention and diagnosis—applied to four major complications (AL, SSI, perioperative haemorrhage, and colovesical fistula), drawn from a comprehensive literature review of recent randomised controlled trials, systematic reviews, meta-analyses, and prospective cohort studies. Preventive strategies discussed include optimisation of surgical techniques (minimally invasive and robotic approaches, indocyanine green perfusion assessment, self-expanding metal stent bridge-to-surgery, and negative pressure wound therapy), modification of patient factors where possible (obesity, anaemia, malnutrition, and immunosuppression), and system-level interventions including Enhanced Recovery After Surgery (ERAS) protocols, perioperative beta-blockade, prehabilitation, and structured quality improvement bundles. Diagnostic strategies have evolved to incorporate biomarker surveillance (CRP and procalcitonin), drain fluid pH analysis, CT imaging (including angiography), endoscopy, and novel digital health tools including wearable monitoring and mobile health applications. Reducing the risk of postoperative complications should involve a multidisciplinary, protocolised approach combining intraoperative technique optimisation with structured perioperative care bundles and close post-discharge surveillance, and centralisation to specialist colorectal surgical units. Full article

Background: This study aimed to evaluate associations between baseline clinical status, radiological findings, prior medical history, procedural characteristics, and recanalization success with neurological outcome at discharge (NIHSS) and functional status at 90 days (mRS). Methods: This single-center retrospective study included 100 consecutive patients with acute ischemic stroke treated with MT within 24 h of symptom onset. Clinical data, CT perfusion parameters, comorbidities, prior therapies, and detailed procedural characteristics (including anesthesia type, recanalization grade, blood pressure variability, hemorrhagic transformation, and procedure duration) were analyzed. Nonparametric tests (Mann–Whitney U, Kruskal–Wallis) and Spearman’s rank correlation were applied. Statistical significance was set at p < 0.05. Results: Early ischemic signs on baseline imaging were associated with higher NIHSS scores at discharge and worse 90-day mRS (p < 0.05). Patients undergoing CT perfusion imaging had higher discharge NIHSS. Admission NIHSS showed a moderate positive correlation with discharge NIHSS (rho = 0.367, p = 0.003). Strong correlations were observed between NIHSS at 24 h and discharge NIHSS (rho = 0.802, p < 0.001), as well as between 24 h NIHSS and 90-day mRS (rho = 0.842, p < 0.001). Successful recanalization was significantly associated with long-term outcomes, with mTICI 3 associated with the lowest 90-day mRS scores (p = 0.003). Intraprocedural blood pressure variability, hemorrhagic transformation, infections, and in-hospital complications were all linked to higher 90-day mRS values. Prolonged procedure duration showed a weak but significant correlation with worse 90-day outcome (rho = 0.232, p = 0.020). In contrast, prior comorbidities and pre-stroke therapy were not significantly associated with outcomes. A multivariable binary logistic regression analysis identified only the NIHSS score at 24 h remained as an independent predictor of favorable functional outcome at 90 days. Conclusions: Baseline stroke severity, early neurological evolution, successful reperfusion, procedural hemodynamic stability, and prevention of in-hospital complications are strongly associated with both early neurological recovery and long-term functional outcome after mechanical thrombectomy. Full article

Marfan syndrome (MFS) is characterized by progressive aortic aneurysm formation resulting from mutations in the fibrillin-1 (Fbn1) gene. Although the thoracic aorta is the primary site of pathology, accumulating evidence indicates that vascular dysfunction in MFS extends beyond the aorta to involve multiple arterial beds. Statins have been shown to attenuate aneurysm progression in experimental models of MFS; however, their effects on systemic vascular remodeling and arterial stiffness outside the aorta remain poorly characterized. In this study, we investigated the impact of chronic atorvastatin therapy on vascular structure and hemodynamic function across multiple vascular beds in the Fbn1^C1041G/+^ mouse model of MFS. Male and female control and MFS mice received drinking water with or without atorvastatin (1 g/kg/day) from 4 weeks to 6 months of age, enabling the effects of atorvastatin to be assessed in both healthy and MFS arteries. High-frequency ultrasound imaging was used to assess vascular parameters in the aorta, left common carotid artery (LCCA), and posterior cerebral artery (PCA). Atorvastatin treatment significantly attenuated aortic root dilation in both male and female MFS mice and reduced aortic pulse wave velocity (PWV), indicating improved arterial compliance. In the carotid circulation, atorvastatin significantly reduced LCCA wall thickness and carotid PWV, although carotid wall strain did not improve. Atorvastatin raised both systolic and diastolic blood pressure in male and female MFS mice relative to untreated MFS animals, reaching levels not significantly different from untreated controls in both sexes, while having little effect in healthy controls apart from a rise in female diastolic pressure. In the posterior cerebral artery, peak systolic velocity, a hemodynamic index rather than a direct measure of perfusion, showed similarly sex-dependent changes, increasing in female MFS mice but decreasing further in males after atorvastatin. Collectively, these findings demonstrate that atorvastatin exerts systemic but heterogeneous vascular effects in MFS, improving arterial stiffness and structural remodeling across multiple arterial beds while producing sex-specific hemodynamic responses that warrant further investigation. Full article

Glaucoma is a chronic, progressive optic neuropathy and the second leading cause of irreversible blindness worldwide. Although elevated intraocular pressure (IOP) remains the principal modifiable risk factor, it is neither necessary nor sufficient for disease development. The literature indicates that systemic conditions such as obstructive sleep apnea (OSA) may contribute to its pathogenesis. The pathophysiology of glaucoma is supported by several theories, primarily the mechanical and vascular theories. This review describes the pathophysiological links between OSA and glaucoma considering current theories. The principal connecting mechanism appears to be chronic intermittent hypoxia and reduced ocular perfusion pressure, which trigger optic nerve head hypoxia, oxidative stress, and biomechanical remodeling of the lamina cribrosa. These processes interact within a vicious cycle that progressively compromises the metabolic support of optic nerve axons. The mechanisms described are particularly relevant to normal-tension glaucoma, which may be associated with OSA. Retinal nerve fiber layer thinning appears among the earliest markers of optic nerve vulnerability, whereas IOP and visual field changes are more variable. These observations underscore the clinical relevance of the OSA–glaucoma relationship and support a multidisciplinary approach incorporating routine ophthalmic screening for subclinical optic nerve damage. Full article

Intraoperative anaesthetic monitoring is essential in rabbits due to their high perioperative morbidity and mortality and the limited availability of species-specific evidence, despite their increasing role as companion animals. This narrative review summarises the available scientific literature on intraoperative monitoring in anaesthetised rabbits, focusing on central nervous system assessment, cardiovascular and respiratory monitoring, and temperature management during general anaesthesia. Findings indicate that anaesthetic depth assessment based solely on ocular reflexes is unreliable and should be integrated with jaw tone, reflex responses, and respiratory patterns. Cardiovascular monitoring relies on heart rate, electrocardiography, and arterial pressure measurement, although invasive and non-invasive techniques have limitations in accuracy and practicability in small-size patients. Pulse oximetry and capnography assess oxygenation and ventilation but may be affected by peripheral perfusion, equipment dead space, and technical limitations. Temperature monitoring is critical due to high risk of hypothermia, with continuous or frequent measurements recommended. Overall, multimodal monitoring improves detection of physiological disturbances and supports safer anaesthetic management. Full article

Background: The Langendorff isolated heart model remains one of the most widely used experimental platforms for cardiovascular research. However, conventional bubble oxygenation is associated with several limitations, including inefficient gas utilization and incompatibility with protein-containing perfusates due to excessive foam formation. The present study evaluated whether membrane oxygenation could improve myocardial preservation and facilitate the use of a protein-enriched perfusion solution in a constant-pressure Langendorff system. Methods: A total of 48 male Wistar rats were allocated to six experimental groups (n = 8 per group). In the first experimental series, myocardial performance was compared between a conventional bubble oxygenator, a Terumo CAPIOX^® FX05 membrane oxygenator, and a Novalung iLA membrane oxygenator. In the second series, standard Krebs–Henseleit buffer was compared with a bovine serum albumin-enriched perfusate under membrane oxygenation. Hemodynamic parameters, coronary flow, and perfusate pH were assessed throughout a 180 min ischemia–reperfusion protocol. Results: Both membrane oxygenators demonstrated significantly improved myocardial preservation compared with the conventional bubble oxygenator, as evidenced by superior systolic and diastolic function, enhanced coronary flow, and improved overall cardiac performance. No significant differences were observed between the two membrane oxygenators. Membrane oxygenation additionally enabled stable supplementation of the perfusate with bovine serum albumin, which resulted in further improvements in ventricular function and coronary perfusion. Perfusate pH remained comparable among groups. Furthermore, membrane oxygenation reduced Carbozen consumption by approximately 33%, increasing the number of experiments that could be performed using a standard gas cylinder. Conclusions: The present findings suggest that membrane oxygenation may represent a simple and effective refinement of the Langendorff isolated heart model. Beyond improving myocardial preservation, it enables the use of protein-enriched perfusates and substantially reduces gas consumption. These findings support the incorporation of membrane oxygenation into modern Langendorff systems and provide a foundation for the development of more physiologically relevant isolated organ perfusion models. Full article

The rising prevalence of chronic kidney disease represents a major global health burden. Limitations of current renal replacement therapies, including donor organ shortages, rejection, and dialysis-related complications, underscore the need for innovative treatment options. This narrative review assesses the feasibility of bioengineered kidneys as an alternative to current treatments by discussing advances in decellularization, recellularization, and the transplantation of cell-on-scaffold kidneys. We propose that the development of functional bioengineered kidneys follows a hierarchical, staged process, in which vascular patency is the primary prerequisite for graft survival, followed by partial restoration of glomerular filtration, with complete tubular function remaining the final and most challenging milestone. Perfusion-based whole-organ decellularization has made significant progress in preserving the extracellular matrix, enabling the production of acellular human kidney scaffolds. However, complete recellularization of whole kidneys has not yet been achieved. Nevertheless, partially repopulated kidney scaffolds have been shown to withstand physiological blood pressure, produce urine, and exhibit filtration in large-animal models. Complete endothelial coverage of the vascular network proved essential for preventing thrombosis after transplantation. Current work on bioengineered kidneys shows promising results regarding feasibility for clinical application. It is important to note that most of the included studies are proof-of-concept, characterized by small sample sizes and short observation periods. Although these findings are crucial for further research, they cannot be generalized, and larger trials are recommended. In addition to cell-on-scaffold kidneys, 3D bioprinting is a promising technique that could eliminate the need for donor scaffolds. Full article

Objective: To determine whether contrast therapy improves recovery after climbing-specific forearm fatigue in amateur climbers. Methods: In a randomized repeated-measures trial, 40 climbers were allocated to passive recovery (n = 20) or Game Ready contrast therapy (n = 20). Both groups completed a fixed-task intermittent fingerboard protocol on a 20 mm edge using a half-crimp grip, with 7 s of work and 3 s of rest for five sets; the load was not individualized to climbing-specific maximal finger-flexor force. The intervention group received bilateral forearm treatment consisting of alternating 1 min cold (3 °C) and heat (45 °C) phases combined with pneumatic compression ranging from 15 to 75 mmHg. Sessions lasted 20 min and were administered immediately after post-fatigue testing, at 24 h and 48 h, and then three times weekly on alternate days for 8 weeks, for a total of 27 sessions. Outcomes were assessed at baseline, immediately after fatigue, at 24 h and 48 h, and after 8 weeks. Outcomes included perfusion, reactive hyperemia, stiffness, pressure pain threshold, grip strength, perceived recovery, creatine kinase, and interleukin-6. Results: Immediate post-fatigue responses were comparable. Contrast therapy produced greater 24 h and 48 h resting perfusion responses (+7.28 percentage points, 95% CI 6.58 to 7.98; +7.62, 95% CI 6.94 to 8.31; both adjusted p < 0.001). At week 8, peak hyperemic perfusion improved more with contrast therapy (+6.21 PU, 95% CI 5.62 to 6.79; p < 0.001). Recovery favored contrast therapy for stiffness at 48 h (−71.7 N/m, 95% CI −75.6 to −67.8), pressure pain threshold at week 8 (+8.1 N/cm², 95% CI 7.3 to 8.8), and grip strength at 48 h (+7.8 kgf, 95% CI 7.3 to 8.3; all p < 0.001). CK and IL-6 differences were transient, and no serious adverse events or intervention-related discontinuations were recorded. Conclusions: Contrast therapy was associated with more favorable cutaneous perfusion, post-occlusive reactive hyperemia-derived, and neuromechanical recovery outcomes, whereas biochemical differences were limited and time-dependent. The vascular findings do not establish improved endothelial function or nitric-oxide-mediated vasodilation because these mechanisms were not directly assessed. Trial registration: ISRCTN49499065 on 23 June 2025. Full article

Moyamoya disease is a progressive steno-occlusive cerebrovascular disorder in which cerebral perfusion may become highly dependent on systemic arterial pressure, arterial carbon dioxide tension, and collateral flow. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization procedure that promotes neovascularization over weeks to months but does not immediately augment cerebral blood flow intraoperatively. Anesthetic management therefore requires preservation of cerebral oxygen delivery during a period of persistent physiologic vulnerability. This narrative review presents a practical perioperative framework for EDAS anesthesia, emphasizing maintenance of mean arterial pressure near baseline or modestly above baseline, avoidance of hypotension and hypovolemia, normoxia, normothermia, and careful regulation of carbon dioxide. Hyperventilation should be avoided because hypocapnia can reduce cerebral blood flow through vasoconstriction, while excessive hypercapnia may contribute to regional maldistribution or steal physiology. Raw electroencephalography may provide cortical ischemia surveillance where available, whereas somatosensory evoked potentials, motor evoked potentials, near-infrared spectroscopy, and transcranial Doppler should be considered adjunctive and institution-dependent. A structured algorithm that integrates hemodynamics, ventilation, oxygen delivery, anesthetic depth, neuromonitoring, and surgical communication may support the timely recognition and correction of intraoperative hypoperfusion. Full article

Background/Objectives: Myocardial blood flow (MBF) and myocardial flow reserve (MFR) are key measurements in myocardial perfusion imaging (MPI), with [¹⁵O]H₂O-PET considered the reference standard. To further establish clinical and research utility, we investigated intra-individual variability of MBF and MFR over time in patients with angina, but no obstructive coronary disease. Methods: In a routine clinical setting, we prospectively studied 21 patients, >50 years with normal left ventricular function and no known coronary stenosis, undergoing clinically indicated PET MPI. Scan and re-scan were conducted within 30 days. Analyses were conducted by general clinical staff and re-evaluated by an expert reader. Reproducibility was assessed using paired t-tests, Bland–Altman analysis, repeatability coefficient (RC), within-subject coefficient of variation (CV) and intraclass correlation coefficient (ICC). Results: Twenty-one patients (mean age 70 ± 8.2 years; 48% female) underwent repeated scans with a median interval of 21 days. Resting MBF was 0.91 ± 0.24 vs. 0.92 ± 0.22 mL/min/g (r = 0.87; RC 0.23 mL/min/g; CV 9%; ICC 0.87). Hyperaemic MBF averaged 3.06 ± 0.9 vs. 2.97 ± 0.78 mL/min/g (r = 0.83; RC 0.98 mL/min/g; CV 11.6%; ICC 0.81). MFR showed only moderate reproducibility (3.47 ± 1.23 vs. 3.23 ± 0.92; RC 1.90; CV 21%; ICC 0.60). Neither expert re-evaluation nor rate–pressure product correction of the resting MBF improved the reproducibility. Variability was largely unaffected by atrial fibrillation and diurnal variation. Conclusions: Resting and hyperaemic MBF are reproducible, whereas MFR shows moderate variability, which should be considered when interpreting changes in individual patients. Full article