Leukocyte-Endothelium Interaction in the Sublingual Microcirculation of Coronary Artery Bypass Grafting Patients.

OBJECTIVE: The aim of this study was to apply an innovative methodology to incident dark-field (IDF) imaging in coronary artery bypass grafting (CABG) patients for the identification and quantification of rolling leukocytes along the sublingual microcirculatory endothelium. METHODS: This study was a post hoc analysis of a prospective study that evaluated the perioperative course of the sublingual microcirculation in CABG patients. Video images were captured using IDF imaging following the induction of anesthesia (T0) and cardiopulmonary bypass (CPB) (T1) in 10 patients. Rolling leukocytes were identified and quantified using frame averaging, which is a technique that was developed for correctly identifying leukocytes. RESULTS: The number of rolling leukocytes increased significantly from T0 (7.5 [6.4-9.1] leukocytes/capillary-postcapillary venule/4 s) to T1 (14.8 [13.2-15.5] leukocytes/capillary-postcapillary venule/4 s) (p < 0.0001). A significant increase in systemic leukocyte count was also detected from 7.4 ± 0.9 × 109/L (preoperative) to 12.4 ± 4.4 × 109/L (postoperative) (p < 0.01). CONCLUSION: The ability to directly visualize leukocyte-endothelium interaction using IDF imaging facilitates the diagnosis of a systemic inflammatory response after CPB via the identification of rolling leukocytes. Integration of the frame averaging algorithm into the software of handheld vital microscopes may enable the use of microcirculatory leukocyte count as a real-time parameter at the bedside.

Mepivacaine reduces calcium transients in isolated murine ventricular cardiomyocytes.

BACKGROUND: The potential mechanism of mepivacaine's myocardial depressant effect observed in papillary muscle has not yet been investigated at cellular level. Therefore, we evaluated mepivacaine's effects on Ca2+ transient in isolated adult mouse cardiomyocytes. METHODS: Single ventricular myocytes were enzymatically isolated from wild-type C57Bl/6 mice and loaded with 10 µM fluorescent Ca2+ indicator Fluo-4-AM to record intracellular Ca2+ transients upon electrical stimulation. The mepivacaine effects at half-maximal inhibitory concentration (IC50) was determined on calibrated cardiomyocytes' Ca2+ transients by non-parametric statistical analyses on biophysical parameters. Combination of mepivacaine with NCX blockers ORM-10103 or NiCl2 were used to test a possible mechanism to explain mepivacaine-induced Ca2+ transients' reduction. RESULTS: A significant inhibition at mepivacaine's IC50 (50 µM) on Ca2+ transients was measured in biophysical parameters such as peak (control: 528.6 ± 73.61 nM vs mepivacaine: 130.9 ± 15.63 nM; p < 0.05), peak area (control: 401.7 ± 63.09 nM*s vs mepivacaine: 72.14 ± 10.46 nM*s; p < 0.05), slope (control: 7699 ± 1110 nM/s vs mepivacaine: 1686 ± 226.6 nM/s; p < 0.05), time to peak (control: 107.9 ± 8.967 ms vs mepivacaine: 83.61 ± 7.650 ms; p < 0.05) and D50 (control: 457.1 ± 47.16 ms vs mepivacaine: 284.5 ± 22.71 ms; p < 0.05). Combination of mepivacaine with NCX blockers ORM-10103 or NiCl2 showed a significant increase in the baseline of [Ca2+] and arrhythmic activity upon electrical stimulation. CONCLUSION: At cellular level, mepivacaine blocks Na+ channels, enhancing the reverse mode activity of NCX, leading to a significant reduction of Ca2+ transients. These results suggest a new mechanism for the mepivacaine-reduction contractility effect.

Microcirculatory Response to Blood vs. Crystalloid Cardioplegia During Coronary Artery Bypass Grafting With Cardiopulmonary Bypass.

Background: Blood cardioplegia attenuates cardiopulmonary bypass (CPB)-induced systemic inflammatory response in patients undergoing cardiac surgery, which may favorably influence the microvascular system in this cohort. The aim of this study was to investigate whether blood cardioplegia would offer advantages over crystalloid cardioplegia in the preservation of microcirculation in patients undergoing coronary artery bypass grafting (CABG) with CPB. Methods: In this prospective observational cohort study, 20 patients who received crystalloid (n = 10) or blood cardioplegia (n = 10) were analyzed. The microcirculatory measurements were obtained sublingually using incident dark-field imaging at five time points ranging from the induction of anesthesia (T0) to discontinuation of CPB (T5). Results: In the both crystalloid [crystalloid cardioplegia group (CCG)] and blood cardioplegia [blood cardioplegia group (BCG)] groups, perfused vessel density (PVD), total vessel density (TVD), and proportion of perfused vessels (PPV) were reduced after the beginning of CPB. The observed reduction in microcirculatory parameters during CPB was only restored in patients who received blood cardioplegia and increased to baseline levels as demonstrated by the percentage changes from T0 to T5 (%Δ)T0-T5 in all the functional microcirculatory parameters [%ΔTVDT0-T5(CCG): -10.86 ± 2.323 vs. %ΔTVDT0-T5(BCG): 0.0804 ± 1.107, p < 0.001; %ΔPVDT0-T5(CCG): -12.91 ± 2.884 vs. %ΔPVDT0-T5(BCG): 1.528 ± 1.144, p < 0.001; %ΔPPVT0-T5(CCG): -2.345 ± 1.049 vs. %ΔPPVT0-T5(BCG): 1.482 ± 0.576, p < 0.01]. Conclusion: Blood cardioplegia ameliorates CPB-induced microcirculatory alterations better than crystalloid cardioplegia in patients undergoing CABG, which may reflect attenuation of the systemic inflammatory response. Future investigations are needed to identify the underlying mechanisms of the beneficial effects of blood cardioplegia on microcirculation.

Case Report: Sublingual Microcirculatory Alterations in a Covid-19 Patient With Subcutaneous Emphysema, Venous Thrombosis, and Pneumomediastinum.

The Corona virus disease 2019 (Covid-19) has brought a wide range of challenges in intensive care medicine. Understanding of the pathophysiology of Covid-19 relies on interpreting of its impact on the vascular, particularly microcirculatory system. Herein we report on the first use of the latest generation hand-held vital microscope to evaluate the sublingual microcirculation in a Covid-19 patient with subcutaneous emphysema, venous thrombosis and pneumomediastinum. Remarkably, microcirculatory parameters of the patient were increased during the exacerbation period, which is not a usual finding in critically ill patients mostly presenting with a loss of hemodynamic coherence. In contrast, recovery from the disease led to a subsequent amelioration of these parameters. This report clearly shows the importance of microcirculatory monitoring for evaluating the course and the adequacy of therapy in Covid-19 patients.

Perioperative risk factors of acute kidney injury after non-cardiac surgery: A multicenter, prospective, observational study in patients with low grade American Society of Anesthesiologists physical status.

BACKGROUND: The aim of this study was to determine the incidence and the perioperative risk factors of acute kidney injury (AKI) using "Kidney Disease: Improving Global Outcomes" (KDIGO) guidelines, in patients with low grade American Society of Anesthesiologists physical status (ASA-PS) undergoing non-cardiac surgery. METHODS: In this multicenter, prospective, observational study, 870 surgical patients older than 40 years with ASA-PS I-II who underwent noncardiac surgery, were included. The primary outcome of this study was perioperative AKI defined by the KDIGO criteria. RESULTS: AKI was detected in 49 (5.63%) of the patients. Multivariate analysis detected the presence of preoperative hypertension (aOR = 0.130; CI = 0.030-0.566; p = 0.007) and intraoperative transfusion of erythrocytes (aOR = 0.076; CI = 0.008-0.752; p = 0.028) as independent predictors of postoperative AKI development. CONCLUSION: Approximately, 6% of patients with ASA I-II presenting for noncardiac surgery developed postoperative AKI. Preoperative hypertension and intraoperative erythrocyte transfusion are independent predictors of AKI after non-cardiac surgery in this patient population.

Relevance of donor-specific antibody monitoring after kidney transplantation: Findings from the Collaborative Transplant Study and the Heidelberg Transplant Center.

Monitoring of donor-specific HLA antibodies (DSA) has become part of the clinical routine in kidney transplantation. This paper gives a brief overview on data from the Collaborative Transplant Study (CTS) and the Heidelberg Transplant Center on the clinical relevance of post-transplant DSA monitoring in patients undergoing renal transplantation. The obtained findings underline the importance of DSA monitoring in the post-operative course in immunologically high-risk patients and patients with deterioration of graft function. Especially in patients with a pre-activated immune system, a gap in the immunosuppressive therapy appear to lead to persistence, reappearance or de novo occurrence of strong, complement-activating DSA, resulting in severe antibody-mediated rejection (AMR) and, without timely intervention, in AMR-related graft loss.

Correction of dilutional anemia induces renal dysfunction in diabetic patients undergoing coronary artery bypass grafting: a consequence of microcirculatory alterations?

BACKGROUND: In this study we aimed to evaluate the effects of dilutional anemia resulting from cardiopulmonary bypass (CPB) and its correction with red blood cell (RBC) transfusion on tissue oxygenation and renal function in diabetic patients undergoing coronary artery bypass grafting (CABG). METHOD: 70 diabetic patients who underwent elective CABG and whose hematocrit values had been between 24-28% at any time during CBP were prospectively randomized and equally allocated to two groups: patients who received RBC during CPB (group I, n = 35) vs. did not receive RBC during CPB (group II, n = 35). Besides routine hemodynamic and biochemical parameters, biomarkers of ischemia and renal injury such as ischemia modified albumin (IMA), protein oxidation parameters [advanced oxidative protein products (AOPP), total thiol (T-SH)], neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rate (eGFR) were measured in both groups. RESULTS: In group I, T-SH, NGAL and urea levels were found to be significantly increased postoperatively compared to preoperative measurements (p < 0.05). Also, postoperatively, NGAL, creatinine, aspartate aminotransferase and AOPP levels were higher in group I than group II (p < 0.05). CONCLUSION: The correction of anemia with RBC transfusion in diabetic patients undergoing CABG could increase the risk of renal injury. Further studies verifying the effects of blood transfusions at the microcirculatory level are needed to optimize the efficacy of transfusions.

Cytocam-IDF (incident dark field illumination) imaging for bedside monitoring of the microcirculation.

BACKGROUND: Orthogonal polarized spectral (OPS) and sidestream dark field (SDF) imaging video microscope devices were introduced for observation of the microcirculation but, due to technical limitations, have remained as research tools. Recently, a novel handheld microscope based on incident dark field illumination (IDF) has been introduced for clinical use. The Cytocam-IDF imaging device consists of a pen-like probe incorporating IDF illumination with a set of high-resolution lenses projecting images on to a computer controlled image sensor synchronized with very short pulsed illumination light. This study was performed to validate Cytocam-IDF imaging by comparison to SDF imaging in volunteers. METHODS: This study is a prospective, observational study. The subjects consist of 25 volunteers. RESULTS: Sublingual microcirculation was evaluated using both techniques. The main result was that Cytocam-IDF imaging provided better quality images and was able to detect 30% more capillaries than SDF imaging (total vessels density Cytocam-IDF: 21.60 ± 4.30 mm/mm(2) vs SDF: 16.35 ± 2.78 mm/mm(2), p < 0.0001). Comparison of the images showed increased contrast, sharpness, and image quality of both venules and capillaries. CONCLUSIONS: Cytocam-IDF imaging detected more capillaries and provided better image quality than SDF imaging. It is concluded that Cytocam-IDF imaging may provide a new improved imaging modality for clinical assessment of microcirculatory alterations.

Factors Affecting Tissue Oxygenation in Erythrocyte Transfusions.

Red blood cell transfusions are used to increase the oxygen-carrying capacity of blood in anemic states. But, because of the changes during storage of blood components and the specifics of preparation, erythrocytes may have controversial effects on tissue oxygenation and microcirculation. Also, the patient situation may play a role in the differing responses in oxygenation and microcirculation. In this review, the studies concerning the effects of banked blood and patient characteristics on microcirculation and tissue oxygenation are summarized.