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Pulse pressure variation (PPV) is a dynamic cardiac preload variable used to predict fluid responsiveness. PPV can be measured non-invasively using innovative finger-cuff systems allowing for continuous arterial pressure waveform recording, e.g., the Nexfin system [BMEYE B.V., Amsterdam, The Netherlands; now Clearsight (Edwards Lifesciences, Irvine, CA, USA)] (PPVFinger). However, the agreement between PPVFinger and PPV derived from an arterial catheter (PPVART) in obese patients having laparoscopic bariatric surgery is unknown. We compared PPVFinger and PPVART at 6 time points in 60 obese patients having laparoscopic bariatric surgery in a secondary analysis of a prospective method comparison study. We used Bland–Altman analysis to assess absolute agreement between PPVFinger and PPVART. The predictive agreement for fluid responsiveness between PPVFinger and PPVART was evaluated across three PPV categories (PPV 13%) as concordance rate of paired measurements and Cohen’s kappa. The overall mean of the differences between PPVFinger and PPVART was 0.5 ± 4.6% (95%-LoA − 8.6 to 9.6%) and the overall predictive agreement was 72.4% with a Cohen’s kappa of 0.53. The mean of the differences was − 0.7 ± 3.8% (95%-LoA − 8.1 to 6.7%) without pneumoperitoneum in horizontal position and 1.1 ± 4.8% (95%-LoA − 8.4 to 10.5%) during pneumoperitoneum in reverse-Trendelenburg position. The absolute agreement and predictive agreement between PPVFinger and PPVART are moderate in obese patients having laparoscopic bariatric surgery.

It remains unknown what constitutes physiologically relevant intraoperative bradycardia. Intraoperative bradycardia is usually defined using absolute heart rate thresholds, ignoring preoperative baseline heart rates. In contrast, we considered defining intraoperative bradycardia relative to preoperative ambulatory nighttime heart rate. Specifically, we hypothesized that the individual mean intraoperative heart rate is lower than the mean preoperative ambulatory nighttime heart rate. We, therefore, sought to investigate the relationship between the intraoperative and preoperative ambulatory nighttime heart rates in adults having noncardiac surgery with general anesthesia. Additionally, we sought to investigate the incidence of intraoperative bradycardia using relative versus absolute heart rate thresholds.We conducted a secondary analysis of a database from a prospective study including preoperative ambulatory and intraoperative heart rates in 363 patients having noncardiac surgery with general anesthesia.The mean intraoperative heart rate was lower than the mean nighttime heart rate (mean difference, -9 bpm; 95% confidence interval [CI], -10 to -8 bpm; P.001). The mean intraoperative heart rate was lower than the mean nighttime heart rate in 319 of 363 patients (88%; 95% CI, 84%-91%). The incidence of intraoperative bradycardia was 42% (95% CI, 38%-47%) when it was defined as intraoperative heart rate30% lower than mean nighttime heart rate and 43% (95% CI, 38%-49%) when it was defined as intraoperative heart rate45 bpm.The mean intraoperative heart rate is lower than the mean nighttime heart rate in about 9 of 10 patients. Intraoperative bradycardia might thus be physiologically and clinically important. Future research needs to investigate whether there is an association between intraoperative bradycardia and postoperative outcomes.

Blood pressure is the main determinant of organ perfusion. Hypotension is common in patients having surgery and in critically ill patients. The severity and duration of hypotension are associated with hypoperfusion and organ dysfunction. Hypotension is mostly treated reactively after low blood pressure values have already occurred. However, prediction of hypotension before it becomes clinically apparent would allow the clinician to treat hypotension pre-emptively, thereby reducing the severity and duration of hypotension. Hypotension cannowbepredictedminutes before it actually occurs from the blood pressure waveform using machine-learning algorithms that can be trained to detect subtle changes in cardiovascular dynamics preceding clinically apparent hypotension. However, analyzing the complex cardiovascular system is a challenge because cardiovascular physiology is highly interdependent, works within complicated networks, and is influenced by compensatory mechanisms. Improved hemodynamic data collection and integration will be a key to improve current models and develop new hypotension prediction models. (C) 2019 Elsevier Ltd. All rights reserved.

Background Pulmonary artery thermodilution is the clinical reference method for cardiac output monitoring. Because both continuous and intermittent pulmonary artery thermodilution are used in clinical practice it is important to know whether cardiac output measurements by the two methods are clinically interchangeable. Methods We performed a systematic review and meta-analysis of clinical studies comparing cardiac output measurements assessed using continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients. 54 studies with 1522 patients were included in the analysis. Results The heterogeneity across the studies was high. The overall random effects model-derived pooled estimate of the mean of the differences was 0.08 (95%-confidence interval 0.01 to 0.16) L/min with pooled 95%-limits of agreement of − 1.68 to 1.85 L/min and a pooled percentage error of 29.7 (95%-confidence interval 20.5 to 38.9)%. Conclusion The heterogeneity across clinical studies comparing continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients is high. The overall trueness/accuracy of continuous pulmonary artery thermodilution in comparison with intermittent pulmonary artery thermodilution is good (indicated by a pooled mean of the differences PROSPERO registration number CRD42020159730.

It remains unclear whether reduced myocardial contractility, venous dilation with decreased venous return, or arterial dilation with reduced systemic vascular resistance contribute most to hypotension after induction of general anesthesia. We sought to assess the relative contribution of various hemodynamic mechanisms to hypotension after induction of general anesthesia with sufentanil, propofol, and rocuronium. In this prospective observational study, we continuously recorded hemodynamic variables during anesthetic induction using a finger-cuff method in 92 non-cardiac surgery patients. After sufentanil administration, there was no clinically important change in arterial pressure, but heart rate increased from baseline by 11 (99.89% confidence interval: 7 to 16) bpm (P −5*m2 (P values

Pulse pressure variation (PPV) and cardiac output (CO) can guide perioperative fluid management. Capstesia (Galenic App, Vitoria-Gasteiz, Spain) is a mobile application for snapshot pulse wave analysis (PWAsnap) and estimates PPV and CO using pulse wave analysis of a snapshot of the arterial blood pressure waveform displayed on any patient monitor. We evaluated the PPV and CO measurement performance of PWAsnap in adults having major abdominal surgery. In a prospective study, we simultaneously measured PPV and CO using PWAsnap installed on a tablet computer (PPVPWAsnap, COPWAsnap) and using invasive internally calibrated pulse wave analysis (ProAQT; Pulsion Medical Systems, Feldkirchen, Germany; PPVProAQT, COProAQT). We determined the diagnostic accuracy of PPVPWAsnap in comparison to PPVProAQT according to three predefined PPV categories and by computing Cohen’s kappa coefficient. We compared COProAQT and COPWAsnap using Bland-Altman analysis, the percentage error, and four quadrant plot/concordance rate analysis to determine trending ability. We analyzed 190 paired PPV and CO measurements from 38 patients. The overall diagnostic agreement between PPVPWAsnap and PPVProAQT across the three predefined PPV categories was 64.7% with a Cohen’s kappa coefficient of 0.45. The mean (± standard deviation) of the differences between COPWAsnap and COProAQT was 0.6 ± 1.3 L min− 1 (95% limits of agreement 3.1 to − 1.9 L min− 1) with a percentage error of 48.7% and a concordance rate of 45.1%. In adults having major abdominal surgery, PPVPWAsnap moderately agrees with PPVProAQT. The absolute and trending agreement between COPWAsnap with COProAQT is poor. Technical improvements are needed before PWAsnap can be recommended for hemodynamic monitoring.

Background: Finger cuff technologies allow continuous noninvasive arterial blood pressure (AP) and cardiac output/index (CO/CI) monitoring. Methods: We performed a meta-analysis of studies comparing finger cuff-derived AP and CO/CI measurements with invasive measurements in surgical or critically ill patients. We calculated overall random effects model-derived pooled estimates of the mean of the differences and of the percentage error (PE; CO/CI studies) with 95%-confidence intervals (95%-CI), pooled 95%-limits of agreement (95%-LOA), Cochran's Q and I2 (for heterogeneity). Results: The pooled mean of the differences (95%-CI) was 4.2 (2.8 to 5.62) mm Hg with pooled 95%-LOA of –14.0 to 22.5 mm Hg for mean AP (Q=230.4 [P

The present study focuses on the identification of the gene expression profile of neonatal rat cardiomyocytes (NRVCMs) after dynamic mechanical stretch through microarrays of RNA isolated from cells stretched for 2, 6 or 24 h. In this analysis, myeloid leukemia factor-1 (MLF1) was found to be significantly downregulated during the course of stretch. We found that MLF1 is highly expressed in the heart, however, its cardiac function is unknown yet. In line with microarray data, MLF1 was profoundly downregulated in in vivo mouse models of cardiomyopathy, and also significantly reduced in the hearts of human patients with dilated cardiomyopathy. Our data indicates that the overexpression of MLF1 in NRVCMs inhibited cell proliferation while augmenting apoptosis. Conversely, knockdown of MLF1 protected NRVCMs from apoptosis and promoted cell proliferation. Moreover, we found that knockdown of MLF1 protected NRVCMs from hypoxia-induced cell death. The observed accelerated apoptosis is attributed to the activation of caspase-3/-7/PARP-dependent apoptotic signaling and upregulation of p53. Most interestingly, MLF1 knockdown significantly upregulated the expression of D cyclins suggesting its possible role in cyclin-dependent cell proliferation. Taken together, we, for the first time, identified an important role for MLF1 in NRVCM proliferation.

Intraoperative hypotension (IOH) i.e., low arterial blood pressure (AP) during surgery is common in patients having non-cardiac surgery under general anaesthesia. It has a multifactorial aetiology, and is associated with major postoperative complications including acute kidney injury, myocardial injury and death. Therefore, IOH may be a modifiable risk factor for postoperative complications. However, there is no uniform definition for IOH. IOH not only occurs during surgery but also after the induction of general anaesthesia before surgical incision. However, the optimal therapeutic approach to IOH remains elusive. There is evidence from one small randomised controlled trial that individualising AP targets may reduce the risk of postoperative organ dysfunction compared with standard care. More research is needed to define individual AP harm thresholds, to develop therapeutic strategies to treat and avoid IOH, and to integrate new technologies for continuous AP monitoring.

Calsarcin-1 deficient mice develop dilated cardiomyopathy (DCM) phenotype in pure C57BL/6 genetic background (Cs1-ko) despite severe contractile dysfunction and robust activation of fetal gene program. Here we performed a microRNA microarray to identify the molecular causes of this cardiac phenotype that revealed the dysregulation of several microRNAs including miR-301a, which was highly downregulated in Cs1-ko mice compared to the wild-type littermates. Cofilin-2 (Cfl2) was identified as one of the potential targets of miR-301a using prediction databases, which we validated by luciferase assay and mutation of predicted binding sites. Furthermore, expression of miR-301a contrastingly regulated Cfl2 expression levels in neonatal rat ventricular cardiomyocytes (NRVCM). Along these lines, Cfl2 was significantly upregulated in Cs1-ko mice, indicating the physiological association between miR-301a and Cfl2 in vivo. Mechanistically, we found that Cfl2 activated serum response factor response element (SRF-RE) driven luciferase activity in neonatal rat cardiomyocytes and in C2C12 cells. Similarly, knockdown of miR301a activated, whereas, its overexpression inhibited the SRF-RE driven luciferase activity, further strengthening physiological interaction between miR-301a and Cfl2. Interestingly, the expression of SRF and its target genes was strikingly increased in Cs1-ko suggesting a possible in vivo correlation between expression levels of Cfl2/miR-301a and SRF activation, which needs to be independently validated. In summary, our data demonstrates that miR-301a regulates Cofilin-2 in vitro in NRVCM, and in vivo in Cs1-ko mice. Our findings provide an additional and important layer of Cfl2 regulation, which we believe has an extended role in cardiac signal transduction and dilated cardiomyopathy presumably due to the reported involvement of Cfl2 in these mechanisms.