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Extracellular vesicles in cardiac repair and regeneration: Beyond stem-cell-based approaches
Front Cell Dev Biol. 2022 Sep 2;10:996887. doi: 10.3389/fcell.2022.996887. eCollection 2022.
ABSTRACT
The adult human heart poorly regenerate after injury due to the low self-renewal capability retained by adult cardiomyocytes. In the last two decades, several clinical studies have reported the ability of stem cells to induce cardiac regeneration. However, low cell integration and survival into the tissue has limited stem-cell-based clinical approaches. More recently, the release of paracrine mediators including extracellular vesicles (EV) has been recognized as the most relevant mechanism driving benefits upon cell-based therapy. In particular, EV have emerged as key mediators of cardiac repair after damage, in terms of reduction of apoptosis, resolution of inflammation and new blood vessel formation. Herein, mechanisms involved in cardiac damage and regeneration, and current applications of EV and their small non-coding RNAs (miRNAs) in regenerative medicine are discussed.
PMID:36120584 | PMC:PMC9479097 | DOI:10.3389/fcell.2022.996887
miR-486 improves fibrotic activity in myocardial infarction by targeting SRSF3/p21-Mediated cardiac myofibroblast senescence
J Cell Mol Med. 2022 Oct;26(20):5135-5149. doi: 10.1111/jcmm.17539. Epub 2022 Sep 18.
ABSTRACT
The regulation of fibrotic activities is key to improving pathological remodelling post-myocardial infarction (MI). Currently, in the clinic, safe and curative therapies for cardiac fibrosis and improvement of the pathological fibrotic environment, scar formation and pathological remodelling post-MI are lacking. Previous studies have shown that miR-486 is involved in the regulation of fibrosis. However, it is still unclear how miR-486 functions in post-MI regeneration. Here, we first demonstrated that miR-486 targeting SRSF3/p21 mediates the senescence of cardiac myofibroblasts to improve their fibrotic activity, which benefits the regeneration of MI by limiting scar size and post-MI remodelling. miR-486-targeted silencing has high potential as a novel target to improve fibrotic activity, cardiac fibrosis and pathological remodelling.
PMID:36117396 | PMC:PMC9575141 | DOI:10.1111/jcmm.17539
Erector spinae plane block versus its combination with superficial parasternal intercostal plane block for postoperative pain after cardiac surgery: a prospective, randomized, double-blind study
BMC Anesthesiol. 2022 Sep 16;22(1):295. doi: 10.1186/s12871-022-01832-0.
ABSTRACT
BACKGROUND: We aimed to compare the effectiveness of bilateral erector spinae plane (ESP) block and superficial parasternal intercostal plane (S-PIP) + ESP block in acute post-sternotomy pain following cardiac surgery.
METHODS: Forty-seven patients aged between 18 and 80 years of age with American Society of Anesthesiologists class II-III due to undergo median sternotomy for cardiac surgery were included in this prospective, randomized, double-blinded study. Following randomization into two groups, one group received bilateral ultrasound-guided ESP and the other S-PIP plus ESP block. Morphine consumption within the first 24 h after surgery was the primary outcome of the study while NRS scores at rest, NRS scores when coughing, time taken until extubation, use of rescue analgesic, presence of nausea/vomiting, length of hospital and intensive care unit (ICU) stay, and patient satisfaction were secondary outcome measures.
RESULTS: Morphine use up to 24 h following surgery was statistically significantly different between the ESP block and ESP + S-PIP block groups (18.63 ± 6.60 [15.84-21.41] mg/24 h vs 14.41 ± 5.38 [12.08-16.74] mg/24 h, p = 0.021). The ESP + S-PIP block group had considerably reduced pain scores compared to the ESP block group across all time points. Rescue analgesics were required in 21 (87.5%) patients in the ESP block group and seven (30.4%) in the ESP + S-PIP group (p < 0.001). PONV, length of stay in the ICU and hospital, and time to extubation were similar between groups.
CONCLUSIONS: In open cardiac surgery, the combination of ESP and S-PIP blocks lowers pain scores and postoperative morphine requirement of patients.
TRIAL REGISTRATION: Clinicaltrials Registration No: NCT05191953, Registration Date: 14/01/2022.
PMID:36114466 | PMC:PMC9479438 | DOI:10.1186/s12871-022-01832-0
Cardiac arrest and complications during non-invasive ventilation: a systematic review and meta-analysis with meta-regression
Intensive Care Med. 2022 Nov;48(11):1513-1524. doi: 10.1007/s00134-022-06821-y. Epub 2022 Sep 16.
ABSTRACT
PURPOSE: The aim of this study was to perform a systematic review and meta-analysis to investigate the incidence rate of cardiac arrest and severe complications occurring under non-invasive ventilation (NIV).
METHODS: We performed a systematic review and meta-analysis of studies between 1981 and 2020 that enrolled adults in whom NIV was used to treat acute respiratory failure (ARF). We generated the pooled incidence and confidence interval (95% CI) of NIV-related cardiac arrest per patient (primary outcome) and performed a meta-regression to assess the association with study characteristics. We also generated the pooled incidences of NIV failure and hospital mortality.
RESULTS: Three hundred and eight studies included a total of 7,601,148 participants with 36,326 patients under NIV (8187 in 138 randomized controlled trials, 9783 in 99 prospective observational studies, and 18,356 in 71 retrospective studies). Only 19 (6%) of the analyzed studies reported the rate of NIV-related cardiac arrest. Forty-nine cardiac arrests were reported. The pooled incidence was 0.01% (95% CI 0.00-0.02, I2 = 0% (0-15)). NIV failure was reported in 4371 patients, with a pooled incidence of 11.1% (95% CI 9.0-13.3). After meta-regression, NIV failure and the study period (before 2010) were significantly associated with NIV-related cardiac arrest. The hospital mortality pooled incidence was 6.0% (95% CI 4.4-7.9).
CONCLUSION: Cardiac arrest related to NIV occurred in one per 10,000 patients under NIV for ARF treatment. NIV-related cardiac arrest was associated with NIV failure.
PMID:36112157 | PMC:PMC9483519 | DOI:10.1007/s00134-022-06821-y
The effects of ultrasound-guided serratus anterior plane block on intraoperative opioid consumption and hemodynamic stability during breast surgery: A randomized controlled study
Medicine (Baltimore). 2022 Sep 2;101(35):e30290. doi: 10.1097/MD.0000000000030290.
ABSTRACT
AIM: To determine effect of ultrasound-guided serratus anterior plane block (SAPB) on intraoperative opioid consumption in patients undergoing oncoplastic breast surgery under general anesthesia.
METHODS: This study was conducted as a prospective, randomized controlled trial. Forty-four patients enrolled, aged 18 to 75 years with American Society of Anesthesiologists physical status I to III, undergoing elective oncoplastic breast surgery. Patients were randomly allocated to receive SAPB with 20 mL of 0.25% bupivacaine + general anesthesia (group SAPB) or only general anesthesia (group control). The primary outcome was assessing the effect of SAPB on intraoperative remifentanil consumption. Patients were assessed for emergence time, hemodynamic parameters, doses of rescue drugs used to control hemodynamic parameters, and duration of stay in the recovery room.
RESULTS: Preoperative SAPB with 0.25% bupivacaine reduced intraoperative opioid consumption (851.2 ± 423.5 vs 1409.7 ± 756.1 µg, P = .019). Emergence time was significantly shorter in group SAPB (6.19 ± 1.90 minutes) compared to group control (9.50 ± 2.39 minutes; P < .001). There were no significant differences in the doses of rescue drugs used for systolic blood pressure and heart rate between the groups.
CONCLUSIONS: Preoperative SAPB with bupivacaine reduced intraoperative opioid consumption and shortened emergence time and duration of stay in the recovery unit, and hemodynamic stability was maintained without block-related complications.
PMID:36107549 | PMC:PMC9439800 | DOI:10.1097/MD.0000000000030290
Are there differences in cardiothoracic surgery performed by trainees versus fully trained surgeons?
J Card Surg. 2022 Nov;37(11):3776-3798. doi: 10.1111/jocs.16925. Epub 2022 Sep 13.
ABSTRACT
OBJECTIVES: We sought to assess the safety of training in cardiothoracic surgery comparing outcomes of cases performed by trainees versus fully trained surgeons.
METHODS: EmBase, Scopus, PubMed, and OVID MEDLINE were searched in August 2021 independently by two authors. A third author arbitrated decisions to resolve disagreements. Inclusion criteria were articles on cardiothoracic surgery reporting on outcomes for trainees. Studies were assessed for appropriateness as per CBEM criteria. Eight hundred and ninety-two results were obtained, 27 represented best evidence (2-meta-analyses, 1-RCT, and 24 retrospective cohort studies).
RESULTS: In all 474,160 operative outcomes were assessed for 434,535 coronary artery bypass grafting (CABG) (431,329 on-pump vs. 3206 off-pump), 3090 AVR, 1740 MVR/repair, 26,433 mixed, 3565 congenital, and 4797 thoracic procedures. In all 398,058 cases were performed by trainees and 75,943 by consultants. One hundred fifty-nine cases were indeterminate. There were no statistically significant differences in the patients' preoperative risk scores. All studies excluded extreme high-risk patients in emergency setting, patients with poor left ventricular function, and reoperation cases that were undertaken by consultants. There were no differences in cardiopulmonary bypass and clamp times for CABG. Times for valve replacement and repair cases were longer for trainees. There were no differences in the postoperative outcomes including perioperative myocardial infarction, resternotomy for bleeding, stroke, renal failure, intensive therapy unit length of stay, and total length of stay. One study reported no differences on angiographic graft patency at 1 year. There were no differences in in-hospital or midterm mortality out to 5-years.
DISCUSSION: Trainees can perform cardiothoracic surgery in dedicated high-volume units with outcomes comparable to those of fully trained surgeons.
PMID:36098376 | DOI:10.1111/jocs.16925
Comparison of the Efficacy of Two Different Plane Blocks in Isolated Bypass Surgery: A Prospective Observational Study
J Cardiothorac Vasc Anesth. 2022 Dec;36(12):4333-4340. doi: 10.1053/j.jvca.2022.08.002. Epub 2022 Aug 12.
ABSTRACT
OBJECTIVE: This study evaluated the effects of serratus anterior plane block (SPB) and its combination with transverse thoracic muscle plane block (TTPB) on analgesia, opioid consumption, incentive spirometry performance, and patient comfort.
DESIGN: A prospective, observational study.
SETTING: A university hospital.
PARTICIPANTS: Adult patients scheduled for elective cardiac surgery with cardiopulmonary bypass.
INTERVENTIONS: Patients who received intravenous patient-controlled analgesia only were labeled as the control group. Patients who received additional SPB were labeled as the SPB group, and patients who received additional SPB and TTPB were labeled as the SPB+TTPB group. The visual analog scores for pain (VAS), time to first analgesic requirement, total tramadol requirement, incentive spirometry values, and patient comfort indices were recorded during the first 36 postoperative hours.
MEASUREMENTS AND MAIN RESULTS: From October 2020 to October 2021, data from 95 patients were analyzed. The VAS score was lower in the SPB+TTPB group at 0, 14, and 18 hours (p < 0.001, p = 0.028, p = 0.047, respectively). Time to first analgesic was longer in the SPB+TTPB group (8 hours v 0-2 hours, p = 0.001). Total tramadol consumption was similar among groups. Incentive spirometer performance was superior in the SPB+TTPB group (p < 0.001). The SPB group had similar success at 0, 14, and 18 hours.
CONCLUSION: Although pain scores and opioid consumption were similar, the addition of TTPB to SPB improved pain scores during patient mobilization and incentive spirometry capacity.
PMID:36100497 | DOI:10.1053/j.jvca.2022.08.002
Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure
Int J Mol Sci. 2022 Aug 31;23(17):9886. doi: 10.3390/ijms23179886.
ABSTRACT
LVAD therapy is an effective rescue in acute and especially chronic cardiac failure. In several scenarios, it provides a platform for regeneration and sustained myocardial recovery. While unloading seems to be a key element, pharmacotherapy may provide powerful tools to enhance effective cardiac regeneration. The synergy between LVAD support and medical agents may ensure satisfying outcomes on cardiomyocyte recovery followed by improved quality and quantity of patient life. This review summarizes the previous and contemporary strategies for combining LVAD with pharmacotherapy and proposes new therapeutic targets. Regulation of metabolic pathways, enhancing mitochondrial biogenesis and function, immunomodulating treatment, and stem-cell therapies represent therapeutic areas that require further experimental and clinical studies on their effectiveness in combination with mechanical unloading.
PMID:36077285 | PMC:PMC9456495 | DOI:10.3390/ijms23179886
