Agregador de feeds

Multimed Man Cardiothorac Surg. 2022 Nov 10;2022. doi: 10.1510/mmcts.2022.079.

ABSTRACT

The extracardiac Fontan can be completed as an interventional procedure when the preparatory stage for Fontan completion is performed at the time of the bidirectional Glenn operation. In this video tutorial, we present the technique for the preparatory stage of an interventional extracardiac Fontan. The interventional aspect offers the advantage of avoiding a redo sternotomy, which involves the risk of cardiac injury, injury to the mediastinal collaterals due to the single-ventricle physiology, the acquired deranged coagulation that may incur morbidity associated with sternal re-entry, and the problems pertinent to cardiopulmonary bypass and/or cardioplegic arrest in this subset of patients.

PMID:36355352 | DOI:10.1510/mmcts.2022.079

J Card Surg. 2022 Nov 9. doi: 10.1111/jocs.17134. Online ahead of print.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a major determinant of short- and long-term morbidity and mortality following cardiac surgery. The present study examines the effect of preoperative nutritional status and frailty on this significant adverse event.

METHODS: The data of 455 patients who underwent on-pump coronary artery bypass grafting (CABG) were analyzed retrospectively. Demographic data were recorded, and intraoperative and postoperative parameters, frailty score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI) were calculated. Risk factors for AKI within 7 postoperative days were investigated in accordance with the kidney disease improving global outcomes classification.

RESULTS: Preoperative urea and creatinine values were significantly higher (p = .006 vs. p = .006), while hemoglobin, hematocrit, and estimated glomerular filtration rate values were significantly lower (p = .011, p = .008 vs. p = .006) in the AKI group than no AKI group. In the intraoperative period, the cardiopulmonary bypass time was longer in the AKI group (p = .031), and the need for dopamine, steradine, and red blood cells transfusion was greater (p = .026, p = .038 vs. p = .015) than no AKI group. The number of patients with a frailty score of 1-3 was significantly higher in the AKI group (p = .042). Similarly, the GNRI and PNI values, indicating nutritional status, were higher in the AKI group (p = .047 vs. p = .024). The independent risk factors for AKI were a GNRI of <91, the intraoperative need for dobutamine, preoperative serum creatinine of >1.3, and hemoglobin of <10 (p < .05).

CONCLUSIONS: Malnutrition and frailty are strongly associated with AKI after CABG. Clinicians can effectively predict the risk of AKI through an evaluation of frailty and nutritional scores, which can be easily calculated in the preoperative period.

PMID:36352787 | DOI:10.1111/jocs.17134

Clin Hemorheol Microcirc. 2022 Nov 1. doi: 10.3233/CH-221473. Online ahead of print.

ABSTRACT

BACKGROUND: Liver transplantation is a life-saving treatment in end-stage liver failure. Hemorheological features as blood fluidity and red blood cell aggregation may alter effective tissue perfusion, graft function and hemodynamic variables.

OBJECTIVE: The aim of the study is to investigate effect of albumin infusion on red blood cell deformability and aggregation, blood viscosity and hemodynamics in liver transplant patients.

METHODS: Seventeen live or cadaveric donors were included in this prospective study. Hemorheological and hemodynamic measurements were performed in order to evaluate the effects of albumin infusion in perioperative period.

RESULTS: Erythrocyte aggregation was significantly reduced 90 minutes after albumin infusion (p < 0.01). Mean blood viscosity revealed significant decrease at 20 rpm and 50 rpm after 90 minutes of albumin infusion (p < 0.05). Plasma viscosity decreased significantly compared to the value before albumin infusion at 20 rpm (p < 0.05). Albumin replacement improved hemodynamic variables in patients with low blood pressure and cardiac index measurements (p > 0.05).

CONCLUSIONS: Human albumin infusion led to decrease in whole blood and plasma viscosities, red blood cell aggregation and induced blood pressure and cardiac index elevation in perioperative liver transplant patients. Determination of hemodynamic and hemorheological effects of human albumin replacement in various patient populations may serve beneficial clinical data.

PMID:36336924 | DOI:10.3233/CH-221473

J Clin Anesth. 2022 Dec;83:110985. doi: 10.1016/j.jclinane.2022.110985. Epub 2022 Oct 27.

ABSTRACT

BACKGROUND AND STUDY OBJECTIVE: Acute kidney injury (AKI) is a sudden deterioration in renal function and is common in pediatric patients undergoing cardiac and non-cardiac surgery. Few studies have investigated the association of postoperative AKI with kidney dysfunction seen long-term and other adverse outcomes in pediatric patients. The study aimed to determine the association between postoperative AKI (mild AKI vs. no AKI and mild AKI vs. moderate-severe AKI) and chronic kidney dysfunction (CKD) seen long-term in pediatric patients undergoing cardiac and non-cardiac major surgery.

DESIGN: Restrospective, cohort study.

SETTING: Tertiary care hospital.

PATIENTS: This retrospective cohort study included patients aged 2-18 years who underwent cardiac and non-cardiac major surgery lasting >2 h at the Cleveland Clinic Main Campus between June 2005 and December 2020.

MEASUREMENTS: Postoperative AKI and CKD seen in long-term were defined and staged according to the Kidney Disease: Improving Global Outcomes criteria.

MAIN RESULTS: Among 10,597 children who had cardiac and non-cardiac major surgery, 1,302 were eligible. A total of 682 patients were excluded for missing variables and baseline kidney dysfunction and 620 patients were included. The mean age was 11 years, and 307 (49.5%) were female. Postoperative mild AKI was detected in 5.8% of the patients, while moderate-severe AKI was detected in 2.4%. There was no significant difference in CKD seen in long-term between patients with and without postoperative AKI, p = 0.83. The CKD seen in long-term developed in 27.7% of patients with postoperative mild AKI and 33.3% of patients with postoperative moderate and severe AKI. Patients without postoperative AKI had an estimated 1.09 times higher odds of having CKD seen in long-term compared with patients who have postoperative mild AKI (odds ratio [95% CI] 1.09 [0.48,2.52]).

CONCLUSION: In contrast to adult patients, the authors did not find any association between postoperative AKI and CKD seen in long-term in pediatric patients.

PMID:36332365 | DOI:10.1016/j.jclinane.2022.110985

J Card Surg. 2022 Nov 2. doi: 10.1111/jocs.17068. Online ahead of print.

ABSTRACT

INTRODUCTION: Coronary artery bypass grafting (CABG) remains a good revascularization strategy in octogenarians with excellent clinical outcomes and quality of life postoperatively. However, the benefits of off-pump over on-pump CABG in the elderly population are still controversial. We investigated this issue in the UK National Audit database.

METHOD: We retrospectively analyzed all octogenarians undergoing nonemergency, isolated CABG from 1996 to 2019. Propensity score matching (PSM) was conducted to adjust for imbalance in the baseline characteristics between the off-pump and on-pump groups. Primary outcome was in-hospital mortality and postoperative cerebrovascular accidents. Secondary outcomes were bleeding requiring reoperation, deep sternal wound infection, and postoperative dialysis.

RESULT: A total of 6436 patients were included for analysis. No differences were observed between off- and on-pump group in-hospital mortality (4% vs. 3.8%, p = .89), return to theater rate (5.4% vs. 6.2%, p = .16) and incidence of deep sternal wound infection (1.1% vs. 1.6%, p = .34). However, octogenarian undergoing off-pump CABG were less likely to experience postoperative transient ischemic attack (TIA)/stroke (1.4% vs. 2.3%, p = .004) but more likely to require renal dialysis (4.8% vs. 3.5%, p = .03).

CONCLUSION: The data show similar in-hospital mortality in octogenarians regardless of the revascularization technique used. Off-pump when compared with on-pump CABG is associated with a lower incidence in postoperative neurological events but a higher need for renal dialysis.

PMID:36321671 | DOI:10.1111/jocs.17068

Biomark Med. 2022 Oct 31. doi: 10.2217/bmm-2022-0341. Online ahead of print.

ABSTRACT

Introduction: Our aim was to use the red cell distribution width-lymphocyte ratio (RLR) as a novel biomarker to predict prolonged intensive-care unit (ICU) length of stay (LOS) among older patients undergoing cardiovascular surgery. Methods: This longitudinal study included older patients admitted to a tertiary cardiovascular surgery hospital between January 2017 and January 2022. Results: A total of 574 patients were studied, including 83 patients (14.5%) who had prolonged ICU LOS and 471 (85.5%) control subjects. After adjustment for the European System for Cardiac Operative Risk Evaluation 2, the RLR score showed a 10% increased risk of prolonged ICU LOS (odds ratio: 1.10; CI: 1.05-1.16; p = 0.01). Conclusion: Preoperative RLR can be used to predict the risk of long-term intensive care stay in older cardiac surgery patients.

PMID:36314262 | DOI:10.2217/bmm-2022-0341

J Cardiothorac Vasc Anesth. 2023 Jan;37(1):65-72. doi: 10.1053/j.jvca.2022.09.094. Epub 2022 Sep 30.

ABSTRACT

OBJECTIVE: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN: Prospective, randomized, double-blind study.

SETTING: Single center, university hospital.

PARTICIPANTS: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass.

INTERVENTIONS: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed.

RESULTS: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041).

CONCLUSION: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.

PMID:36307353 | DOI:10.1053/j.jvca.2022.09.094

Turk Gogus Kalp Damar Cerrahisi Derg. 2022 Jul 29;30(3):354-362. doi: 10.5606/tgkdc.dergisi.2022.23321. eCollection 2022 Jul.

ABSTRACT

BACKGROUND: The aim of this study was to investigate the effects on QT interval of the propofol-ketamine combination and the midazolam-fentanyl combination in anesthesia induction for cardiac surgery.

METHODS: Between September 2020 and June 2021, a total of 9 5 c ardiac s urgery p atients ( 80 m ales, 1 5 f emales; mean age: 57±9.1 years; range, 26 to 76 years) were included. The patients were divided into two groups as Group PK (propofol-ketamine, n=50) and Group MF (midazolam-fentanyl, n=45). The 12-lead electrocardiographic and hemodynamic measurements were performed at three time points: before anesthesia induction, after anesthesia induction, and after endotracheal intubation. The measurements were evaluated with conventional Bazett's formula and a new model called index of cardio-electrophysiological balance.

RESULTS: The evaluated QTc values of 95 patients after anesthesia induction were significantly prolonged with the Bazett's formula and the index of cardio-electrophysiological balance in Group PK (p=0.034 and p=0.003, respectively). A statistically significant QTc prolongation was observed with the index of cardio-electrophysiological balance after laryngoscopy and endotracheal intubation in Group PK (p=0.042). Hemodynamic parameters were also higher in Group PK.

CONCLUSION: Our study shows that the propofol-ketamine combination prolongs the QTc value determined by the Bazett's formula and the index of cardio-electrophysiological balance model. Using both QTc measurement models, the midazolam-fentanyl combination has no prolongation effect on QTc interval in coronary surgery patients.

PMID:36303704 | PMC:PMC9580297 | DOI:10.5606/tgkdc.dergisi.2022.23321

Front Cardiovasc Med. 2022 Oct 10;9:953211. doi: 10.3389/fcvm.2022.953211. eCollection 2022.

ABSTRACT

BACKGROUND: Mechanisms contributing to tissue remodeling of the infarcted heart following cell-based therapy remain elusive. While cell-based interventions have the potential to influence the cardiac healing process, there is little direct evidence of preservation of functional myocardium.

AIM: The aim of the study was to investigate tissue remodeling in the infarcted heart following human embryonic stem cell-derived endothelial cell product (hESC-ECP) therapy.

MATERIALS AND METHODS: Following coronary artery ligation (CAL) to induce cardiac ischemia, we investigated infarct size at 1 day post-injection in media-injected controls (CALM, n = 11), hESC-ECP-injected mice (CALC, n = 10), and dead hESC-ECP-injected mice (CALD, n = 6); echocardiography-based functional outcomes 14 days post-injection in experimental (CALM, n = 13; CALC, n = 17) and SHAM surgical mice (n = 4); and mature infarct size (CALM and CALC, both n = 6). We investigated ligand-receptor interactions (LRIs) in hESC-ECP cell populations, incorporating a publicly available C57BL/6J mouse cardiomyocyte-free scRNAseq dataset with naive, 1 day, and 3 days post-CAL hearts.

RESULTS: Human embryonic stem cell-derived endothelial cell product injection reduces the infarct area (CALM: 54.5 ± 5.0%, CALC: 21.3 ± 4.9%), and end-diastolic (CALM: 87.8 ± 8.9 uL, CALC: 63.3 ± 2.7 uL) and end-systolic ventricular volume (CALM: 56.4 ± 9.3 uL, CALC: 33.7 ± 2.6 uL). LRI analyses indicate an alternative immunomodulatory effect mediated via viable hESC-ECP-resident signaling.

CONCLUSION: Delivery of the live hESC-ECP following CAL modulates the wound healing response during acute pathological remodeling, reducing infarct area, and preserving functional myocardium in this relatively acute model. Potential intrinsic myocardial cellular/hESC-ECP interactions indicate that discreet immunomodulation could provide novel therapeutic avenues to improve cardiac outcomes following myocardial infarction.

PMID:36299872 | PMC:PMC9588936 | DOI:10.3389/fcvm.2022.953211

Turk J Anaesthesiol Reanim. 2022 Oct;50(5):388-391. doi: 10.5152/TJAR.2021.21335.

ABSTRACT

Colour Doppler imaging of the ophthalmic artery is a non-invasive, fast, and easy access ultrasound technique. Estimation of cerebral perfusion from colour Doppler imaging of the ophthalmic artery is a technique with great potential in this field. In the present case, we monitored blood flow of the ophthalmic artery by colour Doppler ultrasonography during heart transplantation, and we obtained information about the adequacy of the perfusion. Colour Doppler imaging of the ophthalmic artery may be a useful method that can be applied for monitoring cerebral perfusion during heart transplantation and all cardiac operations in order to detect impaired cerebral blood flow.

PMID:36301289 | PMC:PMC9682951 | DOI:10.5152/TJAR.2021.21335

JAMA. 2022 Nov 8;328(18):1827-1836. doi: 10.1001/jama.2022.17714.

ABSTRACT

IMPORTANCE: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in critically ill patients, but little is known regarding long-term psychiatric sequelae among survivors after ECMO.

OBJECTIVE: To investigate the association between ECMO survivorship and postdischarge mental health diagnoses among adult survivors of critical illness.

DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study in Ontario, Canada, from April 1, 2010, through March 31, 2020. Adult patients (N=4462; age ≥18 years) admitted to the intensive care unit (ICU), and surviving to hospital discharge were included.

EXPOSURES: Receipt of ECMO.

MAIN OUTCOMES AND MEASURES: The primary outcome was a new mental health diagnosis (a composite of mood disorders, anxiety disorders, posttraumatic stress disorder; schizophrenia, other psychotic disorders; other mental health disorders; and social problems) following discharge. There were 8 secondary outcomes including incidence of substance misuse, deliberate self-harm, death by suicide, and individual components of the composite primary outcome. Patients were compared with ICU survivors not receiving ECMO using overlap propensity score-weighted cause-specific proportional hazard models.

RESULTS: Among 642 survivors who received ECMO (mean age, 50.7 years; 40.7% female), median length of follow-up was 730 days; among 3820 matched ICU survivors who did not receive ECMO (mean age, 51.0 years; 40.0% female), median length of follow-up was 1390 days. Incidence of new mental health conditions among survivors who received ECMO was 22.1 per 100-person years (95% confidence interval [CI] 19.5-25.1), and 14.5 per 100-person years (95% CI, 13.8-15.2) among non-ECMO ICU survivors (absolute rate difference of 7.6 per 100-person years [95% CI, 4.7-10.5]). Following propensity weighting, ECMO survivorship was significantly associated with an increased risk of new mental health diagnosis (hazard ratio [HR] 1.24 [95% CI, 1.01-1.52]). There were no significant differences between survivors who received ECMO vs ICU survivors who did not receive ECMO in substance misuse (1.6 [95% CI, 1.1 to 2.4] per 100 person-years vs 1.4 [95% CI, 1.2 to 1.6] per 100 person-years; absolute rate difference, 0.2 per 100 person-years [95% CI, -0.4 to 0.8]; HR, 0.86 [95% CI, 0.48 to 1.53]) or deliberate self-harm (0.4 [95% CI, 0.2 to 0.9] per 100 person-years vs 0.3 [95% CI, 0.2 to 0.3] per 100 person-years; absolute rate difference, 0.1 per 100 person-years [95% CI, -0.2 to 0.4]; HR, 0.68 [95% CI, 0.21 to 2.23]). There were fewer than 5 total cases of death by suicide in the entire cohort.

CONCLUSIONS AND RELEVANCE: Among adult survivors of critical illness, receipt of ECMO, compared with ICU hospitalization without ECMO, was significantly associated with a modestly increased risk of new mental health diagnosis or social problem diagnosis after discharge. Further research is necessary to elucidate the potential mechanisms underlying this relationship.

PMID:36286084 | PMC:PMC9608013 | DOI:10.1001/jama.2022.17714

Ulus Travma Acil Cerrahi Derg. 2022 Nov;28(11):1563-1569. doi: 10.14744/tjtes.2022.92672.

ABSTRACT

BACKGROUND: Anesthesia management of pheochromocytoma excision surgery is associated with severe hemodynamic fluctuations. The objective of this study is to compare the number of hypertensive crisis requiring sodium nitroprusside (SNP) administration between the groups treated with magnesium (Mg)-dexmedetomidine (Dex) and conventional group in pheochromocytoma.

METHODS: This retrospective cohort study included patients who underwent pheochromocytoma surgery between 2011 and 2020. Patients were examined into two groups: 1-Conventional group (GC) included patients who were operated between 2011 and 2015 under standard anesthesia care and who did not receive perioperative additional medication. 2- Mg-Dex therapy group (GMD) comprised the patients who were operated between 2015 and 2020 and who had received 300 mg Mg per oral daily 1 week before the surgery and Mg-Dex infusion intraoperatively. Blood pressure, heart rate (HR), and SNP requirement were recorded throughout surgery as well as demographics and operative data. Hypertensive crisis was defined as systolic blood pressure (SBP) >180 mmHg, and tachycardia was defined as HR >110 bpm.

RESULTS: A total of 78 patients' data were analyzed from 108 patients' documentary. (38 in GC, 40 in GMD) SNP requirement was significantly higher in GC (39.5%) comparing GMD (7.5%) (p=0.001). SBPs during tumor manipulation period were statistically higher in GC than in GMD at 10th, 15th, 20th, 25th, 30th, and 35th min. HR values were significantly higher in GC compared to GMD at 10th and 15th min of tumor manipulation period (p<0.05).

CONCLUSION: Combination of Mg-Dex seems to be an alternative therapy for reducing vasodilator requirement in perioperative management of pheochromocytoma.

PMID:36282168 | DOI:10.14744/tjtes.2022.92672

Theranostics. 2022 Oct 3;12(16):7009-7031. doi: 10.7150/thno.74563. eCollection 2022.

ABSTRACT

Rationale: Chronic pressure overload is a major trigger of cardiac pathological hypertrophy that eventually leads to heart disease and heart failure. Understanding the mechanisms governing hypertrophy is the key to develop therapeutic strategies for heart diseases. Methods: We built chronic pressure overload mice model by abdominal aortic constriction (AAC) to explore the features of Yes-associated protein 1 (YAP1). Then AAV-cTNT-Cre was applied to Yap1F/F mice to induce mosaic depletion of YAP1. Myh6CreERT2; H11CAG-LSL-YAP1 mice were involved to establish YAP1 overexpression model by Tomaxifen injection. ATAC-seq and bioChIP-seq were used to explore the potential targets of YAP1, which were verified by a series of luciferase reporter assays. Dnm1l and Mfn1 were re-expressed in AAC mice by AAV-cTNT-Dnm1l and AAV-cTNT-Mfn1. Finally, Verteprofin was used to inhibit YAP1 to rescue cardiac hypertrophy. Results: We found that pathological hypertrophy was accompanied with the activation of YAP1. Cardiomyocyte-specific deletion of Yap1 attenuated AAC-induced hypertrophy. Overexpression of YAP1 was sufficient to phenocopy AAC-induced hypertrophy. YAP1 activation resulted in the perturbation of mitochondria ultrastructure and function, which was associated with the repression of mitochondria dynamics regulators Dnm1l and Mfn1. Mitochondrial-related genes Dnm1l and Mfn1, are significantly targeted by TEAD1/YAP complex. Overexpression of Dnm1l and Mfn1 synergistically rescued YAP1-induced mitochondrial damages and cardiac hypertrophy. Pharmacological repression of YAP1 by verteporfin attenuated mitochondrial damages and pathological hypertrophy in AAC-treated mice. Interestingly, YAP1-induced mitochondria damages also led to increased reactive oxidative species, DNA damages, and the suppression of cardiomyocyte proliferation. Conclusion: Together, these data uncovered YAP signaling as a therapeutic target for pressure overload-induced heart diseases and cautioned the efforts to induce cardiomyocyte regeneration by activating YAP.

PMID:36276651 | PMC:PMC9576622 | DOI:10.7150/thno.74563

JTCVS Tech. 2022 May 17;15:95-106. doi: 10.1016/j.xjtc.2022.05.002. eCollection 2022 Oct.

ABSTRACT

OBJECTIVE: We aimed to compare transit-time flow measurement (TTFM) parameters for on-pump (ONCAB) and off-pump (OPCAB) coronary artery bypass procedures.

METHODS: The database of the Registry for Quality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery (REQUEST) study was retrospectively reviewed. Only single grafts were included (ie, no sequential or Y/T grafts). Primary end points were mean graft flow (MGF), pulsatility index (PI), diastolic fraction (DF), and backflow (BF). Unadjusted and propensity score-matching comparisons were performed.

RESULTS: Of 1016 patients in the REQUEST registry, 846 had at least 1 graft for which TTFM was performed. Of these, 512 patients (60.6%) underwent ONCAB and 334 (39.4%) OPCAB procedures. Mean arterial pressure (MAP) during measurements was higher in the OPCAB group. After propensity score-matching, 312 well balanced pairs were left. In these matched patients, MGF was higher for the ONCAB versus the OPCAB group (32 vs 28 mL/min, respectively, for all grafts [P < .001]; 30 vs 27 mL/min for arterial grafts [P = .002]; and 35 vs 31 mL/min for venous grafts [P = .006], respectively). PI was lower in the ONCAB group (2.1 vs 2.3, for all grafts; P < .001). Diastolic fraction was slightly lower in the ONCAB group (65% vs 67.5%; P < .001). The backflow was also lower in the ONCAB group (0.6 vs 1.3; P < .001) with trends similar to MGF and PI for venous and arterial grafts. There were 21 (3.3%) revisions in the OPCAB group and 14 (2.1%) in the ONCAB group (P = .198).

CONCLUSIONS: ONCAB surgery was associated with higher MGF and lower PI values, especially in venous grafts. Different TTFM cutoff values for ONCAB versus OPCAB surgery might be considered.

PMID:36276694 | PMC:PMC9579515 | DOI:10.1016/j.xjtc.2022.05.002

JTCVS Tech. 2022 Aug 7;15:136-143. doi: 10.1016/j.xjtc.2022.07.018. eCollection 2022 Oct.

ABSTRACT

OBJECTIVES: To determine whether hearts reanimated with normothermic regional perfusion (NRP) have clinically detectable changes in function using echocardiography comparing the prearrest and post-NRP imaging. As heart transplantation from donation after circulatory death (DCD) continues to increase, preliminary results suggest outcomes comparable with donation after brain death. It is unknown whether the obligatory period of warm ischemia experienced during DCD withdrawal process causes immediate changes in cardiac allograft function following in situ reanimation.

METHODS: We retrospectively reviewed and compared predonation with postreanimation echocardiographic findings in all DCD donors at our institution from January to October 2021. All DCD donor organs were reanimated with in situ thoracoabdominal NRP after circulatory death. Echocardiographic assessment included (1) 2-dimensional and speckle-tracking measures of chamber size and function; (2) ejection fraction; (3) fractional area change; and (4) global longitudinal strain.

RESULTS: Altogether, 4 DCD heart donations were performed during the study period. Basic demographics and withdrawal ischemic time periods are reported. There were no changes in left ventricular ejection fraction and right ventricular fractional area change when comparing the predonation and the postreanimation echocardiogram. There was a minimal, nonstatistically significant decrease in left ventricular global longitudinal strain and right ventricular free-wall systolic strain in 3 of the 4 donors following reanimation.

CONCLUSIONS: DCD cardiac allografts reanimated with NRP demonstrated no change in echocardiographic parameters used for a standard predonation donor heart evaluation. Findings suggest cardiac function of DCD allografts reanimated with thoracoabdominal NRP is not adversely impacted by limited period of warm ischemia following circulatory arrest.

PMID:36276687 | PMC:PMC9579788 | DOI:10.1016/j.xjtc.2022.07.018

Stem Cell Rev Rep. 2022 Oct 22. doi: 10.1007/s12015-022-10468-z. Online ahead of print.

ABSTRACT

BACKGROUND: Ischemic heart disease, often caused by an acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. Despite significant advances in medical and procedural therapies, millions of AMI patients progress to develop heart failure every year.

METHODS: Here, we examine the combination therapy of human mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) to reduce the early ischemic damage (MSCs) and enhance angiogenesis (ECFCs) in a pre-clinical model of acute myocardial infarction. NOD/SCID mice were subjected to AMI followed by transplantation of MSCs and ECFCs either alone or in combination. Cardiomyocyte apoptosis and cardiac functional recovery were assessed in short- and long-term follow-up studies.

RESULTS: At 1 day after AMI, MSC- and ECFC-treated animals demonstrated significantly lower cardiomyocyte apoptosis compared to vehicle-treated animals. This phenomenon was associated with a significant reduction in infarct size, cardiac fibrosis, and improvement in functional cardiac recovery 4 weeks after AMI.

CONCLUSIONS: The use of ECFCs, MSCs, and the combination of both cell types reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of AMI. These results support the use of this combined cell therapy approach in future human studies during the acute phase of ischemic cardiac injury.

PMID:36271311 | DOI:10.1007/s12015-022-10468-z

ACS Appl Bio Mater. 2022 Nov 21;5(11):5218-5230. doi: 10.1021/acsabm.2c00659. Epub 2022 Oct 20.

ABSTRACT

Cardiac patches are widely investigated to repair or regenerate diseased and aging cardiac tissues. While numerous studies looked into engineering the biochemical/biomechanical/cellular microenvironment and components in the heart tissue, the changes induced by cardiac patches and how they should be controlled to promote cardiac tissue repair/regeneration remains an important yet untapped direction, especially immunological responses. In this study, we designed and fabricated a bilaminated cardiac patch based on extracellular matrix (ECM) materials loaded with the extracellular vesicles (EVs) derived from mesenchymal stromal cells. The function of the biological material to modulate the injury-related microenvironment in a cardiac infarction model in mice was investigated. The study showed that the treatment of EV-ECM patches to the infarcted area increased the level of immunomodulatory major histocompatibility complex class IIlo macrophages in the early stage of myocardial injury to mitigate excessive inflammatory responses due to injury. The intensity of the acquired proinflammatory immune response in systemic immune organs was reduced. Further analyses indicated that the EV-ECM patches exhibited proangiogenic functions and decreased the infarct size with improved cardiac recovery in mice. The study provided insights into shaping the injury-related microenvironment through the incorporation of extracellular vesicles into cardiac patches, and the EV-ECM material is a promising design paradigm to improve the function of cardiac patches to treat myocardial injuries and diseases.

PMID:36265007 | DOI:10.1021/acsabm.2c00659

Sci Rep. 2022 Oct 18;12(1):17409. doi: 10.1038/s41598-022-22225-w.

ABSTRACT

Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating human cardiac microtissues in vitro from hiPSCs-namely human organotypic cardiac microtissues (hOCMTs)-that show some degree of self-organization and can be cultured for long term. This is achieved by the differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated hOCMTs contain multiple cell types that physiologically compose the heart and beat without external stimuli for more than 100 days. We have shown that 3D hOCMTs display improved cardiac specification, survival and metabolic maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hOCMTs by their response to cardioactive drugs in long-term culture. Furthermore, we demonstrated that they could be used to study chemotherapy-induced cardiotoxicity. Due to showing a tendency for self-organization, cellular heterogeneity, and functionality in our 3D microtissues over extended culture time, we could also confirm these constructs as human cardiac organoids (hCOs). This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.

PMID:36257968 | PMC:PMC9579206 | DOI:10.1038/s41598-022-22225-w

Int J Biol Macromol. 2022 Dec 1;222(Pt B):3045-3056. doi: 10.1016/j.ijbiomac.2022.10.079. Epub 2022 Oct 12.

ABSTRACT

Cell therapy is one of the promising approaches for cardiac repair, subsequently after infarction or injury. However, contemporary mesenchymal stromal/stem cell (MSCs) delivery strategies result in low retention and poor engraftment of donor cells, thus limiting the therapeutic efficacy. Here, we developed an engineered biomimetic cardiogel patch (EBCP) comprising of the native decellularized cardiac extracellular matrix (ECM) "cardiogel" and chitosan, leading to the efficient regeneration of injured myocardium. We also developed novel bio-adhesive that is capable of suture-free epicardial placement of EBCP to injured myocardium. We have illustrated the potential of the mussels-inspired bioadhesive system, which comprises gelatin catechol and partially oxidized chitosan, which relies on self-crosslinking capability, to promote wet adhesion. In vitro studies with isolated cardiogel promoted cell proliferation, adhesion, and migration while aiding cardiomyogenic differentiation. The EBCP's ability to protect cells from abrasion due to surrounding tissues in the myocardial infarction (MI) rat model makes it more desirable. Furthermore, the epicardial implantation of the EBCP loaded with MSCs improves the initial retention of cells and subsequent functional cardiac recovery with enhanced myocardial tissue restoration. Histological examination showed the presence of EBCP and infiltration of cells to the infarcted heart tissue. The fast and facile synthesis of bioadhesive and major therapeutic benefits of EBCP make it a potential candidate for recuperating the ailing heart.

PMID:36243159 | DOI:10.1016/j.ijbiomac.2022.10.079

Int J Mol Sci. 2022 Sep 29;23(19):11490. doi: 10.3390/ijms231911490.

ABSTRACT

This review discusses a novel experimental approach for the regeneration of original tissue structure by recruitment of endogenous stem-cells to injured sites following administration of α-gal nanoparticles, which harness the natural anti-Gal antibody. Anti-Gal is produced in large amounts in all humans, and it binds the multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) presented on α-gal nanoparticles. In situ binding of anti-Gal to α-gal nanoparticles activates the complement system and generates complement cleavage chemotactic-peptides that rapidly recruit macrophages. Macrophages reaching anti-Gal coated α-gal nanoparticles bind them via Fc/Fc receptor interaction and polarize into M2 pro-reparative macrophages. These macrophages secrete various cytokines that orchestrate regeneration of the injured tissue, including VEGF inducing neo-vascularization and cytokines directing homing of stem-cells to injury sites. Homing of stem-cells is also directed by interaction of complement cleavage peptides with their corresponding receptors on the stem-cells. Application of α-gal nanoparticles to skin wounds of anti-Gal producing mice results in decrease in healing time by half. Furthermore, α-gal nanoparticles treated wounds restore the normal structure of the injured skin without fibrosis or scar formation. Similarly, in a mouse model of occlusion/reperfusion myocardial-infarction, near complete regeneration after intramyocardial injection of α-gal nanoparticles was demonstrated, whereas hearts injected with saline display ~20% fibrosis and scar formation of the left ventricular wall. It is suggested that recruitment of stem-cells following anti-Gal/α-gal nanoparticles interaction in injured tissues may result in induction of localized regeneration facilitated by conducive microenvironments generated by pro-reparative macrophage secretions and "cues" provided by the extracellular matrix in the injury site.

PMID:36232789 | PMC:PMC9569695 | DOI:10.3390/ijms231911490