Pericytes are essential components of small blood vessels and are found in human aortic vasa vasorum. Prior work uncovered lower vasa vasorum density and decreased levels of pro-angiogenic growth ...factors in adventitial specimens of human ascending thoracic aortic aneurysm. We hypothesized that adventitial extracellular matrix (ECM) from normal aorta promotes pericyte function by increasing pericyte contractile function through mechanisms deficient in ECM derived from aneurysmal aortic adventitia. ECM biomaterials were prepared as lyophilized particulates from decellularized adventitial specimens of human and porcine aorta. Immortalized human aortic adventitia-derived pericytes were cultured within Type I collagen gels in the presence or absence of human or porcine adventitial ECMs. Cell contractility index was quantified by measuring the gel area immediately following gelation and after 48 h of culture. Normal human and porcine adventitial ECM increased contractility of pericytes when compared with pericytes cultured in absence of adventitial ECM. In contrast, aneurysm-derived human adventitial ECM failed to promote pericyte contractility. Pharmacological inhibition of TGFβR1 and antibody blockade of α
β
integrin independently decreased porcine adventitial ECM-induced pericyte contractility. By increasing pericyte contractility, adventitial ECM may improve microvascular function and thus represents a candidate biomaterial for less invasive and preventative treatment of human ascending aortic disease.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recent advances in novel medical gases, including hydrogen and carbon monoxide (CO), have demonstrated significant opportunities for therapeutic use. This study was designed to evaluate the effects ...of inhaled hydrogen or CO, or both, on cold ischemia/reperfusion (I/R) injury of the myocardium.
Syngeneic heterotopic heart transplantation was performed in rats after 6 or 18 hours of cold ischemia in Celsior solution. Survival, morphology, apoptosis and marker gene expression were assessed in the grafts after in vivo inhalation of hydrogen (1% to 3%), CO (50 to 250 ppm), both or neither. Both donors and recipients were treated for 1 hour before and 1 hour after reperfusion.
After 6-hour cold ischemia, inhalation of hydrogen (>2%) or CO (250 ppm) alone attenuated myocardial injury. Prolonged cold ischemia for 18 hours resulted in severe myocardial injury, and treatment with hydrogen or CO alone failed to demonstrate significant protection. Dual treatment with hydrogen and CO significantly attenuated I/R graft injury, reducing the infarcted area and decreasing in serum troponin I and creatine phosphokinase (CPK). Hydrogen treatment alone significantly reduced malondialdehyde levels and serum high-mobility group box 1 protein levels as compared with air-treated controls. In contrast, CO only marginally prevented lipid peroxidation, but it suppressed I/R-induced mRNA upregulation for several pro-inflammatory mediators and reduced graft apoptosis.
Combined therapy with hydrogen and CO demonstrated enhanced therapeutic efficacy via both anti-oxidant and anti-inflammatory mechanisms, and may be a clinically feasible approach for preventing cold I/R injury of the myocardium.
This study evaluated differences in efficacy and safety outcomes with bivalirudin compared with unfractionated heparin (UFH) in patients with cardiogenic shock requiring venoarterial extracorporeal ...membrane oxygenation (VA ECMO). We performed a retrospective study at an academic medical center that included patients greater than 18 years of age supported with VA ECMO due to cardiogenic shock from January 2009 to February 2021. The primary endpoint was ECMO-associated thrombotic events normalized to duration of ECMO support. Secondary safety endpoints included major bleeding (per ELSO criteria) and blood product administration. Overall, 143 patients were included in our analysis with 54 having received bivalirudin and 89 having received UFH. Median duration of ECMO support was 92 (interquartile range, 56-172) hours. ECMO-associated thrombotic events per ECMO day were significantly less among those that received bivalirudin ( P < 0.001). In adjusted regression, bivalirudin was independently associated with an increased time to thrombosis when compared with UFH (ExpB -3.8; 95% confidence interval, 1.7-8.8; P = 0.002). Patients receiving bivalirudin experienced less major bleeding events ( P = 0.02) with less total red blood cell and fresh frozen plasma administration ( P = 0.04 and P = 0.03, respectively). Bivalirudin is a safe and efficacious alternative to UFH in patients requiring VA ECMO for cardiogenic shock.
Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation continues to be a morbid complication. In this study, we hypothesized that a less invasive approach to ...implantation would preserve RV function relative to a conventional sternotomy (CS) approach.
All patients (2013-2017) who underwent LVAD implantation were reviewed. Patients were stratified by surgical approach: less invasive left thoracotomy with hemi-sternotomy (LTHS) and CS. The primary outcome was severe RV failure.
Eighty-three patients (LTHS: 37, CS: 46) were identified. The median Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score was significantly worse in the LTHS compared to the CS cohort, and there was a trend towards higher RV failure scores and HeartMate II mortality scores. Preoperative RV dysfunction, in pulmonary artery pulsatility index and RV stroke work index were similar between the 2 groups. Though operative time did not significantly differ between the 2 groups, cardiopulmonary bypass time was significantly shorter in the LTHS group (61 vs 95 min, P < 0.001). The incidence of postoperative severe RV failure was significantly reduced in the LTHS group (16% vs 39%, P = 0.030), along with the need for temporary right ventricular assist device (3% vs 26%, P = 0.005). Improvement in RV function, along with a change in pulmonary artery pulsatility index, was significantly greater in the LTHS cohort. There was a trend towards improved Kaplan-Meier 1-year survival in the LTHS cohort (91% vs 56%, P = 0.056).
In this cohort, less invasive LVAD implantation appears to be associated with reduced postoperative RV failure, and equivalent or improved survival compared to conventional LVAD implantation.
Lung ischemia-reperfusion injury (LIRI) and primary graft dysfunction are leading causes of morbidity and mortality among lung transplant recipients. Although extensive research endeavors have been ...undertaken, few preventative and therapeutic treatments have emerged for clinical use. Novel strategies are still needed to improve outcomes after lung transplantation. In this review, we discuss the underlying mechanisms of transplanted LIRI, potential modifiable targets, current practices, and areas of ongoing investigation to reduce LIRI and primary graft dysfunction in lung transplant recipients.
Massive pulmonary embolism (PE) is a life-threatening condition with a high mortality. Both systemic thrombolytics and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been used in ...the management of massive PE. However, the safety of VA- ECMO in the setting of recent thrombolytic administration is not clear. The purpose of this study is to analyze the outcomes of patients who received VA-ECMO in the setting of systemic thrombolytics (ST). A single institution retrospective study of PE patients treated with VA-ECMO between December 2015 and December 2020 was performed. Patients who received ST were compared with those who did not receive ST. Outcomes, including mortality, major bleeding, duration of mechanical ventilation, need for renal replacement therapy, and length of hospital stay, were compared. A total of 83 patients with PE required VA-ECMO support and 18 of these received systemic thrombolytics. There was no statistically significant difference in survival to discharge between the patients who received ST compared with those who did not (88.9% vs 84.6%; p = 0.94). Major bleeding events occurred more often in patients who received ST (61.1% vs 26.2%; p = 0.01). There was no significant difference in time on mechanical ventilation, need for renal replacement therapy, or length of stay between the groups. Reasonable survival can be achieved despite an increased frequency of major bleeding events in patients that receive ST prior to VA-ECMO for PE. ST administration should not be considered an absolute contraindication to VA-ECMO. Further multi-center studies are needed to corroborate these findings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Induction immunosuppression in heart transplant recipients varies greatly by center. Basiliximab (BAS) is the most commonly used induction immunosuppressant but has not been shown to ...reduce rejection or improve survival. The objective of this retrospective study was to compare rejection, infection, and mortality within the first 12 months following heart transplant in patients who received BAS or no induction.
Methods
This was a retrospective cohort study of adult heart transplant recipients given BAS or no induction from January 1, 2017 to May 31, 2021. The primary endpoint was incidence of treated acute cellular rejection (ACR) at 12‐months post‐transplant. Secondary endpoints included ACR at 90 days post‐transplant, incidence of antibody‐mediated rejection (AMR) at 90 days and 1 year, incidence of infection, and all‐cause mortality at 1 year.
Results
A total of 108 patients received BAS, and 26 patients received no induction within the specified timeframe. There was a lower incidence of ACR within the first year in the BAS group compared to the no induction group (27.7 vs. 68.2%, p < .002). BAS was independently associated with a lower probability of having a rejection event during the first 12‐months post‐transplant (hazard ratio (HR) .285, 95% confidence interval CI .142–.571, p < .001). There was no difference in the rate of infection and in mortality after hospital discharge at 1‐year post‐transplant (6% vs. 0%, p = .20).
Conclusion
BAS appears to be associated with greater freedom from rejection without an increase in infections. BAS may be a preferred to a no induction strategy in patients undergoing heart transplantation.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Here we present the case of a patient that suffered a cardiac arrest due to pulmonary embolus. The patient was resuscitated using extracorporeal membrane oxygenation and treated with ...ultrasound-accelerated catheter-directed thrombolysis during support on extracorporeal membrane oxygenation, with an excellent outcome. This case demonstrates that the use of extracorporeal membrane oxygenation and ultrasound-accelerated catheter-directed thrombolysis can be highly effective for managing select patients with pulmonary embolus and cardiac arrest.
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