Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.Peer reviewe

Acute changes in inflammatory biomarker levels in recreational runners participating in a marathon or half-marathon

Abstract Background: Strenuous physical activity activates the participant’s immune responses; however, few studies exist, observing exercise-induced simultaneous changes in mediators of inflammation. Methods: We examined individual responses in soluble urokinase-type plasminogen activator receptor (suPAR), a marker of immune activation, soluble endocytic receptor for haptoglobin-hemoglobin complexes (CD163), a marker of monocyte-macrophage activation, C-reactive protein (CRP), and pro- and anti-inflammatory cytokines from blood samples drawn at baseline, at 3- and 48-h post-races from recreational runners who successfully completed the marathon (199 ± 8 min, n = 4) or half-marathon (132 ± 4 min, n = 4) run. For comparisons, biomarkers reflecting muscle, heart, kidney, and liver functions were measured. Results: Significant 3-h post-race increases occurred in levels of suPAR (p < 0.01), CD163 (p < 0.05), white blood cells (p < 0.001), pro-inflammatory cytokines, interleukin-6 (IL-6) (p < 0.001), IL-8 (p < 0.05), and anti-inflammatory cytokine IL-10 (p < 0.05), whereas tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) remained relatively stable. Full-marathon running lead to more pronounced increases in suPAR, CD163, IL-8, and IL-10 than half-marathon running. In addition, 3-h post-race increases of all these parameters correlated significantly with changes in serum TNF-α and cortisol. The 48-h levels of serum suPAR and both pro- and anti-inflammatory cytokines had decreased to baseline levels, whereas CRP, a marker of acute phase response, increased in those with the most prominent IL-6 and IL-10 elevations in their preceding samples. The highest suPAR, CRP, IL-6, TNF-α, IL-10, and cortisol levels were noted in the individual with the most severe post-race fatigue. Conclusions: Prolonged running increases mediators of inflammation in an exercise-dose-dependent manner which should be considered in the assessment of health status of physically active individuals after recent acute bouts of strenuous exercise

Spinal cord injury during selective cerebral perfusion and segmental artery occlusion:an experimental study

Abstract Objectives: Since selective cerebral perfusion (SCP) has been used in aortic arch surgical procedures, the core temperature during lower body circulatory arrest (LBCA) has been steadily rising. Simultaneously, the use of a frozen elephant trunk (FET) graft has been increasing. The safe period of LBCA in relation to spinal cord ischaemic tolerance in combination with segmental artery occlusion by the FET procedure has not been defined. Methods: Sixteen pigs were assigned to undergo 65 (n = 10) or 90 min (n  = 6) of SCP at 28°C with LBCA in combination with occlusion of the 8 uppermost segmental arteries in the thoracic (Th) aorta (15–20 cm FET, Th8-level). The follow-up period consisted of a 6-h intensive period and a 5-day observation period. Near-infrared spectroscopy of the collateral network was used to determine spinal cord oxygenation. The neurological status of the patients was evaluated daily, and the brain and the spinal cord were harvested for a histopathological analysis. Results: Five out of 6 pigs after 90 min and 1 out of 10 pigs after 65 min of LBCA died within 48 h of multiorgan failure. Of the survivors in the 65-min group, 6 out of 9 had paraparesis/paraplegia; the remaining 3 reached normal function. The lone survivor after 90 min of LBCA was paraplegic. Nadir near-infrared spectroscopy of the collateral network values at Th8 and Th10 were 34 (±5) and 39 (±4), and they were reached within 35 min of SCP in both groups. Conclusions: An extended FET graft with LBCA and SCP durations >65 min at 28°C results in a poor outcome

Impact of high-risk features on outcome of acute type B aortic dissection

Abstract Background: Acute type B aortic dissection (TBAD) is a severe condition associated with significant morbidity and mortality. The optimal classification and treatment strategy of TBAD remain controversial and inconsistent. Methods: This analysis includes patients treated for acute TBAD at the Helsinki University Hospital, Finland between 2007 and 2019. The endpoints were early and late mortality, intervention of the aorta, and a composite of death and aortic intervention in uncomplicated patients and high-risk patients. Results: This study included 162 consecutive TBAD patients (27.8% females), 114 in the high-risk group and 48 in the uncomplicated group, with a mean age of 67.6 ± 13.9 years. Intramural hematoma was reported in 63 cases (38.9%). The mean follow-up was 5.1 ± 3.9 years. In-hospital/30-day mortality (n = 4; 3.5%) occurred solely in the high-risk group (P = 0.32). Additionally, TBAD-related adverse events (n = 23; 20.2%) were observed only in the high-risk group (P < 0.001). The cumulative incidences of the composite TBAD outcome with non–TBAD-related death as a competing risk were 6.6% (95% CI, 1.7%–16.5%) in the uncomplicated group and 29.5% (95% CI, 21.1%–38.3%) in the high-risk group at 5 years and 6.6% (95% CI, 1.7%–16.5%) and 33.0% (95% CI, 23.7%–42.6%) at 10 years (P = 0.001, Gray test). Extracardiac arteriopathy (subdistribution hazard ratio [SHR], 2.61; 95% CI, 1.08–6.27) and coronary artery disease (SHR, 2.24; 95% CI, 1.07–4.71) were risk factors for adverse aortic-related events in univariable competing-risk regression analysis. Conclusions: Recognition of risk factors underlying adverse events related to TBAD is essential because the disease progression impacts both early and late outcomes. Early aortic repair in high-risk TBAD may reduce long-term morbidity and mortality

Familial abdominal aortic aneurysms: collection of 233 multiplex families.

OBJECTIVE: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. Subjects and Methods: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags). RESULTS: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively. CONCLUSION: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors

Remote ischemic preconditioning and hypoxia-induced biomarkers in acute myocardial infarction:study on a porcine model

Abstract Objectives: Remote ischemic preconditioning (RIPC) mitigates acute myocardial infarction (AMI). We hypothesized that RIPC reduces the size and severity of AMI and explored molecular mechanisms behind this phenomenon. Design: In two series of experiments, piglets underwent 60 min of the circumflex coronary artery occlusion, resulting in AMI. Piglets were randomly assigned into the RIPC groups (n = 7 + 7) and the control groups (n = 7 + 7). The RIPC groups underwent four 5-min hind limb ischemia-reperfusion cycles before AMI. In series I, the protective efficacy of RIPC was investigated by using biomarkers and echocardiography with a follow-up of 24 h. In series II, the heart of each piglet was harvested for TTC-staining to measure infarct size. Muscle biopsies were collected from the hind limb to explore molecular mechanisms of RIPC using qPCR and Western blot analysis. Results: The levels of CK-MBm (p = 0.032) and TnI (p = 0.007) were lower in the RIPC group. Left ventricular ejection fraction in the RIPC group was greater at the end of the follow-up. The myocardial infarct size in the RIPC group was smaller (p = 0.033). Western blot indicated HIF1α stabilization in the skeletal muscle of the RIPC group. PCR analyses showed upregulation of the HIF target mRNAs for glucose transporter (GLUT1), glucose transporter 4 (GLUT4), phosphofructokinase 1 (PFK1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase 1 (ENO1), lactate dehydrogenase (LDHA) and endothelial nitric oxidate synthase (eNOS). Conclusions. Biochemical, physiologic, and histologic evidence confirms that RIPC decreases the size of AMI. The HIF pathway is likely involved in the mechanism of the RIPC

Reliability of bioreactance and pulse-power analysis in measuring cardiac index in patients undergoing cardiac surgery with cardiopulmonary bypass

Abstract Objectives: Less-invasive and continuous cardiac output monitors recently have been developed to monitor patient hemodynamics. The aim of this study was to compare the accuracy, precision, and trending ability of noninvasive bioreactance-based Starling SV and miniinvasive pulse-power device LiDCOrapid to bolus thermodilution technique with a pulmonary artery catheter (TDCO) when measuring cardiac index in the setting of cardiac surgery with cardiopulmonary bypass (CPB). Design: A prospective method-comparison study. Setting: Oulu University Hospital, Finland. Participants: Twenty patients undergoing cardiac surgery with CPB. Interventions: Cardiac index measurements were obtained simultaneously with TDCO intraoperatively and postoperatively, resulting in 498 measurements with Starling SV and 444 with LiDCOrapid. Measurements and Main Results: The authors used the Bland-Altman method to investigate the agreement between the devices and four-quadrant plots with error grids to assess the trending ability. The agreement between TDCO and Starling SV was qualified with a bias of 0.43 L/min/m² (95% confidence interval [CI], 0.37‐0.50), wide limits of agreement (LOA, –1.07 to 1.94 L/min/m²), and a percentage error (PE) of 66.3%. The agreement between TDCO and LiDCOrapid was qualified, with a bias of 0.22 L/min/m² (95% CI 0.16‐0.27), wide LOA (–0.93 to 1.43), and a PE of 53.2%. With both devices, trending ability was insufficient. Conclusions: The reliability of bioreactance-based Starling SV and pulse-power analyzer LiDCOrapid was not interchangeable with TDCO, thus limiting their usefulness in cardiac surgery with CPB

Comparison of survival of transfemoral transcatheter aortic valve implantation versus surgical aortic valve replacement for aortic stenosis in low-risk patients without coronary artery disease

Abstract Increasing data support transcatheter aortic valve implantation (TAVI) as a valid option over surgical aortic valve replacement (SAVR) in the treatment for severe aortic stenosis (AS) also in patients with low operative risk. However, limited data exist on the outcome of TAVI and SAVR in low-risk patients without coronary artery disease (CAD). The FinnValve registry included data on 6463 patients who underwent TAVI or SAVR with bioprosthesis between 2008 and 2017. Herein, we evaluated the outcome of low operative risk as defined by STS-PROM score <3% and absence of CAD, previous stroke and other relevant co-morbidities. Only patients who underwent TAVI with third-generation prostheses and SAVR with Perimount Magna Ease or Trifecta prostheses were included in this analysis. The primary endpoints were 30-day and 3-year all-cause mortality. Overall, 1,006 patients (175 TAVI patients and 831 SAVR patients) met the inclusion criteria of this analysis. Propensity score matching resulted in 140 pairs with similar baseline characteristics. Among these matched pairs, 30-day mortality was 2.1% in both TAVI and SAVR cohorts (p = 1.00) and 3-year mortality was 17.0% after TAVI and 14.6% after SAVR (p = 0.805). Lower rates of bleeding and atrial fibrillation, and shorter hospital stay were observed after TAVI. The need of new permanent pacemaker implantation and the incidence of early stroke did not differ between groups. In conclusion, TAVI using third-generation prostheses achieved similar early and mid-term survival compared with SAVR in low-risk patients without CAD

Perioperative bleeding requiring blood transfusions is associated with increased risk of stroke after transcatheter and surgical aortic valve replacement

Abstract Objectives: The authors aimed to investigate the impact of severe bleeding and use of red blood cell (RBC) transfusion on the development of postoperative stroke after surgical (SAVR) and transcatheter aortic valve replacement (TAVR), taken from the FinnValve registry. Design: Nationwide, retrospective observational study. Setting: Five Finnish university hospitals participated in the registry. Participants: A total of 6,463 patients who underwent SAVR (n = 4,333) or TAVR (n = 2,130). Interventions: Patients who underwent TAVR or SAVR with a bioprosthesis with or without coronary revascularization. Measurements and Main Results: The incidence of postoperative stroke after SAVR was 3.8%. In multivariate analysis, the number of transfused RBC units (odds ratio [OR], 1.098; 95% confidence interval [CI], 1.064–1.133) was one of the independent predictors of postoperative stroke. The incidence of stroke increased, along with the severity of perioperative bleeding, according to the European Coronary Artery Bypass Grafting (E-CABG) bleeding grades were as follows: grade 0, 2.2% (reference group); grade 1, 3.4% (adjusted OR, 1.841; 95% CI, 1.105–3.066); grade 2, 5.5% (adjusted OR, 3.282; 95% CI, 1.948–5.529); and grade 3, 14.8% (adjusted OR, 7.103; 95% CI, 3.612–13.966). The incidence of postoperative stroke after TAVR was 2.5%. The number of transfused RBC units was an independent predictor of stroke after TAVR (adjusted OR, 1.155; 95% CI, 1.058–1.261). The incidence of postoperative stroke increased, along with the severity of perioperative bleeding, as stratified by the E-CABG bleeding grades: E-CABG grade 0, 1.7%; grade 1, 5.3% (adjusted OR, 1.270; 95% CI, 0.532–3.035); grade 2, 10.0% (adjusted OR, 2.898; 95% CI, 1.101–7.627); and grade 3, 30.0% (adjusted OR, 10.706; 95% CI, 2.389–47.987). Conclusions: Perioperative bleeding requiring RBC transfusion and/or reoperation for intrathoracic bleeding is associated with an increased risk of postoperative stroke after SAVR and TAVR. Patient blood management and meticulous preprocedural planning and operative technique aiming to avoid significant perioperative bleeding may reduce the risk of cerebrovascular complications