Erythrocytes are oxygen carriers and exposed to redox cycle in oxygenation and deoxygenation of hemoglobin. This indicates that circulating erythrocytes are vulnerable to the oxidative injury ...occurring under the imbalance of redox homeostasis. In this review article, two topics are presented concerning the human erythrocytes exposed to the oxidative inflammation including septic and sterile conditions. First, we demonstrate rheological derangement of erythrocytes subjected to acute oxidative injury caused by exogenous generators of reactive oxygen species (ROS). Erythrocyte filterability as whole-cell deformability has been estimated by the gravity-based nickel mesh filtration technique in our laboratory and was dramatically impaired in a time-dependent manner after starting exposure to the ROS generators, that is associated with concurrent progression of membrane protein degradation, phospholipid peroxidation, erythrocyte swelling, methemoglobin formation, and oxidative hemolysis. Second, we introduce an impairment of erythrocyte filterability confirmed quantitatively in diabetes mellitus and hypertension of animal models and patients under treatment. Among the cell geometry, internal viscosity, and membrane property as the three major determinants of erythrocyte deformability, erythrocyte membrane alteration is supposed to be the primary cause of this impairment in these lifestyle-related diseases associated with persistent oxidative inflammation. Excessive ROS trigger the inflammatory responses and reduce the erythrocyte membrane fluidity. Oxidative inflammation increasing erythrocyte membrane rigidity underlies the impaired systemic microcirculation, which is observed in diabetic and/or hypertensive patients. On the other hand, elevated internal viscosity caused by sickle hemoglobin polymerization is a primary cause of impaired erythrocyte filterability in sickle cell disease (SCD). However, oxidative inflammation is also involved in the pathophysiology of SCD. The physiologic level of ROS acts as signaling molecules for adaptation to oxidative environment, but the pathological level of ROS induces suicidal erythrocyte death (eryptosis). These findings provide further insight into the ROS-related pathophysiology of many clinical conditions.
Left ventricular assist device (LVAD) is an important therapeutic option for patients with end-stage advanced heart failure. LVAD can reduce cardiovascular death and improve the quality of life in ...patients with end-stage advanced heart failure. However, as LVAD-implanted patients increase and survival becomes prolonged, many patients experience serious complications. Major complications of LVAD include ischemic and hemorrhagic strokes, bleeding complications, device thrombosis, right heart failure, and LVAD related infections. These complications lead to worse mortality in patients with LVAD. In particular, cerebrovascular events and gastrointestinal bleeding are the most dreaded complications. High molecule weight multimers of von Willebrand factor (vWF-HMWM) play an essential role in platelet adhesion and aggregation, but high shear stress caused by LVAD pump diminishes the vWF-HMWM. In fact, in response to the shear stress of LVAD, vWF exposes cleavage domains of ADAMTS 13 to form smaller multimeric molecules. Therefore, in many patients with LVAD, the vWF reduces its large multimers and lowers the ability to bind sufficiently to platelets and sub-endothelial collagen, resulting in the acquired von Willebrand syndrome. Thus, in LVAD patients with acquired von Willebrand syndrome, vWF function is impaired, and this impairment is associated with hemocompatibility-related adverse events. Based on hemorheology, this review focuses on the pathophysiology of acquired von Willebrand syndrome and its management in patients with LVAD.
Current sophisticated open heart surgical technologies have improved the prognosis of patients undergoing heart valve repair and replacement. Optimal antithrombotic strategy is now established using ...antiplatelet and anticoagulant agents, whereas subclinical erythrocyte damage caused by prosthetic heart valves is drawing less attention. Therefore, the aim of this study is to investigate the erythrocyte damage in prosthetic heart valve recipients from several viewpoints of serum biochemistry, erythrocyte morphology, and clinical hemorheology. Serum lactate dehydrogenase level was elevated significantly (p = 0.007) in patients with metallic heart valves (n = 6) but not in those with bioprosthetic heart valves (n = 8) as compared with healthy controls (n = 8). In the microscopic examination, teardrop cells, fragmented cells, and erythrocyte with local membrane protrusion (so-called budding) were observed in some patients with metallic heart valve replacement but not in the other two groups. Erythrocyte filterability estimated by our specific gravity filtration technique showed significant intergroup difference at low filtration pressure (50 cmH2O) (p < 0.001), but not at high filtration pressure (100 cmH2O). Therefore, damage to the erythrocyte by prosthetic heart valves is evident from morphologic, biochemical, and hemorheological perspectives. These findings indicate that damaged erythrocytes may have rheological impact at low shear rate condition reflecting the complicated relationship between structure and function of erythrocyte membrane regulating whole-cell deformability in concert.
Mechanisms of Left Atrial Enlargement in Obesity Aiad, Norman N.; Hearon, Christopher; Hieda, Michinari ...
The American journal of cardiology,
08/2019, Letnik:
124, Številka:
3
Journal Article
Recenzirano
Left atrial (LA) enlargement is common in obesity. We sought to determine the influence of ventricular (LV) remodeling on LA size in obesity. We studied 50 otherwise healthy obese subjects (body mass ...index 37.2 ± 4.6 kg/m2, 50 ± 6 years) and 58 age and gender-matched nonobese controls (body mass index 26.2 ± 2.9 kg/m2, 52 ± 5 years). Diastolic function, relative wall thickness (RWT), and LV mass were assessed using echocardiography. LA and LV volume was measured by 3D-echocardiography. Primary outcome was the ratio of LA volume indexed to LV volume in obese and control subjects. Obese subjects had substantially larger LA volumes compared with control subjects (61.0 ± 16.9 vs 38.9 ± 9.2 ml, p < 0.0001). When scaled to body size or lean mass, differences in LA size persisted. However, when indexed to LV end-diastolic volume, LA volumes between control and obese subjects were comparable (obese vs controls: 0.44 ± 0.15 vs 0.42 ± 0.10, p = 0.46). A small subset of obese subjects (26%) had LA volume markedly out of proportion to LV volume (LA/LV volume ratio ≥0.5) and displayed concentric LV remodeling with larger RWT and LV mass compared with obese subjects with LA/LV <0.5 (RWT: 0.46 ± 0.09 vs 0.36 ± 0.06, p < 0.0001; LV mass: 79 ± 18 vs 62 ± 13 g/m2 p < 0.01). In conclusion, LA enlargement in patients with obesity generally occurs commensurate with LV enlargement and parallels eccentric LV remodeling. LA enlargement out of proportion to LV size is associated with increased RWT and mass. This unique signature may identify obese subjects with pathologic LA remodeling.
Background: Hypertension is a frequent adverse event caused by vascular endothelial growth factor signaling pathway (VSP) inhibitors. However, the impact of hypertension on clinical outcomes during ...VSP inhibitor therapy remains controversial.Methods and Results: We reviewed 3,460 cancer patients treated with VSP inhibitors from the LIFE Study database, comprising Japanese claims data between 2016 and 2020. Patients were stratified into 3 groups based on the timing of hypertension onset: (1) new-onset hypertension (n=569; hypertension developing after VSP inhibitor administration); (2) pre-existing hypertension (n=1,790); and (3) no hypertension (n=1,101). Time to treatment failure (TTF) was used as the primary endpoint as a surrogate for clinical outcomes. The median (interquartile range) TTF in the new-onset and pre-existing hypertension groups was 301 (133–567) and 170 (72–358) days, respectively, compared with 146 (70–309) days in the non-hypertensive group (P<0.001 among all groups). In an adjusted Cox proportional hazard model, new-onset (hazard ratio HR 0.58; 95% confidence interval CI 0.50–0.68; P<0.001) and pre-existing (HR 0.85; 95% CI 0.73–0.98; P=0.026) hypertension were independent factors for prolonged TTF. The TTF of new-onset hypertension was longer than that of pre-existing hypertension (HR 0.68; 95% CI 0.62–0.76; P<0.001).Conclusions: This study highlighted that new-onset hypertension induced by VSP inhibitors was an independent factor for favorable clinical outcomes. Pre-existing hypertension before VSP inhibitor initiation was also a significant factor.
Abstract
Background
The incidence of venous thromboembolism has been reported as 20% in cancer patients. Anticoagulation therapy is the standard treatment for venous thromboembolism. On the other ...hand, bleeding should be carefully managed, because advanced cancer, particularly gastrointestinal cancer, carries a high risk of bleeding. However, the optimal management for cancer-associated thromboembolism remains to be clarified.
Methods
We retrospectively examined patients with advanced gastrointestinal cancer, including gastric cancer and colorectal cancer, who were treated with chemotherapy between 2014 and 2018 for the incidence and characteristics of venous thromboembolism and bleeding.
Results
In total, 194 patients (120 men, 74 women) were enrolled in this study. The underlying pathology was gastric cancer in 74 cases and colorectal cancer in 120 cases. Of the 194 patients, 40 patients (20.6%) were diagnosed with venous thromboembolism and 10 patients (5.2%) were diagnosed with concomitant pulmonary thromboembolism. Conversely, bleeding was observed in 29 patients (15%). The location of bleeding was the primary tumor in 17 cases, metastatic tumor in 9 and hemorrhagic gastric ulcer in 3. Within the venous thromboembolism group (n = 40), bleeding was observed in 10 patients (25%). Multivariate analysis showed that International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding score ≥7 correlated significantly with major bleeding (P = 0.01). In patients with a low risk of bleeding, major bleeding was observed in only three patients.
Conclusions
IMPROVE bleeding score may predict the risk for bleeding in gastrointestinal cancer patients with venous thromboembolism. Selecting patients with a low risk of bleeding using with IMPROVE bleeding score is expected to contribute to the safer management of anticoagulation therapy for cancer-associated thromboembolism.
Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability ...to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (
> 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (
< 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via β1-adrenergic mechanisms while hyperthermic.
BACKGROUND:Moderate intensity exercise is associated with a decreased incidence of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial ...fibrillation risk. We evaluated the effects of 24 months of high intensity exercise training on left atrial (LA) mechanical and electric remodeling in sedentary, healthy middle-aged adults.
METHODS:Sixty-one participants (53±5 years) were randomized to 10 months of exercise training followed by 14 months of maintenance exercise or stretching/balance control. Fourteen Masters athletes were added for comparison. Left ventricular (LV) and LA volumes underwent 3D echocardiographic assessment, and signal-averaged electrocardiographs for filtered P-wave duration and atrial late potentials were completed at 0, 10, and 24 months. Extended ambulatory monitoring was performed at 0 and 24 months. Within and between group differences from baseline were compared using mixed-effects model repeated-measures analysis.
RESULTS:Fifty-three participants completed the study (25 control, 28 exercise) with 88±11% adherence to assigned exercise sessions. In the exercise group, both LA and LV end diastolic volumes increased proportionately (19% and 17%, respectively) after 10 months of training (peak training load). However, only LA volumes continued to increase with an additional 14 months of exercise training (LA volumes 55%; LV end diastolic volumes 15% at 24 months versus baseline; P<0.0001 for all). The LA:LV end diastolic volumes ratio did not change from baseline to 10 months, but increased 31% from baseline in the Ex group (P<0.0001) at 24 months, without a change in controls. There were no between group differences in the LA ejection fraction, filtered P-wave duration, atrial late potentials, and premature atrial contraction burden at 24 months and no atrial fibrillation was detected. Compared with Masters athletes, the exercise group demonstrated lower absolute LA and LV volumes, but had a similar LA:LV ratio after 24 months of training.
CONCLUSIONS:Twenty-four months of high intensity exercise training resulted in LA greater than LV mechanical remodeling with no observed electric remodeling. Together, these data suggest different thresholds for electrophysiological and mechanical changes may exist in response to exercise training, and provide evidence supporting a potential mechanism by which high intensity exercise training leads to atrial fibrillation.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02039154.
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