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"Bode, Christoph"
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Platelet Contributions to Myocardial Ischemia/Reperfusion Injury
Obstruction of a coronary artery causes ischemia of heart tissue leading to myocardial infarction. Prolonged oxygen deficiency provokes tissue necrosis, which can result in heart failure and death of the patient. Therefore, restoration of coronary blood flow (reperfusion of the ischemic area) by re-canalizing the affected vessel is essential for a better patient outcome. Paradoxically, sudden reperfusion also causes tissue injury, thereby increasing the initial ischemic damage despite restoration of blood flow (=ischemia/reperfusion injury, IRI). Myocardial IRI is a complex event that involves various harmful mechanisms (e.g., production of reactive oxygen species and local increase in calcium ions) as well as inflammatory cells and signals like chemokines and cytokines. An involvement of platelets in the inflammatory reaction associated with IRI was discovered several years ago, but the underlying mechanisms are not yet fully understood. This mini review focusses on platelet contributions to the intricate picture of myocardial IRI. We summarize how upregulation of platelet surface receptors and release of immunomodulatory mediators lead to aggravation of myocardial IRI and subsequent cardiac damage by different mechanisms such as recruitment and activation of immune cells or modification of the cardiac vascular endothelium. In addition, evidence for cardioprotective roles of distinct platelet factors during IRI will be discussed.
Journal Article
Influence of low-flow time on survival after extracorporeal cardiopulmonary resuscitation (eCPR)
Background
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support under extracorporeal cardiopulmonary resuscitation (eCPR) is the last option and may be offered to selected patients. Several factors predict outcome in these patients, including initial heart rhythm, comorbidities, and bystander cardiopulmonary resuscitation (CPR). We evaluated outcomes of all VA-ECMO patients treated within the last 5 years at our center in respect to low-flow duration during CPR.
Methods
We report retrospective registry data on all patients with eCPR treated at a university hospital between October 2010 and May 2016.
Results
A total of 133 patients (mean age 58.7 ± 2.6 years, Simplified Acute Physiology Score II score at admission 48.1 ± 3.4) were included in the analysis. The indication for eCPR was either in-hospital or out-of-hospital cardiac arrest without return of spontaneous circulation (
n
= 74 and 59, respectively). There was a significant difference in survival rates between groups (eCPR in-hospital cardiac arrest [IHCA] 18.9%, eCPR out-of-hospital cardiac arrest [OHCA] 8.5%;
p
< 0.042). Mean low-flow duration (i.e., duration of mechanical CPR until VA-ECMO support) was 59.6 ± 5.0 minutes in all patients and significantly shorter in IHCA patients than in OHCA patients (49.6 ± 5.9 vs. 72.2 ± 7.4 minutes,
p
= 0.001). Low-flow time strongly correlated with survival (
p
< 0.001) and was an independent predictor of mortality.
Conclusions
Time to full support is an important and alterable predictor of patient survival in eCPR, suggesting that VA-ECMO therapy should be established as fast as possible in the selected patients destined for eCPR.
Journal Article
Diabetic Cardiomyopathy: Does the Type of Diabetes Matter?
In recent years, type 2 diabetes mellitus has evolved as a rapidly increasing epidemic that parallels the increased prevalence of obesity and which markedly increases the risk of cardiovascular disease across the globe. While ischemic heart disease represents the major cause of death in diabetic subjects, diabetic cardiomyopathy (DC) summarizes adverse effects of diabetes mellitus on the heart that are independent of coronary artery disease (CAD) and hypertension. DC increases the risk of heart failure (HF) and may lead to both heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Numerous molecular mechanisms have been proposed to underlie DC that partially overlap with mechanisms believed to contribute to heart failure. Nevertheless, the existence of DC remains a topic of controversy, although the clinical relevance of DC is increasingly recognized by scientists and clinicians. In addition, relatively little attention has been attributed to the fact that both underlying mechanisms and clinical features of DC may be partially distinct in type 1 versus type 2 diabetes. In the following review, we will discuss clinical and preclinical literature on the existence of human DC in the context of the two different types of diabetes mellitus.
Journal Article
Serotonin: a platelet hormone modulating cardiovascular disease
Cardiovascular diseases and depression are significant health burdens and increasing evidence suggests a causal relationship between them. The incidence of depression among patients suffering from cardiovascular disease is markedly elevated, and depression itself is an established cardiovascular risk factor. Serotonin 5-hydroxytryptamin (5-HT), a biogenic amine acting as a neurotransmitter and a peripheral hormone, is involved in the pathogenesis of both, cardiovascular disease and depression. Novel cardiovascular functions of 5-HT have recently been described and will be summarized in this review. 5-HT has a broad spectrum of functions in the cardiovascular system, yet the clinical or experimental data are partly conflicting. There is further research needed to characterize the clinical effects of 5-HT in particular tissues to enable targeted pharmacological therapies.
Journal Article
Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice
In Germany, the use of TAVR increased substantially between 2007 and 2013, whereas the use of surgical aortic-valve replacement decreased modestly. Patients undergoing TAVR were older and at higher operative risk. Mortality decreased over time in both groups.
Surgical aortic-valve replacement was a major clinical advance in the 1960s
1
and offered a cure for aortic stenosis, a condition for which no disease-modifying pharmacologic therapy is available. Surgical replacement remained the only treatment option until 2007, when devices for transcatheter aortic-valve replacement (TAVR) were approved.
2
Since then, TAVR has become established not only as an effective therapy for patients for whom surgery is not an option
3
but also as an alternative for high-risk patients.
4
The introduction of TAVR has led to questions about the effect of this relatively new approach on current clinical practice and its effect on surgical . . .
Journal Article
Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction
In patients with acute MI, multivessel coronary artery disease, and other cardiovascular risk factors, CSL112 (human plasma–derived apolipoprotein A1) did not reduce the risk of MI, stroke, or death from cardiovascular causes.
Journal Article
Thrombotic circuit complications during venovenous extracorporeal membrane oxygenation in COVID-19
The novel coronavirus SARS-CoV-2 and the resulting disease COVID-19 causes pulmonary failure including severe courses requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). Coagulopathy is a known complication of COVID-19 leading to thrombotic events including pulmonary embolism. It is unclear if the coagulopathy also increases thrombotic circuit complications of the ECMO. Aim of the present study therefor was to investigate the rate of V-V ECMO complications in COVID-19. We conducted a retrospective registry study including all patients on V-V ECMO treated at our centre between 01/2018 and 04/2020. COVID-19 cases were compared non- COVID-19 cases. All circuit related complications resulting in partial or complete exchange of the extracorporeal system were registered. In total, 66 patients were analysed of which 11 (16.7%) were SARS-CoV-2 positive. The two groups did not differ in clinical parameters including age (COVID-19 59.4 vs. non-COVID-19 58.1 years), gender (36.4% vs. 40%), BMI (27.8 vs. 24.2) and severity of illness as quantified by the RESP Score (1pt. vs 1pt.). 28 days survival was similar in both groups (72.7% vs. 58.2%). While anticoagulation was similar in both groups (p = 0.09), centrifugal pump head thrombosis was more frequent in COVID-19 (9/11 versus 16/55 p < 0.01). Neither the time to first exchange (p = 0.61) nor blood flow at exchange (p = 0.68) did differ in both groups. D-dimer levels prior to the thrombotic events were significantly higher in COVID-19 (mean 15.48 vs 26.59, p = 0.01). The SARS-CoV-2 induced infection is associated with higher rates of thrombotic events of the extracorporeal system during V-V ECMO therapy.
Journal Article
AN EMPIRICAL EXAMINATION OF SUPPLY CHAIN PERFORMANCE ALONG SEVERAL DIMENSIONS OF RISK
This research operationalizes several supply chain risk sources and investigates their relationships with supply chain performance. The responses of 760 executives from firms operating in Germany reveal that demand side and supply side risks do have a negative impact on performance whereas regulatory, legal and bureaucratic risks, infrastructure risks, as well as catastrophic risks do not. The analysis and results augment previous research regarding the impact of supply chain risks on the operational performance of firms and shareholder value and provide a detailed analysis of supply chain risk sources as contextual variables in strategic decision‐making.
Journal Article
SIRT3 deficiency impairs mitochondrial and contractile function in the heart
Sirtuin 3 (SIRT3) is a mitochondrial NAD
+
-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues. The role of SIRT3 in myocardial energetics and in the development of mitochondrial dysfunction in cardiac pathologies, such as the failing heart, remains to be elucidated. To investigate the role of SIRT3 in the regulation of myocardial energetics and function SIRT3
−/−
mice developed progressive age-related deterioration of cardiac function, as evidenced by a decrease in ejection fraction and an increase in enddiastolic volume at 24 but not 8 weeks of age using echocardiography. Four weeks following transverse aortic constriction, ejection fraction was further decreased in SIRT3
−/−
mice compared to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis. In isolated working hearts, a decrease in cardiac function in SIRT3
−/−
mice was accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen consumption, whereas rates of glycolysis were increased. Respiratory capacity and ATP synthesis were decreased in cardiac mitochondria of SIRT3
−/−
mice. HPLC measurements revealed a decrease of the myocardial ATP/AMP ratio and of myocardial energy charge. Using LC–MS/MS, we identified increased acetylation of 84 mitochondrial proteins, including 6 enzymes of fatty acid import and oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile function in the heart, likely due to increased acetylation of various energy metabolic proteins and subsequent myocardial energy depletion.
Journal Article