Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation.

The causative role of inflammation in hypertension-related cardiovascular diseases is evident and calls for development of specific immunomodulatory therapies. We tested the therapeutic efficacy and mechanisms of action of developmental endothelial locus-1 (DEL-1), an endogenous antiinflammatory factor, in angiotensin II- (ANGII-) and deoxycorticosterone acetate-salt-induced (DOCA-salt-induced) cardiovascular organ damage and hypertension. By using mice with endothelial overexpression of DEL-1 (EC-Del1 mice) and performing preventive and interventional studies by injecting recombinant DEL-1 in mice, we showed that DEL-1 improved endothelial function and abrogated aortic adventitial fibrosis, medial thickening, and loss of elastin. DEL-1 also protected the mice from cardiac concentric hypertrophy and interstitial and perivascular coronary fibrosis and improved left ventricular function and myocardial coronary perfusion. DEL-1 prevented aortic stiffness and abolished the progression of hypertension. Mechanistically, DEL-1 acted by inhibiting αvß3 integrin-dependent activation of pro-MMP2 in mice and in human isolated aorta. Moreover, DEL-1 stabilized αvß3 integrin-dependent CD25+FoxP3+ Treg numbers and IL-10 levels, which were associated with decreased recruitment of inflammatory cells and reduced production of proinflammatory cytokines in cardiovascular organs. The demonstrated effects and immune-modulating mechanisms of DEL-1 in abrogation of cardiovascular remodeling and progression of hypertension identify DEL-1 as a potential therapeutic factor.

Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation.

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Aortic valve replacement in noncompaction cardiomyopathy at two-year follow-up.

We report a male patient suffering left ventricular noncompaction cardiomyopathy in combination with low-gradient aortic stenosis. Preoperative echocardiography and magnetic resonance imaging revealed the diagnosis. After aortic valve replacement, the clinical course was uneventful. Two years of follow-up confirmed that the general prognosis was primarily affected by impaired ventricular function, thrombembolism, and arrhythmias.

Mortality after cardiac surgery with or without microwave ablation in patients with permanent atrial fibrillation.

BACKGROUND AND AIM OF THE STUDY: The surgical treatment of atrial fibrillation (AF) by Cox and other ablation methods shows a 50-90% conversion rate to sinus rhythm. However, to date no study has addressed the influence of ablation on the mortality rate. METHODS: The perioperative and postoperative mortalities of 210 consecutive patients with permanent AF was investigated for up to two years after cardiac surgery with (n = 111) or without (n = 99) endocardial microwave ablation within the framework of a prospective register study. All patients were followed up. RESULTS: In the ablation group, one patient (0.9%) died perioperatively, seven died during the first year of follow up (6.3%), and nine in the second year of follow up (8.1%). In the control group, five patients died perioperatively (5.1%), 12 died in the first year of follow up (12.1%), and 22 in the second year of follow up (22.2%). During the two-year follow up period, significantly more patients died in the control group than in the ablation group (Log-Rank test: p = 0.0051). CONCLUSION: The results of this register study showed that among patients with permanent AF who underwent cardiac surgery with ablation, mortality was significantly lower than in those who underwent comparable surgery but without ablation. The marked difference in mortality was essentially based on the typical clinical consequences of AF (e.g. thromboembolic complications, cardiac arrhythmias and bleeding complications due to anticoagulation therapy), which occurred less often in the ablation group.

Influence of ventricular pacing on myocardial oxygen tension.

INTRODUCTION: The influence of heart rate on cardiac output, oxygen consumption, and myocardial activity has been widely investigated. However, the influence of heart rate on myocardial oxygen tension (pO2) remains unclear. Since the introduction of flexible pO2 micro catheters to measure partial oxygen tension in a working muscle, it is possible to investigate the influence of heart rate on myocardial oxygen tension. METHODS: Intraoperatively, a flexible pO2 micro catheter was positioned in the mid-myocardium of 8 male farm pigs. The heart rate was varied via an external pacer from base rate up to fibrillation and the corresponding myocardial pO2 was measured. RESULTS: Within 2 min, the myocardial pO2 adjusted to a change in heart rate. In this animal model, an optimal myocardial pO2 was observed at 109 bpm. A further increase in heart rate led to a decrease in myocardial pO2. When the heart rate was reaching the level of a fibrillation, pO2 dropped to zero. CONCLUSION: In young healthy pigs--with a normal blood vessel regulation and the pharmacologic and experimental conditions used in this study--a significant relation between myocardial pO2 and heart rate was observed. Myocardial oxygen tension increased during cardiac pacing until a heart rate of 109 bpm. Thereafter a decline of pO2 occurred. Each change in heart rate resulted in a corresponding change of pO2 within roughly 2 min.