Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis.

AIMS: Coxsackievirus B3 (CVB3)-induced myocarditis, initially considered a sole immune-mediated disease, also results from a direct CVB3-mediated injury of the cardiomyocytes. Mesenchymal stem cells (MSCs) have, besides immunomodulatory, also anti-apoptotic features. In view of clinical translation, we first analysed whether MSCs can be infected by CVB3. Next, we explored whether and how MSCs could reduce the direct CVB3-mediated cardiomyocyte injury and viral progeny release, in vitro, in the absence of immune cells. Finally, we investigated whether MSC application could improve murine acute CVB3-induced myocarditis. METHODS AND RESULTS: Phase contrast pictures and MTS viability assay demonstrated that MSCs did not suffer from CVB3 infection 4-12-24-48 h after CVB3 infection. Coxsackievirus B3 RNA copy number decreased in this time frame, suggesting that no CVB3 replication took place. Co-culture of MSCs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis, oxidative stress, intracellular viral particle production, and viral progeny release in a nitric oxide (NO)-dependent manner. Moreover, MSCs required priming via interferon-γ (IFN-γ) to exert their protective effects. In vivo, MSC application improved the contractility and relaxation parameters in CVB3-induced myocarditis, which was paralleled with a reduction in cardiac apoptosis, cardiomyocyte damage, left ventricular tumour necrosis factor-α mRNA expression, and cardiac mononuclear cell activation. Mesenchymal stem cells reduced the CVB3-induced CD4- and CD8- T cell activation in an NO-dependent way and required IFN-γ priming. CONCLUSION: We conclude that MSCs improve murine acute CVB3-induced myocarditis via their anti-apoptotic and immunomodulatory properties, which occur in an NO-dependent manner and require priming via IFN-γ.

Local vascular complications after use of the hemostatic puncture closure device Angio-Seal.

BACKGROUND: As an alternative to manual pressure techniques new systems for achieving arterial hemostasis after cardiac catheterization were developed. Here we report about the diagnosis and therapy of femoral artery complications after use of the closure device Angio-Seal, consisting of an intraarterial anchor and extravascular collagen plug. PATIENTS AND METHODS: Angio-Seal was deployed in 350 patients undergoing cardiac catheterization. Vascular investigations after device application consisted of ankle/brachial-pressure-index measurement, duplex sonography, and angiography. RESULTS: Vascular complications occurred in 10 of 350 patients. In two patients complete occlusions of the superficial femoral artery required immediate vascular surgery. Stenoses of the superficial (five patients) and the common (three patients) femoral arteries were diagnosed in 8 cases. Of these 10 patients eight were obese, in 2 cases there was a further catheterization with Angio-Seal device application via the same femoral approach. Until now six patients underwent successful surgery: in 4 cases the whole Angio-Seal device was located intraarterially, there was 1 case of intima-dissection, and 1 case remained unclear due to a diagnostic delay of 7 months. In three patients with stenoses of the common femoral arteries without hemodynamic relevance no therapy was required. CONCLUSIONS: Occlusions or stenoses of femoral arteries after use of Angio-Seal can be diagnosed easily by duplex sonography. All hemodynamic relevant complications (n = 7 of 350 [2%]) concerned a puncture of superficial femoral arteries. In these patients vascular surgery seems to be an adequate therapy.

Incidence of cutaneous vasoactivity in patients with anemia and pulmonary hypoxia.

BACKGROUND: In cutaneous laser Doppler flow (LDF)-recordings, various forms of flowmotion or vasoactivity can be observed. It is still a matter of dispute, whether flowmotion is a phenomenon of physiological or pathophysiological conditions. Therefore, we tested the hypothesis of increased vasoactivity being typical for patients with various degrees of acute and chronic anemia as well as with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We examined 12 healthy controls, 14 patients with COPD with a PO2 below 60 mmHg, 16 patients with chronic and 7 patients with acute anemia with an Hb below 12 g/dl. We used a simple LDF-technique on the dorsum of the forefoot. The regularity of blood flow frequencies was determined by calculation of the coefficient of variation. RESULTS: Periods without vasoactivity (i.e. constant flow pattern) were 21% in normal controls, 7% in patients with COPD and 2% in patients with acute or chronic anemia. Mean frequencies in the four groups varied between 3.8 and 4.8 cpm, with significant changes only in the group with acute blood loss. However, vasoactivity was significantly more regular in the COPD- and anemia-groups as compared to normal controls, with coefficients of variation of 47.4% for controls, 31.8% for COPD- and 29.3% for chronic and 35.1% for acute anemia-patients. CONCLUSIONS: The present paper shows that cutaneous vasoactivity is more regular in the three examined clinical entities of systemic tissue hypo-oxygenation, i.e. chronic and acute anemia and severe COPD as compared to healthy control subjects. Therefore, we hypothesize that increased vasoactivity constitutes a regulatory defense mechanism in cases of reduced oxygenation, by improving microcirculatory blood flow distribution.