A 51-year-old man presented with chest pain, high troponin level, inflammatory syndrome and ST-segment elevation in the anterior leads. While the transthoracic echocardiogram (TTE) showed anteroseptal hypokinesis and apical akinesis, the coronary angiogram was normal. Cardiac MR demonstrated a typical aspect of myocarditis (multiple areas of mid-myocardial late gadolinium enhancement, sparing the subendocardial layer, along with oedema). The initial diagnosis was clinically suspected myocarditis with pseudoinfarct presentation. However, the short-term evolution was not typical of this syndrome, since an apical transmural scar with aneurysm developed within 2 weeks. Seven years later, the patient remained asymptomatic, while Q waves persisted in anterior leads along with an apical aneurysm on TTE. A transmural myocardial necrosis with aneurysm is an unusual complication of acute myocarditis. The potential mechanisms accounting for the development of these lesions are reviewed, and the clinical implications for the diagnosis and monitoring of acute myocarditis are discussed.

The arteriolar myogenic response, which is defined as vasoconstriction to increases in intraluminal pressure and, conversely, dilation to a reduction in pressure, is key in the setting of vascular resistance, local control of microvascular blood flow through autoregulation, and in the control of capillary hydrostatic pressure. Although considerable progress has been made in the quest for understanding the underlying sensory apparatus and cellular mechanisms, fundamental questions remain - particularly if this pathway is to be considered as a target for novel strategies of pharmacological intervention. We propose that an ability to 're-set' myogenic tone would enable modification of systemic vascular resistance and pressure while at the same time preserving existing interactions with neurohumoral regulatory mechanisms. The challenge, therefore, is to identify steps unique to the myogenic signaling pathway to enable specific pharmacological targeting.

Reduced cardiac output is one of the consequences of myocarditis. Bosentan, an endothelin-1 receptor (ET1R) antagonist, could be useful to reduce cardiac afterload, preserving cardiac output. In this study, we investigated the potential therapeutic use of bosentan in an animal model of viral myocarditis. Using a mouse model of coxsackievirus B3 (CVB3)-induced myocarditis, we demonstrated preserved ejection fraction (EF) and fractional shortening (FS) by treatment with bosentan (68+/-5.8% EF and 40+/-3.7% FS for treated versus 48+/-2.2% EF and 25+/-2.6% FS for controls; P=0.028). However, bosentan enhanced cardiac viral load (10.4+/-6.7% in the bosentan group versus 5.0+/-5.5% in control group; P=0.02), likely through enhancement of p38 mitogen-activated protein kinase (MAPK) phosphorylation (0.77+/-0.40% ATF2 activation in the bosentan group versus 0.03+/-0.02% in controls; P=0.0002), mediated by endothelin receptor type-A. We further demonstrate that a water soluble inhibitor of p38 MAPK, SB203580 HCl, is a potent inhibitor of virus replication in the heart (0.28% antisense viral genome stained area for 3 mg/kg dose versus 2.9% stained area for controls; P=0.01), attenuates CVB3-induced myocardial damage (blinded cardiac histopathologic scores of 1.8+/-1.6 and 2.05+/-1.2 for the 3 mg/kg and 10 mg/kg doses, respectively, versus 3.25+/-1.2 for the controls), and preserves cardiac function (69+/-3.5% EF for 3 mg/kg dose and 71+/-6.7% EF for 10 mg/kg dose versus 60+/-1.5% EF control; P=0.038 and P=0.045, as compared to control, respectively). Bosentan, a prescribed vasodilator, improves cardiac function but enhances viral load and myocarditis severity through ETRA mediated p38 MAPK activation; p38 MAPK is a desirable antiviral target. Caution must be exercised during treatment of suspected infectious myocarditis with supportive vasoactive remedies.

The vascular endothelium constitutes approximately 1% of body mass (1kg) and has a surface area of approximately 5000m(2). The endothelium is a multifunctional endocrine organ strategically placed between the vessel wall and the circulating blood, and has a key role in vascular homeostasis. The endothelium is both a target for and mediator of cardiovascular disease. The endothelium releases several relaxing and constricting factors, which can affect vascular homeostasis. Endothelial dysfunction, whether caused by physical injury or cellular damage, leads to compensatory responses that alter the normal homeostatic properties of the endothelium. In this review, we summarized some physiological aspects of endothelial function and then we discussed endothelial dysfunction during some pathological conditions.

Associations between pathogens and hypertension (HT) has been reported, but few studies have focused on the relationship between aggregate pathogens and HT. The present study explored whether the risk of HT is associated with each pathogen (defined as Chlamydia pneumoniae (C. pneumoniaee), mycoplasma pneumoniae (m. pneumoniae), helicobacter pylori (h. pylori) and coxsackie virus) or with aggregate pathogens in chinese mongolians.

One thousand and thirty Chinese Mongolians aged 30 years or more were recruited, including 488 hypertensive and 942 normotensive subjects. Enzyme-linked immunosorbent assay was used to detect IgG antibodies for C. pneumoniaee, M. pneumoniae, H. pylori and Coxsackie virus. The seroprevalence of Coxsackie virus was significantly associated with HT (odds ratio (OR) 3.7 after adjustment for risk factors), but no significant association was found for C. pneumoniae, M. pneumoniae and H. pylori (OR 1.32, 0.75 and 1.19, respectively). The results also showed that the risk of HT was associated with the aggregate pathogens: it increased with the increasing number of pathogens, and the ORs were 1.629, 2.653, 2.129, and 5.146 for 1, 2, 3 and 4 pathogens, respectively, after controlling for risk factors.

The risk of HT is associated with Coxsackie virus and aggregate pathogen load. The mechanism(s) underlying the associations remain to be elucidated further.

Myocarditis is an acute inflammatory disease of the myocardium for which there is currently no specific therapy. We investigated the therapeutic potential of C-type natriuretic peptide (CNP) in acute experimental autoimmune myocarditis. One week after injection of porcine myosin into male Lewis rats, CNP (0.05 microg/kg/min) was continuously administered for 2 weeks. CNP infusion significantly increased maximum dP/dt, decreased left ventricular end-diastolic pressure, and improved fractional shortening compared with vehicle administration. In vehicle-treated hearts, severe necrosis and marked infiltration of CD68-positive inflammatory cells were observed. Myocardial and serum levels of monocyte chemoattractant protein-1 were elevated in myocarditis. However, these changes were attenuated by CNP infusion. In addition, treatment with CNP significantly increased myocardial capillary density. Guanylyl cyclase-B, a receptor for CNP, was expressed in myocarditic heart, and cyclic guanosine monophosphate was elevated by CNP infusion. In conclusion, CNP infusion attenuated cardiac function in acute myocarditis through anti-inflammatory and angiogenic effects.

The objective of this study was to apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Regarding methodology, BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy strain) or a severe (Woodruff strain) myocarditis. Left ventricular dimensions, fractional shortening, and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 wk after infection. As a result, the resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 wk after infection with either virus variant [from 2.5 (SD 0.3) to 1.4 (SD 0.1) in severe and from 2.4 (SD 0.4) to 2.1 (SD 0.3) in mild myocarditis], being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 wk after infection. Fractional shortening decreased to the same levels 1 wk after infection with either virus variant [from 0.54 (SD 0.02) to 0.43 (SD 0.03) in severe and from 0.51 (SD 0.03) to 0.44 (SD 0.02) in mild myocarditis, P < 0.05]. However, 2 wk after infection, mice with severe myocarditis had enlarged left ventricles and lower fractional shortening [0.31 (SD 0.03)] than mice with mild myocarditis [0.47 (SD 0.02), P < 0.01]. In conclusion, CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure, indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.