At the "threshold" of certainty: Risk stratification and clinical assessment incongruity in the diagnosis of aortic dissection.

The use of D-dimer assay to screen for aortic dissection has become routine in clinical practice. Although an uncommon disease entity, aortic dissection is rapidly fatal without prompt diagnosis, and biochemical detection in the proper clinical context is crucial. We performed a retrospective chart review of all aortic dissections presenting to a community tertiary care center between 2000 and 2016 and identified three patients in whom laboratory D-dimer testing was positive and a diagnosis of Stanford Type A aortic dissection was confirmed with computed tomography angiography based on clinical assessment and a newly validated risk stratification tool.

Selective ß2-adrenoreceptor stimulation attenuates myocardial cell death and preserves cardiac function after ischemia-reperfusion injury.

OBJECTIVE: ß(2)-adrenoreceptor activation has been shown to protect cardiac myocytes from cell death. We hypothesized that acute ß(2)-adrenoreceptor stimulation, using arformoterol (ARF), would attenuate myocardial ischemia/reperfusion (R) injury via NO synthase activation and cause a subsequent increase in NO bioavailability. METHODS AND RESULTS: Male C57BL/6J and endothelial NO synthase (eNOS) knockout mice were subjected to 45 minutes of myocardial ischemia and 24 hours of R. ARF or vehicle was administered 5 minutes before R. Serum troponin-I was measured, and infarct size per area-at-risk was evaluated at 24 hours of R. Echocardiography was performed at baseline and 2 weeks after R. Myocardial cAMP, protein kinase A, eNOS/Akt phosphorylation status, and NO metabolite levels were assayed. ARF (1 µg/kg) reduced infarct size per area-at-risk by 53.1% (P<0.001 versus vehicle) and significantly reduced troponin-I levels (P<0.001 versus vehicle). Ejection fraction was significantly preserved in ARF-treated hearts compared with vehicle hearts at 2 weeks of R. Serum cAMP and nuclear protein kinase A C-α increased 5 and 15 minutes after ARF injection, respectively (P<0.01). ARF increased Akt phosphorylation at Thr(308) (P<0.001) and Ser(473) (P<0.01), and eNOS phosphorylation at Ser(1177) (P<0.01). ARF treatment increased heart nitrosothiol levels (P<0.001) at 15 min after injection. ARF failed to reduce infarct size in eNOS(-/-) mice. CONCLUSIONS: Our results indicate that ß(2)-adrenoreceptor stimulation activates cAMP, protein kinase A, Akt, and eNOS and augments NO bioavailability. Activation of this prosurvival signaling pathway attenuates myocardial cell death and preserves cardiac function after ischemia/reperfusion.

The polysulfide diallyl trisulfide protects the ischemic myocardium by preservation of endogenous hydrogen sulfide and increasing nitric oxide bioavailability.

Diallyl trisulfide (DATS), a polysulfide constituent found in garlic oil, is capable of the release of hydrogen sulfide (H(2)S). H(2)S is a known cardioprotective agent that protects the heart via antioxidant, antiapoptotic, anti-inflammatory, and mitochondrial actions. Here, we investigated DATS as a stable donor of H(2)S during myocardial ischemia-reperfusion (MI/R) injury in vivo. We investigated endogenous H(2)S levels, infarct size, postischemic left ventricular function, mitochondrial respiration and coupling, endothelial nitric oxide (NO) synthase (eNOS) activation, and nuclear E2-related factor (Nrf2) translocation after DATS treatment. Mice were anesthetized and subjected to a surgical model of MI/R injury with and without DATS treatment (200 µg/kg). Both circulating and myocardial H(2)S levels were determined using chemiluminescent gas chromatography. Infarct size was measured after 45 min of ischemia and 24 h of reperfusion. Troponin I release was measured at 2, 4, and 24 h after reperfusion. Cardiac function was measured at baseline and 72 h after reperfusion by echocardiography. Cardiac mitochondria were isolated after MI/R, and mitochondrial respiration was investigated. NO metabolites, eNOS phosphorylation, and Nrf2 translocation were determined 30 min and 2 h after DATS administration. Myocardial H(2)S levels markedly decreased after I/R injury but were rescued by DATS treatment (P < 0.05). DATS administration significantly reduced infarct size per area at risk and per left ventricular area compared with control (P < 0.001) as well as circulating troponin I levels at 4 and 24 h (P < 0.05). Myocardial contractile function was significantly better in DATS-treated hearts compared with vehicle treatment (P < 0.05) 72 h after reperfusion. DATS reduced mitochondrial respiration in a concentration-dependent manner and significantly improved mitochondrial coupling after reperfusion (P < 0.01). DATS activated eNOS (P < 0.05) and increased NO metabolites (P < 0.05). DATS did not appear to significantly induce the Nrf2 pathway. Taken together, these data suggest that DATS is a donor of H(2)S that can be used as a cardioprotective agent to treat MI/R injury.