Identifying priority patients for coronary angiography

We conducted an open observational study with blinded endpoint evaluation to validate the use of the Duke treadmill score in identifying patients likely to require coronary intervention. We studied 101 consecutive patients referred for coronary angiography from a cardiology clinic. All patients had a Bruce protocol exercise test. A 70% stenosis was regarded as significant. Patients were referred for percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) surgery, if indicated. The Duke score was calculated as follows: exercise time (min) - (5 x ST segment deviation [mm]) - (4 x angina index [text]). Patients were classified into low, medium and high risk. The patients at high risk are more likely to have a significant stenosis (53/58 vs 30/43: p = 0.01 [OR 4.59 95% CI 1.34-16.6]) and require CABG or PTCA (47/58 vs 16/43: p < 0.001 [OR 7.21 95% CI 2.69-19.8]) than those at medium/low risk. Multiple logistic regression analysis, including ST segment depression, exercise time and symptoms shows that the score independently predicts a significant stenosis (p = 0.002) and the need for coronary intervention (p = 0.001). Introducing the score can help to identify those patients who need priority investigation.     

Hemodynamics and axial strain additively increase matrix remodeling and MMP-9, but not MMP-2, expression in arteries engineered by directed remodeling

We previously demonstrated the ability to create engineered arteries by carefully controlling the mechanical environment of intact arteries perfused ex vivo, yielding engineered arteries with native appearance and vasoactive response. Increased axial strain was sufficient to increase length up to 20% in 9 days through a growth and remodeling response. The amount of the achievable length increase, however, was highly dependent on the hemodynamic conditions acting through unknown mechanisms. Because matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activity is increased, and often required, in mechanically induced remodeling in vivo, MMP-2 and MMP-9 expression was investigated to elucidate the hemodynamic mediation of artery length. Carotid arteries from 30 kg pigs were perfused for 9 days ex vivo at either in situ axial strain or with a gradual 50% increase in axial strain, under either arterial or reduced hemodynamics ( approximately 10% of arterial hemodynamics). MMP-2 protein expression increased roughly twofold, while MMP-9 expression increased threefold under either reduced hemodynamics or increased axial strain (p < 0.05). The combination of reduced hemodynamics with increased axial strain demonstrated an additive increase in MMP-9 protein (p < 0.05) with no further change in MMP-2 expression. To investigate the mechanism by which axial strain and hemodynamics could additively increase MMP-9 expression, the expression of nuclear factor kappa B (NF-kappaB) subunits p50 and p65 was evaluated. Axial strain stimulated p65 expression and localization, while hemodynamics increased p50 expression, with both molecules being expressed only when both mechanical stimuli were applied. These data suggest that MMP-9 expression can be simultaneously stimulated by separate mechanical stimuli mediated by p50 and p65 expression, and that by using conditions that maximize MMP-9 expression, we can create an optimal remodeling environment to better direct the growth of engineered arteries and other tissues.