Spatial orientation of atherosclerotic plaque in non-branching coronary artery segments.

It has been postulated that atherosclerotic plaque deposition is spatially related to regions of low shear in non-branching vessel segments. Intravascular ultrasound (IVUS) allows precise spatial orientation of coronary artery plaque formation in humans. The objective of this study was to test the hypothesis that coronary plaques have a higher prevalence on the myocardial side in regions that encounter low surface shear stress. IVUS allows the determination of the inner versus the outer curve of the vessel based on vascular and perivascular landmarks. We studied 30 consecutive patients pre-intervention using IVUS and measured vessel area, lumen area and plaque area (vessel-lumen area) during a motorized pullback at 1 mm intervals. Vessel segments near a side branch (within two times the diameter of the vessel) were excluded from analysis because of flow disturbances. All plaques were classified as concentric or eccentric and all eccentric plaques were further divided with respect to their spatial orientation in the vessel into quadrants: myocardial (inner curve, lower shear stress), epicardial (outer curve, higher shear stress) and lateral (two quadrants intermediate). A total of 613 cross-sections were analyzed in 14 left anterior descending, six left circumflex, and ten right coronary arteries. Plaque distribution was found to be concentric in 321 (52.4%) and eccentric in 292 (47.6%) cross sections. Of all eccentric plaques, 184 cross sections were oriented toward the myocardial side (62.6%) compared to only 54 toward the epicardial side (17.3%) and 54 in the 2 lateral quadrants (19.5%, P<0.001). No difference in plaque area (6.75+/-2.70 vs. 6.76+/-2.60 mm(2)), vessel area (15.28+/-4.73 vs. 15.35+/-4.40 mm(2)), or plaque thickness (1.26+/-0.37 vs. 1.25+/-0.43 mm) was noted between myocardial or epicardial plaques. These results suggest that atherosclerotic plaques develop more frequently on the myocardial side of the vessel wall, which may relate to lower shear stress. However, plaque size is similar on the epicardial and myocardial side.

Accentuated remodeling on the upstream side of atherosclerotic lesions.

Although it has been postulated that atherosclerotic stenotic lesions cannot remodel in response to altered flow, evidence to support or refute this hypothesis has been elusive. In vitro models have shown that accelerated endothelial shear stress occurs on the upstream side of stenoses, while turbulent lower shear stress is seen on the downstream side. We therefore compared vascular remodeling at paired sites 2 mm upstream and 2 mm downstream of the site of minimal lumen area in 25 atherosclerotic lesions in 23 patients using intravascular ultrasound. Remodeling was compared by 2 methods: normalized vessel area (vessel area(lesion)/vessel(reference) and remodeling index (change in vessel area/change in plaque area from reference). Normalized vessel area was significantly greater upstream than downstream (1.21+/-0.06 vs. 1.12+/-0.09; p<0.05), despite similar plaque burden (8.84+/-0.81 vs. 8.42+/-0.85 mm2) resulting in larger lumen area (8.15+/-1.02 vs. 6.10+/-0.88 mm2; p<0.05). Remodeling index was also significantly higher upstream than downstream (0.67+/-0.20 vs. 0.12+/-0.24, respectively, p<0.05). Accentuation of remodeling on the upstream side was significantly correlated (r = 0.54, p = 0.01) with the mean degree of shear acceleration expected by stenosis severity. Impaired remodeling on the downstream side may partly explain stenosis propagation down a vessel.

Acute myocardial infarction and vascular remodeling.

We used intravascular ultrasound to show that outward remodeling predominates in lesions responsible for acute myocardial infarction, whereas negative remodeling is far more prevalent in lesions responsible for chronic stable angina. The total cholesterol:high-density lipoprotein ratio was also strongly correlated with outward remodeling.

New aspects concerning the regulation of the post-operative acute phase reaction during cardiac surgery.

During a cardio-pulmonary bypass, as well as post-operatively, high levels of endotoxin, interleukin-6 (Il-6) and C-reactive protein (CRP) were measured in 30 patients. A significant increase in endotoxin plasma level occurred during surgery, culminating in a peak during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the fifth day after surgery, whereas those of Il-6 rose at the time the operation came to an end and were at their highest 6 h later. CRP levels were also high, post-operatively, and were markedly raised on day 2. A definite, statistically significant correlation between the plasma levels of endotoxin and Il-6 during the operation was established, leading us to conclude that the endotoxin liberated during cardiac surgery acts as the main trigger in the release of Il-6 and thus induces the post-operative acute phase reaction. There was no evidence of a correlation between CRP and endotoxin or Il-6 plasma levels.

Power-scalable system of phase-locked single-mode diode lasers.

The direct use of diode lasers for high-power applications in material processing is limited to applications with relatively low beam quality and power density requirements. To achieve high beam quality one must use single-mode diode lasers, however with the drawback of relatively low optical output powers from these components. To realize a high-power system while conserving the high beam quality of the individual emitters requires coherent coupling of the emitters. Such a power-scalable system consisting of 19 slave lasers that are injection locked by one master laser has been built and investigated, with low-power diode lasers used for system demonstration. The optical power of the 19 injection-locked lasers is coupled into polarization-maintaining single-mode fibers and geometrically superimposed by a lens array and a focusing lens. The phase of each emitter is controlled by a simple electronic phase-control loop. The coherence of each slave laser is stabilized by computer control of the laser current and guarantees a stable degree of coherence of the whole system of 0.7. An enhancement factor of 13.2 in peak power density compared with that which was achievable with the incoherent superposition of the diode lasers was observed.

Cell-mediated immune responses (CMIR) in human rhinosporidiosis.

Cell mediated immune responses (CMIR) to Rhinosporidium seeberi in human patients with rhinosporidiosis have been studied. With immuno-histochemistry, the cell infiltration patterns in rhinosporidial tissues from 7 patients were similar. The mixed cell infiltrate consisted of many plasma cells, fewer CD68+ macrophages, a population of CD3+ T lymphocytes, and CD56/57+ NK lymphocytes which were positive for CD3 as well. CD4+ T helper cells were scarce. CD8+ suppressor/cytotoxic-cytolytic cells were numerous. Most of the CD8+ cells were TIA1+ and therefore of the cytotoxic subtype. CD8+ T cells were not sub-typed according to their cytokine profile; 1L2, IFN-gamma (Tcl); IL4, ILS (Tc2). In lympho-proliferative response (LPR) assays in vitro, lymphocytes from rhinosporidial patients showed stimulatory responses to Con A but lymphocytes from some patients showed significantly diminished responses to rhinosporidial extracts as compared with unstimulated cells or cells stimulated by Con A, indicating suppressor immune responses in rhinosporidiosis. The overall stimulatory responses with Con A suggested that the rhinosporidial lymphocytes were not non-specifically anergic although comparisons of depressed LPR of rhinosporidial lymphocytes from individual patients, to rhinosporidial antigen with those to Con A, did not reveal a clear indication as to whether the depression was antigen specific or non-specific. The intensity of depression of the LPR in rhinosporidial patients bore no relation to the site, duration, or the number of lesions or whether the disease was localized or disseminated. Rhinosporidial extracts showed stimulatory activity on normal control lymphocytes, perhaps indicating mitogenic activity. These results indicate that CMIR develops in human rhinosporidiosis, while suppressed responses are also induced.