Abstract 12500: Attenuated Basal Left Ventricular Wall Contraction in Patients With Mitral Valve Prolapse Can be Secondary to Annular Dilatation With Augmented Closing Force: Pre- and Post-Operative Speckle Tracking Echocardiographic Study

Introduction: Mitral annulus (MA) is generally enlarged in patients with mitral valve prolapse (MVP), which may raise MV closing force acting to shift the MV and its adjacent basal left ventricular (LV) wall toward left atrium. Hypothesis: MA dilatation with augmented MV closing force may disturb basal LV wall systolic contraction in patients with MVP. Methods: In 11 healthy controls and 34 patients with MVP, 3 apical views were obtained to assess longitudinal strain of basal- and mid-LV segments by speckle tracking analysis. The ratio of basal- to mid-LV strain value was then calculated. MA area was calculated by annulus diameters in apical 4- and 2- chamber views. MV closing force was calculated as MA area х (systolic blood pressure - 10). Results: Patients with MVP showed significantly larger MA area (5.3±1.0 vs 3.8±0.7 cm2/m2) and MV closing force (638±192 vs 431±66 mmHg•cm2/m2), and reduced basal-LV strain (-18±3 vs -21±2%) than controls (all p<0.005), whereas mid-LV strain was similar between the 2 groups (-22±4 vs -22±3%, p=0.4). Consequently, significantly lower basal/middle ratio was observed in patients with MVP compared to controls (0.86±0.11 vs 0.95±0.08, p=0.004). By multivariate analysis, reduced basal/middle strain ratio was associated with augmented MV closing force (β=0.45, p=0.005) (Figure A), independent from the severity of mitral regurgitation (p=0.7). The basal/middle strain ratio significantly increased to 1.07±0.10 after annular size reduction in 5 patients with surgical MV plasty (p=0.04) (Figures B and C). Conclusions: In patients with MVP, an increase in MV closing force corresponding to MA dilatation, as opposed to the severity of mitral regurgitation, was related to attenuated basal LV wall contraction, which can be restored by MV plasty with annular size reduction.

Alterations in Development, Behavior, and Physiology inDrosophila Larva That Have Reduced Ecdysone Production

We investigated behavior, physiology, sensitivity to exogenous application of ecdysone, and nerve terminal structure for differences between the reduced ecdysone genotype, ecd 1 /ecd 1, and wild-type control ecd 1 /TM6Banimals during the early and late third instars when raised at 25°C. The ecd 1 mutants were able to survive through larval development and form pupae. However, the results demonstrate that the time to pupation is lengthened by about 50 h for the ecd 1 /ecd 1 as compared with the wild-type control siblings. In addition to the lengthened larval cycle in the mutant, ecd 1 /ecd 1animals, they also display behavioral differences as compared with controls. The rate of body wall contraction and mouth hook movements are reduced in the early third instar of ecd 1 /ecd 1 as compared with controls. The physiological measure of excitatory junction potential amplitude for the combined Is and Ib terminals did not reveal any differences among the two genotypes during the early third instar but the synaptic strength is reduced in the late third instars for controls. Application of exogenous ecdysone is still effective during the late third instar for the ecd 1 /ecd 1 but not the controls. This suggests that endogenous production of ecdysone have already taken place in the wild-type but not the ecd 1 /ecd 1larvae, thus the rapid nongenomic responses could still be observed in the late third ecd 1 /ecd 1larvae. Structurally the number of varicosities and the terminal length showed significant differences between ecd 1 /ecd 1 and the wild-type ecd 1 /TM6B genotype in the late third instars.

Altered small artery morphology and reactivity in critical limb ischaemia

Although the pathophysiology of critical limb ischaemia is poorly understood, there is evidence that the condition of the small arteries may determine the outcome of revascularization procedures. This study was designed to investigate the effects of critical limb ischaemia on the structure and function of the small arteries in the leg. Small arteries (< 500 μm) from proximal (non-ischaemic) and distal (ischaemic) sites were obtained from patients undergoing bypass surgery for critical limb ischaemia and mounted in a myograph. Reactivity and morphological measurements were carried out and compared with controls. Control vessels from the thigh and calf showed no difference in media to lumen ratio. However, a comparison of ischaemic and non-ischaemic vessels from the patients with critical limb ischaemia showed significant thinning of the ischaemic vessel wall. Contraction studies using noradrenaline and angiotensin II revealed a significant decrease in the response of ischaemic vessels compared with the non-ischaemic vessels from the same patient. Moreover, these differences in reactivity were still apparent after the responses were corrected for wall thickness. Endothelial function assessed using the endothelium-dependent agonists acetylcholine and bradykinin showed a significantly impaired relaxation response to acetylcholine but not to bradykinin in the ischaemic vessels, and acetylcholine-induced relaxation was not improved after incubation with indomethacin. There was no change in the response to the endothelium-independent cAMP-mediated vasodilator iloprost but a significant impairment to sodium nitroprusside which acts via cGMP. These results suggest that small arteries in critical limb ischaemia are altered in both structure and function, with vessel wall thinning and impaired responses to acetylcholine and sodium nitroprusside.