Objective: Valve-preserving aortic replacement has evolved into an accepted therapeutic option for aortic ectasia with morphologically intact leaflets. Some patients, however, exhibit additional ...leaflet prolapse. We compared the results of established valve-preserving techniques with those of the combination of valve-preserving aortic surgery and additional repair of leaflet prolapse. Methods: Between October 1995 and March 2000, 99 patients underwent valve-preserving root replacement by means of root remodeling or valve reimplantation for acute dissection (n = 25), chronic dissection (n = 4), or aneurysm (n = 70). In group A (63 patients) either root remodeling (n = 49) or valve reimplantation (n = 14) was performed with a standard technique. In group B (36 patients) valvepreserving aortic replacement (remodeling, n = 31; reimplantation, n = 5) was combined with repair of leaflet prolapse in the presence of bicuspid (n = 24) or tricuspid (n = 12) valve anatomy. Additional replacement of the aortic arch was required more frequently in group A (group A, n = 43; group B, n = 14; P =.006); otherwise, the groups were comparable. Results: Cardiopulmonary bypass (group A, 133 ± 31 minutes; group B, 117 ± 30 minutes; P =.006) and myocardial ischemia times (group A, 96 ± 25 minutes; group B, 88 ± 20 minutes; P =.05) were significantly longer in group A. Mortality was not significantly different between groups (group A, 4.8%; group B, 0%). One patient in each group underwent secondary valve replacement, and all other patients had stable valve function. Freedom from aortic regurgitation of grade 2 or greater after 48 months was 93.0% in both groups. Conclusion: Repair of leaflet prolapse in conjunction with valve-preserving root replacement leads to midterm results that are equal to those of valve-preserving root replacement for morphologically intact leaflets.
J Thorac Cardiovasc Surg 2001;122:270-7
The structure of a cyclic pentapeptide, cyclo-(
d-Trp-
d-Asp-
l-Pro-
d-Val-
l-Leu), that has high selectivity for the endothelin ETA
A receptor has been determined by NMR spectroscopy using ...constrained molecular dynamics and conformational search procedures. Structures obtained using two methods of refinement, namely (i) constrained molecular dynamics; and (ii) systematic searches of conformational space for optimal satisfaction of distance constraints, were compared to those obtained from systematic searches of conformational space without NMR data. The two different procedures of refinement produce similar conformations that are consistent with the NMR distance constraints. Conformational searches for optimal energy without any NMR distance constraints produced several low-energy structures, two of which have essentially the same backbone as those structures derived from distance-constrained procedures and one of these even reproduces several side-chain positions well. The pentapeptide backbone consists of a linked γ and β-turn conformation, with the leucine and tryptophan as corner residues of the type II β-turn. The side chains are highly ordered both in aqueous solvent and in dimethyl sulfoxide. In aqueous media the leucine side chain is directed towards the indole ring, presumably to reduce the non-polar surface exposure, producing unusual upfield shifts for the methyls (and particularly Hγ). This structural feature was reproduced in one of the structures obtained from conformational searches performed without NMR data. Exhaustive conformational searches appear to provide an alternative method for structure generation for cyclic peptides.
Purified cardiac sarcolemmal membrane vesicles were used to determine if specific prostaglandin (PG) receptors are present on the myocyte. Two binding sites for PGE2 were identified in isolated ...bovine sarcolemmal membranesa high-affinity site with a dissociation constant (K4) of 032 nM and a maximum binding (Bmax of 376 fmol/mg of protein and a lower-affinity site with a K4 of 3.41 nM and a B max of 2,112 fmol/mg of protein. In competition experiments, unlabeled PGE1 displaced HPGE2 from its membrane receptor at concentrations similar to those of unlabeled PGE2. Both PGF2 μ and PGD2 displaced HPGE2 from the membrane, but only at high concentrations (> 10 M and > 10 M, respectively). Digestion of sarcolemmal membrane with trypsin resulted in a threefold decrease in specific HPGE2 binding. Phosphorylation of the membrane with protein kinase A also decreased specific HJPGE2 binding. At concentrations of PGE2} that occupy the high-affinity site, sarcolemmal adenylate cyclase activity was inhibited in the presence of 5ʼ-guanylylimidodiphosphate Gpp(NH)p. We conclude that the isolated cardiac sarcolemmal membrane contains a high-affinity binding site for PGEj that is functionally coupled to adenylate cyclase. The binding site is stereospecific and probably recognizes the 9-keto, ll-hydroxyl portion of the ring structure of these prostaglandins.
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