The location of the primary entry tear in acute type B aortic dissection affects early outcome.

OBJECTIVES: The goal of the retrospective study was to relate the site of the primary entry tear in acute type B aortic dissections to the presence or development of complications. METHODS: A consecutive series of 52 patients referred with acute type B aortic dissection was analysed with regard to the location of the primary entry tear (convexity or concavity of the distal aortic arch) using the referral CT scans at the time of diagnosis. These findings were related to the clinical outcome as well as to the need for intervention. RESULTS: Twenty-five patients (48%) had the primary entry tear located at the convexity of the distal aortic arch, whereas 27 patients (52%) had the primary entry tear located at the concavity of the distal aortic arch. Twenty per cent of patients with the primary entry tear at the convexity presented with or developed complications, whereas 89% had or developed complications with the primary entry tear at the concavity (P < 0.001). Furthermore, in patients with complicated type B aortic dissection, the distance of the primary entry tear to the left subclavian artery was significantly shorter as in uncomplicated patients (8 vs. 21 mm; P = 0.002). In Cox regression analysis, a primary entry tear at the concavity of the distal aortic arch was identified as an independent predictor of the presence or the development of complicated type B aortic dissection. CONCLUSIONS: A primary entry tear at the concavity of the aortic arch as well as a short distance between the primary entry tear and the left subclavian artery are frequently associated with the presence or the development of complicated acute type B aortic dissection. These findings shall help us to further differentiate acute type B aortic dissections in addition to the common categorization in complicated and uncomplicated. These findings may therefore also have an impact on primary treatment.

Use-dependent inhibition of the skeletal muscle ryanodine receptor by the suramin analogue NF676.

The skeletal muscle Ca2+ release channel, the ryanodine receptor, is activated by the trypanocidal drug suramin via the calmodulin-binding site. As calmodulin activates and inhibits the ryanodine receptor depending on whether Ca2+ is absent or present, suramin analogues were screened for inhibition of the ryanodine receptor. Up to 300 microM, the novel suramin analogue, 4,4'-(carbonyl-bis(imino-4,1-phenylene-(2,5-benzimidazolylene)carbonylimino))-bis-benzenesulfonic acid disodium salt (NF676) was not able to significantly inhibit the basal [3H]ryanodine binding. However, kinetic analysis of the high affinity [3H]ryanodine binding elucidates a time-dependent increment of inhibition by NF676, which is indicative for an open channel blocker. Moreover, the ryanodine receptor was much more sensitive towards inhibition by NF676 when preactivated with caffeine or the nonhydrolysable ATP analogue, adenylyl-imidodiphosphate. Nonetheless, the suramin activated ryanodine receptor was not susceptible towards high-affinity NF676 inhibition, indicating an allosteric hindrance between the binding sites of suramin and NF676. In the line of this finding, NF676 per se was not capable to elute the purified ryanodine receptor from a calmodulin-Sepharose, but it prevented the elution by suramin. Other than suramin, NF676 did not inhibit the Ca2+ ATPase of the sarcoplasmic reticulum. However, suramin-induced Ca2+ release from sarcoplasmic reticulum was completely abrogated by preincubation with NF676. Taken together, we conclude from these data that NF676 represents a novel lead compound as a potent use-dependent blocker of the skeletal muscle ryanodine receptor via an allosteric interaction with the suramin-binding site.