Background-Fractional flow reserve (FFR) is an index of stenosis severity validated for isolated stenoses. This study develops the theoretical basis and experimentally validates equations for predicting FFR of sequential stenoses separately. Methods and Results-For 2 stenoses in series, equations were derived to predict FFR (FFR pred ) of each stenosis separately (ie, as if the other one were removed) from arterial pressure (P a ), pressure between the 2 stenoses (P m ), distal coronary pressure (P d ), and coronary occlusive pressure (P w ). In 5 dogs with 2 stenoses of varying severity in the left circumflex coronary artery, FFR pred was compared with FFR app (ratio of the pressure just distal to that just proximal to each stenoses) and to FFR true (ratio of the pressures distal to proximal to each stenosis but after removal of the other one) in case of fixed distal and varying proximal stenoses (nϭ15) and in case of fixed proximal and varying distal stenoses (nϭ20). The overestimation of FFR true by FFR app was larger than that of FFR true by FFR pred (0.070Ϯ0.007 versus 0.029Ϯ0.004, PϽ0.01 for fixed distal stenoses, and 0.114Ϯ0.01 versus 0.036Ϯ0.004, PϽ0.01 for fixed proximal stenoses). This overestimation of FFR true by FFR app was larger for fixed proximal than for fixed distal stenoses. Conclusions-The interaction between 2 stenoses is such that FFR of each lesion separately cannot be calculated by the equation for isolated stenoses (P d /P a during hyperemia) applied to each separately but can be predicted by more complete equations taking into account P a , P m , P d , and P w .

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The aim of this study was 1) to investigate the validity of repeated estimations of blood flow using colored microspheres (CMS) and 2) to develop and validate a method that permits four consecutive estimations in the same animal using nonradiolabeled microspheres (NRMS). Several mixtures of different types of microspheres were injected in dogs, with each mixture containing the radiolabeled microspheres (RMS; labeled with113Sn) with either three CMS, four CMS, or three CMS and one type of fluorescent (crimson labeled) microsphere (FMS). The blood flows estimated with the use of any of the injected microspheres were compared with those measured using the RMS as the “gold standard.” The results were analyzed by 1) regression analysis, 2) variance analysis (ANOVA I), and 3) estimation of the limits of agreement between RMS and NRMS flow rates. The results indicate that simultaneous estimations of blood flow obtained with the use of more than three CMS lack accuracy and reliability. A combination of three types of CMS with crimson-labeled FMS, however, offers the possibility to estimate consecutively four different flow rates in the same animal in an accurate way and with relatively high precision.

Bosentan produces an additional hypotensive effect to that of ACEI, which opens new therapeutic perspectives.