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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A comparison was made of the effects of vasopressin (ADH), methoxamine (MX), and angiotensin II (AN) on coronary and left ventricular dynamics, cardiac output, and regional blood flow distribution in intact, consci9us dogs. At an equal percent pressure elevation, ADH reduced cardiac output and cardiac rate the most, while AN had the least effect. After denervation of arterial baroreceptors, ADH still reduced heart rate, while AN increased it, suggesting nonbaroreceptor negative and positive chronotropic effects, respectively. A differential pattern on peak dP/dt was also observed, with ACH causing a greater reduction than MX while AN did not decrease dP/dt. With heart rate held constant, AN did not reduce dP/dt, suggesting a direct positive inotropic effect since dP/dt should have fallen slightly due to reflex mechanisms, as was observed with MX and ADH. ADH induced the greatest increase in coronary resistance (140%), while the least (46%) was observed with AN, which could be explained, in part, by the differential effects observed on cardiac rate and contractility. The greatest increase in resistance in the iliac bed occurred with ADH (30%), and the least with AN (34%). Conversely, the greatest constriction in the renal bed occurred with AN (95%), and lesser amounts were observed with ADH (36%) and MX (35%). Thus ADH, MX, and AN exert potent yet differential vasoconstricting actions on peripheral beds. In addition, while all three agents elicited coronary vasoconstriction, the differential effects on coronary vascular resistance appeared to be due predominantly to a difference in chronotropic and inotropic actions.

Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow (25 +/- 3% of control) and an elevation of renal vascular resistance (45 +/- 8% of control). Meclofenamate, 4 mg/kg, reduced renal flow (12 +/- 2%) and increased renal vascular resistance 15 +/- 4% in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed after 15 s occlusion from a control of 36 +/- 5 ml to 6 +/- 2 ml, and after 45 s occlusion from a control of 98 +/- 9 ml to 17 +/- 5 ml. Methoxamine (10-50 mug/kg per min) and angiotensin II (0.03-0.12 mug/kg per min), infused in graded doses, induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor role in the control of the renal circulation at rest, but are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.