Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis.

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis. Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation. Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor. Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.

An intact animal model for the assessment of coronary blood flow regulation "Coronary blood flow regulation".

Coronary blood flow adapts to metabolic demand ("metabolic regulation") and remains relatively constant over a range of pressure changes ("autoregulation"). Coronary metabolic regulation and autoregulation are usually studied separately. We developed an intact animal experimental model to explore both regulatory mechanisms of coronary blood flow. Coronary pressure and flow-velocities were measured in four anesthetized and closed-chest pigs using an intracoronary Doppler wire. Metabolic regulation was assessed by coronary flow reserve defined as the ratio between the maximally vasodilated and the basal flow, with hyperemia achieved using intracoronary administration of adenosine (90 µg) or bradykinin (10-6  M) as endothelium-independent and -dependent vasodilators respectively. For both vasodilators, we found a healthy coronary flow reserve ≥ 3.0 at baseline, which was maintained at 2.9 ± 0.2 after a 6-hr period. Autoregulation was assessed by the lower breakpoint of coronary pressure-flow relationships, with gradual decrease in coronary pressure through the inflation of an intracoronary balloon. We found a lower limit of autoregulation between 42 and 55 mmHg, which was stable during a 6-hr period. We conclude that this intact animal model is adequate for the study of pharmacological interventions on the coronary circulation in health and disease, and as such suitable for preclinical drug studies.

Ability of a New Smartphone Pulse Pressure Variation and Cardiac Output Application to Predict Fluid Responsiveness in Patients Undergoing Cardiac Surgery.

BACKGROUND: Pulse pressure variation (PPV) can be used to predict fluid responsiveness in anesthetized patients receiving controlled mechanical ventilation but usually requires dedicated advanced monitoring. Capstesia (Galenic App, Vitoria-Gasteiz, Spain) is a novel smartphone application that calculates PPV and cardiac output (CO) from a picture of the invasive arterial pressure waveform obtained from any monitor screen. The primary objective was to compare the ability of PPV obtained using the Capstesia (PPVCAP) and PPV obtained using a pulse contour analysis monitor (PPVPC) to predict fluid responsiveness. A secondary objective was to assess the agreement and the trending of CO values obtained with the Capstesia (COCAP) against those obtained with the transpulmonary bolus thermodilution method (COTD). METHODS: We studied 57 mechanically ventilated patients (tidal volume 8 mL/kg, positive end-expiratory pressure 5 mm Hg, respiratory rate adjusted to keep end tidal carbon dioxide [32-36] mm Hg) undergoing elective coronary artery bypass grafting. COTD, COCAP, PPVCAP, and PPVPC were measured before and after infusion of 5 mL/kg of a colloid solution. Fluid responsiveness was defined as an increase in COTD of >10% from baseline. The ability of PPVCAP and PPVPC to predict fluid responsiveness was analyzed using the area under the receiver-operating characteristic curve (AUROC), the agreement between COCAP and COTD using a Bland-Altman analysis and the trending ability of COCAP compared to COTD after volume expansion using a 4-quadrant plot analysis. RESULTS: Twenty-eight patients were studied before surgical incision and 29 after sternal closure. There was no significant difference in the ability of PPVCAP and PPVPC to predict fluid responsiveness (AUROC 0.74 [95% CI, 0.60-0.84] vs 0.68 [0.54-0.80]; P = .30). A PPVCAP >8.6% predicted fluid responsiveness with a sensitivity of 73% (95% CI, 0.54-0.92) and a specificity of 74% (95% CI, 0.55-0.90), whereas a PPVPC >9.5% predicted fluid responsiveness with a sensitivity of 62% (95% CI, 0.42-0.88) and a specificity of 74% (95% CI, 0.48-0.90). When measured before surgery, PPV predicted fluid responsiveness (AUROC PPVCAP = 0.818 [P = .0001]; PPVPC = 0.794 [P = .0007]) but not when measured after surgery (AUROC PPVCAP = 0.645 [P = .19]; PPVPC = 0.552 [P = .63]). A Bland-Altman analysis of COCAP and COTD showed a mean bias of 0.3 L/min (limits of agreement: -2.8 to 3.3 L/min) and a percentage error of 60%. The concordance rate, corresponding to the proportion of CO values that changed in the same direction with the 2 methods, was poor (71%, 95% CI, 66-77). CONCLUSIONS: In patients undergoing cardiac surgery, PPVCAP and PPVPC both weakly predict fluid responsiveness. However, COCAP is not a good substitute for COTD and cannot be used to assess fluid responsiveness.