Comparison between Three- and Four-Element Windkessel Models to Characterize Vascular Properties of Pulmonary Circulation

In 11 anaesthetised pigs the accuracy of the three-element (WK3) and the four-element (WK4) Windkessel models to describe hemodynamic properties of the pulmonary circulation was compared during six different experimental conditions increasing pulmonary arterial pressure: increase in left atrial pressure, increase in alveolar pressure, increase in pulmonary blood flow, endotoxin shock, mechanical obstruction of left pulmonary artery or histamine infusion. Our results showed that WK4 fitted better the data than did WK3 because values of 1-R2 decreased from 6 percent (WK3) to 1.4 percent (WK4) when WK4 was used (P < 0.0005). 1-R2 was an adequate marker of the accuracy of the linear regression used to solve equations of both models. Compliance values estimated by WK4 were decreased by 5% comparatively to WK3 (P = 0.008). However, this difference can be considered as not physiologically relevant. Values of characteristic resistance corresponding to R1 + (L/R2C) in WK4 and to R1 in WK3 were not different (P = 0.22). The relative changes in R1, R2, and C observed due to the different experimental conditions were comparable regardless of the model. In conclusion, the conversion of WK3 in WK4 by adding an inductance, whose physiological meaning is not clear, resulted in an increased statistical accuracy of the model, but did not seem to have relevant influence on parameters or their evolution during experimental conditions

Effects of U-46619 on Pulmonary Hemodynamics before and after Administration of Bm-573, a Novel Thromboxane A2 Inhibitor

We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2 (TXA2) agonist, before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in pulmonary hemodynamics, including characteristic resistance, vascular compliance, and peripheral vascular resistance, were continuously assessed during the experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573 completely blocked pulmonary hypertensive effects of U-46619 but pulmonary vascular compliance still decreased. This residual effect can probably be explained by a persistent increase in the tonus of the pulmonary vascular wall smooth muscles sufficient to decrease vascular compliance but not vessel lumen diameter. Such molecule could be a promising therapeutic approach in TXA2 mediated pulmonary hypertension as it is the case in pulmonary embolism, hyperacute lung rejection and endotoxinic shock

Validation of transit-time flowmetry for chronic measurements of regional blood flow in resting and exercising rats

The objective of the present study was to validate the transit-time technique for long-term measurements of iliac and renal blood flow in rats. Flow measured with ultrasonic probes was confirmed ex vivo using excised arteries perfused at varying flow rates. An implanted 1-mm probe reproduced with accuracy different patterns of flow relative to pressure in freely moving rats and accurately quantitated the resting iliac flow value (on average 10.43 ± 0.99 ml/min or 2.78 ± 0.3 ml min-1 100 g body weight-1). The measurements were stable over an experimental period of one week but were affected by probe size (resting flows were underestimated by 57% with a 2-mm probe when compared with a 1-mm probe) and by anesthesia (in the same rats, iliac flow was reduced by 50-60% when compared to the conscious state). Instantaneous changes of iliac and renal flow during exercise and recovery were accurately measured by the transit-time technique. Iliac flow increased instantaneously at the beginning of mild exercise (from 12.03 ± 1.06 to 25.55 ± 3.89 ml/min at 15 s) and showed a smaller increase when exercise intensity increased further, reaching a plateau of 38.43 ± 1.92 ml/min at the 4th min of moderate exercise intensity. In contrast, exercise-induced reduction of renal flow was smaller and slower, with 18% and 25% decreases at mild and moderate exercise intensities. Our data indicate that transit-time flowmetry is a reliable method for long-term and continuous measurements of regional blood flow at rest and can be used to quantitate the dynamic flow changes that characterize exercise and recover