Effect of Transit Time and Gas Density on the Conservation of Agitated Saline Contrast in an in vitro Model of the Pulmonary Circulation

Abstract

Agitated saline contrast echocardiography is often used as a tool to subjectively measure blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA). This method assumes that an intravenous injection of agitated saline contrast will not survive the pulmonary circulation or reach the left heart unless it travels through a shunt. However, agitated saline contrast is unstable, and contrast lost to microbubble dissolution likely impacts its utility for measuring Q̇IPAVA. We applied indicator dilution theory to acoustic intensity‐time curves obtained from a bolus injection of hand‐agitated saline contrast to acquire a quantitative index of contrast mass. Using this methodology and an in vitro model of the pulmonary circulation, the purpose of this study was to determine the effect of transit time on the conservation of contrast mass between two detection sites separated by a convoluted network of vessels with a variable volume (300–600 ml). In addition, we wished to determine if agitating saline with a high density, low solubility gas (sulfur hexafluoride, SF6) could improve contrast mass conservation by minimizing microbubble dissolution. We hypothesized that the contrast lost between the in‐ and out‐flow detection sites would increase with increasing transit times and would be reduced by using microbubbles composed of SF6 instead of air. The experimental apparatus consisted of a reservoir of 0.9% saline connected to a centrifugal pump and a network of latex surgical tubing mimicking the pulmonary circulation. An in‐ and out‐flow detection site passed under a 3.5 MHz ultrasound transducer to record acoustic intensity‐time curves. A 6 ml bolus of agitated saline contrast (10:1 ratio of saline and gas) was injected into the circuit proximal to the in‐flow detection site and distal to a calibrated flow probe. Transit time was manipulated in two ways: (1) setting flow rate to 1.5 or 2.0 l min−1; and, (2) reducing the volume of the circulatory network (no reduction, 25%, 50%, 75%). Five trials were conducted for each combination. Contrast conservation was measured as the ratio of outflow contrast mass to inflow contrast mass, where contrast mass is the respective area under the acoustic intensity‐time curve. Inflow contrast mass did not differ amongst all conditions (P>0.05). Transit time ranged from 9.12 ± 0.03 to 24.47 ± 0.03s as the cross sectional area and flow of the system changed. For air, 53.2 ± 3.4% of contrast was conserved at a transit time of 9.25 ± 0.02s but dropped to 16.0 ± 1.0% at a transit time of 10.17 ± 0.06s. Compared to air, SF6 contrast conservation was significantly greater (P<0.01) with 98.3 ± 11.5 % and 94.8 ± 5.8% of contrast conserved at a transit time of 10.40 ± 0.21s and 13.46 ± 0.04s respectively. In summary, acoustic‐intensity‐time curves can be used to quantify agitated saline contrast mass but loss of contrast due to microbubble dissolution makes measuring Q̇IPAVA across varying transit time difficult. Agitated saline mixed with SF6 is stabilized and may be a suitable alternative for Q̇IPAVA measurement.Support or Funding InformationFunding: NSERC, CFI