Quantification of shunt fraction using contrast ultrasound and indicator dilution in an in vitro model.

Transthoracic saline contrast echocardiography is commonly used to assess intrathoracic shunt flow in vivo. Though the technique has many advantages (safe, simple, repeatable), the measurement technique lacks specificity, and the contrast agent has limited stability. This study sought to determine if the indicator dilution modeling technique could be applied to ultrasound contrast data to quantify shunt fraction and to determine if buoyant force has a significant effect on microbubble pathway determination at a "vascular" bifurcation. A model of the pulmonary circuit was perfused with blood at three distinct flow rates (low, medium and high) over shunt fractions ranging from ∼2-10 %. The buoyancy effect on contrast was quantified using a simplified in vitro model of a vascular bifurcation that had an upper and lower outflow tract where saline contrast formed from carbon monoxide (CO) gas passed through the bifurcation, was collected and quantified. The indicator dilution model was found to have a mean bias of - 3.2 % for the low flow stage, - 2.6 % for the medium flow stage and - 1.4 % for the high flow stage compared to volumetric measurements, suggesting agreement increases with increasing flow rate. Investigations of the buoyant effects revealed that at lower flow rates, contrast bubbles that encounter a bifurcation will favor the upper outflow tract over the lower. However, this effect is reduced by increasing the flow rate two-fold. These data identify that application of indicator dilution theory to contrast ultrasound data and the pathway ultrasound contrast travels in a network of tubules is flow dependent.

Females and males do not differ for fatigability, muscle damage and magnitude of the repeated bout effect following maximal eccentric contractions.

Unaccustomed eccentric (ECC) exercise induces muscle fatigue as well as damage and initiates a protective response to minimize impairments from a subsequent bout (i.e., repeated bout effect; RBE). It is uncertain if the sexes differ for neuromuscular responses to ECC exercise and the ensuing RBE. Twenty-six young adults (13 females) performed 2 bouts (4 weeks apart) of 200 ECC maximal voluntary contractions (MVCs) of the dorsiflexors. Isometric (ISO) MVC torque and the ratio of ISO torque in response to low- versus high-frequency stimulation (10:100 Hz) were compared before and after (2-10 min and 2, 4, and 7 days) exercise. The decline in ECC and ISO MVC torque and the 10:100 Hz ratio following bout 1 did not differ between sexes (P > 0.05), with reductions from baseline of 31.5% ± 12.3%, 24.1% ± 15.4%, and 51.3% ± 12.2%, respectively. After bout 2, the 10:100 Hz ratio declined less (45.0% ± 12.4% from baseline) and ISO MVC torque recovered sooner compared with bout 1 but no differences between sexes were evident for the magnitude of the RBE (P > 0.05). These data suggest that fatigability with ECC exercise does not differ for the sexes and adaptations that mitigate impairments to calcium handling are independent of sex. Novelty: One bout of 200 maximal eccentric dorsiflexor contractions caused equivalent muscle fatigue and damage for females and males. The repeated bout effect observed after a second bout 4 weeks later also had no sex-related differences. Prolonged low-frequency force depression is promoted as an indirect measure of muscle damage in humans.

Influence of blood Po2 on the stability of agitated saline contrast.

The utility of transthoracic saline contrast echocardiography (TTSCE) to assess blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) in humans is limited due to the potential destabilizing effects of the gas concentration gradients established in varied blood-gas environments. This study assessed the specific effect of a hyperoxic and mixed venous blood-gas environment on the stability of saline contrast. We hypothesized that the rate of contrast mass lost in hyperoxic blood would be similar to mixed venous due to the establishment of equal and opposing gas gradients (O2, N2, CO2) created when the partial pressure of dissolved gases is manipulated. Using an in vitro model of the pulmonary circulation perfused with defibrinated sheep blood and a membrane oxygenator to control blood gases, we assessed the percent contrast conserved (an index of contrast stability) between inflow and outflow sites at multiple flow rates (1.8, 2.8, 4.3, and 6.8 L/min) in a hyperoxic (Po2: 646 ± 16 mmHg; Pco2: 0 ± 0 mmHg) and a mixed venous blood gas condition (Po2: 35 ± 3 mmHg; Pco2: 40 ± 0 mmHg). We found significant contrast decay with time in both conditions, with slightly higher contrast conservation in the hyperoxia trials (64 ± 32%) versus the mixed venous trials (55 ± 21%). These findings suggest that contrast stability is not likely a factor affecting the interpretation of TTSCE performed in healthy humans breathing hyperoxia and lends support to the existence of a local O2-dependent mechanism contributing to the regulation of Q̇IPAVA.NEW & NOTEWORTHY Hyperoxic blood has a small stabilizing effect on agitated saline contrast compared with mixed venous blood, lending support to studies that show the reversal of exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) with hyperoxia. These data support the possible presence of a local O2-dependent regulatory mechanism within the pulmonary vasculature that may play a role in Q̇IPAVA regulation.

Prolonged low-frequency force depression is underestimated when assessed with doublets compared with tetani in the dorsiflexors.

Prolonged low-frequency force depression (PLFFD) after damaging eccentric exercise may last for several days. Historically, PLFFD has been calculated from the tetanic force responses to trains of supramaximal stimuli. More recently, for methodological reasons, stimulation has been reduced to two pulses. However, it is unknown whether doublet responses provide a valid measure of PLFFD in the days after eccentric exercise. In 12 participants, doublets and tetani were elicited at 10 and 100 Hz before and after (2, 3, 5 min, 48 and 96 h) 200 eccentric maximal voluntary contractions of the dorsiflexors. Doublet and tetanic torque responses at 10 Hz were similarly depressed throughout recovery (P > 0.05; e.g., 2 min: 58.9 ± 12.8% vs. 57.1 ± 14.5% baseline; 96 h: 85.6 ± 11.04% vs. 85.1 ± 10.8% baseline). At 100 Hz, doublet torque was impaired more than tetanic torque at all time points (P < 0.05; e.g., 2 min: 70.5 ± 14.2% vs. 88.1 ± 11.7% baseline; 96 h: 83.0 ± 14.2% vs. 98.7 ± 9.5% baseline). As a result, the postfatigue reduction of the 10 Hz-to-100 Hz ratio (PLFFD) was markedly greater for tetani than for doublets (P < 0.05; e.g., 2 min: 64.3 ± 15.1% vs. 83.0 ± 5.8% baseline). In addition, the doublet ratio recovered by 48 h (99.2 ± 5.0% baseline), whereas the tetanic ratio was still impaired at 96 h (88.2 ± 9.7% baseline). Our results indicate that doublets are not a valid measure of PLFFD in the minutes and days after eccentric exercise. If study design favors the use of paired stimuli, it should be acknowledged that the true magnitude and duration of PLFFD are likely underestimated. NEW & NOTEWORTHY Prolonged low-frequency force depression (PLFFD) will result from damaging exercise and may last for several days. After 200 eccentric maximal dorsiflexor contractions, we compared the gold-standard measure of PLFFD (calculated using trains of supramaximal stimulation) to the value obtained from an alternative technique that is becoming increasingly common (paired supramaximal stimuli). Doublets underestimated the magnitude and duration of PLFFD compared with tetani, so caution must be used when reporting PLFFD derived from paired stimuli.