Journal of applied physiology
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Managing patients with acute respiratory distress syndrome (ARDS) requires mechanical ventilation that balances the competing goals of sustaining life while avoiding ventilator-induced lung injury (VILI). In particular, it is reasonable to suppose that for any given ARDS patient, there must exist an optimum pair of values for tidal volume (VT) and positive end-expiratory pressure (PEEP) that together minimize the risk for VILI. To find these optimum values, and thus develop a personalized approach to mechanical ventilation in ARDS, we need to be able to predict how injurious a given ventilation regimen will be in any given patient so that the minimally injurious regimen for that patient can be determined. ⋯ We estimated total VILI in two ways: 1) as the sum of the contributions from volutrauma and atelectrauma and 2) as the product of their contributions. We found the product provided estimates of VILI that are more in line with our previous experimental findings. This model may thus serve as the basis for the objective choice of mechanical ventilation parameters for the injured lung.
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Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. ⋯ However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes.
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Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. ⋯ Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation.
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Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). ⋯ As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery.
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This article briefly reviews the fidelity of ground-based methods used to simulate human existence in weightlessness (spaceflight). These methods include horizontal bed rest (BR), head-down tilt bed rest (HDT), head-out water immersion (WI), and head-out dry immersion (DI; immersion with an impermeable elastic cloth barrier between subject and water). Among these, HDT has become by far the most commonly used method, especially for longer studies. ⋯ Also, although weightlessness is the salient feature of spaceflight, several ancillary factors of space travel complicate Earth-based simulation. In spite of these discrepancies and complications, the analogs duplicate many responses to 0 G reasonably well. As we learn more about responses to microgravity and spaceflight, investigators will continue to fine-tune simulation methods to optimize accuracy and applicability.