Journal of applied physiology
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Heart failure is an increasingly common public health problem that is strongly linked to both central and obstructive sleep apnea, collectively referred to as sleep-disordered breathing. Much attention has been given to the deleterious effects of sleep-disordered breathing on the failing heart and potential mechanisms by which treatment of sleep-disordered breathing may result in improved cardiac performance and long-term outcomes. ⋯ Although there is recognized overlap between pathophysiological mechanisms in central sleep apnea and obstructive sleep apnea, data supporting the role of cardiac function are certain forms of central sleep apnea are well established, whereas investigation into the relationship with obstructive sleep apnea is less mature but continues to evolve. This review will examine experimental and observational data that explore possible pathophysiological mechanisms and potential targets for therapy in heart failure and sleep-disordered breathing.
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Acute hypoxia induces pulmonary vasoconstriction and chronic hypoxia causes structural changes of the pulmonary vasculature including arterial medial hypertrophy. Electro- and pharmacomechanical mechanisms are involved in regulating pulmonary vasomotor tone, whereas intracellular Ca(2+) serves as an important signal in regulating contraction and proliferation of pulmonary artery smooth muscle cells. Herein, we provide a basic overview of the cellular mechanisms involved in the development of hypoxic pulmonary vasoconstriction. Our discussion focuses on the roles of ion channels permeable to K(+) and Ca(2+), membrane potential, and cytoplasmic Ca(2+) in the development of acute hypoxic pulmonary vasoconstriction and chronic hypoxia-mediated pulmonary vascular remodeling.
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Review
Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans.
Hemorrhage is a leading cause of death in both civilian and battlefield trauma. Survival rates increase when victims requiring immediate intervention are correctly identified in a mass-casualty situation, but methods of prioritizing casualties based on current triage algorithms are severely limited. Development of effective procedures to predict the magnitude of hemorrhage and the likelihood for progression to hemorrhagic shock must necessarily be based on carefully controlled human experimentation, but controlled study of severe hemorrhage in humans is not possible. ⋯ In this review, we compare physiological responses to hemorrhage and LBNP with particular emphasis on cardiovascular compensations that both share in common. Through evaluation of animal and human data, we present evidence that supports the hypothesis that LBNP, and resulting volume sequestration, is an effective technique to study physiological responses and mechanisms associated with acute hemorrhage in humans. Such experiments could lead to clinical algorithms that identify bleeding victims who will likely progress to hemorrhagic shock and require lifesaving intervention(s).
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A. C. Guyton pioneered major advances in understanding cardiovascular equilibrium. ⋯ In such graphical representations of negative feedback between two subdivisions of a system, one input/output relationship is necessarily plotted backward, i.e., with the input variable on the y-axis (here, the venous return curve). Unfortunately, this format encourages mistaken ideas about the role of Pra as a "back pressure," such as the assertion that elevating Pra to the level of mean systemic pressure would stop venous return. These concepts are reexamined through review of the original experiments on venous return, presentation of a hypothetical alternative way for obtaining the same data, and analysis of a simple model.
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Despite advances in critical care, the mortality rate in patients with acute lung injury remains high. Furthermore, most patients who die do so from multisystem organ failure. It has been postulated that ventilator-induced lung injury plays a key role in determining the negative clinical outcome of patients exposed to mechanical ventilation. ⋯ This information must then be integrated in the nucleus, and an appropriate response must be generated to implement and/or modulate its response and that of neighboring cells. In this review, we present a perspective on ventilator-induced lung injury with a focus on mechanisms and clinical implications. We highlight some of the most recent findings, which we believe contribute to the generation and propagation of ventilator-induced lung injury, placing a special emphasis on their implication for future research and clinical therapies.