Further cautions for the use of ventilatory-induced changes in arterial pressures to predict volume responsiveness

Variations in systemic arterial pressure with positive-pressure breathing are frequently used to guide fluid management in hemodynamically unstable patients. However, because of the complex physiology that determines the response, there are important limitations to their use. Two papers in a previous volume add pulmonary hypertension as limitations. Uncritical use of ventilatory-induced changes in arterial pressure can lead to excessive volume therapy and potential clinical harm, and they must be used with respect and thought

Reactive oxygen species: toxic molecules or spark of life?

Increases in reactive oxygen species (ROS) and tissue evidence of oxidative injury are common in patients with inflammatory processes or tissue injury. This has led to many clinical attempts to scavenge ROS and reduce oxidative injury. However, we live in an oxygen rich environment and ROS and their chemical reactions are part of the basic chemical processes of normal metabolism. Accordingly, organisms have evolved sophisticated mechanisms to control these reactive molecules. Recently, it has become increasingly evident that ROS also play a role in the regulation of many intracellular signaling pathways that are important for normal cell growth and inflammatory responses that are essential for host defense. Thus, simply trying to scavenge ROS is likely not possible and potentially harmful. The 'normal' level of ROS will also likely vary in different tissues and even in different parts of cells. In this paper, the terminology and basic chemistry of reactive species are reviewed. Examples and mechanisms of tissue injury by ROS as well as their positive role as signaling molecules are discussed. Hopefully, a better understanding of the nature of ROS will lead to better planned therapeutic attempts to manipulate the concentrations of these important molecules. We need to regulate ROS, not eradicate them

Mechanical Limits of Cardiac Output at Maximal Aerobic Exercise

This chapter uses an analytic approach to the factors limiting maximal aerobic exercise. A person’s maximal aerobic work is determined by their maximal oxygen consumption (VO2max). Cardiac output is the dominant determinant of VO2 and thus the primary determinant of population differences in VO2max. Furthermore, cardiac output is the product of heart rate and stroke volume and maximum heart rate is determined solely by a person’s age. Thus, maximum stroke volume is the major factor for physiological differences in aerobic performance. Stroke output must be matched by stroke volume return, which is determined by the mechanical properties of the systemic circulation. These are primarily the compliances of each vascular region and the resistances between them. I first discuss the physiological principles controlling cardiac output and venous return. Emphasis is placed on the importance of the distribution of blood flow between the parallel compliances of muscle and splanchnic beds as described by August Krogh in 1912. I then present observations from a computational modeling study on the mechanical factors that must change to reach known maximum cardiac outputs during aerobic exercise. A key element that comes out of the analysis is the role of the muscle pump in achieving high cardiac outputs

Progressions of Conceptual Models of Cardiovascular Physiology and their Relationship to Expertise

The application of scientific principles in diverse science domains is widely regarded as a hallmark of expertise. However, in medicine, the role of basic science knowledge is the subject of considerable controversy. In this paper, w e present a study that examines students' and experts* understanding of complex biomedical concepts related to cardiovascular physiology. In the experiment, subjects were presented with questions and problems pertaining to cardiac output, venous return, and the mechanical properties of the cardiovascular system. The results indicated a progression of conceptual models as a function of expertise, which was evident in predictive accuracy, and the explanation and application of these concepts. The study also documented and characterized the etiology of significant misconceptions that impeded subjects' ability to reason about the cardiovascular and circulatory system. Certain conceptual errors were evident even in the responses of physicians. The scope of application of basic science principles is not as evident in the practice of medicine, as in the applied physical domains. Students and medical practitioners do not experience the same kinds of epistemic challenges to counter their naive intuitions

The use of Guyton’s approach to the control of cardiac output for clinical fluid management

Abstract Infusion of fluids is one of the most common medical acts when resuscitating critically ill patients. However, fluids most often are given without consideration of how fluid infusion can actually improve tissue perfusion. Arthur Guyton’s analysis of the circulation was based on how cardiac output is determined by the interaction of the factors determining the return of blood to the heart, i.e. venous return, and the factors that determine the output from the heart, i.e. pump function. His theoretical approach can be used to understand what fluids can and cannot do. In his graphical analysis, right atrial pressure (RAP) is at the center of this interaction and thus indicates the status of these two functions. Accordingly, trends in RAP and cardiac output (or a surrogate of cardiac output) can provide important guides for the cause of a hemodynamic deterioration, the potential role of fluids, the limits of their use, and when the fluid is given, the response to therapeutic interventions. Use of the trends in these values provide a physiologically grounded approach to clinical fluid management

Intracellular pH Regulation and the Acid Delusion

The concentration H+ ([H+]) in intracellular fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation,failure to consider the roles played by differences in the concentration of strong ions ( SID), the conservation of mass, the principle of electrical neutrality and that [H+] and [HCO3-] are dependent variables. This argument is based on the late Peter Stewart’s physical- chemical analysis of [H+] regulation reported in this journal nearly forty years ago. We start by outlining the principles of Stewart’s analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominanate regulation of [H+]. The primary strong ions are Na+, K+ and Cl-, and a few organic strong anions. The second independent variable, PCO2, can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles potentially will provide new insights into ICF pH regulation.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Preservation of Renal Blood Flow by the Antioxidant EUK-134 in LPS-Treated Pigs

Sepsis is associated with an increase in reactive oxygen species (ROS), however, the precise role of ROS in the septic process remains unknown. We hypothesized that treatment with EUK-134 (manganese-3-methoxy N,N\u27-bis(salicyclidene)ethylene-diamine chloride), a compound with superoxide dismutase and catalase activity, attenuates the vascular manifestations of sepsis in vivo. Pigs were instrumented to measure cardiac output and blood flow in renal, superior mesenteric and femoral arteries, and portal vein. Animals were treated with saline (control), lipopolysaccharide (LPS; 10 µg·kg−1·h−1), EUK-134, or EUK-134 plus LPS. Results show that an LPS-induced increase in pulmonary artery pressure (PAP) as well as a trend towards lower blood pressure (BP) were both attenuated by EUK-134. Renal blood flow decreased with LPS whereas superior mesenteric, portal and femoral flows did not change. Importantly, EUK-134 decreased the LPS-induced fall in renal blood flow and this was associated with a corresponding decrease in LPS-induced protein nitrotyrosinylation in the kidney. PO2, pH, base excess and systemic vascular resistance fell with LPS and were unaltered by EUK-134. EUK-134 also had no effect on LPS-associated increase in CO. Interestingly, EUK-134 alone resulted in higher CO, BP, PAP, mean circulatory filling pressure, and portal flow than controls. Taken together, these data support a protective role for EUK-134 in the renal circulation in sepsis