Effect of acute changes in plasma osmolarity on metabolic and cardiovascular homeostasis

Abstract

Chronic changes in plasma osmolality are known to be indicators of deteriorating physical health. It is not known however, whether large acute changes in osmolality are precursors to sepsis and circulatory distress. To investigate the relationship between altered osmolality and animal health this study assessed 12 anesthetized piglets administered an over-hydration infusion of either hypotonic, hypertonic, or isotonic saline at regular 60 min intervals. Hemodynamic variables, including mean arterial pressure (MAP), heart rate (HR), and end-tidal carbon dioxide levels (ETCO2), were measured continuously throughout the experiment. Whole blood was sampled hourly, allowing hemoglobin content to be measured and plasma to be extracted via centrifugation. Plasma osmolality was assessed via freezing-point depression osmometry and concentrations of various regulatory solutes, such as lactate, Na+, K+, Cl−, Ca2+, and Mg2+, were measured using a critical care analyzer with co-oximeter. Hypertonic solutions significantly increased plasma osmolality as expected, with that population displaying an average of 497 ± 9 mOsm at the conclusion of the experiment. In addition, lactate increased to 10.3 ± 0.7 mM, indicating general systemic stress. Conversely, hypotonic and isotonic populations displayed terminal osmolalities of 246 ± 15 mOsm and 281 ± 3 mOsm and lactate levels of 1.7 ± 0.3 mM and 4.5 ± 2.8 mM respectively. HR for the hypertonic piglets reached an average high of 108 beats per minute, while MAP decreased to a low of 47.0 ± 3.5 mm Hg. The hypotonic and isotonic populations did not exhibit this extreme hemodynamic variation. These data reveal that greater acute changes in osmolality, particularly elevated tonicity, lead to increased metabolite production, and early clinical signs of sepsis and circulatory distress.