Renal Function, Potassium Homeostasis, and Vasopressin Regulation During Acute Hypotensive Stress in a Pig Model of Hemorrhagic Shock

Vasopressin (VP) can regulate potassium excretion in conditions of low urine flow. In severe hemorrhagic shock, the use of pharmacologic doses of VP has advantages over other pressor agents as it can increase urine output. We hypothesized that the physiological response to the rapid rise in plasma potassium (pK+) within minutes of the onset of hemorrhage would involve increased VP synthesis and VP‐mediated maintenance of renal potassium excretion in the face of severely decreased urine flow. In this study we examined the effect of the VP response on renal potassium handling during acute shock stress.Anesthetized, mechanically ventilated Yorkshire cross pigs (body weight 8.8±0.2 kg, n=44) were instrumented with vascular catheters and cardiac Swan Ganz catheter for hemodynamic assessments, and a bladder catheter for continuous urine collection. After baseline measurements, pigs were divided into control (n=14) or hemorrhage (n=30) groups. Hemorrhagic shock was induced by arterial blood withdrawal over 30 minutes (3 ml/kg/min for 7 minutes followed by a rate of 1 ml/kg/min until a goal oxygen debt of over 60 ml/kg was achieved with total shed volume of about 30 ml/kg and decrease in blood pressure by 50%). Blood samples for electrolytes and VP measurements were obtained at 10 minute intervals up to 60 minutes after the start of hemorrhage. Hemodynamics were assessed before resuscitation and up to 4 hours after hemorrhage. Six of the 30 hemorrhaged animals did not survive the acute blood loss beyond the first hour of hemorrhage, so we compared the results of survivors (n=24) to that of non‐survivors (n=6) to determine if altered renal fluid and electrolyte handling may have contributed to non‐survival.Non‐survivors had a higher (p<0.05) pK+ (7.0±0.7 mEq/L) at the end of hemorrhage than survivors (5.4±0.2 mEq/L) vs no change from baseline in controls (4.5±0.1 mEq/L). There was no change in plasma VP in controls whereas hemorrhage increased VP in survivors and non‐survivors (126±14 to 275±41 and 80±18 to 476±211 pg/ml, p<0.05, respectively). Thus, a deficit in VP synthesis and release was not responsible for the fatal hyperkalemia in non‐survivors. Indeed, in hemorrhaged animals VP mRNA, V1aR and V1bR expression in the hypothalamus and pituitary were increased compared to controls. Controls exhibited no change in renal fluid and electrolyte handling. Hemorrhage decreased urine flow (21.0±2.4 to 8.9±1.9 and 20.8±5.8 to 4.0±1.6 ul/min/kg, in survivors and non‐survivors, respectively) along with a decrease in glomerular filtration (p<0.05). Osmotic clearance decreased and was accompanied by increased free water clearance in hemorrhage. Fractional excretion of potassium remained constant. A significantly higher fractional excretion of water distinguished non‐survivors from survivors. A difference in the renal tubular handling of fluid may hinder effective potassium excretion after acute hypotensive stress, and hence results in exacerbated hyperkalemia in non‐survivors despite adequate VP circulating levels.Support or Funding InformationThe views expressed are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.