Establishing Prolonged Hyperlactatemia in a Canine Model

Abstract

The purpose of this study was to maintain acid-base and electrolyte balance while inducing an eight-hour hyperlactatemic clamp of 8-9 mM using the canine model. Six adult dogs were anesthetized using sodium pentobarbital. Indwelling venous catheters were used for the infusion of 650 mM NaLa/HLa (pH 4.6), 80 mM KCl, and 42.5 mM CaCl2. Arterial blood was collected using indwelling catheters for the analysis of PO2, PCO2, pH, [K+], [Na+], [Ca2+], [glucose], and [lactate]. All animals were mechanically ventilated throughout each experiment. Ventilation was decreased to allow hypercapnia for maintenance of normal arterial pH; and oxygen was supplemented for maintenance of normal arterial PO2 levels. Infusion rates fo NaLa/HLa, KCl, and CaCl2 were varied to maintain hyperlactatemia along with normal K+, and Ca2+ levels. The pH of arterial blood fluctuated between 7.44 ± 0.02 and 7.48 ± 0.01. Arterial blood PCO2 increased from 29 ± 5 mmHg at rest to 59 ± 5 mmHg by the end of infusion. Bicarbonate arterial concentrations increased from 20.9 ± 1.5 mM under control conditions to 39.1 ± 3.5 mM after NaLa/HLa infusion. Estimated base excess increased steadily from -2.22 ± 1.40 mM under control conditions to 14.23 ± 3.28 mM after NaLa/HLa infusion. Arterial PO2 fluctuated between 96 ± 11 and 129 ± 19 mmHg throughout the ten-hour experiment. The arterial concentration of glucose fluctuated was maintained around 6.0 ± 0.6 mM throughout the experiment. Sodium concentration in arterial blood rose from 142 ± 1 mM under control conditions to a max concentration of 154 ± 7 mM by nine hours of infusion. Arterial K+ and Ca2+ concentrations decreased slightly throughout the experiment from 3.3 ± 0.2 to 2.9 ± 0.4 mM and 1.28 ± 0.09 to 1.16 ± 0.19 mM, respectively. Blood lactate concentration was successfully increased from 0.7 mM to approximately 8.0-9.0 mM over an eight-hour period. Infusion of K+ and Ca2+ with permissive hypercapnia were required to maintain electrolyte and pH values within the physiological range. This is the first study to maintain hyperlactatemia for greater than three hours without the disturbance of acid-base or ion balance.