Epinephrine induces tissue perfusion deficit in porcine endotoxin shock: evaluation by regional CO2 content gradients and lactate-to-pyruvate ratios

Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it may typically induce or augment lactic acidosis. Ongoing debate addresses the question of whether hyperlactatemia per se is a sign of tissue perfusion deficit or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has selective detrimental effects on visceral perfusion and metabolism. We performed rigorous regional venous blood gas analyses as well as intraperitoneal microdialysis. We used a mathematical model to calculate regional arteriovenous CO2 content gradients and estimated the magnitude of the Haldane effect in a porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or norepinephrine) were administered and adjusted to maintain systemic mean arterial pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate ratios increased. Epinephrine was associated with decreasing portal blood flow despite apparently maintained total splanchnic blood flow. Epinephrine increased gastric venous-to-arterial Pco2 gradients and CO2 content gradients with decreasing magnitude of the Haldane effect, and the regional gastric respiratory quotient remained higher after epinephrine as opposed to norepinephrine infusion. In addition, epinephrine induced intraperitoneal lactate and glycerol release. We did not observe these adverse hemodynamic or metabolic changes related to norepinephrine with the same arterial pressure goal. We conclude that high CO2 content gradients with decreasing magnitude of the Haldane effect pinpoint the most pronounced perfusion deficiency to the gastric wall when epinephrine, as opposed to norepinephrine, is used in experimental endotoxin shock.

Physiological consequences of oxygen-dependent chloride binding to hemoglobin

The Po 2-dependent binding of chloride to Hb decreases the Cl− concentration of the red blood cell (RBC) intracellular fluid in venous blood to ∼1–3 mmol/l less than that in arterial blood. This change is physiologically important because 1) Cl− is a negative heterotropic allosteric effector of Hb that competes for binding sites with 2,3-bisphosphoglycerate and CO2 and decreases oxyhemoglobin affinity in several species; 2) it may help reconcile several longstanding problems with measured values of the Donnan ratios for Cl−, HCO[Formula: see text], and H+ across the RBC membrane that are used to calculate total CO2 carriage, ion flux rates, and membrane potentials; 3) it is a factor in the change in the dissociation constant for the combined nonvolatile weak acids of Hb associated with the Haldane effect; and 4) it diminishes the decrease in strong ion difference in the RBC intracellular fluid that would otherwise occur from the chloride shift and prevent the known increase of HCO[Formula: see text] concentration in that compartment.