Figure 1.
Details of the experimental protocol are shown.
Anesthetized pigs were subjected to hypovolemia (30 ml/kg) for 30 minutes. The animals then received a bolus infusion of NHE1 inhibitor (3 mg/kg, sabiporide) or vehicle, followed by lactic acid infusion for 2 hours. The animals were continuously monitored for additional 3 hours.
Figure 2.
Three of the eight control animals died either during infusion of lactic acid or after its discontinuation. By contrast, all six animals given sabiporide survived. *P = 0.0002 vs. the control group by chi square analysis for trend. BL: at baseline; H30: at 30 min of hemorrhage; T30 min, –T300 min: at 30 min, –and 300 min from lactic acid infusion.
Table 1.
Changes in acid-base parameters and blood oxygenation after hypovolemia and lactic acidosis.
Figure 3.
Changes in pulmonary arterial pressure and pulmonary vascular resistance.
Pulmonary arterial pressure and vascular resistance rose in controls with lactic acid infusions and remained elevated throughout the study. The increase in both parameters was blunted with sabiporide. All values are the mean ± SD. N = 5–6. *p<0.05 vs. the control group; #p<0.05 vs. the baseline value.
Table 2.
Changes in hemodynamics after hypovolemia and lactic acidosis in pigs.
Table 3.
Echocardiographic measurements of left ventricular ejection fraction, fractional shortening and wall motion score index.
Figure 4.
Changes in mixed-venous blood oxygen saturation, oxygen delivery, oxygen extraction ratio and mixed-venous blood oxygenated hemoglobin/total Hb ratio (FO2Hb) ratio.
NHE1 inhibition with sabiporide prevented excessive fall in mixed-venous blood oxygen saturation following hypovolemia and lactic acidosis, and improved mixed-venous blood oxygen binding capacity of hemoglobin, resulting in improved oxygen delivery and decreased oxygen extraction ratio, suggesting improved tissue oxygenation. All values are the mean ± SD. N = 5–6. *p<0.05 vs. the control group; #p<0.05 vs. the baseline value.
Table 4.
Changes of plasma levels of TNF-α, IL-6, troponin-I, ALT, AST and urea following severe lactic acidosis in pigs.