Pathophysiology of type A hypoxic lactic acidosis in dogs

1987 ◽  
Vol 253 (3) ◽  
pp. E271-E276 ◽  
Author(s):  
A. I. Arieff ◽  
H. Graf
Keyword(s):  
Blood Flow ◽  
Lactic Acidosis ◽  
Liver Blood Flow ◽  
Lactate Production ◽  
Arterial Lactate ◽  
Arterial Ph ◽  
Lactate Levels ◽  
Artery Flow ◽  
Arterial Po2 ◽  
Control State

Hypoxic lactic acidosis (HLA) was induced in dogs by ventilating them with a hypoxic gas mixture of 8% O2-92% N2. The animals were studied both in the control state and after development of HLA, where arterial lactate was above 5 mM, pH was below 7.2, bicarbonate was below 12 mM, and arterial PO2 was between 26 and 30 Torr. After hypoxia had been present for 90 min, most of the increase in arterial lactate vs. control was due to increased lactate production from gut and carcass in the presence of a decreased capacity of the liver to extract lactate. The capacity of the liver to extract lactate in the normoxic state was evaluated in another group of six dogs after infusion of L-lactic acid such that arterial pH, lactate, and bicarbonate were similar to hypoxic values. In these experiments it was found that the capacity of the liver to extract lactate was 14.8 +/- 1.7% of the delivered load vs. 4.9 +/- 1.3% observed in hypoxic animals. The decreased liver lactate extraction in HLA was probably secondary to both a decrease in liver oxygen uptake and a decrease in liver intracellular pH and was paralleled by an increase in liver tissue lactate levels. Cardiac output, in contrast to other forms of lactic acidosis, was increased by 40% vs. control and femoral artery flow by 35%, whereas liver blood flow was unchanged and renal blood flow decreased. Hypoxic lactic acidosis thus is the consequence of overproduction of lactate by both gut and carcass, in the presence of impaired utilization of lactate by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

pH effects on lactate and excess lactate in relation to O2 deficit in hypoxic dogs

1977 ◽  
Vol 42 (1) ◽  
pp. 44-49 ◽  
Author(s):  
S. M. Cain
Keyword(s):  
Ph Effect ◽  
Lactate Production ◽  
Ph Effects ◽  
Red Cell ◽  
Arterial Lactate ◽  
Pentobarbital Sodium ◽  
Arterial Ph ◽  
O2 Supply ◽  
Lactate Levels ◽  
O2 Deficit

Both hypoxemia and alkalemia increase arterial lactate levels, but excess lactate (XL) may be better related to the true O2 deficit and less subject to the pH effect upon glycolysis. To test this idea, 50 anesthetized (30 ml/kg pentobarbital sodium) and paralyzed dogs in five groups were ventilated with low O2 mixtures. Arterial pH was altered by CO2, hyperventilation, and HCO3- so that the average pH of the five groups were 6.99, 7.21, 7.34, 7.53, and 7.54 (+ propranolol). Pyruvate and lactate levels rose at rates roughly corresponding to pH. In all animals, rise of lactate (deltaL), XL and net O2 deficit were linear with time and the slope accurately described the rate of rise. When the ratio of XL rate deltaL rate was plotted against pH, it increased toward unity as pH decreased to 6.9. The ratio of deltaL rate to true O2 deficit rate also showed a significant pH effect by increasing with pH. Ratio of XL rate to true O2 deficit rate, on the other hand, was independent of pH. XL may correct for red cell lactate production which is not affected by O2 supply but is influenced by pH.

Oxygen consumption in the fetal lamb during sustained hypoxemia with progressive acidemia

1990 ◽  
Vol 258 (5) ◽  
pp. R1108-R1115 ◽  
Author(s):  
D. W. Rurak ◽  
B. S. Richardson ◽  
J. E. Patrick ◽  
L. Carmichael ◽  
J. Homan
Keyword(s):  
Blood Flow ◽  
Control Level ◽  
Umbilical Blood ◽  
Sustained Reduction ◽  
Arterial Ph ◽  
O2 Concentration ◽  
Umbilical Blood Flow ◽  
Lactate Levels ◽  
O2 Delivery ◽  
Arterial Po2

To investigate the fetal ability to compensate for a sustained reduction in O2 delivery (DO2; umbilical blood flow X umbilical venous O2 content), studies were carried out on eight chronically instrumented fetal lambs made hypoxemic for 7.8 +/- 0.8 (+/- SE) h by lowering maternal inspired O2 concentration to 9-10%. After 1.7 h of hypoxemia, fetal arterial PO2 had fallen from 18.4 +/- 1.2 to 10.4 +/- 0.5 mmHg. Umbilical venous O2 content fell initially by 41.1 +/- 1.8%, but the fall in DO2 was only 23.7 +/- 5.6%, caused by a 29.3 +/- 7.9% rise in umbilical blood flow. Fetal O2 consumption (VO2) was increased significantly by 29.5 +/- 15.2%. However, fetal vascular pH (7.332-7.281) and base excess (0.5 to -4.3 meq/l) were decreased while blood lactate levels were increased (1.55-7.22 mM). With continued hypoxemia, the metabolic acidemia worsened and led to progressive declines in umbilical venous O2 content and DO2. However, VO2 was maintained at the control level until delivery had fallen by 72.5% and arterial pH was 6.843, at which time VO2 decreased by 37.5 +/- 10.7%. It is concluded that the ability of the fetus to compensate for sustained hypoxemia is limited by the progressive metabolic acidemia.

Systemic effects of NaHCO3 in experimental lactic acidosis in dogs

1982 ◽  
Vol 242 (6) ◽  
pp. F586-F591 ◽  
Author(s):  
A. I. Arieff ◽  
W. Leach ◽  
R. Park ◽  
V. C. Lazarowitz
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Lactic Acidosis ◽  
Portal Vein ◽  
Blood Lactate ◽  
Lactate Production ◽  
Systemic Effects ◽  
Arterial Ph ◽  
Hepatic Portal Vein ◽  
Hepatic Portal

Lactic acidosis is characterized by metabolic acidosis due to accumulation of H+ ions from lactic acid with blood lactate of at least 5 mM. The standard treatment is intravenous NaHCO3, with resultant mortality in excess of 50%. Despite the high mortality, the metabolic and systemic effects of NaHCO3 used in the treatment of lactic acidosis have not been extensively studied. The present experiments in diabetic dogs were designed to address these questions. Dogs with phenformin-induced lactic acidosis (blood lactate above 5 mM, arterial pH below 7.20) were treated with equimolar amounts of either NaCl or NaHCO3 or received no therapy. Intravenous NaHCO3 resulted in a decline of cardiac output and intracellular pH (pHi) of liver and erythrocytes, whereas treatment with NaCl did not. With NaHCO3 but not with NaCl infusion gut lactate production increased almost stoichiometrically, with no change in arterial pH or bicarbonate but with a doubling of lactate. Bicarbonate also resulted in a decrease of hepatic portal vein blood flow. The mean survival time and percent mortality were similar in NaCl- vs. NAHCO3(-) treated animals. Although both groups lived longer than did animals receiving no therapy, the differences were not significant. Thus, treatment of experimental lactic acidosis with either NaCl or NaHCO3 or with no therapy results in no change of blood pH and bicarbonate and in a similar mortality. In terms of systemic effects, however, NaHCO3 results in significant decrements of liver and erythrocyte pHi, hepatic portal vein blood flow, and cardiac output and in significant increments of gut lactate production, whereas NaCl does not. The data suggest that the rationale for therapy of lactic acidosis with NaHCO3 should probably be reevaluated.

Metabolic effects of sodium bicarbonate in hypoxic lactic acidosis in dogs

1985 ◽  
Vol 249 (5) ◽  
pp. F630-F635 ◽  
Author(s):  
H. Graf ◽  
W. Leach ◽  
A. I. Arieff
Keyword(s):  
Lactic Acidosis ◽  
Lactate Production ◽  
Treated Group ◽  
Metabolic Effects ◽  
Gas Mixture ◽  
Diminished Capacity ◽  
Blood Ph ◽  
Lactate Levels ◽  
Arterial Po2 ◽  
Hypoxic Gas Mixture

The metabolic effects of NaHCO3 therapy in hypoxic lactic acidosis were evaluated in the anesthetized dog. Hypoxic lactic acidosis was induced by ventilating the dogs with a hypoxic gas mixture of 8% O2/92%N2, resulting in arterial PO2 of less than 30 mmHg, pH below 7.20, bicarbonate less than 12 mM, and lactate more than 7 mM. In this situation lactate accumulates because of overproduction of lactate by gut and carcass in the presence of a diminished capacity of the liver to extract lactate. After the development of hypoxic lactic acidosis the dogs were treated for 60 min with either NaHCO3 or NaCl or had no therapy. Sixty minutes of either treatment resulted in further declines of blood pH and bicarbonate that were similar in all three groups. NaHCO3-treated animals, however, showed an increase in blood lactate that were significantly higher than those treated with NaCl or those that had no therapy. This could be explained by a significantly higher gut lactate production with NaHCO3 therapy than in the NaCl-treated group. Concomitantly NaHCO3-treated animals showed a decrement in liver and gut blood flow that did not occur with NaCl treatment. Only NaHCO3 therapy was associated with a further decrease of liver intracellular pH, which could be attributed to both an increase in the CO2 load to the liver and increased tissue lactate levels, which were not observed with NaCl or no therapy. Additionally, liver lactate extraction was not improved by administration of NaHCO3 or NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional lactate production in early canine endotoxin shock

1988 ◽  
Vol 254 (1) ◽  
pp. E45-E51 ◽  
Author(s):  
A. A. van Lambalgen ◽  
H. C. Runge ◽  
G. C. van den Bos ◽  
L. G. Thijs
Keyword(s):  
Blood Flow ◽  
Lactate Concentration ◽  
Lactate Production ◽  
Endotoxin Shock ◽  
Serum Lactate ◽  
High Serum ◽  
Arterial Lactate ◽  
Endotoxin Challenge ◽  
O2 Extraction ◽  
Anesthetized Dogs

High serum lactate may not reflect the severity of endotoxin shock: the lactate load could even be formed immediately after the endotoxin challenge. During the first 30 min after endotoxin injection (Escherichia coli; 1.5 mg/kg iv) into anesthetized dogs (4 mg.kg-1.h-1 etomidate, n = 19) we studied arterial lactate concentration; contributions of portal and splanchnic (n = 6), renal and pulmonary (n = 7), and femoral (n = 6) vascular beds to the early lactate rise; and regional O2 extraction and blood flow (microspheres). In control dogs (n = 5, no endotoxin), we found no significant hemodynamic and biochemical changes. Endotoxin caused an immediate decrease in blood pressure, cardiac output, and organ perfusion, followed by recovery after approximately 5 min to approximately 75% of preshock values at t = 30 min (except for renal blood flow, which remained low). Arterial lactate concentration started to increase almost immediately after endotoxin and increased rapidly until t = 15 min (to 300%) and then leveled off, but in spite of the hemodynamic recovery it remained elevated. A major part of the early increase in lactate concentration can be explained by splanchnic lactate production. The total splanchnic bed released more lactate than the portal bed, indicating that the liver produces lactate. We conclude that the lactate concentration later in canine endotoxin shock depends on events that occur during early shock in which the liver may play a crucial role.

scholarly journals Effect of Pulsatile Cardiopulmonary Bypass in Adult Heart Surgery

2020 ◽  
Vol 23 (3) ◽  
pp. E258-E263
Author(s):  
Ersin Kadiroğulları ◽  
Onur Sen ◽  
Safa Gode ◽  
Serdar Basgoze ◽  
Barıs Timur ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Oxygen Saturation ◽  
Flow Pattern ◽  
Pulsatile Flow ◽  
Tissue Perfusion ◽  
Cerebral Oxygen Saturation ◽  
Cerebral Oxygen ◽  
Arterial Lactate ◽  
Arterial Ph ◽  
Lactate Levels

Background: This study aimed to examine the effect of pulsatile flow pattern on tissue perfusion, particularly cerebral tissue perfusion, at pre-determined intervals during CPB, as well as its effects on postoperative morbidity and mortality. Methods: This retrospective study included 134 adult patients, who underwent cardiac surgery with cardiopulmonary bypass (CPB). Patients were grouped based on the flow pattern used during CPB: non-pulsatile CPB group (N = 82) and pulsatile CPB group (N = 52). Cerebral oxygen saturation, arterial pH and arterial lactate levels were measured at four time points, during the operation and the 2 groups were compared with regard to changes over time as well as differences in postoperative outcomes. Results: The 2 groups were similar, in terms of mean values and intraoperative changes in cerebral oxygen saturation and arterial pH. Non-pulsatile CABG group had significantly higher arterial lactate levels over the measurement period, which was not affected by the timing of the measurements. Postoperative drainage, duration of ventilation and duration of hospital stay significantly were higher and postoperative blood urea nitrogen significantly was lower in the non-pulsatile CPB group. Other postoperative outcomes were similar across the groups. Conclusion: Findings of this study do not support the superiority of pulsatile flow pattern during CPB, in terms of cerebral oxygen saturation or postoperative mortality/morbidity. Further and larger comparative studies are warranted before pulsatile blood flow pattern can be established as a routine clinical method.

Increasing P50 does not improve Do 2crit or systemicV˙o 2 in severe anemia

2002 ◽  
Vol 283 (1) ◽  
pp. H92-H101 ◽  
Author(s):  
Otto Eichelbrönner ◽  
Mark D'Almeida ◽  
Andreas Sielenkämper ◽  
William J. Sibbald ◽  
Ian H. Chin-Yee
Keyword(s):  
Binding Affinity ◽  
Lactate Production ◽  
Saline Control ◽  
Severe Anemia ◽  
Acid Base Balance ◽  
Acid Base ◽  
Arterial Lactate ◽  
Beneficial Effects ◽  
Arterial Ph ◽  
Base Balance

Reducing the hemolobin (Hb)-O2 binding affinity facilitates O2 unloading from Hb, potentially increasing tissue mitochondrial O2 availability. We hypothesized that a reduction of Hb-O2 affinity would increase O2extraction when tissues are O2 supply dependent, reducing the threshold of critical O2 delivery (Do 2 CRIT). We investigated the effects of increased O2 tension at which Hb is 50% saturated (P50) on systemic O2 uptake (V˙o 2 SYS), Do 2 CRIT, lactate production, and acid-base balance during isovolemic hemodilution in conscious rats. After infusion of RSR13, an allosteric modifier of Hb, P50increased from 36.6 ± 0.3 to 48.3 ± 0.6 but remained unchanged at 35.4 ± 0.8 mmHg after saline (control, CON). Arterial O2 saturations were equivalent between RSR13 and saline groups, but venous Po 2 was higher and venous O2 saturation was lower after RSR13. Convective O2 delivery progressively declined during hemodilution reaching the Do 2 CRIT at 3.4 ± 0.8 ml · min−1 · 100 g−1 (CON) and 3.6 ± 0.6 ml · min−1 · 100 g−1 (RSR13). At Hb of 8.1 g/lV˙o 2 SYS started to decrease (CON: 1.9 ± 0.1; RSR13: 1.8 ± 0.2 ml · min−1 · 100 g−1) and fell to 0.8 ± 0.2 (CON) and 0.7 ± 0.2 ml · min−1 · 100 g−1 (RSR13). Arterial lactate was lower in RSR13-treated than in control animals when animals were O2 supply dependent. The decrease in base excess, arterial pH, and bicarbonate during O2 supply dependence was significantly less after RSR13 than after saline. These findings demonstrate that during O2 supply dependence caused by severe anemia, reducing Hb-O2 binding affinity does not affect V˙o 2 SYS or Do 2 CRIT but appears to have beneficial effects on oxidative metabolism and acid base balance.

scholarly journals Hyperlactatemia and the Outcome of Type 2 Diabetic Patients Suffering Acute Myocardial Infarction

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jovanovic Aleksandar ◽  
Peric Vladan ◽  
Snezana Markovic-Jovanovic ◽  
Radojica Stolic ◽  
Jadranka Mitic ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Lactic Acidosis ◽  
Blood Lactate ◽  
Lactate Production ◽  
Diabetic Patients ◽  
Lethal Outcome ◽  
Lactate Levels

Background.Increased lactate production is frequent in unregulated/complicated diabetes mellitus.Methods.Three groups, each consisting of 40 patients (type 2 diabetics with myocardial infarction, DM+AMI, nondiabetics suffering myocardial infarction, MI, and diabetics with no apparent cardiovascular pathology, DM group), were tested for pH, serum bicarbonate and electrolytes, blood lactate, and CK-MB.Results. Blood lactate levels were markedly higher in AMI+DM compared to MI group (4.54±1.44versus3.19±1.005 mmol/L,p<0.05); they correlated with the incidence of heart failure(ρ=0.66), cardiac rhythm disorders(ρ=0.54), oxygen saturation(ρ=0.72), CK-MB levels(ρ=0.62), and poor short-term outcome. Lactic acidosis in DM+AMI group was not always related to lethal outcome.Discussion. The lactate cutoff value associated with grave prognosis depends on the specific disease. While some authors proposed cutoff values ranging from 0.76 to 4 mmol/L, others argued that only occurrence of lactic acidosis may be truly predictive of lethal outcome.Conclusion. Both defective glucose metabolism and low tissue oxygenation may contribute to the lactate production in diabetic patients with acute myocardial infarction; high lactate levels indicate increased risk for poor outcome in this population comparing to nondiabetic patients. The rise in blood lactate concentration in diabetics with AMI was associated with increased incidence of heart failure, severe arrhythmias, cardiogenic shock, and high mortality rate.

scholarly journals A Hemodynamic Study to Evaluate the Buffer Response in Cirrhotic Patients Undergoing Liver Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Margarita Anders ◽  
Daniel Alvarez ◽  
Emilio Quiñonez ◽  
Federico Orozco ◽  
Nicolas Goldaracena ◽  
...  
Keyword(s):  
Blood Flow ◽  
Isosorbide Dinitrate ◽  
Liver Blood Flow ◽  
Resistance Index ◽  
Portal Blood Flow ◽  
Human Model ◽  
Physiological Regulation ◽  
Meal Ingestion ◽  
Artery Flow ◽  
Liver Transplant Recipients

The physiological regulation of the liver blood flow is a result of a reciprocal portal vein and hepatic artery flow relationship. This mechanism is defined as the hepatic arterial buffer response (HABR). This study was addressed to investigate whether HABR is maintained in denervated grafts in liver transplant recipients. Portal blood flow (PBF) and hepatic arterial resistance index (PI) were measured 6 months after transplantation using Doppler. In each patient we consecutively measured the vasodilator (Ensure Plus PO versus placebo) and vasoconstrictor (isosorbide dinitrate 5 mg SL versus placebo) stimuli. The meal ingestion caused a significant increase of both parameters, PBF (from 1495±260 to 2069±250 mL/min, P<0.05) and PI (from 0.7±0.2 to 0.8±0.2, P<0.05). By contrast, isosorbide dinitrate reduced PBF (from 1660±270 to 1397±250 mL/min, P<0.05) and PI (from 0.7±0.2 to 0.5±0.2, P<0.05). We show that PBF and PI are reciprocally modified with the administration of vasoconstrictor and vasodilator stimuli. These results suggest the persistence of the HABR in a denervated human model, suggesting that this mechanism is independent of the regulation from the autonomic nervous system.

scholarly journals Incidence and Associated Risk Factors for Lactic Acidosis Induced by Linezolid Therapy in a Case–Control Study in Patients Older Than 85 Years

2021 ◽  
Vol 8 ◽  
Author(s):  
Tingting Liu ◽  
Chao Hu ◽  
Jionghe Wu ◽  
Miao Liu ◽  
Yifan Que ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lactic Acidosis ◽  
Predictive Value ◽  
Close Monitoring ◽  
Blood Gas ◽  
Very Elderly ◽  
Arterial Lactate ◽  
Arterial Blood ◽  
Linezolid Therapy ◽  
Lactate Levels

Background: Serum lactic acid is considered a prognostic indicator in critically ill patients. However, studies on linezolid-induced lactic acidosis (LILA) are still limited. Individuals older than 85 years old (very elderly) have limited capacity for organ compensation, and LILA data from these patients are lacking. In this study, we evaluated the risk factors for LILA in patients older than 85 years and established a risk prediction model for geriatric practice.Methods: In this retrospective cohort study, blood gas analysis data and arterial lactate levels were monitored in patients older than 85 years during the use of teicoplanin or linezolid. After propensity score matching analyses, we compared the incidence of lactic acidosis between the teicoplanin and linezolid therapy groups and identified the risk factors of LILA.Results: The incidence of lactic acidosis was found to be much lower in the group receiving teicoplanin than those receiving linezolid therapy (0 vs. 35.7%; p &lt; 0.0001). A duration of linezolid therapy ≥ 9 days [odds ratio (OR), 3.541; 95% confidence interval (CI), 1.161–10.793; p = 0.026], an arterial blood glucose level ≥ 8 mmol/L (OR, 4.548; 95% CI, 1.507–13.725; p = 0.007), and a high sequential organ failure assessment score (OR, 1.429; 95% CI, 1.213–1.685; p &lt; 0.0001) were risk factors for LILA. The constructed risk model could be used to predict LILA (area under the curve, 0.849; specificity, 65.1%; sensitivity, 91.4%, with a negative predictive value of 93.2% and a positive predictive value of 59.3%).Conclusions: LILA can occur in patients older than 85 years after a relatively shorter duration of linezolid therapy. Therefore, close monitoring of blood gas and arterial lactate levels during linezolid therapy in the very elderly population is necessary.

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