Increase In Arterial Lactate Research Articles

Lactic acidosis associated with metformin in patients with diabetic kidney disease; a mini-review

Background: Diabetes mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis. Objective: This study aims to evaluate the side effect of metformin for diabetic kidney disease (DKD) patients. Methods: This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library. Results: Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension. Conclusion: Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.

Lactic Acidosis Associated with Metformin in Patients with Diabetic Kidney Disease.

Background:Diabetes Mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis.Objective:This study aims to evaluate the side effect of Metformin for diabetic kidney diseases (DKD) patients.Method:This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library.Results:Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are considered to be below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension.Conclusion:Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.

Arterial lactate as a prognostic tool to predict mortality and disposition in the emergency department: A prospective observational single-centre study

Background: Point-of-care tools are invaluable in the emergency department. Arterial lactate has been used for prognostication in subsets of population in the emergency department but not often for a heterogeneous population. Objectives: We aimed to study the use of arterial lactate as a prognostication and disposition tool in an undifferentiated population presenting to the emergency department. Methods: We conducted a prospective study among all consenting emergency department patients with age >18 years, who had an arterial blood gas performed as a part of routine care and had a lactate value ⩾2 mmol/L. We collected data on demographics, comorbidities and patient disposition from the emergency department and 28-day mortality as a follow-up telephonically. Results: We included 469 patients with a median age of 37 years. Sixteen provisional diagnoses were made in the emergency department, and pneumonia/lower respiratory tract infection was relatively higher (13.6%). The median lactate was 4.6 (interquartile range = 3.2–7) with 155 patients (33%) being transferred to intensive care unit and 62 deaths (13.2%) recorded at 28 days. Furthermore, we observed optimum values for lactates at 5 mmol/L predicted intensive care unit admissions and 6 mmol/L predicted mortality. A unit increase in arterial lactate in the emergency department significantly increased mortality by 66% (95% confidence interval = 1.45–1.88; p < 0.001) and had a 2.15 times (95% confidence interval = 1.63–2.83; p < 0.001) significantly higher chance of being transferred to the intensive care unit. Conclusion: Arterial lactate can be used as a prognostication tool for a heterogeneous population presenting to the emergency department. Clinical significance: Point-of-care investigations such as arterial lactate can help the emergency physician make quick decisions on the floor and guide prognostication and disposition.

The effect of delayed umbilical cord clamping on cord blood gas analysis in vaginal and caesarean-delivered term newborns without fetal distress: a prospective observational study.

To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress. Prospective observational study. University hospital. CBG from 97 VDs and 124 CDs without fetal distress. Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs. Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage. Arterial cord blood pH, bicarbonate ( , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH=7.23 versus 7.27; P<0.001; =23.3 versus 24.3; P=0.004; BE=-5.1 versus -2.9; P<0.001) and CDs (pH=7.28 versus 7.34; P<0.001; =26.2 versus 27.2; P<0.001; BE=-1.5 versus 0.7; P<0.001). After 3-minute DCC, pCO2 increased in CDs only (57 versus 51; P<0.001), whereas lactate increased more in CDs compared with VDs (lactate, +1.1 [0.9, 1.45] versus +0.5 [-0.65, 2.35]; P=0.01). Postpartum maternal haemorrhage, neonatal maximum bilirubin concentration, and need for phototherapy were similar between the two groups. Newborns born by CD more frequently required postnatal clinical monitoring or admission to a neonatal intensive care unit. After 3-minute DCC, the acid-base status shifted towards mixed acidosis in CDs and prevalent metabolic acidosis in VDs. CDs were associated with a more pronounced increase in arterial lactate, compared with VDs. By 3-minute DCC, acid-base status shifts towards mixed and metabolic acidosis in caesarean and vaginal delivery, respectively.

Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock.

Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS. Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30-35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1). Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL). The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential. VExperimental in vivo study.

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning

Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.

Hemodynamic challenge to early mobilization after cardiac surgery: A pilot study

Background:Active mobilization is a key component in fast-track surgical strategies. Following major surgery, clinicians are often reluctant to mobilize patients arguing that circulatory homeostasis would be impaired as a result of myocardial stunning, fluid shift, and autonomic dysfunction.Aims:We examined the feasibility and safety of a mobilization protocol 12–24 h after elective cardiac surgery.Setting and Design:This observational study was performed in a tertiary nonacademic cardiovascular Intensive Care Unit.Materials and Methods:Over a 6-month period, we prospectively evaluated the hemodynamic response to a two-staged mobilization procedure in 53 consecutive patients. Before, during, and after the mobilization, hemodynamics parameters were recorded, including the central venous oxygen saturation (ScvO2), lactate concentrations, mean arterial pressure (MAP), heart rate (HR), right atrial pressure (RAP), and arterial oxygen saturation (SpO2). Any adverse events were documented.Results:All patients successfully completed the mobilization procedure. Compared with the supine position, mobilization induced significant increases in arterial lactate (34.6% [31.6%, 47.6%], P = 0.0022) along with reduction in RAP (−33% [−21%, −45%], P < 0.0001) and ScvO2 (−7.4% [−5.9%, −9.9%], P = 0.0002), whereas HR and SpO2 were unchanged. Eighteen patients (34%) presented a decrease in MAP > 10% and nine of them (17%) required treatment. Hypotensive patients experienced a greater decrease in ScvO2 (−18 ± 5% vs. −9 ± 4%, P = 0.004) with similar changes in RAP and HR. All hemodynamic parameters, but arterial lactate, recovered baseline values after resuming the horizontal position.Conclusions:Early mobilization after cardiac surgery appears to be a safe procedure as far as it is performed under close hemodynamic and clinical monitoring in an intensive care setting.

Effects of selective β1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis.

IntroductionActivation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.MethodsHyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis.ResultsHyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6.ConclusionsIn sepsis, selective β1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect.

No beneficial effects of levosimendan in acute porcine endotoxaemia

Levosimendan has been proposed as an attractive alternative to adrenergic agents for the treatment of sepsis-induced heart failure and haemodynamic derangements. Its use in this setting is, however, still not well investigated. The aim of this study was to test the hypothesis that levosimendan is able to attenuate endotoxin-induced pulmonary hypertension and improve myocardial function in a porcine model. The secondary aims were to investigate its effect on renal and liver function, and the plasma cytokine response. Endotoxaemia was induced in 18 pigs, randomized to placebo and Levosimendan groups. All pigs were fluid resuscitated and Noradrenalin infusion was given according to a predefined protocol. Systemic haemodynamics and myocardial function were measured using pulmonary artery catheterization and transthoracic echocardiography. Renal and liver function tests and cytokine concentrations were measured in plasma. Levosimendan did not attenuate endotoxin-induced pulmonary hypertension and did not improve myocardial function. There were no differences in renal or liver function. Increases in arterial lactate and decreases in base excess were observed in the Levosimendan group, as well as significant increases in plasma interleukin (IL)-6 and IL-8. Contrary to our hypothesis, levosimendan given in conjunction with a protocolized vasopressor and fluid resuscitation did not improve cardiac, renal or liver function in this model of acute porcine endotoxaemia. Hyperlactataemia, acidosis and increases in plasma pro-inflammatory cytokines were observed, the mechanisms and implications of which remain unclear.

Prolonged Propofol Anesthesia Is Not Associated with an Increase in Blood Lactate

Lactic acidosis is considered an early sign of propofol infusion syndrome. In this study, we investigated the changes in lactate and pH with propofol versus volatile anesthesia (VA) of long duration. Demographic and intraoperative data were recorded retrospectively from the anesthesia records of patients who underwent elective spine surgery longer than 8 h. Propofol patients were matched 1:2 to VA patients, based on anesthesia time (AT) (+/-30 min) and blood loss (BL) (+/-500 mL). Of 246 patients identified, 50 received propofol (AT = 10 +/- 2 h, BL = 1955 +/- 1409 mL) and were matched to 100 VA cases (AT = 10 +/- 1 h, BL = 1801 +/- 1543 mL), and of those, 40 and 72 patients, respectively, had complete lactate data at baseline and at 8 h after anesthesia and were included in the main analysis. The propofol group received 8.8 +/- 2 mg x kg(-1) x h(-1) of propofol. The VA group age was older than the propofol group (58 +/- 12 vs 51 +/- 15 yr, respectively, P = 0.002), but there was no difference between the groups in gender, ASA grade, intraoperative hemodynamic variables, and use of vasopressors. After 8 h, the VA group had a larger increase in arterial lactate from baseline compared with the propofol group (change from baseline: propofol, 0.48 +/- 0.72 mmol/L; VA, 1.2 +/- 1.2 mmol/L, P = 0.001). During prolonged spine surgery >8 h, VA was associated with higher serum lactate, when compared with propofol infusion. Prospective studies are needed to elucidate the exact mechanisms and clinical implications of this finding.

Hepatic lactate uptake versus leg lactate output during exercise in humans

The exponential rise in blood lactate with exercise intensity may be influenced by hepatic lactate uptake. We compared muscle-derived lactate to the hepatic elimination during 2 h prolonged cycling (62 +/- 4% of maximal O(2) uptake, (.)Vo(2max)) followed by incremental exercise in seven healthy men. Hepatic blood flow was assessed by indocyanine green dye elimination and leg blood flow by thermodilution. During prolonged exercise, the hepatic glucose output was lower than the leg glucose uptake (3.8 +/- 0.5 vs. 6.5 +/- 0.6 mmol/min; mean +/- SE) and at an arterial lactate of 2.0 +/- 0.2 mM, the leg lactate output of 3.0 +/- 1.8 mmol/min was about fourfold higher than the hepatic lactate uptake (0.7 +/- 0.3 mmol/min). During incremental exercise, the hepatic glucose output was about one-third of the leg glucose uptake (2.0 +/- 0.4 vs. 6.2 +/- 1.3 mmol/min) and the arterial lactate reached 6.0 +/- 1.1 mM because the leg lactate output of 8.9 +/- 2.7 mmol/min was markedly higher than the lactate taken up by the liver (1.1 +/- 0.6 mmol/min). Compared with prolonged exercise, the hepatic lactate uptake increased during incremental exercise, but the relative hepatic lactate uptake decreased to about one-tenth of the lactate released by the legs. This drop in relative hepatic lactate extraction may contribute to the increase in arterial lactate during intense exercise.

Lung compliance, plasma electrolyte levels and acid–base balance are affected by scorpion envenomation in anesthetized rats under mechanical ventilation

To determine the effects of Tityus serrulatus scorpion toxin on lung compliance and resistance, ionic equilibrium and acid–base balance over time in anesthetized and mechanically ventilated rats, we measured air flow, tracheal and esophageal pressure. Lung volume was obtained by electronic integration of airflow signal. Arterial blood samples were collected through a catheter at baseline (before) and 5, 15, 30 and 60 min after scorpion toxin injection for arterial blood gases, bicarbonate, and alkali reserve levels as well as for, sodium, potassium, magnesium, glucose, lactate, hematocrit, and osmolality analysis. Injection of the gamma fraction of the T. serrulatus scorpion venom in rats under mechanical ventilatory support leads to a continuous decrease in lung compliance secondary to pulmonary edema, but no change in airway resistance. The changes in arterial blood gases characterizing metabolic acidosis were accompanied by an increase in arterial lactate and glucose values, suggesting a scorpion toxin-induced lactic acidosis, in association with poor tissue perfusion (hypotension and low cardiac output). Moreover, scorpion toxin injection resulted in hyperosmolality, hyperkalemia, hypermagnesemia and an increase in hematocrit. The experiments have shown a clinically relevant animal model to study severe scorpion envenoming and may help to better understand the scorpion envenoming syndrome.

The effects of olprinone (a phosphodiesterase III inhibitor) on hepatic vascular bed in a porcine model of endotoxemia.

Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by endotoxin, result in hepatic metabolic deterioration followed by liver dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors, only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous infusion (1.7 microg. kg(-1). h(-1)) of endotoxin (lipopolysaccharide [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 microg. kg(-1). min(-1)) via a central vein from t = 150 min to t = 240 min, whereas the eight remaining pigs served as LPS controls. Continuous infusion of LPS caused significant reductions in hemodynamic variables and a significant increase in arterial lactate. After the administration of olprinone during the LPS infusion, portal venous flow and hepatic oxygen delivery were increased and were higher than in the LPS group. Furthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia. Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.

Coupling of external to cellular respiration during exercise: the wisdom of the body revisited.

The changes in cellular respiration needed to increase energy output during exercise are intimately and predictably linked to external respiration through the circulation. This review addresses the mechanisms by which lactate accumulation might influence O2 uptake (VO2) and CO2 output (VCO2) kinetics. Respiratory homeostasis (a steady state with respect to VO2 and VCO2) is achieved by 3-4 min for work rates not associated with an increase in arterial lactate. When blood lactate increases significantly above rest for constant work rate exercise, VO2 characteristically increases past 3 min (slow component) at a rate proportional to the lactate concentration increase. The development of a similar slow component in VCO2 is not evident. The divergence of VCO2 from VO2 increase can be accounted for by extra CO2 release from the cell as HCO3- buffers lactic acid. Thus the slow component of aerobic CO2 production (parallel to VO2) is masked by the increase in buffer VCO2. This CO2, and the consumption of extracellular HCO3- by the lactate-producing cells, shifts the oxyhemoglobin dissociation curve rightward (Bohr effect). The exercise lactic acidosis has been observed to occur after the minimal capillary PO2 is reached. Thus the lactic acidosis serves to facilitate oxyhemoglobin dissociation and O2 transport to the muscle cells without a further decrease in end-capillary PO2. From these observations, it is hypothesized that simultaneously measured dynamic changes in VO2 and VCO2 might be useful to infer the aerobic and anaerobic contributions to exercise bioenergetics for a specific work task.

Differential effects of hypothermia upon blood acid-base state and blood gases in sodium pentobarbital and urethane anaesthetised rats

1. 1. The effects of two anaesthetics, sodium pentobarbital and urethane, and the effects of anaesthesia-associated hypothermia on acid-base status and blood gases were studied in rats without assisted ventilation. 2. 2. Manipulation of conscious rats produces a progressive increase in arterial lactate associated with slight hyperventilation. 3. 3. Sodium pentobarbital anaesthesia produces mild respiratory acidosis accompanied by increase in lactate arterial values. Urethane anaesthesia leads to partially compensated metabolic acidosis. 4. 4. Hypothermia reduces metabolic acidosis and hypercapnia induced by sodium pentobarbital anaesthesia. No difference between hypothermic and normothermic values was observed in urethane anaesthesia.

Hyperlactataemia and Metabolic Acidosis during Haemofiltration Using Lactate-Buffered Fluids

We have investigated the effect of an exogenous lactate load given during machine haemofiltration treatment in 22 patients with acute renal failure and 12 patients with chronic renal failure, without any overt evidence of liver disease. Hyperlactataemia occurred in all patients, but the expected changes in acid base status, an increase in bicarbonate and a reduction in arterial hydrogen ions were observed in less than 40% of the treatments in the acute renal failure group. Ultrafiltrate losses of lactate and bicarbonate could not alone explain the changes in acid-base status. There was a positive correlation between the increase in arterial lactate and hydrogen ion concentrations, r = 0.52, p less than 0.01. Lactate accumulation in patients at, or close to, their threshold for lactate utilisation may result in further depression of cardiac function and peripheral lactate utilisation. Hyperlactataemia due to use of lactate-based dialysis/haemofiltration solutions in critically ill patients may result in a worsening of the acid-base status, and arterial pH should be monitored so that bicarbonate solutions can be substituted if the changes are progressive.

Myocardial and systemic oxygenation during severe hypoxemia in ventilated lambs

We studied the interrelationships among myocardial oxygenation, cardiac output, and systemic oxygenation during acute progressive hypoxemia in the paralyzed and mechanically ventilated lamb. Fractional inspired concentration of oxygen was reduced in five steps to a minimum of 0.05, decreasing arterial oxygen content (CaO2) from 10.9 +/- 2.4 to 2.8 +/- 0.5 ml/dl. Heart rate and stroke volume did not change at any step so that systemic oxygen transport decreased with CaO2. Systemic oxygen consumption fell at CaO2 less than 6 ml/dl. Left ventricular blood flow at maximal hypoxemia increased 277% (249 +/- 27 to 938 +/- 118 ml.min-1.100 g-1) so that left ventricular oxygen delivery and oxygen consumption were maintained. Evidence of anaerobic metabolism occurred when CaO2 was less than four (increase in arterial lactate and hypoxanthine), whereas at this level there was no evidence of inadequate myocardial oxygenation as determined by normal subepicardial: subendocardial blood flow and absence of net lactate production, although coronary sinus PO2 decreased. Although myocardial, cerebral, and adrenal blood flows increased, there was no redistribution of blood flow away from the viscera and skin.

Arterial Blood Gases, Acid-Base Balance, and Lactate and Gas Exchange Variables During Hypoxic Exercise

To determine the effect of hypoxia on lactate threshold (LT), onset of blood lactate accumulation (OBLA), and gas exchange threshold (GET), the lactate level together with VO2, VCO2, VE, and acid-base status in arterial blood from 12 female distance runners performing a progressive incremental treadmill test under the condition of hypoxic gas inhalation (HC: FIO2 is 16.0% in N2) compared with normoxic conditions (NC: FIO2 is 20.9%; i.e., air) were examined. During exercise, HC shifted LT, GET, and OBLA to a lower VO2 by 12.5%, 12.9%, and 9.3%, respectively. The GET during hypoxic exercise was well correlated with LT (GET = 0.973LT + 0.04; expressed in VO2 l.min-1). The close reciprocal changes in arterial blood lactate and bicarbonate (HCO3-) were observed during hypoxic as well as normoxic exercise. These findings provide evidence for the cause and effect relationship between LT and GET, even in hypoxic exercise. During submaximal exercise below the LT, PaCO2 and HCO3- slightly increased both in NC and HC with pH remaining unchanged. However, during exercise above the LT, the PaCO2, HCO3-, and pH all decreased with pH decreasing more markedly during hypoxia. In conclusion, this study demonstrated a clear increase in arterial lactate during hypoxic exercise above the LT. Both the LT and GET are shifted to a lower work rate by hypoxia in the same manner with the correlation between them remaining high, supporting the cause and effect relationship of these two parameters.

Rates of lactate appearance and disappearance and brain lactate balance after oral glucose in the dog.

After glucose ingestion, arterial lactate concentrations increase. Although it is presumed that this is due to an increase in lactate production, rates of lactate appearance have not been measured after oral glucose nor has the major site of its production been identified. Since brain takes up a substantial portion of an oral glucose load but does not store appreciable amounts of glucose, it is possible that brain could be an important site for postprandial lactate formation. Therefore, to investigate the contribution of the brain to the increase in arterial lactate after glucose ingestion and to determine whether changes in lactate appearance or disappearance were predominantly involved, we measured lactate fluxes and brain lactate balance in dogs after intraduodenal administration of glucose (1.6 g/kg). Although systemic lactate appearance increased significantly after glucose administration (from 22 +/- 3 to 33 +/- 9 umole/kg/min, P less than 0.05), brain lactate output did not change (0.62 +/- 0.5 vs 0.74 +/- 0.5 umole/min). We conclude that after glucose ingestion, arterial lactate increases as a result of an increase in the rate of lactate appearance and that brain does not make a significant contribution to this.

Cerebral Metabolic Response and Mitochondrial Activity following Insulin-Induced Hypoglycemia in Newborn Lambs

We evaluated the newborn lamb's cerebral cellular activity and metabolism following acute insulin-induced hypoglycemia. Eleven animals received an insulin bolus followed by a continuous infusion to maintain a plasma glucose of 1 mM/l for 2 h, while 8 other animals received an equivalent dose of saline. Following the induction of hypoglycemia, the animals became quiet and transient seizures were observed in 3 animals. A significant increase in heart rate (p less than 0.01), and a decrease in arterial PaCO2 at 30 min (p less than 0.01), and pH at 2 h (p = 0.02), following hypoglycemia, were observed in the experimental group. Hypoglycemia did not significantly alter the cerebral blood flow, mitochondrial respiratory control ratio or the state-3 activity. The cerebral arteriovenous difference (CAVD) for oxygen did not change, while the glucose CAVD was significantly reduced from 0.47 +/- 0.21 to 0.24 +/- 0.16 mM/l (p less than 0.05) at the end of the hypoglycemia period, suggesting consumption of alternate substrates of energy by the brain. Insulin-induced hypoglycemia was associated with a significant increase in arterial lactate (p less than 0.01), and a significant correlation (p less than 0.01) between arterial and CAVD for lactate and beta-hydroxybutyrate (BOB) was observed. Cerebral consumption of alternate substrates of energy was inconsistent, and only observed for lactate in 5 and for BOB in 3 experimental animals following hypoglycemia. These data indicate that the newborn lamb's cerebral cellular activity is not affected by the degree of hypoglycemia achieved in these studies.(ABSTRACT TRUNCATED AT 250 WORDS)