The ventilatory threshold gives maximal lactate steady state

Summary The purpose of this study was to examine whether the ventilatory threshold (Th _v) would give the maximal lactate steady state ([1a]_{ss, max}), which was defined as the highest work rate (W) attained by a subject without a progressive increase in blood lactate concentration [1a]_b at constant intensity exercise. Firstly, 8 healthy men repeated ramp-work tests (20 W·min^–1) on an electrically braked cycle ergometer on different days. During the tests, alveolar gas exchange was measured breath-by-breath, and theW atTh _v (W _{Th v}) was determined. The results of two-way ANOVA showed that the coefficient of variation of a singleW _{Th v} determination was 2.6%. Secondly, 13 men performed 30-min exercise atW _{Th v} (Th _v trial) and at 4.9% aboveW _{Th v} (Th _v + trial), which corresponded to the 95% confidence interval of the single determination. The [1a]_b was measured at 15 and 30 min from the onset of exercise. The [1a]_b at 15 min (3.15 mmol·1^–1, SEM 0.14) and at 30 min (2.95 mmol·1^–1, SEM 0.18) were not significantly different inTh _v trial. However, the [1a]_b ofTh _v+ trial significantly increased (P<0.05) from 15 min (3.62 mmol·1^–1, SEM 0.36) to 30 min (3.91 mmol·1^–1, SEM 0.40). These results indicate thatTh _v gives the [1a]_ss,max, at which one can perform sustained exercise without continuous [1a]_b accumulation.     

The effect of stepwise arterial hypotension on blood flow and oxidative metabolism of the brain

Summary With the Kety-Schmidt-technique in ten dogs anaesthetized with 0.5% halothane, blood flow and oxidative metabolism of the brain were studied during stepwise lowering of CPP due to arterial hypotension at 71 and 41 torr. CBF remained constant (65.6 and 64.1 ml/100 g min) when CPP dropped from 98 to 71 torr, but at a CPP of 41 torr CBF fell to 32.2 ml/100 g min, i. e. to about 50% of the resting value. The CMR-oxygen did not change (4.20 and 4.38 ml/100 g min) when CPP was reduced from about 100 to about 70 torr, but decreased to 2.90 ml/100 g min, i. e. about 70% of the resting value in deep arterial hypotension.The uptake of glucose changed from 4.62 to 6.19 mg/100 g min as well as the output of CO₂ and lactate (from 4.64 to 6.57 ml/100 g min and from 0.33 to 1.62 mg/100 g min) when CPP was decreased to 71 torr. It could be demonstrated that at this CPP range the oxidative metabolism was unchanged. It was assumed that the increased uptake of glucose was only to form lactate, and that this non-hypoxic lactate production was responsible for the elevated CO₂ release. At a CPP range of 41 torr the metabolic rates of glucose and CO₂ decreased to 3.33 mg/100 g min and to 3.37 ml/100 g min, respectively, while the output of lactate remained relatively high (1.14 mg/100 g min). These findings support the assumption that at a CPP range of 41 torr the oxidative metabolism of the brain becomes insufficient. All findings demonstrate close interactions between cerebral flow blood and oxidative brain metabolism in arterial hypotension. In deep arterial hypotension respiratory acidosis has an effect on CBF. The increase of CBF is accompanied by an improvement of CMR-oxygen but not of CMR-glucose. Although CMR-lactate is reduced, the lactate/glucose index remains high.     

Contraindications can damage your health—is metformin a case in point?

Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a long list of contraindications precludes millions of patients with type 2 diabetes from using it. This is largely due to the historical experience of lactic acidosis with phenformin, despite the fact that metformin does not predispose to this when compared with other therapies. Contraindications such as old age, renal impairment and cardiac insufficiency are increasingly disregarded in clinical practice, yet there is no evidence that the incidence of lactic acidosis has changed. Metformin has been shown to improve metabolic control without causing lactic acidosis in elderly patients with multiple comorbidities, including explicit contraindications, and its use in patients with type 2 diabetes over the age of 70 with mild renal impairment did not produce a clinically relevant increase in plasma lactate. There is no correlation between levels of metformin and lactate in patients with lactic acidosis, and its prognosis is mainly related to the causal hypoxic underlying disease and comorbidities. These findings raise doubts about the pathogenetic significance of metformin in lactic acidosis. We propose that advanced age per se, mild renal impairment and compensated heart failure can no longer be upheld as contraindications for metformin. A clear re-definition of contraindications to metformin will enable more physicians to prescribe within guidelines.     

Lactate-stress testing in 54 patients with mitochondriopathy

Since there are only few data available about the lactate stress test in a group of patients with mitochondrial myopathy, we investigated the sensitivity of this test in a larger cohort of such patients. Serum lactate was determined before, during and after a 15 minute, constant 30 W workload on a bicycle ergometer in 47 controls, aged 15 to 72 years and 54 patients with mitochondrial myopathy, aged 15 to 74 years. Lactate’s upper reference limits at rest, 5, 10, 15 minutes after starting, and 15 minutes after finishing the exercise were 2.0, 2.1, 2.1, 2.1 and 1.8 mmol/l respectively. The sensitivity of the lactate-stress test was 69%. The lactate-stress test complements electrophysiological and bioptical findings and proved to be helpful in diagnosing mitochondrial myopathy. Received: 2 March 1999 / Accepted: 25 October 1999     

Regulation of red cell 2,3-DPG and Hb-O2-affinity during acute exercise

Summary Reports from the literature and our own data on red cell 2,3-DPG and its importance for unloading O₂ from Hb to the tissues during exhaustive exercise are contradictory. We investigated red cell metabolism during incremental bicycle ergometry of various durations. Furthermore changes in blood composition occurring during exercise were simulated under in vitro conditions. The effect of a moderate (11.2 mmol · l^–1 lactate, pH=7.127) and severe (18 mmol · l^–1 lactate, pH=6.943) lactacidosis on red cell 2,3-DPG concentration was compared with the effect of similar acidosis induced by HCl. Our data indicate that the concentration of 2,3-DPG in red cells depends on the degree of lactacidosis, but not on the duration of exercise. During moderate lactacidosis red cell 2,3-DPG remains unchanged. This can be explained by an interruption of red cell glycolysis on the PK and GAP-DH step caused by a lactate and pyruvate influx into the erythrocyte, as well as an intraerythrocytic acidosis and a drop in the NAD/NADH ratio. During severe lactacidosis and HCL-induced acidosis a decrease in 2,3-DPG due to an inhibition of 2,3-DPGmutase and other glycolytic enzymes can be found. Mathematical correction of the observed P-50 value for the decrease in 2,3-DPG occurring during severe lactacidosis showed that a decrease in Hb-O₂-affinity during strenuous exercise depends on the degree of lactacidosis and temperature elevation.