The purpose of this investigation was to compare the ventilatory threshold (T(vent)) with the lactate threshold (T(lact)) during 60 minutes of steady-state exercise at the calculated thresholds. Eight trained, male cyclists (mean age=23.3 yrs, ht=176.4 cm, wt=70.7 kg, VO₂max=61.02 ml/kg‧minˉ¹) performed a 23 W/min progressive intensity cycling test for determination of T(lact) and T(vent). T(vent) was determined by the non-linear increase in excess CO₂ (ExCO₂) while T(lact) was calculated by the 'individual anaerobic threshold' (IAT) method. Subsequently, subjects performed up to 60 minutes steady-state exercise at the threshold workloads. Results at T(vent) and T(lact) indicate significant differences (p<0.01; T(lact)>T(vent)) between VO₂, ExCO₂, HR, [BLa] and workload as calculated by Hotelling's T²-test. During the steady state exercise at each specified workload, VO₂, [BLa], heart rate and ExCO₂ were measured at 15 minute intervals. All subjects completed the steady-state exercise at T(vent) (VSS) while only 2 subjects completed the steady-state exercise at T(lact) (LSS) (avg time=48.4 min). Comparison of metabolic variables using MANOVA and multiple comparisons revealed significant differences between VSS and LSS for HR and VO₂ at all time intervals, for [BLa] at 30 and 45 minute intervals and for ExCO₂ at the 30 minute interval. Furthermore, examination of [BLa] over time using trend analysis revealed a stabilization during VSS ([formula omitted]=3.05 mmol‧Lˉ¹) whereas [BLa] continuously increased over time during LSS. Findings indicate that T(lact) (IAT method) overestimates the ability to perform prolonged work over 45 min. while T(vent) (ExCO) allows for steady-state exercise greater than 60 minutes. / Education, Faculty of / Curriculum and Pedagogy (EDCP), Department of / Graduate

Two experiments were done to study the effects of L-carnitine supplementation (CNsup) during exercise. EXP 1, examined the effect of CNsup on lipid oxidation and muscle glycogen utilization during submaximal EX. Triglycerides were elevated by a fat feeding (90g fat), 3 h later subjects cycled for 60 min at 70% VO2max (CON). Muscle biopsies were obtained preEX, after 30 and 60 min of EX. Blood samples were taken preEX and every 15 min of EX. Subjects randomly completed two additional trials following 7 and 14 days of CNsup (6 g/day). During one of the trials, subjects received 2000 units of heparin 15 min prior to EX to elevate FFA (CNhep). There were no differences in V02, RER, HR, g of CHO and fat oxidized among the three trials. Serum total acid soluble (TASC) and free carnitine (FC) increased with CNsup (CON, 71.3 ± 2.9; CN, 92.8 ± 5.4; CNhep, 109.8 ± 3.5 mol·g'). Muscle carnitine concentration at rest was unaffected by CNsup. During EX, TASC did not change, FC decreased (p<0.05) and SCAC increased (p<0.05). With CNsup the decrease in FC was less (~50%) (p<0.05) and the increase in SCAC was greater (~200-300%) (p<0.05) compared to CON (free 65%; SCAC 150%). Pre and postEX muscle glycogens were not different. EXP 2, examined the effects of CNsup on blood lactate accumulation during maximal EX. Subjects cycled for 4 min at ~100% VO2max (CON). Exercise was repeated following 6 and 13 days of CNsup (6 g/day). Serum TASC and FC were elevated due to CNsup. Blood Lactate was measured prior to and 0, 3, 5, and 7 min postEX. CNsup resulted in less (p<0.05) lactate accumulation compared to CON. There were no differences between DAY-6 and DAY-13. / Human Performance Laboratory

During sustained exercise, working muscles must be supplied with adequate kinds and amounts of exogenous fuels, and the delivery rates of oxygen and oxidizable substrates should be matched. The study of metabolite fluxes and their regulation is therefore critical to the understanding of exercise metabolism. Lactate has received renewed attention from physiologists and biochemists with the realization that it is not only an end product of glycolysis, but also an important fuel for aerobic work. As an oxidizable fuel, this substrate may provide some performance advantage over other fuels such as glucose and free fatty acids. The goals of this thesis were: 1) to determine whether endurance-adapted animals can support higher plasma lactate turnover rates than sedentary animals; and 2) to investigate the major factors involved in the regulation of plasma metabolite turnover at the whole-organism level - using lactate as a model. Lactate turnover rates were measured by bolus injection of [U-¹⁴C]lactate in skipjack tuna, Katsuwonus pelamis, and in thoroughbred racehorses, Equus caballus. In tuna, turnover rates ranged from 112 to 431 umol min⁻¹ kg⁻¹ and they were positively correlated with lactate concentration (slope = 15.1, r = 0.92). This teleost is able to support higher plasma lactate turnover rates than expected for a mammalian lower temperature, and lactate is probably an important oxidizable fuel in this species. For comparative purposes, resting turnover rates of lactate and glucose were plotted versus body mass on a log-log scale for a wide range of mammalian species. These plots were linear, and they showed the same slope as the classic body mass vs metabolic rate relationship. Thoroughbred horses are likely to have an aerobic scope of 40-fold or more. One of their main physiological adaptations to exercise is the ability to increase hematocrit by more than one and a half-fold in response to exercise. In the present study, this adjustment allowed them to reach an A-V difference in 0₂ content of more than 23 vol% during maximal exercise, a much higher value than other mammals. Their lactate turnover rate and cardiac output were measured at rest and two levels of submaximal exercise (45 and 55 V0₂ max) to investigate the relationship between cardiovascular adjustments on plasma lactate turnover rate. Cardiac output ranged from 106 to 571 ml min⁻¹ kg⁻¹, and mean lactate turnover rate from 9.3 at rest, to 75.9 umol min⁻¹ kg⁻¹ at 55% V0₂ max. In contrast with the situation found in tuna, the lactate turnover rates of thoroughbreds were not elevated compared with other mammals, showing that the metabolic adaptations of these outstanding athletes do not include the ability to sustain higher lactate fluxes than sedentary animals. In horses, the contribution of plasma lactate oxidation to V0₂ is minimal, and this substrate is not an important oxidative fuel; lipid oxidation may represent their major pathway for aerobic energy production during exercise. The ability to oxidize plasma lactate at high rates is therefore not necessarily required for the "elite" performance of endurance exercise. This study also shows that both, plasma lactate concentration and cardiac output are positively correlated with turnover rate. The correlation between cardiac output and lactate turnover rate is independent of the relationship between plasma lactate concentration and turnover rate. Plasma metabolite concentration and cardiac output can be regulators of plasma metabolite turnover rate. It is proposed that these two variables are, respectively, the fine and coarse controls for flux rate adjustments during exercise. / Science, Faculty of / Zoology, Department of / Graduate

This study examined the effects of 14 days of L-carnitine supplementation on blood and muscle lactate concentrations, and carnitine fractions, during high intensity sprint cycling exercise. Eight subjects performed three experimental trials - control I (CON I, 0 days), control II (CON II, 14 days), and L-carnitine (LCN, 28 days). Each trial consisted of a 4 min ride at 90% VO2max, followed by a rest period of 20 min, and then 5 x 1 min rides at 115% VO2max (2 min restbetween each). Following CON II, all subjects began dietary supplementation of L-carnitine for a period of 14 days (4 g/day). L-carnitine supplementation had no significant effect on either muscle carnitine or lactate concentrations following the 4 min 90% ride. Plasma total acid soluable and free carnitine concentrations were significantly higher at all time points following supplementation. Differences observed in blood hydrogen ion and lactate concentrations between CON I and CON II appear to be the result of an order effect. The data from the present investigation indicate that L-carnitine supplementation has no significant effect on blood or muscle lactate accumulation following high intensity sprint cycling exercise. / School of Physical Education

[Truncated abstract] Antimicrobial growth promoters are added to feed to prevent lactic acidosis in ruminant animals by selectively inhibiting rumen bacteria that produce lactic acid. However, recently imposed or impending bans on the use of antimicrobial growth promoters in animal production have lead to a critical need to find practical alternatives that are safe for the animal and consumer and that obtain similar production benefits. I investigated bioactive plants of Australia for their potential to prevent lactic acidosis in ruminants. The unifying hypothesis tested was that plants would be identified that selectively inhibit lactic acid-producing bacteria and consequently protect against lactic acidosis. This hypothesis was tested in a three phase process: phase 1, plant selection and collection; phase 2, a three stage protocol for screening plants and essential oils; phase 3, in vivo experiments and chemical fractionation of the most promising plant. I developed an in vitro bioassay that simulated acidosis by adding glucose to rumen fluid in Bellco tubes and incubating for 5 h (Chapter 4). The pH and gas production were used as indicators of acidosis and fermentation activity. I used this bioassay to screen ninety-five plants (dried and ground material from 79 species) and ten essential oils and included a negative control (oaten chaff) and a positive control (virginiamycin). One plant, Eremophila glabra, produced a similar pH (5.63) to the positive control (5.43) although it inhibited gas production to a moderate extent (P < 0.05). ... Seven serrulatane diterpenes were identified to be the major secondary metabolites in E. glabra. The metabolites were screened using a broth dilution and microtitre spectrophotometry method and were selective against S. bovis at between 320 and 1077 [mu]g/ mL. The serrulatanes from E. glabra were probably responsible for the activity against acidosis that I observed in vitro, because they selectively inhibited lactateproducing bacteria. It is also possible that a synergy between serrulatanes and possibly other metabolites are responsible for the activity observed in vitro. The results from my experiments support the role that bioactive plants may have to replace the antibiotics that are added to livestock feed. Australian plants were identified containing compounds that were active against the bacterial processes responsible for ruminant acidosis. To my knowledge this is the first work undertaken to identify bioactive plants of Australia for their potential to prevent acidosis. I developed in vitro screening bioassays that targeted key indicators of acidosis. These bioassays enabled me to identify 5 plants from the 104 screened that could potentially control acidosis. One of these plants in particular, E. glabra, showed a level of activity in vitro that was comparable to antibiotic protection against acidosis. The exciting in vitro results were not demonstrated in vivo but only one dose level of E. glabra was used, which was based on the in vitro work. In contrast to the in vitro system the rumen is a continuous flow system with greater complexity and it is possible that the concentration of E. glabra that I used in vivo was not optimum. This places importance on future dose response experiments to confirm the efficacy of E. glabra in vivo.

Coronavirus disease 2019 (COVID-19), an infectious respiratory disease propagated by a new virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has resulted in global healthcare crises. Emerging evidence from patients with COVID-19 suggests that endothelial cell damage plays a central role in COVID-19 pathogenesis and could be a major contributor to the severity and mortality of COVID-19. Like other infectious diseases, the pathogenesis of COVID-19 is closely associated with metabolic processes. Lactate, a potential biomarker in COVID-19, has recently been shown to mediate endothelial barrier dysfunction. In this review, we provide an overview of cardiovascular injuries and metabolic alterations caused by SARS-CoV-2 infection. We also propose that lactate plays a potential role in COVID-19-driven endothelial cell injury.