Repeated Ischemic Preconditioning Effects on Physiological Responses to Hypoxic Exercise.

INTRODUCTION: Repeated ischemic preconditioning (IPC) can improve muscle and pulmonary oxygen on-kinetics, blood flow, and exercise efficiency, but these effects have not been investigated in severe hypoxia. The aim of the current study was to evaluate the effects of 7 d of IPC on resting and exercising muscle and cardio-pulmonary responses to severe hypoxia.METHODS: A total of 14 subjects received either: 1) 7 d of repeated lower-limb occlusion (4 × 5 min, 217 ± 30 mmHg) at limb occlusive pressure (IPC) or SHAM (4 × 5 min, 20 mmHg). Subjects were tested for resting limb blood flow, relative microvascular deoxyhemoglobin concentration ([HHB]), and pulmonary oxygen (Vo2p) responses to steady state and incremental exercise to exhaustion in hypoxia (fractional inspired O2 = 0.103), which was followed by 7 d of IPC or SHAM and retesting 72 h post-intervention.RESULTS: There were no effects of IPC on maximal oxygen consumption, time to exhaustion during the incremental test, or minute ventilation and arterial oxygen saturation. However, the IPC group had higher delta efficiency based on pooled results and lower steady state Δ[HHB] (IPC ∼24% vs. SHAM ∼6% pre to post), as well as slowing the [HHB] time constant (IPC ∼26% vs. SHAM ∼3% pre to post) and reducing the overshoot in [HHB]: Vo2 ratio during exercise onset.CONCLUSIONS: Collectively, these results demonstrate that muscle O2 efficiency and microvascular O2 distribution can be improved by repeated IPC, but there are no effects on maximal exercise capacity in severe hypoxia.Chopra K, Jeffries O, Tallent J, Heffernan S, Kilduff L, Gray A, Waldron M. Repeated ischemic preconditioning effects on physiological responses to hypoxic exercise. Aerosp Med Hum Perform. 2022; 93(1):13-21.

Caffeine, exercise physiology, and time-trial performance: no effect of ADORA2A or CYP1A2 genotypes.

The aim of this study was to investigate the influence of ADORA2A and CYP1A2 genotypes on the physiological and ergogenic effects of caffeine. Sixty-six male cyclists were screened for ADORA2A and CYP1A2 genotypes; with 40 taking part subsequently in a randomised, double-blind, placebo-controlled study. Trial 1 was used to establish the oxygen uptake-power output relationship and maximal oxygen uptake. In trials 2 and 3, participants ingested 5 mg·kg-1 of caffeine or placebo 1 h before completing a submaximal incremental cycling test, followed by a time-trial (∼30 min). Relative to placebo, caffeine led to a significant reduction in time to complete the time-trial (caffeine: 29.7 ± 1.8 min; placebo: 30.8 ± 2.3 min); but there was no effect of genotype. During submaximal exercise, caffeine reduced mean heart rate by 2.9 ± 3.7 beats·min-1, with effects dissipating as exercise intensity increased. Caffeine also significantly reduced perceived exertion by 0.5 ± 0.8, and increased blood lactate by 0.29 ± 0.42 mmol·L-1, respiratory exchange ratio by 0.013 ± 0.032, and minute ventilation by 3.1 ± 6.8 L·min-1. Nonetheless, there were no supplement × genotype interactions. In conclusion, caffeine influences physiological responses to submaximal exercise and improves time-trial performance irrespective of ADORA2A or CYP1A2 genotypes. Novelty: Caffeine affects physiological responses at rest and during submaximal exercise independent of ADORA2A or CYP1A2 genotypes. Variability in the effect of caffeine on time-trial performance is not explained by ADORA2A or CYP1A2 genotypes.

Fatal methadone intoxication in an infant.

Presented are the case history and toxicological findings of an infant fatality involving methadone. A mother found her 10-month-old infant unresponsive in a crib. The infant was taken to a hospital; however, she was cold and stiff on arrival and was pronounced dead. Few details regarding the case history were known at the time, and the autopsy findings were unremarkable. Specimens were submitted for a full toxicological analysis, including an alcohol analysis by headspace gas chromatography with flame ionization detection; a screen for drugs of abuse and several prescription drug classes using an enzyme-linked immunosorbent assay technique (ELISA); and a screen for basic compounds using gas chromatography-mass spectrometry (GC-MS). Positive findings were confirmed and quantitated using GC-MS. Methadone was detected in subclavian blood at a concentration of 0.67 mg/L. The cause of death was determined to be "methadone intoxication", and the manner of death was "homicide". A discussion of the case circumstances, the toxicology findings and methadone pharmacokinetics are presented.