COVID-19 Rehabilitation With Herbal Medicine and Cardiorespiratory Exercise: Protocol for a Clinical Study.

BACKGROUND: Recent studies have revealed that many discharged patients with COVID-19 experience ongoing symptoms months later. Rehabilitation interventions can help address the consequences of COVID-19, including medical, physical, cognitive, and psychological problems. To our knowledge, no studies have investigated the effects of rehabilitation following discharge from hospital for patients with COVID-19. OBJECTIVE: The specific aims of this project are to investigate the effects of a 12-week exercise program on pulmonary fibrosis in patients recovering from COVID-19. A further aim will be to examine how Chinese herbal medicines as well as the gut microbiome and its metabolites regulate immune function and possibly autoimmune deficiency in the rehabilitation process. METHODS: In this triple-blinded, randomized, parallel-group, controlled clinical trial, we will recruit adult patients with COVID-19 who have been discharged from hospital in Hong Kong and are experiencing impaired lung function and pulmonary function. A total of 172 eligible patients will be randomized into four equal groups: (1) cardiorespiratory exercise plus Chinese herbal medicines group, (2) cardiorespiratory exercise only group, (3) Chinese herbal medicines only group, and (4) waiting list group (in which participants will receive Chinese herbal medicines after 24 weeks). These treatments will be administered for 12 weeks, with a 12-week follow-up period. Primary outcomes include dyspnea, fatigue, lung function, pulmonary function, blood oxygen levels, immune function, blood coagulation, and related blood biochemistry. Measurements will be recorded prior to initiating the above treatments and repeated at the 13th and 25th weeks of the study. The primary analysis is aimed at comparing the outcomes between groups throughout the study period with an α level of .05 (two-tailed). RESULTS: The trial has been approved by the university ethics committee following the Declaration of Helsinki (approval number: REC/19-20/0504) in 2020. The trial has been recruiting patients. The data collection will be completed in 24 months, from January 1, 2021, to December 31, 2022. CONCLUSIONS: Given that COVID-19 and its sequelae would persist in human populations, important findings from this study would provide valuable insights into the mechanisms and processes of COVID-19 rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04572360; https://clinicaltrials.gov/ct2/show/NCT04572360. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25556.

Redox-regulation of haemostasis in hypoxic exercising humans: a randomised double-blind placebo-controlled antioxidant study.

KEY POINTS: In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation. Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation. Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis. ABSTRACT: In vitro evidence suggests that blood coagulation is activated by increased oxidative stress although the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise. Healthy males were randomly assigned double-blind to either an antioxidant (n = 20) or placebo group (n = 16). The antioxidant group ingested two capsules/day that each contained 500 mg of l-ascorbic acid and 450 international units (IU) of dl-α-tocopherol acetate for 8 weeks. The placebo group ingested capsules of identical external appearance, taste and smell (cellulose). Both groups were subsequently exposed to acute hypoxia and maximal physical exercise with venous blood sampled pre-supplementation (normoxia), post-supplementation at rest (normoxia and hypoxia) and following maximal exercise (hypoxia). Systemic free radical formation (electron paramagnetic resonance spectroscopic detection of the ascorbate radical (A•- )) increased during hypoxia (15,152 ± 1193 AU vs. 14,076 ± 810 AU at rest, P < 0.05) and was further compounded by exercise (16,569 ± 1616 AU vs. rest, P < 0.05), responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation as measured by thrombin-antithrombin complex, at rest in normoxia (28.7 ± 6.4 vs. 4.3 ± 0.2 µg mL-1 pre-intervention, P < 0.05) and was restored but only in the face of prevailing oxidation. Collectively, these findings are the first to suggest that human free radical formation likely reflects an adaptive response that serves to maintain vascular haemostasis.

An elevated systolic blood pressure response at 8 minutes in full contact exercise may identify hypertensive subjects.

The aim of this study was to identify hypertension (HT) in karate competitors (KCs) in high intensity exercise. Values were compared with an exercise control group (EC). The 84 subjects were randomly divided into two groups: KC and EC. Resting blood pressure (BP) was measured the day before and immediately precompetition. A further three measurements were taken postexercise for all subjects at 1-, 2-, and 8- minute intervals. At rest, day one, mean BP of KC was 134/84 ± 3/2 mmHg vs. EC, 124/72 ± 1/2 mmHg and on day 2, was 141/79 ± 3/2 mmHg vs. EC, 125/72 ± 1/2 mmHg, respectively. Eight minutes postcompetition, BP of KCs was 140/77 ± 2/1 mmHg vs. EC 135/75 ± 2/1 mmHg. High blood pressure (HBP) was recorded in 60.5% of KCs on day 2, and essential HT that required medical therapy was subsequently diagnosed in 5% of KCs. Five percent of EC also had HBP, but subsequent medical examination reported normal values.

Vitamin C prophylaxis promotes oxidative lipid damage during surgical ischemia-reperfusion.

Reactive oxygen species (ROS) have been implicated in the cellular membrane damage and postoperative morbidity associated with obligatory ischemia-reperfusion (I-R) during vascular surgery. Thus, a clinical study was undertaken to evaluate the effects of ascorbate prophylaxis on ROS exchange kinetics in 22 patients scheduled for elective abdominal aortic aneurysm (AAA) or infra-inguinal bypass (IIB) repair. Patients were assigned double-blind to receive intravenous sodium ascorbate (2 g vitamin C, n=10) or placebo (0.9% saline, n=12) administered 2 h prior to surgery. Blood samples were obtained from the arterial and venous circulation proximal to the respective sites of surgical repair (local) and from an antecubital vein (peripheral) during cross-clamping (ischemia) and within 60 s of clamp release (reperfusion). Ascorbate supplementation increased the venoarterial concentration difference (v-adiff) of lipid hydroperoxides (LH), interleukin (IL)-6 and vascular endothelial growth factor (VEGF) protein during ischemia. This increased the peripheral concentration of LH, total creatine phosphokinase (CPK), and VEGF protein during reperfusion (P<0.05 vs placebo). Electron paramagnetic resonance (EPR) spectroscopy confirmed that free iron was available for oxidative catalysis in the local ischemic venous blood of supplemented patients. An increased concentration of the ascorbate radical (A.-) and alpha-phenyl-tert-butylnitrone (PBN) adducts assigned as lipid-derived alkoxyl (LO.) and alkyl (LC.) species were also detected in the peripheral blood of supplemented patients during reperfusion (P<0.05 vs ischemia). In conclusion, these findings suggest that ascorbate prophylaxis may have promoted iron-induced oxidative lipid damage via a Fenton-type reaction initiated during the ischemic phase of surgery. The subsequent release of LH into the systemic circulation may have catalyzed formation of second-generation radicals implicated in the regulation of vascular permeability and angiogenesis.