ABSTRACT
The mammalian dive reflex, characterized by bradycardia and peripheral vasoconstriction, occurs in all mammals, including humans, in response to apnea. However, the dive reflex to a single, maximal, dry, dynamic apnea (DYN), and how it compares to a time-matched exercise control trial (EX) or dry static apnea (SA), has not been studied. We examined the hypotheses that, compared to EX and SA, the magnitude of the (a) cardiovascular response and (b) hematological response to DYN would be greater. Cardiovascular parameters (heart rate [HR], systolic [SBP], diastolic [DBP], and mean arterial [MAP] blood pressure) were continuously collected in twenty-three (F=6) moderate and elite freedivers, first during a maximal DYN, then during a time-matched SA and EX on a swimming ergometer in randomized order. Venous blood draws were made prior to and following each trial. The change in calculated oxygen saturation (DYN:-17±13%, EX:-2±1%, ΔSA:-2±1%;P<0.05, all comparisons) was greater during DYN compared to EX and SA. During DYN, ΔSBP (DYN:104±31mmHg, EX:38±23mmHg, SA:20±11mmHg), ΔDBP (DYN:45±12mmHg, EX:14±10mmHg, SA:15±8mmHg) and ΔMAP (DYN:65±17mmHg EX:22±13mmHg, SA:16±9mmHg) were increased compared to EX and SA, while ΔHR was greater during EX (DYN:-24±23bpm, EX:33±13bpm, SA:-1±10bpm) than either DYN or SA (P<0.0001, all comparisons). Females had greater pressor response to EX (ΔSBP:59±30mmHg, ΔDBP:24±14mmHg, ΔMAP:35±8mmHg) than males (ΔSBP:31±15mmHg, ΔDBP:11±6mmHg, ΔMAP:18±8mmHg; P<0.01, all comparisons). Together, these data indicate that DYN elicits a distinct, exaggerated cardiovascular response compared to EX or SA alone.
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Background: The chronic effects of cannabidiol (CBD) supplementation on factors that could impact the quality of life (anxiety, sleeping quality, memory, etc.) are poorly explored. Hence, the aim of this study was to establish whether chronic CBD supplementation will improve self-reported outcomes related to quality of life. Methods: In this randomized crossover trial, 64 patients with primary hypertension were assigned to receive CBD (225-450 mg) for 5 weeks followed by 5 weeks of placebo or vice versa, with a 2-week washout in-between the two. Self-reported outcomes were assessed using short form-36 (SF-36), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), memory complaint questionnaire (MAC-Q), and state-trait anxiety inventory (STAI). Results: Five-week administration of CBD, but not of placebo, resulted in improvement of ESS score (F = 6.738, p = 0.011), as well as fatigue/vitality (ΔCBD = 5.0, p < 0.001) and psychological well-being dimensions of SF-36 (ΔCBD = 7.4, p = 0.039). No overall benefit of CBD on quality of life was noted (p = 0.674). No changes were seen in total scores of MAC-Q, PSQI, or STAI (p = 0.151, p = 0.862, p = 0.702, respectively). No significant correlations were found between plasma CBD concentrations and any of the scores. Conclusions: Chronic CBD administration reduced excessive daytime sleepiness, despite the fact that no change was observed in self-reported quality of sleep. Furthermore, self-reported fatigue and psychological well-being dimensions of quality of life also improved following chronic CBD use.
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AIM: To determine the incidence of metopism in the modern and archaeological Croatian population. METHODS: A total of 800 specimens (454 modern multi-slice computed tomography [MSCT] scans and 346 dry archaeological skulls) were visually examined for metopic suture presence. The metopic suture was deemed complete when aligned nasion to bregma. RESULTS: In the overall sample, the metopic suture was observed in 36 of 800 subjects (4.5%): 19 of 424 (4.5%) men and 17 of 370 (4.6%) women. A significant difference was not observed between modern and archaeological samples (χ2=3.219, P=0.359) or between the sexes (χ2=0.006, P=0.939). The frequency of metopism varied from 3.5% in the modern population to 7.04% in the samples from the Roman period. CONCLUSION: There are no visible secular changes on metopic suture in the Croatian population through time. Some variations can be the result of differences in sample size in different time periods.
Subject(s)
Archaeology , Cranial Sutures , Humans , Croatia , Female , Male , Adult , Middle Aged , Tomography, X-Ray Computed , History, Ancient , Young AdultABSTRACT
Breath-hold diving is explained as an activity that requires enduring muscle asphyxia and acidosis, high anaerobic capacity, and the tactic of the dive. Therefore, this study aimed to construct and validate tests that will mimic anaerobic processes in the specific media of freedivers. The sample of participants included 34 Croatian freedivers (average age: 26.85 ± 4.0 years, competitive age: 3.82 ± 1.92 years, their body height: 180.14 ± 8.93 cm, and their body mass: 76.82 ± 12.41 kg). The sample of variables consists of anthropometric indices, competitive efficiency (maximal length of a dive (DYN)), and specific anaerobic capacities (100 m and 2 min tests). Newly developed tests included the swimming anaerobic sprint test (SAST) and diving anaerobic sprint test (DAST). DAST and SAST variables included the total time of the test (DAST/SAST) and the fastest interval (DASTmax/SASTmax). The results showed good reliability of the tests with high Cronbach alpha coefficients (DAST: 0.98, DASTmax: 0.97, SAST: 0.99, SASTmax: 0.91). Furthermore, pragmatic validity shows a high correlation among all variables and DAST (DYN: -0.70, 100 m: 0.66, 2 min: -0.68). High relation is also found between 100 m (0.96), 2 min (-0.94), and a moderate result for DYN (-0.43) and the SAST test. A factor analysis extracted one significant factor. The factor analysis involved DAST, SAST, DYN, 100 m, and 2 min tests regarding factor 1. After the examination of all variables, the total time of the DAST test showed the best predictive values for the performance of divers. However, both tests could be used for diagnostics and the evaluation of specific condition abilities in freediving.
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The potential therapeutic benefits of cannabidiol (CBD) require further study. Here, we report a triple-blind (participant, investigator, and outcome assessor) placebo-controlled crossover study in which 62 hypertensive volunteers were randomly assigned to receive the recently developed DehydraTECH2.0 CBD formulation or a placebo. This is the first study to have been conducted using the DehydraTECH2.0 CBD formulation over a 12-week study duration. The new formulation's long-term effects on CBD concentrations in plasma and urine, as well as its metabolites 7-hydroxy-CBD and 7-carboxy-CBD, were analyzed. The results of the plasma concentration ratio for CBD/7-OH-CBD in the third timepoint (after 5 weeks of use) were significantly higher than in the second timepoint (after 2.5 weeks of use; p = 0.043). In the same timepoints in the urine, a significantly higher concentration of 7-COOH-CBD was observed p < 0.001. Differences in CBD concentration were found between men and women. Plasma levels of CBD were still detectable 50 days after the last consumption of the CBD preparations. Significantly higher plasma CBD concentrations occurred in females compared to males, which was potentially related to greater adipose tissue. More research is needed to optimize CBD doses to consider the differential therapeutic benefits in men and women.
Subject(s)
Body Fluids , Cannabidiol , Male , Humans , Female , Cannabidiol/therapeutic use , Cross-Over Studies , Double-Blind Method , DronabinolABSTRACT
HYPER-H21-4 was a randomized crossover trial that aimed to determine if cannabidiol (CBD), a non-intoxicating constituent of cannabis, has relevant effects on blood pressure and vascular health in patients with essential hypertension. In the present sub-analysis, we aimed to elucidate whether serum urotensin-II concentrations may reflect hemodynamic changes caused by oral supplementation with CBD. The sub-analysis of this randomized crossover study included 51 patients with mild to moderate hypertension that received CBD for five weeks, and placebo for five weeks. After five weeks of oral CBD supplementation, but not placebo, serum urotensin concentrations reduced significantly in comparison to baseline (3.31 ± 1.46 ng/mL vs. 2.08 ± 0.91 ng/mL, P < 0.001). Following the five weeks of CBD supplementation, the magnitude of reduction in 24 h mean arterial pressure (MAP) positively correlated with the extent of change in serum urotensin levels (r = 0.412, P = 0.003); this association was independent of age, sex, BMI and previous antihypertensive treatment (ß ± standard error, 0.023 ± 0.009, P = 0.009). No correlation was present in the placebo condition (r = -0.132, P = 0.357). In summary, potent vasoconstrictor urotensin seems to be implicated in CBD-mediated reduction in blood pressure, although further research is needed to confirm these notions.
Subject(s)
Cannabidiol , Urotensins , Humans , Blood Pressure , Cross-Over Studies , Blood Pressure Monitoring, Ambulatory , Essential Hypertension/drug therapy , Essential Hypertension/chemically induced , Dietary Supplements , Double-Blind MethodABSTRACT
Background: Recent data indicate that cannabidiol (CBD), a nonintoxicating constituent of cannabis, is involved in several aspects of cardiovascular regulation, including blood pressure (BP). However, the impact of chronic CBD administration on 24-h BP and vascular health has not been previously examined in patients with hypertension. The primary aim of this randomized, triple-blind, placebo-controlled, and crossover study was to examine the influence of chronic CBD on 24-h ambulatory BP and arterial stiffness in hypertensive patients. Methods: Seventy patients with mild or moderate primary hypertension, who were untreated or receiving standard of care therapy, were randomly assigned to receive either 5 weeks of oral CBD or placebo-matched controls. Following a >2-week washout period, patients were crossed over to alternate therapy. The primary outcome of the study was dynamic in 24-h ambulatory BP and was assessed using two-way repeated measure analysis of variance. Results: Administration of CBD reduced average 24 h mean, systolic, and diastolic BP after 2.5 weeks (-3.22±0.90 mmHg [95% confidence interval -1.01 to -5.44 mmHg], -4.76±1.24 mmHg [-1.72 to -7.80 mmHg], and -2.25±0.80 mmHg [-0.30 to -6.01 mmHg], respectively (all p<0.05); however, these values largely remained stable following the uptitration of CBD dosing. There were no changes in liver enzymes or serious adverse events (AEs). There was no significant difference in pulse wave velocity (group×factor interaction: F=1.50, p=0.226) at different time points, regardless of the intervention arm. Conclusions: In conclusion, chronic administration of CBD reduces ambulatory BP in those with untreated and treated hypertension. In addition, lack of serious AEs implies safety and tolerability of the above-noted CBD formulation. ClinicalTrials.gov ID: NCT05346562, Registered April 6th 2022.
ABSTRACT
Data concerning the effects of cannabidiol (CBD) on blood pressure (BP) is controversial. HYPER-H21-4 was a randomized, placebo-controlled, crossover trial which sought to elucidate if 5-week administration of CBD will reduce BP in hypertensive patients. In the substudy of this trial, we aimed to establish the mechanistic background of CBD-induced BP reduction. Specifically, we explored the dynamic of catestatin, a sympathoinhibitory peptide implicated in the pathophysiology of hypertension. In the present analysis, 54 patients with Grade 1 hypertension were included. 5-week administration of CBD but not placebo reduced serum catestatin concentration in comparison to baseline (13.50 [10.85-19.05] vs. 9.65 [6.37-12.26] ng/mL, p < 0.001). Serum catestatin levels at the start of the treatment period demonstrated a negative correlation with the extent of reduction in mean arterial pressure (r = -0.474, p < 0.001). Moreover, the extent of change in catestatin serum levels showed a strong correlation with the extent of mean arterial pressure reduction (r = 0.712, p < 0.001). Overall, the results of the present study imply that the antihypertensive effects of CBD may be explained by its interaction with the sympatho-chromaffin system, although further research is warranted.
Subject(s)
Cannabidiol , Hypertension , Humans , Arterial Pressure , Hypertension/drug therapy , Dietary Supplements , Blood Pressure , Double-Blind MethodABSTRACT
It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM.
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Due to cannabidiol's health benefits and absence of serious side effects, its use is constantly growing. This is a survey-based cross-sectional study that was conducted to determine Croatian pharmacists', physicians', and students' knowledge and attitudes about cannabidiol (CBD). Two questionnaires were created, one for students and the other for physicians and pharmacists. Our participants (in total 874: 473 students and 401 physicians and pharmacists) generally had positive attitudes towards CBD therapy as approximately 60% of them believe that CBD treatment is generally efficacious. Participants had positive attitudes toward the therapeutic value of CBD, especially pharmacists and pharmacy students (63.8% and 72.2%, respectively). Pharmacists were significantly more convinced that CBD could reduce the use of opioids prescribed for chronic pain (p < 0.05). Only 17.5% of students had read scientific papers about CBD, compared to a significantly higher percentage of physicians and pharmacists (43.0% and 47.8%, respectively) (p < 0.05). This study revealed a gap in knowledge regarding CBD, since 89.3% of pharmacists and physicians, as well as 84.8% of students, believe they need more education about CBD. We conclude that it is important to improve the educational curricula so that medical professionals can recommend CBD use to their patients when needed.
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Accumulating data suggests that catestatin, an eclectic neuroendocrine peptide, is involved in the pathophysiology of primary hypertension (PH). Nevertheless, clinical studies concerning its role in PH are still scarce. Therefore, in the present study, we aimed to explore an association between serum catestatin levels, ambulatory blood pressure (BP) and arterial stiffness in patients with PH and healthy controls. In this single-center study, 72 patients aged 40−70 diagnosed with PH, and 72 healthy controls were included. In patients with PH, serum catestatin concentrations were significantly higher in comparison to the healthy controls (29.70 (19.33−49.48) ng/mL vs. 5.83 (4.21−8.29) ng/mL, p < 0.001). Untreated patients had significantly higher serum catestatin than patients treated with antihypertensive drugs (41.61 (22.85−63.83) ng/mL vs. 24.77 (16.41−40.21) ng/mL, p = 0.005). Multiple linear regression analysis showed that serum catestatin levels retained a significant association with mean arterial pressure (ß ± standard error, 0.8123 ± 0.3037, p < 0.009) after model adjustments for age, sex and body mass index. Finally, catestatin levels positively correlated with pulse wave velocity (r = 0.496, p < 0.001) and central augmentation index (r = 0.441, p < 0.001), but not with peripheral resistance. In summary, increased serum catestatin concentration in PH, predominantly in the untreated subgroup, and its association with ambulatory BP and arterial stiffness address the role of this peptide in PH.
Subject(s)
Hypertension , Vascular Stiffness , Antihypertensive Agents/therapeutic use , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Chromogranin A , Humans , Hypertension/drug therapy , Peptide Fragments , Pulse Wave AnalysisABSTRACT
Accumulating data from both human and animal studies suggest that cannabidiol (CBD) may be associated with improved cardiovascular function, markedly with regard to reduction in blood pressure and improved endothelial function. However, there is a lack of randomized studies to support these notions, especially in at-risk populations. The principal aim of this randomized, placebo-controlled, and crossover study is to examine the influence of chronic CBD administration on 24-h blood pressure in individuals with mild or moderate hypertension who are either untreated or receiving standard care therapy. The secondary aims of the study are to determine the safety and tolerability of 5 weeks of CBD administration, and to quantify the effect on arterial stiffness, CBD and vascular health biomarkers, inflammation, heart rate variability, and psychological well-being in both groups of patients. The present single-center study is designed as a triple blind (Participant, Investigator, Outcomes Assessor), placebo-controlled, crossover pilot study in which 70 hypertensive volunteers (aged 40-70 years) will receive DehydraTECH2.0 CBD formulation and placebo in a crossover manner. We believe that comprehensive analyses that will be performed in the present trial will decipher whether CBD is in fact a safe and valuable supplement for patients with treated and untreated hypertension.