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Journal of the American Heart... Jun 2023Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular...
Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. Methods and Results Mice implanted with chronic cranial windows were trained for awake head-fixation before experiments. One-hour occlusion of the anterior middle cerebral artery branch was induced using single-vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion-fixed tissue by labeling lectin and platelet-derived growth factor receptor β. Arterial occlusion induced multiple spreading depolarizations over 1 hour associated with substantially reduced blood flow in the peri-ischemic cortex. Approximately half of the capillaries in the peri-ischemic area were no longer perfused at the 3- and 24-hour follow-up (45% [95% CI, 33%-58%] and 53% [95% CI, 39%-66%] reduction, respectively; <0.0001), which was associated with contraction of an equivalent proportion of peri-ischemic capillary pericytes. The capillaries in the peri-ischemic cortex that remained perfused showed increased point prevalence of dynamic flow stalling (0.5% [95% CI, 0.2%-0.7%] at baseline, 5.1% [95% CI, 3.2%-6.5%] and 3.2% [95% CI, 1.1%-5.3%] at 3- and 24-hour follow-up, respectively; =0.001). Whisker stimulation at the 3- and 24-hour follow-up led to reduced neurovascular coupling responses in the sensory cortex corresponding to the peri-ischemic region compared with that observed at baseline. Conclusions Arterial occlusion led to contraction of capillary pericytes and capillary flow stalling in the peri-ischemic cortex. Capillary dysfunction was associated with neurovascular uncoupling. Neurovascular coupling impairment associated with capillary dysfunction may be a mechanism that contributes to futile recanalization. Hence, the results from this study suggest a novel treatment target to improve neurological outcome after stroke.
Topics: Mice; Animals; Ischemic Stroke; Microcirculation; Brain; Stroke; Brain Ischemia; Arterial Occlusive Diseases; Cerebrovascular Circulation
PubMed: 37232244
DOI: 10.1161/JAHA.123.029527 -
Journal of the American College of... Aug 2023Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We... (Observational Study)
Observational Study
BACKGROUND
Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation.
STUDY DESIGN
A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors.
RESULTS
A total of 1,051 patients in hemorrhagic shock met all enrollment criteria. The cohort was severely injured with >70% of patients requiring massive transfusion. After propensity adjustment, no significant 4-hour mortality difference across LTOWB and component patients was found (relative risk [RR] 0.90, 95% CI 0.59 to 1.39, p = 0.64). Similarly, no adjusted mortality differences were demonstrated at 24 hours or 28 days for the enrolled cohort. When patients with an elevated prehospital probability of mortality were analyzed, LTOWB resuscitation was independently associated with a 48% lower risk of 4-hour mortality (relative risk [RR] 0.52, 95% CI 0.32 to 0.87, p = 0.01) and a 30% lower risk of 28-day mortality (RR 0.70, 95% CI 0.51 to 0.96, p = 0.03).
CONCLUSIONS
Early LTOWB resuscitation is safe but not independently associated with survival for the overall enrolled population. When patients were selected with an elevated probability of mortality based on prehospital injury characteristics, LTOWB was independently associated with a lower risk of mortality starting at 4 hours after arrival through 28 days after injury.
Topics: Humans; Prospective Studies; Blood Transfusion; Blood Component Transfusion; Hemorrhage; Resuscitation; Probability; Wounds and Injuries
PubMed: 37039365
DOI: 10.1097/XCS.0000000000000708 -
Annals of Medicine Dec 2023In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in...
BACKGROUND
In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls.
PATIENTS AND METHODS
In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status.
RESULTS
24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged.
CONCLUSIONS
Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.
Topics: Male; Humans; Female; Blood Pressure; Ischemic Stroke; Blood Pressure Monitoring, Ambulatory; Foramen Ovale, Patent; Case-Control Studies; Stroke; Hypertension
PubMed: 37086083
DOI: 10.1080/07853890.2023.2203513 -
Frontiers in Psychiatry 2023This study aims to understand the relationship between Lifetime Classic Psychedelic Use (LCPU), employment status, and weekly work hours on levels of psychological...
This study aims to understand the relationship between Lifetime Classic Psychedelic Use (LCPU), employment status, and weekly work hours on levels of psychological distress. The data used for this analysis is pooled from the National Survey of Drug Use and Health (NSDUH) from 2008-2019 and includes a sample size of 484,732 individuals. The findings suggest that LCPU and being employed are independently associated with better health. Additionally, the results indicate that psychedelic use is associated with lower distress for those who are employed, volunteer, retired, or permanently disabled. However, those who are unemployed, full-time students, or homemakers may experience higher levels of distress with psychedelic use. Interestingly, the analysis also suggests that those who use psychedelics are working longer hours per week before experiencing an increase in stress. Overall, the study suggests that psychedelics are not likely to have a negative impact on employment outcomes.
PubMed: 37398579
DOI: 10.3389/fpsyt.2023.1186541