Changes In Systemic Blood Pressure Research Articles

The role of neuroendothelial cells in aging-related vascular cognitive impairment

Vascular cognitive impairment (VCI) is a growing health problem in many developed countries due to aging of its population. Aging-induced impairment of neurovascular coupling (NVC) responses and brain microvascular rarefaction have been implicated as major driving mechanisms in age-related cognitive decline. One of the cellular hallmarks of NVC involve the release of vasodilator nitric oxide (NO) by endothelial cells in response to mediators released from activated neurons. Recent studies from our group identified and characterized a novel, minority subtype of scattered ECs with endothelial and neuronal characteristics, hence the name neuroendothelial cell (NECs). NECs present a well-defined arteriovenous zonal localization exclusively in small resistance arterioles with the highest density in the brain followed by the kidney. Intravital multiphoton microscopy (MPM) of intact brain arterioles in vivo suggest that NECs play an important role in regulating blood flow to the brain and able to detect changes in systemic blood pressure, hypoxia and perhaps other metabolic changes in the local microenvironment. Our central hypothesis is that NECs are novel key players in blood flow autoregulation, vascular control of organ functions in both short-term (hemodynamics) and long-term (angiogenesis, tissue regeneration). We further hypothesize that the decrease in NEC density and function in aged subjects is a major player in the development of age-related cerebral microvascular pathologies and that augmenting NEC number and function in aged animals will provide therapeutic benefit. This study used a NEC specific comprehensive research toolbox including NEC-GFP transgenic mouse models and high-resolution single-cell based transcriptome analysis to establish the NEC specific molecular atlas in young adult (3 month of age) and aged (2 years of age) animals. Furthermore, transgenic animal models combined with serial intravital imaging of the same tissue volume over consecutive days was used to study changes in vascular endothelial cell composition in response to NEC stimuli in young adult and aged mice. Cell fate tracking studies of the Nos1-lineage combined with Nos1 immunostaining revealed that NECs represent a permanent cell type with terminal neuronal differentiation. Importantly, NEC density is reduced with aging in all organs including the brain. High resolution single-cell based transcriptome analysis of 100K endothelial cells isolated from mouse brain demonstrated that, in contrast to other ECs, NECs highly express several traditional (e.g., Nos1, Angpt1, Egfl8) and novel (e.g., Cytl1, MGP, Gkn3) tissue trophic factors that are known to play important roles in acute hemodynamic responses including NO mediated functional hyperemia, and in chronic settings in angiogenesis, aging, vascular (dys)function, and chronic vascular diseases. Furthermore, the expression of many of these factors were significantly reduced in NECs isolated from aged animals. In conclusion, the newly discovered NEC-specific molecular and signaling mechanisms may play a role in the age-related decrease in NVC capacity and microvascular rarefaction and may be targeted for therapeutic benefits in age related VCI. American Society of Nephrology Carl W. Gottschalk Research Scholar Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebral Autoregulation-guided Management of Adult and Pediatric Traumatic Brain Injury.

Cerebral autoregulation (CA) plays a vital role in maintaining cerebral blood flow in response to changes in systemic blood pressure. Impairment of CA following traumatic brain injury (TBI) may exacerbate the injury, potentially impacting patient outcomes. This focused review addresses 4 key questions regarding the measurement, natural history of CA after TBI, and potential clinical implications of CA status and CA-guided management in adults and children with TBI. We examine the feasibility and safety of CA assessment, its association with clinical outcomes, and the potential for reversing deranged CA following TBI. Finally, we discuss how the knowledge of CA status may affect TBI management and outcomes.

Lateral position does not cause an interhemicerebral difference of cerebral hemodynamic in healthy adult volunteers

Cerebral perfusion is maintained at a consistent value irrespective of changes in systemic blood pressure or disease-induced changes in general physical condition. This regulatory mechanism is effective despite postural changes, working even during changes in posture, such as those from sitting to standing or from the head-down to the head-up position. However, no study has addressed changes in perfusion separately in the left and right cerebral hemispheres, and there has been no specific investigation of the effect of the lateral decubitus position on perfusion in each hemisphere. Surgery, particularly respiratory surgery, is often performed with the patient in the lateral decubitus position, and since intraoperative anesthesia may also have an effect, it is important to ascertain the effect of the lateral decubitus position on perfusion in the left and right cerebral hemispheres in the absence of anesthesia. The effects of the lateral decubitus position on heart rate, blood pressure, and hemodynamic in the left and right cerebral hemispheres assessed by regional saturation of oxygen measured by near-infrared spectroscopy were investigated in healthy adult volunteers. Although the lateral decubitus position causes systemic circulatory changes, it may not cause any difference in hemodynamic between the left and right cerebral hemispheres.

Sex differences in middle cerebral artery reactivity and hemodynamics in 6-month-old Sprague-Dawley rats independent from systemic arterial stiffness or blood pressure

Cerebrovascular disease (CVD) is a major risk factor for developing cognitive impairment. Young women are protected against CVD compared with older women or men, however the underlying mechanisms are not well understood. Greater peripheral arterial stiffness has been linked to increased cerebral flow pulsatility and cognitive impairment. In this study we determined whether sex differences in middle cerebral artery (MCA) reactivity are associated with changes in cerebral [MCA, intracranial internal carotid artery (ICA)] or systemic [common carotid artery (CCA), thoracic aorta (TAo)] arterial resistance and stiffness in six month-old Sprague-Dawley (SD) rats. No differences in systolic or diastolic blood pressures measured by tail-cuff method were observed between sexes. Heart rate was higher in the female versus male SD (438±9 vs. 343±10 bpm, p<0.05, n=8-12). The pulsatility (PI) and resistance indexes (RI) of left MCA and left intracranial ICA were calculated as follows: PI=(Peak systolic velocity (Vs)-End-diastolic velocity (Vd))/Vmean, or RI=(Vs-Vd)/Vs (Vevo LAZR, FUJIFILM VisualSonics). Left MCA PI and RI indexes were lower in the female versus male SD (PI: 0.75±0.09 vs. 1.17±0.11; RI: 0.49±0.04 vs. 0.63±0.03, all p<0.05; n=7-8), while no differences in left ICA blood flow (n=4-9) or resistance (n=7-10) were observed between sexes. There were no differences in arterial stiffness of TAo or left CCA evaluated by pulse wave velocity (PWV) measurements. To investigate vascular reactivity, left MCA segments were isolated and mounted on a wire Multi Myograph (DMT-USA). Data were acquired and analyzed with Powerlab 8 and LabChart v8 (ADInstruments). Female left MCA had lower contraction to potassium (K+: 0.6±0.1 vs. 1±0.2 mN/mm, p<0.05), but similar maximal contraction (109±10 vs. 116±6 %KMAX, p>0.05) and sensitivity (7.3±0.2 vs. 7.2±0.2, p>0.05) to thromboxane A2 receptor agonist U46619. Pre-incubation with indomethacin lowered maximal response (97±5 vs. 116±6 %KMAX, p<0.05) and sensitivity (6.8±0.1 vs. 7.2±0.2, p<0.05) to U46619 in male MCA, with no effect in female MCA (Male: 109±9 vs. 113±7 %KMAX; Female: 7.3±0.2 vs. 7.3±0.2). MCA collagen deposition (by trichrome staining) was similar between sexes, however eNOS immunoreactivity tended to increase in the female versus male MCA (7.3±2 vs. 1.2±0.6; n=3-4, p=0.07). No sex differences in MCA COX-2 expression were found. In summary, lower PI and RI of MCA in 6-month-old females suggests decreased cerebrovascular resistance compared with age-matched male SD. Increased eNOS expression may contribute to the lower contraction observed in female MCA, whereas vasoconstrictor prostaglandins appear to have a greater role in male versus female MCA. Our results demonstrate sex differences in MCA vascular reactivity associated with a protective functional profile of MCA in 6-month-old female versus male SD rats independent from changes in systemic arterial stiffness or blood pressure. Studies were supported by the WFUSM CVSC Pilot Award and NIH 5R01HL155420. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of urgent blood pressure reduction on left atrial strain in patients with hypertensive attack : Blood pressure lowering affects LA strain.

Left atrial (LA) strain is a robust measure of LA function and is a useful parameter to assess left ventricular filling pressure. While initially considered as a "load-independent" parameter of LA function, later studies have found that acute changes in LA preload may affect LA reservoir and contractile strains. Acute alterations in blood pressure (BP) induces a change in left ventricular (LV) filling pressure without imposing a volume load, thus providing an opportunity to assess the effects of the change in LA afterload on LA mechanics. This study aims to understand the effect of acute BP changes on LA strain. A total of 40 patients admitted to the emergency department with hypertensive urgency were included. All patients underwent a comprehensive echocardiographic examination including measurement of LA reservoir, conduit and contractile strains. A repeat set of measurements were obtained after BP lowering. Average drop in mean BP following intervention was 18.1 ± 5.4%. LV end-systolic and end-diastolic volumes, as well as maximum and minimum LA volumes were decreased significantly after BP reduction. The absolute increases in reservoir and contractile strains were 2.3 ± 4.7% (7.9% ± 13.8% relative to baseline) and 2.5 ± 3.3% (13.5 ± 19.0% relative to baseline), respectively, with both changes being statistically significant (p = 0.003 for reservoir and p < 0.001 for contractile strains). There were no significant changes in conduit strain after BP intervention (p = 0.79). The change in both LA reservoir and contractile strains were more evident in those with a previous diagnosis of hypertension and those with a smaller degree of change in mean BP after intervention. In patients with an acute hypertension, lowering BP leads to an acute improvement in LA reservoir and contractile strains. Thus, acute changes in systemic BP should be considered when LA mechanics are evaluated.

Factors affecting intradialytic hepatic oxygenation: Associations between ultrafiltration rate and changes in systemic blood pressure

Hepato-splanchnic circulation influences the oxygenation of abdominal organs and is important in preventing a reduction in intradialytic blood volume. However, the association between changes in intradialytic hepato-splanchnic circulation and clinical factors remain unknown. We enrolled 91 hemodialysis (HD) patients (20 with intradialytic hypotension (IDH) and 71 without IDH). During HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting hepato-splanchnic circulation and oxygenation, was monitored. Changes in hepatic rSO2 at the lowest systolic blood pressure (BP) during HD were analyzed to identify associations with clinical factors. Hepatic rSO2 levels were 55.8 ± 15.3% before HD and 53.8 ± 14.9% at the lowest systolic BP; therefore, % changes in hepatic rSO2 were -2.7 ± 11.3%. These values were significantly lower in patients with IDH than in those without IDH (-13.8 ± 9.3% vs 0.4 ± 9.8%, p < 0.001). Multivariable regression analysis showed that % changes in hepatic rSO2 were independently associated with % changes in systolic BP (standardized coefficient: 0.416) and ultrafiltration rate (-0.206). Furthermore, % changes in mean BP (0.304) were identified as affecting % changes in hepatic rSO2 instead of those in systolic BP. Changes in intradialytic hepatic oxygenation is associated with ultrafiltration rate and changes in systemic BP. Further studies are required to clarify the directionality of the association between changes in hepatic oxygenation and changes in systemic BP during HD.

Diurnal variation of pulmonary artery pressure in ambulatory heart failure patients

Background There is limited information on diurnal variation in pulmonary artery pressures (PAP) in ambulatory heart failure (HF) patients. We aimed to study the variation in morning and night-time PAP in HF patients with an implanted CardioMEMS® sensor. Methods In this prospective, single centre study we enrolled patients who had a cardioMEMS sensor and consented to participate (End stage renal disease and recent hospitalisation for acute HF were exclusions). Subjects were asked to transmit PAP and non-invasive blood pressure information in morning and at night-time for 7 consecutive days. Categorical and continuous variables were reported as percentages and mean ± SD respectively. Repeated measure ANOVA was used to compare the diurnal changes in PAP among different subgroups. Pierson correlation coefficient was performed to assess correlation between diurnal variation of PAP and left ventricular ejection fraction Results Thirty subjects were included in analysis. There was a significant nocturnal rise in PASP and mPAP compared to morning readings (+2.59 mmHg, p = 0.003 and +1.24 mmHg with p = 0.02 respectively) while night-time PADP did not change significantly (+0.48 mmHg, p = 0.18) without significant change in systemic blood pressure or pulse rate. Conclusion The described diurnal changes in PAP should be considered when managing ambulatory HF patients based on these readings. PADP can be used reliably without concern for the time of day the readings were recorded. Highlights There is a diurnal variation in PAP in ambulatory heart failure patients Pulmonary artery systolic and mean pulmonary artery pressures are higher at night-time than in morning. Pulmonary artery diastolic pressures do not vary significantly with time of day. These findings should inform clinical decisions in management of these patients about the time of the day readings are taken

THE EFFECT OF RENAL DENERVATION ON PERIPHERAL AND CEREBRAL VASOREACTIVITY IN PATIENTS WITH RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Objective: Vasoreactivity is fundamental mechanisms of the control of tissue perfusion, that distributes supply of blood flow according to metabolic needs and protecting the organs from changes in systemic blood pressure (BP). The presence of vascular risk factors such as hypertension (HTN) and diabetes mellitus (DM) impairs vasoreactivity, leading to an increased risk of stroke and myocardial infarction. The aim of this study was to evaluate the effect of renal denervation (RDN) on peripheral and cerebral vasoreactivity in patients with resistant HTN (RHTN) and type 2 DM at 6 month after procedure. Design and method: The assessment of the effect of RDN on peripheral vasoreactivity was performed in 31 patients with RHTN and type 2 DM, participants in single-arm prospective interventional studies (protocol numbers NCT02667912 and NCT01499810 at ClinicalTrials.gov) (mean age 59.1 ± 8.6 years, mean office (systolic/diastolic) BP (SBP/DBP) 167.7 ± 18.5/86.7 ± 16.6 mmHg, HbA1c 7.8 ± 1.8%, 22 (68%) men), of which cerebral vasoreactivity was evaluated in 21 patients with good visualization. All patients underwent ambulatory 24-hour BP. Flow-mediated dilation (FMD) of brachial artery and vasoreactivity of middle cerebral artery (MCA) during both breath-holding and hyperventilation testes were measured by high-resolution ultrasound at baseline and 6 month follow-up. Results: RDN led to a decrease in mean 24-hour BP (SBP/DBP) (from 157.5 ± 18.2/76.5 ± 9.7 to 147.8 ± 15.6/71 ± 12.8mmHg, p = 0.049/0.096) without significant changes in number of antihypertensive drugs (from 4.7 ± 0.9 to 4.5 ± 1.2, p = 0.52). There were increase in FMD (from 3.4 ± 5.5 to 7.7 ± 4.2%, p = 0.004), but vasoreactivity of MCA to hyperventilation and breath-holding test was not changed. The degree of improvement of FMD not correlated with the baseline BP and its change after RDN. Conclusions: According to our results, RDN in diabetic patients with RHTN improved peripheral vasoreactivity regardless of the degree of BP reduction, but did not significantly change cerebral vasoreactivity at 6 month follow up.

Arterial Compliance and Continuous-Flow Left Ventricular Assist Device Pump Function.

Durable continuous-flow left ventricular assist devices (cfLVADs) demonstrate superior survival, cardiac functional status, and overall quality of life compared to medical therapy alone in advanced heart failure. Previous studies have not considered the impact arterial compliance may have on pump performance or developed arterial pressure. This study assessed the impact of alterations in arterial compliance, preload, and afterload on continuous-flow pump function and measured hemodynamics using an in-vitro pulsatile mock circulatory loop. Decreased arterial compliance was associated with a significant increase in arterial pressure pulsatility which was not evident in the flow pulsatility, as displayed in pump flow waveforms. There were marked changes in the pump flow waveforms due to the significant alteration in the aortoventricular gradient during diastole according to the changes in compliance. This study demonstrates that changes in systemic blood pressure, afterload, and left ventricular contractility each significantly affects the flow waveform. The association of hypertension with lower aortic compliance results in markedly decreased diastolic flow rates which may be important in contributing to a greater risk of adverse events under cfLVAD support.

Gastrocnemius Muscle Contraction and Its Role in Orthostatic Anti-Gravity Adjustment – The Effects of Body Mass Index

BACKGROUND: Obesity is a global concern with severe detrimental health and economic effect. Body mass index (BMI) is an inexpensive, non-invasive indicator for different diseases, and associated with abnormal weight. AIM: The aim of the study was to investigate the relationship between BMI and the contraction of gastrocnemius muscle (GM) and its possible role in peripheral muscle pump activity and pathogenesis of orthostatic intolerance. METHODS: One hundred and four volunteers (63 women and 41 men, mean age 39 ± 14 years) were divided into three subgroups according to their BMI values (with normal weight, overweight, and obesity). Changes in the transverse diameter and pennation angle of GM at rest and during maximal active plantar flexion (MAPF) were measured with multimodal ultrasound imaging. An active orthostatic test was performed and changes in systemic blood pressure and heart rate in supine position and active standing on the 1st, 5th, and 10th min were monitored. The results were statistically processed with alternative, variational, and correlational analysis. RESULTS: Patients with abnormal BMI were significantly older and had higher anthropometrical parameters compared to the subgroup with normal weight. They showed a significantly larger diameter and pennation angles at rest and during maximal active plantar flexion of GM bilaterally, which was more pronounced for the dominant right leg. However, the amount of changes in the GM diameter and pennation angles was similar in the different subgroups. CONCLUSION: The study showed that BMI affects predominantly the initial values of GM parameters at rest and MAPF without influence on its antigravity contractility associated with active straightening.

The effect of systemic and topical ophthalmic medications on choroidal thickness: A review.

The choroid plays an important role in various ocular pathologies and retinal blood supply. There is a knowledge gap on how the choroid is affected by systemic and topical medications. Systemic medications that affect microvasculature elsewhere in the body can also affect the microvasculature of the choroid. This review summarizes current knowledge on associations between systemic and topical medications and changes in choroidal thickness (CT). This review included 71 studies on mydriatics/cycloplegics, intraocular pressure (IOP)-lowering therapies, antihypertensives, adrenergic antagonists, statins, corticosteroids, hydroxychloroquine, isotretinoin, hormonal contraceptives, phosphodiesterase inhibitors, antipsychotics, antineoplastic agents, ethanol, caffeine and nicotine. IOP-lowering therapies, atropine eye drops, and systemic administration of β blockers and ethanol are associated with a significant increase in CT. Cyclopentolate and phenylephrine are associated with a CT reduction. Systemic medications that decrease CT include caffeine and nicotine. Tropicamide, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, corticosteroids, hydroxychloroquine and hormonal contraceptives have mixed findings. CT increase associated with IOP-lowering therapies is possibly achieved by enhancing aqueous humour flow to the choroid thus elevating choroidal blood flow and thickness. CT changes appear to be independent from systemic blood pressure changes, suggesting that a significant association with an antihypertensive could be due to an idiosyncratic drug property. Statins and candesartan decrease macrophage accumulation and intercellular adhesion molecule 1 expression in the choroid. The choroid and its response to various disease processes and systemic medication can be further investigated to improve patient care, particularly in patients with choroid and retina pathologies.

Risk factors for intradialytic decline in cerebral perfusion and impaired cerebral autoregulation in adults on hemodialysis.

Hemodialysis (HD) patients have significant burden of cerebral ischemic pathology noted on brain imaging. These ischemic type lesions maybe due to cerebral hypoperfusion that may be occurring during blood pressure (BP) fluctuations commonly noted during HD sessions. We evaluated changes in cerebral perfusion and measured an index of cerebral autoregulation (CA index) during HD to identify potential risk factors for intradialytic decline in cerebral perfusion and impaired cerebral autoregulation. In this cross-sectional study, we included HD patients age 50 years or older receiving conventional in-center HD. We measured cerebral perfusion during HD, using cerebral oximetry, and calculated the correlation between cerebral perfusion and BP during HD as an index of CA. We measured the association between potential risk factors for intradialytic decline in cerebral perfusion and CA index. We included 32 participants and 118 HD sessions in our analysis. The mean ± SD decline in cerebral oxygen saturation during HD was 6.5% ± 2.9% with a relative decline from baseline values of 9.2% ± 4.4%. Greater drop in systolic BP (SBP) during HD was associated with decline in cerebral oxygen saturation, p=0.02. Impaired CA index was noted in 37.3% of HD sessions. Having diabetes and >20 mmHg drop in SBP during HD were associated with increased (worse) CA index with an increase of 0.24 95%CI [0.06, 0.41] for diabetes and increase of 0.43 95%CI [0.27, 0.56] for a >20 mmHg drop in SBP during HD. Cerebral perfusion can decline during HD and is associated with changes in systemic BP. This may be due to impaired cerebral autoregulation in HD patients. Risk factors for worse CA index include diabetes and >20 mmHg drop in SBP during HD. This study highlights the risk of intradialytic decline in cerebral perfusion and impaired cerebral autoregulation in HD patients.

Study of 24 Hours/2 day Monitoring of Blood Pressure in Subjects with Traumatic Paraplegia

Cardiovascular dysfunction and cognitive decline are more common in traumatic spinal cord injury (SCI). Most people with a cervical or upper-thoracic SCI usually experience conditions called orthostatic hypotension and autonomic dysreflexia, which are described by the serious changes in systemic blood pressure. To evaluate baseline heart rate (HR), baseline blood pressure (BP) and ABPM monitoring in traumatic paraplegia patients. In this study, total 36 diagnosed of paraplegia patients was based on Asia Impairment Scale (AIS), paralysed by RTA, or fall from height within 7 days of injury were included in this study. The blood pressure was monitoring for 24 hour/2 day and repeated after 12th day of first monitoring. Ambulatory blood pressure was monitored by ABPM machine at HALF hourly from 6 am – 10 pm and one hourly from 10 pm – 6 am. All the continuous variables were compared by t- test. The night dipping (Systole) and morning surge (Systole) were significantly lower at 12th days as compared to within 7 Days (p=0.002). Whereas the diurnal Index (Diastole) and diurnal Index (MAP) were comparable in between within 7 days and 12th days. The mean SBP max and SBP min were significantly lower at 12th day as compared to within 7 days. Whereas DBP max and min were comparable in between within 7 days and at 12th days. The changes in min., max and mean double product (All, active periods, and passive periods) were also not found to be statistically significant in between within 7 days and at 12th day. The traumatic paraplegic patients have altered diurnal index, morning surge, night dipping and systolic blood pressure on APBM monitoring.

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease

BackgroundThe cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow.MethodsTranscranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol.ResultsAfter elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [− 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001).ConclusionsThe observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.

Photoacoustic imaging of in vivo hemodynamic responses to sodium nitroprusside.

The in vivo hemodynamic impact of sodium nitroprusside (SNP), a widely used antihypertensive agent, has not been well studied. Here, we applied functional optical-resolution photoacoustic microscopy (OR-PAM) to study the hemodynamic responses to SNP in mice in vivo. As expected, after the application of SNP, the systemic blood pressure (BP) was reduced by 53%. The OR-PAM results show that SNP induced an arterial vasodilation of 24% and 23% in the brain and skin, respectively. A weaker venous vasodilation of 9% and 5% was also observed in the brain and skin, respectively. The results show two different types of blood oxygenation response. In mice with decreased blood oxygenation, the arterial and venous oxygenation was respectively reduced by 6% and 13% in the brain, as well as by 7% and 18% in the skin. In mice with increased blood oxygenation, arterial and venous oxygenation was raised by 4% and 22% in the brain, as well as by 1% and 9% in the skin. We observed venous change clearly lagged the arterial change in the skin, but not in the brain. Our results collectively show a correlation among SNP induced changes in systemic BP, vessel size and blood oxygenation.

Evaluation of changes in blood pressure in patients submitted to dental surgical procedures

The present study aimed to evaluate the occurrence of significant changes in systemic blood pressure (SBP) during surgical-dental procedures. A prospective study was performed with a sample of 135 randomly selected individuals who underwent surgical procedures at the Bucomaxillofacial Surgery Clinic of the Dentistry School of the ESFA (ES) between the second half of 2017 and April 2018. After consent, sociodemographic, lifestyle data, weight and height were obtained through a questionnaire, weighing and measurement, respectively. BP measurements were performed at three moments: preoperative (BP1), intraoperative (BP2) and postoperative (BP3) using a mercury column sphygmomanometer and stethoscope. Values ​​&lt;120/80 mmHg were used as normal values. When BP1 and BP2 were compared, 63.0% remained within normal values ​​and 22.2% reached the stage of hypertension. In the comparison of BP1 and BP3, 66.7% remained normal, and only 7.4% reached the stage of hypertension. When BP2 and BP3 were compared, 53.6% remained within the normality stage and 12.2% reached the stage of hypertension. It was concluded that there were variations in blood pressure, being the largest variation found in BP2, and can be attributed to the stress caused by the surgical act, since no statistically significant connections were found between the changes in blood pressure and the anesthetics used in the research.

Animal model of assessing cerebrovascular functional reserve by imaging photoplethysmography

Assessment of the cerebral blood-flow-reserve in patients with cerebrovascular diseases is extremely important in terms of making prognosis, determining treatment tactics, and controlling the revascularization outcome in the case of reconstructive interventions on the brain vessels. However, there is no easy-to-use, contactless method for either assessing the functional reserve of the cortical vascular network or intraoperative monitoring of surgical intervention. Our study aims to demonstrate feasibility of green-light imaging photoplethysmography (iPPG) to estimate cerebrovascular functional reserve in animal model of craniosurgical intervention. Custom-made iPPG system was exploited to visualize intracranial vessels in anesthetized Wistar rats (n = 15). Video frames of rat’s cortex were recorded concurrently with systemic blood pressure, end-tidal CO2, and electrocardiogram. We found that injection of dorzolamide (carbonic-anhydrase inhibitor) significantly increased the blood-pulsations amplitude in all animals by 35 ± 19% (p < 0.001). Such an increase negatively correlated with significant decrease in end-tidal CO2 by 32 ± 7% (p < 0.001). It is noteworthy that the dorzolamide injection did not lead to significant changes in systemic blood pressure. Concluding, pulsations amplitude is a marker of the vascular tone that can be used to evaluate the functional cerebrovascular reserve. Imaging PPG is a simple and convenient method to assess cerebral blood flow, including during various neurosurgical interventions.

ACUTE HEMODYNAMIC IMPROVEMENT IN CHRONIC PULMONARY ARTERIAL HYPERTENSION ON DUAL THERAPY FOLLOWING RT234 INHALATION

SESSION TITLE: Advances in the Diagnosis and Management of Pulmonary Hypertension SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: RT234 is an inhaled formulation of the phosphodiesterase type-5 inhibitor (PDE5i) vardenafil, and is being developed for ‘as-needed’ use for episodic symptoms of pulmonary arterial hypertension (PAH). This study assessed the hemodynamic (HD) response to RT234. METHODS: A multicentre, open label, Phase 2a escalating dose ongoing clinical trial to evaluate acute changes in pulmonary vascular resistance (PVR) and other HD parameters in PAH patients on stable maintenance dual therapy. Three cohorts of 5 subjects each were to receive 0.2, 0.6, 1.2 mg RT234 during right heart catheterization. HD parameters were recorded at 5, 15, 30, 45, and 60-min post-inhalation. RESULTS: Of the 14 subjects enrolled, mean age was 54±14 years (79% females). 57% of subjects were functional class (FC) II, 36% FC III, and 7% FC IV. All subjects took a long-term oral endothelin receptor antagonist combined with oral PDE5i. Mean baseline PVR was 635±344, 469±431, 579±337 dyn/sec/cm-5 for the 0.2 mg, 0.6 mg and 1.2 mg cohorts respectively. RT234 administration at 0.2 mg, 0.6 mg and 1.2 mg dosages reduced PVR by -6.6% (-22.2 to 2.7), -23.7% (-44.7 to -18.6), and -16.0% (-22.7 to -10.5), respectively. With the 0.6 and 1.2 mg doses, PVR fell by >10% at 5 min, and the reduced PVR was sustained at least 60 mins. PVR/SVR ratio changed by -8.0% (-27.1 to 14.1), -18.4% (-37.8 to 0.9) and -11.9% (-23.9 to -0.3) for the 0.2, 0.6 and 1.2 mg doses respectively, indicating that the 0.6 mg dose may offer the greatest pulmonary selectivity. No clinically significant changes in systemic blood pressure or heart rate were observed. The change in PaO2 was +1.8% (-13.5 to 27.4), +8.1% (-13.5 to 22.6) and +4.3% (-1.4 to 9.9) for the three dose levels. Improvements in pulmonary HD with 0.6mg inhaled RT234 were on par with 20mg oral vardenafil, but with less systemic hypotension and higher oxygenation. The only treatment related adverse events (AE) observed were a mild headache and mild throat irritation, each in a single subject. No respiratory AEs (cough, dyspnoea, wheezing, bronchospasm) occurred. CONCLUSIONS: RT234 inhalation resulted in rapid reduction in PVR that was sustained for at least 60 min post-administration and was well tolerated. The optimally effective dose of RT234 appears to be 0.6 mg. RT234 is well-suited for further clinical development as an “as-needed” or even pre-emptive therapy in PAH. CLINICAL IMPLICATIONS: The observed acute improvements in HD should enable PAH patients to perform more of their activities of daily living, resulting in an improved quality of life. DISCLOSURES: Advisory Committee Member relationship with Actelion Please note: $1001 - $5000 Added 03/22/2020 by Nathan Dwyer, source=Web Response, value=Consulting fee Advisory Committee Member relationship with GSK Please note: $1001 - $5000 Added 03/22/2020 by Nathan Dwyer, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bayer Please note: $1001 - $5000 Added 03/22/2020 by Nathan Dwyer, source=Web Response, value=Consulting fee Institutional Funding to Conduct Study relationship with Respira Therapeutics Please note: $20001 - $100000 Added 03/22/2020 by Nathan Dwyer, source=Web Response, value=Grant/Research Support No relevant relationships by David Kaye, source=Admin input No relevant relationships by Anne Keogh, source=Web Response No relevant relationships by Eugene Kotlyar, source=Web Response Employee relationship with Respira Therapeutics, Inc. Please note: >$100000 Added 03/23/2020 by Mari Maurer, source=Web Response, value=Salary Consultant relationship with Respira Therapeutics Please note: $20001 - $100000 Added 03/26/2020 by Ed Parsley, source=Web Response, value=Consulting fee Employee relationship with Respira Therapeutics Please note: >$100000 Added 03/22/2020 by Jeffry Weers, source=Web Response, value=Salary

Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve

Selective interfacing to small multifunctional nerves such as the vagus nerve (VN) which is the main multimodal autonomic nerve that provides a major communication pathway from vital peripheral organs to the brain, can have significant potential in treating and diagnosing diseases as well as enhancing our understanding of peripheral nerve circuits. Here we describe the fabrication of a 16-channel intraneural electrode array with ultramicro-dimensioned electrodes to achieve improved functionally selective recording. We demonstrate that the amorphous silicon carbide ultramicroelectrode arrays (a-SiC UMEAs) provide selectivity in the detection of neural activity in the cVN related to changes in systemic oxygenation and blood pressure. We will also demonstrate spatially selective recording of micro-compound action potentials (μCAPs) by electrical stimulation of the subdiaphragmatic branches of the VN. Distinct neural activity was recorded on electrodes separated by less than about 100 μm. This is the first time that this level of spatially selectivity recording has been demonstrated in the cVN with an intraneural multielectrode array.

Immediate changes in blood pressure during intravitreal anti-VEGF agents' applications in exudative age-related macular degeneration patients

To determine the short-term changes in systemic arterial blood pressure (SABP) during intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in patients with exudative age-related macular degeneration (ARMD). This study retrospectively reviewed the data of 550 patients with exudative ARMD, who received intravitreal anti-VEGF (bevacizumab or ranibizumab; selected randomly) injections. Patients with hypertension on medication with antihypertensive drugs were assigned to the hypertension group (HTG; n = 278); those with normal blood pressure and not on antihypertensive drugs were assigned to the normotensive group (NTG; n = 272). The SABP levels were measured 30min before anti-VEGF injection (baseline = B), during anti-VEGF injection (DI), as well as 30th (I30) and 60th (I60)min after anti-VEGF injection. Both groups had significantly higher systolic blood pressure (SBP) at DI than that of the baseline values (p < 0.001), whereas the diastolic blood pressures (DBP) increased significantly at DI, I30, and I60 compared with baseline (p < 0.001). In NTG, SBP was significantly higher in patients at I30 (p = 0.019), whereas that in HTG was significantly higher at all measurements (p < 0.05) only in patients who received intravitreal bevacizumab injection. Our study results show that intravitreal anti-VEGF injection is associated with a short-term increase in SABP. To prevent potential systemic complications during anti-VEGF administration, the systemic status of patients with ARMD should be evaluated before the injection and those with a risk of high SABP during injection should be closely monitored.