Systemic Arterial Blood Pressure Research Articles

Relationship between Blood Pressure and Rates of Glaucomatous Visual Field Progression: The Vascular Imaging in Glaucoma Study

PurposeTo examine the relationship between systemic arterial blood pressure (BP) and the rate of change in standard automated perimetry (SAP) in eyes with glaucoma and glaucoma suspects. DesignProspective cohort study. Participants124 eyes (91 glaucoma, 33 suspects) of 64 subjects (mean age 68.4±7.6 years) followed at the Bascom Palmer Eye Institute, Palm Beach Gardens, FL. MethodsParticipants underwent ophthalmic examination, BP measurement, and SAP at 4-month intervals. 24-hour ambulatory blood pressure monitoring (ABPM) was acquired at the baseline visit. Linear mixed models (adjusted for inclusion of both eyes, age, gender, race, intraocular pressure, baseline severity, and central corneal thickness) were used to investigate the effect of BP on the rates of SAP mean deviation (MD) change over time. Main Outcome MeasuresEffect of baseline 24-hour and follow-up mean arterial (MAP), systolic (SBP), and diastolic blood pressure (DBP) on change in SAP MD. ResultsEyes had an average of 8.9±1.5 SAP exams over 28.3±6.0 months of follow-up. The median rate of MD change was 0.14dB/year (range -1.21 to 0.96dB/year) with 9 (7%) eyes presenting moderate to fast progression (MD change ≤ -0.50 dB/year). Each 10mmHg lower in 24-hour average MAP and SBP were associated with -0.171 dB/year (P=0.045) and -0.137 dB/year (P=0.023) faster rates of MD loss. Lower mean SBP during follow up was significantly (P = 0.003) associated with MD progression. ConclusionsLower baseline 24-hour ABPM measurements, as well as low SBP during follow-up, were significantly associated with faster rates of glaucomatous SAP progression and may be used as a predictor of risk of glaucomatous progression.

The relevance of vascular adjustments to hemodynamic control in the face of temperature change in Crotalus durissus.

The presence of cardiac shunts in ectothermic tetrapods is thought to be consistent with active vascular modulations for proper hemodynamic support. Local control of blood flow modulates tissue perfusion and thus systemic conductance (Gsys) is assumed to increase with body temperature (Tb) to accommodate higher aerobic demand. However, the general increase of Gsys presses for a higher right-to-left (R-L) shunt, which reduces arterial oxygen concentration. In contrast, Tb reduction leads to a Gsys decrease and a left-to-right shunt, which purportedly increases pulmonary perfusion and plasma filtration in the respiratory area. This investigation addressed the role of compensatory vascular adjustments in the face of the metabolic alterations caused by Tb change in the South American rattlesnake (Crotalus durissus). Cardiovascular recordings were performed in decerebrated rattlesnake preparations at 10, 20 and 30°C. The rise in Tb increased metabolic demand, and correlated with an augmentation in heart rate. Although cardiac output increased, systemic stroke volume reduced while pulmonary stroke volume remained stable. Although that resulted in a proportionally higher increase in pulmonary blood flow, the R-L shunt was maintained. While the systemic compliance of large arteries was the most relevant factor in regulating arterial systemic blood pressure, peripheral conductance of pulmonary circulation was the major factor influencing the final cardiac shunt. Such dynamic adjustment of systemic compliance and pulmonary resistance for shunt modulation has not been demonstrated before and contrasts with previous knowledge on shunt control.

Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

Ventricular pre-excitation in an elderly cat

An 18-year-old female neutered Domestic Shorthair cat was referred for investigation of seizure-like episodes. Physical and neurological examination were unremarkable, as were systemic arterial blood pressure, cardiac troponin I, complete blood count and biochemistry profile. Diagnostic tests included transthoracic echocardiography which ruled out any structural cardiomyopathy, and electrocardiography which showed an underlying regular wide QRS-complex rhythm with pronounced shortening of the PR interval. Considering the findings, a diagnosis of suspected ventricular pre-excitation secondary to an accessory pathway was made. Further investigations were declined and, as no periods of tachycardia were seen on the five-minute electrocardiogram, no antiarrhythmic treatment was started.

Novel pathways linked to the expression of temperament in Merino sheep: a genome-wide association study

Animal temperament refers to the inherent behavioural and emotional characteristics of an animal, influencing how it interacts with its environment. The selection of sheep for temperament can change the temperament traits of the selected line and improve the welfare and production (reproduction, growth, immunity) of those animals. To understand the genetics that underly variation in temperament in sheep, and how selection on temperament can affect other production traits, a genome-wide association study was carried out. Merino sheep from lines selected for traits of calm and nervous temperament, and a commercial population, on which the temperament traits had never been assessed, were used. Blood samples from the three populations were genotyped using an Illumina GGP Ovine 50 K Genotyping BeadChip. The calm and nervous populations in the selected lines presented as distinct genetic populations, and 2 729 of the 45 761 single nucleotide polymorphisms (SNPs) had significantly different proportions between the two lines. Of those 2 729 SNPs, 2 084 were also associated with temperament traits in the commercial population. A genomic annotation identified 81 candidate genes for temperament, nearly half of which are associated with disorders of social behaviour in humans. Five of those 81 candidate genes are related to production traits in sheep. Two genes were associated with personality disorders in humans and with production traits in sheep. We identified significant enrichment in genes involved in nervous system processes such as the regulation of systemic arterial blood pressure, ventricular myocyte action, multicellular organismal signalling, ion transmembrane transport, and calcium ion binding, suggesting that temperament is underpinned by variation in multiple biological systems. Our results contribute to understanding of the genetic basis of animal temperament which could be applied to the genetic evaluation of temperament in sheep and other farm animals.

A retrospective case-control study evaluating systemic blood pressure and heart rate in dogs with brain herniation under general anesthesia

ObjectiveTo examine whether increased systemic arterial blood pressure (ABP) and decreased heart rate (HR) under inhalant anesthesia were suggestive of the Cushing reflex (CR) in dogs with neurological diseases based on magnetic resonance imaging (MRI) findings. Study designRetrospective case-control study. AnimalsA sample of 137 client-owned dogs admitted to two veterinary teaching hospitals for diagnosis and patient care owing to suspected intracranial disease from 2005 to 2020. All dogs underwent general anesthesia for MRI of the brain. MethodsBased on MRI study reports, dogs were divided into three study groups: group A, dogs with suspected brain herniation; group B, dogs with an abnormal MRI finding but without suspicion of herniation; and group C, dogs with structurally unremarkable brains (control). Initial evaluation by an anesthesiologist resulted in 58 cases selected for further review based on suspicion of having intracranial hypertension, as indicated by ABP and HR changes under anesthesia. Anesthetic records were randomized and independently reviewed by three board-certified anesthesiologists blinded to MRI diagnosis who allocated each dog into one of three groups: 1) likely to have CR; 2) unlikely to have CR; or 3) insufficient data for determination. ResultsOf the 58 cases evaluated, nine were considered likely to have CR and 48 were considered unlikely to have CR. In one case, the anesthesiologists were unable to determine whether CR occurred. Of the nine dogs with likely CR, three had an MRI diagnosis of intracranial herniation. The remaining six dogs suspected of CR belonged to the normal brain group. Conclusions and clinical relevanceThe ABP and HR changes associated with CR are not reliably associated with brain herniation in dogs undergoing general anesthesia.

The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats

BackgroundIn people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight.ResultsAt baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17–29%), with a median reduction in body fat mass of 45% (26–64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction.ConclusionAn increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.

Health pulse initiative: tracking blood pressure in akshaya group's teaching and non-teaching staff

Hypertension refers to a condition where the systemic artery blood pressure exceeds normal levels, necessitating increased cardiac effort to counteract the elevated pressure and ensure adequate blood flow to tissues. The heightened systemic arterial pressure places stress on the heart and other arteries, contributing to the development of hypertension. In our cross-sectional observational study, we employed questionnaires to gather data from volunteers over a three-month period. The inclusion and exclusion criteria were carefully applied to ensure the relevance of the collected data. Our study included 120 individuals from the selected region, aiming to assess blood pressure monitoring. The study revealed a dominance of males, constituting 51.67% of the total participants, while women accounted for 48.33%. The age distribution showed that 46.67% of the volunteers fell within the 31 to 40 age group. Our findings indicated that age, gender, and occupation significantly influenced blood pressure monitoring. Upon analysis, we observed a statistically significant improvement in volunteers' knowledge, attitudes, and practices regarding hypertension following counseling. This suggests the potential efficacy of intervention strategies in enhancing awareness and management of hypertension among the studied population.

Antihypertensive Medications Can Prevent Fostamatinib-Induced Blood Pressure Elevation

Fostamatinib is a tyrosine kinase inhibitor that has been shown in clinical trials to be effective against spleen tyrosine kinase in patients suffering from rheumatoid arthritis. Fostamatinib medication was linked in clinical trials to a slight increase in systemic arterial Blood Pressure (BP). This observation is consistent with other kinase inhibitors, particularly those that obstruct VEGFR2 signaling. In conscious rats, we examined the relationship between the elevation of blood pressure caused by fostamatinib and the plasma levels of the fostamatinib-active metabolite R940406. We discovered that there was a strong correlation between changes in R940406 plasma concentration and the time course of the blood pressure effect, suggesting a direct pharmacological relationship. The experiments yielded free plasma levels of R940406 up to 346 nmol/L, which is greater than the mean peak free plasma concentration of 49 nmol/L that has been recorded in clinical settings. We beyond the clinically noted mean peak free plasma concentration of 49 nmol/L, up to 346 nmol/L. We’ve shown that there are several effective ways to reduce the blood pressure elevation caused by fostamatinib dosing, including simple drug withdrawal or condoning with a variety of common antihypertensive medications like atenolol, captopril, and nifedipine. These results provide credence to prospective strategies for preserving patient safety during fostamatinib therapy. Additionally, we have shown—using nifedipine as an example drug—that this blood pressure control was not brought about by a decrease in R940406’s plasma exposure, indicating that potential pharmacological benefits of the investigational drug may be preserved while blood pressure control is managed with the use of conventional medications.

Protective effect of novel angiotensin receptor neprilysin inhibitor S086 on target organ injury in spontaneously hypertensive rats

BackgroundHypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure associated with injury to the heart, kidney, brain, and other organs. Angiotensin receptor neprilysin inhibitors (ARNi), including angiotensin receptor blockers (ARBs) and neprilysin inhibitors (NEPi), have been shown to be safe and effective at reducing blood pressure and alleviating development of target organ injury. This study was used to develop S086 as a novel ARNi and conducted preclinical studies in animal models to evaluate the protective effects of S086 on target organs. MethodsThis study used a 14-month-old spontaneously hypertensive rat (SHR) model to evaluate the protective effects of S086 on the cardiovascular system and organs such as heart and kidney by blood pressure monitoring, urine and blood examination, pathological examination, and immunological index detection. ResultsAfter administering S086 orally to the SHR, their blood pressure and levels of renal injury indicators such as serum creatinine and urinary microalbumin were reduced, and myocardial cell necrosis and cardiac fibrosis of the heart were significantly improved. In addition, there were also significantly improvements in the histological lesions of blood vessels and the kidneys. ConclusionsThe findings showed that S086 effectively reduced the blood pressure of SHR and had effects on alleviating development of heart, blood vessels and kidney.

Angiotensin-Converting Enzyme (ACE) gene polymorphism and arterial blood pressure among the Tawang Monpa of Eastern Himalayan Mountains: Is there a signature of natural selection?

The present paper aims to characterize the Angiotensin-converting enzyme (ACE) genotype, with particular emphasis on its association with arterial oxygen saturation, arterial blood pressure, hemoglobin [Hb] concentration, and ventilatory measures among the Tawang Monpa, a high-altitude native population of the Eastern Himalaya, India. A cross-sectional sample of 168Monpa participants from Tawang town, Arunachal Pradesh, India, was selected who live at an altitude of ∼3,200 meters (m) above sea level. For each participant, height, weight, and skinfold thickness were measured, based on which body mass index (BMI, kg/m2) and percentage of body fat (%BF) were calculated. Physiological measures, such as the transcutaneous arterial oxygen saturation (SaO2), hemoglobin [Hb] concentration, forced vital capacity (FVC), forced expiratory volume in 1-second (FEV1), and systemic arterial blood pressure were measured. First, the peripheral venous blood samples (four ml) were drawn, and then white blood cells were separated for the ACE genotyping of each participant. Unlike high-altitude natives from Peru and Ladakh, who exhibit high frequencies of II homozygotes, the Tawang Monpa shows a significantly high frequency of ID heterozygotes (p<0.0001). In addition, no significant association was identified between ACE gene polymorphism and arterial blood pressure, oxygen saturation at rest, vital capacity, or [Hb] concentration. The results suggest that the association of the ACE gene with resting SaO2 is inconsistent across native populations living under hypobaric hypoxia. Further, ACE I/D gene polymorphism may not be under natural selection in specific native populations, including Tawang Monpa, for their adaptation to high-altitude hypoxia.

Validity of a novel optical coherence tomography angiography flow index in a cohort of primary open angle glaucoma

BackgroundVascular mechanisms are implicated in many ocular diseases. Therefore, different vascular imaging modalities are used in management of such conditions. Optical coherence tomography angiography (OCTA) has high spatial resolution and segmentable 3D volumetric sampling enabling isolation of retinal and peripapillary vascular beds. However, OCTA only indirectly derives quantitative flow data i.e. velocimetry through methods and algorithms liable to limitations like signal saturation. This study introduces and validates novel mathematical OCTA flow indices that may compensate for some OCTA velocimetric limitations.MethodsThirty-seven eyes of 23 POAG patients were included. Each underwent baseline and follow-up assessment one month thereafter. Assessment comprised full ophthalmological examination, intraocular pressure (IOP), systemic arterial blood pressure (SABP) and OCTA macula and ONH. Angiograms were processed using ImageJ to calculate OCTA intensity-based flow indices (FIOs), for superficial vascular plexus (SVP), deep vascular plexus (DVP) and optic nerve head vascular plexus (ONH-RPC), i.e. SFIO, DFIO and ONHFIO respectively. Mean ocular perfusion pressure (MOPP) was calculated using IOP and SABP. OCTA vascular densities (VD) and MOPP were used to calculate three respective mathematical flow indices (FIMs) for SVP, DVP and ONH-RPC, based on Hagen-Poiseuille law, i.e. SFIM, DFIM, ONHFIM respectively. Pearson test was used for correlation between the two sets of indices. Intraclass correlation coefficient (ICC) was tested for baseline and follow-up values for each index.ResultsThere was positive correlation between the three FIMs and their respective FIOs at baseline and follow-up ranging between high and moderate. Correlation coefficients (CCs) were 0.773 and 0.609 for SFIM and SFIO P-value < 0.001, 0.829 and 0.624 for DFIM and DFIO P-value < 0.001 and 0.516 and 0.737 for ONHFIM P-value = 0.001 for baseline and follow-up respectively. ICCs were 0.772 P-value < 0.001, 0.328 P-value = 0.022 and 0.888 P-value < 0.001 for SFIM, DFIM and ONHFIM respectively. For SFIO, DFIO and ONHFIO, ICCs were 0.420 P-value = 0.004, 0.079 P-value = 0.320 and 0.833 P-value < 0.001 respectively.ConclusionThe novel FIMs are reliable alternatives to FIOs and may compensate for OCTA signal saturation in extremes of MOPP. SFIM and ONHFIM showed high ICCs with excellent reliability. While DFIM demonstrated low ICC indicating poor reliability, it still performed better than its corresponding DFIO.

Abstract P3168: Identification Of Exosome MicroRNA In Association With Severe Calcification In Coronary Chronic Total Occlusion

Backgrounds: Coronary artery calcification (CAC) is prevalent in patients with coronary chronic total occlusion (CTO). We investigated the association between plasma miRNAs and coronary artery calcification in patients with CTO. Methods: Blood samples were collected from 18 patients who underwent percutaneous coronary intervention (PCI) of CTO. Exosomal small RNA sequencing was performed from plasma to quantify miRNA expression. Calcium volume was quantified in computed tomography (CT) in CTO. Gene ontology and functional pathway were analyzed in the miRNAs that significantly correlates with calcium volume. Results: Calcium volume was positively correlated with miR-1-3p and miR-708-3p (p &lt;0.05), and was negatively correlated with 4 miRNAs -including let-7d-5p (p &lt;0.05). Gene enrichment and pathway analysis showed that the target genes of the 2 positively correlated miRNAs were involved in regulation of osteoblast differentiation and osteopontin signaling pathway. In contrast, the target genes of the 4 negatively correlated miRNAs were enriched in acetylcholine-mediated vasodilation involved in regulation of systemic arterial blood pressure, blood vessel development and response to sterol. Multiple linear regression showed that miR-1-3p and let-7d-5p could be key predictors of the calcium volume of CTO (adjusted R 2 = 0.798 and p &lt;0.001). Conclusions: We identified miR-1-3p and let-7d-5p could be related with CAC in patients with CTO.

Effect of gabapentin on ambulatory, direct, systemic arterial blood pressure in apparently healthy cats in the at-home and in-clinic environments.

Situational increases in blood pressure (BP) frequently confound the accurate diagnosis of pathological systemic hypertension in cats. The objective of this study was to investigate the effect of gabapentin on direct, ambulatory systolic arterial BP (SBP) in cats in at-home and in-clinic environments. Six adult purpose-bred cats with surgically implanted femoral artery telemetric BP-sensing catheters were administered 100 mg of gabapentin or a placebo orally in two randomized, masked, crossover study phases. In the first, direct BP was measured continuously in undisturbed cats for 24 h before (at-home baseline) and 4 h after administration of study drug. The mean SBP after administration of the drug was compared between treatments. In the second study period, cats were administered gabapentin or placebo 90 mins before transport to a clinic, where direct BP was measured continuously during a simulated veterinary visit that included an indirect BP measurement session. Changes in mean direct SBP relative to the 24-h at-home pre-treatment period were calculated for each of one waiting room and two examination-room periods, and compared between treatments. Concurrent in-clinic direct and indirect SBP measurements were compared within-cat. Data were compared using linear mixed models. Direct SBP data from one cat were excluded due to implant failure. There were no differences in at-home or in-clinic SBP between treatment groups, with large inter-individual variability. Cats in both treatment groups experienced in-clinic increases in direct SBP relative to at-home baseline (range 11-50 and 10-52 mmHg in placebo- and gabapentin-treated cats, respectively). Across all visits, direct SBP was 15.6 mmHg higher than indirect SBP (P <0.001). No effects of treatment on difference between direct and indirect SBP were identified. Significant effects of gabapentin on direct SBP were not identified, though a type II error is possible. Situational increases cannot be excluded in gabapentin-treated cats with high SBP.

Close Relationship between Systemic Arterial and Portal Venous Pressure in an Animal Model with Healthy Liver.

It is unclear to what extent systemic arterial blood pressure influences portal pressure. This relationship is clinically important as drugs, which are conventionally used for therapy of portal hypertension, may also influence systemic arterial blood pressure. This study investigated the potential correlation between mean arterial (MAP) and portal venous pressure (PVP) in rats with healthy livers. In a rat model with healthy livers, we investigated the effect of manipulation of MAP on PVP. Interventions consisted of 0.9% NaCl (group 1), 0.1 mg/kg body weight (bw) Sildenafil (low dose), an inhibitor of phosphodiesterase-5 (group 2), and 1.0 mg/kg bw Sildenafil (high dose, group 3) in 600 µL saline injected intravenously. Norepinephrine was used to increase MAP in animals with circulatory failure while PVP was monitored. Injection of the fluids induced a transient drop in MAP and PVP, probably due to a reversible cardiac decompensation. The drop in MAP and drop in PVP are significantly correlated. The time lag between change in MAP and change in PVP by 24 s in all groups suggests a cause-and-effect relationship. Ten minutes after the injection of the fluid, cardiac function was normalized. Thereafter, MAP gradually decreased. In the NaCl group, PVP decreases by 0.485% for a 1% drop of MAP, by 0.550% in the low-dose sildenafil group, and by 0.651% in the high-dose sildenafil group (p < 0.05 for difference group two vs. group one, group three vs. group one, and group three vs. group two). These data suggest that Sildenafil has an inherent effect on portal pressure that exceeds the effect of MAP. Injection of norepinephrine led to a sudden increase in MAP followed by an increase in PVP after a time lag. These data show a close relationship between portal venous pressure and systemic arterial pressure in this animal model with healthy livers. A change in MAP is consequently followed by a change in PVP after a distinct time lag. This study, furthermore, suggests that Sildenafil influences portal pressure. Further studies should be performed in a model with cirrhotic livers, as these may be important in the evaluation of vasoactive drugs (e.g., PDE-5-inhibitors) for therapy of portal hypertension.

Evaluation of the short-term echocardiographic effects of two loop diuretics, furosemide and torsemide, in a group of dogs.

Two loop diuretics, torsemide and frusemide, can affect the urinary system and consequently the cardiordiovascular haemodynamics in different ways. This study compared a number of echocardiographic parameters and systemic arterial blood pressure (ABP) changes following administration of furosemide or torsemide. Five shelter dogs underwent transthoracic two-dimensional M-mode echocardiography to obtain the following measurements: left ventricular internal dimension at end-systole (LVIDs), left ventricular internal dimension at end-diastole (LVIDd), fractional shortening (FS), heart rate (HR) and the distance between the mitral valve socket and the ventricle wall (septal to E Point, SEP). Arterial blood pressure was measured using the oscillometric method. Measurements recorded before treatment (baseline data) were compared to those after the dogs received furosemide (5mg/kg) or torsemide (0.5mg/kg). Torsemide significantly reduced blood pressure 1 h after administration, but this was not seen with furosemide. Fractional shortening, LVIDd and SEP decreased following both treatments, but there were no significant differences between the treatment groups. Torsemide increased heart rate above that seen in the furosemide groups. The results of this study indicate that 1 h after administration, torsemide increases heart rate and decreases blood pressure when compared to furosemide, but both drugs have similar effects on measured cardiovascular indices.

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&lt;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&lt;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&lt;0.05), but similar maximal contraction (109±10 vs. 116±6 %KMAX, p&gt;0.05) and sensitivity (7.3±0.2 vs. 7.2±0.2, p&gt;0.05) to thromboxane A2 receptor agonist U46619. Pre-incubation with indomethacin lowered maximal response (97±5 vs. 116±6 %KMAX, p&lt;0.05) and sensitivity (6.8±0.1 vs. 7.2±0.2, p&lt;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.

CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension.

Hypertension is a clinical syndrome characterized by increased systemic arterial blood pressure, affecting about 1.4 billion people currently worldwide with only one in seven cases adequately controlled. It is the main contributing factor of cardiovascular diseases (CVDs), often co-existing with other CVDs risk factors to impair the structure and function of important organs such as heart, brain, and kidney, and ultimately lead to multi-organ failure. Vascular remodeling is a critical process in the development of essential hypertension, and phenotype switching of vascular smooth muscle cells (VSMCs) was reported contributing substantially to vascular remodeling. circHIPK2 is a circular RNA (circRNA) derived from the second exon of homeodomain-interacting protein kinase 2 (HIPK2). Several studies revealed that circHIPK2 functions in various diseases by serving as a microRNA (miRNA) sponge. However, the functional roles and molecular mechanisms of circHIPK2 in VSMC phenotype switching and hypertension are not clear. In the present study, we showed that the expression of circHIPK2 was significantly upregulated in the VSMCs of hypertensive patients. Functional studies showed that circHIPK2 promoted the Angiotensin II (AngII)-induced VSMC phenotype switching by acting as the sponge of miR-145-5p, thereby upregulating the expression of a disintegrin and metalloprotease (ADAM) 17. Collectively, our study provides a new therapeutic target for hypertension.

The haemodynamic effects of phenylephrine after cardiac surgery.

Phenylephrine increases systemic- and pulmonary resistances and therefore may increase blood pressures at the expense of blood flow. Cardio-pulmonary bypass alters vasoreactivity and many patients exhibit chronotropic insufficiency after cardiac surgery. We aimed to describe the haemodynamic effects of phenylephrine infusion after cardiac surgery. Patients in steady state after low-risk cardiac surgery received incremental infusion rates of phenylephrine up to 1.0 μg/kg/min with the aim of increasing systemic mean arterial blood pressure 20 mmHg. Invasive haemodynamic parameters, including pulmonary wedge pressures, were captured along with echocardiographic measures of biventricular function before, during phenylephrine infusion at target systemic blood pressure, and 20 min after phenylephrine discontinuation. Thirty patients were included. Phenylephrine increased mean arterial pressure increased from 78 (±9) mmHg to 98 (±10) mmHg with phenylephrine infusion. Also, pulmonary blood pressure as well as systemic- and pulmonary resistances increased. The ratio between systemic- and pulmonary artery resistances did not change statistically significantly (p = .59). Median cardiac output was 4.35 (interquartile range [IQR] 3.6-5.4) L/min at baseline and increased significantly with phenylephrine infusion (median Δcardiac output was 0.25 [IQR 0.1-0.6] L/min) (p = .012). Pulmonary artery wedge pressure increased from 10.2 (±3.0) mmHg to 11.9 (±3.4) mmHg (p < .001). This was accompanied by significant increases in central venous pressure. Phenylephrine infusion increased left ventricular end-diastolic volume from 105 (±46) mL to 119 (±44) mL (p < .001). All results of phenylephrine infusion were reversed with discontinuation. In haemodynamically stable patients after cardiac surgery, phenylephrine increased PVR and SVR, but did not change the PVR/SVR ratio. Phenylephrine increased biventricular filling pressures and left ventricular end-diastolic area. Consequently, CO increased as ejection fraction was maintained. These findings do not discourage the use of phenylephrine after low-risk cardiac surgery. clinicaltrial.gov (identifier NCT04419662).

Novel avenues to control blood pressure: targeting the renal lymphatic system.

Hypertension is associated with the activation of the immune and lymphatic systems as well as lymphangiogenesis. The changes in the lymphatic system are considered an adaptive response to mitigate the deleterious effects of immune and inflammatory cells on the cardiovascular system. In the article recently published in Clinical Science by Goodlett and collaborators, evidence is shown that inducing renal lymphangiogenesis after the establishment of hypertension in mice is an effective maneuver to reduce systemic arterial blood pressure. In this commentary, we will briefly review what is known about the relationship between the activation of the immune and lymphatic systems, and the resulting effects on systemic blood pressure, summarize the findings published by Goodlett and collaborators, and discuss the impact of their findings on the field.