Control Of Arterial Blood Pressure Research Articles

On the Regulation of Arterial Blood Pressure by an Intracranial Baroreceptor

Introduction: There is significant evidence for the existence of an intracranial baroreceptor mechanism(s) capable of sensing physiological changes in cerebral blood flow (Marina et al., 2020). However, little is known about the sensitivity of this mechanism to changes in brain perfusion and its interaction with inputs from the peripheral (arterial) baroreceptors. The aim of this study was to characterise the cardiovascular responses to physiological changes in cerebral perfusion induced by experimental manipulations of intracranial pressure (ICP). Methods: The experiments were performed in adult Sprague-Dawley rats (250–300 g), anesthetized with urethane (induction: 1.3 g kg−1, i.p.; maintenance: 10–25 mg kg−1 h−1, i.v.). The femoral artery and vein were cannulated for measurement of arterial blood pressure (ABP) and administration of anaesthetic. The trachea was cannulated, and the animal was mechanically ventilated. The lateral cerebral ventricles were cannulated and connected via saline-filled catheters to a pressure transducer to record ICP and to a “water column” to allow controlled manipulation of ICP. The experiments included the denervation of the arterial baroceptors, stimulation of the aortic depressor nerve and recording of renal sympathetic nerve activity. Results: The resting ICP in rats anesthetized with urethane was 6.2 ± 0.7 mmHg (n=8). Following a small craniotomy that reduced ICP to 0 mmHg, ABP decreased by 11.2 mmHg (n=6) within 30 min. Restoring the integrity of the intracranial space increased ABP to the baseline level. Progressive increases in ABP were observed in response to experimentally-induced increases in ICP by 5, 10, 15 and 20 mmHg, revealing a linear relationship between ICP and systemic arterial pressure within the physiological range of ICP changes. In the absence of inputs from the arterial baroceptors (bilateral sino-aortic denervation and vagotomy) the ABP responses to ICP increases were preserved. Analysis of the ABP and heart rate responses to the electrical stimulation of the aortic depressor nerve suggested baroreflex re-setting at raised ICP. Renal nerve recordings demonstrated increased sympathetic activity at raised ICP (172 ± 34.91 % at 20 mmHg ICP (p=0.003; n=7) with markedly enhanced bursts of activity during the inspiratory phase of the respiratory cycle. Conclusion: These data demonstrate that the intracranial baroceptor mechanism is highly sensitive to changes in cerebral perfusion within the physiological range and suggest that cerebral blood flow is an important determinant of systemic ABP. The data suggest that at raised ICP the baroreflex control of sympathetic vasomotor activity is reset and provides effective control of arterial blood pressure at a higher level required to compensate for reduced brain perfusion. Marina, N., Christie, I.N., Korsak, A., Doronin, M., Brazhe, A., Hosford, P.S., Wells, J.A., Sheikhbahaei, S., Humoud, I., Paton, J.F. and Lythgoe, M.F., 2020. Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow. Nature Communications, 11(1), 131. This PhD Studentship is funded by the British Heart Foundation. 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.

Antioxidant-induced modulation of sympathetic transduction to arterial blood pressure in humans

Purpose: Excess plasma free fatty acids (FAA) promote oxidative stress and an increase in peripheral resistance. Therefore, we tested the hypothesis that excess FAA limits sympathetic control of arterial blood pressure (BP) and that sympathetic control would be restored during co-administration of ascorbic acid, which is an antioxidant with vasodilatory properties. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 5 lean, healthy adults with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Sympathetic control of BP was examined by determining the BP response to individual bursts of muscle sympathetic nerve activity (MSNA) (microneurography). Briefly, beat-to-beat mean arterial pressure (MAP) was measured continuously (finger cuff) and signal-averaged over 15 cardiac cycles following each detected burst of MSNA over a 10-min resting period. Results: In contrast to our hypothesis, no change was observed in sympathetic transduction during lipid infusion (1.5 ± 0.4 vs. 1.4 ± 3 mmHg, P=0.75). However, co-infusion of ascorbic acid significantly increased sympathetic transduction compared with baseline (1.5 ± 0.4 vs. 2.0 ± 3 mmHg, P=0.04), in addition to reducing peripheral resistance (0.73 ± 0.11 vs. 0.53 ± 12 mmHg·min·mL−1, P=0.07). MSNA and MAP were not significantly changed during the 2-hr infusions. Conclusions: These preliminary findings suggest that excess FAA do not modulate sympathetic transduction in lean, healthy adults. However, ascorbic acid infusion reduces peripheral resistance and increases sympathetic transduction, demonstrating an inverse relation between peripheral resistance and sympathetic transduction in healthy adults. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366) The contents are solely the responsibility of the authors and do not necessarily represent the offcial views of the NIH or NCATS. 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.

Skeletal muscle contractions attenuate the norepinephrine-related reduction in interstitial oxygen pressures in the rat spinotrapezius

Increased sympathetic nerve activity with exercise plays a key role in the control of arterial blood pressure and redistribution of blood flow. Within the microcirculation, elevated sympathetic outflow promotes the release of norepinephrine and smooth muscle contraction. Exercise-induced attenuation of sympathetic vasoconstriction (i.e., functional sympatholysis) is thus critical for active muscle oxygen delivery-utilization matching. However, the extent to which muscle contractions impact noradrenergic regulation of interstitial oxygen pressures (PO2is) is unknown. This is important because, as dictated by Fick’s law, PO2is provides the sole driving force for oxygen diffusion into the myocyte thereby supporting oxidative phosphorylation. PURPOSE: To determine the effects of norepinephrine administration on resting and contracting rat skeletal muscle PO2is. We tested the hypothesis that topical application (superfusion) of norepinephrine would result in blunted decreases in skeletal muscle PO2is during contractions compared to rest. METHODS: PO2is was determined via phosphorescence quenching in the exposed spinotrapezius muscle of anesthetized male Sprague-Dawley rats (n=7, 2-3 months old) at rest and during electrically-induced submaximal contractions (0.5 Hz, 3-6 V) for 6 minutes in response to norepinephrine superfusion (5x10−4 M). Functional sympatholysis was determined as the difference between the norepinephrine-induced changes in PO2is at rest and during the contraction steady-state (i.e., 2 min following the onset of muscle contractions) using (i) the absolute PO2is fall with norepinephrine (ΔPO2is), and (ii) the area under the PO2is curve plotted as a function of time (AUC). The tail (caudal) artery was cannulated for measurements of mean arterial pressure (MAP) and heart rate (HR). RESULTS: Consistent with our hypothesis, skeletal muscle contractions attenuated norepinephrine-evoked reductions in spinotrapezius interstitial oxygenation as evaluated by ΔPO2is (rest: -8.7±1.4, contractions: -4.3±1.1 mmHg, p<0.05) and AUC (rest: 2246±368, contractions: 1066±273 mmHg·s, p<0.05). Although MAP increased significantly with norepinephrine both at rest (+5±1%, p<0.05) and during contractions (+8±1%, p<0.05), this mild hypertensive response to norepinephrine was not different between conditions (p>0.05). Norepinephrine superfusion did not affect HR at rest or during contractions (p>0.05). CONCLUSIONS: That muscle contractions blunted the decrease in spinotrapezius PO2is with norepinephrine compared to the resting condition is consistent with functional sympatholysis. The latter serves to match active muscle O2 delivery-utilization in the face of elevated sympathetic nerve activity during exercise. The current results indicate that a novel combination of phosphorescence quenching (interstitial oxygenation, PO2is) and superfusion techniques may be used to evaluate functional sympatholysis in the intact rat spinotrapezius muscle. Showalter Research Trust, Purdue University. 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.

Clinical Review of Hypertensive Acute Heart Failure.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year (from 20% to 36%) mortality. Considering the high rate of rehospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Facial fanning reduces heart rate but not tolerance to a simulated hemorrhagic challenge following exercise heat stress in young healthy humans.

We investigated whether reducing face skin temperature alters arterial blood pressure control and lower body negative pressure (LBNP) tolerance after exercise heat stress. Eight subjects (1 female; age, 27 ± 9 yr) exercised at ∼63% V̇o2max until core temperature had increased ∼1.5°C before undergoing LBNP to presyncope either with fanning to return face skin temperature to baseline (Δ-5°C, Fan trial) or without (No Fan trial). LBNP tolerance was quantified as cumulative stress index (CSI; mmHg·min). Before LBNP, whole body and face skin temperatures were elevated from baseline in both trials (38.0 ± 0.5°C and 36.3 ± 0.5°C, respectively, both P < 0.001). During LBNP, face skin temperature decreased in the Fan trial (30.9 ± 1.0°C) but was unchanged in the No Fan trial (36.1 ± 0.6°C, between trials P < 0.001). Mean arterial pressure was not different between trials (P = 0.237) and was similarly reduced at presyncope in both trials (from 82 ± 7 to 67 ± 8 mmHg, P < 0.001). During LBNP, heart rate was attenuated in the Fan trial at Mid LBNP (146 ± 16 vs. 158 ± 12 beats/min, P = 0.036) and at peak heart rate (158 ± 15 vs. 170 ± 15 beats/min; P < 0.001). LBNP tolerance was not different between trials (321 ± 248 vs. 328 ± 115 mmHg·min, P = 0.851). In exercise heat-stressed individuals, lowering face skin temperature to normothermic values suppressed heart rate thereby altering cardiovascular control during a simulated hemorrhagic challenge without reducing tolerance.

Cardiovascular physiology of embryonic neotropic cormorants (Phalacrocorax brasilianus)

Cardiovascular maturation in avian species has primarily been studied in precocial species of birds, with few studies conducted on altricial species, which make up the majority of avian species. In the precocial species of birds studied to date, cardiovascular regulation is derived primarily from an adrenergic receptor stimulation that is present from approximately 50% to 60% of incubation until hatching. Conversely, the cholinergic modulation of heart rate differs in its timing of activation, as it is reported to be present in some studies at 60% of incubation to as late as after hatching in others. This has led to the speculation that, although adrenergic stimulation is critical to cardiovascular homeostasis, cholinergic stimulation prior to hatching in birds is species-specific and therefore is not critical for cardiovascular homeostasis in embryonic birds. In this work, we conducted a series of studies on an altricial species, the neotropic cormorant (Phalacrocorax brasilianus), to gain novel data regarding cardiovascular development in a largely unstudied group of birds. We investigated cholinergic and adrenergic receptor mediated control of both arterial blood pressure and heart rate. We predicted that, given the state of this altricial species at hatching, both cholinergic and adrenergic tone on the cardiovascular system would be functional in the embryo. Our findings indicate that cholinergic tone was present at 90% of incubation. However, there was a pronounced adrenergic tone on the cardiovascular system that was relatively greater than that reported in the other studies of avian embryos. Therefore, our findings support our prediction regarding the function of cholinergic tone and adrenergic tone prior to hatching.

Obesity as a risk factor for chronic kidney disease: a contemporary view on the problem. Review

The review article is devoted to an actual clinical problem of participation of obesity in development and progression of chronic kidney disease (CKD). Some pathogenic links due to which a negative renal effect of obesity is mediated including in particular, dyslipidemia (DLP), endothelial dysfunction (ED) of renal vessels, activation of renin‑angiotensin‑aldosterone system (RAAS), arterial hypertension (AH), a production of adipose tissue mediators with renal injuring properties such as leptin, tumor necrosis factor‑α, interleukines 1,6,8 are discussed. The data about the main factors of progression of renal damage associated with obesity included insulin resistance (IR), hyperinsulinemia, DLP, systemic and renal hemodynamic disorders caused by activation of RAAS (AH, intraglomerular hypertension) are given. The role of metabolic syndrome and its components in pathogenesis of CKD as well as a role of diabetes mellitus (DM) frequently combined with obesity in development of diabetic kidney disease (diabetic nephropathy) is generalized. Among adipokines a special attention in the present review is paid for pathogenic role of leptin and adiponektin in obesity with its conditions promoted renal damage. The participation of resistance to leptin in the pathogenesis of CKD through such links as IR, ED, oxidative stress and inflammation is discussed. The role of ED and glomerular hyperfiltration in pathogenesis of microalbuminuria is elucidated. The significance of injury of kidney tubular cell structures so called podocytes in pathogenesis of CKD in obesity is uncovered. The clinical significance of early revealing of renal pathology as well as body weight, glycemia level, arterial blood pressure control and following of healthy mode of life in reduction of risk development of CKD associated with obesity, DM and other metabolic disorders is generalized. It’s emphasized that evaluation of lipid and carbohydrate exchange parameters, serum leptin level, IR indices is considered to be perspective for diagnostics of renal damage in obesity.

EVALUATION OF THE EFFICACY AND SAFETY OF MEDICAL TREATMENT WITH LOWER DOSES OF SPIRONOLACTONE IN A COHORT OF PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Treatment with mineralocorticoid receptor antagonists is recommended for patients with bilateral forms of primary aldosteronism or with unilateral forms unwilling or unable to undergo surgery, using spironolactone as the primary choice, with a suggested dose of 1 to 2 mg/Kg/day. In clinical practice, however, the dose prescribed has been progressively decreased to achieve a better tolerance of the drug and, consequently, a higher compliance to treatment. Our aim was to evaluate how the lowering of spironolactone dose could have impacted on arterial blood pressure control and on the prevalence of adverse effects. Design and method: We retrospectively included 394 patients with primary aldosteronism receiving a medical treatment with spironolactone, with a minimum follow-up of 1 month after the initiation of medical treatment. Patients were divided into two groups, according to the median prescribed dose of spironolactone in our population (50 mg, 25 – 75): subjects treated with &gt;50 mg and patients treated with &lt; = 50 mg of spironolactone daily. Results: The median follow-up after the introduction of spironolactone was 6 months, and 135 patients experienced spironolactone-related adverse effects (34.3%), with a higher proportion in men than in women (76.30% vs. 23.70%). The most frequently reported adverse effect was gynecomastia, followed by erectile dysfunction. Subjects receiving a dose &gt;50 mg of spironolactone daily displayed a significantly higher prevalence of side effects (42.2%), while a prevalence of 30.5% was described in the &lt; = 50 mg group. Patients in the lower dose group were treated with a higher number of anti-hypertensive drugs, especially diuretics. No statistically significant differences were seen between the two subgroups in blood pressure measurements at follow-up. Conclusions: Treatment with low doses of spironolactone could help achieve a better adherence in patients with primary aldosteronism, with a lower rate of adverse effects compared to patients treated with higher doses, with no differences in blood pressure control at follow-up. This goal could be achieved by prescribing a higher number of anti-hypertensive drugs. These findings could help the clinician in choosing the best therapeutical option for each patient.

Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy.

Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy.

Abstract 14102: The Joint Effect of Arterial Stiffness and High Central Blood Pressure on Risk of Stroke Among Hypertensive Adults

Introduction: The increases in arterial stiffness and central blood pressure (cBP) suggest significant status of vascular damages with different physio-pathological progress. However, the joint effect of them on risk of first stroke have remained uncertain. And the predictive value of CAP over peripheral blood pressure (bBP) is controversial. Hypothesis: This study aims to test the hypothesis that the combination of elevated arterial stiffness and central systolic blood pressure (cSBP) can predict first stroke and is associated with highest risks among hypertensive adults. Methods: A total of 7531 hypertensive adults without prior history of stroke were analyzed. cSBP was measured noninvasively using A-Pulse CASPro device. Arterial stiffness was measured by carotid-femoral pulse wave velocity using the noninvasive PulsePen device (WPP001-ET, DiaTecne s.r.l). Whole data was collected from July 2016 to December 2019. Increased arterial stiffness was defined as cfPWV ≥10 m/s. The primary outcome was first all-cause stroke. Results: Of the 7531 participants, mean age was 61.3 ± 9.3 years, 37.2% were male, the mean brachial blood pressure is the mean cfPWV was 9.4 ± 2.2 m/s, the mean cSBP is 131.3 ± 12.8 mmHg. During a mean follow-up time of 3.3 years, 432 (5.2%) participants developed stroke, of which 380 were ischemic strokes. Compared with the reference group (low cfPWV and cSBP), only the group with both high cfPWV and cSBP was significantly associated with risk of stroke after adjusted for covariates (HR: 1.51, 95% CI 1.10, 2.07). Similar result was found in Kaplan Meier Curve. Such association appears robust in different sub-group analysis. Conclusion: The combination of higher arterial stiffness and central systolic blood pressure is associated with highest risk of first stroke compared to other groups. The combined control of arterial stiffness and central blood pressure serves the purpose of primary prevention of first all-cause stroke among hypertensive population.

Differential contributions of cardiac, coronary and pulmonary artery vagal mechanoreceptors to reflex control of the circulation.

Distinct populations of stretch‐sensitive mechanoreceptors attached to myelinated vagal afferents are found in the heart and adjoining coronary and pulmonary circulations. Receptors at atrio‐venous junctions appear to be involved in control of intravascular volume. These atrial receptors influence sympathetic control of the heart and kidney, but contribute little to reflex control of systemic vascular resistance. Baroreceptors at the origins of the coronary circulation elicit reflex vasodilatation, like feedback control from systemic arterial baroreceptors, as well as having characteristics that could contribute to regulation of mean pressure. In contrast, feedback from baroreceptors in the pulmonary artery and bifurcation is excitatory and elicits a pressor response. Elevation of pulmonary arterial pressure resets the vasomotor limb of the systemic arterial baroreflex, which could be relevant for control of sympathetic vasoconstrictor outflow during exercise and other states associated with elevated pulmonary arterial pressure. Ventricular receptors, situated mainly in the inferior posterior wall of the left ventricle, and attached to unmyelinated vagal afferents, are relatively inactive under basal conditions. However, a change to the biochemical environment of cardiac tissue surrounding these receptors elicits a depressor response. Some ventricular receptors respond, modestly, to mechanical distortion. Probably, ventricular receptors contribute little to tonic feedback control; however, reflex bradycardia and hypotension in response to chemical activation may decrease the work of the heart during myocardial ischaemia. Overall, greater awareness of heterogeneous reflex effects originating from cardiac, coronary and pulmonary artery mechanoreceptors is required for a better understanding of integrated neural control of circulatory function and arterial blood pressure.

Design of a fractional order two layer fuzzy logic controller for drug delivery to regulate blood pressure

The main objective of this research work is to propose an effective, robust, optimal and oscillation free controller for automatic drug infusion in mean arterial blood pressure (MAP) control for anaesthesia administration, accidental case, cardiac surgery, critically-ill and post-surgery recovery wherein this system also faces uncertainties like external disturbances or noises and parameter uncertainties that adversely affect the system performance. As a consequence, the controllers designed for the MAP become indispensable to compensate such uncertainties and it is quite a complicated task for control engineers. Therefore, a controlled drug administration is required to regulate the MAP of a person during surgery/observation. In this research work, a new fractional order two layer fuzzy logic controller (FO-TLFLC) is designed to regulate MAP of a patient by administering the drug sodium nitroprusside (SNP) in a controlled manner for tracking desired blood pressure of patient in various conditions. Further, a well-established optimization technique named as grey wolf optimization (GWO) is employed to obtain optimal values of control parameters while minimizing integral absolute error (IAE). In order to present the effectiveness and robustness of proposed FO-TLFLC controller, the performance of proposed controller is compared with integer order two layer fuzzy logic controller (IO-TLFLC), single layer fuzzy logic controller (SLFLC), and proportional integral derivative (PID) controllers for maintaining the MAP to 100 mmHg in reasonable limit through SNP drug infusion. From the experimental results, it is concluded that FO-TLFLC controller can not only maintain the desired MAP but also improve the overshoot, settling-time, and error along with robustness.

Spinal Reflex Control of Arterial Blood Pressure: The Role of TRP Channels and Their Endogenous Eicosanoid Modulators.

The spinal cord is an important integrative center for blood pressure control. Spinal sensory fibers send projections to sympathetic preganglionic neurons of the thoracic spinal cord and drive sympathetically-mediated increases in blood pressure. While these reflexes responses occur in able-bodied individuals, they are exaggerated following interruption of descending control – such as occurs following spinal cord injury. Similar reflex control of blood pressure may exist in disease states, other than spinal cord injury, where there is altered input to sympathetic preganglionic neurons. This review primarily focuses on mechanisms wherein visceral afferent information traveling via spinal nerves influences sympathetic nerve activity and blood pressure. There is an abundance of evidence for the widespread presence of this spinal reflex arch originating from virtually every visceral organ and thus having a substantial role in blood pressure control. Additionally, this review highlights specific endogenous eicosanoid species, which modulate the activity of afferent fibers involved in this reflex, through their interactions with transient receptor potential (TRP) cation channels.

Intenzivno lečenje pacijenata sa kraniocerebralnom traumom - kako nam akronimi mogu pomoći?

Traumatic brain injury (TBI) is considered to be a "silent global epidemic" and is the leading cause of death in young males in developed countries, major cause of disability, morbidity, and mortality worldwide. The classification of TBI severity was performed using the Glasgow coma scale (GCS) into mild (GCS = 15-13), moderate (GCS = 12-9), and severe (GCS = 8-3). Despite developments in modern intensive care, improvements in resuscitation and vital organ support, the management of critically ill patients with traumatic brain injury presents a challenge to all members of the critical care team. Since severe head injury is often associated with poor functional outcomes due to secondary brain insults, the benefits of intensive treatment and care may not become apparent until months or years later during rehabilitation after injury. Due to the complexity and specificity of TBI, implementation of an easy-to-remember mnemonic can significantly help anesthesiologists and clinicians in conducting intensive therapy. Mnemonic GOST CAP was implementing to help with treatment of patients with primary craniocerebral trauma and prevention of secondary brain injury. GOST CAP acronym emphasizes the significance of glycemic control in neurotrauma, maintaining haemoglobin levels, oxygen support, sodium concentration, temperature maintenance, pain and agitation control, arterial blood pressure control in maintaining cerebral perfusion pressure, and partial pressure of CO2 control. The aim of this paper is to display acronyms that address the most important steps in treating patients with TBI.

Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System.

Nitric oxide (NO), the neuromodulator/neurotransmitter formed from l-arginine by neuronal, endothelial and inducible NO synthases, is involved in numerous functions across the body, from the control of arterial blood pressure to penile erection, and at central level from energy homeostasis regulation to memory, learning and sexual behavior. The aim of this work is to review earlier studies showing that NO plays a role in erectile function and sexual behavior in the hypothalamus and its paraventricular nucleus and the medial preoptic area, and integrate these findings with those of recent studies on this matter. This revisitation shows that NO influences erectile function and sexual behavior in males and females by acting not only in the paraventricular nucleus and medial preoptic area but also in extrahypothalamic brain areas, often with different mechanisms. Most importantly, since these areas are strictly interconnected with the paraventricular nucleus and medial preoptic area, send to and receive neural projections from the spinal cord, in which sexual communication between brain and genital apparatus takes place, this review reveals that central NO participates in concert with neurotransmitters/neuropeptides to a neural circuit controlling both the consummatory (penile erection, copulation, lordosis) and appetitive components (sexual motivation, arousal, reward) of sexual behavior.

The ClearSight System for Postoperative Arterial Blood Pressure Monitoring After Carotid Endarterectomy: A Validation Study.

BACKGROUNDThe majority of postoperative events in patients undergoing carotid endarterectomy (CEA) are of hemodynamic origin, requiring preventive strict postoperative arterial blood pressure (BP) control. This study aimed to assess whether BP monitoring with noninvasive beat-to-beat ClearSight finger BP (BPCS) can replace invasive beat-to-beat radial artery BP (BPRAD) in the postoperative phase.METHODSThis study was a single-center clinical validation study using a prespecified study protocol. In 48 patients with symptomatic carotid artery stenosis, BPCS and BPRAD were monitored ipsilateral in a simultaneous manner during a 6-hour period on the recovery unit following CEA. Primary endpoints were accuracy and precision of BP derived by ClearSight (Edward Lifesciences, Irvine, CA) vs. the reference standard (Arbocath 20 G, Hospira, Lake Forest, IL) to investigate if BPCS is a reliable noninvasive alternative for BP monitoring postoperatively in CEA patients. Validation was guided by the standard set by the Association for Advancement of Medical Instrumentation (AAMI), considering a BP-monitor adequate when bias (precision) is <5 (8) mm Hg. Secondary endpoint was percentage under- and overtreatment, defined as exceedance of individual postoperative systolic BP threshold by BPRAD or BPCS in contrast to BPCS or BPRAD, respectively.RESULTSThe bias (precision) of BPCS compared to BPRAD was −10 (13.6), 8 (7.2) and 4 (7.8) mm Hg for systolic, diastolic and mean arterial pressure (MAP), respectively. Based on BPCS, undertreatment was 5.6% and overtreatment was 2.4%; however, percentages of undertreatment quadrupled for lower systolic BP thresholds.CONCLUSIONSNoninvasive MAP, but not systolic and diastolic BP, was similar to invasive BPRAD during postoperative observation following CEA, based on AAMI criteria. However, as systolic BP is currently leading in postoperative monitoring to adjust BP therapy on, BPCS is not a reliable alternative for BPRAD.

An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is).

GLP-1 receptor agonists (GLP-1RAs) and SGLT-2 inhibitors (SGLT-2is) are novel antidiabetic medications associated with considerable cardiovascular benefits therapying treatment of diabetic patients. GLP-1 exhibits atherosclerosis resistance, whereas SGLT-2i acts to ameliorate the neuroendocrine state in the patients with chronic heart failure. Despite their distinct modes of action, both factors share pathways by regulating the central nervous system (CNS). While numerous preclinical and clinical studies have demonstrated that GLP-1 can access various nuclei associated with energy homeostasis and hedonic eating in the CNS via blood–brain barrier (BBB), research on the activity of SGLT-2is remains limited. In our previous studies, we demonstrated that both GLP-1 receptor agonists (GLP-1RAs) liraglutide and exenatide, as well as an SGLT-2i, dapagliflozin, could activate various nuclei and pathways in the CNS of Sprague Dawley (SD) rats and C57BL/6 mice, respectively. Moreover, our results revealed similarities and differences in neural pathways, which possibly regulated different metabolic effects of GLP-1RA and SGLT-2i via sympathetic and parasympathetic systems in the CNS, such as feeding, blood glucose regulation and cardiovascular activities (arterial blood pressure and heart rate control). In the present article, we extensively discuss recent preclinical studies on the effects of GLP-1RAs and SGLT-2is on the CNS actions, with the aim of providing a theoretical explanation on their mechanism of action in improvement of the macro-cardiovascular risk and reducing incidence of diabetic complications. Overall, these findings are expected to guide future drug design approaches.

Reduced resting beat‐to‐beat blood pressure variability in multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease associated with central nervous system demyelination known to impair healthy autonomic function. We have previously demonstrated individuals with MS exhibit lower resting muscle sympathetic nerve activity and impaired carotid baroreflex control of arterial blood pressure compared to controls. Recently, increased resting beat-to-beat blood pressure variability (BPV) has been shown to be a strong predictor of cardiovascular risk in other clinical populations. Taken together, the aim of the current investigation was to test the hypothesis that resting beat-to-beat BPV is increased in individuals with MS compared to matched healthy controls. In 7 patients with relapsing-remitting MS (5 females/2 males, EDSS <4) and 7 sex-, age-, and weight-matched healthy controls, beat-to-beat blood pressure (Finometer) was recorded during 10 minutes of quiet supine rest. Individuals with MS had similar resting mean blood pressure (BP) compared to healthy controls (P= 0.736), however the BP standard deviation (SD) and coefficient of variation (CV) was less in MS (BP SD; MS: 3.2 ± 0.2 vs. CON: 4.0 ± 0.2, P=0.022 and BP CV; MS: 3.8 ± 0.3 vs. CON: 4.7 ± 0.2, P=0.025). Similarly, mean resting systolic blood pressure (SBP) was not different between MS and healthy controls (P=0.207) but the SBP standard deviation and coefficient of variation was less in MS (SBP SD; MS: 4.7 ± 0.4 vs. CON: 6.6 ± 0.5, P=0.013 and SBP CV; MS: 4.3 ± 0.4 vs. CON: 5.8 ± 0.4, P=0.033). In contrast, there was no difference in the DBP standard deviation or coefficient of variation between the two groups (P= 0.321 and P=0.295; respectively). In summary, contrary to our original hypothesis, individuals with MS exhibited reduced resting beat-to-beat BPV compared to healthy controls. These preliminary findings may be related to altered autonomic function in this clinical population.

Effects of Mental Stress and Slow Breathing on Autonomic Control of Arterial Blood Pressure (ABP) in Young Normotensives with Hypertensive Parents (FH+) Relative to Those with Normotensive Parents (FH‐)

Young normotensive (FH+) have greater risk of hypertension than FH-. Whether mental stress differentially affects autonomic control of ABP in young normotensive FH+ relative to FH- and whether slow breathing might reduce risk of hypertension in FH+ is not known.In 25 FH- and 23 FH+ (aged 18-25 years), we recorded ABP, ECG and respiratory frequency (Rf); Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were derived from the pulse contour. The vagal component of baroreflex sensitivity (BRS) was tested by the sequence method at rest and during mental stress (Colour Stroop test). The vagosympathetic BRS was recorded as change in R-R interval evoked by the depressor response to stand from squat before and 0, 3, 6 min after mental stress. Heart rate variability (HRV) was analysed in time- and frequency-domains. Comparisons within and between FH- and FH+ were made by paired and unpaired t-tests. FH- and FH+ had similar mean ABP (ABP: 85±0.8 vs 88±1.8 mmHg) and Rf (15.9±0.6 vs 15.9±0.5 breaths/min) at rest. Mental stress increased ABP, HR, and Rf in both FH+ and FH-, but the increase in ABP was greater in FH+ (ABP: 82.0±2.0 to 109.0±4.0*; 78.3±1.8 to 98.5±2.2*†mmHg, respectively, *: P<0.05 within group, †: P<0.05 between groups). Further, CO increased in FH- only (FH-: 4.9±0.2 to 5.6±0.3*; FH+: 4.9±0.2 to 5.2±0.4 L/min), whereas TPR increased in FH+ only (FH-: 1.0±0.04 to 1.2±0.1; FH+: 1.1±0.1 to 1.8±0.3* units). Meanwhile, in the frequency domain, sympathetic indices increased and vagal indices of HRV decreased (LF increased, HF fell; LF/HF increased) in both FH- and FH+; vagal indices also decreased in the time domain (RMSSD: 60.5±7.2 to 46.8±4.8ms*; 65.8±7.9 to 47.7±6.7ms*, respectively). BRS decreased in mental stress during up- and down-sequences in SP in both FH- and FH+. Further, following the stress test, tachycardic BRS during squat to stand was preserved in FH+, but attenuated in FH- (0.50±0.05 to 0.29±0.07*; 0.50±0.05 to 0.47±0.07ms/mmHg respectively). Considering slow breathing, ABP decreased in both FH- and FH+ (ABP: 78.3±1.8 to 76.1±2.0*; 82.0±2.0 to 79.4±1.9*mmHg, respectively). Further, BRS during up-sequences increased in FH+ (0.98±0.09 to 1.2±0.09*ms/mmHg) to equal that of FH- (1.16±0.06 to 1.2±0.07ms/mmHg), while vagal indices of HRV increased and sympathetic indices decreased in FH- and FH+ (Log HF:1.7±0.03 to 1.93±0.01*; 1.7±0.03 to 1.94.01*, Log LF: 0.78±0.06 to 0.38±0.08*; 0.8±0.05 to 0.28±0.06*ms2). These findings suggest that young normotensive FH+ show an exaggerated pressor response to mental stress relative to FH- that is associated with enhanced sympathetic vasoconstriction in FH+. Further, although the vagal component of HRV and BRS was attenuated during mental stress in FH+ and FH-, the persistent tachycardic baroreflex for several minutes after stress in FH+ but not FH- suggests further baroreflex sympathetic activation can still occur in FH+. Such autonomic disturbances would be expected to increase future risk of hypertension in FH+. However, our findings with slow breathing suggest regular slow breathing may reduce this risk in FH+ by increasing cardiac vagal tone and reducing sympathetic tone.

Fluid Resuscitation for Refractory Hypotension.

Hypotension is a common occurrence, especially in anesthetized patients and in critical patients suffering from hypovolemia due to shock and sepsis. Hypotension can also occur in normovolemic animals, anesthetized or conscious, under conditions of vasodilation or decreased cardiac function. The main consequence of hypotension is decreased organ perfusion and tissue injury/dysfunction. In the human literature there is no consensus on what is the threshold value for hypotension, and ranges from < 80 to < 100 mmHg for systolic blood pressure and from < 50 to < 70 mmHg for mean arterial blood pressure have been referenced for intraoperative hypotension. In veterinary medicine, similar values are referenced, despite marked differences in normal arterial blood pressure between species and with respect to humans. Therapeutic intervention involves fluid therapy to normalize volemia and use of sympathomimetics to enhance cardiac function and regulate peripheral vascular resistance. Despite these therapeutic measures, there is a subset of patients that are seemingly refractory and exhibit persistent hypotension. This review covers the physiological aspects that govern arterial blood pressure control and blood flow to tissues/organs, the pathophysiological mechanisms involved in hypotension and refractory hypotension, and therapeutic considerations and expectations that include proper interpretation of cardiovascular parameters, fluid recommendations and therapy rates, use of sympathomimetics and vasopressors, and newer approaches derived from the human literature.