Variations Of Mean Arterial Blood Pressure Research Articles

Dynamic Cerebral Autoregulation Impairment Persists Past Resolution of Symptoms in Collegiate Athletes Following Concussion

ObjectivesDespite 3.8 million concussions occurring annually in the United States, the pathophysiological sequelae of the injury are still poorly understood. Animal and human studies have consistently reported deficits in cerebral blood flow (CBF) following concussion suggesting impairments in CBF regulation. Reductions in CBF are also associated with functional outcomes. The purpose of the study was to examine dynamic cerebral autoregulation (dCA) in an ongoing prospective cohort of collegiate athletes 3 days, 21 days, and 90 days following a concussion and compare them with non‐injured controls.Materials and MethodsTwenty‐seven NCAA and recreational athletes (20±1 years) with a physician diagnosed sports‐related concussions were enrolled in the study. For the injured athletes, data was collected on days 3,21, and 90 following concussion. Twenty‐five age and sports matched non‐injured controls (20±1 years) were also enrolled. For non‐injured controls, data was collected at one time point. Symptom number and severity was measured using the Sports Concussion Assessment Tool (SCAT‐3). Depression scores were assessed with Patient Health Questionnaire‐9 (PHQ‐9). Continuous mean arterial blood pressure (MBP) was obtained with finger photoplethysmography and middle cerebral artery blood flow velocity (MCAV) was obtained with a 2 MHz transcranial Doppler ultrasonography while subjects were seated in an upright position. dCA was estimated from transfer function (Tf) analysis of beat‐to‐beat spontaneous fluctuations in MBP and MCAV within the low (LF, 0.07–0.20 Hz) and high (HF, 0.20–0.35 Hz) frequency ranges. Effective dCA would attenuate spontaneous changes in MCAV in response to variations in MBP, which would correspond to relatively low transfer function gain. Independent and paired t‐tests were used to compare dCA between days 3, 21, and 90 following concussion with the non‐injured controls.ResultsCompare to the controls, concussed athletes exhibited greater symptom number on day‐3 (12.2±6.8 vs. 2.4±3.4; p<0.001) and higher PHQ‐9 score (8.7±5.6 vs. 2.1±2.1; p<0.001). LF Tf gain was higher on day‐3 (1.26±0.34U vs. 1.04±0.28U; p=0.016) compared to the controls. LF Tf gain continued to be high on day‐21 (1.30±0.45U; p=0.025) compared to the non‐injured controls despite no differences in symptoms number or depression scores between the groups. LF Tf gain was comparable to the controls on day‐90.ConclusionsDynamic cerebral autoregulation appears to be impaired at least up to 21 days following concussion despite improvement in symptom and depression. Cerebral autoregulation estimated from transcranial Doppler ultrasonography may be useful as a potential vascular biomarker for return‐to‐play decisions following a concussion preventing the risk of second‐impact syndrome.Support or Funding InformationThis work was supported by SMU University Research Council Grant, Spring 2015 & Texas Institute for Brain Injury and Repair (TIBIR) Pilot Grant 2016.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MPS 18-01 MODE OF ACTION OF RB150, AN AMINOPEPTIDASE A INHIBITOR PRODRUG AS A CENTRALLY-ACTING ANTIHYPERTENSIVE AGENT IN DOCA-SALT HYPERTENSIVE RATS

Objective: In the brain, angiotensin III (AngIII) generated from angiotensin II (AngII) by aminopeptidase A (APA) exerts a tonic stimulatory action on the control of blood pressure (BP) in hypertensive rats. Inhibition of brain APA by RB150, an orally active prodrug of the specific and selective APA inhibitor, blocks brain AngIII formation and normalizes BP in hypertensive rats. Since following blockade of brain AngIII formation by RB150, no AngII accumulation was observed, we aimed to delineate if this treatment induces the activation of another metabolic pathway of brain AngII, in particular angiotensin converting enzyme type 2 (ACE2) which converts AngII into angiotensin 1–7 (Ang1–7). Design and Method: For this purpose, RB150 and MLN4760, an ACE2 inhibitor, were administered by intracerebroventricular (ICV) route after insertion of an intracerebral cannula to alert DOCA-salt rats, a model of salt-dependent hypertension. Mean arterial blood pressure (MABP) was recorded via an arterial femoral catheter. Maximal MABP decrease and area under the curve (AUC) of the variations in MABP were calculated. Results: ICV administration of RB150 (100 μg) significantly decreased MABP compared to vehicle (−23 ± 3 mmHg vs −6 ± 2 mmHg; AUC: 17.6 ± 2 vs 2.1 ± 3). Administration of MLN4760 (10 μg) didn’t induce any significant change of MABP compared to vehicle (−10 ± 3 mmHg; AUC: 1.4 ± 2). Co-administration of MLN4760 (10 μg) with RB150 (100 μg) partially inhibits RB150-induced BP decrease. Conclusions: In conclusion, ICV administration of the ACE2 inhibitor alone has no effect on BP indicating that in DOCA-salt rats, brain Ang1–7 does not exert a tonic stimulatory effect on the control of BP. However, when conversion of brain AngII into AngIII is blocked by RB150, there is an activation of the conversion by ACE2 of brain AngII into Ang1–7, which by acting on the Mas receptor, may participate to the RB150-induced BP decrease in hypertensive rats.

OP.6D.03] MODE OF ACTION OF RB150, AN AMINOPEPTIDASE A INHIBITOR PRODRUG AS A CENTRALLY-ACTING ANTIHYPERTENSIVE AGENT IN DOCA-SALT HYPERTENSIVE RATS

Objective: In the brain, angiotensin III (AngIII) generated from angiotensin II (AngII) by aminopeptidase A (APA) exerts a tonic stimulatory action on the control of blood pressure (BP) in hypertensive rats. Inhibition of brain APA by RB150 (also known as QGC001), an orally active prodrug of the specific and selective APA inhibitor EC33, blocks brain AngIII formation and normalizes BP in hypertensive rats. Thus, RB150 has emerged as the prototype of a new class of centrally-acting antihypertensive agents and is currently evaluated in a phase II clinical trial in hypertensive patients. Since following blockade of brain AngIII formation by RB150, no AngII accumulation was observed, we aimed to delineate if this treatment induces the activation of another metabolic pathway of brain AngII, in particular angiotensin converting enzyme type 2 (ACE2) which converts AngII into angiotensin 1–7 (Ang1-7). Design and method: For this purpose, RB150 and MLN4760, an ACE2 inhibitor, were administered by intracerebroventricular (ICV) route after insertion of an intracerebral cannula to alert DOCA-salt rats, a model of salt-dependent hypertension. Mean arterial blood pressure (MABP) was recorded via an arterial femoral catheter. Maximal MABP decrease and area under the curve (AUC) of the variations in MABP were calculated. Results: ICV administration of RB150 (100 μg) significantly decreased MABP compared to vehicle (−23 ± 3 mmHg vs −6 ± 2 mmHg; AUC: 17.6 ± 2 vs 2.1 ± 3). Administration of MLN4760 (10 μg) didn’t induce any significant change of MABP compared to vehicle (−10 ± 3 mmHg; AUC: 1.4 ± 2). Experiments in progress show that a co-administration of MLN4760 (10 μg) with RB150 (100 μg) partially inhibits the RB150-induced BP decrease. Conclusions: In conclusion, ICV administration of the ACE2 inhibitor alone has no effect on BP indicating that in DOCA-salt rats, brain Ang1-7 does not exert a tonic stimulatory effect on the control of BP. However, when conversion of brain AngII into AngIII is blocked by RB150, there is an activation of the conversion by ACE2 of brain AngII into Ang1-7, which by acting on the Mas receptor, may participate to the RB150-induced BP decrease in hypertensive rats.

Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function

The assessment of cerebrovascular regulatory mechanisms often requires flexibly controlled and precisely timed changes in arterial blood pressure (ABP) and/or inspired CO₂. In this study, a new system for inducing variations in mean ABP was designed, implemented and tested using programmable sequences and programmable controls to induce pressure changes through bilateral thigh cuffs. The system is also integrated with a computer-controlled switch to select air or a CO₂/air mixture to be provided via a face mask. Adaptive feedback control of a pressure generator was required to meet stringent specifications for fast changes, and accuracy in timing and pressure levels applied by the thigh cuffs. The implemented system consists of a PC-based signal analysis/control unit, a pressure control unit and a CO₂/air control unit. Initial evaluations were carried out to compare the cuff pressure control performances between adaptive and non-adaptive control configurations. Results show that the adaptive control method can reduce the mean error in sustaining target pressure by 99.57 % and reduce the transient time in pressure increases by 45.21 %. The system has proven a highly effective tool in ongoing research on brain blood flow control.

Cerebral Tissue Oxygenation and Regional Oxygen Saturation Can Be Used to Study Cerebral Autoregulation in Prematurely Born Infants

The coupling of cerebral intravascular oxygenation (dHbD) with mean arterial blood pressure (MABP) was taken as a reflection of autoregulation assuming constant arterial oxygen content. However, this method is sensitive to movement artifacts. We examined whether the cerebral tissue oxygenation index (cTOI) and regional oxygen saturation (rScO2) may replace dHbD and changes in total Hb (dHbT), respectively. Correlation (COR) and coherence (COH) were used to measure the agreement of MABP with rScO2/dHbT and cTOI/dHbD. dHbD/cTOI and dHbT/rScO2 recordings of, respectively, 34 and 20 preterm infants in need for intensive care were studied during the first days of life. dHbD and cTOI were obtained with the NIRO300 and rScO2 and dHbT with the INVOS4100. Invasive MABP was measured continuously. COR and COH scores of MABP versus dHbD/dHbT were compared with the corresponding ones by replacing dHbD/dHbT by cTOI/rScO2, respectively. Generally, no significant score differences were found for dHbD/cTOI. Differences for dHbT/rScO2 were slightly larger but still within the normal variation of the parameters. Differences become insignificant when restricting calculations to epochs of larger variation in MABP (>10 mm Hg). Hence, we suggest that cTOI and rScO2 can be used to study cerebral autoregulation in newborns.

Spinal Anesthesia for Cesarean Delivery in Severely Preeclamptic Women: Don???t Throw Out the Baby with the Bathwater!

T he optimal anesthetic technique for cesarean delivery in severely preeclamptic women remains controversial. Recent clinical practice, however, indicates that spinal anesthesia can be, and is, safely used. In the past, there has been concern that intravascular volume contraction related to preeclampsia could result in catastrophic hypotension that would be difficult to treat (1). As a result, epidural anesthesia became the preferred neuraxial technique for cesarean delivery in women with severe preeclampsia because of a more gradual onset of sympathectomy. In fact, we now know that hypotension may occur less frequently when spinal anesthesia is administered to preeclamptic as compared with normotensive women having a cesarean delivery in modern day practice (2). Smalldose spinal as part of a combined spinal-epidural technique with subsequent top-off of the epidural component has also been advocated, but there are many anesthesiologists and obstetricians who are still concerned about the use of spinal anesthesia in preeclampsia (3). There are now several studies that support the use of spinal anesthesia in the severely preeclamptic (2–6). In the first, a prospective and randomized trial, there was no significant difference in the incidence of hypotension in severely preeclamptic women having spinal as compared with epidural anesthesia for cesarean delivery (4). The findings of this paper resonated among anesthesiologists and obstetricians because it was performed at Parkland Hospital in Dallas, Texas, an institution that for many years taught that spinal anesthesia was absolutely contraindicated in severely preeclamptic women. The second study, a retrospective review, reported that there was no significant difference in the lowest mean arterial blood pressure (MABP) between severely preeclamptic women having spinal as compared with epidural anesthesia for cesarean delivery (5). Most recently, Aya et al. (2) in a prospective cohort study reported that the incidence and severity of hypotension were in fact less in severely preeclamptic women as compared with normotensive women having a cesarean delivery with spinal anesthesia. In this issue of Anesthesia & Analgesia, two more studies weigh in on the subject, one by Visalyaputra et al. (6) and the other, a follow-up study, by Aya et al. (11). There is good news and bad news. First, the potentially bad news for advocates of spinal anesthesia is that Visalyaputra et al. (6) report that the use of spinal anesthesia for cesarean delivery in severely preeclamptic women was more likely to result in mild hypotension and to require more ephedrine to correct than epidural anesthesia. However—before we throw the baby out with the bathwater—there is also good news if we look at this finding in perspective. The hypotension was mild and the difference in the median lowest MABP measured in the spinal as compared with epidural anesthesia group was small and transient (generally 1 min). The current study by Visalyputra et al. (6) selected a group of preeclamptic women who were categorized as “severe” and thus would be at greatest risk to develop hypotension related to sympathectomy. They also excluded women who were in labor because labor can decrease the incidence of hypotension under regional anesthesia (7). Women were prepared for surgery with hydration and hydralazine administration (to decrease the diastolic blood pressure to at least 90 mm Hg), and most received magnesium sulfate. The authors attempted to standardize obstetric and Accepted for publication May 12, 2005. Address correspondence and reprint requests to David J. Birnbach, MD, Professor and Executive Vice Chair, Department of Anesthesiology University of Miami School of Med, 1611 NW 12th Avenue Miami, FL 33136. Address electronic mail to dbirnbach@miami.edu.

Diurnal variations of glomerular filtration rate and albuminuria in diabetic nephropathy

The aim of our study was to evaluate the diurnal variation in glomerular filtration rate (GFR), and the potential mechanisms responsible for such variations in GFR and albuminuria in diabetic nephropathy. In three 24-hour urine samples, divided into a night- and daytime portion, diurnal variation in albuminuria (ELISA) was assessed. Furthermore, during recumbency changes in albuminuria, GFR (51Cr-EDTA plasma clearance) and arterial blood pressure (TM2420) from nighttime (00:00 to 05:00 hours) to subsequent daytime (08:00 to 13:00 hours) were examined in 20 type 1 diabetic patients with diabetic nephropathy. The 24-hour urine collections showed an average rise in albuminuria from night- to daytime of 51% (95% CI; 16 to 95; P < 0.01). During recumbency a non-significant rise was recorded from night- to daytime in albuminuria (22%, -8 to 61, P=0.15), simultaneously with an increase in GFR of 9.0% (3.4 to 14.5, P < 0.005) and mean arterial blood pressure (MABP) of 8.0% (4.3 to 11.7, P < 0.0001). No diurnal variation in fractional clearance of albumin was found. Significant associations between MABP and albuminuria were demonstrated during night- (R2=0.50; P < 0.001) and daytime (R2=0.48; P < 0.005). A linear regression analysis between diurnal variations in MABP and GFR showed that an increase in MABP (of 10%) from night- to daytime was associated with a significant increase in GFR (of 8.0%, 0.2 to 4.1, P < 0.02). Our study revealed diurnal variations in GFR, albuminuria and MABP in diabetic nephropathy, with lowest values during sleep at night. The observed diurnal variation in albuminuria seems to be explained partly by mechanisms related to orthostasis, and partly by the diurnal variation in GFR and serum albumin concentration. The diurnal variation of blood pressure seems to play a role for the diurnal changes in GFR and albuminuria.

Changes of blood pressure, sodium excretion and sodium balance due to variations of the renin-angiotensin-aldosterone system

Studies were performed in partly free moving Beagle dogs, kept under standardized environmental and dietetic conditions (food intake: once daily at 8:30 a.m., 5.5 mmol Na/kg body weight per 24 h). The dogs were chronically instrumented with an inflatable cuff around the aorta above the renal arteries, two aortic catheters above and below the cuff, and a bladder catheter. Three protocols were performed in 7 dogs each: ( i) Control: urine collection in 20-min intervals and measurement of Na excretion, continuous registration of mean arterial blood pressure (MABP) and heart rate for 4 consecutive days. ( ii) As ( i), but additional servocontrolled reduction of the renal perfusion pressure (rRPP) to stimulate renin secretion and the formation of angiotensin II and aldosterone. ( iii) As ( ii), but additional constant infusion of the angiotensin converting enzyme inhibitor Captopril. Despite rRPP Na is only transiently retained (pressure escape). MABP level is elevated, as long as total-body Na is augmented. In protocol iii no Na retention occurs, indicating that rRPP per se causes no Na retention. MABP level remained unchanged. Independent of the preset MABP level similar diumal variation in MABP are present in all protocols. During control days major amounts of Na are excreted postprandially. Up to 5:00 p.m. 65% of the daily Na intake is excreted. After disturbance of Na control (protocols ii and iii) the Na excretion is shifted to the evening and night. Probably due to this shift Na retention can be prevented. Furthermore, these results demonstrate that rRPP-induced increases of total body Na and MABP are solely mediated by the activation of the renin-angiotensin-aldosterone system.

Effects of ITF 296 on Epicardial Coronary Artery Diameter During Acute and Long-Term Treatment in the Conscious Dog

The action of the newly developed organic nitrate ITF 296 on large coronary arteries was investigated during acute and long-term treatment in the conscious dog, chronically instrumented for recording of large coronary artery diameter (CD), mean arterial blood pressure (MBP), and heart rate (HR). Short-term steady-state infusion of ITF 296 at doses of 0.1-30 micrograms/kg/min induced a dose-dependent increase in CD. Maximal coronary artery dilation (+11%) was reached at 10 micrograms/kg/min and no further increase was observed at 30 micrograms/kg/min. At the same doses no significant variations of MBP or HR were observed. Long-term administration (5-day infusion) of ITF 296 at 20 micrograms/kg/min resulted in a 10% increase in CD, and the effect was well maintained over the entire infusion period. MBP did not change significantly, whereas HR rose by 21% by the second day of infusion and remained elevated until the end of the treatment. These results confirm that ITF 296 is an effective dilator of large coronary arteries at doses devoid of peripheral hemodynamic effects. Moreover, the vasodilating effect on coronary arteries is well maintained during long-term administration, suggesting a reduced tolerance development.

Persistence of impaired autoregulation of cerebral blood flow in the postictal period in piglets.

Cerebral blood flow (CBF) autoregulation was evaluated in the postictal period in unanesthetized term newborn piglets with a mean age of 5.7 +/- 3 days. Seven animals (group 1) received 1 mg/kg bicuculline to induce brief generalized seizures, and six control animals (group II) received saline. Twenty to 90 min after the end of seizure activity in group I or saline injection in group II, CBF was measured by the radioactive labeled microspheres method at three levels of mean arterial blood pressure (MABP) obtained by controlled blood withdrawal within the normal range for autoregulation. In the postictal period, baseline CBF was higher in group I than in group II (85 +/- 21 vs. 48 +/- 7 ml/min/100 g, p less than 0.001). During hypotension, total CBF was positively correlated with variations of MABP in group I (r = 0.739, p less than 0.01) but not in group II. Regional CBF showed the same correlation with MABP. These data show that after seizures in piglets, the rise in CBF is associated with a persistent impairment of CBF autoregulation. These hemodynamic alterations may be relevant in the pathogenesis of hemorrhagic or ischemic brain lesions.