Baseline Mean Arterial Blood Pressure Research Articles

Haemodynamic effects of intravenous acetaminophen in critically ill paediatric patients: a retrospective chart review

ObjectivesHaemodynamic changes following intravenous acetaminophen are well studied in adults. Limited data are published in critically ill paediatric patients, especially from the Middle East. We aim to investigate haemodynamic effects...

Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.

Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.

892-P: Influence of Preceding Medications on the Renal Outcomes of Japanese Diabetics Treated with SGLT2 Inhibitors and GLP-1 Receptor Agonists

Background/Objective: Evidence of cardiovascular and renal outcomes has already been shown for SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1Ras); therefore, combination therapy with these drugs is of clinical interest. This study aimed to evaluate the effect of the preceding drug for patients with the combination treatment of SGLT2i and GLP1Ra on renal outcomes. Methods: We retrospectively extracted data of patients with type 2 diabetes mellitus who had received both SGLT2i and GLP1Ra treatment for at least 1-year at 18 medical facilities in Japan. Finally, 341 patients in the GLP1Ra-preceding group and 319 in the SGLT2i-preceding group were analyzed. The renal composite outcome was progression of the albuminuria stage, ≥30% decrease in eGFR, or both. The multiple imputation method for missing values and an inverse probability weighting method using the propensity score were used for the comparison of outcome. Results: The median observation period and the incidence of the renal composite outcome in the SGLT2i-preceding group and the GLP1Ra-preceding group was 55.1months, 26.9% and 58.7months, 25.6%, respectively, with an odds ratio (OR) [95% confidence interval] of 1.50 [0.89, 2.53] (p=0.13). The ORs for the ≥30% decrease in eGFR and the progression of albuminuria stage were 0.96 [0.47, 2.00] (p=0.93) and 1.76 [0.97, 3.69] (p=0.06), respectively. Compared to the GLP1Ra-preceding group, the annual change in eGFR and change in the logarithmic value of urine albumin-to-creatinine ratio (LnACR) was 0.27mL/min/1.73 m2/year [-0.60, 1.14], and 0.18 [-0.10, 0.43] respectively. LnACR at baseline, pioglitazone use, and baseline mean arterial blood pressure were independent factors for renal composite outcome with ORs [95% CI] of 1.15 [1.01, 1.31], 0.47 [0.23, 0.96], and 1.03 [1.01, 1.05], respectively. Conclusion: In combination therapy with SGLT2i and GLP1Ra, the difference in the preceding drug did not affect the renal composite outcome. Disclosure K.Kobayashi: None. M.Toyoda: None.

Predictability of Radiologically Measured Psoas Muscle Area for Intraoperative Hypotension in Older Adult Patients Undergoing Femur Fracture Surgery

This retrospective study aimed to determine the predictive value of radiologically measured psoas muscle area (PMA) for intraoperative hypotension (IOH) using receiver operating characteristic (ROC) curves in older adult patients with hip fractures. The cross-sectional axial area of the psoas muscle was measured by CT at the level of the 4th lumbar vertebrae and normalized by body surface area (BSA). The modified frailty index (mFI) was used to assess frailty. IOH was defined as an absolute threshold of mean arterial blood pressure (MAP) < 65 mmHg or a relative decrease in MAP > 30% from baseline MAP. Among the 403 patients, 286 (71.7%) had developed IOH. PMA normalized by BSA in male patients was 6.90 ± 0.73 in the no-IOH group and 4.95 ± 1.20 in the IOH group (p < 0.001). PMA normalized by BSA in female patients was 5.18 ± 0.81 in the no-IOH group and 3.78 ± 0.75 in the IOH group (p < 0.001). The ROC curves showed that the area under the curve for PMA normalized by BSA and modified frailty index (mFI) were 0.94 for male patients, 0.91 for female patients, and 0.81 for mFI (p < 0.001). In multivariate logistic regression, low PMA normalized by BSA, high baseline systolic blood pressure, and old age were significant independent predictors of IOH (adjusted odds ratio: 3.86, 1.03, and 1.06, respectively). PMA measured by computed tomography showed an excellent predictive value for IOH. Low PMA was associated with developing IOH in older adult patients with hip fractures.

EFFECT OF SEVERE FOOD RESTRICTION ON BLOOD PRESSURE REGULATION IN THE FEMALE SPRAGUE DAWLEY RAT

Objective: Eating disorders have both short term and long term consequences that can be present years after recovery. However, the molecular mechanisms contributing to the increased cardiovascular risk for “recovered’’ individuals is still largely unknown. We have previously found that inbred female F344 rats have altered renin-angiotensin-aldosterone-system regulation of mean arterial blood pressure(MAP) following a 60% food restriction (to achieve a 15–20% body weight drop in F344). The purpose of this work was to see if these are robust changes that can be replicated in an outbred strain which is a better model of the human population. Design and method: Two-month-old female Sprague Dawley(SD) rats were divided into control(CON) that had access to food ad libitum and a food restricted(FR) that received a 56% food restriction (to achieve a 15–20% body weight drop in SD). After 2 weeks, CON (n = 5) and FR (n = 5) rats were sacrificed, the remaining FR (n = 4) and CON (n = 4) rats received chow ad libitum for 5 months. Prior to sacrifice, an acute MAP response to 200ng/kg Angiotensin II(ANGII) was recorded from the femoral artery under anesthesia by indwelling catheter. Results: We found that after 14 days of food restriction the FR rats had lower baseline MAP compared to CON rats (CON = 92 ± 3.0 vs. FR = 75 ± 0.4mmHG, p &lt; 0.05), however, both groups had the same absolute response in MAP to ANGII infusion (CON = 19 ± 2.8 vs. FR = 18 ± 2.0 mmHG). After 5 months of refeeding we found that there were no statistical differences in baseline MAP between the groups (CON = 86 ± 2.2 vs. FR = 91 ± 4.8mmHg), however, there was a trend towards an increase in peak MAP response to ANGII (CON = 19 ± 1.5 vs. FR = 27 ± 3.0mmHg, p = 0.056). Conclusions: When compared to F344, we found similar trends in baseline MAP immediately following food restriction and months after refeeding. We did not detect a blunting of the ANGII response immediately following food restriction as in F344. We did find similarities between F344 and SD in response to ANGII months after refeeding. Food restriction appears to create a robust change in the response to ANGII months after refeeding, that is not strain specific.

Deletion of the Transient Receptor Vanilloid‐1 (TRPV1) Channel in Rats Attenuates 2‐Kidney‐1‐Clip Hypertension

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel Trpv1‐/‐ rat using CRISPR/Cas9 and deletion of exon 3. Male and female Trpv1‐/‐ and wild‐type littermates (8‐12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male Trpv1‐/‐ and wild‐type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7‐9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male Trpv1‐/‐ versus wild‐type rats (125±8 vs 155±2 mmHg, respectively: P&lt;0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male Trpv1‐/‐ versus wild‐type rats (‐53±4 vs ‐86±3 mmHg, respectively; P&lt;0.001). On the other hand, female Trpv1‐/‐ and wild‐type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6‐9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female Trpv1‐/‐ versus wild‐type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female Trpv1‐/‐ versus wild‐type rats (‐64±7 vs ‐65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that Trpv1‐/‐ channels contribute to the established phase of renovascular hypertension in male rats.

Renal chemosensitive and mechanosensitive afferent responses are preserved in TRPV1 knockout rats

The transient receptor potential vanilloid type‐1 (TRPV1) channel is expressed in renal sensory nerves, and intrarenal administration of the TRPV1 agonist capsaicin increases renal afferent nerve activity (ARNA). Nonselective denervation of renal sensory nerves using high concentration capsaicin reduces arterial blood pressure (ABP) in experimental models of hypertension. Pharmacological blockade of TRPV1 using renal pelvic infusion of capsazepine attenuates ARNA responses to capsaicin, CGRP, and elevated pelvic pressure. Thus, TRPV1 channels mediate activation of renal sensory nerves.To test this hypothesis, we generated a novel TRPV1 knockout rat (TRPV1‐/‐) using CRISPR/Cas9 to produce a 26bp deletion in exon 3. Multifiber ARNA responses to chemical (bradykinin and capsaicin) and mechanical (elevated renal pelvic pressure) stimuli were compared in Inactin‐anesthetized male and female wild‐type and TRPV1‐/‐ littermates (250‐400g). There were no significant differences in baseline mean ABP between wild‐type and TRPV1‐/‐ rats (122±2 mmHg vs 122±3 mmHg, respectively; p=0.48, n=8‐10), or baseline ARNA between wild‐type and TRPV1‐/‐ rats (14±3 Hz vs 18±5 Hz, respectively; p=0.24, n=8‐10).Intrarenal artery infusion of capsaicin (0.1–10μM, 50μL per 15s) significantly increased ipsilateral ARNA in wild‐type but not TRPV1‐/‐ rats (Δ discharge 65±14 Hz vs 9±3 Hz at 10μM, respectively; p&lt;0.05, n=7). As a second chemosensitive stimulus, intrarenal artery infusion of bradykinin (0.1–10μM, 50μL per 15s) produced significant increases in ARNA in ­both wild‐type and TRPV1‐/‐ rats that were not significantly different between groups (Δ discharge of 10μM: 52±11 Hz vs 76±21 Hz, respectively; p=0.33, n=7). Elevated renal pelvic pressure (0–20mmHg; 30s) significantly increased ARNA in both wild‐type and TRPV1‐/‐ rats; however, ARNA responses were significantly smaller in wild‐type versus TRPV1‐/‐ rats (Δ discharge with 20mmHg: 17±3 Hz versus 29±6 Hz, respectively; p=0.03, n=8‐9).The preservation of ARNA responses in TRPV1‐/‐ rats contradicts prior studies using pharmacological TRPV1 antagonists. A final set of experiments tested whether intrapelvic capsazepine infusion (200μM, 200μl per 3 min) attenuates ARNA responses to elevated pelvic pressure (20mmHg) in both wild‐type and Trpv1‐/‐ rats. Interestingly, pelvic administration of capsazepine attenuated mechanosensitive ARNA responses in both wildtype (saline: 31±3 Hz vs capsazepine: 8±1 Hz; n=3) and TRPV1‐/‐ (saline: 20±7 Hz vs capsazepine: 6±1 Hz; n=3) rats thereby suggesting a TRPV1‐independent action of capsazepine.In conclusion, TRPV1 channels are dispensable for the activation of chemo‐ and mechanosensitive renal sensory nerves.

HEMODYNAMIC RESPONSES BETWEEN I-GEL AND ENDOTRACHEAL TUBE IN PATIENTS UNDERGOING LAPAROSCOPIC SURGERIES

Background: Laparoscopic surgeries are commonly performed under general anesthesia using endotracheal intubation. Laryngoscopy and endotracheal intubation cause exaggerated hemodynamic response which may be detrimental to hypertensive patients and those with cardiac issues. I-gel, a second generation supraglottic airway device mitigates this effect and can be safely used under general anesthesia. Methods: This was a prospective comparative study consisting of 64 patients undergoing laparoscopic surgery. The patients were divided into endotracheal tube group and I-gel group, each group with 32 patients, which was done according to convenience sampling method. Patient’s baseline heart rate, systolic, diastolic and mean arterial blood pressure was recorded. These parameters were recorded at one, three and five minutes of placement of airway device, after creating caboperitonium and after extubation which were compared statistically. Results: Exaggerated hemodynamic response was observed in endotracheal tube group after endotracheal intubation and immediately after extubation as compared to I-gel group which were more stable. However, both the group had similar hemodynamic response during carboperitonium. Conclusions: I-gel can be safely used in laparoscopic surgeries under general anesthesia and also lessens the hemodynamic response as compared to endotracheal tube during laryngoscopy and intubation.

Comparison of an ephedrine infusion with lidocaine %5 for prevention of hypotension during spinal anesthesia in cesarean section

BackgroundSpinal anesthesia is the method of choice for cesarean section and in most cases causes hypotension. ObjectiveThe aim of this study was to treat hypotension by ephedrine in order to prevent maternal and fetal complications, and also to determine the effective amount of ephedrine for reducing arterial hypertension in order to prevent its complications, including cardiac arrhythmias. MethodThis cross-sectional descriptive study was conducted on 131 patients. Mean arterial blood pressure (MAP) of the candidates for cesarean section in the supine position was measured and recorded as mean baseline blood pressure. 75 mg of lidocaine (5%) was used as spinal anesthesia, following which the average blood pressure was measured every 1 min. In the event of a decrease in the mean arterial blood pressure of at least 20% of the mean baseline blood pressure, ephedrine 0.1/mg/kg was injected intravenously and after 1 min of MAP was measured. ResultThe prevalence of hypotension was 89.30%. 25.60% of patients with hypotension had 30–34.99% reduction in MAP compared to baseline MAP. 12% patients had 40% drop in their MAP. 4 min following spinal anesthesia, the incidence of hypotension reduced by 20%. The average dose of ephedrine required to reduce the incidence of hypotension was 20.5 mg. ConclusionReduction in MAP following spinal anesthesia using lidocaine is common. Ephedrine at the dose of 20 mg is effective to reduce the incidence of perioperative hypotension.

Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P&lt;0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P&lt;0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

Abstract MP48: Crispr/cas9 Trpv1 Deletion In Rats Does Not Impair Mechano- And Chemo-sensory Renal Afferent Nerve Responses

Elevated renal afferent nerve activity (ARNA) or dysfunctional renal reflexes contributes to hypertension and chronic kidney disease. The transient receptor potential vanilloid type-1 (TRPV1) channel is expressed in renal sensory nerves, and intrarenal administration of the TRPV1 agonist capsaicin increases ARNA. Nonselective denervation of renal sensory nerves using high-concentration capsaicin reduces arterial blood pressure (ABP) in experimental models of hypertension. However, the role of TRPV1 channels in ARNA responses to chemo- and mechano-sensitive stimuli has not been directly tested. To test this hypothesis, we generated a novel TRPV1 rat knockout model (TRPV1 -/- ) using CRISPR/CAS9 to delete exon 3 . ARNA multifiber recordings were performed in male and female TRPV1 -/- and wild-type littermates (250-400g) after decerebration or Inactin anesthesia (data combined). Wild-type and TRPV1 -/- rats had no significant differences in baseline mean ABP (126±4 mmHg vs 138±5 mmHg, respectively; n=8-10) or heart rate (451±25 bpm vs 432±24 bpm, respectively; n=8-10). Baseline ARNA was not different between wild-type and TRPV1 -/- rats (16±3 Hz vs 28±6 Hz, respectively; n=8-10). Intrarenal artery infusion of the TRPV1 agonist capsaicin (0.1-10μM, 50μL per 15s) significantly increased ipsilateral ARNA in wild-type but not TRPV1 -/- rats (Δ discharge with 10μM: 65±3 Hz vs 6±1 Hz, respectively; n=5-7). As a second chemosensitive stimulus, intrarenal artery infusion of bradykinin (0.1-10μM, 50μL per 15s) produced similar increases in ipsilateral ARNA between wild-type and TRPV1 -/- rats (Δ discharge with 10μM: 52±6 Hz vs 73±18 Hz, respectively; n=5-6). Finally, elevated renal pelvic pressures (0-20mmHg; 30s) significantly increased ipsilateral ARNA in both wild-type and TRPV1 -/- rats; however, the ARNA response was significantly greater in TRPV1 -/- versus wild-type rats (Δ discharge with 20mmHg: 47±14 Hz versus 18±6 Hz, respectively; n=5-8). In conclusion, mechanosensitive and chemosensitive ARNA responses remain intact in TRPV1 -/- rats. The mechanisms responsible for renal sensory nerve activation remain unidentified and the impact of TRPV1 deletion in rat models of hypertension and kidney disease remains to be tested.

Abstract MP21: Circadian Cycle Exaggerates Sympathoexcitatory Responses To Activation Of Chemosensitive Renal Sensory Nerves

Renal sensory nerves contribute to hypertension and renal dysfunction in chronic kidney disease. Selective chemokines (e.g., bradykinin or capsaicin) activate renal sensory nerves and produce reflexive efferent sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses. SNA, ABP, and renal function exhibit circadian patterns; yet the impact of circadian cycle on chemosensitive responses is unknown. We hypothesized that SNA and hemodynamic responses would be greater during the active phrase or nighttime versus the inactive phase or daytime. In Inactin anesthetized rats, simultaneous renal and splanchnic SNA and ABP were measured during intrarenal arterial infusion of capsaicin or bradykinin (0.1 μM - 30.0 μM; 50 μl over 15 s) at nighttime (N; 20:00-04:00; n= 12M, 10F) versus daytime (D; 09:00-16:00; n= 8M, 8F). Baseline mean ABP was significantly elevated during nighttime (N: 104±2 mmHg; D: 97±2 mmHg, p=0.04). Intrarenal capsaicin infusion produced concentration-dependent increases in renal and splanchnic SNA. Renal SNA increased more at nighttime versus daytime at 10 μM (N: 723±136 vs D: 409±79 %; p=0.03) and 30 μM (N: 826±181 vs D: 509±80 %; p=0.03). Similarly, splanchnic SNA was greater during nighttime versus daytime at 10 μM (N: 501±117 vs D: 204±53 %, p=0.03) and 30 μM (N: 537±101 vs D: 295±68 %; p=0.03). However, ABP responses were similar between nighttime versus daytime (30uM: 7±1 vs 6±1 mmHg, respectively). Intrarenal infusion of bradykinin produced concentration-dependent increases in renal and splanchnic SNA. Renal SNA increased more at nighttime versus daytime at 10 μM (N: 1773±216 vs D: 1249±112 %; p=0.01) and 30 μM (N: 2605±263 vs D: 1783±163 %; p=0.001). Similarly, splanchnic SNA was exaggerated at nighttime versus daytime at 0.1 μM (N: 163±65 vs D: 0±0 %; p=0.02), 1.0 μM (N: 566±114 vs D: 184±52 %; p=0.005), 10 μM (N: 1110±193 vs D: 583±87 %; p=0.006) and 30 μM (N: 2008±193 vs D: 1044±162 %; p&lt;0.001). ABP response were similar between nighttime versus daytime at 30 μM (10±2 vs 6±1 mmHg, respectively). Circadian cycle exaggerates sympathoexcitatory responses produced by chemosensitive renal sensory nerve activation.

Abstract MP22: Dietary Salt Restriction And High Salt Intake Exaggerate Sympathetic Reflexes And Sensitize Central Autonomic Networks: Potential Mechanisms Of The J-shaped Curve

Observational cohort studies suggest that severe salt restriction increases cardiovascular morbidity/mortality, and the relationship between cardiovascular morbidity and dietary salt intake resembles a J-shaped curve. A high salt diet exaggerates sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses to several cardiovascular reflexes in salt-resistant animals. This study assessed whether salt restriction also exaggerates cardiovascular reflex responses and sensitizes central autonomic networks. To test this hypothesis, male Sprague-Dawley rats were fed low (0.01% NaCl), normal (0.1% NaCl), and high (4.0% NaCl) salt diet for 14-21 days. Baseline mean ABP was not different across groups (low: 104±4, normal: 107±4, high: 107±4mmHg). Activation of sciatic afferents (1ms pulse, 500uA, 5s duration, 2-20Hz) produced significantly greater increases in renal SNA (5Hz; low: 196±12, normal: 136±9, high: 177±8%, n=8, P&lt;0.05) and ABP (5Hz; low: 29±3, normal: 16±1, high: 24±2 mmHg, n=8, P&lt;0.05) of rats fed low and high versus normal NaCl diets. Activation of the aortic depressor nerve (2ms pulse, 500uA, 15s duration, 2-20Hz) produced significantly greater decreases in renal SNA (5Hz; low: -55±9, normal: -34±8, high: -63±13%, n=7-8, P&lt;0.05) and ABP (5Hz; low: -31±3, normal: -15±5, high: -32±5 mmHg, n=7-8, P&lt;0.05) of rats fed low and high versus normal NaCl diets. To test whether dietary salt intake sensitized central sympathetic circuits, microinjection of L-glutamate (0.1-1nmol, 30nL) in the rostral ventrolateral medulla produced significantly greater increases in renal SNA (0.1nmol; low: 212±15, normal: 149±8, high: 183±17%, n=7-8, P&lt;0.05) and ABP (0.1Hz; low: 20±2, normal: 12±2, high: 22±2 mmHg, n=7-8, P&lt;0.05) of rats fed low and high versus normal NaCl diets. Finally, rats fed low or high NaCl versus normal NaCl diets displayed exaggerated cardiovascular responses to cage switch or mild restraint and increased 24-h blood pressure variability. The present findings show that severe salt restriction and excess dietary salt intake exaggerate sympathetic and cardiovascular responses, and may be explained by a parallel change in the sensitivity of central autonomic networks to resemble a J-shaped curve.

428 Baroreflex sensitivity during handgrip in obstructive sleep apnea with and without CPAP

Abstract Introduction Obstructive sleep apnea (OSA) disrupts multiple aspect of autonomic regulation; it is unclear whether intervention with continuous positive airway pressure (CPAP) can correct such disruptions. One key index of autonomic regulation is baroreflex sensitivity (BRS), an index that indicates heart rate (HR) changes to blood pressure (BP) alterations, and which is a significant measure for evaluating long-term cardiovascular changes induced by OSA. BRS can be assessed from BP and HR changes during an autonomic challenge task such as handgrip (HG). In a cross-sectional study, we assessed BRS during HG in untreated OSA (OSA_un) and CPAP treated OSA (CPAP), together with healthy control (CON) participants to determine if CPAP can recover BRS. Methods We collected ECG and continuous beat-by-beat BP from 95 people: 32 newly-diagnosed OSA_un (51.5±13.9years; AHI 21.0±15.3events/hour; 20male); 31 CPAP (49.4±14.0years; 22.4±14.1events/hour in initial diagnosis; 23male); and 32 CON (44.1±13.8years; 10male). We acquired data over 7 mins, during which people performed three 30s HGs (60 s baseline, 90 s recovery, 80% maximum strength). We calculated BRS over the 7 min period using sequence analysis in AcqKnowledge 5.0 BRS, followed by group comparisons using ANOVA. We also analyzed BP, HR and their variabilities: BPV and HRV (sympathetic-vagal). Results Mean arterial BP increases during HG were similar in all groups, although baseline mean arterial BP was higher in OSA_unc and CPAP, relative to CON (p &amp;lt; 0.05; OSA_un:mean±std, 90±11mmHg; CPAP: 88±10mmHg; CON 82±13mmHg). BRS was lower in OSA_un and CPAP, relative to CON (p &amp;lt; 0.05; OSA_un: 13.1±7.6 ms/mmHg; CPAP: 13.7±9.0 ms/mmHg; control 18.3±11.9 ms/mmHg). Other cardiovascular measures of BPV, HR and HRV in addition to BP showed significant increases in response to HG, but these changes were similar in all 3 groups. Conclusion BRS during HG was reduced in both OSA_un and CPAP compared to CON, while HG evoked similar overall changes in BP and HR in all three groups. Although CPAP reduces sympathetic tone measured as Muscle Sympathetic Nerve Activity (MSNA), BRS appears to be unaffected by the intervention. Irreversible changes in the baroreflex network may occur with OSA that are not altered with CPAP usage. Support (if any) NR-017435, HL135562

432 Brain Structure and Baroreflex Sensitivity Associations in Obstructive Sleep Apnea with and without CPAP

Abstract Introduction Obstructive sleep apnea (OSA) disrupts multiple aspects of autonomic regulation; it is unclear whether intervention with continuous positive airway pressure (CPAP) can correct such disruptions. One key index of autonomic regulation is baroreflex sensitivity (BRS), an index that indicates heart rate (HR) changes to blood pressure (BP) alterations, and which is a significant measure for evaluating long-term cardiovascular changes induced by OSA. BRS can be assessed from BP and HR changes during an autonomic challenge task such as handgrip (HG). In a cross-sectional study, we assessed BRS during HG in untreated OSA (OSA_un) and CPAP treated OSA (CPAP), together with healthy control (CON) participants to determine if CPAP can recover BRS. Methods We collected ECG and continuous beat-by-beat BP from 95 people: 32 newly-diagnosed OSA_un (51.5±13.9years; AHI 21.0±15.3events/hour; 20male); 31 CPAP (49.4±14.0years; 22.4±14.1events/hour in initial diagnosis; 23male); and 32 CON (44.1±13.8years; 10male). We acquired data over 7 mins, during which people performed three 30s HGs (60 s baseline, 90 s recovery, 80% maximum strength). We calculated BRS over the 7 min period using sequence analysis in AcqKnowledge 5.0 BRS, followed by group comparisons using ANOVA. We also analyzed BP, HR, and their variabilities: BPV and HRV (sympathetic-vagal). Results Mean arterial BP increases during HG were similar in all groups, although baseline mean arterial BP was higher in OSA_unc and CPAP, relative to CON (p &amp;lt; 0.05; OSA_un:mean±std, 90±11mmHg; CPAP: 88±10mmHg; CON 82±13mmHg). BRS was lower in OSA_un and CPAP, relative to CON (p &amp;lt; 0.05; OSA_un: 13.1±7.6 ms/mmHg; CPAP: 13.7±9.0 ms/mmHg; control 18.3±11.9 ms/mmHg). Other cardiovascular measures of BPV, HR, and HRV in addition to BP showed significant increases in response to HG, but these changes were similar in all 3 groups. Conclusion BRS during HG was reduced in both OSA_un and CPAP compared to CON, while HG evoked similar overall changes in BP and HR in all three groups. Although CPAP reduces sympathetic tone measured as Muscle Sympathetic Nerve Activity (MSNA), BRS appears to be unaffected by the intervention. Irreversible changes in the baroreflex network may occur with OSA that are not altered with CPAP usage. Support (if any) NR-017435, HL135562

Pilot Study to Characterize Middle Cerebral Artery Dynamic Response to an Acute Bout of Moderate Intensity Exercise at 3- and 6-Months Poststroke.

BackgroundThe primary aim of this study was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise in humans at 3‐ and 6‐months poststroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or nonresponder. We tested whether physical activity, aerobic fitness, and exercise mean arterial blood pressure differed between groups.Methods and ResultsTranscranial Doppler ultrasound measured MCAv during a 90‐second baseline followed by a 6‐minute moderate intensity exercise bout. Heart rate, mean arterial blood pressure, and end‐tidal CO2 were additional variables of interest. The MCAv dynamic response variables included the following: baseline, time delay, amplitude, and time constant. Linear mixed model revealed no significant differences in our selected outcomes between 3‐ and 6‐months poststroke. Individuals characterized as responders demonstrated a faster time delay, higher amplitude, and reported higher levels of physical activity and aerobic fitness when compared with the nonresponders. No between‐group differences were identified for baseline, time constant, or exercise mean arterial blood pressure. In the nonresponders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near baseline values, while the responders showed an exponential rise until steady state was reached.ConclusionsThe MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported statin use and regular participation in exercise.

Plasminogen Deficiency and Amiloride Mitigate Angiotensin II-Induced Hypertension in Type 1 Diabetic Mice Suggesting Effects Through the Epithelial Sodium Channel.

BackgroundDiabetic nephropathy is a common diabetes mellitus complication associated with hypertension, proteinuria, and excretion of urinary plasmin that activates the epithelial sodium channel, ENaC, in vitro. Here we hypothesized that the deletion of plasminogen and amiloride treatment protect against hypertension in diabetes mellitus.Methods and ResultsMale plasminogen knockout (plasminogen‐deficient [Plg−/−]) and wild‐type mice were rendered diabetic with streptozotocin. Arterial blood pressure was recorded continuously by indwelling catheters before and during 10 days of angiotensin II infusion (ANGII; 30–60 ng/kg per minute). The effect of amiloride infusion (2 mg/kg per day, 4 days) was tested in wild‐type, diabetic ANGII‐treated mice. Streptozotocin increased plasma and urine glucose concentrations and 24‐hour urine albumin and plasminogen excretion. Diabetic Plg−/− mice displayed larger baseline albuminuria and absence of urine plasminogen. Baseline mean arterial blood pressure did not differ between groups. Although ANGII elevated blood pressure in wild‐type, diabetic wild‐type, and Plg−/− control mice, ANGII did not change blood pressure in diabetic Plg−/− mice. Compared with ANGII infusion alone, wild‐type ANGII‐infused diabetic mice showed blood pressure reduction upon amiloride treatment. There was no difference in plasma renin, ANGII, aldosterone, tissue prorenin receptor, renal inflammation, and fibrosis between groups. Urine from wild‐type mice evoked larger amiloride‐sensitive current than urine from Plg−/− mice with or without diabetes mellitus. Full‐length γ‐ENaC and α‐ENaC subunit abundances were not changed in kidney homogenates, but the 70 kDa γ‐ENaC cleavage product was increased in diabetic versus nondiabetic mice.ConclusionsPlasmin promotes hypertension in diabetes mellitus with albuminuria likely through the epithelial sodium channel.

Comparing the effect of positioning on cerebral autoregulation during radical prostatectomy: a prospective observational study

PurposeSurgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We hypothesized that robot-assisted radical prostatectomy with head-down tilt causes impairment of cerebral autoregulation compared with open retropubic radical prostatectomy in the supine position.MethodsPatients scheduled for elective radical prostatectomy were included at a tertiary care prostate cancer clinic. Continuous monitoring of the cerebral autoregulation was performed using the correlation method. Based on measurements of cerebral oxygenation with near-infrared spectroscopy and invasive mean arterial blood pressure (MAP), a moving correlation coefficient was calculated to obtain the cerebral oxygenation index as an indicator of cerebral autoregulation. Cerebral autoregulation was measured continuously from induction until recovery from anesthesia.ResultsThere was no significant difference in cerebral autoregulation between robot-assisted and open retropubic radical prostatectomy during induction (p = 0.089), intraoperatively (p = 0.162), and during recovery from anesthesia (p = 0.620). Age (B = 0.311 [95% CI 0.039; 0.583], p = 0.025) and a higher difference between baseline MAP and intraoperative MAP (B = 0.200 [95% CI 0.073; 0.327], p = 0.002) were associated with impaired cerebral autoregulation, whereas surgical technique was not (B = 3.339 [95% CI 1.275; 7.952], p = 0.155).ConclusionCompared with open radical prostatectomy in the supine position, robot-assisted surgery in the extreme Trendelenburg position with capnoperitoneum did not lead to an impairment of cerebral autoregulation during the perioperative period in our study population.Trial registration number: DRKS00010014, date of registration: 21.03.2016, retrospectively registered.

Acute hypotensive effect of EET‐A, a stable analog of epoxyeicosatrienic acid (EET), in spontaneously hypertensive rats: dependence on endogenous EETs activity

IntroductionArterial hypertension and related disorders are one of the main mortality causes world‐wide. Recent evidence points to epoxyeicosatrienoic acids (EETs) as significant factors in blood pressure regulation. These cytochrome P‐450 dependent metabolites of arachidonic acid, exhibit vasodilator and natriuretic activity. Therefore EETs might contribute to reduction of elevated blood pressure and have therapeutic potential. In our spontaneously hypertensive rats (SHR), potential hypotensive efficiency was examined of EET‐A (disodium (S)‐2‐(13‐(3‐entyl)ureido)‐tridec‐8(Z)‐enamido) succinate), a stable 14,15‐EET analog. EET‐A effects were studied in animals that were or were not pretreated with c‐AUCB (cis‐4‐[4‐(3‐adamantan‐1‐yl‐ureido)‐ cyclohexyloxy]‐benzoic acid), an inhibitor of soluble epoxide hydrolase (sEH) which prevents degradation of EETs. Inhibition of sEH increases endogenous EETs levels.MethodsAnesthetized SHR aged 16 weeks (established hypertension) received 1‐hour infusion of EET‐A (5 mg/kg BW iv) or its solvent. These acute experiments were performed in rats pretreated for 14 days with oral c‐AUCB (8.5 mg/kg/24 h, in drinking water) or in untreated rats receiving c‐AUCB solvent. Throughout experiments mean arterial blood pressure (MABP) and left kidney total blood flow (RBF, renal artery probe) and perfusion of the cortex, outer‐ and inner medulla (CBF, OMBF, IMBF; laser‐Doppler fluxes) were measured, along with renal excretion of water (V), total solute (UosmV), and sodium (UNaV).ResultsBasal MABP measured after chronic treatments tended to be lower after c‐AUCB compared to solvent‐treated group; otherwise no meaningful between‐group differences in renal hemodynamics and excretion parameters were seen. In control group pretreated with c‐AUCB‐solvent, EET‐A administration was followed by a delayed significant progressive decrease in MABP, down to a value 6% below control (p=0.01). In AUCB‐pretreated group no significant post‐EET‐A change in MABP was seen. During EET‐A infusion RBF and CBF significantly and fairly rapidly increased, to 130% and 124% of the control levels, respectively, comparably in untreated and c‐AUCB pretreated group and became almost always significant within the first 30 minutes of EET‐A infusion.SummaryIn acute experiments with anesthetized SHR, administration of EET analog (EET‐A) caused a significant delayed reduction of MABP. Not unexpectedly, previous enhancement of endogenous EETs activity after sEH blockade tended to reduce baseline MABP and virtually abolished the pressure reduction in response to exogenous EET analog. Irrespective of the baseline endogenous EET activity, EET‐A invariably induced renal vasodilation. The data indicate that in adult SHR a hypotensive effect can be obtained both by administration of EET analog and by enhancing endogenous EETs activity. On the other hand, only EET‐A treatment was found to improve renal hemodynamics.Support or Funding InformationNational Science Centre 2017/26/M/NZ5/00367

Implantation of subcutaneous defibrillator is feasible and safe with monitored anesthesia care.

The perioperative anesthesia care during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is still evolving. To assess the feasibility and safety of S-ICD implantation with monitored anesthesia care (MAC) versus general anesthesia (GA) in a tertiary care center. This is a single-center retrospective study of patients undergoing S-ICD implantation between October 2012 and May 2019. Patients were categorized into MAC and GA group based on the mode of anesthesia. Procedural success without escalation to GA was the primary endpoint of the study, whereas intraprocedural hemodynamics, need of pharmacological support for hypotension and bradycardia, length of the procedure, stay in the post-anesthesia care unit, and postoperative pain were assessed as secondary endpoints. The study comprises 287 patients with MAC in 111 and GA in 176 patients. Compared to MAC, patients in GA group were younger and had a higher body mass index. All patients had successful S-ICD implantation. Only one patient (0.9%) in the MAC group was converted to GA. Despite a similar baseline heart rate (HR) and mean arterial blood pressure (MAP) in both groups, patients with GA had significantly lower HR and MAP during the procedure and more frequently required pharmacological hemodynamic support. Length of the procedure, stay in the postanesthesia care unit, and postoperative pain was similar in both groups. This retrospective experience suggests that implantation of S-ICD is feasible and safe with MAC. Use of GA is associated with more frequent administration of hemodynamic drugs during S-ICD implantation.