Maintenance Of Arterial Pressure Research Articles

Comparison of intravenous bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial blood pressure during spinal anaesthesia in caesarean section

Background: Subarachnoid block, although being highly efficient, often has limitation such as hypotension which can result in adverse maternal and fetal outcome, continues to be a matter of concern to the Anesthesiologist. The study was to compare the effect of phenylephrine, ephedrine and mephentermine, for maintenance of arterial pressure during spinal anaesthesia for caesarean section. Methodology: A prospective randomized double blinded study involving 90 patients with hypotension after subarachnoid block under spinal anesthesia was conducted, dividing them into three groups: P (Phenylephrine) 100 mcg, E (Ephedrine) 6 mg, and M (Mephentermine) 6 mg. Patients were compared based on age, weight, height, hemodynamic parameters, complications, and neonatal APGAR scores. Results: On inter-group comparison rise in systolic, diastolic and mean arterial blood pressure at 1,2,4 and 6min after drug administration were significantly high in phenylephrine group (p <0.01) compared to ephedrine and mephentermine group. Thereafter the differences narrowed off. Heart rate was raised during episodes of hypotension. The mean heart rate was decreased significantly (p<0.05) in phenylephrine group compared to other two groups. The neonatal APGAR score were >/= 7 in the three groups at the 1st and 5th min. Conclusion: The study found that phenylephrine, ephedrine, and mephentermine effectively maintained arterial blood pressure in intravenous bolus form during subarachnoid block for caesarean section. Phenylephrine, a fast-acting, short-lived normotensive drug, significantly reduced heart rate compared to ephedrine and mephentermine, but did not cause significant adverse effects on mother and fetus. Keywords: hypotension; ephedrine; mephentermine; phenylephrine; subarachnoid block

Differential relationship between decreased muscle oxygenation and blood pressure recovery during supraventricular and ventricular tachycardia

Vasoconstriction during tachyarrhythmia contributes to maintenance of arterial pressure (AP) by decreasing peripheral blood flow. This cross-sectional observational study aimed to ascertain whether the relationship between peripheral blood flow and AP recovery occurs during both paroxysmal supraventricular (PSVT, n = 19) and ventricular tachycardias (VT, n = 17). Peripheral blood flow was evaluated using forearm tissue oxygen index (TOI), and mean AP (MAP) was measured using a catheter inserted in the brachial or femoral artery during an electrophysiological study. PSVT and VT rapidly decreased MAP with a comparable heart rate (P = 0.194). MAP recovered to the baseline level at 40 s from PSVT onset, but not VT. The forearm TOI decreased during both tachyarrhythmias (P ≤ 0.029). The TOI response was correlated with MAPrecovery (i.e., MAP recovery from the initial rapid decrease) at 20–60 s from PSVT onset (r = -– 0.652 to – 0.814, P ≤ 0.0298); however, this association was not observed during VT. These findings persisted even after excluding patients who had taken vasoactive drugs. Thus, restricting peripheral blood flow was associated with MAP recovery during PSVT, but not VT. This indicates that AP recovery depends on the type of tachyarrhythmia: different cardiac output and/or vasoconstriction ability during tachyarrhythmia.

Comparison of single dose phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anesthesia in caesarean section

Comparison of single dose phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anesthesia in caesarean section

A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery.

SummaryAcute kidney injury is common after cardiac surgery. Vasoplegic hypotension may contribute to kidney injury, and different vasopressors may have variable effects on kidney function. We conducted a double‐blind, randomised feasibility trial comparing peri‐operative angiotensin‐2 with noradrenaline. We randomly allocated 60 patients at two centres to a blinded equipotent angiotensin‐2 or noradrenaline infusion intra‐operatively and for up to 48 h postoperatively, titrated to mean arterial pressure of 70–80 mmHg. Primary feasibility outcomes included consent rate, protocol adherence, infusion duration, mean arterial pressure maintenance in the target range and major adverse outcomes. Secondary outcomes included kidney injury rate. The consent rate was 47%. Protocol adherence was 100% in the angiotensin‐2 group and 94% in the noradrenaline group. Study drug duration was median (IQR [range]) 217 (160–270 [30–315]) vs. 185 (135–301 [0–480]) min (p = 0.78) min intra‐operatively, and 5 (0–16 [0–48]) vs. 14.5 (4.8–29 [0–48]) hours (p = 0.075) postoperatively for angiotensin‐2 and noradrenaline, respectively. The mean arterial pressure target was achieved postoperatively in 25 of 28 (89%) of the angiotensin‐2 group and 27 of 32 (84%) of the noradrenaline group. One participant had a stroke, one required extracorporeal support and three required renal replacement therapy, all in the noradrenaline group (p = 0.99, p = 0.99 and p = 0.1). Acute kidney injury occurred in 7 of 28 in the angiotensin‐2 group vs. 12 of 32 patients in the noradrenaline group (p = 0.31). This pilot study suggests that a trial comparing angiotensin‐2 with noradrenaline is feasible. Its findings justify further investigations of angiotensin‐2 in cardiac surgery.

Randomized trial of bolus ephedrine or mephentermine for maintenance of arterial pressure and fetal outcome during spinal anesthesia for the cesarean section

Background and Aims: Spinal anesthesia remains the preferred choice for cesarean deliveries, but hypotension is one of the common complications which may have detrimental effects on both the mother and fetus. In this study, we compared the efficacy and adverse effects of bolus doses of ephedrine hydrochloride and mephentermine sulfate administered intravenously to treat spinal-induced hypotension and the fetal outcomes through Apgar scores and umbilical cord blood gas analysis in the lower segment cesarean section. Material and Methods: In this prospective, randomized, double-blind study, 60 patients undergoing the lower segment cesarean section (LSCS) under spinal anesthesia were randomized into two groups of 30 each using computer-generated random numbers which were kept in an opaque envelope. Patients were pre-loaded with Ringer's lactate solution 10 ml/kg before the spinal anesthesia. Hypotension was defined as the fall in systolic blood pressure of less than or equal to 20% of the baseline or systolic blood pressure of less than 90 mmHg. Whenever hypotension occurred, patients in group E (ephedrine) received a bolus dose of ephedrine 6 mg intravenous and patients in group M (mephentermine) received a bolus dose of mephentermine 6 mg intravenous. Intra-operative recording included maternal hemodynamic parameters and the number of bolus doses of study drugs required to treat maternal hypotension and the adverse effects of study drugs. The Apgar score and umbilical cord blood gas values were recorded. Data were analyzed by analysis of variance test, Student's t-test, and Chi-square test. A P value of < 0.05 was considered as significant. Results: There was a statistically significant (p < 0.05) increase in systolic and mean arterial blood pressure at the second min and fourth min after administration of ephedrine in group E compared to mephentermine in group M. The systolic blood pressure at the second min in the ephedrine group was 114.3 ± 12.06, whereas in the mephentermine group, it was 106.10 ± 8.41 and was statistically significant (p < 0.05). At the fourth min, the systolic blood pressure in the ephedrine group was 115.03 ± 8.87, whereas in the mephentermine group, it was 108.46 ± 8.10 and was statistically significant (p < 0.05). There was a transient increase in heart rate immediately after administration of spinal anesthesia. The mean number of bolus doses of vasopressor consumption was 2.4 (14.4 mg) in the ephedrine group and 2 (12 mg) in the mephentermine group. The umbilical cord blood gas analysis and Apgar scores were similar in both the groups. Three patients (10%) developed bradycardia in the mephentermine group compared to the ephedrine group (0%). The incidence of nausea (13.3% vs 3.3%) and vomiting (10% vs 1%) was higher in the ephedrine group compared to the mephentermne group, and it was not statistically significant (p > 0.05). No significant differences were observed in the umbilical arterial blood pH and Apgar scores. Conclusion: In conclusion, after hypotension, ephedrine and mephentermine administration as bolus doses are equally efficacious in preventing spinal-induced hypotension in patients undergoing the cesarean section and are associated with similar neonatal outcomes.

EFFICACY OF PHENYLEPHRINE AND EPHEDRINE IN MAINTAINING MATERNAL BLOOD PRESSURE INTRA OPERATIVELY DURING SPINAL ANESTHESIA FOR CAESAREAN SECTION

Introduction: Spinal anaesthesia has become a popular technique for caesarean section. It however has the potential to cause rapid onset of maternal hypotension which may have detrimental maternal and neonatal effects. Thus, a number of strategies for treating hypotension have been investigated. Careful positioning and volume preloading with crystalloid or colloids have been used to prevent it, but these are not complete measures and vasopressor is required to correct hypotension quickly . Methodology: 100 parturients ASA I and II scheduled for elective as well as emergency Caesarean section under sub arachnoid block (SAB) were studied. All parturients were at term, had uncomplicated singleton pregnancy with cephalic presentation. Results: Phenylephrine and Ephedrine are effective given prophylactically IV bolus followed by infusion in maintenance of arterial pressure within 15% limit of baseline. Phenylephrine has quicker and shorter duration of action effect in comparison to Ephedrine. Conclusion: Vasopressor drugs Phenylephreine and Ephedrine, effectively maintained arterial blood pressure during spinal anaesthesia for caesarean section

Mean arterial pressure maintenance following spinal cord injury: does meeting the target matter?

The American Association of Neurological Surgeons recommends maintaining a mean arterial pressure (MAP) of 85 or greater after spinal cord injury (SCI), despite relatively weak evidence. This target can be difficult to meet and often puts significant burden of cost and attention on the healthcare system.

Comparison of bolus phenylephrine, Ephedrine and Mephentermine for maintenance of arterial pressure during Spinal anaesthesia in Caesarean section

Background: Hemodynamic changes during cesarean delivery after spinal anesthesia are common. The hypotension seen after spinal anesthesia in a cesarean delivery can be treated by many agents. In the management of hypotension during spinal anesthesia for cesarean section, the effects of Phenylephrine, Ephedrine and Mephentermine were compared in this study based on the following parameters-1. The efficacy of the vasopressor in treating hypotension 2. Incidence of undesirable side effects. Materials and method: This study included a total of 120 patients (ASA Grade I and II) undergoing elective cesarean section (with a normal singleton pregnancy, full term/near term) under spinal anesthesia. The patients were randomly allocated into three groups of 40 each. Group ‘P’ was given prophylactic bolus dose of Phenylephrine 100 mcg IV, Group ‘E’ was given prophylactic bolus dose of Ephedrine 10 mg IV and Group ‘M’ received prophylactic bolus dose of Mephentermine 6 mg IV. Blood pressure and heart rate was recorded every 2 minutes for 20 minutes and thereafter every 5 minutes till the end of the surgery. Results: In managing hypotension between the three groups, no difference was found between them. The incidence of bradycardia was higher in the Phenylephrine group. Conclusion: All the three vasopressors are effective (in intravenous form) in maintenance of maternal arterial pressure. Although Phenylephrine has quicker peak effect, in comparison to Ephedrine and Mephentermine and it causes reduction in heart rate.

Mean arterial pressure maintenance following spinal cord injury: Does meeting the target matter?

Neurosurgical guidelines recommend maintaining mean arterial pressure (MAP) between 85 and 90 mm Hg following acute spinal cord injury (SCI). In our hospital, SCI patients receive orders for MAP targeting for 72 hours following admission, but it is unclear how often the patient's MAP meets the target and whether or not this affects outcome. We hypothesized that the proportion of MAP measurements ≥85 mm Hg would be associated with neurologic recovery. Spinal cord injury patients with blunt mechanism of injury admitted between 2014 and 2019 were identified from the registry of a level 1 trauma center. Proportion of MAP values ≥85 mm Hg was calculated for each patient. Neurologic improvement, as measured by positive change in American Spinal Injury Association (ASIA) impairment scale by ≥1 level from admission to discharge was evaluated with respect to proportion of elevated MAP values. A total of 136 SCI patients were evaluated. Average proportion of elevated MAP values was 75%. Admission ASIA grades were as follows: A, 30 (22.1%); B, 20 (14.7%); C, 28 (20.6%); and D, 58 (42.6%). One hundred six patients (77.9%) required vasopressors to elevate MAP (ASIA A, 86.7%; B, 95.0%; C, 92.9%; D, 60.3%). Forty patients (29.4%) were observed to have improvement in ASIA grade by discharge (admission ASIA A, 15%; B, 33%; C, 40%; D, 13%). The proportion of elevated MAP values was higher for patients with neurologic improvement (0.81 ± 0.15 vs. 0.72 ± 0.25, p = 0.014). Multivariate modeling demonstrated a significant association between proportion of elevated MAP values and neurologic improvement (p = 0.028). An interaction revealed this association to be moderated by vasopressor dose (p = 0.032). The proportion of MAP measurements ≥85 mm Hg was determined to be an independent predictor of neurologic improvement. Increased vigilance regarding MAP maintenance above 85 mm Hg is warranted to optimize neurologic recovery following SCI. Therapeutic/care management, level IV.

The neural control of arterial pressure by non‐catecholaminergic RVLM

Tonic sympathetic nerve activity (SNA) is necessary for the maintenance of arterial pressure (AP) under anesthesia, and this tone is dependent on supraspinal input. Over the last two centuries, numerous studies have collectively identified the rostral ventrolateral medulla (RVLM) as a critical region for neural control of AP and SNA in anesthetized animals, however the relevance of these results to conscious animals and the nature of the RVLM neurons responsible remain conjectural. The RVLM has direct projections onto sympathetic preganglionic neurons, but the evidence that this is the critical pathway for AP regulation and SNA in conscious animals is not definitive—and even if this is the principal BP regulatory pathway of the RVLM, the bulbospinal neurons that produce these effects are still debated.Historically, the most prominent pressor candidate within the RVLM has been the rostral portion of the catecholaminergic C1 group. Rostral C1 neurons are glutamatergic, occupy a ventral region of the medulla that is coextensive with the vasomotor RVLM region, are barosensitive, directly innervate sympathetic preganglionic neurons, and activate sympathetic nerve discharge upon stimulation. Despite these data, optogenetic stimulation of C1 in conscious and anesthetized rodents has thus far failed to achieve the magnitude of increases in arterial pressure predicted by pharmacological stimulation of the RVLM.Here, we show that stimulation of a non‐catecholaminergic population within the RVLM is sufficient to increase AP in conscious mice, even after C1 lesion. We then targeted bulbospinal neurons using a retrograde virus and demonstrated that optogenetic activation of only bulbospinal RVLM neurons increases AP in conscious mice, and in anesthetized mice, stimulation increases AP and renal sympathetic nerve activity. Unlike optogenetic stimulation of C1 neurons, stimulation of non‐catecholaminergic bulbospinal RVLM causes robust and sustained increases in AP in both conscious and anesthetized states, and sustained increases in SNA under anesthesia. This data suggests non‐catecholaminergic bulbospinal neurons are powerful activators of AP and SNA and may play an important role along with C1 in arterial pressure maintenance.Support or Funding InformationAmerican Heart Association Predoctoral Fellowship; University of Virginia Wagner FellowshipThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Maintenance of Arterial Pressure During Spinal Anaesthesia in Caesarean Section – Comparison of Intravenous Phenylephrine Hydrochloride and Ephedrine

Maintenance of Arterial Pressure During Spinal Anaesthesia in Caesarean Section – Comparison of Intravenous Phenylephrine Hydrochloride and Ephedrine

Role of intramuscular injections of vasopressors in combating spinal hypotension during caesarean sections: A prospective, randomized, double-blinded controlled clinical trial

Background: Hypotension following spinal anaesthesia (SA) is a common problem. Vasopressors play an important role in its management. The common approach in the routine clinical setting is immediate action after detection of hypotension rather than as a preventive measure. There are studies which compare bolus and intravenous (IV) infusion in the management of maternal hypotension, but literature about comparison of efficacy of intramuscular (IM) vasopressors is very limited. Hence, this study was planned in elective caesarean deliveries to compare the efficacy of IM phenylephrine, ephedrine, and mephentermine for the maintenance of arterial pressure during SA. Materials and Methods: A prospective, randomized, double-blind study was conducted where 120 parturients belonging to American Society of Anaesthesiologists II undergoing elective caesarean section under SA were evaluated after being randomized into four groups receiving either preemptive phenylephrine 4 mg IM, ephedrine 45 mg IM, mephentermine 30 mg IM, or normal saline 0.9% 2 ml IM as placebo, immediately following SA. The mean arterial blood pressure and heart rate were primarily evaluated and any other complications were also recorded. Results: It points toward significantly decreased incidence of hypotension in phenylephrine group compared to the other groups (P = 0.034). The incidence of rescue IV ephedrine requirement was maximum with the placebo group, least with mephentermine compared to ephedrine and placebo group. However, there was no statistical difference between the groups with respect to doses of IV ephedrine used (P = 0.08). Maternal nausea, vomiting, and newborn Apgar score were also comparable. Conclusion: All the vasopressors are effective in reducing the severity of hypotension, though phenylephrine was found to be better for the prevention of hypotension.

Hemodynamic Stability to Surface Warming and Cooling During Sustained and Continuous Simulated Hemorrhage in Humans.

One in 10 deaths worldwide is caused by traumatic injury, and 30% to 40% of those trauma-related deaths are due to hemorrhage. Currently, warming a bleeding victim is the standard of care due to the adverse effects of combined hemorrhage and hypothermia on survival. We tested the hypothesis that heating is detrimental to the maintenance of arterial pressure and cerebral perfusion during hemorrhage, while cooling is beneficial to victims who are otherwise normothermic. Twenty-one men (31 ± 9 y) were examined under two separate protocols designed to produce central hypovolemia similar to hemorrhage. Following 15 min of supine rest, 10 min of 30 mm Hg of lower body negative pressure (LBNP) was applied. On separate randomized days, subjects were then exposed to skin surface cooling (COOL), warming (WARM), or remained thermoneutral (NEUT), while LBNP continued. Subjects remained in these thermal conditions for either 40 min of 30 mm Hg LBNP (N = 9), or underwent a continuous LBNP ramp until hemodynamic decompensation (N = 12). Arterial blood pressure during LBNP was dependent on the thermal perturbation as blood pressure was greater during COOL (P >0.001) relative to NEUT and WARM for both protocols. Middle cerebral artery blood velocity decreased (P <0.001) from baseline throughout sustained and continuous LBNP, but the magnitude of reduction did not differ between thermal conditions. Contrary to our hypothesis, WARM did not reduce cerebral blood velocity or LBNP tolerance relative to COOL and NEUT in normothermic individuals. While COOL increased blood pressure, cerebral perfusion and time to presyncope were not different relative to NEUT or WARM during sustained or continuous LBNP. Warming an otherwise normothermic hemorrhaging victim is not detrimental to hemodynamic stability, nor is this stability improved with cooling.

Hemodynamic responses to cooling and warming during a continuous simulated hemorrhage ramp

One in 10 deaths worldwide is caused by traumatic injury, and 30–40% of those trauma‐related deaths are due to hemorrhage. Currently, warming a hemorrhaging victim is the standard of care due to the adverse effects of combined hemorrhage and hypothermia on survival. However, heating can be detrimental to the maintenance of arterial pressure and cerebral perfusion during a continuous hypotensive challenge.PURPOSETo test the hypothesis that warming a normothermic individual during a continuous simulated hemorrhage ramp is harmful to the maintenance of arterial pressure and cerebral perfusion, while skin surface cooling is beneficial.METHODSTwelve men (mean ± SD: age, 29 ± 8 y; weight, 82 ± 16 kg) underwent a randomized crossover study performed over 3 separate days. Following 15 min of supine rest, 10 min of 30 mmHg of lower body negative pressure (LBNP) was applied to simulate a mild hemorrhagic challenge. With LBNP continuing, subjects were then exposed to mild whole‐body warming (WARM; mean skin temperature (Tsk): 36.4 ± 0.5°C), skin surface cooling (COOL; Tsk: 30.5 ± 0.9°C), or remained thermoneutral (NEUT; Tsk: 33.9 ± 0.6°C). Five min after the thermal provocation, a continuous LBNP ramp was applied at a rate of 5 mmHg·min−1 until pre‐syncope. Hemodynamic and thermal variables were measured continuously.RESULTSNeither average time to pre‐syncope (P = 0.14) nor the LBNP level at pre‐syncope (P = 0.09) were different between thermal conditions. However, mean arterial blood pressure was elevated (92 ± 11 mmHg; P = 0.01) during COOL across the LBNP period, relative to NEUT (83 ± 9 mmHg) and WARM (79 ± 11 mmHg) trials. Middle cerebral artery blood velocity decreased (26 ± 1 cm·sec−1; P &lt; 0.001) to a similar extent from baseline to pre‐syncope, regardless of the thermal conditions applied.CONCLUSIONSContrary to our hypothesis, WARM did not impair LBNP tolerance or cerebral blood flow velocity. Although COOL increased blood pressure during the LBNP ramp, LBNP tolerance and cerebral perfusion were not different relative to the NEUT or WARM trials. These data indicate that mild whole‐body warming of a continuously hemorrhaging victim is not detrimental to hemodynamic stability.Support or Funding InformationProject funded by DOD‐W81XWH‐12‐1‐0152.

Efficacy of Phenylephrine and Ephedrine inmaintainingmaternal blood pressure intra operatively during spinal anesthesia for caesarean section

Introduction: Spinal anaesthesia has become a popular technique for caesarean section. It however has the potential to cause rapid onset of maternal hypotension which may have detrimental maternal and neonatal effects. Thus, a number of strategies for treating hypotension have been investigated. Careful positioning and volume preloading with crystalloid or colloids have been used to prevent it, but these are not complete measures and vasopressor is required to correct hypotension quickly. Methodology: After approval from our institutional ethics committee, 100 parturients ASA I and II scheduled for elective as well as emergency Caesarean section under sub arachnoid block (SAB) were studied. All parturients were at term, had uncomplicated singleton pregnancy with cephalic presentation. Results: Phenylephrine and Ephedrine are effective given prophylactically IV bolus followed by infusion in maintenance of arterial pressure within 15% limit of baseline. Phenylephrine has quicker and shorter duration of action effect in comparison to Ephedrine. Conclusion: Vasopressor drugs Phenylephreine and Ephedrine, effectively maintained arterial blood pressure during spinal anaesthesia for caesarean section. Key words: Phenylephrine, Ephedrine, Caesarean section

Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.

Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001), but was similar in obese and lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ≤ 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.

Cannabinoids‐Induced Vasodilation in Rat Mesenteric Artery: Possible Mechanisms of Action

Mesenteric artery is a resistance vessel, which has an important function in the arterial pressure maintenance. The vascular tone can be modulated through synthesis and release of vasoactive substances of the endothelium as well as through substances that can cause relaxation or contraction of the arterial smooth muscle. Some of these modulator substances are the cannabinoids. It has been shown that cannabinoids are able to produce changes in the vascular tone through different mechanisms including the activation of the cannabinoid receptors (CB1 and CB2). The aim of this study was to analyze the possible mechanisms through which cannabinoids cause rat mesenteric artery vasodilation. We have done tension experiments using synthetic cannabinoids that are selective agonists for CB1 (ACPA) and CB2 (JWH‐133) receptors, and selective antagonists (AM281 and AM630). The cannabinoids were applied in arterial rings with or without endothelium. The results show that ACPA and JWH‐133 activate cannabinoid receptors, to produce vasodilator effect in both intact‐endothelium and no‐endothelium rings, this effect was partially reverted when antagonist were used. Furthermore, involvement of big‐conductance voltage and calcium‐activated potassium (BKCa2+) channels was demonstrated by blocking with iberiotoxin. Moreover, using confocal microscopy we observed the cannabinoid receptors expression in transversal cuts, and the co‐localization of CB1 receptors and BKCa2+ channels was proved in dispersed smooth muscle cells. Therefore, cannabinoids elicit a vasodilator effect, through a mechanism dependent of the BKCa2+ channels activation.

Hemodynamic Responses to Mild Warming during Simulated Hemorrhage

Warming a hemorrhaging victim is the standard of care. However, heating can be detrimental to the maintenance of arterial pressure and cerebral perfusion.PurposeTo test the hypothesis that moderately warming a normothermic individual can be detrimental to the maintenance of arterial pressure and cerebral perfusion during a hemorrhagic insult.MethodsFive men (age, 33 ± 9 y) underwent the following repeated measures design: following 15 min of supine rest, 10 min of 30 mmHg of lower body negative pressure (LBNP) was applied to simulate a moderate hemorrhagic challenge while subjects were normothermic. With LBNP continuing, subjects were exposed to warming (mean skin temperature (Tsk): 36.8 ± 0.4°C), skin surface cooling (Tsk: 29.7 ± 1.2°C), or thermoneutral (Tsk: 33.4 ± 0.4°C) for 40 min via water perfused suit.ResultsInteraction between the thermal perturbation and LBNP time did not reveal statistically distinguishable changes in blood pressure (P = 0.15), cardiac output (P = 0.14), stroke volume (P = 0.74) or cerebral perfusion (P = 0.13). However, the elevation in heart rate was greater (P = 0.01) during warming (22 ± 6 bpm) relative to cooling (7 ± 10 bpm) and thermoneutral (10 ± 6 bpm) conditions.ConclusionsThese preliminary data suggest that mild warming during the applied level of simulated hemorrhage does not compromise arterial blood pressure or cerebral perfusion. It remains unknown whether mild warming would be detrimental during a more profound hemorrhagic challenge.

Neuro-humoral control during orthostasis in health and disease.

Different from many other species, human beings spend nearly two-thirds of the day in an upright posture. Due to gravity, about 700 to 900 ml of blood shift into the lower body during quiet standing. As a result, central blood volume decreases and this leads to a series of neural-humoral adjustments that aim to maintain the mean arterial pressure during orthostasis. Both the sympathetic nervous system and the renin-angiotensin-aldosterone system contribute importantly to the arterial pressure maintenance in upright humans. There is a growing interest in the blood pressure regulation during orthostasis in healthy individuals and patient populations. This e-book provides some updates on sympathetic neural control and renal-adrenal function in health and disease. Sympathetic neural activity regulates blood pressure mainly through the baroreflex-mediated vasoconstriction during orthostasis. The baroreflex is a closed-loop feedback system, but requires open-loop experiments to identify its characteristics, which is impossible in human research. Kamiya et al. demonstrated that system identification based analysis and numerical simulation using baroreflex subsystem characteristics identified in animal models may contribute to our understanding of human sympathetic physiology under orthostasis (Kamiya et al., 2014). Neural and renal-adrenal control of blood pressure can be affected by not only age but also race and physical fitness. For example, it was found that young normotensive Caucasian women may rely on sympathetic neural activity more so than African-American women who had a tendency to rely on the renal-adrenal system to regulate blood pressure during orthostatic challenges (Jarvis et al., 2014). Conversely, Sugawara et al. reported that endurance-trained men had increased orthostatic tachycardia and enhanced cardiovagal baroreflex sensitivity, which may favorably mitigate accumulated risks for post-exercise orthostatic intolerance (Sugawara et al., 2014). Failure of the sympathetic nervous system during orthostasis may result in syncope (Iwase et al., 2014). However, orthostatic tolerance does not seem to be related to resting sympathetic neural activity or sympathetic baroreflex sensitivity (Hinojosa-Laborde et al., 2014). Studies in healthy young individuals indicate that in addition to sympathetic vasoconstriction, the heart rate response may also contribute importantly to orthostatic tolerance (Convertino, 2014). On the other hand, it is argued that cardiac effector mechanisms appear not to be important for the adjustment of arterial pressure to the upright posture in humans (Wieling et al., 2014). Indeed, investigations into the role of the sympathetic nervous system in orthostatic intolerance have yielded mixed results. The review article by Lambert and Lambert (2014) outlines the current knowledge of the function of the sympathetic nervous system in vasovagal syncope and the Postural Orthostatic Tachycardia Syndrome (POTS, also called Chronic Orthostatic Intolerance). There are multiple pathophysiological mechanisms that underlie POTS; some POTS patients have evidence of elevated sympathoneural tone, others have a hypovolemic state, and many patients have a perturbed renin-angiotensin-aldosterone system profile (Mar and Raj, 2014). Patients with POTS have acute changes in cognitive performance in response to orthostatic challenges, and these patients also have an increased prevalence of depression and higher levels of anxiety (Anderson et al., 2014). Impaired cerebral autoregulation may underlie upright cognitive dysfunction in POTS (Medow et al., 2014). Finally, patients with autonomic failure often have orthostatic hypotension and (pre)syncopal symptoms. Arnold et al. showed that ergotamine combined with caffeine could be used as an alternate treatment in carefully selected patients without comorbid coronary artery disease (Arnold et al., 2014). Taken together, this e-book highlights only a small portion of the recent advances in neural-humoral control during orthostasis in humans. More research is needed to better understand the role of the sympathetic nervous system and the renin-angiotensin-aldosterone system in the regulation of blood pressure in health and disease.

Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome.

Orthostatic intolerance is the inability to tolerate the upright posture and is relieved by recumbence. It most commonly affects young women and has a major impact on quality of life and psychosocial well-being. Several forms of orthostatic intolerance have been described. The most common one is the recurrent vasovagal syncope (VVS) phenotype which presents as a transient and abrupt loss of consciousness and postural tone that is followed by rapid recovery. Another common type of orthostatic intolerance is the postural orthostatic tachycardia syndrome (POTS) which is characterized by an excessive rise in heart rate upon standing and is associated with symptoms of presyncope such as light-headedness, fatigue, palpitations, and nausea. Maintenance of arterial pressure under condition of reduced central blood volume during the orthostasis is accomplished in large part through sympathetic efferent nerve traffic to the peripheral vasculature. Therefore sympathetic nervous system (SNS) dysfunction is high on the list of possible contributors to the pathophysiology of orthostatic intolerance. Investigations into the role of the SNS in orthostatic intolerance have yielded mixed results. This review outlines the current knowledge of the function of the SNS in both VVS and POTS.