Fall In Mean Blood Pressure Research Articles

The diagnostic accuracy of preoperative perfusion index as a predictor of postspinal anesthesia hypotension in parturients undergoing cesarean delivery: A prospective non-blinded observational study.

Spinal anesthesia is the technique of choice for elective cesarean section with a prominent side effect of postspinal anesthesia hypotension (PSH). This needs an early prediction to avoid feto-maternal complication. This study aimed to assess the diagnostic accuracy of perfusion index (PI) and inferior vena cava collapsibility index (IVCCI) in the prediction of PSH. Thirty parturients of American Society of Anesthesiologists Physical Status (ASA-PS) 1 and two undergoing cesarean delivery participated in the study. IVCCI, PI, baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR) were noted in the preoperative period. The fall of MBP by 20% from baseline or below 65 mm Hg was considered PSH. After spinal anesthesia, SBP, DBP, MBP, and HR were noted again for diagnosing PSH. It did not show any statistical difference when comparing the PI between the PSH and non-PSH groups in both the PSH definition groups. IVCCI was significantly higher when PSH was considered MBP <65 mm Hg (P = 0.01). However, IVCCI was found to be statistically insignificant if PSH was considered a 20% reduction in baseline MBP. The correlation matrix between IVCCI and PI showed Pearson's r-value of 0.525, indicating a substantial relationship between the two (P = 0.003). Multivariate logistic regression analysis had shown that neither IVCCI nor PI was a good predictor of PSH in parturients for both definition groups for PSH. Although there is a modest correlation between PI and IVCCI, both cannot be used to predict postspinal hypotension in parturients undergoing elective lower-segment cesarean section (LSCS).

Electrical stimulation of the ventromedial prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure.

We recently showed that transcranial alternating current stimulation of the dorsolateral prefrontal cortex modulates spontaneous bursts of muscle sympathetic nerve activity, heart rate, and blood pressure (Sesa-Ashton G, Wong R, McCarthy B, Datta S, Henderson LA, Dawood T, Macefield VG. Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans. Cereb Cortex Comm. 2022:3:2tgac017.). Stimulation was delivered between scalp electrodes placed over the nasion and electroencephalogram (EEG) electrode site F3 (left dorsolateral prefrontal cortex) or F4 (right dorsolateral prefrontal cortex), and therefore the current passed within the anatomical locations underlying the left and right ventromedial prefrontal cortices. Accordingly, we tested the hypothesis that stimulation of the left and right ventromedial prefrontal cortices would also modulate muscle sympathetic nerve activity, although we predicted that this would be weaker than that seen during dorsolateral prefrontal cortex stimulation. We further tested whether stimulation of the right ventromedial prefrontal cortices would cause greater modulation of muscle sympathetic nerve activity, than stimulation of the left ventromedial prefrontal cortices. In 11 individuals, muscle sympathetic nerve activity was recorded via microelectrodes inserted into the right common peroneal nerve, together with continuous blood pressure, electrocardiogram, and respiration. Stimulation was achieved using transcranial alternating current stimulation, +2 to -2mA, 0.08Hz, 100cycles, applied between electrodes placed over the nasion, and EEG electrode site FP1, (left ventromedial prefrontal cortices) or FP2 (right ventromedial prefrontal cortices); for comparison, stimulation was also applied over F4 (right dorsolateral prefrontal cortex). Stimulation of all three cortical sites caused partial entrainment of muscle sympathetic nerve activity to the sinusoidal stimulation, together with modulation of blood pressure and heart rate. We found a significant fall in mean blood pressure of ~6mmHg (P = 0.039) during stimulation of the left ventromedial prefrontal cortices, as compared with stimulation of the right. We have shown, for the first time, that transcranial alternating current stimulation of the ventromedial prefrontal cortices modulates muscle sympathetic nerve activity and blood pressure in awake humans at rest. However, it is unclear if this modulation occurred through the same brain pathways activated during transcranial alternating current stimulation of the dorsolateral prefrontal cortex.

Comparing the Effect of Phenylephrine Bolus and Phenylephrine Infusion for Maintaining Arterial Blood Pressure During Cesarean Delivery Under Spinal Anesthesia: A Randomized Prospective Study.

Maternal hypotension is a common complication of spinal anesthesia in cesarean section and requires immediate intervention. Phenylephrine is most commonly used as a vasopressor agent for the treatment of hypotension due to subarachnoid block.Our aim was to compare the bolus dose of 50 µg of phenylephrine with a fixed infusion at 50 µg.min-1 of phenylephrine for maintaining arterial blood pressure during cesarean delivery. This was a prospective, randomized comparative study. One hundred normotensive pregnant females aged 18-35 years, body mass index 18-29kg.m2, American Society of Anesthesiologists (ASA) physical status classificationIIscheduled to undergo cesarean section (elective/emergency) under spinal anesthesia were randomly divided into two groups of 50 each. Group PB received a bolus dose of phenylephrine 50 µg after they developed hypotension i.e., a decrease in systolic blood pressure (SBP) ≥ 20% from the baseline. Similarly, patients in Group PI were administered prophylactic infusion using a syringe pump of phenylephrine 50 µg.min-1, started just after the administration of subarachnoid block. The phenylephrine infusion was continued either till the delivery of the baby or when SBP rises >20% above the baseline. Parameters like blood pressure, heart rate, and peripheral oxygen saturation were recorded.After the delivery of the baby, theneonatal APGAR score was assessed at one minute and five minutes. Demographic data were comparable in terms of demographic profile, duration of surgery, and ASA physical status classificationbetween the groups. The heart rate was higher in Group PB compared to Group PI throughout the monitoring period (P<0.001). The fall in mean blood pressure was more in Group PB compared to Group PI till 18 minutes of surgery and was statistically significant (P<0.05). After 18 minutes of surgery, mean blood pressure stabilized and was comparable between the groups. Other variables like APGAR score at one minute and five minutes were comparable between the groups.Bradycardia and hypertension were more common in Group PI whereas hypotension, nausea, and vomiting were more common in group PB. We concluded that during cesarean section under spinal anesthesia, phenylephrine infusion provides better hemodynamic stability and APGAR score during the perioperative period.

Vasoplegia induces high energy demand and depletes cardiac energetics: a new insight into physiological concepts of cardiac work and a model for acute heart failure?

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): British Heart Foundation Background / Introduction Hearts subjected to constant high workload will, over time, fail. We hypothesized vasoplegia would create a high cardiac energy demand and deplete cardiac energy reserves, a mechanism causing failure. With 31Phosphorus Magnetic Resonance Spectroscopy, we can measure energy: ATP usage (via creatine kinase flux) and reserves of phosphocreatine (PCr/ATP ratio). Methods: Ten healthy volunteers were recruited mean age 37, mean BMI 22.4, 5 male, 5 female. A nitrate vasodilator (Glyceryl trinitrate, GTN) was used to induce vasoplegia, with MRI and MRS measurements taken before and during. Results There was reduced preload (falls in end diastolic volume and right atrial area) and afterload (mean blood pressure fall 14mmHg, p &amp;lt;0.0001). Subjects mounted reflex tachycardia (mean heart rate rise 9bpm, p &amp;lt; 0.0001) and inotropy (mean baseline ejection fraction increase 5%, p = 0.0002) hence cardiac output and rate pressure product were maintained (baseline CO 6.24 ± 1.45 L/min vs GTN 6.49 ± 1.43 L/min, p = 0.37; baseline RPP = 6929 ± 976 mmHg.bpm vs GTN 7214 ± 1051 mmHg.bpm, p = 0.06). There was a 58% increase in Creatine Kinase activity (kf) (baseline 0.158 s-1 vs GTN 0.249 s-1, p = 0.006) and CK flux (baseline 1.79 ± 0.78 umol/g/s vs GTN 2.59 ± 1.07 umol/g/s, p = 0.03), demonstrating increased ATP transfer. PCr/ATP fell (from 2.17 ± 0.2 to 1.99 ± 0.22, p = 0.027). Baseline PCr/ATP positively correlated with the change in stroke volume (R2 = 0.66, p = 0.005) during administration of GTN. In addition, whilst at rest, CK kf correlated with rate pressure product (R2 = 0.56, p = 0.03), there was no correlation seen during GTN. Conclusions We have shown vasoplegia increases energy demand upon the heart, despite unchanged cardiac output and rate pressure product. Further, we have shown a fall in Phosphocreatine/ATP ratio, suggesting this ATP transfer outstripped oxidative phosphorylation and the phosphocreatine pool was depleted in order to maintain ATP delivery. We speculate that progressive depletion of energetics in the context of high energy demand drives hearts under constant stress into failure. In addition, we demonstrate that the magnitude of the resting phosphocreatine pool relates to ability to augment stroke volume during stress and suggest that this may be protective against a decline into failure. Further work is needed, but PCr/ATP may be an important biomarker for treatments that target myocardial energetics to protect against failure. Abstract Figure 1

Outcome of Labetalol and Methyldopa as Oral Antihypertensive Agent in the Treatment of Pregnancy Induced Hypertension

Background: In a developing country like Bangladesh pregnancy induced hypertension is an important medical problem and a major cause of maternal and perinatal mortality and morbidity. Antihypertensive drugs are often used to lower blood pressure and also help in reducing maternal and fetal complications.&#x0D; Objective: To compare the efficacy and safety of labetalol and methyldopa in management of pregnancy induced hypertension.&#x0D; Methods: A total of 100 patients having newly onset hypertension during pregnancy were taken and divided randomly into two groups. Group A was given labetalol and group B methyldopa. In both groupsmean blood pressure was measured on 1stday as pretreatment and at 48th hour and 8th day as post-treatment measurement, total dose of each drug require per day and side effects were recorded.Reduction in blood pressure, doseand side effects were compared.&#x0D; Results: Labetalol treated group of patients showed significant fall in mean blood pressure from 1st day to 48th hour and 1st day to 8th day.In patients treated with labetalol mean blood pressure on 1st day was 123.9 ± 17.11 mmHg and was controlled to 100.03 ± 6.38 mmHg on 48th hour and 94.13 ± 4.3 mmHg on day 8, while in methyldopa treated group on 1st day was 121.23 ± 13.597 mmHg which was reduced to 105.8 ± 6.53 mmHg on 48th hour and 97.96 ± 4.11 mmHg on day 8.The mean drug dosage required to control BP in group A was 380 ± 259.5 mg and in group B was 1540 ± 503.45 mg. Group A had less side effects.&#x0D; Conclusion: Labetalol is safe more efficacious and quicker control of blood pressure withless maternal adverse effects and thus advantageous over methyldopa.&#x0D; Mediscope Vol. 8, No. 1: January 2021, Page 19-26

Efficacy of Intravenous Fluid Plasmalyte and 6% Hetastarch in Preventing Spinal Anaesthesia Induced Hypotension in Patients undergoing Lower Abdominal Surgeries: A Randomised Clinical Study

Introduction: Both crystalloids and colloid preloading is recommended for spinal anaesthesia. Preloading of intravenous fluids increases circulating volume and cardiac output; thus preventing spinal anaesthesia-induced hypotension. Crystalloids have a short intravascular half-life, poor plasma expanders and large volumes are thus required. Aim: To compare the efficacy of 5 mL/kg of 6% Hetastarch (colloid) to that of 15 mL/kg of Plasmalyte (crystalloid) solution to prevent hypotension during spinal anaesthesia in patients undergoing lower abdominal surgeries. Materials and Methods: This was a randomised clinical trial from June 2016 to April 2017 on a total 80 patients, belonging to American Society of Anaesthesiologist (ASA) Grade I and II scheduled for lower abdominal surgeries under spinal anaesthesia. They were divided into two groups- Group H and Group P. Patients in group H were preloaded with 5 mL/kg solution of 6% Hetastarch, whereas those in group P were preloaded with 15 mL/kg of Plasmalyte solution. After institution of spinal anaesthesia with 3.0 mL of hyperbaric Bupivacaine using 25G Quincke’s needle, Blood Pressure (BP) and other vital parameters were monitored intraoperatively every 3 minutes for first 30 minutes and then every 5 minutes till the end of surgery. Descriptive statistics, frequency (n) and percentages (%) were calculated and the variables between the groups were compared by Students t-test, Fischers exact test and Mann Whitney U-test. Results: Both the groups showed a fall in Mean Blood Pressure (MBP) immediately after the block. Group P showed more decline in MBP and Diastolic Blood Pressure (DBP) after the block and thedifference was statistically significant at 9, 12, 15, 18 and 21minute (p-value &lt;0.05). A 30% patients in group P as comparison to 10% in Group H required ephedrine for the treatment of hypotension and found significant (p-value=0.025). Systolic Blood Pressure (SBP), pulse rate changes and nausea and vomiting among both groups was non-significant (p-value &gt;0.05). Conclusion: Pre-loading with 5ml/kg of 6% Hetastarch is more effective than 15ml/kg of Plasmalyte in preventing hypotension in patients undergoing lower abdominal surgeries under spinal anaesthesia.

The Comparative Study of Azilsartan with Telmisartan in Terms of Efficacy, Safety and Cost - Effectiveness in Hypertension

Introduction: Hypertension (HT) represents the most common cardiovascular risk factor amongst the cluster group of Cardiovascular Diseases (CVD). Clinically, HT might be defined as that level of Blood Pressure (BP) at which the institution of therapy reduces the BP-related morbidity and mortality. Azilsartan (AZL) is a relatively new Angiotensin Receptor Blocker (ARB) available for the treatment of any stage of HT. Aim: To compare the efficacy, safety and cost-effectiveness of AZL 40-80 mg once daily versus telmisartan 40-80 mg once daily in patients of stage-I HT. Methods: A prospective, open, randomized parallel group comparative study of AZL versus telmisartan was done in patients of stage-I HT. The study included 80 patients, 40 in each group (group I and group II) coming to the department of Medicine, Rajindra Hospital attached to Government Medical College, Patiala. The study was conducted over 8 weeks. Group I, patients received Azilsartan 40-80 mg per day in divided doses and group II, patients received telmisartan 40-80 mg per day in divided doses according to severity of hypertension. The therapeutic efficacy of drugs was evaluated by monitoring BP. Adverse drug reactions were monitored in patients. The daily cost for each medication was noted and total cost of drugs taken over 8 weeks was calculated. Effectiveness of the drugs was calculated in terms of mm Hg fall in mean BP. All the observations thus made were statistically analyzed using appropriate tests. Results: Patients receiving AZL 40mg and telmisartan 40mg showed a significant fall (p<0.05) in systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 4 weeks and 8 weeks, when compared to baseline. The difference in SBP and DBP between Group I (AZL) and II (Telmisartan) was statistically significant at 4 weeks (p<0.05) and was highly significant at 8 weeks (p<0.001). Adverse effects such as nasopharyngitis, upper respiratory tract infection, gastroenteritis, headache, dizziness, and fatigue were reported with both drugs. Conclusions: Reduction of BP with AZL was more as compared to telmisartan at 4 weeks and 8 weeks. Safety and tolerability was similar in both groups.

A comparative evaluation of Equi-sedative doses of dexmedetomidine and propofol for peri-operative sedation in surgeries under regional anaesthesia

Objective: This study was conducted to compare the effects of equi-sedative doses of dexmedetomidine and propofol in patients undergoing elective surgical procedures after taking place regional anesthesia. Method: A prospective double-blind study was carried out in 80 patients of either sex, aged between 20 to 60 years and American Society of Anaesthesiologist (ASA) grade I, II and III. Patients were randomly allocated into two groups of 40 patients in each group.Group I (D) received i.v. dexmedetomidine (1 μg/kg initial loading dose for 10min, maintenance 0.5-0.7μg/kg/min). GroupII (P) received i.v. propofol (75μg/kg/min for 10min; maintenance 30-60μg/kg/min), two groups were compared in terms of cardio-respiratory effects, time to achieve and terminate sedation (using BIS index and OAA/S score), post-operative analgesia, side effects and complications of these drugs. Results: Both groups were comparable with regard to demographic variables. Time to achieve sedation was early in group II (10-15 min) as compared to group I (25 min). In post-operative period, the value of OAA/S after 5 min was lower (4.22±0.42) in group I as compared to group II (4.45±0.50) and termination of sedation in group I was late as compared to group II. Intraoperatively, fall in mean blood pressure and heart rate were statistically significant in both groups but fall in MBP was more in group II and fall in HR was more in group I (p

Assessment of the effect of two doses of prophylactic onandsetron on maternal hemodynamics, neonatal outcome and spinal blockade specifications, in parturients scheduled for cesarean delivery

Objective To compare between two doses of ondansetron (2 mg, 4 mg) and ephedrine in prevention of maternal hypotension and bradycardia induced by spinal anesthesia, their effects on specifications of spinal blockade, neonatal outcome, and their side effects. Patients and methods One hundred twenty parturients ASA І or ІІ aged between 18 and 40 years, scheduled for elective cesarean section under spinal anesthesia. They were randomly divided into four equal groups. First group received intravenous I.V. 2 mg ondansetron, second group received I.V. 4 mg ondansetron, third group received 10 mg ephedrine, and the fourth group received normal saline. All the test drugs were administered as bolus dose five minutes before intrathecal injection. Mean blood pressure, heart rate, vasopressor use, spinal anesthesia specifications, neonatal outcome, and side effects were assessed. Results The fall in mean blood pressure after spinal anesthesia in ondansetron 4 mg group was the least and the greatest was in the control group. There was dropping in heart rate values after spinal anesthesia started from 5 minutes value with significance to the control group only. No significant difference between the four groups in the spinal anesthesia characters. Slight acidosis was noticed in the ephedrine group which doesn’t affect the clinical neonatal outcome. Conclusion Prophylactic bolus intravenous ondansetron 4 mg and to less extent 2 mg could decrease the fall in mean blood pressure of parturients following spinal anesthesia as well as intravenous ephedrine 10 mg with added advantage that it could decrease neonatal acidosis associated with ephedrine use.

Hemodialysis immediately after cardiac catheterization is a risk factor for intradialytic hypotension.

Many hemodialysis clinicians have noticed that patients frequently develop intradialytic hypotension (IDH) immediately after cardiac catheterization (CC). However, precise data about the incidence of IDH immediately after CC are scarce. This study involved a single-center, retrospective, cross-sectional design. We reviewed the medical records of all HD patients who underwent CC between January 2009 and March 2012 at Hiroshima Prefectural Hospital. IDH was defined as a fall of systolic blood pressure of more than 20 mm Hg or a fall of mean blood pressure of more than 10 mm Hg, with symptoms according to the K/DOQI criteria. Data on a total of 112 patients were obtained: 64 patients commenced HD immediately after CC (IA group) and 48 patients underwent HD on the day after CC (ND group). The overall incidence of IDH was 34% (38/112). The incidence of IDH was significantly higher in the IA group than in the ND group (27/64, 42% vs. 11/48, 23%; P < 0.05). Multivariate logistic regression analysis showed that IA (odds ratio, 5.39; 95% confidence interval, 1.76 to 16.49; P < 0.01), coronary stenosis (odds ratio, 4.16; 95% confidence interval, 1.49 to 11.64; P < 0.05) were independently associated with IDH. This study revealed that HD immediately after CC is associated with a higher incidence of IDH. Clinicians should consider that HD following CC be scheduled for the next day, especially in patients with coronary stenosis.

Predictors of Blood Pressure Fall With Continuous Positive Airway Pressure Treatment in Hypertension With Coronary Artery Disease and Obstructive Sleep Apnea

BackgroundThe present study aimed to investigate the predictors of changes in blood pressure (BP) with continuous positive airway pressure (CPAP) treatment in hypertensive patients with coronary heart disease (CHD) and obstructive sleep apnea (OSA). MethodsSeventy-one hypertensive patients with CHD and OSA were enrolled in this study. Daytime systolic BP (SBP), diastolic BP (DBP), Epworth Sleepiness Scale (ESS), and anthropometric characteristics were assessed at baseline and follow-up. ResultsSixty-six patients completed the study. The median follow-up period was 36 months (interquartile range, 24-60 months). The mean duration of CPAP application was 4.3 ± 1.2 hours per night. From baseline to follow-up, SBP and DBP were reduced by 5.6 mm Hg (95% confidence interval [CI], 3.0-8.1) and 3.0 mm Hg (95% CI, 0.8-5.3), respectively. Daytime somnolence was significantly improved (ESS, from 9.5 ± 3.4 at baseline to 3.6 ± 2.0 at follow-up; P < 0.001); the mean improvement in ESS was 6.0 (95% CI, 5.1-6.9). Correlation analysis of the fall in mean BP (MBP) showed that baseline MBP, change in ESS, heart rate, and CPAP compliance showed a positive correlation, whereas the baseline body mass index (BMI) and ESS had an inverse relationship. Stepwise multiple linear regression analysis, however, indicated that only baseline BMI, baseline MBP, and CPAP compliance were independently correlated with the fall in MBP. ConclusionsLong-term CPAP treatment reduces BP in hypertensive patients with CHD and moderate/severe OSA; baseline BMI, baseline MBP, and CPAP compliance are independent predictors of the decrease in BP with CPAP treatment in these patients.

Nighttime Blood Pressure in Cluster Headache

It has been proposed that desaturation of oxygen during an apnea event is the trigger for cluster headache. Obstructive sleep apnea has been associated with a higher than normal cardiovascular morbidity and mortality. Some obstructive sleep apnea syndrome patients lack the sleep-related, nocturnal decrease, or "dip" in blood pressure, which is seen in normal individuals. The aim of this study is to assess whether this non-dipper pattern is present in cluster headache patients. A total of 30 normotensive cluster headache patients underwent an ambulatory blood pressure monitoring. "Non dippers" were defined as patients with a nighttime mean blood pressure fall <10%. Fifteen cluster headache patients (50%) were non-dippers, a frequency higher than expected. The pattern of nocturnal non-dipping is associated with a higher body mass index. Non-dipper patients displayed higher mean nighttime systolic and diastolic blood pressure. No significant difference was observed in the mean 24-hour and daytime blood pressure. The high incidence (50%) of non-dipper pattern in both processes, cluster headache and obstructive sleep apnea syndrome, provides support for the hypothesis of a relationship between theses 2 disorders.

Autonomic nervous system and endothelial peripheral dysfunction in normal tension glaucoma patients

Abstract Purpose To define parameters of autonomic nervous system activity and peripheral vascular reactive hyperemia in normal tension glaucoma patients. Methods Ambulatory 24‐hour electrocardiogram and blood pressure (BP) monitoring by using Lifecard CF and SpaceLab 90207‐30 combined with occlusion provocation test were carried out in 54 NTG patients (44 women, mean age 59.7) and 43 matched control subjects (34 women, mean age 57.0). Heart rate variability (HRV) time and frequency domain parameters [low‐frequency (LF), high‐frequency (HR) and LF/HF ratio], and blood pressure variability (BPV) were calculated and analyzed for both study groups. Postocclusive hyperemia response parameters (TM ‐ time to peak flow, TH –half‐time hyperaemia, TR –time to rest flow, BZ‐biological zero and MAX – maximum hyperemic response) were compared for patients with a nocturnal fall in mean BP (MPB) of less than 10% (non‐dippers), of 10‐20% (dippers) and of more than 20% (over‐dippers) Results NTG patients demonstrated higher LF and LF/HF values for 24‐hour period, day‐time and night time than control subjects. There was no difference in BPV between study groups (10.4 ± 1.9 vs. 10.5 ± 2.1, p=0.790). In NTG patients, TH was significantly higher (79.0 ± 80.9 s vs. 51.5 ± 35.3 s, p=0.028) and BZ was significantly lower (2.3 ± 1.0 vs. 3.1 ± 2.0, p=0.009) as compared to the control group. There was statistically significant difference between NTG non‐dippers, dippers and over–dippers in the BZ parameter (2.3 ± 0.9 vs. 2.7 ± 1.3 vs. 1.4 ± 0.4 p=0.024). Conclusion NTG patients exhibit abnormal ANS system activity and a different systemic hyperemia response as compared with healthy subjects.

Hyperbaric oxygen therapy prevents coagulation disorders in an experimental model of multiple organ failure syndrome

To evaluate the effects of hyperbaric oxygen (HBO) therapy on the coagulation cascade using an experimental model of multiple organ failure syndrome (MOFS). MOFS was induced by zymosan (500mg/kg i.p.) in rats. HBO therapy (2ATA) was administered in a cylindrical steel chamber 4 and 11h after zymosan administration. In a separate set of experiments animals were monitored for 72h, and systemic toxicity was scored. Eighteen hours after zymosan administration, rats were killed and blood samples were used for analysis of hemocoagulative parameters, hemodynamics, and arterial blood gas. Zymosan administration caused MOFS by affecting the coagulation cascade, as shown by a significant increase in plasma levels of fibrinogen, tissue plasminogen activator, inhibitor of tissue plasminogen activator of type 1, and plasma levels of fibrin degradation products vs. control rats. Zymosan-induced MOFS was also characterized by a significant increase in von Willebrand antigen plasma levels vs. controls. Moreover, zymosan administration induced a significant fall in mean arterial blood pressure and alteration in blood gas values. HBO therapy significantly reduced the derangements of coagulation cascade, the fall in mean blood pressure and alteration in blood gas induced by zymosan administration. The hypercoagulability induced by zymosan could be responsible for organ failure and death. Our data demonstrate that HBO therapy significantly prevents the alteration in the coagulation cascade and arterial blood gas in an experimental model of MOFS.

Sympathetic activation and tachycardia in lipopolysaccharide treated rats are temporally correlated and unrelated to the baroreflex

The goal of this study was to investigate the sustained sympatho-excitation which occurs in sepsis and which accompanies the fall in blood pressure and to analyze its time-correlation with heart rate and the role of the baro-chemoreflexes. Rats anesthetized with pentobarbital were treated with lipolysaccharide (LPS) 20 mg/kg / 20 min i.v. and mean blood pressure (MBP), heart rate (HR), rectal temperature and renal sympathetic nerve activity (RSNA) were recorded. LPS induced a fall in blood pressure, an increase in HR (+ 20%) and RSNA (+ 355%); the arterial PO 2 and PCO 2 remained stable and the injection was fatal within 4 h. Baroreceptor and chemoreceptor denervation accelerated the fall in MBP but did not change the survival time. Under those conditions; RSNA excitation was slightly more pronounced. During treatment with gallamine and under artificial respiration to avoid possible respiratory changes through the chemoreflex pathway, the effects of LPS remained, except for a decrease in arterial PO 2. Electrolytic lesioning of the nucleus tractus solitarius or blocking the effects of baroreflex efferents by either an α 1 or α 2-adrenoceptor antagonists failed to alter the effects of LPS. After treatment with a β-adrenoceptor antagonist, LPS increased RSNA but not HR and the survival time of the rats shortened. LPS administered i.c. (1 mg/kg) induced, with a short latency, effects comparable to those produced by i.v. injection. Surprisingly, the time correlation between RSNA and HR rhythms persisted when MBP dropped after LPS and moreover it reappeared in baroreceptor denervated rats after LPS. Thus under these conditions of altered baroreflex pathway and LPS induced sympathetic activation, the sympathetic output from the medulla appears to play a role in the correlation between heart rate and sympathetic nerve activity. These data indicate that the marked RSNA activation and the tachycardia are correlated and that the baroreflex and chemoreflex are not inhibited during sepsis but appear to be of minor importance in the sympathetic activation and in the blood pressure modifications.

Hemodynamic effects of phosphodiesterase 5 and angiotensin-converting enzyme inhibition alone or in combination in conscious SHR.

The regional hemodynamic responses to continuous 4-day infusion of UK-357,903 [1-ethyl-4-{3-[3-ethyl-6,7-dihydro-7-oxo-2-(2-pyridylmethyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-2-(2-methoxyethoxy)-5-pyridylsulphonyl}piperazine] (266 microg kg(-1) h(-1)) alone and in combination with a low dose of enalapril (10 microg kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats to test the hypothesis that the renin-angiotensin system may influence the cardiovascular consequences of inhibition of phosphodiesterase 5 (PDE5) by UK-357,903 or vice versa. UK-357,903 alone caused a fall in mean blood pressure (-12.1 mm Hg) associated with vasodilatation in the mesenteric and hindquarters vascular beds. The only way in which the effects of enalapril given alone differed significantly from those of the vehicle was in causing mesenteric vasodilatation, which developed over the 4 days of infusion. UK-357,903 given in combination with enalapril caused hypotension (-17.8 mm Hg) and vasodilatation in the renal, mesenteric, and hindquarter vascular beds. There was evidence of a significant interaction between the effects of the two compounds on renal Doppler shift and vascular conductance with the combined action of the two compounds being greater than the sum of their individual effects. However, although there was a trend for the combination to have greater effects than either of the individual agents on blood pressure and mesenteric vascular conductance, there was no statistical evidence of an interaction. The results indicate that inhibition of the renin-angiotensin system uncovers additional renal vasodilator effects of UK-357,903, and/or inhibition of PDE5 enhances the renal vasodilator effects of angiotensin-converting enzyme inhibition.

Cannabidiol lacks the vanilloid VR1-mediated vasorespiratory effects of capsaicin and anandamide in anaesthetised rats

The results of vasorespiratory studies in rats anaesthetised with pentobarbital show that (±) cannabidiol, a cannabinoid that lacks psychotropic actions and is inactive at cannabinoid (CB) receptors, does not affect respiration or blood pressure when injected (1–2000 μg; 3.2–6360 nmol i.a.). Cannabidiol in doses up to 2 mg (6360 nmol) i.a. or i.v. did not affect the fall in mean blood pressure or the increase in ventilation (respiratory minute volume) caused by capsaicin and high doses of anandamide, responses that are mediated by activation of vanilloid VR1 (TRPV1) receptors in this species. Similar results were obtained with (−) cannabidiol (30–100 μg i.a.; 95–318 nmol). It has previously been shown using human embryonic kidney (HEK) cells over-expressing vanilloid human VR1 (hVR1) receptors that cannabidiol is a full agonist at vanilloid VR1 receptors in vitro. However, in the intact rat cannabidiol lacked vanilloid VR1 receptor agonist effects. We conclude that there are substantial functional differences between human and rat vanilloid VR1 receptors with respect to the actions of cannabidiol as an agonist at vanilloid VR1 receptors. Studies in vivo show that cannabidiol lacks any significant effect on mean blood pressure or respiratory minute volume when injected i.a. or i.v., and that this cannabinoid does not modulate the vanilloid VR1 receptor-mediated cardiovascular and ventilatory changes reflexly evoked by capsaicin or anandamide in rats anaesthetised with pentobarbital.

Haemodynamic effects of the selective phosphodiesterase 5 inhibitor, UK‐357,903, in conscious SHR

1. Regional haemodynamic responses to a continuous, 4-day infusion of the selective phosphodiesterase type 5 inhibitor, UK-357,903 (0.133 or 1.33 mg x kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats, and compared with those of enalapril (1 mg x kg(-1) h(-1)). 2. Both doses of UK-357,903 caused modest reductions in mean blood pressure that were not dose-dependent and only significantly different from the vehicle effects on Day 1 of the study (mean -11.8 and -15.3 mmHg for low and high doses, respectively). UK-357,903 had mesenteric and hindquarters vasodilator effects, which were, again, similar for both dose levels and only significantly different from vehicle on Day 1. Neither dose of UK-357,903 affected renal vascular conductance or heart rate. 3. Although the haemodynamic effects of UK-357,903 were not clearly dose-related and some appeared to wane with time, geometric mean plasma levels of UK-357,903 increased in proportion to dose, and were sustained throughout the infusion period. Furthermore, plasma cyclic guanosine monophosphate, a biomarker of phosphodiesterase 5 inhibition, was persistently elevated, and increased with increasing dose. 4. Enalapril caused a fall in mean blood pressure on day 1 (-14.1 mmHg) that was associated with dilatation in renal, mesenteric and hindquarters vascular beds. The haemodynamic effects of enalapril were sustained or increased over the 4-day infusion, although plasma free drug levels were stable. 5. In conclusion, we have shown regional and temporal changes in the haemodynamic effects of UK-357,903, which may be due to activation of compensatory mechanisms, but there were no signs of functional compensation to the cardiovascular effects of enalapril.

The effect of elevation on digital blood pressure

Elevation of the hand is recommended for all patients undergoing hand surgery to decrease the swelling in the hand. This study was designed to look at the effects of elevation of the hand on digital blood pressure at different elevation positions. Digital blood pressure was recorded using a digital plethysmograph in 30 subjects for increasing levels of elevation above the heart. Friedman's test was applied to the blood-pressure changes recorded in the four positions of the upper limb and showed a significant sustained fall in mean blood pressure with increasing elevation, bringing into question the use of elevation in certain clinical situations.

Plasma Adrenomedullin Levels in Patients on Hemodialysis

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 ± 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 ± 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.