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Resuscitation Oct 2023The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC)... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC.
METHODS
The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin.
RESULTS
The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs.
CONCLUSION
Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo.
Topics: Humans; Methylprednisolone; Cardiopulmonary Resuscitation; Heart Arrest; Vasopressins; Vasoconstrictor Agents; Hemodynamics; Norepinephrine; Hospitals; Gases
PubMed: 37543161
DOI: 10.1016/j.resuscitation.2023.109922 -
European Journal of Pharmacology Jul 2023A role for mitochondrial fission in vascular contraction has been proposed based on the vasorelaxant activity of the dynamin (and mitochondrial fission) inhibitors...
A role for mitochondrial fission in vascular contraction has been proposed based on the vasorelaxant activity of the dynamin (and mitochondrial fission) inhibitors mdivi-1 and dynasore. However, mdivi-1 is capable to inhibit Ba currents through Ca1.2 channels (I), stimulate K1.1 channel currents (I), and modulate pathways key to the maintenance of vessel active tone in a dynamin-independent manner. Using a multidisciplinary approach, the present study demonstrates that dynasore, like mdivi-1, is a bi-functional vasodilator, blocking I and stimulating I in rat tail artery myocytes, as well as promoting relaxation of rat aorta rings pre-contracted by either high K or phenylephrine. Conversely, its analogue dyngo-4a, though inhibiting mitochondrial fission triggered by phenylephrine and stimulating I, did not affect I but potentiated both high K- and phenylephrine-induced contractions. Docking and molecular dynamics simulations identified the molecular basis supporting the different activity of dynasore and dyngo-4a at Ca1.2 and K1.1 channels. Mito-tempol only partially counteracted the effects of dynasore and dyngo-4a on phenylephrine-induced tone. In conclusion, the present data, along with previous observations (Ahmed et al., 2022) rise caution for the use of dynasore, mdivi-1, and dyngo-4a as tools to investigate the role of mitochondrial fission in vascular contraction: to this end, a selective dynamin inhibitor and/or a different experimental approach are needed.
Topics: Rats; Animals; Mitochondrial Dynamics; Dynamins; Niacinamide; Phenylephrine
PubMed: 37179045
DOI: 10.1016/j.ejphar.2023.175786 -
Experimental Physiology Dec 2023What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding...
NEW FINDINGS
What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries.
ABSTRACT
Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (K , BK and K ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that K and K channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model.
Topics: Pregnancy; Female; Humans; Umbilical Arteries; Serotonin; Acetylcholine; Minoxidil; Pre-Eclampsia; Vasodilation; Vasoconstrictor Agents; Phenylephrine; Homocysteine; Adenosine Triphosphate
PubMed: 37837634
DOI: 10.1113/EP091374 -
Tzu Chi Medical Journal 2023The bladder and urethra work as a physiologically functional unit to facilitate continence in the storage and voiding phase. Sex differences have been found in the...
OBJECTIVES
The bladder and urethra work as a physiologically functional unit to facilitate continence in the storage and voiding phase. Sex differences have been found in the urethral contraction in response to α-adrenergic receptor activation. This study aimed to investigate the role of adrenergic receptors in the proximal urethra of male and female mice.
MATERIALS AND METHODS
Urinary bladder and proximal urethral smooth muscle (USM) samples from male and female C57BL/6 mice were isolated and mounted in an organ bath.
RESULTS
Acetylcholine-induced contraction of the urinary bladder was compared in male and female mice. Phenylephrine and norepinephrine (NE) induced little contraction at a lower concentration, but a relaxing phase of female proximal USM was observed at a higher concentration. This contraction profile was inhibited by N-nitro-L-arginine, lidocaine, and capsaicin. In addition, the NE-induced contraction was greater in the incubation of propranolol than that of L-NNA or lidocaine. These results suggested that the β-adrenoceptor may be the dominant receptor of female proximal USM, and the activity of calcitonin gene-related peptide sensory nerves and nitrergic nerves may pose an anti-contraction effect on the proximal urethra in female mice.
CONCLUSION
β-adrenoceptor may be the dominant receptor of female proximal USM. The use of β-adrenergic receptor blocker agents might have the potential for the treatment of female voiding dysfunction.
PubMed: 37545797
DOI: 10.4103/tcmj.tcmj_221_22 -
Surgical Endoscopy Aug 2023Although it is known that excessive intraoperative fluid and vasopressor agents are detrimental for anastomotic healing, optimal anesthesiology protocols for colorectal... (Observational Study)
Observational Study
BACKGROUND
Although it is known that excessive intraoperative fluid and vasopressor agents are detrimental for anastomotic healing, optimal anesthesiology protocols for colorectal surgery are currently lacking.
OBJECTIVE
To scrutinize the current hemodynamic practice and vasopressor use and their relation to colorectal anastomotic leakage.
DESIGN
A secondary analysis of a previously published prospective observational study: the LekCheck study.
STUDY SETTING
Adult patients undergoing a colorectal resection with the creation of a primary anastomosis.
OUTCOME MEASURES
Colorectal anastomotic leakage (CAL) within 30 days postoperatively, hospital length of stay and 30-day mortality.
RESULTS
Of the 1548 patients, 579 (37%) received vasopressor agents during surgery. Of these, 201 were treated with solely noradrenaline, 349 were treated with phenylephrine, and 29 received ephedrine. CAL rate significantly differed between the patients receiving vasopressor agents during surgery compared to patients without (11.8% vs 6.3%, p < 0.001). CAL was significantly higher in the group receiving phenylephrine compared to noradrenaline (14.3% vs 6%, p < 0.001). Vasopressor agents were used more often in patients treated with Goal Directed Therapy (47% vs 34.6%, p < 0.001). There was a higher mortality rate in patients with vasopressors compared to the group without (2.8% vs 0.4%, p = 0.01, OR 3.8). Mortality was higher in the noradrenaline group compared to the phenylephrine and those without vasopressors (5% vs. 0.4% and 1.7%, respectively, p < 0.001). In multivariable analysis, patients with intraoperative vasopressor agents had an increased risk to develop CAL (OR 2.1, CI 1.3-3.2, p = 0.001).
CONCLUSION
The present study contributes to the evidence that intraoperative use of vasopressor agents is associated with a higher rate of CAL. This study helps to create awareness on the (necessity to) use of vasopressor agents in colorectal surgery patients in striving for successful anastomotic wound healing. Future research will be required to balance vasopressor agent dosage in view of colorectal anastomotic leakage.
Topics: Adult; Humans; Anastomotic Leak; Colorectal Surgery; Risk Factors; Vasoconstrictor Agents; Anastomosis, Surgical; Phenylephrine; Norepinephrine; Colorectal Neoplasms
PubMed: 37126191
DOI: 10.1007/s00464-023-09980-1 -
Journal of Anaesthesiology, Clinical... 2023Pre-eclamptic parturients may have an exaggerated response to vasopressors. This study compares the efficacy of a 50 μg fixed bolus of phenylephrine for treatment of...
BACKGROUND AND AIMS
Pre-eclamptic parturients may have an exaggerated response to vasopressors. This study compares the efficacy of a 50 μg fixed bolus of phenylephrine for treatment of post-spinal hypotension in pre-eclamptic versus normotensive parturients.
MATERIAL AND METHODS
After written informed consent and ethics committee approval, 30 normotensive and 30 pre-eclamptic parturients between 18 and 40 years with singleton term pregnancy about to undergo cesarean section (CS) under spinal anesthesia were included. Post-spinal hypotension was treated with a 50 μg fixed bolus of phenylephrine. The cumulative dose of phenylephrine, the number of boluses, and the median dose required to treat the first hypotensive episode, total number of hypotensive episodes, maternal side effects, neonatal appearance, pulse, grimace, activity, and respiration (APGAR) scores, and umbilical arterial cord blood pH were noted. Statistical analysis was done using Student's t-test, Mann-Whitney U-test, Chi-square test/Fisher's exact test as appropriate. A <0.05 was considered significant.
RESULTS
The cumulative dose and number of boluses of phenylephrine required to treat post-spinal hypotension were comparable. The median dose required to treat the first episode of post-spinal hypotension was also similar ( = 0.792). The time to develop the first hypotensive episode was significantly earlier for group N ( = 0.002). The efficacy of a single fixed bolus of 50 μg phenylephrine was similar in both groups ( = 1.000). Neonatal median APGAR scores at 1 min after birth were significantly higher for group N ( = 0.016).
CONCLUSION
A fixed-dose bolus of 50 μg phenylephrine is safe and effective in treating post-spinal hypotension in pre-eclampsia. The efficacy of phenylephrine is comparable in pre-eclamptic and normotensive parturients.
PubMed: 38025583
DOI: 10.4103/joacp.joacp_518_21 -
Cureus Jul 2023Background Maternal hypotension following spinal anesthesia can be actively countered by the use of vasopressors. Prophylactic infusion of vasopressors with a rescue...
Background Maternal hypotension following spinal anesthesia can be actively countered by the use of vasopressors. Prophylactic infusion of vasopressors with a rescue bolus dosing was observed to be more effective for hemodynamic stability when compared to administering a bolus dose alone. Although phenylephrine is the recommended drug to treat spinal hypotension, many recent studies have focussed on the role of norepinephrine infusions during cesarean section. In this study, we compared prophylactic fixed-rate intravenous infusions of phenylephrine and norepinephrine during cesarean delivery under spinal anesthesia and the requirement of intraoperative provider-administered rescue bolus of phenylephrine needed to overcome post-spinal anesthesia hypotension. Methodology A total of 208 patients undergoing elective cesarean section under spinal anesthesia were randomly assigned to two groups (group P and group N). Group N included 104 patients who received norepinephrine infusion at a rate of 2.5 μg/minute (0.04 μg/kg/minute), and group P included 104 patients who received phenylephrine infusion at a rate of 50 μg/minute (0.8 μg/kg/minute) to treat spinal hypotension. The primary outcome of our study was to compare the reduction in the number and total dose of intraoperative provider-administered rescue bolus of phenylephrine needed to maintain systolic blood pressure. The secondary outcome of our study was to compare the neonatal outcome using umbilical venous blood gas sampling and Apgar score at one and five minutes. Results The total number of phenylephrine rescue bolus required to treat hypotension was significantly lower in group N (p = 0.0005) compared to group P. The neonatal outcome was similar between the two groups. Conclusions Prophylactic norepinephrine infusion when compared to prophylactic phenylephrine infusion is associated with a lesser requirement of rescue phenylephrine boluses.
PubMed: 37529826
DOI: 10.7759/cureus.41251 -
Scientific Reports Aug 2023The present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and...
The present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and triglycerides level and vascular function in streptozotocin (STZ) -induced diabetic rats. Male Sprague Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (50 mg/kg). Rutin and metformin were orally administered to diabetic rats at a dose of 100 mg/kg and 300 mg/kg body weight/day, respectively, for 4 weeks. Plasma analysis was conducted to determine changes in the plasma glucose and lipid levels. Rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the α1-adrenergic agonist phenylephrine (PE) were recorded. Histology of pancreas, liver and kidney were evaluated. In results, rutin and metformin alone and in combination has led to significant improvements in blood glucose, cholesterol and triglyceride levels compared to diabetic group. Diabetic aortic rings showed significantly greater contraction in response to PE, and less relaxation in response to ACh and SNP. Treatment with rutin and metformin in combination significantly reduced PE-induced contraction and increased ACh-induced and SNP-induced relaxation in diabetes when compared to rutin or metformin alone. Significant histological improvements were seen with combination therapy. In conclusion, rutin and metformin combination therapy has the most potentiality for restoring blood glucose and lipid level as well as vascular function.
Topics: Rats; Male; Animals; Metformin; Rats, Sprague-Dawley; Diabetes Mellitus, Type 1; Rutin; Diabetes Mellitus, Experimental; Blood Glucose; Phenylephrine; Acetylcholine; Cholesterol; Lipids; Endothelium, Vascular
PubMed: 37528147
DOI: 10.1038/s41598-023-39442-6 -
Clinical Autonomic Research : Official... Aug 2023Orthostatic hypotension is a common condition with heterogeneous and, in many cases, unclear underlying pathophysiology. Frequent symptoms are syncope and falls with a...
PURPOSE
Orthostatic hypotension is a common condition with heterogeneous and, in many cases, unclear underlying pathophysiology. Frequent symptoms are syncope and falls with a strong impact on daily life. A two-generation family with eight individuals segregating early-onset severe orthostatic hypotension with persistent tachycardia in upright position and repeated faints was identified. Our aim was to elucidate the underlying pathophysiology.
METHODS
One severely affected individual underwent thorough investigation with neurophysiological and blood pressure (BP) measurements, including direct recording of baroreflex-governed sympathetic nerve signalling and induction of BP rise with phenylephrine. Family members underwent parts of the examination. Genetic analysis using exome sequencing was performed.
RESULTS
Marked postural hypotension with greatly reduced cardiac preload was observed, but without signs of autonomic nervous system dysfunction: sympathetic nerve signalling was normal, as were catecholamine levels, and phenylephrine stimulation revealed a normal increase in BP. The results of the genetic analysis using exome sequencing comprising all known genes associated with the regulation of BP and catecholamine metabolism were normal.
CONCLUSION
The combined findings suggest an autosomal dominant form of early-onset orthostatic hypotension with variable clinical expression and without any additional autonomic dysfunction. It is possible that further investigation will reveal an as yet undescribed entity of orthostatic hypotension transmitted as an autosomal dominant trait.
Topics: Humans; Hypotension, Orthostatic; Sweden; Autonomic Nervous System Diseases; Syncope; Phenylephrine; Catecholamines
PubMed: 37460866
DOI: 10.1007/s10286-023-00963-9 -
International Journal of Molecular... Jul 2023Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule...
Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3 mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in mice without notable changes in pulmonary vasculature under CIH conditions.
Topics: Animals; Mice; Chronic Disease; Endothelins; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Mice, 129 Strain; Sleep Apnea, Obstructive; Disease Models, Animal
PubMed: 37511045
DOI: 10.3390/ijms241411284