Rapid Decrease In Blood Pressure Research Articles

ФИКСИРОВАННАЯ КОМБИНАЦИЯ ИРБЕСАРТАН/ГИДРОХЛОРТИАЗИД В ЛЕЧЕНИИ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ

Almost a third of the population of the Republic of Belarus suffers from elevated blood pressure which results in a high risk of cardiovascular disease developing. Despite the availability of numerous antihypertensive drugs, more than 40% of patients receiving antihypertensive therapy do not achieve target blood pressure levels and continue to be at an increased risk of cardiovascular events. A fixed combination drug irbesartan/hydrochlorothiazide, which includes two active ingredients in one dosage form of a tablet, is an anti-hypertensive combination balanced on the basis of clinical and pharmacological properties, which is approved by the Ministry of Health of the Republic of Belarus for use in patients when indicated in case of essential arterial hypertension. This fixed-dose combination is intended for adult patients whose blood pressure is not adequately controlled by irbesartan or hydrochlorothiazide monotherapy. The clinical efficacy and safety of this combination was demonstrated in randomized clinical trials, including patients with a combination of hypertension and type 2 diabetes, metabolic syndrome, and obesity. The use of the fixed-dose combination of irbesartan/hydrochlorothiazide leads to a more rapid decrease in blood pressure compared to irbesartan monotherapy, allows the majority of patients with severe hypertension to achieve the target blood pressure, and increases drug compliance. Thus, the irbesartan/hydrochlorothiazide combinationis a valuable addition to clinicians’ armamentarium for the treatment of hypertension.

Pulsed Infrared Stimulation of Vertical Semicircular Canals Evokes Cardiovascular Changes in the Rat.

A variety of stimuli activating vestibular end organs, including sinusoidal galvanic vestibular stimulation, whole body rotation and tilt, and head flexion have been shown to evoke significant changes in blood pressure (BP) and heart rate (HR). While a role for the vertical semicircular canals in altering autonomic activity has been hypothesized, studies to-date attribute the evoked BP and HR responses to the otolith organs. The present study determined whether unilateral activation of the posterior (PC) or anterior (AC) semicircular canal is sufficient to elicit changes in BP and/or HR. The study employed frequency-modulated pulsed infrared radiation (IR: 1,863 nm) directed via optical fibers to PC or AC of adult male Long-Evans rats. BP and HR changes were detected using a small-animal single pressure telemetry device implanted in the femoral artery. Eye movements evoked during IR of the vestibular endorgans were used to confirm the stimulation site. We found that sinusoidal IR delivered to either PC or AC elicited a rapid decrease in BP and HR followed by a stimulation frequency-matched modulation. The magnitude of the initial decrements in HR and BP did not correlate with the energy of the suprathreshold stimulus. This response pattern was consistent across multiple trials within an experimental session, replicable, and in most animals showed no evidence of habituation or an additive effect. Frequency modulated electrical current delivered to the PC and IR stimulation of the AC, caused decrements in HR and BP that resembled those evoked by IR of the PC. Frequency domain heart rate variability assessment revealed that, in most subjects, IR stimulation increased the low frequency (LF) component and decreased the high frequency (HF) component, resulting in an increase in the LF/HF ratio. This ratio estimates the relative contributions of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activities. An injection of atropine, a muscarinic cholinergic receptor antagonist, diminished the IR evoked changes in HR, while the non-selective beta blocker propranolol eliminated changes in both HR and BP. This study provides direct evidence that activation of a single vertical semicircular canal is sufficient to activate and modulate central pathways that control HR and BP.

Unjustified Referral of Adult Patients with Hypertensive Crisis from a First Level of Care to the Emergency Department

Hypertensive crisis is one of the main complications of systemic arterial hypertension, which is defined as severe elevation of blood pressure, with figures of more than 220/130 mmHg, these in turn are divided into urgency and emergency, which occurs when there is damage to a target organ. According to the literature, the majority of hypertensive crises that occur are of an urgency type, reported in up to 80% of cases, the latter do not require a rapid decrease in blood pressure, taking up to 72 hours to control them, so they must be treated in a first-level care unit, however, a high number of referrals to the emergency department for hypertensive crisis of an urgency type have been detected, which have no justification for their referral.

Severe hypotension during vertebral derotation in surgical correction of scoliosis

Hypotension event in intraoperative settings may cause postoperative morbidity in surgical correction of scoliosis. Most often complications of intraoperative hypotension are postoperative ischemic optic neuropathy and postoperative ischemic stroke due to global hypoperfusion. Hypovolemic shock due to bleeding or blood loss is the most common cause of intraoperative hypotension in surgical correction of scoliosis. However, bleeding is not only the main cause of hypotension. A young female underwent surgical correction of scoliosis, during the operation she had a sudden and rapid decrease of blood pressure (BP) but then rapidly improved after the surgeon stopped the surgery which was a de-rotational procedure. Neurogenic shock is one of the complications that may occur during the manipulation of the spinal cord which is marked by a sudden and rapid decrease of BP and usually accompanied by bradycardia due to sudden and rapid loss of autonomic tone. Hypotension in neurogenic shock usually is refractory hypotension which cannot be treated only with fluid resuscitation but also needs vasopressor, thus this neurogenic shock should get immediate and prompt treatment to avoid further complications.

Racial Differences in Postpartum Blood Pressure Trajectories Among Women After a Hypertensive Disorder of Pregnancy

Maternal morbidity and mortality are increasing in the United States, most of which occur post partum, with significant racial disparities, particularly associated with hypertensive disorders of pregnancy. Blood pressure trajectory after a hypertensive disorder of pregnancy has not been previously described. To describe the blood pressure trajectory in the first 6 weeks post partum after a hypertensive disorder of pregnancy and to evaluate whether blood pressure trajectories differ by self-reported race. This prospective cohort study included deliveries between January 1, 2018, and December 31, 2019. Women with a clinical diagnosis of a hypertensive disorder of pregnancy were enrolled in a postpartum remote blood pressure monitoring program at the time of delivery and were followed up for 6 weeks. Statistical analysis was performed from April 6 to 17, 2020. Mixed-effects regression models were used to display blood pressure trajectories in the first 6 weeks post partum. A total of 1077 women were included (mean [SD] age, 30.2 [5.6] years; 804 of 1017 White [79.1%] and 213 of 1017 Black [20.9%]). Systolic and diastolic blood pressures were found to decrease rapidly in the first 3 weeks post partum, with subsequent stabilization (at 6 days post partum: mean [SD] peak systolic blood pressure, 146 [13] mm Hg; mean [SD] peak diastolic blood pressure, 95 [10] mm Hg; and at 3 weeks post partum: mean [SD] peak systolic blood pressure, 130 [12] mm Hg; mean [SD] peak diastolic blood pressure, 85 [9] mm Hg). A significant difference was seen in blood pressure trajectory by race, with both systolic and diastolic blood pressure decreasing more slowly among Black women compared with White women (mean [SD] peak systolic blood pressure at 1 week post partum: White women, 143 [14] mm Hg vs Black women, 146 [13] mm Hg; P = .01; mean [SD] peak diastolic blood pressure at 1 week post partum: White women, 92 [9] mm Hg vs Black women, 94 [9] mm Hg; P = .02; and mean [SD] peak systolic blood pressure at 3 weeks post partum: White women, 129 [11] mm Hg vs Black women, 136 [15] mm Hg; P < .001; mean [SD] peak diastolic blood pressure at 3 weeks post partum: White women, 84 [8] mm Hg vs Black women, 91 [13] mm Hg; P < .001). At the conclusion of the program, 126 of 185 Black women (68.1%) compared with 393 of 764 White women (51.4%) met the criteria for stage 1 or stage 2 hypertension (P < .001). This study found that, in the postpartum period, blood pressure decreased rapidly in the first 3 weeks and subsequently stabilized. The study also found that, compared with White women, Black women had a less rapid decrease in blood pressure, resulting in higher blood pressure by the end of a 6-week program. Given the number of women with persistent hypertension at the conclusion of the program, these findings also appear to support the importance of ongoing postpartum care beyond the first 6 weeks after delivery.

Management of acute ischemic stroke in the practice of anesthesiologist

Background. Stroke is a major cause of severe disability. Working capacity is restored only in 10-20 % of stroke survivors. Stroke mortality in Ukraine is twice as high as in Western Europe. About 87 % of all strokes are ischemic strokes (II). Leading risk factors for stroke include hypertension, hypercholesterolemia, smoking, obesity, and diabetes.&#x0D; Objective. To describe the management of acute IS (AIS) in the practice of an anesthesiologist.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. The ideal therapeutic approach for AIS should include reperfusion, inhibition of inflammatory processes, cytoprotection, prevention of complications and their treatment. Extreme caution should be exercised during thrombolytic therapy, as thrombolysis increases the risk of intracerebral hemorrhage. However, a meta-analysis by Y. Shoujiang et al. (2018) found that symptomatic intracerebral hemorrhage occurs in 1.9 % of patients who had received intravenous recombinant tissue plasminogen activator. These hemorrhages did not increase mortality. Excellent treatment results were observed in 74.8 % of patients with AIS. According to the analysis of the VISTA database, the end result of thrombolytic therapy can be predicted based on the initial severity of stroke on the NIHHS scale. Interestingly, hemorrhagic transformation after thrombolysis is associated with lower serum calcium. Lower blood calcium levels are associated with an increased incidence of cerebral hemorrhage in patients with AIS due to atrial fibrillation or rheumatic heart disease. In the treatment of patients with AIS it is advisable to use Neurocytin (“Yuria-Pharm”), which contains citicoline and a balanced isotonic electrolyte solution. Neurocytin helps to avoid hypocalcemia and, consequently, brain hemorrhages. Citicoline is a multimodal agent with neuroprotective and neuroregenerative properties. Citicoline has a wide therapeutic window, as this substance is effective at different time and biochemical stages of the ischemic cascade. The maximum effect of citicoline is observed in cases when it is administered as early as possible after AIS in patients who cannot undergo reperfusion therapy. Citicoline is able to reduce the size of the ischemic focus in the brain. Intensive blood pressure (BP) control also reduces the risk of intracranial hemorrhages without increasing mortality, although previous studies have suggested that a rapid decrease in BP may exacerbate cerebral ischemia. Endovascular treatment of AIS in the most acute phase involves selective thrombolysis, or mechanical thrombextraction, or thromboaspiration. The therapeutic window for the last two procedures for vessels of the carotid pool is 6 hours. When deciding to perform thromboaspiration, it is mandatory to perform and evaluate computed tomography-perfusiography of the brain. About 80-85 % of patients with AIS do not meet the selection criteria for revascularization therapy. There is also no effective therapy for such patients in the acute period. In recent years, it has been proposed to replace the term “neuroprotection” with the term “brain cell cytoprotection”, as the former does not reflect the direction of the impact on all components of the neurovascular unit and white matter. A separate aspect of brain cytoprotection is protection against ischemic reperfusion injury. For this purpose, edaravon (Ksavron, “Yuria-Pharm”) is used, which eliminates free radicals, reduces calcium flow into the cells, prevents cell adhesion to the endothelium, enhances the release of nitric oxide and inhibits the inflammatory response, neutralizing all stages and consequences of ischemic stroke. In Japan, edaravon has been included into AIS treatment guidelines since 2009. T. Yamaguchi et al. (2017) found that co-administration of edaravon and recombinant tissue plasminogen activator within 4.5 hours after AIS led to less intracranial hemorrhages and better treatment outcomes. Early use of edaravon also reduces mortality. S. Kono et al. (2013) also state that edaravon may be a good adjunct to alteplase to enhance recanalization and reduce the likelihood of hemorrhagic transformation. With the administration of edaravon within the first 24 hours after stroke, one in three patients has no post-stroke sequelae, and 70 % of patients have a significant improvement in general neurological status. If edaravon is prescribed within the first 72 hours after AIS, the general condition improves significantly in half of the patients. Edaravon (Ksavron) increases the frequency of early recanalization during thrombolysis.&#x0D; Conclusions. 1. Citicoline is a multimodal agent with neuroprotective and neuroregenerative properties. 2. Edaravon (Ksavron) is an ischemic cascade blocker for the empirical treatment of AIS or transient ischemic attacks. 3. The combination of edaravon (Ksavron) and citicoline (Neurocytin) as part of comprehensive therapy allows to each the advanced protection of the neurovascular unit in AIS.

Characterization of an Artificial Liver Support System-Related Vasovagal Reaction.

Objective An artificial liver support system (ALSS) is an effective therapy for patients with severe liver injury. A vasovagal reaction (VVR) is a common complication in various treatment settings but has not been reported previously in ALSS. Methods This study retrospectively evaluated patients who suffered an ALSS-related VRR between January 2018 and June 2019. We collected data from VVR episodes including onset time, duration, changes in heart rate (HR) and blood pressure (BP), and drug treatment. Results Among 637 patients who underwent ALSS treatment, 18 were included in the study. The incidence of VVR was approximately 2.82%. These patients were characterized by a rapid decrease in BP or HR with associated symptoms such as chest distress, nausea, and vomiting. The majority of patients (78%) suffered a VVR during their first ALSS treatment. Sixteen patients (89%) had associated symptoms after treatment began. Sixteen patients (89%) received human albumin or Ringer's solution. Atropine was used in 11 patients (61%). The symptoms were relieved within 20 min in 15 patients and over 20 min in 3 patients. Conclusions A VVR is a rare complication in patients with severe liver injury undergoing ALSS treatment. Low BP and HR are the main characteristics of a VVR.

MON-208 Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan

Context: In patients with aldosterone-producing adenomas (APAs), adrenalectomy causes a rapid decrease in blood pressure and increase in blood potassium levels; however, the effects of these intensive metabolic changes on kidney function with age have not yet been examined in Japan. Objective: To investigate factors related to the progression of kidney dysfunction after adrenalectomy in different age groups. Participants: Fifty Japanese patients with APAs with 27,572 health check-up subjects as controls were examined. Main Outcome Measures: We investigated changes in eGFR after adrenalectomy and characterized patients who progressed to chronic kidney disease (CKD).Results: Receiver Operating Characteristic and multivariate analyses revealed the postoperative cut-off age of CKD to be 50 years (sensitivity, 57%; specificity; 82%; AUC, 0.69) and identified age as a unique factor for the progression of CKD after adrenalectomy. Among preoperative patients with APAs, CKD was 6% for those younger than 50 years (<50) and 40% for those 50 years and older (≥50). As a control, in 27,572 health check-up subjects, the prevalence of CKD was 4.2% in men and 2.5% in women aged 41-50 years and 18.9% in men and 13.3% in women older than 61 years, clearly demonstrating the higher prevalence of CKD in patients with APAs than in healthy subjects, particularly those with APAs ≥50 years. In patients with APAs <50 years, median eGFR before and after adrenalectomy were 95 mL/min/1.73m2 and 88 mL/min/1.73m2, respectively, indicating that the percentage of the decrease in eGFR was -7%, which was not significant (paired t-test, p=0.13). In contrast, in patients with APAs ≥50 years, median eGFR after adrenalectomy decreased to 42 mL/min/1.73m2 from 67 mL/min/1.73m2 (adjusted by age, paired t-test, p=0.01) (percent decrease in eGFR, -24%) Patients with APAs ≥50 years who progressed to CKD showed higher preoperative aldosterone/renin ratios, lower potassium and chloride levels, lower BMI, and a higher incidence of a history of cardiovascular events and KCNJ5 mutation rates.Conclusion: Age is the most important predictor of the progression of kidney dysfunction after adrenalectomy in Japanese patients with APAs, particularly those with a history of cardiovascular events and positivity for KCNJ5 mutations.

A Clinical Significance of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared to Hemodialysis: A Multicenter Randomized Controlled Crossover Trial

Background: Intermittent infusion hemodiafiltration ­(I-HDF) using repeated infusion of ultrapure dialysis fluid through a dialysis membrane or sterile nonpyrogenic substitution fluid was developed to prevent a rapid decrease in blood pressure by increasing the patient’s circulating blood volume, to enhance the plasma refilling rate by improving peripheral circulation, and to enhance solute transfer from the extravascular space to the intravascular space by enhancing the plasma refilling rate. Furthermore, the effect of fouling caused by attachment of proteins to the membrane as a result of ultrafiltration can be reduced by backflushing of the membrane with the purified dialysate in I-HDF. Although there have been several clinical trials of I-HDF, there have been no comparisons of the clinical significance of and indications for ­I-HDF with those of conventional hemodialysis (HD). Objective: The aim of this multicenter randomized controlled crossover trial was to compare the clinical significance of ­I-HDF with that of HD in Japan. Method: Patients were randomized to receive HD, I-HDF, and HD (group A) or I-HDF, HD, and I-HDF (group B) in that order for 14 weeks each. The sample size of 70 was determined based on the operability and patient availability. Treatment outcomes were evaluated 5 and 14 weeks after the start of each treatment period. The patients received 4-h treatment sessions with no changes in session duration or anticoagulant therapy during the study. I-HDF was performed using a GC-110N dialysis machine. Two hundred milliliters of ultrapure dialysis fluid were infused at a rate of 150 mL/min by backfiltration every 30 min during treatment. The first and last infusions were performed 30 min after the start and 30 min before the end of treatment, respectively. The total estimated infusion volume per session was 1.4 L (i.e., 200 mL × 7 infusions). I-HDF is a type of online HDF with a small fluid replacement volume. An ABH-P polysulfone membrane hemodiafilter was used for ­I-HDF and a class 1 or 2 hemodialyzer with a polysulfone membrane not coated with vitamin E and approved by the Japanese reimbursement system was used for HD. The primary outcomes were the Short Form-36 version 2 summary scores for quality of life and the visual analog scale scores for clinical symptoms. Secondary outcomes were vital signs, number of interventions, and pre-treatment blood test results. These variables were evaluated 1 week before at the start of the study, and at 5 and 14 weeks after the start of each treatment period. The removal characteristics of the various solutes were evaluated when possible on the first day of each treatment period. All patients provided written informed consent to participate. Results: Thirty-two patients in group A and 32 patients in group B completed the trial. There were no differences in the primary or secondary outcomes between I-HDF and HD. Serum α₁-microglobulin (MG) levels at 14 weeks were significantly lower for I-HDF than for HD. During treatment, the removal rates for urea and creatinine, which are low molecular weight substances, were significantly lower during I-HDF than during HD. In contrast, the β₂-MG and α₁-MG removal rates were significantly higher during I-HDF than during HD. Furthermore, there was significantly less albumin leak during I-HDF than during HD. The solute removal results reflect the difference in pore size between the hemodiafilter used for I-HDF and the hemodialyzer used for HD and the difference in convective transport attributable to filtration between the 2 methods. Conclusions: These findings show that the removal rates of low molecular weight substances are significantly lower and those of medium to high molecular weight substances are significantly higher with I-HDF than with HD. They also indicate that there is significantly less albumin leak during I-HDF than during HD, meaning that I-HDF may be a particularly suitable dialysis modality for patients with malnutrition and the elderly in Japan.

Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan.

ContextIn patients with aldosterone-producing adenomas (APAs), adrenalectomy causes a rapid decrease in blood pressure and increase in blood potassium levels; however, the effects of these intensive metabolic changes on kidney function with age have not yet been examined in Japan.ObjectiveTo investigate factors related to the progression of kidney dysfunction after adrenalectomy in different age groups.ParticipantsFifty Japanese patients with APAs and 27,572 health checkup patients as controls were examined.Main Outcome MeasuresWe investigated changes in estimated glomerular filtration rate (eGFR) after adrenalectomy and characterized patients who progressed to chronic kidney disease (CKD).ResultsThe postoperative cutoff age of CKD is 50 years and age is a unique factor for the progression of CKD after adrenalectomy. Among preoperative patients, CKD was 6% for those <50 years old and 40% for those ≥50 years old, indicating a higher prevalence of CKD with APAs than in control subjects. Median eGFR <50 mL/min/1.73 m2 did not significantly change after adrenalectomy but decreased from 67 to 42 mL/min/1.73 m2 in those with APAs ≥50 years old. Patients with APAs ≥50 years old who progressed to CKD showed higher preoperative aldosterone/renin ratios, lower potassium and chloride levels, lower body mass index, and a higher incidence of a history of cardiovascular events and KCNJ5 mutation rates.ConclusionAge is the most important predictor of the progression of kidney dysfunction after adrenalectomy in Japanese patients with APAs, particularly those with a history of cardiovascular events and positivity for KCNJ5 mutations.

Acute toxic effects of telmisartan in spontaneously hypertensive rats fed a high fructose diet.

Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome proliferator activated receptor gamma (PPARG) modulator. Recently, we tested metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously hypertensive rats (SHR) fed a diet containing 60 % fructose, a widely used model of the metabolic syndrome. Surprisingly, we observed acute toxic effects of telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and treated with telmisartan exhibited rapid decrease in blood pressure when compared to the SHR fed a high fructose diet and treated with valsartan. Concentrations of both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR rats fed a high fructose diet were approximately 4 fold higher when compared to Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated telmisartan in the SHR were about 5 fold higher when compared to BN rats while plasma levels of telmisartan glucuronide were similar between the strains. Testing of other rat strains, diets, and the ARB valsartan showed that toxic effects of telmisartan in combination with high fructose diet are specific for the SHR. These results are consistent with the possibility that in some circumstances, SHR are predisposed to telmisartan toxicity possibly because of a genetically determined disturbance in telmisartan metabolism.

Sténose de l’artère rénale à distance d’une dénervation rénale pour HTA résistante

The onset of renal artery stenosis following a renal denervation is rare and occurs in the first few months after renal denervation. We report the onset of renal artery stenosis a long time after the renal denervation for resistant hypertension. This is a 74 year-old patient who stopped smoking in 1980 and who was treated for dyslipidemia with a revascularized coronary artery disease in 2011, a well-stabilized peripheral arterial disease since 2001, a stable asymptomatic carotid atheroma and a good kidney function. His hypertension known since 1995 became resistant. After the control of renal arteries by angio-CT scan, he had a renal denervation in October 2012. His blood pressure decreased 3 months later confirmed by self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM) with a CT scan with a non-significant renal artery stenosis in January 2014. He remained normotensive under treatment until July 2015 but his hypertension became uncontrolled at the end of 2015 then resistant and severe confirmed by SBPM in April 2017, despite a 5-drug antihypertensive treatment associated to atorvastatin and clopidogrel confirmed by SBPM in April 2017. A left post-ostial renal artery stenosis with decrease in size of left kidney and cortex as compared to 2011 was detected at CT and treated by angioplasty. It was associated with a rapid decrease in blood pressure but unfortunately a new increase related to a restenosis occurred at the end of 2017, which justified a new angioplasty. Discussion about the etiology and the management of this renal post-denervation late stenosis.

Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration–approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.

Analysis of toxic Veratrum alkaloids in plant samples from an accidental poisoning case

Four individuals (aged 50–60 years) at a dinner ate a wild plant that had been collected in a forest and looked similar to the edible wild plant Hosta montana (plantain lily). About 30–40 min after eating the plant, two of these individuals suffered from severe vomiting and a rapid decrease in blood pressure, and were hospitalized. Another individual initially showed mild symptoms, but was then hospitalized as symptoms increased in severity. The last person did not show any symptoms. The plant was found to be the very toxic Veratrum species. Although biological specimens were not available in this case, the remaining uncooked Veratrum sample was analyzed to determine what compounds contributed to the poisoning symptoms by liquid chromatography—tandem mass spectrometry. Two toxic alkaloids, protoveratrines A and B, were identified and quantified at 146 and 1302 µg/g, respectively. Reproducible experiments showed that the cooked samples contained 400-600 µg/g levels of protoveratrine B. Protoveratrine A and B are the most toxic compounds in Veratrum alkaloids. Other toxic Veratrum alkaloids were also present in trace amounts or not detected. Thus, the patients’ symptoms were assigned to protoveratrine B poisoning. To prevent further poisoning, wild Veratrum species were collected from two other colonies over years and analyzed. The composition of Veratrum alkaloids of the poisoning sample and that of the young Veratrum sprout samples of two other colonies were very similar, and had not changed largely over the years when they were young sprouts, showing that all the young sprouts of Veratrum species are dangerous to eat. This is a rare report on the direct correlation of protoveratrine B ingestion with poisoning symptoms.

P2Y₂ receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37.

Nucleotides are important paracrine regulators of vascular tone. We previously demonstrated that activation of P2Y₂ receptors causes an acute, NO-independent decrease in blood pressure, indicating this signalling pathway requires an endothelial-derived hyperpolarization (EDH) response. To define the mechanisms by which activation of P2Y₂ receptors initiates EDH and vasodilation, we studied intermediate-conductance (KCa3.1, expressed in endothelial cells) and big-conductance potassium channels (KCa1.1, expressed in smooth muscle cells) as well as components of the myoendothelial gap junction, connexins 37 and 40 (Cx37, Cx40), all hypothesized to be part of the EDH response. We compared the effects of a P2Y₂/₄ receptor agonist in wild-type (WT) mice and in mice lacking KCa3.1, KCa1.1, Cx37 or Cx40 under anaesthesia, while monitoring intra-arterial blood pressure and heart rate. Acute activation of P2Y₂/₄ receptors (0.01-3 mg kg(-1) body weight i.v.) caused a biphasic blood pressure response characterized by a dose-dependent and rapid decrease in blood pressure in WT (maximal response % of baseline at 3 mg kg(-1) : -38 ± 1%) followed by a consecutive increase in blood pressure (+44 ± 11%). The maximal responses in KCa3.1(-/-) and Cx37(-/-) were impaired (-13 ± 5, +17 ± 7 and -27 ± 1, +13 ± 3% respectively), whereas the maximal blood pressure decrease in response to acetylcholine at 3 μg kg(-1) was not significantly different (WT: -53 ± 3%; KCa3.1(-/-) : -52 ± 3; Cx37(-/-) : -53 ± 3%). KCa1.1(-/-) and Cx40(-/-) showed an identical biphasic response to P2Y2/4 receptor activation compared to WT. The data suggest that the P2Y2/4 receptor activation elicits blood pressure responses via distinct mechanisms involving KCa3.1 and Cx37.

Rapid Decreases in Blood Pressure from Antihypertensive Treatment were Associated with Increased Cancer Mortality in the Systolic Hypertension in the Elderly Program

Research on the association between antihypertensive drug treatment (HTDT) and cancer is equivocal. We tested the hypothesis that large, rapid decreases in blood pressure following HTDT are associated with higher cancer mortality. Data from the Systolic Hypertension in the Elderly Program (SHEP) with 15-year cause-specific follow-up for mortality were used. We used changes from baseline in seated and standing systolic blood pressure (SBP) measurements at 3, 6, 9, and 12 months after the initiation of HTDT. Hazard ratios adjusted for demographics, comorbidities, and competing risk of non-cancer-related deaths were estimated to determine the association between SBP change, as a continuous or time-dependent measure, and cancer-related death. SHEP participants taking antihypertensive medication who exhibited a decrease in seated SBP of 29 mm Hg or more (50th percentile and above) at 3 months were at a 58% greater risk of cancer-related death during a 15-year follow-up compared with those with no decrease in SBP (P = 0.007, 42% increased risk P = 0.02 for standing SBP). Those participants whose maximal seated SBP change occurred in the first 3 months of treatment had 2.6-times greater risk of cancer mortality compared with those whose maximal seated SBP change occurred at 12 months (P = 0.004). Large SBP decreases early in HTDT were associated with an increased risk of cancer-related death during a 15-year follow-up. Further studies are needed to confirm and explore the potential mechanisms for this association. Rapid decreases in blood pressure following HTDT may be a risk factor for cancer. Cancer Epidemiol Biomarkers Prev; 23(8); 1589-97. ©2014 AACR.

Japanese Society for Dialysis Therapy Guidelines for Management of Cardiovascular Diseases in Patients on Chronic Hemodialysis

Hideki Hirakata, Kosaku Nitta, Masaaki Inaba, Tetsuo Shoji, Hideki Fujii, Shuzo Kobayashi, Kaoru Tabei, Nobuhiko Joki, Hiroki Hase, Masato Nishimura, Shigeyuki Ozaki, Yuji Ikari, Yoshitaka Kumada, Kazuhiko Tsuruya, Shouichi Fujimoto, Tohru Inoue, Hiroyoshi Yokoi, Sumio Hirata, Kazuaki Shimamoto, Kiyotaka Kugiyama, Takashi Akiba, Kunitoshi Iseki, Yoshiharu Tsubakihara, Tadashi Tomo, and Tadao Akizawa

Cardiovascular Actions of Leptin in the Subfornical Organ are Abolished by Diet‐Induced Obesity

The subfornical organ (SFO), a sensory circumventricular organ lacking the normal blood-brain barrier with well documented roles in cardiovascular regulation, has recently been identified as a potential site at which the adipokine, leptin, may act to influence central autonomic pathways. Systemic and central leptin administration has been shown to increase blood pressure and it has been suggested that selective leptin resistance contributes to obesity-related hypertension. Given the relationship between obesity and hypertension, the present study aimed to investigate the cardiovascular consequences of the direct administration of leptin into the SFO of young lean rats and in the diet-induced obesity (DIO) rat model, which has been shown to be leptin-resistant. Leptin administration (500 fmol) directly into the SFO of young rats resulted in rapid decreases in blood pressure (BP) [mean area under the curve (AUC) = -677.8 ± 167.1 mmHg*s; n = 9], without an effect on heart rate (mean AUC = -21.2 ± 13.4 beats; n = 9), and these effects were found to be dose-related as microinjection of 5 pmol of leptin into the SFO had a larger effect on BP (mean AUC = -972.3 ± 280.1 mmHg*s; n = 4). These BP effects were also shown to be site-specific as microinjection of leptin into non-SFO regions or into the ventricle was without effect on BP (non-SFO: mean AUC = -22.4 ± 55.3 mmHg*s; n = 4; ventricle: mean AUC = 194.0 ± 173.0 mmHg*s; n = 6). By contrast, microinjection of leptin into leptin-resistant DIO rats was without effect on BP (mean AUC = 205.2 ± 75.1 mmHg*s; n = 4). These observations suggest that the SFO may be an important relay centre through which leptin, in normal weight, leptin responsive rats, acts to maintain BP within normal physiological limits through descending autonomic pathways involved in cardiovascular control and that, in obese, leptin-resistant, rats leptin no longer influences SFO neurones, resulting in an elevated BP, thus contributing to obesity-related hypertension.

Clevidipine in Acute Hypertension: The Evidence of its Therapeutic Value

While the chronic form of hypertension is most common; the acute form presents the greater danger, with more frequent and severe complications and poorer short‑term prognosis compared to chronic hypertension. Antihypertensive drugs are used to treat acute hypertension according to the condition of the patient, target organ injured, and the resources available to monitor the patient. However, the limited number of medications intended for the aggressive management of acute hypertensive has highlighted the need for newer drugs that offer a rapid decrease of blood pressure (BP) without increasing the possible complications. After ten years of research and trials, clevidipine was approved by the FDA in 2008, and has been widely used to reduce BP when oral therapy is inappropriate. Compared to the few agents previously used for this purpose clevidipine takes the lead due to its shorter duration of action and its lower incidence of adverse events and toxicity rates.

Intravenous clevidipine for management of hypertension

Hypertension remains one of the most prevalent diseases affecting our society, and its complications lead the list of causes of mortality all over the world. Most efforts to control the disease are unsuccessful, failing in at least two-thirds of affected patients, despite the availability of multiple drugs for its treatment. The limited number of medications available for aggressive management of hypertensive crises has intensified the search for novel drugs that can achieve a rapid decrease in blood pressure without increasing the possible complications. Clevidipine is a novel, vasculoselective, dihydropyridine calcium channel blocker characterized by a very fast onset and offset of action. Metabolism of clevidipine does not occur in the liver or kidneys, and thus there are no restrictions to using clevidipine in patients with hepatic or renal dysfunction. This agent has been widely used to reduce blood pressure when oral therapy is not appropriate, and its use in the perioperative setting has been shown to be beneficial. This manuscript reviews the key characteristics of clevidipine and its role in the management of acute hypertension.