Successful treatment of severe calcium channel blocker poisoning, new experience with the guidance of invasive hemodynamic monitoring in a 17-year-old girl: a case report.

BACKGROUND: Calcium channel blocker poisoning is one of the most lethal cardiac drugs overdoses. Calcium and high-dose insulin infusion are the first-line therapy for symptomatic patients, and Intralipid emulsion infusion is useful for refractory cases. CASE PRESENTATION: In this report, we describe a 17-year-old Iranian girl who took 250 mg of the drug for a suicidal attempt and presented with refractory hypotension and non-cardiogenic pulmonary edema treated successfully with the guidance of invasive hemodynamic parameters. CONCLUSION: For complicated cases, in addition to supportive care and adjuvant therapy such as high-dose insulin and Intralipid, it is mandatory to utilize advanced hemodynamic monitoring to treat hypotension in severe calcium channel blocker poisoning to guide the treatment.

Efficacy of Low Dose Intravenous Epinephrine Infusion in Improving Perioperative Outcomes in Patients Undergoing Transurethral Resection of Prostate: A Prospective Parallel Arm Double-Blind Randomized Control Trial.

OBJECTIVE: To determine the efficacy of intraoperative low-dose intravenous epinephrine infusion in improving intraoperative bleeding and perioperative outcomes of transurethral resection of prostate (TURP) surgery. METHODS: This was a double-blinded, randomized control trial in which all patients undergoing bipolar TURP were included. Patients with uncontrolled hypertension, cardiac disease, and on anticoagulants were excluded. The study group received intravenous epinephrine, whereas the control group received normal saline at the same rate (0.05 µg/kg/min) throughout the procedure. Intraoperative blood loss was the primary outcome. The secondary outcomes were incidence of intraoperative hypotension (due to spinal anesthesia), resection time, indwelling catheter time, and length of hospitalization. RESULTS: Thirty-six patients were included in each group. Demographic and clinical profiles were comparable with an overall median prostate size of 41 (34-52) gram in both groups. The primary objective, mean intraoperative blood loss in the study group was lower than the control group but statistically insignificant (67.91+/-18.7 mL vs 75.14 +/-17.1 mL; P = .086). Incidence of intraoperative hypotension was significantly lower in the study group (8.3% vs 33.3%; P = .01). Rest of the secondary outcomes, resection time (83 (64-111.5) minutes vs 86 (68-94.75) minutes; P = .97), mean indwelling catheter time (P = .94), postoperative complications (P = .73), and length of hospitalization (P = .87) were comparable. CONCLUSION: In this first-of-its-kind trial, low-dose epinephrine infusion did not reduce intraoperative blood loss in patients undergoing TURP. However, it significantly reduced intraoperative hypotension, which complicates spinal anesthesia particularly in elderly population.

The Hypotensive and Vasodilatory Effects Observed in Rats Exposed to Chiranthodendron pentadactylon Larreat Flowers Can Be Attributed to Cyanidin 3-O-Glucoside.

Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3-O-glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.

Insulin concentrations following termination of high-dose insulin euglycemic therapy.

INTRODUCTION: High-dose insulin therapy is used in patients with calcium channel blocker and beta-adrenergic antagonist overdoses. The pharmacokinetics of insulin are scantly reported following high-dose insulin therapy. We present two cases of persistently elevated insulin concentrations following high-dose insulin therapy. CASE REPORTS: A 50-year-old woman and a 45-year-old man experienced hypotension after overdosing on amlodipine and atenolol. They were treated with high-dose insulin therapy for 54 hours at 2 units/kilogram/hour and 48 hours at 10 units/kilogram/hour, respectively. Following termination, serum insulin elimination was studied. Insulin concentrations remained greater than 1,000 µU/mL (fasting reference 2.6-24.9 µU/mL) for longer than 4 hours (case 1) and 11 hours (case 2) and greater than 300 µU/mL for longer than 8 hours and 21 hours, respectively. Insulin concentrations decreased with apparent first-order elimination half-lives of 13.0 hours and 6.0 hours. DISCUSSION: Following high-dose insulin therapy, insulin concentrations remained elevated for longer than expected based on normal pharmacokinetics in therapeutic dosing. Three previous cases reported insulin half-lives of between 2.2 hours and 18.7 hours. The current cases add to the existing data that insulin has a variable but prolonged half-life following high-dose insulin therapy. CONCLUSIONS: These findings suggest that patients are at prolonged risk of hypoglycemia following cessation of high-dose insulin infusions.

Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines.

Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning.Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code "Calcium Antagonists" in which the therapy "High Dose Insulin/Glucose" was "performed, whether or not recommended" from 2019-2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia.Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2-5; range 0-6) and 2 in the non-DHP group (IQR: 1-3; range 0-5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0-2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009).Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

Toxicity of phosphate enemas - an updated review.

INTRODUCTION: Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse effects of phosphate enemas from January 1957 to March 2007 and identified 12 deaths. These were thought due to electrolyte disturbances, heart failure and kidney injury. These data raised concerns about the use of phosphate enemas in routine practice. Newer osmotic-based enema alternatives are now available that do not contain absorbable ions. We sought to review the literature since this review and evaluate the latest data on the toxicity of phosphate-containing enemas. To gain a fuller picture we included case series and larger studies as well as case reports. OBJECTIVES: To review the toxicity of phosphate enemas, particularly with respect to acute metabolic consequences and their associated clinical features. To identify risk factors for metabolic toxicity and consider whether phosphate enemas should be relatively contra-indicated in specific patient groups. METHODS: A systematic literature review was conducted in PubMed, Google Scholar, and Cochrane Reviews (2005-2021) using the search terms 'phosphate enema or sodium phosphate enema' or 'phosphate-based enema' or (phosphate AND enema) or (Fleet AND enema) or 'sodium phosphate laxatives' or 'sodium phosphate catharsis' or 'sodium phosphate cathartic'. Relevant papers were read, and data were extracted. RESULTS: The searches identified 489 papers of which 25 were relevant: seven papers were case reports or small case series of metabolic abnormalities from the use of phosphate enemas in nine children, six were case reports on 16 adults. Nine papers were large case series or clinical studies that included data on systemic metabolic effects, of varying size from 24 healthy volunteers to a cohort of 70,499 patients. Case reports identified seven adult deaths but none in children. Children most often presented with decreased consciousness (6/9), and tetany (4/9). In adults overall only five cases had clinical features reported, hypotension was seen in four and QT prolongation in two. Treatment was generally symptomatic, with intravenous fluid and calcium salts for electrolyte changes and hypocalcaemia, and vasopressors for severe hypotension. Haemodialysis was used in three children and peritoneal dialysis in one, all of whom survived. In adults, haemodialysis did not prevent death in two of four cases in whom it was used. Common factors underlying toxicity were inappropriately high phosphate dose, or enema retention, both resulting in greater absorption of phosphate. Associated pre-disposing conditions included Hirschsprung disease in children and co-morbidity and renal impairment (2/5) in older adults. Absolute reported changes in serum phosphate or calcium were not accurate indicators of outcome. Larger case series and clinical trials confirm an acute effect of phosphate enemas on serum phosphate, which was related to both dose and retention time. These effects were not seen with non-phosphate preparations. In these cases series, adverse events were rarely reported. CONCLUSION: Phosphate enemas are potentially toxic, particularly in young children with Hirschsprung disease and in the elderly with co-morbidity. Raised awareness of the risk of phosphate enemas is still required. Other less toxic enema preparations are available and should be considered in patients at extremes of age. If phosphate enemas are the only clinical option careful monitoring of biochemical sequelae should be undertaken.

The effect of Taohong Siwu decoction combined with antihypertensive medicine in the treatment of hypertension: Meta-analysis.

BACKGROUND: Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine. Recent research has shown that the practical components of THSWD have specific curative effects on various cardiovascular diseases, including hypertension, suggesting THSWD could effectively lower blood pressure (BP) with fewer side effects. However, little information is available regarding the effectiveness of THSWD combined with antihypertensive medicine on hypertension. OBJECTIVE: This meta-analysis aimed to study the efficacy and safety of THSWD in treating hypertension. METHODS: According to the search strategy, 8 databases were searched, including China Knowledge Network (CNKI), Wanfang Database, VIP Database, Pubmed, China Biomedical Literature Database (CBM), web of science, EMBASE and Cochrane Library, for the randomized controlled trial of THSWD on hypertension. 9 RCTs were included and 827 patients were involved. This meta-analysis used RevMan 5.4 to evaluate the articles. RESULTS: This review included 9 RCTs. All studies were THSWD with the antihypertensive drug compared with single antihypertensive western medicine. The total effective rate of THSWD combined with corresponding western medicine was significantly improved (Relative risk = 1.26; 95% CI: 1.16-1.37, P < .00001), which could effectively reduce the systolic BP (MD = -15.28 mm Hg; 95% CI: -20.17 to -10.40, P < .00001=, diastolic BP (MD = -9.70 mm Hg; 95% CI: -12.66 to -6.73, P < .00001), Triglycerides (MD = -1.48, 95%CI: -2.09 to -0.87, P < .00001), total cholesterol (MD = -1.43, 95% CI: -1.63 to -1.24, P < .00001) and low density lipoprotein cholesterol (MD = -0.93, 95% CI: -1.07 to -0.80, P < .00001). Compared with the single routine western medicine group, THSWD combined with the corresponding western medicine increased serum high-density lipoprotein (MD = 0.41, 95% CI: 0.35 to 0.46, P < .00001). CONCLUSION: THSWD combined with antihypertensive drugs in treating hypertension was curative in lowering BP, improving blood lipid levels and reducing the incidence of adverse reactions compared to antihypertensive medications treatment. However, more high-quality studies are needed due to the biased results and the small number of studies for further verification of the effectiveness of THSWD, and providing a new treatment for clinical reference.

Hypotensive and antihypertensive effects of an aqueous extract from Guinep fruit (Melicoccus bijugatus Jacq) in rats.

Melicoccus bijugatus Jacq (Mb) has been reported to have cardiovascular modulatory effects. In this study, we evaluated the antihypertensive effects and mechanism of action of Mb on NG-Nitro-L-arginine Methyl Ester (L-NAME) and Deoxycorticosterone Acetate (DOCA) rat models. Aqueous extract of Mb fruit (100 mg/kg) was administered for 6 weeks to rats by gavage and blood pressure was recorded. Effects of the extract on vascular reactivity was evaluated using isolated organ baths, and tissues were collected for biochemical and histological analysis. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were significantly (P < 0.05) reduced with extract (100 mg/kg) administration and treatment compared to the hypertensive models. Mb (100 µg/mL) reduced the vascular contractility induced by phenylephrine (PE), and caused a dose-dependent relaxation of PE-induced contraction of aortic vascular rings. The vasorelaxation properties seemed to be endothelium dependent, as well as nitric oxide (NO) and guanylyl cyclase, but not prostaglandin dependent. Histomicrograph of transverse sections of the ventricles from the Mb group did not show abnormalities. The extract significantly (P < 0.05) reduced an L-NAME induced elevation of cardiac output and Creatine Kinase Muscle-Brain (CKMB), but had no significant impact on the activities of arylamine N-acetyltransferase. In conclusion, Mb significantly decreased blood pressure in hypertensive models. The extract possesses the ability to induce endothelium dependent vasodilation, which is dependent on guanylyl cyclase but not prostaglandins.

Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report.

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.

Refractory Hypotension Following Elective Total Hip Replacement Surgery in a Patient Treated With Herbal Medicine: A Case Report.

We describe refractory postoperative hypotension due to adrenal insufficiency in a patient treated with steroid-adulterated herbal medicine. A 62-year-old man underwent an elective total hip replacement. Surgery was uneventful, but he became profoundly hypotensive 8 hours later, requiring intensive care unit admission, intubation, vasopressor support, and renal replacement therapy. Subsequent workup revealed that he had been consuming a herbal medication adulterated with prednisolone. Adrenal insufficiency secondary to chronic exogenous steroids was diagnosed following cortisol measurements and an adrenocorticotropic hormone stimulation test. He responded well to steroid therapy and made a full recovery. The use of herbal medicine should not be overlooked.

Hypotensive effect of Eugenia dysenterica leaf extract is primarily related to its vascular action: The possible underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia dysenterica (ED) leaves are used in Brazil to treat cardiac diseases; however, there are no scientific data describing the effects of this species on cardiac activity. AIM OF THE STUDY: To investigate the effect of ED aqueous leaf extract (EDLE) on hear rate (HR) and mean arterial pressure (MAP) of anaesthetised rats and its underlying mechanism of action. MATERIAL AND METHODS: EDLE was analysed, and its proanthocyanidin composition was determined. After performing dose-effect curves for EDLE on HR and MAP, EDLE-induced hypotension was evaluated before and after atropine (AT), L-N(ω)-nitro-L-arginine methyl ester (L-NAME), hexamethonium (HXT), indomethacin (IND), carbenoxolone (CBX), or nifedipine (NFD) administration. The effect of proanthocyanidin-depleted extract (EDLE/P-) was also determined and compared to that of the EDLE with proanthocyanidins. RESULTS: EDLE decreased the MAP in a dose-dependent manner; HR was decreased only with the highest and most toxic dose. Only CBX and NFD decreased EDLE-induced hypotension. Five polymeric series of proanthocyanidins were identified, which were mainly constituted by procyanidin and prodelphinidin units with B-type linkage and up to 12 flavan-3-ol units. EDLE/P- induced hypotension did not differ from that induced by EDLE. CONCLUSIONS: The cardiovascular effects of EDLE were primarily related to its vascular action. EDLE-induced hypotensive effect appeared to involve L-type calcium channel blockage as well as myoendothelial gap junction signalling. The higher molecular weight proanthocyanidins from EDLE are unlikely to contribute to its cardiovascular effect.

Evaluation of safety for flibanserin.

Introduction: Hypoactive sexual desire disorder (HSDD) is the most prevalent sexual dysfunction in women, previously managed with off-label therapies. Indicated for premenopausal women, flibanserin is the first FDA-approved medication to treat HSDD.Areas covered: This review summarizes flibanserin's pharmacokinetics, proposed mechanism of action, and safety data in clinical trials with a focus on sedation- and hypotension-related adverse events, and drug interactions with alcohol and antidepressants. Sources included peer-reviewed publications and internal data from the manufacturer.Expert opinion: Flibanserin is a well-tolerated and effective treatment that decreases distress and restores sexual desire to a level that is normative for the individual patient with HSDD. Simplification of a risk mitigation program for flibanserin in the US is likely to increase the number of prescribing clinicians if accompanied with educational efforts to clarify flibanserin's risk-benefit profile. As flibanserin is dosed daily and may be used for a decade or more in the typical premenopausal patient, long-term pharmacovigilance data will be essential. Over time, HSDD will be treated by more nonspecialist health care professionals and flibanserin will likely become established as a significant treatment option along with other medications approved for this indication in the context of a holistic biopsychosocial treatment paradigm.

What is the Best Way to Treat Patients with Raynaud's Phenomenon and a Tendency towards Hypotension?

Episodes of excessive vasospasm are common in patients with Raynaud's phenomenon (RP). Pharmacological treatment may often result in side-effects such as hypotension, leading to discontinuation of treatment. Review of therapeutic interventions with regard to tendency towards hypotension was done in medical databases including PubMed, Scopus, and Medline to summarize the current state of the knowledge. Despite the episodes of blood pressure drops caused by hypotension, calcium channel blockers (CCB) have been widely used in RP as first-line treatment medication. The use of other CCB apart from nifedipine is controversial due to the variety of results in clinical trials. A clinical study comparing the efficacy and tolerability of losartan with nifedipine revealed a significant reduction in RP severity, frequency of episodes, and reported adverse effects. Application of oral sildenafil 100 mg/d as an add-on therapy increased microvascular blood flow in secondary RP, while being well-tolerated and with no withdrawal from the study. Topical vasodilators may be applied as an adjuvant therapy for patients with RP. Clinical studies approved 10% nifedipine cream and 10% nitroglycerine gel as an efficient RP therapy with side-effects comparable with placebo usage. Non-pharmacological interventions, such as cold avoidance, stress management, and smoking cessation are recommended in reducing episodes of RP. Calcium channel blockers, with a particular emphasis on nifedipine, in combination with non-pharmacological management seem to be the optimal way to treat the patients with a tendency to hypotension.

Hyperbaric oxygen therapy for perioperative posterior ischemic optic neuropathy: a case report.

PURPOSE: To report the successful treatment of postoperative posterior ischemic optic neuropathy (PION) with hyperbaric oxygen therapy and to review the current literature on the pathogenesis and treatment of PION. OBSERVATIONS: During an angiographic procedure at a community hospital, an elderly woman had a transient drop in blood pressure after receiving an intravenous dose of hydralazine. During recovery, the patient experienced bilateral vision loss. She was transferred to our specialty referral center for treatment with hyperbaric oxygen. We followed Table 5 in the U.S. Navy Diving Manual, the protocol for decompression sickness. Our patient's vision improved markedly immediately after the first session and continued to improve throughout the course of treatment to its completion. Follow-up ophthalmology visits found the patient's vision to be close to baseline. CONCLUSIONS AND IMPORTANCE: PION is a rare condition. It has been difficult to determine a successful therapeutic approach because of the lack of large case-controlled studies. Hyperbaric oxygen has been used to treat other ischemic ophthalmic conditions, but there are only few reports of its use in patients with PION. Systemic steroids and antiplatelet therapy have also been used, with mixed success. In our patient, the combination of hyperbaric oxygen therapy and steroids was successful in restoring vision after postoperative PION.

Dexmedetomidine Sedation for Paroxysmal Supraventricular Tachycardia Ablation Is Not Associated With Alteration of Arrhythmia Inducibility.

BACKGROUND: Dexmedetomidine (Dex) is an attractive agent for procedural sedation due to its unique pharmacodynamic profile, specifically affording predictable sedation without concurrent respiratory depression. However, Dex has previously been reported to prevent or terminate arrhythmias. The purpose of this study was to investigate paroxysmal supraventricular tachycardia (PSVT) inducibility and homeostatic stability during electrophysiology studies (EPSs) and ablation when a standardized Dex protocol was used as the primary sedation agent. METHODS: We performed a retrospective review of 163 consecutive procedures for PSVT ablation that received Dex as the primary sedative with adjunct fentanyl and midazolam boluses (DEX-FENT-MIDAZ). This cohort was compared to 163 consecutive control procedures wherein strictly fentanyl and midazolam were used for sedation. The primary outcome reviewed was PSVT inducibility assessed before ablation. Reviewed secondary outcomes included level of sedation and intraprocedure hemodynamics and oxygenation. RESULTS: The arrhythmia profiles of the DEX-FENT-MIDAZ and control cohorts were very similar. The overall incidence of a "negative" EPSs in which arrhythmia was not induced was 24% in the DEX-FENT-MIDAZ group and 26% in the control group (P = .7). Unintended deep sedation was significantly less with DEX-FENT-MIDAZ (4.3% vs 27%; P ≤ .0001). However, DEX-FENT-MIDAZ use was associated with a higher incidence of intraprocedure hypotension. CONCLUSIONS: Dex sedation during EPSs is not associated with a reduction in PSVT inducibility. The therapeutic utility of Dex during EPS arises from the predictable sedation Dex affords but is associated with an increased incidence of intraprocedure hypotension.

[Acute kidney failure in differentiation syndrome: a possible complication during therapy with differentiating agents for acute promyelocytic leukemia. A case report].

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.

Arginine and tetrahydrobiopterin supplementation in rats with salt-induced blood pressure increase: minor hypotensive effect but improvement of renal haemodynamics.

High salt (HS) intake can lead to hypertension, probably the result of the predominance of vasoconstrictor reactive oxygen species over vasodilator nitric oxide (NO). We aimed to examine if the supposed NO deficiency and the resultant blood pressure increase could be corrected by supplementation of L-arginine, the substrate, and tetrahydrobiopterin (BH4), a co-factor of NO synthases. Wistar rats without known genetic background of salt sensitivity were exposed to HS diet (4%Na) for 10 or 26 days, without or with supplementation with oral L-arginine, 1.4 mg/kg b.w. daily, alone or together with intraperitoneal BH4, 10 mg/kg daily. Systolic blood pressure (SBP, tail-cuff method) was measured repeatedly and found to increase ~40 mmHg after 26 days; L-arginine and BH4 did not significantly attenuate this increase. At the end of chronic studies, in anaesthetized rats the diet- and treatment-induced changes in renal haemodynamics were assessed. HS diet selectively decreased (-30%, P < 0.03) the inner medullary blood flow (IMBF, laser-Doppler flux) without changing total or cortical renal perfusion. Arginine supplementation tended to raise all renal circulatory parameters, and distinctly increased IMBF, to 61% above the HS diet level (P < 0.05). In conclusion, unlike in confirmed genetically determined salt-dependent hypertension, L-arginine and BH4 supplementation failed to attenuate the SBP increase observed after exposure to HS diet. On the other hand, arginine increased total and regional renal perfusion, especially IMBF. This suggests that the delivery of arginine increased intrarenal NO synthesis, an action of renoprotective potential which presumably countered the harmful influence of the local tissue oxidative stress.

Preclinical investigation of the cardiovascular actions induced by aqueous extract of Pimpinella anisum L. seeds in rats.

ETHNOPHARMACOLOGY RELEVANCE: Pimpinella anisum is used in traditional medicine because of its pharmacological properties which include cardiovascular action. However, no scientific information supports this use. AIM OF THE STUDY: This study investigated the effects of Pimpinella on arterial blood pressure (BP) and its pharmacological mechanism of action. MATERIAL AND METHODS: Pimpinella seeds were extracted with water, concentrated and freeze-dried yielding the aqueous extract (AE). A non-invasive BP assessment method was used (via the caudal artery) on Wistar, Wistar Kyoto, SHRs and rats that were submitted to high intake of dietary salt. Direct BP and heart rate were evaluated in Wistar rats in the absence or presence of atropine, L-NAME and angiotensin II. Spontaneous diuresis and the effect of AE on depolarized portal vein of Wistar rats was also examined. RESULTS: The data revealed that AE reduced BP in all groups evaluated and its effects were not due to diuretic, sympatholytic or parasympathomimetic actions. Additionally, it was shown that AE does not act as an angiotensin receptor blocker and does not induce hypotension by reducing vascular resistance induced by oxide nitric. In the depolarized portal vein, AE inhibited calcium influx, which indicates that AE acts as calcium channel blocker. CONCLUSION: This study validates the cardiovascular actions of Pimpinella and characterizes the hypotensive effects of Pimpinella that are related to the blockade of calcium channels.

A Swine Model of Severe Propranolol Toxicity Permitting Direct Measurement of Brain Tissue Oxygenation.

INTRODUCTION: High-dose insulin (HDI) therapy has been used successfully for beta-blocker toxicity, but needs further study when hypotension persists despite HDI. The objective was to develop a model of propranolol toxicity with persistent hypotension despite HDI and to develop means to measure cerebral oxygen tension (PbrO2). METHODS: Eight anesthetized Yorkshire pigs were instrumented with a tracheostomy, Swan-Ganz catheter, arterial catheter, and intra-cerebral pressure and oxygen monitor. Intravenous propranolol was given until the initial point of toxicity (POT); 25% reduction from baseline mean arterial pressure (MAP) × heart rate (HR). At the initial POT, normal saline (NS) bolus and infusion along with HDI infusion were started. The propranolol infusion was titrated up slowly to induce hypotension. Group 2 pigs received a norepinephrine (NE) infusion after a secondary POT defined as a MAP < 50 mmHg. NE was titrated to maintain subsequent MAPs > 50 mmHg. Cardiac output, HR, MAP, PbrO2, and intracranial pressure were then recorded every 5 min until death or 4 h. Systemic vascular resistance, potassium, and glucose were also measured. Surviving pigs were euthanized. RESULTS: Two pigs received unique doses for protocol development. One pig developed a tachyarrhythmia prior to protocol, one failed to reach secondary POT, leaving 2 pigs in each group reaching secondary POT. The range of PbrO2 recordings for group 1 was 12.7-48.5 mmHg and 9.2-26.2 mmHg for group 2. CONCLUSION: We report a pilot study swine model of propranolol toxicity with hypotension despite HDI, in which physiologic measures including PbrO2 are achieved. Our toxicity model can be used in the future, and the hemodynamic and brain monitoring model may prove important for subsequent research in various contexts.