ABSTRACT
BACKGROUND: Liquorice consumption can cause pseudohyperaldosteronism and potentially lead to life-threatening complications. Besides correcting hypokalemia and hypertension, finding the triggering factor for pseudohyperaldosteronism is essential to prevent recurrence. CASE DESCRIPTION: A 68-year-old Syrian man presented in the Emergency Department with complaints of fatigue, weakness and exercise-related shortness of breath. Blood tests revealed severe hypokalemia for which suppletion and cardiac rhythm surveillance was necessary. Talking to the patient's son, it occurred that our patient drank copious amounts of Erk Sous, a thirst-quenching drink made from liquorice. The diagnosis pseudohyperaldosteronismwas confirmed by a high level of glycyrrhetinic acid in the patient's urine. After correction of the hypokalemia, our patient recovered successfully. CONCLUSION: Erk Sous is a thirst-quenching drink that can cause pseudohyperaldosteronism. The drink is popular in the Middle East during summer and Ramadan. If a patient from the Middle East presents with hypokalemia and/or hypertension, ask for consumption of Erk Sous.
Subject(s)
Beverages/adverse effects , Glycyrrhiza/adverse effects , Hypokalemia/chemically induced , Aged , Glycyrrhetinic Acid/urine , Humans , Hyperaldosteronism/chemically induced , MaleSubject(s)
Death, Sudden, Cardiac/etiology , Glycyrrhetinic Acid/adverse effects , Glycyrrhiza/adverse effects , Hyperaldosteronism/diagnosis , Mineralocorticoids/blood , Aldosterone/blood , Blood Chemical Analysis , Cardiac Catheterization , Cardiopulmonary Resuscitation , Diagnosis, Differential , Electroencephalography , Fatal Outcome , Glycyrrhetinic Acid/pharmacology , Humans , Hydrocortisone/urine , Hyperaldosteronism/chemically induced , Hypokalemia/diagnosis , Hypokalemia/etiology , Male , Middle Aged , Tomography, X-Ray Computed , Ventricular Fibrillation/complicationsABSTRACT
INTRODUCTION: Intoxication induced by glycyrrhizin is a common cause of hypokalaemia by pseudo-hyperaldosteronism. OBSERVATION: We hereby present the observation of a 68-year old patient hospitalised following a full hip-prosthesis operation after a deep hypokalaemia at 2.5mM was observed, with ECG signs (flat T waves and appearance of U waves). The kaliuresis was not adapted at 8,4mmol/mmol of creatininuria. We noted a history of axonal and demyelinising polyneuropathy, of psoriasis and chronic ethylism.The evolution after intravenous potassic supplementation and then per os was favourable leading to a normalisation of the blood and urinary potassic concentrations. The blood concentrations of renin and of aldosterone upon admission were lower than the detection threshold and the tests carried out 7 days later were normal with a plasmatic renin of 35.2 pg/mL and a plasmatic aldosterone of 74 pg/mL, therefore indicating a toxic cause. It is the interview of the patient that allowed for the diagnosis, identifying a daily, prolonged and important consumption (around 1L every 2-3 days for several years) of a pastis produced by supermarket brand Lidl®. The composition of the drink mentions 'liquorice infusion' without giving any more information as regards to the real concentration; it was later estimated at 170 mg/L by the distributor. DISCUSSION: The consumption of glycyrrhizin is a well-known aetiology for pseudo-hyperaldosteronism. It is commonly mentioned amongst excessive consumers of liquorice or of non-alcoholic anise drinks. Drinks that are derived from original pastis contain varying levels of glycyrrhizin, which is used as a flavour enhancer and can become toxic in cases of prolonged and important consumption.
Subject(s)
Glycyrrhiza , Glycyrrhizic Acid/poisoning , Hyperaldosteronism/chemically induced , Hypokalemia/chemically induced , Aged , Humans , Male , SyndromeABSTRACT
Recent reports described cases of severe hypertension and hypokalemia accompanied by low renin and aldosterone levels during antifungal therapy with posaconazole and itraconazole. These conditions represent characteristics of secondary endocrine hypertension caused by mineralocorticoid excess. Different mechanisms can cause mineralocorticoid excess, including inhibition of the adrenal steroidogenic enzymes CYP17A1 and CYP11B1, inhibition of the peripheral cortisol oxidizing enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) or direct activation of the mineralocorticoid receptor (MR). Compared to previous experiments revealing a threefold more potent inhibition of 11ß-HSD2 by itraconazole than with posaconazole, the current study found sevenfold stronger CYP11B1 inhibition by posaconazole over itraconazole. Both compounds most potently inhibited CYP11B2. The major pharmacologically active itraconazole metabolite hydroxyitraconazole (OHI) resembled the effects of itraconazole but was considerably less active. Molecular modeling calculations assessed the binding of posaconazole, itraconazole and OHI to 11ß-HSD2 and the relevant CYP enzymes, and predicted important interactions not formed by the other systemically used azole antifungals, thus providing an initial explanation for the observed inhibitory activities. Together with available clinical observations, the presented data suggest that itraconazole primarily causes pseudohyperaldosteronism through cortisol-induced MR activation due to 11ß-HSD2 inhibition, and posaconazole by CYP11B1 inhibition and accumulation of the mineralocorticoids 11-deoxycorticosterone and 11-deoxycortisol because of hypothalamus-pituitary-adrenal axis (HPA) feedback activation. Therapeutic drug monitoring and introduction of upper plasma target levels may help preventing the occurrence of drug-induced hypertension and hypokalemia. Furthermore, the systemically used azole antifungals voriconazole, isavuconazole and fluconazole did not affect any of the mineralocorticoid excess targets, offering alternative therapeutic options.
Subject(s)
Hyperaldosteronism/genetics , Hypertension/genetics , Steroid 11-beta-Hydroxylase/genetics , Steroid 17-alpha-Hydroxylase/genetics , Aldosterone/metabolism , Animals , Antifungal Agents/adverse effects , Antifungal Agents/pharmacology , Azoles/adverse effects , Azoles/metabolism , Cricetinae , Disease Models, Animal , Drug Monitoring , HEK293 Cells , Humans , Hydrocortisone/biosynthesis , Hydrocortisone/metabolism , Hyperaldosteronism/chemically induced , Hyperaldosteronism/metabolism , Hyperaldosteronism/pathology , Hypertension/chemically induced , Hypertension/metabolism , Hypertension/pathology , Hypothalamo-Hypophyseal System/drug effects , Itraconazole/adverse effects , Itraconazole/pharmacology , Mineralocorticoids/pharmacology , Triazoles/adverse effects , Triazoles/pharmacologySubject(s)
Emergency Medical Services , Glycyrrhiza/adverse effects , Hyperaldosteronism/chemically induced , Hypertension/chemically induced , Hypokalemia/chemically induced , Plants, Medicinal/adverse effects , Tea/adverse effects , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Directive Counseling , Food-Drug Interactions , Glycyrrhiza/chemistry , Humans , Hyperaldosteronism/blood , Hypertension/blood , Hypokalemia/blood , Male , Medical History Taking , Plants, Medicinal/chemistry , Treatment OutcomeABSTRACT
Secondary hyperaldosteronism is respondent aldosterone secretion increase, occurring due to some diseases or drug use. It may be accompanied by normal arterial pressure with/without water retention or arterial hypertension without water retention. Secondary hyperaldosteronism without arterial hypertension and without water retention is usually caused by the use of laxative and diuretic drugs. This condition is characterized by the lack of salt wasting symptoms, presence of myalgia and muscle weakness resulting from hypokalemia, calcium oxalate crystalluria and sonographic signs of medullary nephrocalcinosis. Such characteristics of water-salt exchange and presence of nephrocalcinosis in combination with hypercalciuria are defined as Bartter-like syndrome. Peculiarity of the given clinical case is determined not by a diagnostic difficulty of secondary hyperaldosteronism but concealment of long term self-administered use of laxatives 2 years without medical indications in a female patient, resulting in medullary nephrocalcinosis. A well-informed patient may endanger medical practice, because it is impossible to foresee everything including the uncontrolled self-administered drug use leading to the undesirable consequences.
Subject(s)
Hyperaldosteronism , Laxatives/adverse effects , Nephrocalcinosis , Adolescent , Bartter Syndrome , Female , Humans , Hyperaldosteronism/chemically induced , Hypokalemia/chemically induced , Nephrocalcinosis/chemically inducedABSTRACT
Hypokalaemia can be treated with potassium chloride mixture. Some mixtures contain liquorice extract (glycyrrhizin) as a supplement to improve taste. Glycyrrhizin can cause pseudohyperaldosteronism and thereby result in hypertension and hypokalaemia. We here present a case where treatment with potassium chloride mixture causes hypertension and hypokalaemia in a 50-year-old woman. After unravelling differential diagnosis, the potassium chloride mixture was stopped. After the discontinuation, the patient's blood pressure was well managed and the potassium levels normalised.
Subject(s)
Glycyrrhiza/adverse effects , Glycyrrhizic Acid/adverse effects , Hyperaldosteronism/chemically induced , Hypertension/drug therapy , Hypokalemia/chemically induced , Potassium Chloride/adverse effects , Verapamil/therapeutic use , Diagnosis, Differential , Female , Glycyrrhizic Acid/therapeutic use , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/diagnosis , Hypertension/blood , Hypertension/diagnosis , Hypokalemia/blood , Hypokalemia/diagnosis , Hypokalemia/etiology , Middle Aged , Potassium/blood , Potassium Chloride/pharmacology , Potassium Chloride/therapeutic use , Treatment OutcomeSubject(s)
Benzalkonium Compounds/adverse effects , Fludrocortisone/analogs & derivatives , Hyperaldosteronism/chemically induced , Hypokalemia/etiology , Lidocaine/adverse effects , Neomycin/adverse effects , Oral Ulcer/drug therapy , Polymyxin B/adverse effects , Syncope/etiology , Administration, Topical , Aged, 80 and over , Benzalkonium Compounds/administration & dosage , Drug Combinations , Electrocardiography , Female , Fludrocortisone/administration & dosage , Fludrocortisone/adverse effects , Humans , Hydrocortisone/blood , Hyperaldosteronism/blood , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Hypokalemia/diagnosis , Lidocaine/administration & dosage , Neomycin/administration & dosage , Polymyxin B/administration & dosage , Syncope/diagnosisABSTRACT
RATIONALE: Glycyrrhizin is the main active component of licorice. Licorice and glycyrrhizin induced hypertension has been widely reported, yet licorice and glycyrrhizin induced hypertensive crisis has been rarely known. PATIENT CONCERNS: The case of this report was a 47-year-old woman, who took 225âmg of glycyrrhizin daily for 3 years due to primary biliary cholangitis. She was found to have a dramatically elevated blood pressure of about 230/110âmmHg without a history of hypertension and was referred to the emergency department. DIAGNOSES: Hypokalemia, hypertensive retinopathy, and nephropathy were found during the following work-up. Since no other risk factors of hypertension were identified, she was suspected to have glycyrrhizin induced pseudo-hyperaldosteronism. INTERVENTIONS: Glycyrrhizin was discontinued. Intravenous sodium nitroprusside was used during the first few days. Nifedipine and irbesartan were taken after discharge, and the dosage was reduced gradually under supervision. OUTCOMES: She stopped all the anti-hypertensive drugs 6 months since glycyrrhizin was stopped. Her blood pressure was about 110/60âmmHg after repetitive measurement. Her serum potassium and urine albumin/creatinine ratio were also normalized. LESSONS: Licorice and glycyrrhizin induced hypertension due to pseudo-hyperaldosteronism has been widely reported, yet only 3 cases reported that excessive consumption of licorice could lead to hypertensive emergencies. This is the first case that glycyrrhizin induced hypertensive crisis with target organ impairment. By presenting this case, we remind clinicians of glycyrrhizin induced hypertension, a condition which could lead to medical emergencies.
Subject(s)
Biphenyl Compounds/administration & dosage , Glycyrrhizic Acid , Hypertension, Malignant , Hypertensive Retinopathy , Kidney Diseases , Nifedipine/administration & dosage , Nitroprusside/administration & dosage , Tetrazoles/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Cholangitis/drug therapy , Female , Glycyrrhizic Acid/administration & dosage , Glycyrrhizic Acid/adverse effects , Humans , Hyperaldosteronism/chemically induced , Hyperaldosteronism/diagnosis , Hypertension, Malignant/chemically induced , Hypertension, Malignant/drug therapy , Hypertensive Retinopathy/diagnosis , Hypertensive Retinopathy/etiology , Irbesartan , Kidney Diseases/diagnosis , Kidney Diseases/etiology , Middle Aged , Treatment Outcome , Withholding TreatmentABSTRACT
A woman in her late 60s with disseminated histoplasmosis was treated with posaconazole because first-line therapies were not tolerated. She subsequently presented with decompensated heart failure, hypertension, and hypokalemia. Laboratory tests revealed low renin and aldosterone levels. A potential mechanism is inhibition of the enzyme 11ß-hydroxysteroid dehydrogenase 2, with resultant apparent mineralocorticoid excess.
Subject(s)
Antifungal Agents/adverse effects , Heart Failure/chemically induced , Hydroxysteroid Dehydrogenases/antagonists & inhibitors , Hyperaldosteronism/chemically induced , Hypertension/chemically induced , Hypokalemia/chemically induced , Mineralocorticoid Excess Syndrome, Apparent/chemically induced , Triazoles/adverse effects , Aged , Antifungal Agents/therapeutic use , Histoplasmosis/drug therapy , Humans , Hyperaldosteronism/diagnosis , Mineralocorticoid Excess Syndrome, Apparent/diagnosis , Triazoles/therapeutic use , Voriconazole/therapeutic use , Mineralocorticoid Excess Syndrome, ApparentABSTRACT
Hypertension is one of the most common problems encountered in the primary care setting. Numerous secondary causes of hypertension exist and are potentially reversible. The ability to screen for such causes and manage them effectively may spare patients from prolonged medical therapy and hypertensive complications. Licorice can cause hypertension and hypokalemia due its effects on cortisol metabolism. We report a case of jelly bean ingestion that highlights the presentation, pathophysiology and management of licorice-induced hypertension.
Subject(s)
Glycyrrhiza/adverse effects , Hyperaldosteronism/chemically induced , Hypertension/chemically induced , Hypokalemia/chemically induced , Glycyrrhiza/metabolism , Humans , Male , Middle AgedABSTRACT
Resolution of edema requires a correct interpretation of body fluids-related renal function, to excrete the excess volume while restoring systemic hemodynamics and avoiding renal failure. In heart failure, the intensive diuresis should be matched by continuous fluids refeeding from interstitium to plasma, avoiding central volume depletion. The slowly reabsorbed ascites cannot refeed this contracted volume in cirrhosis: the ensuing activation of intrathoracic receptors, attended by increased adrenergic and Renin release, causes more avid sodium retention, producing a positive fluid and Na balance in the face of continuous treatment. High-dose-furosemide creates a defect in tubular Na causing diuresis adequate to excrete the daily water and electrolyte load in Chronic Renal Failure. Diuretic treatment requires care, caution and bedside "tricks" aimed at minimizing volume contraction by correctly assessing the homeostatic system of body fluids and related renal hemodynamics.
Subject(s)
Diuretics/adverse effects , Diuretics/classification , Diuretics/therapeutic use , Edema/drug therapy , Kidney/physiopathology , Ascites/drug therapy , Heart Failure/drug therapy , Humans , Hyperaldosteronism/chemically induced , Hyponatremia/chemically induced , Kidney Failure, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Plasma Volume , Water-Electrolyte Balance/drug effectsABSTRACT
Urinary exosomes are vesicles derived from renal tubular epithelial cells. Exosomes often contain several disease-associated proteins and are thus useful targets for identifying biomarkers of disease. Here, we hypothesized that the phosphorylated (active) form of the sodium chloride cotransporter (pNCC) or prostasin could serve as biomarkers for aldosteronism. We tested this in 2 animal models of aldosteronism (aldosterone infusion or low-sodium diet) and in patients with primary aldosteronism. Urinary exosomes were isolated from 24-hour urine or spot urine using ultracentrifugation. In rats, a normal or a high dose of aldosterone for 2, 3, or 8 days increased pNCC 3-fold in urinary exosomes (P<0.05 for all). A low-sodium diet also increased pNCC in urinary exosomes approximately 1.5-fold after 4 and after 8 days of treatment. The effects of these maneuvers on prostasin in urinary exosomes were less clear, showing a significant 1.5-fold increase only after 2 and 3 days of high-aldosterone infusion. In urinary exosomes of patients with primary aldosteronism, pNCC was 2.6-fold higher (P<0.05) while prostasin was 1.5-fold higher (P=0.07) than in patients with essential hypertension. Urinary exosomal pNCC and, to a lesser extent, prostasin are promising markers for aldosteronism in experimental animals and patients. These markers may be used to assess the biological activity of aldosterone and, potentially, as clinical biomarkers for primary aldosteronism.
Subject(s)
Exosomes/metabolism , Hyperaldosteronism/diagnosis , Hyperaldosteronism/urine , Serine Endopeptidases/urine , Sodium Chloride Symporters/urine , Aldosterone/adverse effects , Aldosterone/pharmacology , Animals , Biomarkers/urine , Diet, Sodium-Restricted/adverse effects , Disease Models, Animal , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Exosomes/drug effects , Humans , Hyperaldosteronism/chemically induced , Kidney Tubules/drug effects , Kidney Tubules/metabolism , Male , Phosphorylation , Predictive Value of Tests , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Serine Endopeptidases/drug effects , Sodium Chloride Symporters/drug effects , Sodium, Dietary/pharmacologyABSTRACT
Mineralocorticoid receptor blockers (MRBs) have proven highly successful in the treatment of congestive heart failure and resistant hypertension. In contrast, their use in chronic kidney disease (CKD) has lagged due to the concern of hyperkalemia and, possibly, because of the incorrect assumption that traditional therapy with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers consistently reduce aldosterone activity in all patients. Low-dose MRB therapy may offer additional antihypertensive and unique anti-inflammatory benefits in select CKD populations.
Subject(s)
Aldosterone/therapeutic use , Kidney Failure, Chronic/drug therapy , Mineralocorticoid Receptor Antagonists , Animals , Diabetes Complications/drug therapy , Humans , Hyperaldosteronism/chemically induced , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Receptors, Mineralocorticoid/metabolismABSTRACT
The potential role of aldosterone in the pathophysiology of depression is unclear. The aim of this study was to test the hypothesis that prolonged elevation of circulating aldosterone induces depression-like behaviour accompanied by disease-relevant changes in gene expression in the hippocampus. Subchronic (2-wk) treatment with aldosterone (2 µg/100 g body weight per day) or vehicle via subcutaneous osmotic minipumps was used to induce hyperaldosteronism in male rats. All rats (n = 20/treatment group) underwent a modified sucrose preference test. Half of the animals from each treatment group were exposed to the forced swim test (FST), which served both as a tool to assess depression-like behaviour and as a stress stimulus. Affymetrix microarray analysis was used to screen the entire rat genome for gene expression changes in the hippocampus. Aldosterone treatment induced an anhedonic state manifested by decreased sucrose preference. In the FST, depressogenic action of aldosterone was manifested by decreased latency to immobility and increased time spent immobile. Aldosterone treatment resulted in transcriptional changes of genes in the hippocampus involved in inflammation, glutamatergic activity, and synaptic and neuritic remodelling. Furthermore, aldosterone-regulated genes substantially overlapped with genes affected by stress in the FST. This study demonstrates the existence of a causal relationship between the hyperaldosteronism and depressive behaviour. In addition, aldosterone treatment induced changes in gene expression that may be relevant to the aetiology of major depressive disorder. Subchronic treatment with aldosterone represents a new animal model of depression, which may contribute to the development of novel targets for the treatment of depression.
Subject(s)
Aldosterone/administration & dosage , Aldosterone/blood , Depression/blood , Depression/chemically induced , Depressive Disorder, Major/genetics , Aldosterone/toxicity , Animals , Depressive Disorder, Major/blood , Depressive Disorder, Major/chemically induced , Gene Expression Regulation , Hyperaldosteronism/blood , Hyperaldosteronism/chemically induced , Male , Random Allocation , Rats , Rats, Wistar , Treatment OutcomeABSTRACT
Hyperaldosteronim is associated with left ventricular (LV) hypertrophy (LVH) and fibrosis. Cardiotrophin (CT)-1 is a cytokine that induces myocardial remodeling. We investigated whether CT-1 mediates aldosterone (Aldo)-induced myocardial remodeling in two experimental models. Wistar rats were treated with Aldo-salt (1 mg·kg(-1)·day(-1)) with or without spironolactone (200 mg·kg(-1)·day(-1)) for 3 wk. Wild-type (WT) and CT-1-null mice were infused with Aldo (1 mg·kg(-1)·day(-1)) for 3 wk. Hemodynamic parameters were analyzed. LVH, fibrosis, inflammation, and CT-1 expression were evaluated in both experimental models by histopathological analysis, RT-PCR, Western blot analysis, and ELISA. Hypertensive Aldo-treated rats exhibited increased LV end-diastolic pressure and -dP/dt compared with controls. The cardiac index, LV cross-sectional area and wall thickness, cardiomyocyte size, collagen deposition, and inflammation were increased in Aldo-salt-treated rats. Myocardial expression of molecular markers assessing LVH and fibrosis as well as CT-l levels were also augmented by Aldo-salt. Spironolactone treatment reversed all the above effects. CT-1 correlated positively with hemodynamic, histological, and molecular parameters showing myocardial remodeling. In WT and CT-1-null mice, Aldo infusion did not modify blood pressure. Whereas Aldo treatment induced LVH, fibrosis, and inflammation in WT mice, the mineralocorticoid did not provoke cardiac remodeling in CT-1-null mice. In conclusion, in experimental hyperaldosteronism, the increase in CT-1 expression was associated with parameters showing LVH and fibrosis. CT-1-null mice were resistant to Aldo-induced LVH and fibrosis. These data suggest a key role for CT-1 in cardiac remodeling induced by Aldo independent of changes in blood pressure levels.
Subject(s)
Aldosterone , Cytokines/metabolism , Hyperaldosteronism/complications , Hypertension/metabolism , Hypertrophy, Left Ventricular/metabolism , Myocardium/metabolism , Ventricular Remodeling , Animals , Blood Pressure , Blotting, Western , Collagen/metabolism , Cytokines/deficiency , Cytokines/genetics , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Fibrosis , Heart Rate , Hyperaldosteronism/chemically induced , Hyperaldosteronism/drug therapy , Hyperaldosteronism/metabolism , Hyperaldosteronism/pathology , Hyperaldosteronism/physiopathology , Hypertension/etiology , Hypertension/genetics , Hypertension/pathology , Hypertension/physiopathology , Hypertension/prevention & control , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/genetics , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/prevention & control , Inflammation/etiology , Inflammation/metabolism , Inflammation/physiopathology , Inflammation Mediators/blood , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mineralocorticoid Receptor Antagonists/pharmacology , Myocardium/pathology , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Sodium Chloride, Dietary , Spironolactone/pharmacology , Ventricular Function, Left , Ventricular Pressure , Ventricular Remodeling/drug effectsSubject(s)
Alkalosis/chemically induced , Glycyrrhiza/adverse effects , Hyperaldosteronism/chemically induced , Hypokalemia/chemically induced , Adult , Atrial Fibrillation/complications , Atrial Fibrillation/therapy , Defibrillators, Implantable , Drug Therapy, Combination , Heart Failure/complications , Heart Failure/therapy , Humans , Hyperaldosteronism/drug therapy , Magnesium/administration & dosage , Male , Potassium/administration & dosage , Treatment OutcomeABSTRACT
Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent. In controls and each treatment group, we monitored: (1) electrocardiogram, ventricular electrogram, and arterial pressure before, during, and after bipolar electrical stimulation of the right ventricular outflow tract and apex at a strength 3× the pacing threshold, using both programmed stimulation with premature extra stimuli and 50-Hz burst pacing for 3 different durations; and (2) myocardial collagen volume fraction (CVF) as a marker of cardiac fibrosis. We found that VA (duration >200 ms accompanied by declining arterial pressure) was more inducible (P < 0.05) at 4 weeks (4 of 6) and with even greater frequency at 6 weeks (9 of 10) of ALDOST versus controls (0 of 6) and A+Spiro for 6 weeks (2 of 11). CVF (%) was proportionally increased (P < 0.05) at 4 and 6 weeks (8.4 ± 0.74 and 13.9 ± 1.9, respectively) of ALDOST compared with control group (2.6 ± 0.4) and A+Spiro group (5.3 ± 0.7). However, the effective refractory period was indistinguishable between groups, whereas the probability of VA was nonlinearly related to CVF. Thus, in rats with aldosteronism, in which a reduction in effective refractory period was not evident, the mechanism for VA susceptibility is presumably linked to a decrease in conduction velocity and/or increased dispersion of refractoriness, probably caused by consequential myocardial fibrosis.