Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans

Montanari A, Lazzeroni D, Pelà G, Crocamo A, Lytvyn Y, Musiari L, Cabassi A, Cherney DZ. Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans. Am J Physiol Renal Physiol 312: F870–F878, 2017. First published February 8, 2017; doi:10.1152/ajprenal.00568. 2016.—Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 g·kg1·min1 NG-nitro-L-arginine methyl ester (L-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2V; an oxidative stress marker) were measured. With PL L -NAME, the following changes were observed: 6% MAP (P 0.005 vs. baseline), 10% GFR, 20% RBF, 49% UNaV (P 0.001), and 120% U8-iso-PGF2V (P 0.01). In contrast, MAP did not increase during LOS L-NAME or MANI L-NAME (P 0.05 vs. baseline), whereas renal changes were the same during LOS L-NAME vs. PL L-NAME (ANOVA, P 0.05). However, during MANI L-NAME, changes vs. baseline in GFR (6%), RBF (12%), and UNaV (34%) were blunted vs. PL L-NAME and LOS L-NAME (P 0.005), and the rise in U8-iso-PGF2V was almost abolished (37%, P 0.05 vs. baseline; P 0.01 vs. PL L-NAME or LOS L-NAME). We conclude that, since MANI blunted L-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2V was essentially prevented during MANI L-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability

Hypertrophic cardiomyopathy and nephrogenic diabetes insipidus associated with chronic lithium carbonate use

Lithium carbonate is an effective mood stabilizer. We treated a patient for hypertrophic cardiomyopathy due to chronic unsupervised lithium carbonate use. We noted: a) a previously normal ECG; b) the absence of any familiarity for sudden cardiac death; c) the associated nephrogenic diabetes insipidus; d) probable exaggerated lithium plasma concentrations, which had not been monitored over the past few years; and e) the unusual traits of the right ventricle. We would like to stress the need for regular cardiologic follow-up in psychiatric patients treated with lithium carbonate, to minimize its potential cardiac untoward consequences

Un raro caso di cardiomiopatia ipertrofica biventricolare e diabete insipido nefrogenico indotto da terapia con litio in una paziente affetta da sindrome bipolare

Il litio, utilizzato nel trattamento di pazienti psichiatrici, può indurre complicanze cardiache quali aritmie, miocardite, cardiomiopatia dilatativa, cardiopatie congenite. Riportiamo un raro caso di cardiomiopatia ipertrofica (CMI) ostruttiva in una donna di 81 anni trattata per circa 40 anni con carbonato di litio (450mg/die) per sindrome bipolare e ricoverata nella nostra Unità in seguito a sincope seguita da stato confusionale. La paziente, negli ultimi anni, non si era più sottoposta a controlli della litiemia, causa la perdita dello psichiatra di fiducia. All’ingresso si rilevava magrezza (peso corporeo 35Kg) e all’auscultazione soffio mesotelesistolico al mesocardio irradiato ai vasi della base. L’ECG mostrava un netto incremento dei voltaggi del QRS nelle derivazioni sinistre associato a marcate alterazioni della ripolarizzazione ventricolare caratterizzate da ST sotto, T negative diffuse e QT lungo. Un precedente ECG, di 5 anni prima, era del tutto normale. Agli esami laboratoristici, la troponina era negativa mentre elevati erano il BNP (500pg/mL), la sodiemia (149mEq/L) e la cloremia (117mEq/L) associate a ridotto peso specifico urinario (1004) e sindrome polidipsico-poliurica. L’ecocardiogramma mostrava una marcata ipertrofia del setto interventricolare (18mm) e spostamento sistolico del lembo mitralico determinanti ostruzione sottovalvolare severa (gradiente 100mmHg); la cinetica ventricolare era nei limiti ma le velocità sistoliche e diastoliche miocardiche, ricavate con il Doppler tissutale, erano diffusamente ridotte. Il cateterismo cardiaco escludeva una malattia coronarica e confermava il gradiente subaortico mentre la RMN evidenziava anche il coinvolgimento del ventricolo destro. L’ECG holter escludeva aritmie significative. L’attività della pompa sodio-litio, valutata dal rapporto litio eritrocitario/litio plasmatico, era normale potendosi così escludere un accumulo intracellulare di questo elettrolita. Conclusioni: Noi possiamo speculare che questo caso di CMI sia secondario a tossicità miocardica da parte del litio per le seguenti ragioni: il coinvolgimento biventricolare evidenziato alla RMN, la presenza di un associato quadro di diabete insipido nefrogenico, il precedente tracciato ECG del tutto normale, l’assenza di familiarità per morte improvvisa o CMI e il probabile sovradosaggio del farmaco per mancati monitoraggi della litiemia durante il trattamento. Tali ipotesi trova conferma in modelli sperimentali sul ratto in cui è stato dimostrato che il litio modula la crescita miocardica mediante azione di blocco della glicogenosintetasi chinasi-3, enzima che inibisce la risposta ipertrofica. L’inattivazione di questo enzima è un importante meccanismo nella stimolazione dell’ipertrofia cardiaca. Questo caso potrebbe essere quindi il primo caso descritto di CMI biventricolare da litio e conferma la necessità non solo di un regolare controllo della litiemia ma di uno stretto follow-up cardiologico nei pazienti psichiatrici

Hemodynamic and ECG responses to stress test in early adolescent athletes explain ethnicity-related cardiac differences

Background: Ethnicity is an important determinant of athletes' cardiovascular adaptation. Black adolescent and adult athletes exhibit a left ventricular (LV) hypertrophy with a concentric remodelling higher than their Caucasian counterparts. Scant data, however, are available on race-related differences in hemodynamic response of adolescent athletes to exercise and its relation with heart remodelling. We evaluated if race-specific, sport-related structural and electrical remodelling in adolescent athletes of Caucasian and African ethnicity exclusively depends on race itself rather than on different cardiovascular responses to physical exercise. Methods: We examined 90 adolescent athletes, 60 Caucasian (WA) and 30 Black (BA). All participants underwent thorough clinical, echocardiographic and stress test evaluations. Results: BA had greater indexed LV mass (LVM/BSA) with increased relative wall thickness (RWT) implying a concentric remodelling. BA showed higher systolic blood pressure (SBP) compared to WA during the whole exercise test. ECG data showed that BA vs WA had a significant shorter QRS duration in each step considered with a significant greater QT dispersion. BA reached a higher relative pressure peak as compared to WA. RWT was strongly influenced by ethnicity and less by SBP at peak of exercise (PE), although LVM/BSA was significantly related to SBP at PE and just marginally to age and not significantly to race. Conclusions: Black adolescent athletes showed higher SBP during all steps of exercise associated to a different trend. Ethnicity was the main determinant of RWT, suggesting that LV geometry is principally race-related rather than influenced by a different hemodynamic profile to physical activity

Metabolic cardiomyopathy with heart failure: a late, reversible complication of bariatric surgery

Introduction: Dilated cardiomyopathy (DCM) is characterized by cardiac enlargement and impaired left ventricular systolic function, mostly caused by coronary artery disease, which may be effectively treated with myocardial revascularization techniques. However, besides other generally progressive aetiologies of DCM, such as the idiopathic form, there are also reversible causes of DCM, including those secondary to arterial hypertension and alcoholism or to metabolic-nutritional imbalances, such those operating in the present case. Case presentation: We report the case of a 74 years old woman, referred to the University Hospital of Parma because of progressive dyspnoea and peripheral oedema lasting from three months. In her clinical history, almost 30 years before the onset of the symptoms, she underwent a jejuno-ileal bypass surgery for severe obesity, with consequent 40 Kg weight loss. First clinical examination showed an undernourished (body mass index 16 Kg/m2), symptomatic subject with marked peripheral oedema and resting dyspnoea. Blood pressure levels were low (82/59 mmHg). ECG showed a sinus tachycardia with non-specific intraventricular conduction delay and flattened T-waves in the left precordial leads (Fig.1). An early echocardiogram demonstrated a left ventricular dilation with severe systolic dysfunction (end-diastolic diameter 60 mm, ejection fraction 22 %) and severe functional mitral regurgitation (MR) (Fig. 2). Coronary angiogram excluded significant coronary artery disease. Laboratory blood tests showed: normal renal function, markedly reduced values of the main serum electrolytes (2.1 mEq/L potassium; 0.76 mEq/L ionized calcium; 0.6 mg/dL magnesium; 1.4 mg/dL inorganic phosphorus) and of the albumin (1.9 g/dL); significant anaemia (8.7 g/dL haemoglobin) and depletion of iron, folate and Vitamin D; a 346 pg/mL serum concentration of PTH indicated secondary hyperparathyroidism; BNP was elevated (1647 pg/mL), while enzymes of myocardial injury were negative. On the assumption of a malabsorption syndrome as the cause of dilated cardiomyopathy resulting in congestive heart failure, the patient received transfusion of 3 red blood cell units and a three-weeks’ lasting intravenous supplementation of potassium, magnesium, calcium, phosphorus, iron and vitamins, with early clinical and laboratory improvement. Then a sustained oral supplementation was initiated and continued after discharge from the Hospital. She also received pharmacological therapy with beta-blocker and angiotensin-receptor blocker (ARB), while loop diuretic treatment, initially needed to control oedema and dyspnoea, was permanently discontinued. At the follow-up the patient felt progressively better with significant improvement of the functional class ( NYHA – from IV to I). Serial echocardiographic exams showed a left ventricular ejection fraction rising to 35% within one month, with downgrading of MR to a moderate degree, and to 65% after eight months, with complete regression of left ventricular dilation (51 mm end-diastolic diameter) and a further recovery of MR to a mild degree (Fig. 3). Conclusions: This observation reports a rare case of bariatric surgery induced metabolic cardiomyopathy, which completely regressed after correction of nutritional abnormalities

Key enabling technologies for point-of-care diagnostics

A major trend in biomedical engineering is the development of reliable, self-contained point-of-care (POC) devices for diagnostics and in-field assays. The new generation of such platforms increasingly addresses the clinical and environmental needs. Moreover, they are becoming more and more integrated with everyday objects, such as smartphones, and their spread among unskilled common people, has the power to improve the quality of life, both in the developed world and in low-resource settings. The future success of these tools will depend on the integration of the relevant key enabling technologies on an industrial scale (microfluidics with microelectronics, highly sensitive detection methods and low-cost materials for easy-to-use tools). Here, recent advances and perspectives will be reviewed across the large spectrum of their applications