RESUMO
Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.
Assuntos
Arritmias Cardíacas/etiologia , Dopamina/urina , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Fumantes , Fumar/efeitos adversos , Potenciais de Ação , Adulto , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/urina , Biomarcadores/urina , Cotinina/urina , Eletrocardiografia , Ex-Fumantes , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , não Fumantes , Fumar/fisiopatologia , Fumar/urina , UrináliseRESUMO
BACKGROUND: Using engineered nanomaterial-based toners, laser printers generate aerosols with alarming levels of nanoparticles that bear high bioactivity and potential health risks. Yet, the cardiac impacts of printer-emitted particles (PEPs) are unknown. Inhalation of particulate matter (PM) promotes cardiovascular morbidity and mortality, and ultra-fine particulates (< 0.1 µm aerodynamic diameter) may bear toxicity unique from larger particles. Toxicological studies suggest that PM impairs left ventricular (LV) performance; however, such investigations have heretofore required animal restraint, anesthesia, or ex vivo preparations that can confound physiologic endpoints and/or prohibit LV mechanical assessments during exposure. To assess the acute and chronic effects of PEPs on cardiac physiology, male Sprague Dawley rats were exposed to PEPs (21 days, 5 h/day) while monitoring LV pressure (LVP) and electrocardiogram (ECG) via conscious telemetry, analyzing LVP and heart rate variability (HRV) in four-day increments from exposure days 1 to 21, as well as ECG and baroreflex sensitivity. At 2, 35, and 70 days after PEPs exposure ceased, rats received stress tests. RESULTS: On day 21 of exposure, PEPs significantly (P < 0.05 vs. Air) increased LV end systolic pressure (LVESP, + 18 mmHg) and rate-pressure-product (+ 19%), and decreased HRV indicating sympathetic dominance (root means squared of successive differences [RMSSD], - 21%). Overall, PEPs decreased LV ejection time (- 9%), relaxation time (- 3%), tau (- 5%), RMSSD (- 21%), and P-wave duration (- 9%). PEPs increased QTc interval (+ 5%) and low:high frequency HRV (+ 24%; all P < 0.05 vs. Air), while tending to decrease baroreflex sensitivity and contractility index (- 15% and - 3%, P < 0.10 vs. Air). Relative to Air, at both 2 and 35 days after PEPs, ventricular arrhythmias increased, and at 70 days post-exposure LVESP increased. PEPs impaired ventricular repolarization at 2 and 35 days post-exposure, but only during stress tests. At 72 days post-exposure, PEPs increased urinary dopamine 5-fold and protein expression of ventricular repolarizing channels, Kv1.5, Kv4.2, and Kv7.1, by 50%. CONCLUSIONS: Our findings suggest exposure to PEPs increases cardiovascular risk by augmenting sympathetic influence, impairing ventricular performance and repolarization, and inducing hypertension and arrhythmia. PEPs may present significant health risks through adverse cardiovascular effects, especially in occupational settings, among susceptible individuals, and with long-term exposure.
Assuntos
Poluentes Atmosféricos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Sistema de Condução Cardíaco/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Material Particulado/toxicidade , Sistema Nervoso Simpático/efeitos dos fármacos , Aerossóis , Animais , Arritmias Cardíacas/sangue , Arritmias Cardíacas/urina , Eletrocardiografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Impressão , Ratos Sprague-Dawley , Pressão Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Intravenous magnesium is routinely administered in intensive care units (ICU) to treat arrhythmias after cardiothoracic surgery. There are no data on the pharmacokinetics of continuous magnesium infusion therapy. OBJECTIVE: To investigate the pharmacokinetics of continuous magnesium infusion, focusing on serum and urinary magnesium concentration, volume of distribution and half-life. METHODS: We administered a 10â¯mmol bolus of magnesium-sulfate followed by a continuous infusion of 3â¯mmol/h for 12â¯h in twenty cardiac surgery patients. We obtained blood and urine samples prior to magnesium administration and after one, six, and 12â¯h. RESULTS: Median magnesium levels increased from 1.09 (IQR 1.00-1.23) mmol/L to 1.59 (1.45-1.76) mmol/L after 60â¯min (pâ¯<â¯.001), followed by 1.53 (1.48-1.71) and 1.59 (1.48-1.76) mmol/L after 6 and 12â¯h. Urinary magnesium concentration increased from 9.2 (5.0-13.9) mmol/L to 17 (13.6-21.6) mmol/L after 60â¯min (pâ¯<â¯.001). Cumulative urinary magnesium excretion was 28â¯mmol (60.9% of the dose given). The volume of distribution was 0.25 (0.22-0.30) L/kg. There were no episodes of severe hypermagnesemia (≥3â¯mmol/L). CONCLUSION: Combined bolus and continuous magnesium infusion therapy leads to a significant and stable increase in magnesium serum concentration despite increased renal excretion and redistribution.
Assuntos
Antiarrítmicos/farmacocinética , Procedimentos Cirúrgicos Cardíacos , Rim/fisiologia , Sulfato de Magnésio/farmacocinética , Idoso , Análise de Variância , Antiarrítmicos/administração & dosagem , Arritmias Cardíacas/sangue , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/urina , Cuidados Críticos/métodos , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Infusões Intravenosas , Magnésio/sangue , Magnésio/urina , Sulfato de Magnésio/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 µg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 µg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 µg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 µg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 µg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.
Assuntos
Arritmias Cardíacas/urina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Eletrocardiografia , Proteínas de Ligação a Ácido Graxo/urina , Insuficiência Renal Crônica/urina , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/urina , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/urina , Cistatina C/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Troponina T/sangueRESUMO
BACKGROUND: Air pollution has been associated with an increased risk of cardiopulmonary mortality and decreased heart rate variability (HRV). However, it is unclear whether coke oven emissions (COEs) and polycyclic aromatic hydrocarbons (PAHs) are associated with HRV. OBJECTIVES: Our goal in the present study was to investigate the association of exposure to COEs and the urinary metabolite profiles of PAHs with HRV of coke oven workers. METHODS: We measured benzene soluble matter, carbon monoxide, sulfur dioxide, particulate matters, and PAHs at different workplaces of a coke oven plant. We determined 10 urinary PAH metabolites and HRV indices of 1333 workers using gas chromatography-mass spectrometry and a 3-channel digital Holter monitor, respectively. RESULTS: Our results showed that there was a significant COEs-related dose-dependent decrease in HRV, and an inverse relationship between the quartiles of urinary 2-hydroxynaphthalene and five HRV indices (p(trend)<0.01 for all). After adjustment for potential confounders, elevation per interquartile range (IQR) (1.81 µg/mmol creatinine) of urinary 2-hydroxynaphthalene was associated with a 5.46% (95% CI, 2.50-8.32) decrease in standard deviation of NN intervals (SDNN). As workers worked more years, SDNN gradually declined in the same quartiles of 2-hydroxynaphthalene levels (p(trend)â=â1.40×10(-4)), especially in workers with the highest levels of 2-hydroxynaphthalene. CONCLUSIONS: Occupational exposure to COEs is associated with a dose-response decrease in HRV. In particular, increased exposure to 2-hydroxynaphthalene is associated with significantly decreased HRV. Increase of working years and exposure levels has resulted in a gradual decline of HRV.
Assuntos
Poluentes Atmosféricos/toxicidade , Coque/toxicidade , Frequência Cardíaca , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/urina , Hidrocarbonetos Policíclicos Aromáticos/químicaRESUMO
It has been well established that in acute myocardial infarction (MI) many patients display low serum magnesium (Mg). This is associated with complex ventricular arrhythmias. The question arises whether predischarge arrhythmias occurring late after MI might also be related to Mg imbalance. In 118 patients subjected to heart rhythm 24 h Holter monitoring in the second or third week after MI, we investigated (1) the relationship between serum Mg, urinary Mg loss, and ventricular arrhythmias, and (2) the effect of Mg supplementation on heart rhythm disturbances. In patients with undisturbed rhythm or monomorphic ventricular ectopic beats (VEB) (Lown 0-2; n = 84), mean serum Mg level (mg% +/- SD) was 1.83 +/- 0.21, whereas in patients with multifocal VEB, pairs, or nonsustained ventricular tachycardia (VT) (Lown 3-4; n = 34) serum Mg was decreased to 1.68 +/- 0.27 (p < 0.01). Serum Mg normal range in our laboratory is 1.7-2.6 mg%. The lowest serum Mg reaching 1.55 +/- 0.27 was found in nonsustained VT (Lown 4 b) subgroup (n = 14). Urinary Mg loss measured in 81 patients was more pronounced in those with Lown 3-4 arrhythmias (n = 26) than with Lown 0-2 (n = 55). The daily values were 73 +/- 22 and 54.4 +/- 26 mg, respectively (p < 0.001). Thirteen patients with complex arrhythmias and low serum Mg received Mg supplementation (MgSO4, 8 g in 500 ml 5% glucose intravenously during 24 h). This resulted in restoration of almost undisturbed rhythm in 10 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Arritmias Cardíacas/etiologia , Magnésio/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/sangue , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/urina , Feminino , Humanos , Magnésio/sangue , Magnésio/urina , Sulfato de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
The prognostic importance of levels of urinary excretion of cyclic GMP (cGMPu), the second messenger of the atrial natriuretic factor (ANF) was studied in different cardiac pathologies in 31 patients (19 males and 12 females, average age 66 +/- 15 years) and compared with 31 control subjects of the same age (+/- 4 years) and sex. In the control group, the average cGMPu was 0.35 +/- 0.17 mumoles/24 hours/m2, and, with respect to urinary creatinine, increased with age (r = 0.54, p = 0.002). In the 16 patients with cardiac failure, the cGMPu was very high (1.03 +/- 0.59 mumoles/24 hours/m2, p less than 0.001) without any significant correlation with NYHA functional class although it fell after treatment. After myocardial infarction (8 cases including 3 with cardiac failure), the cGMPu was also high (0.49 +/- 0.33 mumoles/24 hours/m2) but it did not differ significantly from the control values in the 9 atrial arrhythmias without cardiac failure. The cGPMu was related to the cardiothoracic ratio but not to any blood gas parameter or echocardiographic measurement. In conclusion, the cGMPu is more stable and easier to measure than the ANF. It would seem to be a sensitive marker of cardiac failure complicating the most common cardiac pathologies observed in clinical practice.
Assuntos
GMP Cíclico/urina , Cardiopatias/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/urina , Fator Natriurético Atrial/análise , Feminino , Átrios do Coração , Insuficiência Cardíaca/urina , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/urinaRESUMO
We examined cross-country skiing-related strain in 10 less experienced postinfarction patients, performing a skiing test, covering a distance of approximately 7 km in 90 min. Heart rates, cardiac arrhythmia, lactic acid levels and catecholamine excretions were determined as strain indicators. The patients' exercise capacity, estimated during graded ergometric cycling, was 2.1 +/- 0.4 watts.kg-1, indicating a nearly age-appropriate submaximum performance ability. They had suffered myocardial infarction 2.8 +/- 0.7 years previously, participated regularly in a rehabilitation program for at least one year, and they did not show coronary insufficiency or significant cardiac dysrhythmias during laboratory testing under their usual medications. They went cross-country skiing during a 4-day instruction period and subsequently performed a cross-country skiing test on the 5th day. Mean skiing-related heart rates (124 +/- 9 bpm) and adrenaline excretions (124 +/- 88 pmol.min-1) corresponded on average to an exercise level of 1.85-2.0 watts.kg-1 during laboratory testing, and mean noradrenaline excretions (586-343 pmol.kg-1) and lactate concentrations (3.83 +/- 2.18 mmol.l-1) to a level of 1.48-1.73 watts.kg-1. Cardiac dysrhythmias were observed in a moderate number of 6-8 SVES, 9 to 12 VES and 4 to 7 couplets of VES per 1000 beats during cross-country skiing. The present results point to a comparatively high cardiovascular strain in less experienced postinfarction patients during a cross-country skiing test at an intensity level thought to be moderate.
Assuntos
Arritmias Cardíacas/fisiopatologia , Epinefrina/urina , Frequência Cardíaca , Lactatos/sangue , Infarto do Miocárdio/fisiopatologia , Norepinefrina/urina , Esqui , Adulto , Arritmias Cardíacas/sangue , Arritmias Cardíacas/urina , Humanos , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/urinaRESUMO
Dietary iodine intake was estimated by measurement of iodide in random overnight 12 hr and 24 hr urine samples. Urinary iodide excretion was measured in 231 healthy females comprising 127 female secondary students (ages 16-19), 27 female tertiary students (17-23 yr), 42 female laundry workers (18-52 yr) and 26 pregnant women in the third trimester (18-40 yr). Urine iodide excretion was also examined in a group of 28 patients attending a thyroid clinic, with thyroid disease of diverse aetiology and in 34 patients taking the antiarrhythmic drug amiodarone for control of cardiac arrhythmias. The mean daily urine iodide excretion was 2.4 mumol/day (0.9-5.8 mumol/day) and iodide to creatinine ratio 0.21 mumol/mmol (0.09-0.29). Iodine deficiency (less than 0.4 mumol/day) was not observed in any subject. Excessive iodine (greater than 8 mumol/day) was found only in patients known to be taking iodine-containing drugs and in one normal individual. The urine iodide was normal in 154 female students, 14 of whom had a trivial thyroid enlargement. The study suggests that dietary sources other than iodised salt contribute significantly to dietary iodine intake and that residual goitre in the community is not secondary to deficiency or excess of dietary iodine.
Assuntos
Iodo/administração & dosagem , População Urbana , Adolescente , Adulto , Idoso , Arritmias Cardíacas/urina , Creatinina/urina , Dieta , Feminino , Humanos , Iodo/urina , Pessoa de Meia-Idade , Nova Zelândia , Gravidez , Terceiro Trimestre da Gravidez , Doenças da Glândula Tireoide/urinaRESUMO
In 36 patients with cardiac arrhythmias (predominantly ventricular premature beats), who were on oral aprindine long-term therapy with 50 to 400 mg daily, plasma levels were measured by gas chromatography after 3.5 hours of the last administration. There was a general dependency of plasma levels on the given dose, however, with considerable overlapping in individual values. In 24 patients the arrhythmias ceased, in six patients there was a clear, in two a moderate improvement. There was no clear therapeutic effect in four patients who were treated with a daily dose of 50 and 100 mg, respectively. Among the 36 patients, three who had plasma levels exceeding 2 micrograms/ml developed tremor and dizziness. After dose-reduction these side effects disappeared. The present results suggest that therapeutic plasma levels of aprindine are in the range of 1.0 to 1.75 micrograms/ml. A plasma level of 2 micrograms/ml should not be exceeded because of the possibility of side-effects. In six healthy males time-concentration curves of aprindine and its metabolites in plasma and urine were measured by gas chromatography. From the results a two-compartment model may be applied, the half-life of elimination was calculated to be 37 hours (plasma) and 31 hours (urine). With respect to the metabolites, in plasma only des-ethyl-aprindine (DEAP), in urine DEAP, hydroxy-, des-phenyl- and des-indanyl-aprindine could be found. Unlike aprindine, the DEAP-concentration curve in plasma showed a very slight decrease until the end of the 96-hour period of determination.
Assuntos
Aprindina , Indenos , Aprindina/sangue , Aprindina/urina , Arritmias Cardíacas/sangue , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/urina , Fenômenos Químicos , Química , Cromatografia Gasosa , Humanos , Indenos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Cardiovascular toxicity including ventricular extrasystoles associated with pheniramine overdosage has been documented in the absence of factors recognised to aggravate this toxicity. The presence of pheniramine and the absence of other compounds was established using analytical techniques. It is concluded that patients with pheniramine overdosage should be treated exercising the same precautions as with tricyclic overdosage. Several sudden and unexpected deaths have occurred due to pheniramine overdosage in both adults and children. The cause of death in each case was not known. The purpose of this report is to document clinical features of pheniramine overdosage, in particular previously unsuspected cardiovascular toxicity manifesting as clinically significant ventricular arrhythmias. Pheniramine was positively identified in the overdosed patient, and the presence of other agents excluded.
Assuntos
Arritmias Cardíacas/induzido quimicamente , Feniramina/intoxicação , Adulto , Arritmias Cardíacas/urina , Humanos , Masculino , Feniramina/urinaRESUMO
During 1970-75 a total of 42 patients have been subjected to long-term treatment with procaine amide (PrA) because of different cardiac arrhythmias and have been observed up to over 5 years. Among these patients 35 (83%) developed a significantly increased titer of ANF and of these, 12 patients (29%) developed a "classical" drug-induced SLE syndrome. In the SLE group all but 2 improved rapidly after cessation of PrA, and the ANF titer decreased continuously but slowly in both groups. Acetylation test with sulphamidine and/or isoniazid in 11 patients among the SLE cases showed 8 slow and 3 fast acetylators. Among 12 patients who also had received PrA for a long time, but had not shown any signs of an SLE syndrome, there were 10 fast and 2 slow acetylators.
Assuntos
Anticorpos Antinucleares , Arritmias Cardíacas/tratamento farmacológico , Lúpus Eritematoso Sistêmico/induzido quimicamente , Neutrófilos , Procainamida/uso terapêutico , Acetilação , Adulto , Idoso , Anticorpos Antinucleares/análise , Arritmias Cardíacas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Procainamida/administração & dosagem , Procainamida/efeitos adversos , Sulfanilamidas/urina , Fatores de TempoRESUMO
Cardiac arrhythmias, digoxin concentration in plasma and urine, digoxin and creatine clearances, electrolytes in plasma and in erythrocytes, and subjective symptoms have been carefully studied for 5 consecutive days in 19 patients with definite or suspected digitalis intoxication. The digoxin treatment was discontinued during the observation period. Eleven controls without any signs of toxicity were similarly followed on unchanged maintenance dosage. All patients were independently classified as toxic or non-toxic from the follow-up of extended ECG recordings and subjective symptoms. In 9 definitely toxic patients a plasma digoxin concentration 3.1 plus or minus 0.7 ng/ml was found, as compared to 1.4 plus or minus 0.5 ng/ml for the 11 controls. In the suspect toxic group 1.5-3.9 ng/ml was found. The high digoxin level in the toxic group corresponds to a low digoxin clearance. In the toxic patients cardiac arrhythmias were related in most cases to a plasma digoxin level above 2.5 ng/ml and usually disappeared when the concentration had decreased below this. Suspect toxic patients, classified as probably non-toxic, and controls had with two exceptions plasma digoxin levels below 2 ng/ml. It is suggested that digitalis toxicity should be considered at a plasma digoxin concentration above 2 ng/ml. It must be stressed that this limit is not absolute and is affected by, among other things, a disturbance of intra- and extracellular electrolytes.