Avaliação dos efeitos da cafeína sobre a modulação autonômica e o ritmo cardíaco em pacientes com queixa de palpitações / Evaluation of the caffeine effects about the cardiac autonomic modulation and rhythm in patients with palpitations

A cafeína pertence ao grupo das metilxantinas e apresenta efeitos farmacológicos que podem contribuirpara o desencadeamento de arritmias cardíacas, com o aumento da estimulação simpática. Objetivo: Avaliara associação entre o consumo de cafeína e o desencadeamento ou o agravamento de arritmias cardíacas e suainfluência sobre o tônus autonômico. Método: Foram avaliados 51 pacientes submetidos ao Holter de 24 horasdevido a queixa de palpitação. O Holter avaliou a presença de diferentes arritmias e tônus autonômico por meiode índices de variabilidade da frequência cardíaca, principalmente do SDNN. Todos os pacientes preencheramum diário alimentar durante o período do registro. Estes foram avaliados por uma nutricionista por meio dosoftware NutWin 1.5 para quantificar a ingestão de cafeína e outros nutrientes. Os indivíduos foram divididos emdois grupos de acordo com a mediana do consumo de cafeína (35 mg). Resultados: O consumo médio diário decafeína foi de 14 ± 15 mg no grupo de menor consumo (n=27) vs. 100 ± 61 mg no grupo de maior consumo (n=24)(p<0,0001). Não foi observada associação entre o maior consumo de cafeína e qualquer extrassístole ventricular ousupraventricular isolada, pareada, > 10 ectopias/hora ou taquicardia ventricular ou supraventricular (p>0,05). Nogrupo de maior consumo, observou-se tendência de maior estimulação simpática, predominantemente durante operíodo do sono. Contudo, a análise restrita a esse período também não mostrou associação com o desencadeamentode qualquer arritmia. Conclusão: O consumo leve a moderado de cafeína (aproximadamente 100 mg/dia) não seassociou com o desencadeamento de qualquer arritmia, apesar de acarretar um discreto aumento da estimulaçãosimpática, principalmente durante o período do sono.

Abstract: Objective: Caffeine belongs to the methylxanthine group and has pharmacological effects that maycontribute to the onset of cardiac arrhythmias such as sympathetic overstimulation. The objectives were to evaluatethe association between caffeine intake and the onset or worsening of cardiac arrhythmias and their influenceon the cardiac autonomic tonus. Methods: Fifty-one patients underwent a 24-hour Holter due to complaintsof palpitations. The Holter evaluated the presence of different arrhythmias and autonomic tonus according toheart rate variability rates, mainly the SDNN. A food diary was filled out by all patients throughout their Holterrecording and were evaluated by a dietician using the NutWin 1.5 software to quantify the intake of caffeine andother nutrients. Subjects were divided into two groups according to the median caffeine intake (35 mg). Results:The mean daily consumption of caffeine was 14 ± 15 mg in the lowest consumption group (n=27) vs. 100 ± 61 mgin the highest consumption group (n=24) (p<0.0001). No association was observed between higher caffeine intakeand supraventricular or ventricular isolated premature beats, paired premature beats, > 10 premature beats perhour or ventricular or supraventricular tachycardia (p>0.05). A trend of sympathetic overstimulation was observed.

To study the relationship of caffeine elimination and Child's Pugh classification in groups of patients with liver cirrhosis

Serum Caffeine clearance determination is a useful method to evaluate the severity of liver disease and predict short-term survival of cirrhotic patients. Caffeine concentrations correlated well with the score indicating the sufficiency of the organ according to Child- Turcotte classification score. It offers another choice for the quantitative measurement of liver functional reservoir. Study is designed to find out the relationship of Caffeine elimination and child's classification in groups of patients with liver cirrhosis. Cross sectional Study. The study was conducted at the Medical Ward of Services Hospital Lahore from July 2004 to December 2004. Forty patients with liver cirrhosis with age range 40-55 years and 20 aged matched normal healthy volunteers were enrolled in this study. Patients were taken from the medical ward of Services Hospital Lahore. After an overnight fast, the first blood sample was collected at 8 a.m., immediately followed by an oral administration of 200 mg Caffeine. Subsequent samples of venous blood were obtained at 8.30 a.m., 9 a.m., 11 a.m., 2 p.m. and 5 p.m. The Caffeine clearance was determined by reversed-phase high pressure liquid chromatography using a Phenomenex Gemini C18 column using a wavelength of 273 nm. [Jaundice presented with highest frequency distribution and percentages. This was followed with ascities, edema. Family history of hepatitis/jaundice and anemia. Ultrasonographic findings showed that in 50% of the patients. Other 50% of patients have normal and shrunken liver]. Caffeine concentration in child class A was significantly decreased at base line [P<0.001], 3 hours [P<0.05], 6 hour [P<0.001] and 9 hour [P<0.001] as compared to the controls. In child class B the Caffeine concentration was significantly to the controls. On the other hand in child class C the Caffeine concentration was remaining same as in their controls. Caffeine clearance could provide a practical assessment of hepatic function in cirrhotic patients. Our data emphasize the value of the child-Turcotte or child-Pugh classification in assessing the severity of liver cirrhosis in a simple and less time-consuming way than using quantitative liver function tests

Níveis plasmáticos de cafeína no cordão umbilical e apneia da prematuridade / Serum levels of caffeine in umbilical cord and apnea of prematurity

OBJETIVO: Determinar a influência da presença de cafeína no sangue de cordão umbilical na ocorrência de apneia. MÉTODOS: Estudo de coorte prospectivo de recém-nascidos pré-termo com peso de nascimento menor que 2.000 g. Os critérios de exclusão foram: mães que receberam opioides; ventilação mecânica durante os primeiros 4 dias de vida; malformações cerebrais e cardíacas maiores; asfixia perinatal; hemorragia peri-intraventricular grave; exsanguineotransfusão antes do quarto dia de vida; e uso de metilxantina antes da extubação. Os recém-nascidos foram divididos em com e sem cafeína detectável no sangue de cordão umbilical, sendo acompanhados nos primeiros 4 dias para verificar ocorrência de apneia. RESULTADOS: Oitenta e sete recém-nascidos com e 40 sem cafeína detectável no sangue de cordão umbilical foram estudados. A mediana da concentração de cafeína dos 87 pacientes com cafeína detectável no sangue de cordão umbilical foi 2,3 µg/mL (0,2-9,4 µg/mL). Não houve associação entre ocorrência de apneia e presença de cafeína no sangue de cordão umbilical. Recém-nascidos com cafeína detectável no cordão umbilical tiveram tendência a apresentar apneia mais tardiamente (66,3±4,14 horas) do que aqueles com níveis indetectáveis (54,2±6,26 horas). CONCLUSÃO: A detecção de níveis de cafeína no sangue de cordão umbilical não diminuiu a ocorrência de apneia da prematuridade, mas teve um efeito limítrofe atrasando sua ocorrência, o que sugere que mesmo um nível baixo de cafeína no sangue de cordão umbilical pode retardar a ocorrência de apneia.

OBJECTIVE: To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. METHODS: A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxantine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. RESULTS: Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 µg/mL (0.2-9.4 µg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3±4.14 hours) than those with undetectable levels (54.2±6.26 hours). CONCLUSION: Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Paraxanthine/caffeine ratio: as an index for CYP1A2 activity in polycyclic aromatic hydrocarbons exposed subjects.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and originate from incomplete combustion process of organic materials. These compounds are bioactivated to reactive metabolites which bind covalently to DNA and subsequently initiate carcinogenesis. PAHs have been well established as an enzyme inducer of cytochrome P450 (CYP) such as CYP1A1 and CYP1A2. Caffeine is primarily metabolized by CYP1A2 to paraxanthine, so it has been used as a specific probe for assessing CYP1A2 activity. The purpose of this study was to compare CYP1A2 activity in female subjects that were automobile exhaust exposed and non-automobile exhaust exposed using serum paraxanthine/caffeine ratio as an index. Each subject took a 180 mg single oral dose of caffeine solution. Blood samples were collected before and 5 hours after caffeine intake. Serum samples were separated by centrifugation and stored at -20 degrees C until analysis by high performance liquid chromatography (HPLC). Carbon monoxide (CO) level in blood was also detected using spectrophotometer. The results showed that serum paraxanthine/caffeine ratio in exposed subjects was significantly higher than non-exposed subjects (mean +/- SE of 0.45 +/- 0.05 and 0.33 +/- 0.03, respectively; p < 0.05). CO level in exposed subjects was also significantly higher than non-exposed subjects (mean +/- SE of 4.03 +/- 0.21 and 3.01 +/- 0.18, respectively; p < 0.05). Conclusion: Paraxanthine/caffeine ratio, as an index for CYP1A2 activity, can be used to determine PAHs exposure. Automobile exhaust exposed subjects demonstrated significantly higher CYP1A2 activity than that of the non-exposed subjects. Exposed subjects have a possibly higher risk of chemical carcinogenesis.

Comparison of the quantification of caffeine in human plasma by gas chromatography and ELISA

In the present study we evaluated the precision of the ELISA method to quantify caffeine in human plasma and compared the results with those obtained by gas chromatography. A total of 58 samples were analyzed by gas chromatography using a nitrogen-phosphorus detector and routine techniques. For the ELISA test, the samples were diluted to obtain a concentration corresponding to 50 per cent of the absorbance of the standard curve. To determine whether the proximity between the I50 of the standard curve and that of the sample would bring about a more precise result, the samples were divided into three blocks according to the criterion of difference, in modulus, of the I50 of the standard curve and of the I50 of the sample. The samples were classified into three groups. The first was composed of 20 samples with I50 up to 1.5 ng/ml, the second consisted of 21 samples with I50 ranging from 1.51 to 3 ng/ml, and the third of 17 samples with I50 ranging from 3.01 to 13 ng/ml. The determination coefficient (R² = 0.999) showed that the data obtained by gas chromatography represented a reliable basis. The results obtained by ELISA were also reliable, with an estimated Pearson correlation coefficient of 0.82 between the two methods. This coefficient for the different groups (0.88, 0.79 and 0.49 for groups 1, 2 and 3, respectively) showed greater reliability for the test with dilutions closer to I50.

Caffeine clearance study in hepatocellular carcinoma.

The purpose of this study was to evaluate hepatic metabolic capacity in cirrhotic patients with hepatocellular carcinoma (HCC). We compared plasma caffeine clearance, calculated by two point analysis, between patients with cirrhosis alone and cirrhosis complicated with HCC. These two groups were comparable with regards to age, sex, and the severity of liver disease, graded by Child-Pugh score as compensated and decompensated cases. From our result, caffeine clearance in compensated cases was clearly higher than that of decompensated cases in both groups studied, particularly in the HCC group (p = 0.001). The mean value of caffeine clearance in HCC patients correlated well with the tumor staging as classified by Okuda's criteria. There was also a reversal correlation between tumor size and the clearance tested in compensated cases of HCC (p = 0.046), but this finding was not detected in decompensated cases (p > 0.05). We conclude that the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in cirrhotic patients complicated with HCC, and may be a useful predictor for survival outcome.

Effects of caffeine on time to exhaustion in exercise performed below and above the anaerobic threshold

Controversy still exists concerning the potential ergogenic benefit of caffeine (CAF) for exercise performance. The purpose of this study was to compare the effects of CAF ingestion on endurance performance during exercise on a bicycle ergometer at two different intensities, i.e., approximately 10 percent below and 10 percent above the anaerobic threshold (AT). Eight untrained males, non-regular consumers of CAF, participated in this study. AT, defined as the intensity (watts) corresponding to a lactate concentration of 4mM, was determined during an incremental exercise test from rest to exhaustion on an electrically braked cycle ergometer. On the basis of these measurements, the subjects were asked to cycle until exhaustion at two different intensities, i.e., approximately 10 percent below and 10 percent above AT. Each intensity was performed twice in a double-blind randomized order by ingesting either CAF (5 mg/kg) or a placebo (PLA) 60 min prior to the test. Venous blood was analyzed for free fatty acid, glucose, and lactate, before, during, and immediately after exercise. Rating of perceived exertion and time to exhaustion were also measured during each trial. There were no differences in free fatty acids or lactate levels between CAF and PLA during and immediately after exercise for either intensity. Immediately after exercise glucose increased in the CAF trial at both intensities. Rating of perceived exertion was singificantly lower (CAF = 14.1 + 2.5 vs PLA = 16.6 + 2.4) and time to exhaustion was significantly higher (CAF = 46.54 + 8.05 min vs PLA = 32.42 + 14.81 min) during exercise below AT with CAF. However, there was no effect of CAF treatment on rating of perceived exertion (CAF = 18.0 + 2.7 vs PLA = 17.6 + 2.3) and time to exhaustion (CAF = 18.45 + 7.28 min vs PLA = 19.17 + 4.37 min) during exercise above AT. We conclude that in untrained subjects caffeine can improve endurance performance during prolonged exercise performed below AT and that decrease of perceived exertion can be involved in this process.

Effect of caffeine on the metabolism of rats exercising by swimming

Several studies have demonstrated that caffeine improves endurance exercise performance but the mechanisms are not fully understood. Possibilities include increased free fatty acid (FFA) oxidation with consequent sparing of muscle glycogen as well as enhancement of neuromuscular function during exercise. The present study was designed to investigate the effects of caffeine on liver and muscle glycogen of 3-month old, male Wistar rats (250-300 g) exercising by swimming. Caffeine (5 mg/kg) dissolved in saline (CAF) or 0.9 percent sodium chloride (SAL) was administered by oral intubation (1 µl/g) to fed rats 60 min before exercise. The rats (N = 8-10 per group) swam bearing a load corresponding to 5 percent body weight for 30 or 60 min. FFA levels were significantly elevated to 0.475 + or - 0.10 mEq/l in CAF compared to 0.369 + or - 0.06 mEq/l in SAL rats at the beginning of exercise. During exercse, a significant difference in FFA levels between CAF and SAL rats was observed at 30 min (0.325 + or - 0.06 vs 0.274 + or - 0.05 mEq/l) but not at 60 min (0.424 + or - 0.13 vs 0.385 + or - 0.10 mEq/l). Blood glucose showed an increase due to caffeine only at the end of exercise (CAF = 142.1 + or - 27.4 and SAL = 120.2 + or - 12.9 mg/100 ml). No significant difference in liver or muscle glycogen was observed in CAF as compared to SAL rats, at rest or during exercise. Caffeine increased blood lactate only at the beginning of exercise (CAF = 2.13 + or - 0.2 and SAL = 1.78 + or - 0.2 mmol/l). These data indicate that caffeine (5 mg/kg) has no glycogen-sparing effect on rats exercising by swimming even though the FFA levels of CAF rats were significantly higher at the beginning of exercise

Salivary caffeine as indicator for liver function

This study was carried on 15 patients and 6 normal controls matched as regard weight, age and sex., eight patients proved to be post hepatitis liver cirrhosis [4 males and 4 females] and seven patients was proved to be hepatic bilharzial fibrosis [4 females and 3 males]. After withdrawal of fasting blood samples for liver function, caffeine was given [3.5 mg/kg body weight] orally. Then, blood and salivary samples were taken 2h. and 4 hours for estimation of caffeine. The mean 2h salivary caffeine of bilharzial group was significantly higher than that of the control group but other serum and salivary caffeine levels showed insignificant changes. This can be explained by the opend porto-systemic collaterals which facilitate the absorbed caffeine to by-passes the liver

A monitorizaçäo plasmática das metilxantinas do guaraná e a importancia na agregaçäo plaquetária / The plasma monitoring of methylxanthines of guarana and its importance in platelet aggregation

Num estudo placebo randomizado, 14 voluntários sadios foram tratados durante dois dias com extrato bruto de Guaraná. A suspensäo aquosa foi administrada em doses de 4 e 8g, três vezes ao dia. Após um período de "wash out", seguiu-se o tratamento com placebo, no mesmo esquema anterior. Desenvolveu-se uma técnica de análise simultânea das metilxantinas envolvidas (teofilina, cafeína e teobromina) em cromatografia líquida de alta pressäo após extraçäo conveniente do plasma em meio ácido com solvente orgânico. O método proposto se mostrou sensível, linear, reprodutível, seletivo, específico e portanto adequado à análise destes compostos em plasma após ingestäo do componente terapêutico nas doses de 4 a 8g. A administraçäo do produto aos voluntários evidenciou níveis plasmáticos dose dependentes para as metilxantinas envolvidas. Verificou-se ainda que houve uma correlaçäo linear positiva apenas entre níveis plasmáticos da cafeína e a inibiçäo da agregaçäo plaquetária em sangue total, mas näo em plasma rico em plaquetas. Näo houve correlaçäo entre doses, efeito biológico e níveis plasmáticos das demais metilxantinas ou por estas näo exercem influência digna de nota sobre a agregaçäo plaquetária ou abtençäo de concentraçäo plasmática subterapêutica utilizando aquelas doses