Consumption of sugar-sweetened soft drinks and risk of metabolic syndrome and its components: results of the ELSA-Brasil study (2008-2010 and 2012-2014).

AIM: To estimate the association between consumption of sugar-sweetened soft drinks and unsweetened fruit juice with metabolic syndrome (MetS) and its components in participants of the Brazilian Longitudinal Adult Health Study (ELSA-Brasil) after 4 years of follow-up. METHODS: We used data from ELSA-Brasil cohort (N = 15,105). The sample consisted of 6,124 civil servants free of the MetS at baseline (35 to 74 years, both sexes). The consumption of sugar-sweetened soft drinks and unsweetened fruit juice was estimated by a food frequency questionnaire previously validated. The outcome was MetS and its components (Joint Interim Statement criteria). To test the association between beverage consumption at baseline (2008-2010) and MetS and its components at follow-up (2012-2014), we used Poisson regression models with robust variance adjusting for potential confounders. RESULTS: After 4-year follow-up, the higher consumption of sugar-sweetened soft drinks (≥ 1 serving/day = 250 mL/day) increased the relative risk of MetS (RR = 1.22; 95% CI 1.04-1.45), high fasting glucose (RR = 1.23; 95% CI 1.01-1.48), and high blood pressure (RR = 1.23; 95% CI 1.00-1.54). Moderate consumption of this beverage (0.4 to < 1 serving/day) increased the relative risk of high waist circumference (WC) (RR = 1.21; 95% CI 1.02-1.42). After adjustment for confounding variables, the consumption of unsweetened fruit juice was not associated with the MetS and its components. CONCLUSION: Higher sugar-sweetened soft drinks consumption was associated with a higher risk relative of MetS, high fasting glucose, and high blood pressure, while moderate consumption of this beverage increased the relative risk of high WC in Brazilian adults.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients.

AIMS: The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. METHODS: We cross-sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. RESULTS: Genotype frequencies in the whole population were consistent with the Hardy-Weinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 ± 0.1 vs. 6.2 ± 0.1 mmol/l, P = 0.020) and waist circumference (94.5 ± 0.6 vs. 96.3 ± 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. CONCLUSIONS: These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.

Association between dietary patterns and renal function in a cross-sectional study using baseline data from the ELSA-Brasil cohort.

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP ("traditional", "fruits and vegetables", "bakery", and "low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between "bakery" and "fruits and vegetables", and both were associated with decreased eGFR and albuminuria in both genders, compared with "traditional" and "low sugar/low fat" patterns in the general population. There was a direct association of the "bakery" pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The "fruits and vegetables" pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The "fruits and vegetables" and "bakery" DPs were associated with renal dysfunction. The only independent, direct association was between "bakery" DP and MA in men, raising concerns about DP and renal damage in men.

TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population.

BACKGROUND: Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. METHODS: We genotyped the single nucleotide polymorphisms (SNP) rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study) Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population. RESULTS: SNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032), confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776). CONCLUSION: TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world. Finally, confirming the biological association of a genetic marker does not guarantee improvement on already established screening tools based solely on demographic variables.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (ß: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (ß: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

[A patient with feigned mental incompetence requiring medical treatment]. / Een patiënt die wilsonbekwaamheid simuleert en voor wie somatische behandeling is geïndiceerd.

A woman at the presumed age of 60 years was suspected of malingering cognitive impairment, due to her social circumstances (illegal residency) and was consequently unable to give permission for treatment. She was suffering from locally advanced mammary carcinoma, diagnosed according to the Breast Imaging Reporting and Data System in stage 5. In order to assess mental incompetence, an algorithm from the Royal Dutch Medical Association (KNMG) is a useful tool. The algorithm contains questions for determining whether a patient is able to make choices, if he/she understands medical information and can apply this to his/her own situation and whether he/she is able to logically consider the choice. Mental incompetence is a legally defined status - there is no straightforward relation between mental incompetence and the underlying diagnosis, in this case malingering. Since feigning mental incompetence has its own limitations, the subjective judgment of the physician is important. In the case presented, medical treatment i.e. chemotherapy was started in accordance with the Dutch Medical Treatment Contracts Act (WGBO) for a patient with cognitive impairment. Compulsory treatment was not necessary because the patient did not resist either physically or verbally. If a critical situation is to be prevented or is threatening, then there is no difference between genuine or feigned mental incompetence.

Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction.

Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.

Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure.

BACKGROUND: A causal relationship between plasma cholesterol and blood pressure remains poorly understood. It has been postulated that the decrease in nitric oxide (NO) availability is a potential mechanism by which hypercholesterolemia may stimulate blood pressure elevation. However, evidence supporting the role of the L-arginine-NO pathway on the relationship between hypertension and hypercholesterolemia is still lacking. METHODS AND RESULTS: We tested for an association of the expressed NO synthase (eNOS) Glu298Asp gene variant and plasma levels of lipids and lipoproteins in the determination of systolic blood pressure levels in a 1577 individuals randomly selected from the general population. Significant interactions could be disclosed either between the Glu298Asp gene variant and total-cholesterol (p = 0.02), log-transformed triglycerides (p = 0.004) or non-HDL-cholesterol (p = 0.003) in the determination of systolic blood pressure. In addition, although the presence of the AspAsp genotype did not significantly increase the risk of hypertension in individuals in the 50% lowest percentile of total-cholesterol, presence of this genotype significantly increased the risk of hypertension in individuals in the 50% highest percentile. Finally, in a multiple logistic regression model adjusting for age, sex, diabetes, ethnicity, smoking status and BMI, the AspAsp genotype significantly increased the risk of hypertension only in individuals with total-cholesterol above 209 mg/dL (p = 0.05, odds ratios (OR) = 2.0). CONCLUSION: Taken together, these results provide evidence supporting the role of the eNOS Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels.

Low-salt diet increases NO bioavailability and COX-2 vasoconstrictor prostanoid production in spontaneously hypertensive rats.

AIMS: The ability of dietary sodium restriction to reduce the incidence of cardiovascular mortality and improve vascular function in hypertension still remains poorly understood. The aim of this study was to observe the effects of a long period of salt restriction on the vascular reactivity of mesenteric resistance arteries of SHRs. METHODS: Male SHRs received either standard-salt diet (0.3% NaCl) or low-salt diet (0.03% NaCl) for 28weeks. Vascular reactivity was studied in mesenteric artery segments and the influence of cyclooxygenase-2 (COX-2), reactive oxygen species (ROS) and participation of the renin-angiotensin system were analyzed. KEY FINDINGS: Decreased salt intake did not affect phenylephrine-induced vasoconstriction but increased acetylcholine-induced vasodilatation and also increased the response to phenylephrine after inhibition of NO synthase by L-NAME (100µM) and iNOS protein expression was elevated. Cyclooxygenase inhibitor indomethacin (10µM) and COX-2 inhibitor NS 398 (1µM) decreased the reactivity to phenylephrine in low-salt-treated group, and COX-2 protein expression was elevated in low-salt group. The effects of apocynin (10µM); superoxide anion scavenger, tiron (1mM); hydrogen peroxide scavenger, catalase (1000UmL(-1)); and ACE and AT1 receptor blockers, enalapril (10µM) and losartan (10µM) on vascular reactivity were not different between two groups. The levels of AT1 protein expression were similar in both groups. SIGNIFICANCE: Low-salt diet modulates mesenteric vascular responses via increased NO bioavailability suggested by increased iNOS protein expression and vasoconstrictor prostanoid production via COX-2 pathway, in SHRs. Neither ROS nor the local renin-angiotensin system is involved in these responses.

Left ventricular length dependent activation in the isovolumetric rat heart.

STUDY OBJECTIVE: The aim of the study was to examine, in a whole heart preparation, the relationship between length changes in cardiac muscle and tension development and length dependent activation. DESIGN: Rat hearts were perfused by the Langendorff technique and isovolumetric pressure changes in the left ventricle, produced by increasing diastolic pressures (0, 5, 10, 15, 20, 25 mm Hg), were studied at different calcium concentrations (0.5, 1.25, 2.5, 3.75 mmol.litre-1). EXPERIMENTAL MATERIALS: 20 whole heart preparations were obtained from albino rats of either sex, weight 180-240 g (females) and 220-330 g (males). MEASUREMENTS AND MAIN RESULTS: In a comparison of ventricular diastolic upsilon systolic pressure curves, normalised with respect to maximum isovolumetric systolic pressure, there was a separation and an upward displacement of the curves with increments in calcium concentration in the perfusate. CONCLUSIONS: The results show, as in isolated preparations, that there is length dependent activation in the whole rat heart.

Changes in performance of the surviving myocardium after left ventricular infarction in rats.

STUDY OBJECTIVE: The aim was to investigate left ventricular performance of infarcted hearts during scar formation and development of hypertrophy in the surviving myocardium. DESIGN: Hearts were perfused according to the Langendorff technique and left ventricular function curves were obtained by inserting a distensible balloon into the ventricular cavity. The isovolumetric systolic pressure was measured as diastolic pressure was changed from 0 to 25 mm Hg and during inotropic interventions produced by Ca and isoprenaline. EXPERIMENTAL MATERIALS: Hearts were obtained from albino rats of either sex, 180-250 g, killed 1, 3, 7 or 14 d after left coronary artery ligation (n = 24) or sham operation (n = 26). Normal rats (n = 6) were used as additional controls. MEASUREMENTS AND MAIN RESULTS: After infarction, there was a progressive and almost parallel displacement of the ventricular function curves toward higher diastolic pressures. The positive chronotropic response to isoprenaline was similar in infarcted and non-infarcted hearts. The inotropic response to Ca and isoprenaline, however, was significantly depressed in the infarcted hearts throughout the observation period. CONCLUSIONS: Hypertrophy in the surviving myocardium did not result in improvement of the left ventricular systolic function assessed under in vitro conditions during the first two weeks after infarction. The decreased inotropic response of the infarcted left ventricle to isoprenaline is likely to be dependent on the reduced Ca sensitivity of the surviving myocardium.

Relationship between salt consumption measured by 24-h urine collection and blood pressure in the adult population of Vitória (Brazil).

High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of 24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4±4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4±5.0 vs 9.8±3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population.

Association between dietary patterns and renal function in a cross-sectional study using baseline data from the ELSA-Brasil cohort

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP ("traditional", "fruits and vegetables", "bakery", and "low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between "bakery" and "fruits and vegetables", and both were associated with decreased eGFR and albuminuria in both genders, compared with "traditional" and "low sugar/low fat" patterns in the general population. There was a direct association of the "bakery" pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The "fruits and vegetables" pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The "fruits and vegetables" and "bakery" DPs were associated with renal dysfunction. The only independent, direct association was between "bakery" DP and MA in men, raising concerns about DP and renal damage in men.

Racial differences in aortic stiffness in normotensive and hypertensive adults.

OBJECTIVE: To investigate whether differences exist in the mechanical properties of large arteries between white and black subjects. DESIGN: Eighty-two white (49 normotensive and 33 untreated hypertensive) and 38 black (24 normotensive and 14 untreated hypertensive) adult male volunteers were studied in a cross-sectional study. METHODS: Carotid-femoral pulse wave velocity was measured as an index of arterial stiffness, using a recently developed non-invasive automatic device, and compared between white and black subjects before and after the adjustment for age. The slope of regressions for pulse wave velocity and systolic blood pressure were also compared between racial groups. RESULTS: In the normotensive group, white subjects presented higher mean values of pulse wave velocity than blacks while the opposite behavior was found in the hypertensive group. After adjustment for age, significant differences in pulse wave velocity between whites and blacks became evident in the normotensive (whites 8.15 +/- 0.04 versus blacks 7.75 +/- 0.02 m/s; P < 0.001) and hypertensive (whites 8.88 +/- 0.02 versus blacks 9.30 +/- 0.17 m/s; P < 0.001) groups. Linear regression analysis for age-adjusted pulse wave velocity and systolic blood pressure showed that the slope was significantly greater in blacks than in whites (0.040 +/- 0.002 versus 0.019 +/- 0.001 m/s; P < 0.001). CONCLUSION: These data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.

Electrophysiological effects of labetalol on canine atrial, cardiac Purkinje fibres and ventricular muscle.

1. Using conventional microelectrode techniques for the intracellular recordings of the membrane potential, the effects of labetalol were studied on cardiac Purkinje, atrial and ventricular muscle fibres of the dog. 2. Labetalol (1-10 microM) reduced, in a concentration-dependent manner, the action potential amplitude (APA) and the maximum rate of rise of the action potential (Vmax) in Purkinje fibres. 3. The action potential duration (APD) was decreased in Purkinje fibres but significantly increased in ventricular fibres after small concentrations of labetalol (1-3 microM). The atrial fibres were not very sensitive to labetalol. 4. Depolarization of the cardiac Purkinje fibres by increasing the external potassium concentration (8-12 mM), potentiated the labetalol effects on APA and Vmax but blocked its effects on the APD. 5. The effects of labetalol on Vmax of Purkinje fibres were dependent on the frequency of stimulation. 6. The ratio of the effective refractory period to the APD was increased both in normally polarized and depolarized Purkinje fibres after treatment with labetalol (10 microM). 7. Labetalol (10 microM) shifted the membrane responsiveness curve of Purkinje fibres by about 10 mV in the hyperpolarizing direction. 8. The slow response obtained in K-depolarized, Ba-treated Purkinje fibres was not significantly affected by labetalol (10-100 microM). 9. It is suggested that labetalol can exert Class I and Class III antiarrhythmic actions in cardiac muscle of the dog in vitro.

Effects of verapamil on blood pressure and heart rate in neurogenic hypertensive rats.

The effects of verapamil (220 micrograms/kg per min i.v.) on blood pressure and heart rate were studied in sinoaortic baroreceptor denervated and sham-operated rats. In the conscious animals the verapamil-induced hypotension was accompanied by a significant heart rate increase in the first group (from 352 +/- 7 to 422 +/- 10 beats/min) and a decrease in the second group (from 485 +/- 13 to 400 +/- 9 beats/min). The verapamil-induced tachycardia observed in sham-operated rats was prevented by atropine plus propranolol but not by adrenal demedullation. Tachycardia was present in urethane-anesthetized sham-operated rats, similar to the sinoaortic baroreceptor-denervated rats. After verapamil a significant heart rate reduction was observed in sham-operated but not in sinoaortic baroreceptor-denervated rats. The results in conscious rats suggest that the direct inhibitory action of this drug on sinus node automaticity is suppressed by baroreflex tachycardia and that anesthesia masks this response.

Changes in collagen content in the residual myocardium surviving after infarction in rats. Influence of propranolol or hydralazine therapy.

The changes occurring in the collagen content in the residual myocardium after infarction have been poorly studied. The aim of this study was to determine the changes in the collagen content in the right and left ventricular muscle of chronically infarcted hearts. Male albino rats were submitted to ligature of the left coronary artery to produce infarction (Inf). Controls underwent a sham surgery (Sh). Inf rats were divided into groups designed to receive chronic therapy with propranolol (Prop, 1 g/l, n = 10) or hydralazine (Hydr, 0.125 g/l, n = 10) dissolved in the drinking water. One group of Inf rats (n = 12) and the Sh group (n = 10) received no treatment. The animals were killed 1 month after surgery to obtain the cardiac wet weights and to determine protein and hydroxyproline (OH-Pro) concentrations in the right ventricle (RV) free wall and in the left ventricular remaining muscle (LV), including the interventricular septum. Inf determined a 42% increase of the RV weight to body weight ratio (Sh = 0.57 +/- 0.04 mg/g; Inf = 0.81 +/- 0.06 mg/g; p < 0.05) and a 64% increase of OH-Pro concentration (Sh = 450 +/- 25 micrograms/g; Inf = 738 +/- 32 micrograms/g; p < 0.05). In Inf hearts the LV OH-Pro concentration increased similarly as in the RV. No effect of drug therapy was observed in the LV. In the RV however, propranolol reduced the hypertrophy and the OH-Pro concentration by the same amount (around 30%). Hydr on the other hand reduced OH-Pro and tended to increase hypertrophy. We conclude that a similar collagen deposition occurs in the myocardium of both ventricles after infarction in rats. Prop and Hydr were able to partially reduce this collagen increase in the right but not in the left ventricle.

Characteristics of myocardial contractions activated under depolarizing conditions.

Guinea pig papillary muscles were used to study the activation of myocardial contractions under depolarizing conditions. Depolarization promoted by TKBa (normal Tyrode solution containing KCl and BaCl2) and TKAdr (normal Tyrode solution containing KCl and adrenaline) inactivates the fast Na current and under these conditions only slow responses are available to activate contractions. Since the slow response is sensitive to changes in rate and rhythm, we searched for mechanical correlates using isometrically contracting preparations to study the force-frequency relationship as well as rest potentiation. We also investigated if contractions are dependent only on the slow response or if the complete action potential plays a special role in the activation of contractions. We conclude that the slow response is the main mechanism for the activation of myocardial contraction, because complete mechanical activation was observed under depolarizing conditions. However, the electrical behavior of the slow response is reflected in the mechanical behavior of the depolarized preparations. At high rates, disturbances of excitation occur in depolarized cells and contractions appear to be bigeminal or with 2:1 block. Furthermore, after long pauses, post-rest contractions are depressed and increase progressively with repetitive stimulation, probably due to changes in the latency and threshold of the slow response. The complete action potential also plays a role in the activation of myocardial contractions which is necessary for the resting potentiation phenomena and also to avoid the larger depression of the rest contractions that can be seen in depolarized muscles when the pause is prolonged. This behavior seems to be related to the decrease of intracellular Na concentration produced by the inhibition of the fast inward Na-current.