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Biomedical subjects

Tomas Kara

Publications and source records attributed to Tomas Kara.

15 recordsLinked to original sources

Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure.

OBJECTIVE: Sympathetic activation may contribute to both cardiovascular morbidity and the progression of chronic kidney disease. The role of the chemoreceptors in determining sympathetic nerve discharge in patients with chronic renal failure (CRF) is unknown. We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in patients with CRF. METHODS: Utilizing a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation on muscle sympathetic nerve activity (MSNA). We compared effects of breathing 100% oxygen for 15 min with effects of breathing room air for 15 min in 12 stable patients with CRF and in 12 control individuals with similar age, gender, blood pressure and body mass index. RESULTS: The baseline MSNA was elevated significantly in the patients with CRF as compared with the control individuals (50 +/- 2 vs 42 +/- 2 bursts/min; P < 0.05). Reductions in systolic blood pressure and pulse pressure in response to the administration of 100% oxygen were significantly different from those observed during administration of room air in patients with CRF. In patients with CRF, MSNA decreased by 29 +/- 7% (P < 0.01) during hyperoxia but did not change during administration of room air (5 +/- 6%; P = NS). By contrast, neither 100% oxygen or room air changed any measures in control individuals. CONCLUSIONS: Tonic activation of excitatory chemoreflex afferents contributes to increased efferent sympathetic activity to muscle circulation and to blood pressure control in patients with CRF. These findings may have important implications for understanding mechanisms underlying the link between CRF and cardiovascular disease.

Administration, Inhalation↗

Electrocardiography cannot reliably differentiate transient left ventricular apical ballooning syndrome from anterior ST-segment elevation myocardial infarction.

OBJECTIVE: The presentation and electrocardiographic (ECG) characteristics of transient left ventricular apical ballooning syndrome (TLVABS) can be similar to that of anterior ST-segment elevation myocardial infarction (STEMI). We tested the hypothesis that the ECG on presentation could reliably differentiate these syndromes. SUBJECTS AND METHODS: Between January 1, 2002 and July 31, 2004, we identified 18 consecutive patients with TLVABS who were matched with 36 subjects presenting with acute anterior STEMI due to atherothrombotic left anterior descending coronary artery occlusion. RESULTS: All patients with TLVABS were women (mean age, 72.0 +/- 13.1 years). The heart rate, PR interval, QRS duration, and corrected QT interval were similar between groups. Distribution of ST elevation was similar, but patients with anterior STEMI exhibited greater ST elevation. Regressive partitioning analysis indicated that the combination of ST elevation in lead V2 of less than 1.75 mm and ST-segment elevation in lead V3 of less than 2.5 mm was a suggestive predictor of TLVABS (sensitivity, 67%; specificity, 94%). Conditional logistic regression indicated that the formula: (3 x ST-elevation lead V2) + (ST-elevation V3) + (2 x ST-elevation V5) allowed possible discrimination between TLVABS and anterior STEMI with an optimal cutoff level of less than 11.5 mm for TLVABS (sensitivity, 94%; specificity, 72%). Patients with TLVABS were less likely to have concurrent ST-segment depression (6% vs 44%; P = .003). CONCLUSIONS: Women presenting with TLVABS have similar ECG findings to patients with anterior infarct but with less-prominent ST-segment elevation in the anterior precordial ECG leads. These ECG findings are relatively subtle and do not have sufficient predictive value to allow reliable emergency differentiation of these syndromes.

Aged↗

Sympathetic neural responses to smoking are age dependent.

OBJECTIVE: Smoking is an important risk factor for cardiovascular disease. Sympathetic responses to cigarette smoking may be implicated in the link between smoking and cardiovascular disease. We tested the hypothesis that the sympathetic neural responses to smoking are age dependent. METHODS: We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 14 normotensive middle-aged (49 +/- 4 years) and 12 young (29 +/- 4 years) habitual smokers matched for body mass index (25 +/- 2 kg/m2 in both groups). RESULTS: Sham smoking had no significant effect on sympathetic drive, blood pressure or heart rate in either group. Cigarette smoking increased heart rate in both middle-aged subjects and young subjects. In comparison to younger subjects, middle-aged smokers showed similar smoking-related increases in systolic blood pressure (SBP) [10 +/- 3 versus 12 +/- 2 mmHg, respectively, not significant (NS)]. Smoking decreased sympathetic nerve activity by 28 +/- 12% of baseline values (P < 0.01) in young subjects. However, muscle sympathetic nerve activity did not change significantly after smoking in middle-aged subjects (5 +/- 8%, NS), despite the increased blood pressures, which would be expected to inhibit sympathetic activity. By contrast, in young subjects, the heart rate increase (22 +/- 2 bpm) was greater than that seen in middle-aged subjects (13 +/- 2 bpm, P < 0.01). CONCLUSIONS: The autonomic responses to smoking are age dependent. While blood pressure increases are similar in both groups, young subjects respond to smoking by marked increases in heart rate and suppression of central sympathetic outflow. In middle-aged subjects, the heart rate increase is less marked, but sympathetic vasoconstrictor activity is not suppressed.

Adult↗

Sympathetic neural outflow and chemoreflex sensitivity are related to spontaneous breathing rate in normal men.

Respiration contributes importantly to short-term modulation of sympathetic nerve activity. However, the relationship between spontaneous breathing rate, chemoreflex function, and direct measures of sympathetic traffic in healthy humans has not been studied previously. We tested the hypothesis that muscle sympathetic nerve activity and chemoreflex sensitivity are linked independently to respiratory rate in normal subjects. We studied 69 normal male subjects aged 29.6+/-8.1 years. Subjects were subdivided according to the tertiles of respiratory rate distributions. Mean respiration rate was 10.6 breaths/min in the first tertile, 14.8 breaths/min in the second tertile, and 18.0 breaths/min in the third tertile. Subjects from the third tertile (faster respiratory rate) had greater sympathetic activity than subjects from the first tertile (slower respiratory rate; 29+/-3 versus 17+/-2 bursts/min; P<0.001). Stepwise multiple linear regression analysis revealed that only respiratory rate was linked independently to sympathetic activity (r=0.42; P<0.001). In comparison to subjects with slow respiratory rate, subjects with fast respiratory rate had greater increases in minute ventilation during both hypercapnia (7.3+/-0.8 versus 3.2+/-1.0 L/min; P=0.005) and hypoxia (5.7+/-0.8 versus 2.4+/-0.7 L/min; P=0.007). Muscle sympathetic nerve activity and chemoreflex sensitivity are linked to spontaneous respiratory rate in normal humans. Faster respiratory rate is associated with higher levels of sympathetic traffic and potentiated responses to hypoxia and hypercapnia. Spontaneous breathing frequency, central sympathetic outflow, and chemoreflex sensitivity exhibit significant and hitherto unrecognized interactions in the modulation of neural circulatory control.

Adult↗

Menopause, hormone replacement and RR and QT modulation during sleep.

BACKGROUND AND PURPOSE: Sleep affects the RR interval in electrocardiogram (ECG) recordings and ventricular repolarization differentially in men and women. Compared to men, pre-menopausal women have a more pronounced shortening of RR interval and prolongation of QT and QT corrected (QTc, by Bazett's formula) ECG waves during rapid eye movement (REM) sleep. The aim of the present study was to evaluate sleep-related RR and QT changes: (1) with the physiological decline in female hormones occurring with menopause, and (2) after hormone replacement therapy with estrogen and progesterone (HRT). PATIENTS AND METHODS: We analyzed ECG recordings from 14 post-menopausal women (48-61 years old) who underwent polysomnography before HRT (T1) and after 6 months of HRT (T2) with estrogen and progesterone. Eight of the post-menopausal women (48-54 years) were also compared to eight age-matched pre-menopausal women. In all subjects, mean RR interval, mean QT interval and QTc, were obtained from 1-min recordings selected from wakefulness, stage 2 and REM sleep. RESULTS: Pre-menopausal and post-menopausal women showed similar changes in RR, QT and QTc intervals from wakefulness through sleep. Specifically, in both pre-menopausal and post-menopausal women the RR interval was shorter during REM sleep compared to wakefulness (P=0.009) and stage 2 sleep (P=0.001); the QT interval was more prolonged during stage 2 (P=0.002) and REM (P=0.006); and the QTc interval was significantly prolonged during stage 2 (P=0.01) and REM (P=0.0003) sleep compared to wakefulness. Among post-menopausal women, both before and after HRT (T1 and T2), RR interval shortened significantly during REM compared to wakefulness (P=0.03) and to stage 2 (P=0.002); the absolute QT interval was longer during stage 2, compared to both wakefulness (P<0.001) and REM (P<0.001); the QTc interval was increased during REM sleep compared to wakefulness (P=0.003). CONCLUSIONS: Sleep-related RR and QT changes in women are not altered by menopausal status nor by post-menopausal hormonal replacement with estrogen and progesterone.

Age Factors↗

Cardiopulmonary consequences of obstructive sleep apnea.

Ongoing research in obstructive sleep apnea (OSA) suggests strong associations with cardiopulmonary disorders. There is an abundance of studies describing physiological pathways in OSA that acutely impact the cardiovascular system. These mechanisms, if proven to carry over into the daytime hours, could form the basis for clinical disease. The challenge remains in disentangling these mechanistic processes from the many comorbid conditions often present in patients with OSA. Examples include male gender, obesity, and diabetes mellitus, all of which exert their own influence on the development of cardiopulmonary disease. This review discusses some of the physiological mechanisms associated with disordered breathing during sleep and explores putative cardiopulmonary disease associations.

Cardiovascular Diseases↗

Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction.

The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. In this paper, we review case series that report on patients with the transient left ventricular apical ballooning syndrome to better characterize patients presenting with the syndrome. We identified 7 case series that reported on at least 5 consecutive patients with the transient left ventricular apical ballooning syndrome. The syndrome more often affects postmenopausal women (82% to 100%) (mean age, 62 to 75 years). Patients commonly present with ST-segment elevation in the precordial leads, chest pain, relatively minor elevation of cardiac enzyme and biomarker levels, and transient apical systolic left ventricular dysfunction despite the absence of obstructive epicardial coronary disease. An episode of emotional or physiologic stress frequently precedes presentation with the syndrome. The in-hospital mortality rate seems to be low, as does the risk for recurrence.

Cardiomyopathies↗

Serum amyloid a in obstructive sleep apnea.

BACKGROUND: Patients with severe obstructive sleep apnea (OSA) may have increased risk for cardiovascular and cerebrovascular diseases. Serum amyloid A (SAA) protein has recently been linked to the development of atherosclerosis, stroke, diabetes, and dementia. We tested the hypothesis that plasma SAA levels are increased in otherwise healthy subjects with OSA. METHODS AND RESULTS: Plasma SAA levels were measured in 10 male patients with moderate to severe OSA before sleep, after 5 hours of untreated OSA, and in the morning after effective continuous positive airway pressure treatment. SAA levels were also measured in 10 closely matched control subjects at similar time points. Baseline plasma SAA levels before sleep were strikingly higher in patients with moderate to severe OSA than in controls (18.8+/-2.6 versus 7.2+/-2.6 microg/mL, respectively; P=0.005) and remained unchanged in both groups throughout the night. SAA levels in 10 male patients with mild OSA were comparable with controls (P=0.46). Plasma SAA in 7 female patients with moderate to severe OSA was also markedly higher compared with matched control female subjects (24.1+/-2.4 versus 10.2+/-2.4 microg/mL, respectively; P=0.0013) but was not different from male patients with moderate to severe OSA (P=0.3). There was a significant positive correlation between SAA and apnea-hypopnea index (r=0.40, P=0.03). CONCLUSIONS: Plasma SAA levels are more than 2-fold greater in patients with moderate to severe OSA compared with subjects with mild OSA or healthy controls regardless of gender. Elevated SAA may contribute to any increased risk for cardiovascular and neuronal dysfunction in patients with OSA.

Enzyme-Linked Immunosorbent Assay↗

Sympathetic nerve activity in the congenital long-QT syndrome.

BACKGROUND: Patients with congenital long-QT syndrome (LQTS) are susceptible to life-threatening arrhythmias. The sympathetic nervous system may have an important triggering role for cardiovascular events in LQTS. We therefore examined measurements of sympathetic neural traffic in patients with LQTS and matched control subjects. METHODS AND RESULTS: Twelve patients with congenital LQTS and 12 healthy volunteers matched for age, sex, and body mass index were studied. Heart rate, respiration, blood pressure, and sympathetic nerve activity to the skeletal muscle blood vessels (muscle sympathetic nerve activity) and to the skin (skin sympathetic nerve activity) were monitored and recorded continuously. Resting heart rate (P=0.03), muscle sympathetic nerve activity burst rate (P=0.008), and burst incidence (P=0.02) were lower in patients with LQTS than in control subjects. However, skin sympathetic nerve activity was very similar in patients with LQTS and control subjects. Spectral analysis of RR variability showed a decreased low-frequency component, an increased high-frequency component, and a decrease in the ratio of the low-frequency component to the high-frequency component in patients with LQTS (P=0.01). CONCLUSIONS: LQTS is associated with a selective reduction in sympathetic drive to muscle blood vessels and perhaps also to the heart.

Adult↗

Sex-selective QT prolongation during rapid eye movement sleep.

BACKGROUND: We examined the effects of the various sleep stages on RR and QT intervals in healthy subjects and tested the hypothesis that there is a differential effect of sleep stage on QT interval in women compared with men. METHODS AND RESULTS: Eighteen healthy subjects (9 women, age 22 to 45 years) underwent polysomnography and simultaneous recording of ECG, blood pressure, and respiration. RR interval, RR variability, and QT values were measured in stable conditions (no abrupt changes of heart rate or blood pressure, stable breathing pattern) during inactive wakefulness during stages 2 and 3 to 4 of non-REM sleep and during REM sleep. The absolute QT interval was normalized for variations of RR (QTc). In men, RR interval and RR variability increased through all sleep stages. The QTc remained stable from wakefulness through all sleep stages. In women, however, RR interval increased only during non-REM and was virtually identical in wakefulness and in REM. RR variability remained very stable from wakefulness through all stages of sleep. Also, during REM in women, both absolute QT interval and QTc, regardless of the correction maneuver used, increased compared with wakefulness. CONCLUSIONS: The influence of sleep on RR, RR variability, and QTc is sex-dependent. We speculate that these differential sex effects on cardiac rate and repolarization may have important implications for sleep-selected cardiac arrhythmias in women.

Adult↗

Elevated C-reactive protein in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP). METHODS AND RESULTS: We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P<0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F=6.8, P=0.032). CONCLUSIONS: OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level.

Adult↗