Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men.

Various cardiac arrhythmias frequently occur in patients with sleep apnea, but complex analysis of the relationship between their severity and the probable arrhythmogenic risk factors is conflicting. The question is what cardiovascular risk factors and how strongly they are associated with the severity of cardiac arrhythmias in sleep apnea. Adult males (33 with and 16 without sleep apnea), matched for cardiovascular co-morbidity were studied by polysomnography with simultaneous ECG monitoring. Arrhythmia severity was evaluated for each subject by a special 7-degree scoring system. Laboratory, clinical, echocardiographic, carotid ultrasonographic, ambulatory blood pressure, and baroreflex sensitivity values were also assessed. Moderate sleep apnea patients had benign, but more exaggerated cardiac arrhythmias than control subjects (2.53 ± 2.49 vs. 1.13 ± 1.64 degrees of cumulative severity, p < 0.05). We confirmed strong correlations between the arrhythmia severity and known arrhythmogenic risk factors (left ventricular ejection fraction and dimensions, right ventricular diameter, baroreflex sensitivity, carotid intima-media thickness, age, previous myocardial infarction, and also apnea-hypopnea index). In multivariate modelling only the apnea-hypopnea index indicating the sleep apnea intensity remained highly significantly correlated with the cumulative arrhythmia severity (beta = 0.548, p < 0.005). In conclusion, sleep apnea modifying cardiovascular risk factors and structures or functions provoked various nocturnal arrhythmias. The proposed scoring system allowed a complex analysis of the contribution of various triggers to arrhythmogenesis and confirmed the apnea-hypopnea index as an independent risk for nocturnal cardiac arrhythmia severity in sleep apnea.

Carotid intima-media thickness in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Several large population-based cohort studies identified an association between reduced lung function and increased intima-media thickness (IMT). Nevertheless, a vast majority of subjects in these studies did not suffer from COPD and thus it remains unclear whether IMT differs among various stages of COPD severity. The aim of the present pilot study was to evaluate IMT in central European patients with moderate, severe and very severe COPD. METHODS: In forty-nine patients (34 men, 15 women; mean age 66.1 +/- 10.9 years) with COPD, the combined thickness of intima and media layers of the common carotid arteries was measured using B-mode ultrasound imaging. RESULTS: Increased cardiovascular disease risk as evidenced by carotid IMT values greater or equal to 75th percentile were present in 14 (28.6%), whereas IMT hypertrophy (IMT values greater or equal 0.80 mm) was present in 24 (49.0%) of patients. Average IMT in the entire cohort was 0.85 +/- 0.21 mm, with no significant differences from stage II to stages III and IV of COPD. CONCLUSION: Present results indicate a high prevalence of IMT hypertrophy and increased cardiovascular disease risk as assessed by carotid ultrasonography in COPD patients with a broad spectrum of airway obstruction severity. The lack of differences in carotid IMT between various stages of lung impairment severity suggests that atherosclerosis starts early in the course of COPD. Therefore, the need to screen patients for the presence of concomitant atherosclerosis in early stages of COPD severity may be warranted (Tab. 2, Ref. 33).

Severe nocturnal cardiac arrhythmias caused by sleep apnea-induced hypoxemia in males.

Nocturnal cardiac arrhythmias (NCA) were analyzed in patients with sleep apnea/hypopnea syndrome (SAHS) and controls. Occurrence and severity of NCA were compared in 33 SAHS patients and 16 control subjects, matched for cardiovascular risk factors. Continuous overnight polysomnography provided ECG, respiratory and sleep parameters for a comparative analysis. Various types and severity of NCA were detected already in moderate SAHS (apnea/hypopnea index = 26 ±15.6/h), reflecting the respiratory and atherosclerotic changes. Moderately severe arrhythmias, represented with benign and 2 complex types were caused by hypoxemia characterized by AHI, minimal SaO2, and lower values after desaturation. Three-time higher prevalence of complex arrhythmias in SAHS patients was not significantly different by usual statistical comparison, likely due to a low number of controls and a joint occurrence of various types and complex severity of arrhythmias in some patients. Therefore, a complex assessment of different types and varying severity of arrhythmias would require a scale specifically constructed for their evaluation.

[Traditional risk factors of atherosclerosis in patients with obstructive sleep apnoe-hypopnoe syndrome]. / Tradicné rizikové faktory aterosklerózy u pacientov so syndrómom obstrukcného spánkového apnoe-hypopnoe.

UNLABELLED: Cardiovascular morbidity and mortality of patients with obstructive sleep apnoe-hypopnoe syndrome (OSAHS) is higher than in matched population. The aim of the study was to analyse, whether high prevalence of risk factors of atherosclerosis in patients with OSAHS can explaine their higher cardiovascular morbidity. METHODS: 2 groups of 33 males with moderate OSAHS and 16 males without OSAHS were subdivided into subgroups of apparently healthy subjects, hypertonics and patients with coronary artery disease. We compared the presence of traditional risk factors of atherosclerosis (age, hyperlipoproteinaemia, diabetes mellitus, arterial hypertension, obesity, smoking habit, obesity, family history), compensation of metabolic risk factors, morphometry of the heart, haemodynamic parameters, markers of atherosclerosis, microalbuminuria and some respiratory parameters. RESULTS: Patients with/without OSAHS had a comparable risk profile at all grades of cardiovascular pathology, they differed only in respiratory parameters (characteristic for OSAHS). Moreover, OSAHS patients without cardiovascular diseases vs. matched non OSAHS subjects had higher thickness of posterior wall of the left ventricule (9.73 +/- 1.17 vs 8.29 +/- 1.38 mm, p < 0.04), intima-media thickness of carotid artery (0.83 +/- 0.14 vs 0.63 +/- 0.08 mm, p < 0.001) and OSAHS patients with hypertension vs non OSAHS hypertonics presented higher dimension of right ventricule (28.4 +/- 2.7 vs 26.25 +/- 0.96 mm, p < 0.02), and left ventricule (47.6 +/- 3.3 vs 43.75 +/- 0.96 mm, p < 0.01). CONCLUSION: Patients with OSAHS had severe atherosclerosis and worse morphological alteration of the heart compared to subjects without OSAHS. According to comparable presence and possibility of sufficient control of risk factors, OSAHS can be considered to be a risk factor for cardiovascular diseases. However, this statement has to be further confirmed in prospective studies.

Sleep apnoea inducing hypoxemia is associated with early signs of carotid atherosclerosis in males.

The intima-media thickness (IMT) of carotid arteries as a marker of preclinical atherosclerosis was measured by ultrasonography in 49 subjects to determine, how strongly the obstructive sleep apnoea (OSA) syndrome is associated with atherosclerosis. Maximal IMT was higher in patients with cardiovascular diseases and with or without risk factors of atherosclerosis, presenting also OSA (apnoea-hypopnoea index=26.1+/-15.6/h) compared to controls without OSA (0.91+/-0.21 mm versus 0.77+/-0.18 mm, p<0.05). The prevalence of IMT > or = 0.85 mm was also higher in patients with cardiovascular pathology presenting OSA than without it (p<0.05). IMT(max) was increased in subjects with mild to moderate OSA alone (AHI=20.4+/-8.7/h) versus healthy controls (0.83+/-0.14 mm versus 0.63+/-0.08 mm, p<0.01). Regression analysis revealed a correlation of IMT(max) with the frequency, intensity and duration of intermittent hypoxemia reflected by AHI (p<0.01), minimal oxygen saturation (p<0.01) and time spent with Sa(O2) < 90% (p<0.05) in patients presenting OSA. The results indicate clear association between early signs of carotid atherosclerosis and moderate OSA in males with and without concomitant cardiovascular pathology.

[Nocturnal cardiac dysrhythmias associated with obstructive sleep apnea]. / Výskyt nocných kardiálnych dysrytmií v súvislosti s obstrukcným spánkovým apnoe.

The occurrence of cardiac dysrhythmias have been analysed in 16 adult patients suffering from obstructive sleep apnea syndrome of various severity randomly selected from more than 300 persons examined in our sleep laboratory from 1996 with a complex polysomnography Alice 3 (Healthdyne). The number of apneic episodes emerging in the first, second and third part of sleep was practically the same although their duration prolonged during the night culminating with an average of 25 sec (p < 0.02). OSA episodes caused a decrease of oxyhaemoglobin saturation to lower values during REM compared to NREM sleep (76.1% versus 81.7%, p < 0.05). Cardiac dysrhythmias occurred more frequently during and immediately after, than before OSA episodes demonstrating their causal relations.

Carotid intima-media thickness in type 2 diabetes is more strongly related to serum apoprotein A-I in females.

BACKGROUND: Dyslipidemia in type 2 diabetes has been shown to be related to the incidence of macrovascular events. Increased carotid intima-media thickness is considered to be a marker of macrovascular disease. MAIN PURPOSE: To investigate a possible relationship between lipoprotein levels and carotid intima-media thickness as a marker of early atherosclerosis in patients with type 2 diabetes. METHODS: Seventy-one consecutively selected eligible patients (31 males, 40 females) with type 2 diabetes were studied. Common carotid intima-media thickness was measured bilaterally by high-resolution ultrasound and the mean value from both sides was used for further analysis. Fasting blood samples were taken from each individual and their serum was analyzed for lipoprotein levels. RESULTS: In the entire group of patients, intima-media thickness was inversely related to apoprotein A-I (r = -0.33, p = 0.008) and HDL cholesterol (r = -0.23, p = 0.059) in univariate correlation analysis, and a positive correlation between intima-media thickness and apoprotein B/apoprotein A-I ratio was found (r = 0.33, p = 0.007). When genders were analyzed separately, intima-media thickness was significantly correlated with apoprotein A-I and apoprotein B/apoprotein A-I ratio in females, while no significant correlation of any lipid variable with intima-media thickness was observed in males. In multiple linear regression analysis, age (p = 0.005), male gender (p = 0.002) and apoprotein A-I (p = 0.035) were the only risk factors in the entire group of diabetic patients, which significantly predicted carotid intima-media thickness in models adjusted for demographic and other known risk factors. As was the case in the univariate analysis, no risk factor significantly predicted carotid intima-media thickness in males while age, apoprotein A-I and B significantly predicted intima-media thickness in females. CONCLUSIONS: In the present study, low serum apoprotein A-I, a major protein component of HDL, was found to be related to increased carotid intima-media thickness. This relationship was stronger in females than in males, which suggests possible gender differences in the relationship between apoprotein A-1 and early atherosclerotic lesions in subjects with type 2 diabetes mellitus.

[Mechanisms in the development of cardiovascular complications in obstructive sleep apnea]. / Mechanizmy rozvoja kardiovaskulárnych následkov obstrukcného spánkového apnoe.

Obstructive sleep apnoea may be accompanied by various cardiovascular consequences resulting from alteration of the activity of the autonomous nervous system. These changes are mediated by: a--hypoxemia developing during the apnoea, b--severe hypoxemia, hypercapnia and acidosis in postapnoea, c--powerful but ineffective ventilatory efforts causing arousal and stimulation of the cardioexcitatory and vasomotor centres. There are four main pathogenetic mechanisms implementing the cardiovascular changes: 1--Functional alteration in the conduction system and the myocardium resulting in nocturnal cardiac dysrhythmias. 2--Vasoconstriction manifesting as angina pectoris, myocardial infarction, brain attacks and pulmonary or systemic hypertension. 3--Pulmonary congestion leading to cardiac or bronchial asthma or even lung oedema. 4--Neuroendocrine activation, including the sympathetic nervous system, renin-angiotensin-aldosterone system, atrial natriuretic peptide and erythropoietin, which may result in nycturia, nocturnal hypotension and diurnal hypertension.

[Interesting cases of ventilatory therapy of sleep apnea in a group of our patients]. / Niektoré zaujímavé prípady ventilacnej liecby spánkového apnoe zo súboru nasich pacientov.

UNLABELLED: In the group of patients investigated in our sleep laboratory and successfully treated by positive pressure applied in to the upper airways through nasal mask (nCPAP) some interesting cases appeared. These cases show beneficial effect of nCPAP therapy, unfortunately not widely spread and recognized in our country. These patients were unsuccessfully treated before by conventional methods, which did not improve their situation for a longer time. Only after polysomnography carried out in our sleep laboratory and after home treatment with nCPAP or BiPAP machine, the situation radically improved. FIRST CASE: In a director of important enterprise after unrelated car accident atrial fibrillation caused by dilation was discovered, which did not respond even on Electro cardioversion. After recognition of severe obstructive sleep apnoea syndrome (OSAS) this patient was treated successfully by BiPAP. The second case: a bus driver, who falls asleep on the traffic light with full buss of passengers. A diagnose OSAS with a multiple sleep latency test result below 2.5 minutes. The nCPAP treatment allowed him to continue to work, but transiently on different position. The third: 40-year-old patient with a body mass index (BMI) 38 and with dysrhythmias IIIb-IVb according to Lown. The respiratory disturbance index (RDI) was 40 and oxygen desaturation bellow 77%. There was bigeminia on ECG. During four hour with nCPAP treatment there was only two randomly ventricular extrasystols appeared, confirming the beneficial effect of treatment. These cases demonstrate a wide spectrum of cardiac dysrhythmias, which have only functional character, but are important for the practice. The demonstrated cases highlighted the importance of home nCPAP therapy in OSAS patients.

Interaction of sleep apnoea syndrome with various diseases.

Sleep disordered breathing (SDB), particularly their clinically most serious and at the same time common form-sleep apnoea syndrome-caused by structural or functional abnormalities in the area of upper airways, are frequently linked with other diseases. The accompanying respiratory, cardiovascular, neuropsychic, sympathoadrenal and endocrine-metabolic disorders and their variable intensity determine the character and severity of patients complaints. The coincidence of SDB with alteration in one or another system produces mutual potentiation of their negative effects appearing as serious, not rarely even life threatening acute complications or chronic consequences manifesting exactly in the area of the afflicted system. The paper illustrates on several examples the development of pathological signs of SDB concerning practically all medical branches and at the same time demonstrating the multidisciplinary character of sleep medicine. (Fig. 1, Ref. 27.)

[Obstructive sleep apnea as a cause of dysrhythmia in sudden cardiac death]. / Obstrukcné spánkové apnoe ako prícina dysrytmií a náhlej srdcovej smrti.

BACKGROUND: Sleep apnoea is often accompanied by severe disturbances in heart rate and cardiac rhythm. SUBJECTS AND METHODS: Various respiratory parameters were continuously recorded 6-9 hours during sleep in ten patients with sleep apnoea syndrome, paralley with direct ECG recording (8 cases) or Holter monitoring (2 cases). The rate, development and reversibility of various dysrrhythmias were evaluated. RESULTS: Obstructive, central and mixed sleep apnoeas (OSA, CSA, MSA) and hypopnoea occurred in each patient (52.5%, 3.5%, 10% and 34%, respectively). Lighter dysrrhythmias (sinus arrest, atrioventricular block and occasional supraventricular premature contractions) were in patients with frequent CSA, whereas the most severe ones (higher degrees of AVCB, premature ventricular contractions and tachyarrhythmias) occurred during OSA. Stronger hypoxaemia and myocardial acidosis, as well as severe alteration in sympathetic and vagal tone probably contributed to the development of life-threatening brady- and tachyarrhythmias in OSA, based on alteration in effective refractory period and reentry phenomenon. CONCLUSION: Dysrrhythmias often occur during OSA and they may result in acute cardiovascular complications. Due to their functional character and reversibility, the development of nocturnal dysrrhythmias can be prevented by early diagnosis and effective treatment of sleep related breathing disorders, which at the same time decreases, the risk of both cardiovascular complications and diseases.

[Use of urinary furazolidone determination in calves in laboratory diagnosis]. / Vyuzitie stanovenia furazolidonu v moci teliat pri laboratórnej diagnostike.

We examined 41 samples of calf urine in order to determine the urinary furazolidone excretion. 26 calves were administered furazolidone in the form of Terapeutan T in a therapeutic dose of 5 kg per os individually, which represents approx. 3 mg of furazolidone per kg body weight per day over 5 days. 11 calves were administered with twice the therapeutic dose, i.e. 6 mg furazolidone per kg live body weight over the same 5 days. A triple strength dose was administered to two calves on the 2nd and 3rd days and after administration we observed the furazolidone excretion in urine. The dynamics of furazolidone excretion in urine of one calf we determined even after the fivefold dose in comparison with the therapeutic dose, administered in the course of 2 days after application of the double dose, which was administered over 4 days. During administration of 3 mg and 6 mg furazolidone respectively per kg of live weight per kg furazolidone was excreted in urine minimally and only rarely (7.6%). During administration of higher doses furazolidone was found in the urine of all individuals. The highest urinary concentration of furazolidone in calves was determined after administration of the fivefold dose in comparison with the therapeutic dose, i.e. 15 mg furazolidone per kg live weight in the 4th hour after urine collection (23.0 mg furazolidone per liter urine). When this dose was administered over 2 days, it did not effect any clinical symptoms of disease. It has proved to be well founded to determine the furazolidone level in calf urine in laboratory diagnostics. The examination contributes to the estimation of the furazolidone dose, administered to calves. Urinary furazolidone concentrations greater than 1.0 mg.l-1 provide warning signals of overdosage with this chemotherapeutic. For urine furazolidone determination we utilized the photometric method, described by Herret and Buzard (1960).

[Determination of delta aminolevulinic acid in the urine of cows in acute mass lead poisoning]. / Vyuzitie stanovenia kyseliny delta amínolevulovej v moci kráv pri akútnej hromadnej otrave olovom.

The concentration of delta aminolevulinic acid (ALA) in the urine of dead heifers (n = 3), diseased cows (n = 13) and clinically healthy cows (n = 29) was determined in the course of acute mass intoxication with lead. At the same time, the content of lead was determined in kidney, liver, in rumen contents of dead heifers and in the beet pulp fed to the animals. The ALA concentrations were converted to values per uniform specific weight of urine and per gram of creatinine secreted with urine. As found, the determination of ALA concentration per gram of creatinine is diagnostically insignificant in the case of lead poisoning. The average ALA values in the urine of the dead and clinically diseased cows (221.0, 119.9 and 72.3 mumol per litre) markedly differed from the average values of ALA concentrations in the urine of the clinically healthy animals (41.2, 32.8 and 25.6 mumol per litre). Owing to the wide variability of the determined ALA concentration in urine it appeared useful in cases of suspicion of lead poisoning of cattle to determine ALA concentration in the urine of the group of clinically diseased animals and in the group of clinically healthy animals in order to compare ALA secretion with urine in the two groups. A 2.9-fold average increase of ALA in the urine of clinically diseased animals, compared with the ALA values in the urine of clinically healthy animals, already testifies to lead intoxication.

[Urinary delta-aminolevulinic acid levels in dairy cows during lead loading from feed rations under normal conditions of rearing in the Western Slovakia Region]. / Koncentrácie kyseliny delta-aminolevulovej v moci dojníc pri zátazi olovom z krmnych dávok v bezných podmienkach chovov Západoslovenského kraja.

The concentration of delta-amino levulinic acid (ALA) was determined in the urine of clinically healthy cows of 14 herds in the West-Slovakian region. The content of lead was determined at the same time in the components of feed rations. The ALA concentration values were converted to values per uniform specific weight of urine and per gram of secreted creatinine to match literary sources where the ALA concentration is given in these two quantities. The approximate intake of lead by the animal bodies in milligrams per head/day and per kg of live weight was calculated from lead content in feed rations. The average ALA concentration in the urine of dairy cows was 42.7 +/- 20.2 mu mol per 1 of urine (36.8 +/- 18.7 mu mol per g of creatinine), the average lead intake from feed being 0.157 mg per kg of live weight. The ALA concentrations in urine refer to animals given normal feeds with no lead contamination and as such can be considered as physiological values. Statistically significant correlations were recorded between ALA concentrations per litre of urine at the uniform specific weight of 1030 g per litre and the values converted per gram of secreted creatinine (r = 0.789). The upper biological tolerance limit of ALA concentration in urine (105.0 mu mol per litre) was determined by mathematico-statistical methods. Values above this limit could be indicative of an increased lead stress of the cows' bodies.

[Relation between the concentration of sodium and potassium in the erythrocytes of dairy cows and the concentration of these elements in the plasma and urine and the level of blood glucose]. / Vztah koncentrácie sodíka a draslíka v erytrocytoch dojníc ku koncentrácii týchto prvkov v plazme a moci a glukózy v krvi.

Blood and urine samples of 180 dairy cows from 12 herds were examined. Sodium and potassium concentrations were determined in erythrocytes, whole blood, plasma, urine, and glucose concentration in blood: the interrelations were compared. Sodium and potassium concentrations in erythrocytes were 85.15 +/- 11.45 mmol/l, and 25.93 +/- 7.81 mmol/l, respectively. A statistically significant relation was found between sodium and potassium concentrations in erythrocytes (r = 0.3467+++) and the content of electrolyte in blood cells and in whole blood (Na: r = 0.5336+++; K: r = 0.3561+++). No statistically significant relation of intraerythrocyte concentration of both electrolytes was confirmed with respect to the other characteristics (sodium and potassium concentrations in plasma and urine, and glucose concentration in blood). In the conditions of routine laboratory diagnostics in clinically healthy cows, determinations of intraerythrocyte sodium and potassium do not broaden possibilities of evaluating the metabolic state of these electrolytes and cannot be used as the characteristics of energy insufficiency. The cannot replace the analyses performed in serum and urine.

[Dynamics and diagnostic use of ALP activity in the blood of cattle exposed to a temperature of 56 degrees C]. / Dynamika a diagnostické vyuzitie aktivity ALP v sére hovädzieho dobytka pri pôsobení teploty 56 stupnu C.

Possibilities of the diagnostic utilization of determined thermostable portion of the ALP activity in bovine serum were studied. The work is based on the finding that the total ALP activity is formed by two fractions with different sensitivity to the temperature of 56 degrees C. Dynamics of the loss of ALP activity during serum heating was of an equal character in all four tested groups. The loss was always highest during the first minutes of heating, after 15 to 20 minutes it became equal. A period of 15 minutes of the serum heating is sufficient for obtaining information on the size of the ALP thermostable fraction. The ALP activity and its residue after 15-minute thermal inhibition (thermostable portion) were tested in the sera of 163 head of cattle divided into seven groups. The size of this residue was related to the age of animals, degree of gravidity did not affect the residue. The thermostable portion in 6 to 10 months old bullocks was 14.86 +/- 4.93%, in 2.5 to 5 years old heifers 41.20 +/- 20.37% and in clinically healthy dairy cows 54.35 +/- 18.26%. In a group of calved breeding cows 44.13 +/- 19.74% of the initial activity remained. Determination of the thermostable ALP fraction can be applied with certain limitation in pre-clinical diagnostics of disorders of mineral metabolism in bones of cattle. In herds of healthy dairy cows the value of thermostable portion should not be lower than 45% of the original ALP activity. In 2.5 to 3 years old heifers this level is considered to be 35%.

[The usefulness of determining urea levels and the acidity of milk for evaluating protein nutrition in cows]. / Vhodnost stanovenia mocoviny a kyslosti mlieka na posúdenie proteínovej výzivy dojníc.

Samples of blood, urine and milk were examined in 94 clinically healthy cows of 10 herds. The average milk samples and the feed ration used in these herds were also examined. The determination of urea concentration and milk acidity was evaluated as to its suitability for the assessment of the protein-glycide ratio and acid-base activity of feed ration. The determination of urea content in an average milk sample was found to be an expeditious procedure. The results of this examination can be used for the evaluation of the protein supply to cows with the same reliability as the determination of serum urea. The passage of urea from serum to milk was proportional. The correlation coefficient for the relation of both parameters was statistically highly significant (r = 0.940). According to the calculated equation of regression line (f2 = 0.734 + 0.669 X f1), the values from 2.94 to 4.10 mmol/l are approximately adequate to the reference range of serum urea from 3.30 to 5.00 mmol/l in milk used in Czechoslovakia. The acidity of milk was found to have a low sensitivity for being used with success for the determination of the acid-base activity of feed ration. The examination of the net acid-base urinary output cannot be replaced by the determination of milk acidity.