Sympathoadrenal system under conditions of increased left and right ventricular afterload

Adrenergic plexuses in the myocardium and adrenal medulla were studied histochemically under conditions of increased left or right ventricular afterload. Under conditions of high afterload not accompanied by heart failure the density of sympathetic myocardial innervation remained unchanged in the loaded ventricle, but increased in the intact ventricle. Comparison of the state of the sympathoadrenal system under conditions of increased afterload complicated or uncomplicated by heart failure revealed common prognostically unfavorable changes: sharp decrease in the density of adrenergic nerve plexuses in the ventricular myocardium and activation of adrenal chromaffin cells.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 11, pp. 597–600, November, 2004     

Intrathoracic pressure changes and cardiovascular effects induced by nCPAP and nBiPAP in sleep apnoea patients

SUMMARY  The effect of nasal continuous positive airway pressure (nCPAP) and nasal bi-level positive airway pressure (nBiPAP) on intrathoracic pressure and haemodynamics during wakefulness was studied in a group of nine patients with severe sleep apnoea. No patient took cardiovascular medication.
Patients were studied with a Swan Ganz catheter, an arterial line and an oesophageal balloon. nCPAP and nBiPAP were applied in the following pressure sequence: 5, 10 and 15 cm H₂O of CPAP and 10/5 and 15/10 cm H₂O of nBiPAP. Measurements were made at the end of a 5-min period at each pressure level. Intrathoracic pressure was noted to increase to a level of approximately 50% of the pressure delivered at the mask. At a CPAP of 10 cm H₂O and above, as well as at BiPAP of 10/5 or higher, there was a decrease in cardiac output (CO) and cardiac index (CI). CI fell below the normal value in two of the patients. Transmural pulmonary artery pressure (PPA_tm) decreased at a CPAP of 15 cm H₂O and at both BiPAP levels. Transmural right atrial pressure (PRA_tm) decreased at both BiPAP levels. There were no differences in CO, CI, PPA_tm and PRA_tm between nCPAP and nBiPAP at equal inspiratory pressures. SaO₂ increased during BiPAP 15/10 cm H₂O, whereas heart rate and arterial blood pressure did not change significantly. The data presented here are consistent with the literature on positive end-expiratory pressure (PEEP) applied via intratracheal tube and are likely to be due to a reduced venous return. It is concluded that nasally applied positive pressure may have acute negative effects on cardiac function in patients with sleep apnoea.     

Comparative pathomorphological study of contractile myocardium under conditions of increased left and right ventricular afterload

Structural changes in the myocardium under conditions of increased left and right ventricular afterload were studied using polarization microscopy and histological, histochemical, and stereological methods. Increased afterload not complicated by heart failure was characterized by low number of damaged cardiomyocytes (3.3–6.5%) and moderate structural changes in the ventricular myocardium (contractures of different severity). Increased afterload complicated by heart failure was characterized by high ratio of damaged cardiomyocytes (5.6–19.2%) and severe reversible (grade I and II contractures) and irreversible (grade III contractures and lump degradation of myofibrils) structural changes. Irreversible damage to most cardiomyocytes included plasmatic impregnation, which was most pronounced in the sub-endocardial layer of ventricles operating under conditions of increased afterload. Comparative study showed that increased left and right ventricular afterload induces similar pathomorphological changes in the contractile myocardium. Our results indicate that increased afterload to the right or left ventricle is accompanied by the development of stereotypical structural changes in the myocardium. Profound and severe disturbances can cause heart failure.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 12, pp. 693–697, December, 2004This revised version was published online in April 2005 with a corrected cover date.     

Effect of hypertension on upper airway function and sleep apnoea

SUMMARY  Current evidence suggests that elevations in blood pressure during obstructive apnoeic episodes increase pharyngeal collapsibility and the severity of obstructive sleep apnoea.     

The effect of clustered versus regular sleep fragmentation on daytime function

Previously, we found that regular sleep fragmentation, similar to that found in patients with sleep apnoea/hypopnoea syndrome (SAHS), impairs daytime function. Apnoeas and hypopnoeas occur in groups in patients with REM or posture related SAHS. Thus, we hypothesised that clustered sleep fragmentation would have a similar impact on daytime function as regular sleep fragmentation. We studied 16 subjects over two pairs of 2 nights and 2 days. The first night of each pair was for acclimatisation. On the second night, subjects either had their sleep fragmented regularly every 90 s, or fragmented every 30 s for 30 min every 90 min, the remaining 60 min being undisturbed. We fragmented sleep with tones to produce a minimum 3 s increase in EEG frequency. During the days following each pair of nights we tested subjects daytime function. Total sleep time (TST) and microarousal frequency were similar no both study nights. We found significantly less stage 2 (55 SD 4, 62 +/- 7%; P = 0.001) and more slow wave sleep (21 SD 3, 12 +/- 6%; P < 0.001) on the clustered night. Mean sleep onset latency was similar on MSLT (clustered 10 SD 5, regular 9 +/- 4 min; P = 0.7) and MWT (clustered 32 SD 7, regular 30 +/- 7 min; P = 0.2). There was no difference in subjects mood or cognitive function after either study night. These results suggest that although there is more slow wave sleep (SWS) on the clustered night, similar numbers of sleep fragmenting events produced similar daytime function whether the events were evenly spaced or clustered.     

Pathomorphology of myocardial circulation: Comparative study in increased left or right ventricle afterload

Comparative study of pathomorphology of myocardial circulation under conditions of increased afterload of the left or right ventricles showed similar changes. All compartments of the coronary bed were plethoric, capillary blood stasis and perivascular edema, more pronounced in arterial vessels, were detected in both cases. These changes equally involved both ventricles and the ventricular septum. Significant differences consisted in local increase in the density of functioning capillaries. The increase was the maximum in hemodynamically overloaded ventricle and ventricular septum, presumably due to increase of their contractile activity. The density of functioning capillaries in the intact (vs. pressure overloaded) ventricle also increased, but to a lesser degree, which could be due to systemic neurohumoral effects. If increased afterload was complicated by the development of heart failure, circulatory disorders in the myocardium progressed. Significant increase in the density of functioning capillaries in all cardiac compartments indicated decreased vascular tone and exhaustion of coronary reserve. This was paralleled by a sharp arterial plethora in case of increased afterload of the left ventricle and sharp blood stasis in the microcirculatory bed in case of increased right ventricle afterload. Reduction of effective perfusion pressure in the presence of coronary dystonia can cause coronary insufficiency and myocardial ischemia in case of increased right ventricle afterload. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 352–356, March, 2008     

Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea

Treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (NCPAP) has become a standard treatment since its introduction in 1981. Following such treatment the apnoeas disappear, sleep quality improves as apparently do daytime symptoms of sleepiness. Sleepiness is an unusual symptom and its impact on conventional indices of quality of life has rarely been measured. To allow comparison of NCPAP therapy with treatments for other conditions, measurements of quality of life before and after treatment using standard techniques are required. It is not clear which of the standard measures is most suited to measuring the health gain from nasal NCPAP, and indeed whether the disability of excessive sleepiness is included in all such measures. This study looks at three well recognized quality of life measures in OSA, before and after NCPAP therapy; the Short Form 36 (SF-36), Functional Limitations Profile (FLP), and the EuroQol (EQ-5D). The results were compared with data from normal populations. One hundred and eight patients with OSA undergoing a therapeutic assessment of NCPAP completed the three quality of life questionnaires before and 5 weeks after commencing treatment. Over 90 subjects completed all sections of the three measures on both occasions. The SF-36 revealed substantial adverse effects on subjective health of OSA and that NCPAP treatment produced dramatic positive effects. For example, the effect sizes (difference in score, divided by SD of baseline score) in the Energy/Vitality dimension was 0.98 and for the overall Mental and Physical Component Scores, 0.76 and 0.57, respectively: an effect size over 0.5 is considered moderate and over 0.8 as large. The FLP data showed similar pre treatment decrements in quality of life and substantial improvements following NCPAP. The changes with treatment in the majority of the dimensions from both the SF-36 and FLP were statistically significant (P<0.01). In contrast the EQ-5D did not show significant improvements with therapy, presumably because of its failure to measure the aspects of quality of life related to severe sleep fragmentation and daytime sleepiness. In conclusion, this study has clearly shown considerable decrements in quality of life in patients with OSA, similar to other chronic disabling conditions. Furthermore, NCPAP therapy returns patients to a quality of life similar to the normal population.     

Effect of nasal CPAP treatment on plasma volume, aldosterone and 24-h blood pressure in obstructive sleep apnoea

Polycythaemia, peripheral oedema formation and hypertension have classically been described in association with obstructive sleep apnoea (OSA). However, there is very limited information about blood volume in OSA and how it changes during long-term treatment with nasal continuous positive airway pressure (nCPAP). Plasma (PV) and red-cell volumes (RCV), 24-h ambulatory blood pressure (BP), 24-h natriuresis and morning plasma aldosterone, renin activity and atrial natriuretic peptide in 11 men with a mean age of 47 y (range 37–55), apnoea index (AI) of 55 (22–106), body mass index of 36 (30–43) and seated BP of ≥140/90 mmHg without any medication were measured. BP-measurements were repeated after 3 weeks and all measurements after 3 mo of nCPAP treatment. Aldosterone and 24-h mean heart rates decreased during treatment. Twenty-four-h BP decreased after 3 weeks but that decrease did not persist after 3 mo of treatment. There was a relationship between changes in night-time mean BP and PV and aldosterone. The haematocrit declined in every patient. No significant changes were found in the mean PV or RCV. They were in all instances lower than has earlier been described for normal, non-obese subjects. These data also suggest that OSA causes divergent individual disturbances in blood volume homeostasis which can be corrected by nCPAP.     

主动脉出口血压对左心室血流特性的影响

采用Mimics对心脏进行三维重构,用3-matic进行模型优化以及模型误差分析,对左心室室壁运动做速度分布假设,基于UDF宏文件对左心室室壁运动编写程序,将血液视为非牛顿流体,采用动网格技术研究不同血压对左心室血液流动的影响。模拟发现当左心室收缩时,压力梯度明显,内部压力减小。当左心室舒张时,内部压力逐渐增高。二尖瓣口处的速率先增大后减小。血压升高,左心室内剪切应力持续增大,极易破坏红细胞结构,产生溶血现象,导致心脏功能紊乱。     

The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease and sympathetic activation. However, it is unclear whether this association is independent of obesity and to what extent treatment with nasal continuous positive airway pressure (CPAP) alleviates the vascular inflammation that underpins cardiovascular disease. We therefore evaluated whether short-term withdrawal from CPAP therapy in subjects with moderate-severe OSA would result in increased levels of sympathetic activity and circulating inflammatory cytokines independent of weight. Vascular inflammatory markers (hsCRP, hsIL-6 and hsTNF-alpha) were assessed in 20 subjects after one and seven nights of withdrawal from CPAP together with the hypoxia-responsive angiogenic marker VEGF and urinary catecholamines. Compared with baseline on CPAP, withdrawal from therapy resulted in an immediate return of OSA with an increase in RDI to 26.7 +/- 5.2 and 39.0 +/- 5.9 events per hour after one and seven nights without CPAP, respectively (both P < 0.0001). This was accompanied by a concomitant rise in daytime urinary noradrenaline (P < 0.0001) after seven nights CPAP withdrawal that was positively associated with the severity of hypoxaemia. In contrast, withdrawal from CPAP therapy was not accompanied by any change in measured cytokines or VEGF (all P > 0.1). In conclusion, 1 week of CPAP withdrawal was associated with a return of OSA and a marked increase in sympathetic activity without a concomitant elevation of vascular inflammatory markers.     

Specific function and morphology of the right ventricle of the heart during ischemic injury of the left ventricle

Focal ischemia of the left ventricular myocardium was modeled by surgical ligation of the descending branch of the left coronary artery at the junction of the lower and middle thirds of this artery in anesthetized rabbits. Contractility and morphological characteristics of the right ventricular myocardium were evaluated 24, 72, and 120 h after treatment. Significant morphofunctional changes in the right ventricle manifested in the development of severe extracellular edema and increase in the area of damaged and destroyed myofibrils. However, the actual and maximum intraventricular pressure remained unchanged under these conditions. The degree of cardiomyocyte apoptosis increased on day 1, but returned to normal in the follow-up period. Our study demonstrated high sensitivity of the right ventricle to left ventricular dysfunction and early activation of compensatory mechanisms. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 392–394, April, 2008     

Effects of continuous positive airway pressure treatment on glycaemic control and insulin sensitivity in patients with obstructive sleep apnoea and type 2 diabetes: a meta-analysis

Introduction

Obstructive sleep apnoea (OSA) is a prevalent disorder characterised by repetitive upper-airway obstruction during sleep, and it is associated with type 2 diabetes. Continuous positive airway pressure (CPAP) is the primary treatment for OSA. Prior studies investigating whether CPAP can improve insulin resistance or glucose control in OSA patients have resulted in conflicting findings. This meta-analysis investigated whether CPAP treatment could improve glucose metabolism and insulin resistance in patients with OSA and type 2 diabetes.

Material and methods

We performed a systematic literature search using Medline, Cochrane, EMBASE, and Google Scholar databases for randomised controlled prospective studies that investigated the effect of CPAP on glycaemic control or insulin sensitivity in subjects with type 2 diabetes.

Results

The combined standard (STD) paired difference in mean change in the levels of glycated haemoglobin (HbA_1c) was –0.073% (standard error (SE): 0.126), indicating that CPAP treatment did not alter HbA_1c levels. The combined STD paired difference in mean change of insulin sensitivity was observed as 0.552 µmol/kg • min (SE = 0.196) and indicated insulin sensitivity significantly increased with CPAP treatment (p = 0.005).

Conclusions

We found that the CPAP treatment did not alter HbA_1c levels but did significantly improve insulin resistance, indicating treating OSA can positively impact the symptoms of type 2 diabetes.     

Congestive heart failure and sleep apnoea—possible mechanisms and effect of CPAP therapy

SUMMARY  Sleep-disordered breathing has been associated with increased cardiovascular morbidity and mortality. However, despite several plausible mechanisms whereby obstructive sleep apnoea might be associated with left ventricular dysfunction and congestive heart failure, only limited data exist linking those disorders. These studies are reviewed along with possible mechanisms leading to left ventricular dysfunction in obstructive sleep apnoea. Recent investigations demonstrating improvement in left ventricular function after CPAP therapy in patients with congestive heart failure are reviewed as well. Finally, new data are presented from an animal model of congestive heart failure demonstrating a beneficial effect of CPAP on cardiac index in association with a decline in systematic vascular resistance. Remarkably, these effects persisted even after CPAP was removed. Possible mechanisms whereby CPAP may lead to improvement in cardiac output are discussed.     

Effects of continuous positive airway pressure on blood pressure in obstructive sleep apnea patients: The Apnea Positive Pressure Long‐term Efficacy Study (APPLES)

Obstructive sleep apnea is associated with hypertension, and short‐term studies have demonstrated a modest reduction in blood pressure with continuous positive airway pressure therapy. We evaluated the effects of continuous positive airway pressure versus sham continuous positive airway pressure on blood pressure in 1,101 participants with obstructive sleep apnea from the Apnea Positive Pressure Long‐term Efficacy Study, a randomized, sham‐controlled double‐blinded study designed to assess the impact of continuous positive airway pressure on neurocognition. Participants with apnea?hypopnea index ≥ 10 were randomly assigned to continuous positive airway pressure or sham continuous positive airway pressure. Blood pressures measured in the morning and evening at baseline, 2 months and 6 months were analysed post hoc using a mixed‐model repeated‐measures analysis of variance. The largest magnitude reduction was approximately 2.4 mmHg in morning systolic pressure that occurred at 2 months in the continuous positive airway pressure arm as compared with an approximate 0.5 mmHg reduction in the sham group (continuous positive airway pressure effect ?1.9 mmHg, p = .008). At 6 months, the difference between groups was diminished and no longer statistically significant (continuous positive airway pressure effect ?0.9 mmHg, p = .12). Sensitivity analysis with use of multiple imputation approaches to account for missing data did not change the results. Treatment with continuous positive airway pressure for obstructive sleep apnea reduces morning but not evening blood pressure in a population with well‐controlled blood pressure. The effect was greater after 2 than after 6 months of treatment.     

Evolution of upper airway resistance syndrome

The question of whether upper airway resistance syndrome (UARS) is a distinct disease or an initial feature of obstructive sleep apnoea syndrome is still a matter of debate. We evaluated a retrospective group of UARS patients to determine the evolution of UARS over time and the relationship between clinical evolution and subjects' phenotype. Investigations were performed in 30 patients, in whom UARS was diagnosed between 1995 and 2000 by the use of full polysomnography (PSG) without oesophageal pressure (Pes) measurement. The time between initial and follow-up investigations was 6.6 ± 2.6 years. All subjects had full PSG with Pes measurement and completed a sleep questionnaire, including the Epworth Sleepiness Scale. In 19 subjects, PSG results were compatible with UARS. In nine subjects, obstructive sleep apnoea–hypopnoea syndrome (OSAHS) was diagnosed. In two subjects, PSG did not demonstrate breathing abnormalities. The mean ± SD apnoea–hypopnoea index in the UARS group was 1.5 ± 1.7 h⁻¹ and 25.2 ± 19 h⁻¹ in the OSAHS group ( P  <   0.01). The increase in body mass index (BMI) between initial and follow-up investigations in the UARS group was from 29.4 ± 4 to 31 ± 5.7 kg m⁻² ( P  =   0.014) and in the OSAHS group from 30 ± 4.1 to 32.4 ± 4.7 kg m⁻²( P  =   0.004). Amplitude of Pes swings during respiratory events was significantly higher in OSAHS than that in UARS ( P  =   0.014). Our results suggest that UARS is part of a clinical continuum from habitual snoring to OSAHS. Progression from UARS to OSAHS seems to be related to an increase in the BMI.     

Determinants of circadian blood pressure rhythm and blood pressure variability in obstructive sleep apnoea

SUMMARY  The prevalence of hypertension in patients with obstructive sleep apnoea (OSA) is high and blood pressure profile is characterized by nocturnal blood pressure (BP) elevation and increased nocturnal BP variability. Ambulatory 24-hour-biood pressure monitoring (ABPM) is a valid, non-invasive method to describe circadian BP variation. Circadian BP profile and nocturnal BP variability were related to OSA severity (apnoea-hypopnoea index, mean low O₂), age and body mass index (BMI) in 73 patients with OSA. Prevalence of hypertension was 75%, and in 59% BMI was greater than 30 kg m^-2. A nocturnal decline of at least 10% from daytime mean BP values (night/day BP ratio <0.9; dipper) was found in only 25% of hypertensive patients and 39% of normotensive patients. Comparison between dippers and non-dippers showed significant differences in apnoea severity (apnoea-hypopnoea index 32 + 19 vs. 50 + 23/h, P <0.01; mean low O₂ 84.5 + 4 vs. 80.2 + 5.8%, P< 0.01) but not for age and BMI. In multiple regression analyses with age, body mass index, apnoea-hypopnoea index and mean low O₂ as independent and BP ratios and BP variability as dependent variables, sleep apnoea severity was the only independent predictor for circadian BP rhythm and nocturnal BP variability. The results presented here suggest that independent of age and obesity the severity of sleep apnoea is an important determinant of circadian BP variation and nocturnal BP variability.     

Influence of obstructive sleep apnoea on circadian blood pressure profile

SUMMARY  A high prevalence of systemic hypertension in obstructive sleep apnoea (OSA) has been described but data on circadian blood pressure (BP) profile are limited and give inconsistent results. The present study examines 24-h BP in 106 patients referred because of loud snoring or excessive daytime sleepiness in combination with snoring. Patients were classified as OSA ( n = 62) or habitual snorers (HS) ( n = 44). Respiratory disturbance index (RDI) in OSA was 47 ± 24 vs. 2 ± 2 in HS. Mean age and body mass index in OSA was significantly higher.
BP was measured non-invasively at 15-min intervals during a 24-h period. Daytime and night-time BP was higher in OSA compared to HS. BP night/day ratio in OSA was 0.92 ± 0.07 vs. 0.86 ± 0.06 in HS ( P < 0.05). To investigate the influence of variables other than breathing abnormalities during sleep on our results we compared BP profiles of 25 OSA and 25 HS matched for sex, age and body weight. Again differences in daytime and night-time BP and BP night/day ratio were significant. Using a value of at least 10% fall in nocturnal BP to describe a regular BP profile (dipper) 68% of OSA were classified as non-dippers vs. 24% of HS.
Influence of short-term (2–4 days) nCPAP therapy on circadian BP profile was investigated in 34 patients with OSA. Systolic and diastolic nocturnal (but not daytime) BP was significantly reduced. The percentage of non-dippers was 79% before and 50% after treatment. In conclusion results of this study indicate a causal link between OSA and abnormal circadian BP profile.     

左心室辅助装置控制模式影响双心室搏动同步性的数值研究

右心室(RV)衰竭已成为左心室辅助装置(LVAD)治疗的一种致命并发症。由LVAD引起的双心室搏动的不同步是引发RV功能障碍的重要因素。本文采用数值方法研究LVAD的控制模式对左、右心室搏动同步性的影响。数值结果表明:左心室(LV)与RV的收缩持续时间在无泵模式下没有显著差异(分别为48.52%和51.77%)。连续模式下,LV收缩期明显短于RV收缩期(LV vs.RV:24.38%vs.49.16%)和无泵模式的LV收缩期。搏动模式下,LV收缩期明显短于RV收缩期(LV vs.RV:28.38%vs.50.41%)但长于连续模式的LV收缩期。反搏动模式中的LV、RV收缩期差异较小(LV vs.RV:43.13%vs.49.23%),而LV收缩期短于无泵模式,并且长于连续模式。与连续和搏动模式相比,由反搏动模式提供的收缩期转速(RS)降低显著地校正了LV收缩持续时间,连续模式下缩短的收缩持续时间在反搏动模式下被校正为LV和RV之间的重新同步。因此,本文认为LV和RV收缩的再同步有助于预防RV功能障碍。总之,使用在收缩期间降低RS的反搏动模式有望用于由LVAD引起的双心室搏动不同步的临床校正。     

Influence of Changes in Intrathoracic and Central Venous Pressure on Cardiac Filling Dynamics

Changes in the ratio between intrathoracic and central venous pressure were studied in narcotized cats under conditions of constant positive or negative pressure ventilation. Transformation of elastic characteristics in the respiratory system caused by changes in intrathoracic pressure led to inversion of the ratio between transpulmonary intrathoracic and central venous pressure determining right atrial filling pressure.