Permanent brain ischemia induces marked increments in hsp72 expression and local protein synthesis in synapses of the ischemic hemisphere

Transient focal ischemia induced in rat brain by occlusion of the middle cerebral artery (MCAo) elicits a generalized induction of the 72 kDa heat-shock protein (hsp72) heralding functional recovery. As this effect implies activation of protein synthesis, and local systems of protein synthesis are present in brain synapses, and may be analyzed in preparations of brain synaptosomes, we evaluated hsp72 expression and protein synthesis in synaptosomal fractions of spontaneously hypertensive rats (SHRs) subjected to permanent MCAo. SHRs were randomly divided in ischemics and sham controls, anaesthesia controls and passive controls. Focal ischemia was induced under chloral hydrate anaesthesia by unilateral permanent MCAo. Protein synthesis was determined by [³⁵S]methionine incorporation into synaptosomal proteins from ischemic and contralateral cortex/striatum, and from cerebellum. Hsp72 expression was measured in the same fractions by immunoblotting. Our data demonstrate that under these conditions synaptic hsp72 markedly increases in the ischemic hemisphere 1 and 2 days after MCAo, progressively declining in the following 2 days, while no significant change occurs in control rats. In addition, in the ischemic hemisphere the rate of synaptic protein synthesis increases more than two-fold between 1 and 4 days after MCAo, without showing signs of an impending decline. The present data provide the first demonstration that synaptic protein synthesis is massively involved in brain plastic events elicited by permanent focal ischemia.     

Flow resistance in patients with chronic obstructive pulmonary disease in acute respiratory failure. Effects of flow and volume

The flow and volume dependence of the total resistance of the respiratory system (Rrs) was investigated in six mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) using a simple, rapid method. Isovolume Rrs-flow (V) relationships obtained at different inflation volumes (range 0.1 to 1 L) fitted (p less than 0.001) the following function: Rrs = a/V + b + cV, where a, b, and c are constants. The term "a/V" in this equation represents the hyperbolic decrease in thoracic tissue resistance with increasing flow; the term "cV" represents the linear increase in airway resistance with increasing flow. Rrs initially decreased with increasing V because at low flow the weight of the a/V was greater than that of the cV. At higher flow, however, cV became predominant and hence Rrs tended to increase. At an inflation volume of 0.5 L, minimum Rrs occurred at average inflation flow of 1.28 L/s. At low flow, Rrs increased progressively with increasing inflation volume; at inflation V greater than 1 L/s, the highest values of Rrs were obtained at low inflation volumes. The flow and volume dependence of Rrs implies that, for comparative purposes, measurements of Rrs should be standardized to a fixed inflation flow and volume.     

Oronasal masks require higher levels of positive airway pressure than nasal masks to treat obstructive sleep apnea

Purpose

The purpose of this study was to compare the therapeutic pressure determined by an automated CPAP device (AutoCPAP) during the titration period, between nasal and oronasal mask and the residual apnea-hypopnea index (AHI) on a subsequent poligraphy performed with the established therapeutic CPAP.

Methods

As a retrospective study, 109 subjects with moderate and severe obstructive sleep apnea-hypopnea (apnea-hypopnea index?≥?15 events/h) were studied. CPAP titration was performed using an auto-titrating device.

Results

There was significant difference in the mean pressure delivered with autoCPAP between the group of patients using the nasal mask (mean 10.0 cmH₂O?±?2.0 SD) and the group which used the oronasal mask (mean 11.2 cmH₂O?±?2.1) (p?p?r?=?0.245, p 0.008).

Conclusions

Therapeutic CPAP level for OSAH is higher when administered via oronasal mask, leaving more residual events. These findings suggest that nasal mask should be the first choice for OSAH treatment.     

Influence of upper airway size on volume exhaled under negative pressure during evaluation of upper airway collapsibility

Study objectives  

It has been shown that volume exhaled in the first 0.5 s after application at the mouth of 5 cmH₂O negative pressure (V,NEP_0.5) during wakefulness strongly reflects critical pressure (Pcrit) during sleep but only in males with neck circumference (NC) >37 cm. The aim of this study was to establish the relationship between upper airway (UA) size and V,NEP_0.5, to obtain V,NEP_0.5 values as percent predicted and then correlate them with Pcrit obtained in the same subjects.     

Expiratory flow limitation is associated with orthopnea and reversed by vasodilators and diuretics in left heart failure

BACKGROUND: In patients with acute left heart failure (LHF), orthopnea has also been related to the occurrence or worsening of expiratory flow limitation (EFL) in the supine position. We wished to assess whether short-term treatment with vasodilators and diuretics was able to abolish supine EFL and whether this could help to control orthopnea in patients with acute LHF. METHODS: In nine nonobese (ie, mean [+/- SD] body mass index, 24 +/- 5 kg/m2), never-smoker patients (two men and seven women; mean age, 77 +/- 7 years) with acute LHF (mean ejection fraction, 43 +/- 15%), we assessed EFL by the negative expiratory pressure method and dyspnea by the Borg scale, with patients in both the seated and supine positions, before and after short-term treatment with vasodilators and diuretics until hospital discharge. Orthopnea was defined as a positive difference in the Borg score between measurements made with the patient in the supine and seated positions. Postural variations in the end-expiratory lung volume were inferred from changes in inspiratory capacity (IC) that were measured under the same circumstances. RESULTS: Before treatment, with the patient in the seated position the mean dyspnea score was 1.5 +/- 0.5, the mean IC was 1.49 +/- 0.38 L, seven patients were non-flow-limited, and two patients were flow-limited. During recumbency, the mean dyspnea score was 2.7 +/- 0.5 (p < 0.01 vs seated position values), the mean IC was 1.66 +/- 0.45 L, and seven patients exhibited EFL. After a mean duration of 17 +/- 8 days of treatment (range, 7 to 28 days), EFL was detected in two patients only in the supine position, IC increased both in the seated position (1.65 +/- 0.34 L; p < 0.01) and the supine position (1.81 +/- 0.41 L; p = 0.07) position, and, although only two patients denied orthopnea, the mean dyspnea score during recumbency actually decreased to 1.9 +/- 1.0 (p < 0.05). CONCLUSIONS: Our results indicate that short-term treatment with vasodilators and diuretics is able to control orthopnea and to remove supine EFL in most patients with acute LHF, suggesting a posture-related increase in bronchial obstruction as the main mechanism of EFL, which appears to play a role in the occurrence and severity of orthopnea in these circumstances.     

Sleep apnea syndrome in endocrine diseases

It is increasingly recognized that sleep-disordered breathing (SDB) - from snoring to apnea-hypopnea syndrome (SAHS) - can affect patients with various endocrine diseases (ED). Different mechanisms are implied in SDB, promoting either central or, more frequently, obstructive apnea in different ED. In the past, acromegaly and hypothyroidism were first associated with both central and obstructive SAHS. Today, great attention is placed on the complex cause-effect relationship between diabetes mellitus and obstructive SAHS (and vice versa). Symptoms and signs of SAHS may complicate the clinical course of these diseases and should be promptly suspected to detect and possibly treat the accompanying SDB.     

EEG power spectra changes and forebrain ischemia in rats

BACKGROUND: Several animal models of cerebral ischemia have been developed to investigate both pathophysiology and pharmacological treatment. The aim of this study was to verify the prognostic value of EEG power spectra analysis in a two-vessel plus hypotension rat model of transient global ischemia. METHODS: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were subjected to 20 min bilateral common carotid artery occlusion plus hypotension by sodium nitroprusside followed by reperfusion for seven days. Sham-operated animals served as controls. The changes after ischemia in EEG power spectra, and their relations with neuronal damage and astrocytic response were investigated. RESULTS: The EEG analysis revealed that in SHRs and WKYs, ischemia produced a dramatic increase in delta activity and a decrease in theta, beta and alpha activities derived from both cortical and hippocampal areas. EEG activity reverted to normal values more quickly in WKYs than in SHRs which did not recover cortical and hippocampal alpha and beta activities even at six days of reperfusion. SHRs presented more severe damage and intense astrocytosis than WKYs in almost all the brain regions analyzed. In SHRs, hippocampal delta activity was positively correlated with the degree of neuronal necrosis and astrocytic activation, whereas theta, alpha and beta activities correlated negatively. No correlations were found in WKYs. CONCLUSIONS: These data indicate that the hippocampal bioelectrical activity recorded in SHRs from the beginning of reperfusion could be useful for predicting the ischemic outcome and evaluating the effects of pharmacological interventions.     

Effects of light physical exercise on sleep regulation in rats

PURPOSE: Acute physical exercise is known to enhance slow-wave sleep (SWS) and reduce paradoxical sleep (PS) in humans. In this study, we examined the effects of moderate physical exercise on sleep in rats. METHOD: Young adult Wistar rats underwent a 4-h baseline electroencephalographic (EEG) recording session. The following day, they were induced to walk (0.8 m x min(-1)) or run (4 m x min(-1)) for 45 min in a rota-rod treadmill. Active control rats (ACR) were placed on the locked rota-rod for 45 min, whereas passive control rats (PCR) remained in their home cages. They were then left free to sleep for 4 h during which EEG activity was recorded. Rectal temperature (Tre) was monitored before and after exercise in ACR, walking and running rats (WR and RR, respectively) and at 45 min intervals in PCR. RESULTS: WR were able to walk for 45 min consecutively whereas in RR performances differed. Posttraining Tre was unchanged in ACR, PCR, and WR and resulted about 1.8 degrees C above baseline in RR. In both WR and RR after exercise i) length of SWS and PS, ii) intensity of SWS (spectral power density in 1-4 Hz range), and iii) propensity for falling asleep were enhanced. Interestingly, there was a more conspicuous increment in PS than SWS. In ACR and PCR there were no changes in sleep. CONCLUSIONS: Due to the complexity of sleep regulation, the interaction of several factors might underlie the observed increment in SWS and PS. Nevertheless, it is interesting that light physical exercise favors sleep and above all a harmonic enhancement of both sleep phases.