Ivana Pavlinac Dodig

The evaluation of the Croatian version of the Epworth sleepiness scale and STOP questionnaire as screening tools for obstructive sleep apnea syndrome

PurposeGrowing awareness of obstructive sleep apnea syndrome (OSAS) has increased the need for concise and reliable screening tools. The Epworth sleepiness scale (ESS) has been validated in numerous languages and ethnic groups, since it was originally designed for the English-speaking population. The STOP questionnaire was developed as a novel OSAS screening tool in surgical patients, but has not been validated in the general population. The present study was undertaken to provide reliable and validated ESS in the Croatian language and to evaluate the ESS and STOP as screening instruments for OSAS.MethodsThe Croatian version of ESS and STOP questionnaire was administered to 217 patients referred to the Split Sleep Medicine Center and 208 healthy control subjects. Test–retest reliability was investigated in 20 healthy subjects.ResultsThe ESS score was significantly higher for the patients referred to the Split Sleep Medicine Center compared to the control group (8.2 ± 5.0 vs. 5.9 ± 3.8, p < 0.001). Cronbachs alpha coefficient for the ESS Croatian version was 0.84 indicating an excellent internal consistency. Reproducibility revealed no significant difference in each item or in the total ESS scores. Receiver operating curve of the ESS for identification of cases with AHI >5/h was 0.64, and for the STOP questionnaire, it was 0.84.ConclusionsBoth ESS and STOP questionnaires successfully distinguished healthy subjects from subjects with OSAS. The STOP questionnaire had better probability to correctly predict high-risk patients for OSAS compared to ESS. We propose that the STOP questionnaire could be used as an easy-to-use and accurate screening tool in identification of patients with risk for OSAS in the general population, but it has not been tested in the Croatian population yet.

Intermittent hypercapnia-induced phrenic long-term depression is revealed after serotonin receptor blockade with methysergide in anaesthetized rats.

What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long‐term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long‐term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long‐term depression was revealed in animals pretreated with the serotonin broad‐spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats.

Acute intermittent hypoxia induces phrenic long‐term facilitation which is modulated by 5‐HT1A receptor in the caudal raphe region of the rat

Obstructive sleep apnoea (OSA) is characterized by periods of upper airway collapse accompanied by repeated episodes of hypoxia. In experimental animals repeated bouts of hypoxia may evoke sustained augmentation of phrenic nerve activity, known as phrenic long‐term facilitation (pLTF). This form of physiological compensation might contribute to stable breathing, minimizing the occurrence of apnoeas and/or hypopnoeas during sleep in patients with OSA. Serotonin (5‐HT) has been shown to modulate respiratory neuronal activity, possibly via projections originating in the raphe nuclei. Our model focuses on the effects of 5‐HT1A receptors blockade by selective antagonist WAY‐100635 into the caudal raphe region on phrenic long‐term facilitation after exposure to acute intermittent hypoxia (AIH) episodes. Adult, male, urethane‐anaesthetized, vagotomized, paralyzed and mechanically ventilated Sprague–Dawley rats were exposed to AIH protocol. Experimental group received microinjection of WAY‐100635 into the caudal raphe nucleus, whereas the control group received saline into the same site. Peak phrenic nerve activity and respiratory rhythm parameters were analysed during five hypoxic episodes, as well as at 15, 30 and 60 min after the end of hypoxias. In the control group, 1 h post‐hypoxia pLTF was developed. Microinjections of selective 5‐HT1A receptor antagonist WAY‐100635 into the raphe nuclei prior to the AIH protocol prevented induction of pLTF. These results suggest that 5‐HT1A receptor activation at supraspinal level is important for induction of pLTF, which is suggested to be an important respiratory neuroplasticity model in animal studies that possibly correlates with OSA in humans.

Phrenic long-term depression evoked by intermittent hypercapnia is modulated by serotonergic and adrenergic receptors in raphe nuclei

Intermittent hypercapnia evokes prolonged depression of phrenic nerve activity (phrenic long-term depression, pLTD). This study was undertaken to investigate the role of 5-HT and α2-adrenergic receptors in the initiation of pLTD. Adult male urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to a protocol of acute intermittent hypercapnia (AIHc; 5 episodes of 15% CO2 in air, each episode lasting 3 min). The experimental group received microinjection of the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), the broad-spectrum 5-HT antagonist methysergide, or the α2-adrenergic antagonist yohimbine, whereas the control group received microinjection of 0.9% saline into the caudal raphe region. Peak phrenic nerve activity (pPNA) and burst frequency ( f) were analyzed during baseline (T0), during 5 hypercapnic episodes (THc1-THc5), and at 15, 30, and 60 min after the end of the last hypercapnic episode. In the control group, pPNA decreased 60 min after the end of the last hypercapnic episode compared with baseline values, i.e., pLTD developed ( P = 0.023). In the 8-OH-DPAT group, pPNA significantly decreased at T15, T30, and T60 compared with baseline values, i.e., pLTD developed ( P = 0.01). In the methysergide and yohimbine groups, AIHc did not evoke significant changes of the pPNA at T15, T30, and T60 compared with baseline values. In conclusion, activation of 5-HT1A receptors accentuated induction of pLTD, whereas blockade of α2-adrenergic receptors prevented development of pLTD following AIHc in anesthetized rats. These results suggest that chemical modulation of 5-HT and α2-adrenergic receptors in raphe nuclei affects hypercapnia-induced pLTD, offering important insights in understanding the mechanisms involved in development of respiratory plasticity. NEW & NOTEWORTHY Hypercapnia is a concomitant feature of many breathing disorders, including obstructive sleep apnea. In this study, acute intermittent hypercapnia evoked development of phrenic long-term depression (pLTD) 60 min after the last hypercapnic episode that was preserved if the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide was microinjected in the caudal raphe region before the hypercapnic stimulus. This study highlights that both 5-HT and adrenergic receptor activation is needed for induction of pLTD in urethane-anesthetized rats following intermittent hypercapnia exposure.

Sevoflurane and isoflurane monoanesthesia abolished the phrenic long-term facilitation in rats

Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity, manifested by prolonged increase in peak amplitude of phrenic nerve activity (PNA) after episodes of acute intermittent hypoxia (AIH). The aim was to investigate the effects of sevoflurane and isoflurane monoanesthesia at equipotent anesthetic doses on the expression of amplitude pLTF. Experiments were performed on Sprague-Dawley anesthetized, vagotomized, and mechanically ventilated rats. Two experimental groups, sevoflurane and isoflurane, and a control group (urethane-anesthetized) were formed. Peak amplitude of phrenic nerve activity, respiratory frequency and breathing rhythm parameters (Ti, inspiratory duration; Te, expiratory duration; and Ttot, total respiratory time duration) were analyzed during hypoxic episodes, and at 15, 30, and 60min after the last hypoxic episode. In the control group average PNA increased by 173.03±70.16% (p<0.001), at 60min after the last hypoxic episode compared to baseline values. Therefore amplitude pLTF was induced. In the sevoflurane and isoflurane groups PNA failed to increase, and in fact decreased by 15.79±15.18% and 31.00±11.00%, respectively (p>0.05). Amplitude pLTF was abolished during sevoflurane and isoflurane monoanesthesia.