Blockade of alpha2-adrenergic receptors in the caudal raphe region enhances the renal sympathetic nerve activity response to acute intermittent hypercapnia in rats.

The study investigated the role of alpha2-adrenergic receptors of the caudal raphe region in the sympathetic and cardiovascular responses to the acute intermittent hypercapnia (AIHc). Urethane-anesthetized, vagotomized, mechanically ventilated Sprague-Dawley rats (n=38) were exposed to the AIHc protocol (5×3 min, 15 % CO2+50 % O2) in hyperoxic background (50 % O2). alpha2-adrenergic receptor antagonist-yohimbine was applied intravenously (1 mg/kg, n=9) or microinjected into the caudal raphe region (2 mM, n=12) prior to exposure to AIHc. Control groups of animals received saline intravenously (n=7) or into the caudal raphe region (n=10) prior to exposure to AIHc. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored before exposure to the AIHc protocol (T0), during five hypercapnic episodes (THc1-5) and at 15 min following the end of the last hypercapnic episode (T15). Following intravenous administration of yohimbine, RSNA was significantly greater during THc1-5 and at T15 than in the control group (P<0.05). When yohimbine was microinjected into the caudal raphe region, AIHc elicited greater increases in RSNA during THc1-5 when compared to the controls (THc1: 138.0+/-4.0 % vs. 123.7+/-4.8 %, P=0.032; THc2: 137.1+/-5.0 % vs. 124.1+/-4.5 %, P=0.071; THc3: 143.1+/-6.4 % vs. 122.0±4.8 %, P=0.020; THc4: 146.1+/-6.2 % vs. 120.7+/-5.7 %, P=0.007 and THc5: 143.2+/-7.7 % vs. 119.2+/-7.2 %, P=0.038). During THc1-5, significant decreases in HR from T0 were observed in all groups, while changes in MAP were observed in the group that received yohimbine intravenously. These findings suggest that blockade of the alpha2-adrenegic receptors in the caudal raphe region might have an important role in sympathetic responses to AIHc.

Hyperoxia blunts renal sympathetic nerve activity response to acute intermittent hypercapnia in rats.

Activation of the sympathetic nervous system plays an important role in the pathophysiology of sleep-related breathing disorders. The aim of the present study was to examine the effects of different levels of hypercapnia in the presence of various background oxygen levels on the magnitude of sympathoexcitation, measured by the renal sympathetic nerve activity (RSNA) in the acute intermittent hypercapnia (AIHc) rat model. The study was conducted on 56 urethane-anesthetized, vagotomized and mechanically ventilated Sprague-Dawley rats (n = 7/group). Each experimental group was subjected to a distinct AIHc protocol that varied in the applied levels of hypercapnia and background oxygen. Mean arterial pressure and RSNA were analyzed in 7 experimental time points: baseline, five hypercapnic episodes (each lasting 3 min) and 15 minutes following the last hypercapnic episode. Exposure to severe hypercapnia (FiCO2 = 0.15) evoked an increase in RSNA, which was preserved throughout the protocol, whereas in moderate hypercapnia (FiCO2 = 0.05) groups there was a trend of progressive diminution of RSNA magnitude following the first hypercapnic episode. Exposure to severe hypercapnia elicited significantly greater RSNA response during first hypercapnic episode and it was enhanced during subsequent episodes compared to exposure to moderate hypercapnia. Additionally, hyperoxic2 background (50% O2) blunted the RSNA response to AIHc compared to room air background, both in severe and moderate hypercapnia groups. Mean arterial blood pressure was preserved throughout the experimental protocol in all studied groups. These findings indicate that acute intermittent hypercapnia evokes increased renal sympathetic nerve activity that is dependent on the severity of hypercapnic exposures and the background oxygen level.

Periodicity during hypercapnic and hypoxic stimulus is crucial in distinct aspects of phrenic nerve plasticity.

This study was undertaken to determine pattern sensitivity of phrenic nerve plasticity in respect to different respiratory challenges. We compared long-term effects of intermittent and continuous hypercapnic and hypoxic stimuli, and combined intermittent hypercapnia and hypoxia on phrenic nerve plasticity. Adult, male, urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypercapnia (AIHc or AIHc(O2)), acute intermittent hypoxia (AIH), combined intermittent hypercapnia and hypoxia (AIHcH), continuous hypercapnia (CHc), or continuous hypoxia (CH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures, at 15, 30, and 60 min (T60) after the end of the stimulus. Exposure to acute intermittent hypercapnia elicited decrease of phrenic nerve frequency from 44.25+/-4.06 at T0 to 35.29+/-5.21 at T60, (P=0.038, AIHc) and from 45.5+/-2.62 to 37.17+/-3.68 breaths/min (P=0.049, AIHc(O2)), i.e. frequency phrenic long term depression was induced. Exposure to AIH elicited increase of pPNA at T60 by 141.0+/-28.2 % compared to baseline (P=0.015), i.e. phrenic long-term facilitation was induced. Exposure to AIHcH, CHc, or CH protocols failed to induce long-term plasticity of the phrenic nerve. Thus, we conclude that intermittency of the hypercapnic or hypoxic stimuli is needed to evoke phrenic nerve plasticity.

The relationship between sleep habits and academic performance in dental students in Croatia.

INTRODUCTION: It is well accepted that sleep and lifestyle habits affect academic success in students. However, sleep patterns and sleep problems amongst dental students have been insufficiently addressed in the literature. The purpose of this study was to evaluate sleep habits of dental students and the relationship between sleep habits and academic performance. MATERIALS AND METHODS: A self-administered questionnaire on sleep habits, academic performance and lifestyle was administered. The participants were 447 dental students from Split University Dental Medicine School and Zagreb University Dental Medicine School from the six academic years. The subjects were classified into two groups based on academic success (high-performing vs. low-performing students) for comparison of sleep and lifestyle habits. RESULTS: Amongst the whole group of students, average bedtime and wake time during weekday was significantly earlier compared with weekend. Main findings indicate that students with high academic performance had earlier bedtimes during weekdays and weekends, earlier wake times during weekends and shorter sleep latency compared with low academic performing students. CONCLUSION: Self-reported academic performance of dental students in Croatia is associated with timing of sleep and wakefulness, rather than with total sleep time duration.

Remifentanil reversibly abolished phrenic long term facilitation in rats subjected to acute intermittent hypoxia.

The aim was to investigate whether intravenous infusion of remifentanil would depress phrenic long term facilitation (pLTF) evoked by acute intermittent hypoxia (AIH) in adult, male, urethane anaesthetized Sprague-Dawley rats, bilaterally vagotomized, paralyzed and mechanically ventilated. The experimental group received a remifentanil infusion (0.5 µg/kg/min i.v., n=12), whereas the control group (n=6) received saline. Rats were exposed to AIH protocol. Phrenic nerve amplitude (PNA), burst frequency (f) and breathing rhythm parameters (Ti, Te, Ttot) were analyzed during 5 hypoxias and at 15, 30, and 60 minutes after the final hypoxia, and compared to baseline values. At the end of the experiment, the infusion of remifentanil was stopped and phrenic nerve activity was compared to baseline values prior to remifentanil infusion. In the control group, peak phrenic nerve activity (pPNA) significantly increased at 60 min (T60, increase by 138.8±28.3%, p=0.006) after the last hypoxic episode compared to baseline values, i.e. pLTF was induced. In remifentanil treated rats, there were no significant changes in peak phrenic nerve activity at T60 compared to baseline values (decrease by 5.3±16.5%, p>0.05), i.e. pLTF was abolished. Fifteen minutes following cessation of remifentanil infusion, pPNA increased by 93.2±40.2% (p<0.05) and remained increased compared to pre-remifentanil-infusion values for more than 30 minutes, i.e. pLTF could be observed after cessation of the remifentanil infusion. In conclusion, the short acting µ-opioid receptor agonist, remifentanil, reversibly abolished phrenic long term facilitation in urethane anesthetized rats.

Propofol abolished the phrenic long-term facilitation in rats.

The aim was to investigate the effect of propofol anesthesia on the phrenic long-term facilitation (pLTF) in rats. We hypothesized that pLTF would be abolished during propofol-compared with urethane anesthesia. Fourteen adult, male, anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats (seven per group), were exposed to the acute intermittent hypoxia (AIH) protocol. Peak phrenic nerve activity (PNA), burst frequency (f), and breathing rhythm parameters (Ti, Te, Ttot) were analyzed during the first hypoxia (TH1), as well as at 15 (T15), 30 (T30), and 60min (T60) after the final hypoxic episode, and compared to the baseline values. In propofol-anesthetized rats no significant changes of PNA were recorded after the last hypoxic episode, i.e. no pLTF was induced. There was a significant increase of PNA (59.4+/-6.6%, P<0.001) in urethane-anesthetized group at T60. AIH did not elicit significant changes in f, Ti, Te, Ttot in either group at T15, T30, and T60. The pLTF, elicited by AIH, was induced in the urethane-anesthetized rats. On the contrary, pLTF was abolished in the propofol-anesthetized rats.

The acute hypoxic ventilatory response under halothane, isoflurane, and sevoflurane anaesthesia in rats.

The relative order of potency of anaesthetic agents on the hypoxic ventilatory response has been tested in humans, but animal data are sparse. We examined the effects of 1.4, 1.6, 1.8, and 2.0 MAC halothane, isoflurane, and sevoflurane on phrenic nerve activity in euoxia (baseline) and during acute normocapnic hypoxia (inspired oxygen fraction 0.09) in adult male Sprague-Dawley rats. With halothane, all animals became apnoeic even in euoxia, and the hypoxic response was completely abolished at all anaesthetic levels. With isoflurane, 5 of 14 animals exhibited phrenic nerve activity in euoxia at 1.4 MAC and demonstrated a hypoxic response (302% of baseline activity), but all became apnoeic and lost the hypoxic response at higher doses. With sevoflurane, phrenic nerve activity and a hypoxic response was preserved in at least some animals at all doses (i.e. even the highest dose of 2.0 MAC). Similar to the rank order of potency previously observed in humans, the relative order of potency of depression of the hypoxic ventilatory response in rats was halothane (most depressive) > isoflurane > sevoflurane (p = 0.01 for differences between agents).

Blockade of 5-HT(1A) receptors in the phrenic nucleus of the rat attenuated raphe induced activation of the phrenic nerve activity.

Stimulation of the raphe pallidus nucleus produces facilitatory effects on respiratory activity. Numerous serotonergic projections from the raphe pallidus have been shown to terminate in the phrenic nucleus. This study was undertaken to examine the role of 5-hydroxytryptamine 1A (5-HT(1A)) receptors in the phrenic nucleus on the excitatory response of the phrenic nerve activity elicited from the raphe pallidus. We hypothesized that blockade of 5-HT(1A) receptors in the phrenic nucleus will attenuate raphe-induced facilitation of the phrenic nerve. Chemical stimulation of the raphe pallidus by synaptic excitant D,L-homocysteic acid produced increase in the amplitude of the phrenic nerve activity. After microinjection of the specific 5-HT(1A) receptor antagonist WAY, N-(2-(4,2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl-cyclohexane-carboxamide maleate into the phrenic nucleus, the raphe-induced facilitation of the phrenic nerve was attenuated. These data suggest that excitation of the phrenic nerve activity elicited by activation of the neurons in the raphe pallidus is mediated by 5-HT(1A) receptors in the phrenic nucleus.

Phrenic nerve activity is enhanced by 5-HT1A receptor agonist 8-OH-DPAT in spontaneously breathing anesthetized rats.

Activation of serotonin 1A (5-HT(1A)) receptors has been shown to have diverse effects on respiration. The purpose of this study was to determine changes in respiratory motor pattern of phrenic nerve activity and respiratory rhythm after systemic application of specific 5-HT(1A) receptor agonist 8-hydroxy-2-di-npropylamino-tetralin (8-OH-DPAT). We hypothesized that systemic application of specific 5-HT(1A) receptor agonist 8-OH-DPAT in spontaneously breathing anaesthetized rats will enhance phrenic motor output and phrenic respiratory rate. The study was performed in spontaneously breathing urethane anesthetized rats. Intravenous application of 8-OH-DPAT produced dose dependent increase in the amplitude of integrated phrenic nerve activity and disturbances in respiratory rhythm. Stimulating effect of 8-OH-DPAT on phrenic nerve activity was abolished by intravenous application of the selective 5-HT(1A) receptor antagonist WAY, N-(2-(4,2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinyl-cyclohexane-carboxamide maleate (WAY-100635). These results show that stimulation of 5-HT(1A) receptors by intravenous application of 8-OH-DPAT enhances phrenic nerve activity in spontaneously breathing rats.