Publications by authors named "Yasuyuki Kaneko"

18 Publications

  • Page 1 of 1

ATF5 deficiency causes abnormal cortical development.

Sci Rep 2021 Mar 31;11(1):7295. Epub 2021 Mar 31.

Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.

Activating transcription factor 5 (ATF5) is a member of the cAMP response element binding protein (CREB)/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5) mice exhibited behavioural abnormalities, including abnormal social interactions, reduced behavioural flexibility, increased anxiety-like behaviours, and hyperactivity in novel environments. ATF5 mice may therefore be a useful animal model for psychiatric disorders. ATF5 is highly expressed in the ventricular zone and subventricular zone during cortical development, but its physiological role in higher-order brain structures remains unknown. To investigate the cause of abnormal behaviours exhibited by ATF5 mice, we analysed the embryonic cerebral cortex of ATF5 mice. The ATF5 embryonic cerebral cortex was slightly thinner and had reduced numbers of radial glial cells and neural progenitor cells, compared to a wild-type cerebral cortex. ATF5 deficiency also affected the basal processes of radial glial cells, which serve as a scaffold for radial migration during cortical development. Further, the radial migration of cortical upper layer neurons was impaired in ATF5 mice. These results suggest that ATF5 deficiency affects cortical development and radial migration, which may partly contribute to the observed abnormal behaviours.
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http://dx.doi.org/10.1038/s41598-021-86442-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012588PMC
March 2021

Pseudorabies virus infection in hunting dogs in Oita, Japan: Report from a prefecture free from Aujeszky's disease in domestic pigs.

J Vet Med Sci 2021 Apr 15;83(4):680-684. Epub 2021 Feb 15.

Centre for Animal Disease Control, University of Miyazaki, 1-1 Gakuen Kibanadai-nishi, Miyazaki 889-2192, Japan.

We isolated two pseudorabies virus (PRV) isolates (designated OT-1 and OT-2) from two hunting dogs exhibiting neurological manifestations after eating the flesh of wild boar hunted in Oita prefecture, Kyushu Island, Japan. The isolates corresponded to a previously reported PRV (MY-1 strain) isolated from a hunting dog in neighboring Miyazaki prefecture, and it clustered into genotype II based on the glycoprotein C sequence. Our results suggest that this common PRV strain may have been maintained in wild boars on Kyushu Island even though domestic pigs in this area have attained an Aujeszky's disease-free status.
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http://dx.doi.org/10.1292/jvms.20-0450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111351PMC
April 2021

Severe Degenerative Changes in Cryptorchid Testes in Japanese Black Cattle.

Vet Pathol 2020 05 25;57(3):418-426. Epub 2020 Feb 25.

Department of Veterinary Pathology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.

This is a histopathologic and endocrinologic study of 6 calves diagnosed with cryptorchidism. Cases 1-3 were diagnosed as resembling testicular regression syndrome. In cases 1 and 2, the extracted tissue was a small, firm, gray-white mass, and there was lack of obvious testicular tissue in case 3. Histopathologically, the excised tissue in cases 1-3 was a fibrotic testicular remnant with inflammation, mineralization, hemosiderin-laden macrophages or lipofuscin-laden macrophages, and lack of germ cells and interstitial endocrine cells. These findings were compared with cases 4-6, which were diagnosed as testicular hypoplasia due to cryptorchidism. These cases had small but otherwise grossly unremarkable intra-abdominal testicular tissue and histologically had a few germ cells and sustentacular cells with arrested spermatogenesis and an increase in interstitial endocrine cells. Cases 1-3 had more severe degenerative changes compared with cases 4-6. In case 2, the average diameter of the seminiferous tubules was much smaller than in cases 4-6, and there were few tubule cross sections. Anti-Müllerian hormone (214 pg/ml) was detected in the plasma of case 2. Based on the macroscopic and histopathologic findings as well as endocrinologic profiles, the testicular degeneration in cases 1-3 was considered similar to that of testicular regression syndrome. In this condition, it is thought that a normally developing intra-abdominal testis undergoes degeneration due to heat or a vascular disorder such as torsion.
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http://dx.doi.org/10.1177/0300985820906891DOI Listing
May 2020

Effects of a single-bolus bupivacaine injection into the coccygeal spinal canal of rabbits.

J Vet Med Sci 2020 Feb 22;82(2):197-203. Epub 2020 Jan 22.

Veterinary Teaching Hospital, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-Nishi, Miyazaki 889-2192, Japan.

It has been reported that drugs intended for epidural administration through the lumbosacral junction are accidentally administered into the subarachnoid space frequently in rabbits. Therefore, we evaluated the epidural single-bolus injection technique for the administration of bupivacaine into the coccygeal spinal canal of rabbits. After epidural distribution was confirmed by the injection of iohexol into the coccygeal spinal canal, 0.3 ml/kg 0.5% bupivacaine or 0.3 ml/kg normal saline was injected via the same needle. After the first attempt of iohexol injection, although the contrast was found in the epidural space in all rabbits, the additional contrast was also found in blood vessel in 3 rabbits and in muscular layer in 1 rabbit. Subarachnoid distribution was not observed in any of the rabbits. The time taken to regain normal anal reflex, movement of the hind limbs during walking, conscious proprioception of the hind limbs, and pain sensation of the tail and left hind limb, following coccygeal spinal canal injection, were significantly longer in the bupivacaine group than in the normal saline group. These findings indicated that coccygeal epidural injection of bupivacaine in rabbits may provide anesthesia for the hind limbs, perineum, and tail, but inadvertent vascular entry of the epidural drug may occur.
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http://dx.doi.org/10.1292/jvms.19-0555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041980PMC
February 2020

Usefulness of Urinary Creatinine/Urea Nitrogen Ratio as Indicator of Body Protein Catabolism in Dogs Fed Low Protein Diets.

Front Vet Sci 2019 10;6:449. Epub 2019 Dec 10.

Faculty of Agriculture, Veterinary Teaching Hospital, University of Miyazaki, Miyazaki, Japan.

Low protein diets (LPs) constitute a reportedly effective form of nutritional therapy for canine chronic kidney disease and cirrhosis. These diets have long been feared to result in reduced muscle mass due to protein catabolism. This adverse effect, however, remains largely unrecognized in veterinary medicine as there are no easily applicable catabolism indicators. Therefore, we focused on urinary creatinine, a metabolite of protein in the urine, and examined whether its ratio to urinary urea nitrogen (UCrn/UN) can be used to assess protein catabolism. In Experiment 1, we first consecutively fed seven healthy beagles an LP, standard protein (SP), and high protein (HP) diet for 1 week each and then measured the UCrn/UN ratio at 2-h intervals from fasting to 16 h post-prandially. We consequently found that the UCrn/UN ratio was significantly elevated in the LP pre-prandially and at all post-prandial measurement points ( < 0.01). No significant differences were observed between the SP and HP. Analysis of fasting plasma amino-acid concentrations revealed that the concentration of methionine was significantly lower in the LP than in the other diets ( < 0.05). Although the effects of this change in amino-acid concentration were unclear, the UCrn/UN ratio was considered having increased due to a deficiency in protein and/or amino acids during LP feeding. In Experiment 2, we continuously fed five healthy beagles an LP for 18 weeks and then measured the UCrn/UN ratio as described above. We also measured changes in body composition with computed tomography. At weeks 10 and 18, the fasting UCrn/UN ratio was significantly higher than it was prior to the start of the LP; however, post-prandially, the UCrn/UN ratio decreased to the point that the significant difference disappeared. Muscle mass decreased at weeks 10 and 18. These results suggest that the fasting UCrn/UN ratio could be used as an indicator of protein catabolism in LP feeding. Our experiments thus indicate that examination of potential increases in the UCrn/UN ratio 1 week after introduction of LP feeding to healthy dogs could enable detection of body protein catabolism in long-term feeding of LP before muscle breakdown occurs.
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http://dx.doi.org/10.3389/fvets.2019.00449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914702PMC
December 2019

Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles.

J Vet Med Sci 2017 Feb 17;79(2):366-374. Epub 2016 Dec 17.

University of Miyazaki Veterinary Teaching Hospital, 1-1 Gakuen Kibana-dai Nishi, Miyazaki City, Miyazaki 889-2192, Japan.

The pathophysiology of canine gallbladder diseases, including biliary sludge, gallbladder mucoceles and gallstones, is poorly understood. This study aimed to evaluate the component of gallbladder contents and bacterial infection of the gallbladder in order to elucidate the pathophysiology of biliary sludge and gallbladder mucoceles. A total of 43 samples of canine gallbladder contents (biliary sludge, 21 and gallbladder mucoceles, 22) were subjected to component analysis by infrared spectroscopy, and the resultant infrared spectra were compared with that of swine mucin. Of the 43 samples, 41 were also evaluated by aerobic and anaerobic bacterial culture. The contents of 20 (95.2%) biliary sludge and 22 (100%) gallbladder mucocele samples exhibited similar infrared spectra as swine mucin. Although biliary sludge and gallbladder mucocele contents exhibited similar infrared spectra, one sample of biliary sludge (4.8%) was determined to be composed of proteins. The rate of bacterial infection of the gallbladder was 10.0% for biliary sludge and 14.3% for gallbladder mucoceles. Almost all of the identified bacterial species were intestinal flora. These results indicate that the principal components of gallbladder contents in both gallbladder mucoceles and biliary sludge are mucins and that both pathophysiologies exhibit low rates of bacterial infection of the gallbladder. Therefore, it is possible that gallbladder mucoceles and biliary sludge have the same pathophysiology, and, rather than being independent diseases, they could possibly represent a continuous disease. Thus, biliary sludge could be considered as the stage preceding the appearance of gallbladder mucoceles.
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http://dx.doi.org/10.1292/jvms.16-0562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326943PMC
February 2017

A case report of suspected hepatopulmonary syndrome secondary to ductal plate malformation with chronic active hepatitis in a dog.

J Vet Med Sci 2016 Mar 30;78(3):493-7. Epub 2015 Nov 30.

Veterinary Teaching Hospital, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen Kibanadai-nishi, Miyazaki 889-2192, Japan.

Hepatopulmonary syndrome (HPS) is a respiratory complication of hepatic disease, that is well recognized in humans and defined by the presence of 1) liver disease, 2) hypoxemia and/or high alveolar-arterial oxygen gradient (AaDO2) and 3) intrapulmonary vasodilatation. The present report describes a similar case of HPS in a dog. A six-month-old Papillon was diagnosed with ductal plate malformation with chronic active hepatitis and showed progressive increases in AaDO2 over the course of the following six months. The presence of intrapulmonary vasodilatation was confirmed by agitated saline contrast transthoracic echocardiography. Also, the absence of congenital cardiac defect was confirmed by transthoracic echocardiography. From these results, we suspected that this dog had HPS. This is the first description of suspected canine HPS.
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http://dx.doi.org/10.1292/jvms.15-0425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829524PMC
March 2016

Arterial blood gas anomaly in canine hepatobiliary disease.

J Vet Med Sci 2016 Jan 8;77(12):1633-8. Epub 2015 Aug 8.

Veterinary Teaching Hospital, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen Kibanadai-nishi, Miyazaki-shi, Miyazaki 889-2192, Japan.

Arterial blood gas analysis is an important diagnostic and monitoring tool for respiratory abnormalities. In human medicine, lung complications often occur as a result of liver disease. Although pulmonary complications of liver disease have not been reported in dogs, we have frequently encountered hypoxemia in dogs with liver disorders, especially extrahepatic biliary obstruction. In addition, respiratory disorders account for 20% of perioperative fatalities in dogs. Therefore, in this study, we evaluated the respiratory status in dogs with hepatobiliary disease by arterial blood gas analysis. PaO2 and PaCO2 were measured. Alveolar-arterial oxygen difference (AaDO2), the indicator of gas exchange efficiency, was calculated. Compared to healthy dogs (control group), hepatobiliary disease dogs had significantly lower PaO2 and higher AaDO2. Hypoxemia (PaO2 of ≤80 mmHg) was observed in 28/71 dogs with hepatobiliary disease. AaDO2 was higher (≥30 mmHg) than the control group range (11.6 to 26.4 mmHg) in 32/71 hepatobiliary disease dogs. By classifying type of hepatobiliary disease, dogs with extrahepatic biliary obstruction and chronic hepatitis showed significantly lower PaO2 and higher AaDO2 than in a control group. Dogs with chronic hepatitis also had significantly lower PaCO2. The present study shows that dogs with hepatobiliary disease have respiratory abnormalities more than healthy dogs. Preanesthetic or routine arterial blood gas analysis is likely beneficial to detect the respiratory abnormalities in dogs with hepatobiliary disease, especially extrahepatic biliary obstruction and chronic hepatitis.
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http://dx.doi.org/10.1292/jvms.15-0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710720PMC
January 2016

Effects of ozonated autohemotherapy on the antioxidant capacity of Thoroughbred horses.

J Vet Med Sci 2016 Jan 10;77(12):1647-50. Epub 2015 Jul 10.

Laboratory of Veterinary Surgery, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.

The performance of horses undergoing regular intense exercise is adversely affected by oxidative stress. Thus, it is important to increase antioxidant production in horses in order to reduce oxidative stress. Ozonated autohemotherapy (OAHT) reportedly promotes antioxidant production. This study aimed to evaluate the effects of OAHT on antioxidant capacity. Ten Thoroughbred horses were used in this study. After the OAHT, we collected serum samples and measured biological antioxidant potential (BAP). We found that BAP began to increase after the OAHT and was significantly higher in the OAHT group than at 3 (P<0.01) and 7 days (P<0.05) after OAHT than in the control group at 3 and 7 days after starting collection of blood samples. Therefore, it was shown that OAHT improved the antioxidant capacity of the horses.
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http://dx.doi.org/10.1292/jvms.15-0225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710722PMC
January 2016

Laparoscopic cryptorchidectomy in standing bulls.

J Vet Med Sci 2015 May 10;77(5):631-5. Epub 2015 Feb 10.

Veterinary Teaching Hospital, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen Kibanadai-nishi, Miyazaki-shi, Miyazaki 889-2192, Japan.

Laparoscopic cryptorchidectomy without insufflation was applied in 10 standing bulls aged 3 to 15 months. Nine bulls were preoperatively pointed out intra-abdominal testes by computed tomography. Preoperative fasting for a minimum of 24 hr provided laparoscopic visualization of intra-abdominal area from the kidney to the inguinal region. Surgical procedure was interrupted by intra-abdominal fat and testis size. It took 0.6 to 1.5 hr in 4 animals weighing 98 to 139 kg, 0.8 to 2.8 hr in 4 animals weighing 170 to 187 kg, and 3 and 4 hr in 2 animals weighing 244 and 300 kg to complete the cryptorchidectomy. In conclusion, standing gasless laparoscopic cryptorchidectomy seems to be most suitable for bulls weighing from 100 to 180 kg.
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http://dx.doi.org/10.1292/jvms.14-0587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478748PMC
May 2015

[Overlap syndrome involving obstructive sleep apnea syndrome associated with chronic obstructive pulmonary disease].

Nihon Kokyuki Gakkai Zasshi 2008 Aug;46(8):673-8

Department of Internal Medicine, Ohta Nishinouchi Hospital, Ohta General Hospital Foundation.

We reported a case of overlap syndrome involving severe obstructive sleep apnea syndrome (OSAS) associated with chronic obstructive lung disease (COPD). This patient was a 52-year-old heavy smoking man, who had suffered from snoring and apnea for five years, and was admitted to our hospital because of worsening dyspnea. His BMI was 25 Kg/M2, His jaw was very small and he had a narrow upper airway. Chest X-ray showed hyperlucency throughout both lung fields with a markedly dilatation pulmonary arteries. His PaO2 was 62Torr, PaCO2 was 47Torr, FEV(1.0%) was 59%, mean pulmonary artery pressure was 27 mmHg, PSG showed that AHI was 70, were most pronounced during rapid eye movement sleep. He was given a diagnosis of overlap syndrome of OSAS associated with COPD. Generally, Overlap syndrome was believed that chronic bronchitis type (blue bloater) was more frequent than emphysema type. This case was a very rare case, with no obesity, moderate COPD, associated with pulmonary hypertension and hypercapnea, and then to be severe OSAS. However we should be more careful about the OSAS associated with overlap syndrome of the Japanese patients, because to be one factor of exacerbation of respiratory failure.
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August 2008

[Clinical usefulness and health-economic benefits of a new sheet-like medical device (SD-101) for the diagnosis of sleep apnea syndrome].

Nihon Kokyuki Gakkai Zasshi 2008 Mar;46(3):181-8

Center for Sleep Disorders, Ohta General Hospital.

The SD-101 (Kenzmedico co. Ltd., Saitama, Japan), a non-invasive medical device capable of measuring respiratory parameters during sleep, has recently been developed. It operates while placed under the body like a bed pad equipped with 162 pressure sensors, with the patient in bed. To evaluate the efficacy and safety of the SD-101 for the diagnosis of sleep apnea syndrome (SAS), we enrolled 52 patients with suspected SAS (45 men and 7 women; mean age, 45.6 +/- 10.9 years) in this study. Each subject underwent measurement using the SD-101 and a polysomnograph simultaneously, and we analyzed and compared them. In addition, health-economic benefits of the SD-101 were estimated based on the results. A significantly strong correlation was obtained between the apnea hypopnea index of PSG and its of SD-101 (r = 0.86, p < 0.0001). No adverse event due to the SD-101 occurred, while use of the SD-101 greatly reduced "feeling of being constrained" and discomfort during examination (Wilcoxon test: p < 0.0001). These findings could indicate that the SD-101 is clinically useful and will make a contribution to health-economic benefits for SAS in Japan.
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March 2008

Continuous positive airway pressure increases heart rate variability in heart failure patients with obstructive sleep apnoea.

Clin Sci (Lond) 2008 Feb;114(3):243-9

Sleep and Cardiovascular Physiology Research Laboratories, Mount Sinai Hospital, Toronto, ON, Canada.

Patients with heart failure or OSA (obstructive sleep apnoea) have reduced HF-HRV (high-frequency heart rate variability), indicating reduced cardiac vagal modulation, a marker of poor prognosis. CPAP (continuous positive airway pressure) abolishes OSA in patients with heart failure, but effects on daytime HF-HRV have not been determined. We hypothesized that, in patients with heart failure, treatment of coexisting OSA by CPAP would increase morning HF-HRV. In 19 patients with heart failure (left ventricular ejection fraction <45%) and OSA (>/=20 apnoeas and hypopnoeas/h of sleep), HF-HRV was quantified before and 1 month after randomization to a control or CPAP-treated group. In the control group (n=7), there were no changes in HF-HRV over the 1 month study during wakefulness in the morning. In the CPAP-treated group (n=12) HF-HRV increased significantly during wakefulness in the morning [from 2.43+/-0.55 to 2.82+/-0.50 log(ms(2)/Hz); P=0.002] due to an increase in transfer function between changes in lung volume and changes in HF-HRV (92.37+/-96.03 to 219.07+/-177.14 ms/l; P=0.01). In conclusion, treatment of coexisting OSA by nocturnal CPAP in patients with heart failure increases HF-HRV during morning wakefulness, indicating improved vagal modulation of heart rate. This may contribute to improved prognosis.
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http://dx.doi.org/10.1042/CS20070172DOI Listing
February 2008

Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea.

Hypertension 2005 Dec 14;46(6):1327-32. Epub 2005 Nov 14.

University Health Network, Mount Sinai Hospital, Division of Cardiology, Department of Medicine, University of Toronto, Ontario, Canada.

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.
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http://dx.doi.org/10.1161/01.HYP.0000193497.45200.66DOI Listing
December 2005

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure.

J Am Coll Cardiol 2005 Jun;45(12):2008-11

University Health Network, University of Toronto, 600 University Avenue, Toronto, Ontario M5G 1XS, Canada.

Objectives: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone.

Background: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP.

Methods: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control).

Results: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013).

Conclusions: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.
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http://dx.doi.org/10.1016/j.jacc.2004.12.080DOI Listing
June 2005

Cheyne-Stokes respiration in stroke: relationship to hypocapnia and occult cardiac dysfunction.

Am J Respir Crit Care Med 2005 May 21;171(9):1048-52. Epub 2005 Jan 21.

Sleep Research Laboratory of the Toronto Rehabilitation Institute, Centre for Sleep Medicine and Circadian Biology of the University of Toronto, Toronto, Ontario, Canada.

Background: Central sleep apnea (CSA) and Cheyne-Stokes respiration have been reported in association with stroke, but their pathophysiologic correlates have not been well described.

Objective: To test the hypotheses that (1) CSA in patients with stroke is associated with nocturnal hypocapnia and (2) in those stroke patients with CSA and with left ventricular (LV) systolic dysfunction, periodic breathing (PB) will have a Cheyne-Stokes respiration pattern in which cycle duration is greater than in those without LV systolic dysfunction.

Methods: We prospectively performed polysomnography and echocardiography in 93 patients with stroke. CSA was defined as central apneas and hypopneas occurring at a rate of 10 or more per hour of sleep. In patients with CSA, we compared PB cycle duration between those with normal and impaired LV systolic function (LV ejection fraction [LVEF] > 40% and < or = 40%, respectively).

Results: CSA was found in 19% of subjects who had lower nocturnal transcutaneous PCO2 (39.3 +/- 0.9 vs. 42.8 +/- 0.8 mmHg, p = 0.015) and a higher prevalence of LVEF of 40% or less (22 vs. 5%, p = 0.043) than stroke patients without CSA. There was no significant difference in stroke location or type between the two groups. In patients with CSA, those with LVEF of 40% or less had a longer PB cycle than those with an LVEF of more than 40% (66.6 +/- 5.6 vs. 46.6 +/- 2.9 seconds, p = 0.006), but had no symptoms of heart failure.

Conclusion: In patients with stroke, CSA is associated with hypocapnia and occult LV systolic dysfunction but is not related to the location or type of stroke. The presence of LV systolic dysfunction is associated with a Cheyne-Stokes pattern of hyperpnea.
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http://dx.doi.org/10.1164/rccm.200411-1591OCDOI Listing
May 2005

Relationship of sleep apnea to functional capacity and length of hospitalization following stroke.

Sleep 2003 May;26(3):293-7

Sleep Research Laboratory of the Toronto Rehabilitation Institute, the Centre for Sleep Medicine and Circadian Biology of the University of Toronto, Ontario, Canada.

Study Objectives: Recent evidence indicates that sleep apnea is common in patients with stroke. We hypothesized that the presence of sleep apnea among stroke patients would be associated with a greater degree of functional disability and longer hospitalization following stroke.

Design: Prospective study.

Setting And Patients: Sixty-one stroke patients admitted to a stroke rehabilitation unit.

Interventions: N/A.

Measurements And Results: Sleep studies were performed on all patients, and sleep apnea was defined as an apnea-hypopnea index of 10 or more per hour of sleep. Patients underwent functional assessments, including the Functional Independence Measure. Sleep apnea was found in 72% of patients; 60% had predominantly obstructive sleep apnea, while 12% had predominantly central sleep apnea. Although the severity of stroke was similar in the 2 groups, compared to patients without sleep apnea, those with sleep apnea had lower functional capacity [Functional Independence Measure score (mean +/- SEM) 80.2 +/- 3.6 versus 94.7 +/- 4.3, p < 0.05 at admission, and 101.5 +/- 2.8 versus 112.9 +/- 2.7, p < 0.05 at discharge] and spent significantly more days in rehabilitation (45.5 +/- 2.3 versus 32.1 +/- 2.7 days, p < 0.005). In addition, multiple regression analysis showed that obstructive sleep apnea was significantly and independently related to functional impairment and length of hospitalization.

Conclusions: Sleep apnea is very common among stroke patients undergoing rehabilitation, and its presence is associated with worse functional impairment and a longer period of hospitalization and rehabilitation. These data suggest that sleep apnea may be contributing to functional impairment and prolonged hospitalization following stroke.
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http://dx.doi.org/10.1093/sleep/26.3.293DOI Listing
May 2003

Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea.

N Engl J Med 2003 Mar;348(13):1233-41

Sleep Research Laboratories, Toronto Rehabilitation Institute, Toronto General Hospital, ON M5G 2C4, Canada.

Background: Obstructive sleep apnea subjects the failing heart to adverse hemodynamic and adrenergic loads and may thereby contribute to the progression of heart failure. We hypothesized that treatment of obstructive sleep apnea by continuous positive airway pressure in patients with heart failure would improve left ventricular systolic function.

Methods: Twenty-four patients with a depressed left ventricular ejection fraction (45 percent or less) and obstructive sleep apnea who were receiving optimal medical treatment for heart failure underwent polysomnography. On the following morning, their blood pressure and heart rate were measured by digital photoplethysmography, and left ventricular dimensions and left ventricular ejection fraction were assessed by echocardiography. The subjects were then randomly assigned to receive medical therapy either alone (12 patients) or with the addition of continuous positive airway pressure (12 patients) for one month. The assessment protocol was then repeated.

Results: In the control group of patients who received only medical therapy, there were no significant changes in the severity of obstructive sleep apnea, daytime blood pressure, heart rate, left ventricular end-systolic dimension, or left ventricular ejection fraction during the study. In contrast, continuous positive airway pressure markedly reduced obstructive sleep apnea, reduced the daytime systolic blood pressure from a mean (+/-SE) of 126+/-6 mm Hg to 116+/-5 mm Hg (P=0.02), reduced the heart rate from 68+/-3 to 64+/-3 beats per minute (P=0.007), reduced the left ventricular end-systolic dimension from 54.5+/-1.8 to 51.7+/-1.2 mm (P=0.009), and improved the left ventricular ejection fraction from 25.0+/-2.8 to 33.8+/-2.4 percent (P<0.001).

Conclusion: In medically treated patients with heart failure, treatment of coexisting obstructive sleep apnea by continuous positive airway pressure reduces systolic blood pressure and improves left ventricular systolic function. Obstructive sleep apnea may thus have an adverse effect in heart failure that can be addressed by targeted therapy.
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http://dx.doi.org/10.1056/NEJMoa022479DOI Listing
March 2003