Comparison of thiopental and ketamine+xylazine anesthesia in ischemia/reperfusion-induced arrhythmias in rats

Background/aim: To investigate the influence of thiopental (85 mg/kg, intraperitoneally (ip)), and ketamine+xylazine (ketamine 75 mg/kg and xylazine 8 mg/kg, ip) anesthesia on the incidence and duration of ischemia/reperfusion-induced arrhythmias. Materials and methods: Myocardial ischemia was induced by a 6-min ligation of the left anterior descending coronary artery, followed by a 6-min reperfusion. Measurements were taken of the incidence and duration of ventricular arrhythmias, the mean arterial blood pressure and heart rate, and the pressure rate-product (as an index of myocardial oxygen consumption). Results: The arrhythmia score and the incidence of ventricular fibrillation and tachycardia were significantly decreased in the ketamine+xylazine-anesthetized rats compared with the thiopental-anesthetized group (arrhythmia score: 2.0 ± 2.1 versus 3.7 ± 1.2, P < 0.05). The heart rate was significantly lower in the ketamine+xylazine group during the entire experiment, whilst the pressure-rate product was also significantly lower in the ketamine+xylazine group at different time points of the ischemia and reperfusion periods. Conclusion: Ketamine+xylazine anesthesia has a strong antiarrhythmic effect and an apparent depressive action on the heart rate and the myocardial oxygen consumption index. Therefore, ketamine+xylazine anesthesia is not appropriate for the evaluation of possible antiarrhythmic agents. Thiopental anesthesia is preferable to ketamine+xylazine anesthesia in the in vivo ischemia-reperfusion arrhythmia model.Background/aim: To investigate the influence of thiopental (85 mg/kg, intraperitoneally (ip)), and ketamine+xylazine (ketamine 75 mg/kg and xylazine 8 mg/kg, ip) anesthesia on the incidence and duration of ischemia/reperfusion-induced arrhythmias. Materials and methods: Myocardial ischemia was induced by a 6-min ligation of the left anterior descending coronary artery, followed by a 6-min reperfusion. Measurements were taken of the incidence and duration of ventricular arrhythmias, the mean arterial blood pressure and heart rate, and the pressure rate-product (as an index of myocardial oxygen consumption). Results: The arrhythmia score and the incidence of ventricular fibrillation and tachycardia were significantly decreased in the ketamine+xylazine-anesthetized rats compared with the thiopental-anesthetized group (arrhythmia score: 2.0 ± 2.1 versus 3.7 ± 1.2, P < 0.05). The heart rate was significantly lower in the ketamine+xylazine group during the entire experiment, whilst the pressure-rate product was also significantly lower in the ketamine+xylazine group at different time points of the ischemia and reperfusion periods. Conclusion: Ketamine+xylazine anesthesia has a strong antiarrhythmic effect and an apparent depressive action on the heart rate and the myocardial oxygen consumption index. Therefore, ketamine+xylazine anesthesia is not appropriate for the evaluation of possible antiarrhythmic agents. Thiopental anesthesia is preferable to ketamine+xylazine anesthesia in the in vivo ischemia-reperfusion arrhythmia model

Sıçanlarda, adenozin agonisti, CCPA, ve antagonisti DPCPX’in iskemi / reperfüzyon ile uyarılan aritmiler üzerine etkisi

Amaç: Adenozin supraventriküler taşikardili hastaların tedavisinde kullanılan etkili bir ilaçtır. Ancak, adenozinin iskemi ve reperfüzyon aritmileri üzerine adsenozin etkisi ile ilgili sadece bir kaç çalışma vardır ve bunlarında sonuçları tartışmalıdır. Bu çalışmada adenozinin iskemi-reperfüzyon aritmileri üzerine etkisinin araştırılması amaçlanmıştır. Yöntem ve gereç: Sol koroner arter bağlanarak 6 dakika iskemi ve bağ gevşetilerek 15 dakika reperfüzyon yapılmıştır. Bir A1 adenozin reseptor agonisti olan CCPA (2 Chloro - N6 – Cyclopentyl-adenosine) ve anatgonisti, DPCPX (8- Cyclopentyl-1,3-dipropylxanthine), 5 ?g/kg dozunda tek ve birlikte iskemiden önce, iskeminin ikinci dakikasında ve reperfüzyonu hemen takiben intravenöz olarak verilmiştir. Bulgular: Sadece ligasyonun ikinci dakikasında verilen CCPA, 15 dakikalık reperfüzyon boyunca oluşan aritmi süresini azaltmıştır. Bu dönemde verilen adenozin antagonisti, DPCPX, adenozinin bu antiaritmik etkisini ortadan kaldırmıştır. Reperfüzyon sırasında ve ligasyondan önce verilen adenozinin reperfüzyonu takiben oluşan aritmiler üzerine bir etkisi olmamıştır. Sonuç: İskemi ve reperfüzyon sırasında veriliş zamanı, adenozinin etkisinde önemlidir. Bu çalışma adenozin ile oluşturulan antiaritminin, A1 adenozin reseptorlarının aktivasyonu ile ilgili olduğunu göstermiştir.Aim: Adenosine has been commonly used to treat supraventricular tachycardia in clinics. However, there are only a few studies on the effects of adenosine on ischemia or reperfusion induced arrhythmia and they conflict with the results of the present study. During this study, we aimed to clarify the effect of adenosine on ischemia-reperfusion induced arrhythmia. Materials and methods: Left coronary artery was ligated for 6 min and it was released for 15 min to produce reperfusion. A1 adenosine agonist CCPA (2 Chloro - N6 &amp;#8211; Cyclopentyl-adenosine), and A1 selective antagonist DPCPX (8 &amp;#8211; Cyclopentyl - 1,3 -dipropylxanthine) in 5 &amp;#956;g/kg dose alone and in combination were given intravenously before ligation, at the second minute of the ligation and just following the reperfusion. Results: Adenosine given only at the second minute of the ligation is found to decrease the total duration of arrhythmia observed in the reperfusion stage. DPCPX given in this period is found to block the antiarrhythmic effect of adenosine. Adenosine given after reperfusion and before ligation was not effective in decreasing reperfusion induced arrhythmia. Conclusion: The time dependent effect of the administration during ischemia and reperfusion was important for the effect of adenosine. The present study showed that antiarrhythmia produced by adenosine is related to the activation of A1 adenosine receptor

5-Lipoksigenaz inhibitörü zileutonun miyokardiyal iskemi/reperfüzyon hasarına karşı kalp koruyucu etkisi

Background: This study aims to evaluate the effects of zileuton on myocardial ischemia/reperfusion injury and ischemia-induced ventricular arrhythmias and to investigate the role of 5-lipoxygenase pathway in the pathogenesis of myocardial ischemia/reperfusion injury. Methods: In anesthetized rats, myocardial ischemia was induced by the ligation of the left main coronary artery for 30 min before 120-min reperfusion period. Zileuton was given both at the doses of 3 and 10 mg/kg 15 min before the ligation. During the experiment, electrocardiography, blood pressure, and heart rate were recorded. The duration of arrhythmia types were determined during the ischemic period. To evaluate the ischemia/reperfusion injury in the myocardial tissue, histopathological examination was performed and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Results: Zileuton at a dose of 3 mg/kg significantly decreased the infarct size and the tissue injury score obtained using histopathological examinations (infarct size [% of the area at risk]: zileuton 3 mg/kg 36±7% versus control 66±6%, p<0.05). Zileuton 10 mg/kg was found to be ineffective. Both 3 and 10 mg/kg doses of zileuton did not shorten the duration of arrhythmias during the ischemic period. Conclusion: Our study results showed that 3 mg/kg dose of zileuton protected the heart against myocardial ischemia/ reperfusion injury. However, it was ineffective to reduce the ischemia-induced ventricular arrhythmias. Based on these results, zileuton may be a promising drug for the treatment of myocardial ischemia/reperfusion injury.Amaç: Bu çalışmada zileuton’un miyokardiyal iskemi/ reperfüzyon hasarı ve iskemi ile uyarılan ventriküler aritmiler üzerine olan etkileri değerlendirildi ve 5-lipoksigenaz yolağının miyokardiyal iskemi/reperfüzyon hasarının patofizyolojisindeki rolü araştırıldı. Çalış­ma­ planı:­ Anestezi altındaki sıçanlarda, miyokardiyal iskemi 120 dakikalık reperfüzyon periyodundan önce sol ana koroner arterin 30 dakikalık ligasyonu ile oluşturuldu. Zileuton 3 ve 10 mg/kg’lik dozlarda ligasyondan 15 dakika önce verildi. Deney süresince elektrokardiyografi, kan basıncı ve kalp atımı kayıt edildi. İskemik periyot boyunca aritmi tiplerinin süreleri tespit edildi. Miyokard dokusunda iskemi/reperfüzyon hasarını değerlendirmek için, histopatolojik inceleme yapıldı ve enfarkt alan 2,3,5 -trifenil tetrazolyum klorit boyaması ile tespit edildi. Bulgu­lar:­ Zileuton 3 mg/kg dozda enfarkt alan ve histopatolojik incelemeler sonucu elde edilen doku hasarı skorunda anlamlı bir azalmaya neden oldu (enfarkt alan [% risk alanı]: zileuton 3 mg/kg %36±7’ye kıyasla kontrol %66±6; p<0.05). 10 mg/kg zileuton etkili bulunmadı. Zileutonun 3 ve 10 mg/kg’lik dozu iskemi periyodunda ventriküler aritmilerin süresini kısaltmadı. Sonuç:­ Çalışma sonuçlarımız zileutonun 3 mg/kg’lik dozda kalbi miyokardiyal iskemi/reperfüzyon hasarına karşı koruduğunu gösterdi. Ancak, zileuton iskemi ile uyarılan aritmileri azaltmada etkili değildi. Bu sonuçlara göre, zileuton miyokardiyal iskemi/reperfüzyon hasarının tedavisi için umut verici bir ilaç olabilir

Antiarrhythmic activity of a new spiro-cyclic benzopyran activator of the cardiac mitochondrial ATP dependent potassium channels

‘Compound A’ (4ı-(N-(4-acetamidobenzyl))-2,2- dimethyl-2,3-dihydro-5ıH-spiro[chromene-4,2ı-[1,4]oxazinan]- 5ı-one) is a new spiro-cyclic benzopyran activator of the mitochondrial ATP-dependent potassium channels (mitoKATP). We researched the effect of compound A on ischemia/reperfusion (I/R)-induced ventricular arrhythmias. We also tested the hypothesis that the application of the activation of mitoKATP in combination with the inhibition of sarcolemmal ATP-dependent potassium channels (sarcKATP) may produce a stronger antiarrhythmic effect. In anesthetized rats, myocardial ischemia was performed by ligating the left main coronary artery followed by reperfusion. At a dose of 10 mg/kg, compound A significantly decreased arrhythmia scores and the total length of arrhythmias, whereas this was found to be ineffective at a dose of 3 mg/kg. Pre-treatment with 5-HD, a selective mitoKATP blocker, abolished the antiarrhythmic effect of compound A. Both diazoxide, a selective mitoKATP opener and HMR 1098, a selective sarcKATP blocker, significantly decreased the total length of arrhythmias. However, the combination of neither diazoxide nor compound A with HMR 1098 showed no additional therapeutic benefit. These results reveal that compound A may have a dose-dependent antiarrythmic effect, which is more pronounced than the antiarrhythmic effect of diazoxide. The antiarrhythmic effect of compound A may possibly depend on mitoKATP activation

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey

Background A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data

Background. We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV₁) decline and LT candidates without rapid FEV₁ decline in the last year to identify a preventable cause in patients with such rapid FEV₁ decline. Methods. All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV₁ below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV₁ decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. Results. Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV₁ in 2017 in Group 1 and between FEV₁ values in 2017 and 2018 in Group 2. Conclusions. There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care

Background Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. Methods Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. Results There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). Conclusions The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care

Background Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. Methods Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. Results There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). Conclusions The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF