Öz
Amaç: Bu in vitro çalışmada uzun etkili ve potent bir lokal anestezik olan bupivakainin endotelli ve endotelsiz dana kardiyak ven düz kası üzerine etkileri araştırılmıştır.Gereç ve Yöntem: Dana kardiyak ven halkaları %95 O2 ve %5 CO2 ile gazlandırılan ve sıcaklığı 37°C’de sabit tutulan KHS içeren izole organ banyolarına alındı. Uygulanan ajanlara verilen yanıtlar izometrik olarak kaydedildi.Bulgular: Bupivakain 10-8 – 10-4 M endotelli ve endotelsiz ven halkalarının bazal tonusunu etkilemedi. 5-HT 10-5 M ile maksimum kasılma cevabı alındıktan uygulanan bupivakain düşük konsantrasyonlarda 10-8 – 10-6 M kasılma cevaplarını anlamlı olarak azalttı, yüksek konsantrasyonlarda 10-5 – 10-4 M ise kardiyak ven halkalarında kasılma gözlendi. 10-4 M bupivakain ilavesinden sonra oluşan maksimum kasılma 5-HT ile elde edilen maksimum kasılma cevabına benzerdi. Dokuların L-NAME 10-3 M ile inkübasyonu bupivakainin düşük konsantrasyonlarında oluşan gevşeme cevaplarını inhibe etti; 10-5 ve 10-4 M bupivakain varlığında ise ven halkalarının kasılma cevapları kontrol 5-HT kasılmalarına göre anlamlı olarak yüksekti. İndometazinle 10-5 M inkübe edilen dokularda 10-8 – 10-6 M aralığında verilen bupivakain, kontrol dokulardakine benzer şekilde, doza bağlı olarak artan gevşeme cevapları oluşturdu. Bupivakainin yüksek dozlarında gözlenen kasılma cevapları ise indometazin varlığında inhibe edildi. Endotelsiz ven halkalarında ise banyoya bupivakain ilavesi 10-8 – 10-6 M 5-HT’ye bağlı maksimum kasılma cevaplarını değiştirmedi Sonuç: Bulgularımız; dana kardiyak veninde bupivakainin bazal tonusunu etkilemediğini, 5-HT ile önkasılma yapılan dokularda ise gevşeme ve kasılma tarzında bifazik cevap oluşturduğunu endotelden salıverilen NO’in bupivakainin gevşetici etkilerinde, sikloooksijenaz ürünlerinin ise kasıcı etkilerinde rol oynadığını göstermektedir
Anahtar Kelimeler
Kaynakça
- Al Saffar, MT, AL-Sandook TA, & Mahmoud YA. Possible New Concept in the Mechanism of Action of Local Anest- hesia. American J Med Biol Res 2013; 1: 134-7.
- Becker DE, Reed KL. Essentials of Local Anesthetic Phar- macology. Anesthesia Progress 2006; 53: 98-109.
- Zhang X, Zhang L, Zhang Y. Side Effects of Long-Acting Local Anaesthetics in Patients with Preexisting Cardiovas- cular Condition . Cell Biochem Biophys 2014; 69:405–9.
- Süzer MA, Özhan MÖ, Eşkin MB ve ark. Lipit İnfüzyonu Kullanılarak Başarıyla Tedavi Edilen Bir Lokal Anestezik Toksisitesi. Türk Anest Rean Der 2011; 39:159-63.
- Mclure HA, Rubin AP. Review of local anaesthetic agents. Minerva Anestesiol 2005; 71: 59-74.
- Barışkaner H, Tuncer S, Taner A, Dogan N. Effects of bu- pivacaine and ropivacaine on the isolated human umbilical artery. Int J Obstet Anesth 2003; 12: 261-5.
- Noren H, Lindblom B, Källfelt B. Effects of bupivacaine and calcium antagonists on the rat uterine artery. Acta Anaest- hesiol Scand 1991; 35: 77–80.
- Guo H, Zhang H, Xu W et al. Differential effects of short- and long-term bupivacaine treatment on α1-adrenocep- tor-mediated contraction of isolated rat aorta rings and the reversal effect of lipid emulsion. Acta Pharmacologica Sini- ca 2015; 36: 976–86.
- Mukozawa M, Takakura K, Mizogami M. Direct vasocont- ractile activities of bupivacaine enantiomers on the isolated rat thoracic aorta. Anesthesiol Res Pract 2010; 82:186-9.
- Gherardini G, Samuelson U, Jernbeck J, Aberg B, Sjostrand N. Comparison of vascular effects of ropivacaine and lido- caine on isolated rings of human arteries. Acta Anaesthesiol Scand 1995; 39: 765–8.
- Kılıcaslan A, Duman A, Sahin A S. In Vitro Vasoactive Ef- fects of Levobupivacaine and Ropivacaine on the Isolated Human Umbilical Artery and Vein. Balkan Med J 2011; 28: 164-8.
- Nakamura K, Toda H, Kakuyama M, et al. Direct vascular effect of ropivacaine in femoral artery and vein of the dog. Acta Anaesthesiologica Scandinavica. 1993; 37(3): 269–73.
- Menezes LS, Souza MA, Santos MR et al. Levobupivacai- ne induces vasodilatation, but not vasoconstriction, in rat mesenteric artery. Rev Odontol UNESP 2016; 45: 258-64.
- Aps C, Reynolds F . The effect of concentration on vaso- activity of bupivacaine and lignocaine. Br J Anaesth 1976; 48: 1171-4.
- Ignarro L J, Lippton H, Edward JC. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nit- roprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 1981; 218:739-49.
- YS Choi, YS Jeong, SH Ok et al. The direct effect of levo- bupivacaine in isolated rat aorta involves lipoxygenase pat- hway activation and endothelial nitric oxide release, Anest- hesia and Analgesia 2010; 110: 341–9.
- Hogan QH, Stadnicka A, Bosnjak ZJ, Kampine JP. Effects of lidocaine and bupivacaine on isolated rabbit mesenteric capacitance veins. Reg Anesth Pain Med 1998; 23: 409-17.
- Ok S H, Bae S, Kwon S C et al. Bupivacaine-induced Vaso- dilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine. Korean J Pain 2014;27: 229-38.
- Stankevicius E, Kevelaitis E, Vainorius E, Simonsen U. Role of nitric oxide and other endothelium-derived factors. Me- dicina (Kaunas). 2003;39:333-41.
- Y. S. Choi, Y. S. Jeong, S.-H. Ok et al., “The direct effect of levobupivacaine in isolated rat aorta involves lipoxygena- se pathway activation and endothelial nitric oxide release,” Anesthesia and Analgesia 2010; 110: 341–9.
- Lee HM, Ok SH, Sung HJ, Eun SY, Kim HJ, Lee SH, et al. Mepivacaine-induced contraction involves phosphorylati- on of extracellular signalregulated kinase through activati- on of the lipoxygenase pathway in isolated rat aortic smoo- th muscle. Can J Physiol Pharmacol 2013; 91: 285–94.
- Timponi CF, Oliveira NE, Arruda RM, Meyrelles SS, Vasquez EC. Effects of the local anaesthetic ropivacaine on vascular reactivity in the mouse perfused mesenteric arte- ries. Basic Clin Pharmacol Toxicol 2006; 98: 518–20.
- Ok SH, Han JY, Sung HJ, Yang SM, Park J, Kwon SC, Choi MJ, Sohn JT. Ropivacaine-induced contraction is attenua- ted by both endothelial nitric oxide and voltage-dependent potassium channels in isolated rat aorta. Biomed Res Int 2013; 13: 565.
Öz
Objective: In this in-vitro study effects of long acting and potent local anesthetic bupivacaine at intact and endothelium denuded calf cardiac vein were investigated.Material and Methods: Calf cardiac vein rings were placed in tissue bath containing Krebs-Henseleit Solution gassed with %95 O2 and %5 CO2at 37°C. Changes in tension produced by the agents recorded isometrically.Results: Cumulative bupivacaine did not affect basal tonus of intact and endothelium denuded vein rings. After maximum contraction response taken with 5-HT 10M , lower concentrations of 10-8 – 10-6 M bupivacaine significantly reduced contraction responses precontracted with 5-HT. At higher concentrations 10-5 – 10-4 M bupivacaine produced contraction. Incubation with 10-3 M L-NAME inhibited relaxation responses to low concentrations of bupivacaine. At higher concentrations 10-5 – 10-4 M bupivacaine produced contraction significantly higher than control . Incubation with 10-5 M indomethacin produced dose dependent relaxation responses similar with control at low concentrations of 10-8 – 10-6 M bupivacaine. Contraction response to higher concentrations 10-5 – 10-4 M of bupivacaine inhibited by Indomethacin. At endothelium denuded rings cumulative bupivacaine did not alter maximum contraction response preduced with 5-HT 10-5 M . Conclusion: Results demonstrate that bupivacain did not affect basal tonus of calf cardiac vein rings and produced biphasic effects, from relaxation to contraction at 5-HT precontracted rings. Endothelium derived NO seems to have role on bupivacaine induced relaxation and cyclooxygenase products seems to have role on bupivacaine induced contraction
Anahtar Kelimeler
Kaynakça
- Al Saffar, MT, AL-Sandook TA, & Mahmoud YA. Possible New Concept in the Mechanism of Action of Local Anest- hesia. American J Med Biol Res 2013; 1: 134-7.
- Becker DE, Reed KL. Essentials of Local Anesthetic Phar- macology. Anesthesia Progress 2006; 53: 98-109.
- Zhang X, Zhang L, Zhang Y. Side Effects of Long-Acting Local Anaesthetics in Patients with Preexisting Cardiovas- cular Condition . Cell Biochem Biophys 2014; 69:405–9.
- Süzer MA, Özhan MÖ, Eşkin MB ve ark. Lipit İnfüzyonu Kullanılarak Başarıyla Tedavi Edilen Bir Lokal Anestezik Toksisitesi. Türk Anest Rean Der 2011; 39:159-63.
- Mclure HA, Rubin AP. Review of local anaesthetic agents. Minerva Anestesiol 2005; 71: 59-74.
- Barışkaner H, Tuncer S, Taner A, Dogan N. Effects of bu- pivacaine and ropivacaine on the isolated human umbilical artery. Int J Obstet Anesth 2003; 12: 261-5.
- Noren H, Lindblom B, Källfelt B. Effects of bupivacaine and calcium antagonists on the rat uterine artery. Acta Anaest- hesiol Scand 1991; 35: 77–80.
- Guo H, Zhang H, Xu W et al. Differential effects of short- and long-term bupivacaine treatment on α1-adrenocep- tor-mediated contraction of isolated rat aorta rings and the reversal effect of lipid emulsion. Acta Pharmacologica Sini- ca 2015; 36: 976–86.
- Mukozawa M, Takakura K, Mizogami M. Direct vasocont- ractile activities of bupivacaine enantiomers on the isolated rat thoracic aorta. Anesthesiol Res Pract 2010; 82:186-9.
- Gherardini G, Samuelson U, Jernbeck J, Aberg B, Sjostrand N. Comparison of vascular effects of ropivacaine and lido- caine on isolated rings of human arteries. Acta Anaesthesiol Scand 1995; 39: 765–8.
- Kılıcaslan A, Duman A, Sahin A S. In Vitro Vasoactive Ef- fects of Levobupivacaine and Ropivacaine on the Isolated Human Umbilical Artery and Vein. Balkan Med J 2011; 28: 164-8.
- Nakamura K, Toda H, Kakuyama M, et al. Direct vascular effect of ropivacaine in femoral artery and vein of the dog. Acta Anaesthesiologica Scandinavica. 1993; 37(3): 269–73.
- Menezes LS, Souza MA, Santos MR et al. Levobupivacai- ne induces vasodilatation, but not vasoconstriction, in rat mesenteric artery. Rev Odontol UNESP 2016; 45: 258-64.
- Aps C, Reynolds F . The effect of concentration on vaso- activity of bupivacaine and lignocaine. Br J Anaesth 1976; 48: 1171-4.
- Ignarro L J, Lippton H, Edward JC. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nit- roprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 1981; 218:739-49.
- YS Choi, YS Jeong, SH Ok et al. The direct effect of levo- bupivacaine in isolated rat aorta involves lipoxygenase pat- hway activation and endothelial nitric oxide release, Anest- hesia and Analgesia 2010; 110: 341–9.
- Hogan QH, Stadnicka A, Bosnjak ZJ, Kampine JP. Effects of lidocaine and bupivacaine on isolated rabbit mesenteric capacitance veins. Reg Anesth Pain Med 1998; 23: 409-17.
- Ok S H, Bae S, Kwon S C et al. Bupivacaine-induced Vaso- dilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine. Korean J Pain 2014;27: 229-38.
- Stankevicius E, Kevelaitis E, Vainorius E, Simonsen U. Role of nitric oxide and other endothelium-derived factors. Me- dicina (Kaunas). 2003;39:333-41.
- Y. S. Choi, Y. S. Jeong, S.-H. Ok et al., “The direct effect of levobupivacaine in isolated rat aorta involves lipoxygena- se pathway activation and endothelial nitric oxide release,” Anesthesia and Analgesia 2010; 110: 341–9.
- Lee HM, Ok SH, Sung HJ, Eun SY, Kim HJ, Lee SH, et al. Mepivacaine-induced contraction involves phosphorylati- on of extracellular signalregulated kinase through activati- on of the lipoxygenase pathway in isolated rat aortic smoo- th muscle. Can J Physiol Pharmacol 2013; 91: 285–94.
- Timponi CF, Oliveira NE, Arruda RM, Meyrelles SS, Vasquez EC. Effects of the local anaesthetic ropivacaine on vascular reactivity in the mouse perfused mesenteric arte- ries. Basic Clin Pharmacol Toxicol 2006; 98: 518–20.
- Ok SH, Han JY, Sung HJ, Yang SM, Park J, Kwon SC, Choi MJ, Sohn JT. Ropivacaine-induced contraction is attenua- ted by both endothelial nitric oxide and voltage-dependent potassium channels in isolated rat aorta. Biomed Res Int 2013; 13: 565.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Original Article |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Ocak 2019 |
| Yayımlandığı Sayı | Yıl 2019 Cilt: 29 Sayı: 1 |
Genel Tıp Dergisi Creative Commons Atıf-GayriTicari 4.0 Uluslararası Lisansı (CC BY NC) ile lisanslanmıştır.