Turkiye Klinikleri Journal of Cardiology

.: ORIGINAL RESEARCH
Adenozin Reseptör Antagonisti Olarak Teofilinin İskemik Ön Koşullanmayı Gösteren Warm-Up Fenomeni Üzerine Etkisi
THE EFFECT OF THEOPHYLLINE AS A ADENOSINE RECEPTOR ANTAGONIST ON ISCHEMIC PRECONDITIONING SHOWING WARM-UP PHENOMENON
Haldun AKGÖZ*, Şennur ÜNAL DAYİ*, Seden ÇELİK*, Onur ERDOĞMUŞ*, Hasan SAMUR*, Ufuk GÜRKAN*, Gülşah TAYYARECİ*, Tezer ULUSOY*
*, Siyami Ersek Göğüs Kalp veDamar Cerrahisi Merkezi, Kardiyoloji Kliniği, İSTANBUL
Turkiye Klinikleri J Cardiol. 2002;15(6):389-93
Article Language: TR
Full Text
ÖZET
 Amaç: Stabil anjina pektorisli hastalar kısa süre içinde ardışık iskemi epizodlarına maruz kaldıklarında miyokardiyal iskemiye karşı artan bir tolerans gösterirler. Ardışık egzersiz testlerinde ortaya çıkan bu durum warm-up fenomeni olarak adlandırılmıştır. Çalışmamızın amacı iskemik ön koşullanmada önemli bir rol oynadığı düşünülen adenozinin etkisini, onun reseptör antagonisti olan teofilin ile bloke ederek warm-up fenomeni üzerinde değerlendirmektir.Materyel ve metod: Stabil koroner arter hastalığı olan ve standart egzersiz testinde en az 1 evre tamamlamış ve 1 mm veya daha fazla horizontal ST segment depresyonu saptanan 27 olgu çalışmaya alındı. Olgulara iki ayrı günde modifiye Bruce protokolü kullanılarak semptomla sınırlı 4 egzersiz testi uygulandı. Birinci gün 4 mg/kg intravenöz teofilin perfüzyonunu takiben 20 dakika ara ile 48 saat sonra ise plasebo olarak aynı miktarda %0.9luk NaCl çözeltisi kullanılarak yine 20 dakika ara ile ikişer egzersiz testi uygulandı. Birinci testen sonra olgulardan kan örneği alınarak teofilin düzeyleri ölçüldü. Egzersiz testlerine göre 1 mm ST segment çökme zamanı, total egzersiz süresi, hız basınç çarpımı ve pik egzersizde oluşan ST segment depresyonu kaydedildi.Bulgular: Plasebo ile yapılan testlerde 1 mm ST segment depresyonu oluşma zamanı ortalama 478±207 snden 562±210 snye (P=0.001), total egzersiz süresi 589±228 snden 643±222 snye yükseldi (P=0.009). İskemik ön koşullanma 1 mm ST depresyonu oluşma zamanındaki hız basınç çarpımında görülen artış ile de destekleniyordu (19442±3447den 21220±4739, P=0.001). Maksimum ST segment depresyonu ise plasebo ile yapılan testler esnasında anlamlı değişiklik göstermiyordu (1.25±0.4 mm den 1.27±0.4 mm, P=0.8). Teofilin ile yapılan testler incelendiğinde 1 mm ST depresyonu görülme zamanı ortalama 515±212 snden 575±209 snye artıyordu (P=0.002), ancak total egzersiz süresi ortalama 666±218 snden 672±230 snye (P=0.7), 1 mm ST depresyonu anındaki hız basınç çarpımı 21820±3689dan 22227±4282ye (P=0.07) artıyordu ve istatistiki olarak anlamlı değildi. Maksimum ST segment depresyonu ise plaseboya benzer şekilde değişiklik göstermiyordu (1.39±0.58 mmden 1.31±0.48 mm, P=0.34). Olgularda ölçülen ortalama teofilin düzeyi 11.5±4.1 ug/ml idi.Sonuç: Çalışmamızın bulguları iskemik ön koşullanmada miyositlerden salınan adenozinin aracı rolünü desteklemektedir. Teofilinin antagonist etkisi iskemik toleransı azaltarak warm-up fenomeninin tam ve belirgin olarak ortaya çıkışını engellemiştir.

Anahtar Kelimeler: Warm-up fenomeni, İskemik ön koşullanma, Teofilin
ABSTRACT
 Purpose: Patients with stable angina frequently exhibit increased tolerance to myocardial ischemia when several episodes of ischemia, separated by a brief recovery period, occur in a short time. This is so called warm-up phenomenon can be documented during serial exercise test. Aim of this study is to evaluate whether the adenosine receptor antagonist theophylline prevents warm-up in patients with stable angina.Materials and Methods: The study included 27 patients.All of them had stable coronary artery disease and had completed at least 1 stage of a standard exercise protocol, with the exercise resulting in >0.1 mV of ST segment depression. Each underwent 4 exercise test with modified Bruce protocol on 2 separate days.On study day 1, patients received theophylline (4 mg/kg) intravenously over 20 minutes immediately before exercise testing. Two exercise tests separated by a 20 minute recovery period were then performed. On study day 2, the protocol was repeated after administiration of the plasebo.After the first exercise test samples of whole blood were collected in a tube for theophylline measured. Data obtained from the electrocardigrams included time to onset of 1 mm ST segment depression, rate-pressure product at onset of 1 mm ST segment depression, magnitude of ST segment depression at peak exercise and total exercise duration.Results: Time to onset of ST segment depression and total exercise duration was significantly prolonged during the second exercise test compared with the first exercise test after placebo (478±207 vs 562±210 seconds; p=0.001, 589±228 vs 643±222 seconds p=0.009). Rate-pressure product at onset of ST segment depression was increased at second exercise test (19442±3447 vs 21220±4739, p=0.001).Maximum ST segment depression was not changed significantly during the second exercise test (1.25±0.4 vs 1.27±0.4 mm, p=0.8). Mean time to 1 mm ST segment depression increased during the second exercise test compared with the first after theophylline (515±212 vs 575±209 seconds, p=0.002), but total exercise duration, mean rate-pressure product at onset of ST segment depression and maximum ST segment depression was not increased significantly during the second exercise test. The mean theophylline level was 11.5±4.1 ug/ml.Conclusion: Our study results supports the role of adenosine, that is released from ischemic myosite, on ischemic preconditioning. The antagonist effect of theophylline had decreased the tolerance of ischemia and had blocked the warm-up phenomenon occur completely.

Keywords: Warm-up phenomenon, Ischemic preconditioning, Theophylline

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