The Effect of Diprydamole on Flow-Mediated Dilatation in Patients with Slow Coronary Flow

Öz

Aim: The slow coronary flow (SCF), a distinct angiographic finding characterized by presence of Thrombolysis in Myocardial Infarction (TIMI) –2 flow in the absence of coronary disease, pathophysiologically related to endothelial and microvascular dysfunction. Previous studies, it has been shown that oral diprydamole could correct the SCF angiographically. The aim of this study is to evaluate the effect of diprydamole on endothelial functions tested from the forearm, SCF which is physiopathologically related to endothelial dysfunction. Material and methods: 28 patients (22 male, 6 female, mean age 50±8.0) with angiographically-proven slow coronary flow at one or more coronary arterieswere included in study. All drugs that may interact with endothelial functions were stopped 15 days before the study. At the end of 15 days, baseline brachial artery Doppler examinations were performed and diprydamole 75 mg tid. was given to all patients during the nex tone month, and at the end of one month, brachial artery Doppler examinations were reperformed. Results: When the results of the patients before and after use of diprydamole were compared, it was observed that post-diprydamole flow mediated vasodilatation (FMD) value was significantly higher than the basal FMD value (FMD-prediprydamole: 2.7%±1.9, FMD-postdiprydamole: 3.1%±1.8, p=0.001). Nitroglyserine (NTG), thus shows endothelium-independent vasodilatation, showed no significant difference in prediprydamole and postdiprydamole period (NTG-prediprydamole: 13.1%±3.3, NTG-postdiprydamole: 13.0%±3.0, p=0.9). It was also noted that mean corrected TIMI frame count showed strong but inverse relationship with baseline FMD percent (r=-0.26, p<0.05). Conclusion: In patients with SCF, diprydamole improves FMD related to endothelial dysfunction. Key words: Slow Coronary Flow, Flow-Mediated Vasodilatation, Endothelial Dysfunction

Anahtar Kelimeler

• Slow Coronary Flow, Flow-Mediated Vasodilatation, Endothelial Dysfunction

Yavaş Koroner Akımlı Hastalarda Dipridamol’ün Akım Aracılı Dilatasyon Üzerine Etkisi

Öz

Amaç: Yavaş koroner akım (YKA), anjiyografik olarak belirgin koroner arter hastalığı yokluğunda, Thrombolysis in Myocardial Infarction (TIMI)-2 akımın izlendiği farklı bir anjiyografik bulgu olup patofizyolojisi ile ilgili olarak endotel ve mikrovasküler disfonksiyon üzerinde durulmaktadır. Önceki çalışmalarda oral başlanan dipridamolün anjiyografik olarak YKA'ı düzelttiği gösterilmiştir. Bu çalışmanın amacı;fizyopatolojisinde endotel disfonksiyonunun düşünüldüğü YKA'da, dipridamolün endotel fonksiyonları üzerine olan etkisini değerlendirmektir. Gereç ve yöntem: Çalışmaya anjiyografik olarak bir veya daha fazla koroner arterinde yavaş akımın tespit edildiği, 28 hasta (ortalama yaşları 50 ± 8.0 olan 22 erkek 6 kadın) alındı. Çalışmaya katılan hastalarda endotel fonksiyonlarını etkileyebilecek olan ilaçlar 15 gün öncesinden kesildi. 15. gün sonunda bazal brakiyal arter Doppler incelemesi yapıldıktan sonra hastalara 1 ay süre ile 75 mg dipridamol günde 3 defa verildi ve 1. ay sonunda brakiyal arter Doppler incelemesi tekrarlandı. Bulgular: Hastaların dipridamol öncesi ve sonrası değerleri karşılaştırıldığında bazal akım aracılı vazodilatasyon (AAD) % değerine göre dipridamol sonrası bakılan % AAD değerinde anlamlı artış izlendi (AAD dipridamol öncesi: %2.7±1.9, AAD dipridamol sonrası: %3.1±1.8, p=0.001). Nitrogliserin (NTG), yani endotel bağımsız dilatasyonda dipridamol öncesi ve sonrası açısından farklılık tespit edilmedi (NTG dipiridamol öncesi: %13.1±3.3, NTG dipiridamol sonrası: %13.0±3.0, p=0.9). Ortalama düzeltilmiş TIMI frame sayısının bazal AAD yüzdesi ile güçlü fakat ters bir ilişki gösterdiği belirlendi. (r=-0.26, p<0.05) Sonuç: YKA'lı hastalarda dipridamol, endotel disfonksiyonuna bağlı olarak gelişen bozulmuş AAD üzerine olumlu etki gösterir. Anahtar kelimeler: Yavaş Koroner Akım, Akım Aracılı Vazodilatasyon, Endotel Disfonksiyonu

Anahtar Kelimeler

• Yavaş Koroner Akım, Akım Aracılı Vazodilatasyon, Endotel Disfonksiyonu

Kaynakça

1. Tambe AA, Demany MA, Zimmerman HA, Mascarenhas E. Angina pectoris and slow flow velocity of dye in coronary arteries. A new angiographic finding. Am Heart J 1972; 84: 66-71.
2. Mangieri E, Macchiarelli G, Ciavolella M, Barillà F, Avella A, Martinotti A, Dell'Italia LJ, Scibilia G, Motta P, Campa PP. Slow coronary flow: Clinical and histopathological fetures in patients with otherwise normal epicardial coronary arteries. Cathet and Cardiovasc Diagn 1996; 37: 375-81.
3. Goel PK, Gupta SK, Agarwai A, Kapoor A. Slow coronary flow: A distinct angiographic subgroup in syndrome X. Angiology 2001; 52:507-14.
4. Celermajer DS, Sorensen KE, Gooch VM, Spi egelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-15.
5. Laurent S, Lacolley P, Brunel P, Laloux B, Pannier B, Safar M. Flow-dependent vasodilation of brachial artery in essential hypertension. Am J Physiol 1990; 258: H100-11.
6. Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation 1989; 79: 93- 100.
7. Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, Deanfield JE. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J 1995; 74: 247- 53.
8. Motz W, Vogt M, Rabenau O, Scheler S, Lückhoff A, Strauer BE. Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. Am J Cardiol 1991; 68: 996-03.

9. Sun D, Huang A, Smith CJ, Stackpole CJ, Connetta JA, Shesely EG, Koller A, Kaley G. Enhanced release of prostaglandins contributes to flow-induced arteriolar dilatation in eNOS knockout mice. Circ Res 1999 ; b85:288–293.
10. KurtogluN, Akcay A, Dindar I. Usefulness of oral dipyridamol theraphy for angiographic slow coronary flow. Am J Cardiol 2001; 87: 777-79.
11. Gibson CM, Cannon CP, Daley WL, Dodge JT, Alexander B, Marble SJ, McCabe CH, Raymond L, Fortin T, Poole WK, Braunwald E. TIMI frame count. A quantitative method of assessing coronary artery flow. Circulation 1996; 93: 879-88.
12. Mosseri M, Yarom R, Gotsman MS, Hasin Y. Histologic evidence for small-vessel coronary artery disease in patients with angina pectoris and patent large coronary arteries. Circulation 1986; 5: 964-72.
13. Sezgin A.T, Sığırcı A, Barutcu I, Topal E, Sezgin N, Ozdemir R, Yetkin E, Tandogan I, Kosar F, Ermis N, Yologlu S, Bariskaner E, Cehreli S. Vascular endothelial function in patients with slow coronary flow. Coron Arter Disease 2003; 14: 155-61.
14. Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of the endothelium in the vasodilator response to flow in vivo. Hypertension 1985; 8: 37-44.
15. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Lüscher TF. Nitric oxide is responsible for flow- dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995; 91: 1314-19.
16. Rossen JD, Oskarsson H, Minor Rl Jr, et Talman CL, Winniford MD. Effect of adenosine antagonism on metabolically mediated coronary vasodilation in humans. J Am Coll Cardiol 1994; 23: 1421- 26.
17. Feletou M, Vanhoutte PM. The alternative: EDHF. J Moll Cell Cardiol 1999; 31: 15-22.
18. Baursachs J, Popp R, Fleming I, Busse R. The coronary endothelium-derived hyperpolarizing factor (EDHF) stimulates multiple signalling pathways and proliferation in vascular cells. Pflugers Arch 2001; 442: 511-8.
19. Yada T, Richmond KN, Van Bibber R, Kroll K, Feigl EO. Role of adenozin in local metabolic coronary vasodilation. Am J Physiol 1999; 276: H1425-33.
20. Defily DV, Chilian WM, Coronary microcirculation: autoregulation and metabolic control. Basic Res Cardiol 1995; 90: 112-18.
21. Smits P, Williams SB, Lipson DE, Banitt P, Rongen GA, Creager MA. Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. Circulation 1995; 92: 2135-41.
22. Lücher TF, Richard V, Tschudi M, Yang ZH, Boulanger C. Endothelial control of vascular tone in large and small coronary arteries. J Am Coll Cardiol 1990; 15: 519-27.