Sodium-Hydrogen Exchange Inhibition by Cariporide to Reduce the Risk of Ischemic Cardiac Events in Patients Undergoing Coronary Artery Bypass Grafting: Results of the EXPEDITION Study

Mentzer, Robert M.; Bartels, Claus; Bolli, Roberto; Boyce, Steven W.; Buckberg, Gerald D.; Chaitman, Bernard R.; Haverich, Axel; Knight, John L.; Menasché, Philippe; Myers, Mary Lee; Nicolau, José Carlos; Simoons, Maarten L.; Thulin, L; Weisel, Richard D.

doi:10.1016/j.athoracsur.2007.10.054

Cited by 246 publications

(203 citation statements)

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“…Nevertheless, NHE inhibitors (eniporide or cariporide) were used as an adjunct to therapy in patients in order to delay pHi recovery during reperfusion in ESCAMI, GUARDIAN and EXPEDITION trials and gave largely disappointing results [36][37]. Further research is needed to investigate the relationship between acidosis, ROS signaling and other mechanisms of PostC cardioprotection and to identify potential ways to translate this knowledge to the treatment of patients undergoing reperfusion.…”

Section: Clinical Considerationsmentioning

confidence: 99%

Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart

Penna

Perrelli

Tullio

et al. 2013

Journal of Surgical Research

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Section: Clinical Considerationsmentioning

confidence: 99%

Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart

Penna

Perrelli

Tullio

et al. 2013

Journal of Surgical Research

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“…In animal studies it exerted a powerful anti-infarct effect when present during an ischemic insult, but showed no benefit when present only after reperfusion. 39 In the EXPEDITION trial, 40 cariporide was tested in patients undergoing coronary bypass surgery. It was started prior to surgery and infusion continued for 24 h. Unfortunately, mortality caused by cerebrovascular events increased in the treatment group.…”

Section: Circulation Journal Vol73 July 2009mentioning

confidence: 99%

Why Do We Still Not Have Cardioprotective Drugs?

Downey

Cohen

2009

Circ J

125

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Despite thousands of publications describing agents that limit infarct size in animals, all we have available today is reperfusion therapy. In this review, we examine why these drugs have not been translated into clinical practice.Many of the first interventions tested in clinical trials were very controversial in animal trials and their actual efficacy is still in question. Interventions based on the preconditioning mechanism have been very reproducible in animals, but clinical testing of them has just begun. Only approximately 25% of reperfused patients have infarcts large enough to put them at risk of heart failure and would require additional treatment. Inclusion of the 75% of patients with small infarcts in treatment groups has greatly diluted the significance of data in past clinical trials. Size of the risk zone has emerged as a reliable way to identify the vulnerable 25%. Recent small-scale clinical trials using risk stratification algorithms have shown clear infarct size limitation using ischemic and pharmacological postconditioning, confirming that the human heart responds like hearts of animal models. Most cardioprotectants have been studied in healthy animals, but recent studies indicate that aging and diabetes, common in coronary patients, do interfere with preconditioning-based interventions in animals. Clearly more study is needed to identify which interventions are adversely affected by comorbidities. (Circ J 2009; 73: 1171 -1177

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“…İlk olarak GUARDİAN çalışmasında ST-segment yükselmesi olmayan akut koroner sendrom hastalarında (NSTE-ACS) veya planlanmış elektif revaskülarizasyonlarda (PCI ya da CABG) değerlendirilmiş-tir (40) . CABG'de bir efi kasite sinyali kaydedilmiş ve sonrasında ilaç daha büyük CABG çalışmasına konu edilmiştir (41) . EXPEDİTİON çalışmasının birincil sonlanım noktasına (ölüm ve Mİ), kariporid grubunda plasebo grubuna kıyasla daha az rastlanmıştır (19) .…”

Section: Kardi̇yopleji̇k Arrest Sonrasi İ/r Hasarina Müdahaleunclassified

Ischemia-Reperfusion Injury

Songur¹

2015

Kosuyolu Heart Journal

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Genel kanı olarak, reperfüzyon hasarı, epikardial büyüme ve antegrat kan akımının normale dönmesiyle iliş-kili infarksiyon sürecinin bir bileşeni olmasına rağmen, kateterizasyon laboratuvarında, iskemi -reperfüzyon hasarı (İ/R) sık sık "no refl ow" fenomeni ile eş anlamlı olarak kullanılır. Reperfüzyon sırasında ise, iyon akışında hızlı bir değişim meydana gelir ve pH'ın normale dönüşü sırasında sitotoksisite oluşur. Na + -H + ve Na + -HCO3 + transportunu içeren Na + bağımlı pH düzenleme mekanizmaları aktive olur ki bu olay hücre içi Na + birikimine yol açar. Yüksek Na + konsantrasyonu Na + -Ca + değişimi ile intraselüler Ca + konsantrasyonunu artırır. Hücre içinde Ca +2 iyon konsantrasyonunun artışı hücre için sitotoksiktir. Kardiyak cerrahi sonucu ortaya çıkan İ/R, spontan miyokart infarktüsüne bağlı olan İ/R'den farklıdır. Cerrahi tamamlandığında kros klemp kaldırılır, kalp birden bire yüksek oranda antikoagülan içeriği olan, kardiyopulmoner baypas cihazının immünolojik etkilerine maruz kalmış ve yüksek oranda oksijen içeren kan ile reperfüze olur. Sonuç olarak, kardiyak cerrahi sonrası myokard, aşırı iskemi ve reperfüzyona maruz kalır. Klinik olarak ameliyat sonrası İ/R hasarı; aritmi, myokardiyal stunning, düşük kalp debisi veya ameliyat sonrası miyokart infarktüsü ile kendini gösterebilir. Kardiyak cerrahide kalp korunmasında en önemli köşe taşı kardiyoplejik solüsyondur. Bu solüsyon potasyum, mannitol ve glukoz içerir. Arrest edilmiş ve soğutulmuş kalpte metabolik ihtiyaçlar minimize edilmiş olur. Yıllar içinde gelişen tecrübeyle birlikte, kardiyoplejik solüsyonların içeriklerinde ufak değişiklikler meydana gelmiştir. Tüm bunlara rağmen kardiyopleji sonrası İ/R hala gözlemlenmektedir.Anahtar Kelimeler: Hasar; iskemi-reperfüzyon; açık kalp cerrahisi; miyokart Ischemia-Reperfusion Injury ABSTRACTWhile reperfusion injury is widely considered to represent a component of the infarction process related to epicardial growth and normalization of antegrade blood fl ow, the term ischemia/reperfusion (I/R) injury is frequently used synonymously with the "no refl ow" phenomenon. I/R injury after cardiac surgery is completely different from I/R injury after spontaneous myocardial infarction (MI). During reperfusion, ion transfer is rapidly altered and cytotoxicity develops as pH is normalized. Na + dependent pH regulation mechanisms such as, Na + -H + and Na + -HCO 3+ transport are activated, triggering the accumulation of intracellular Na + . Elevated intracellular Na+ levels are associated with increased intracellular Ca +2 concentrations through the activity of the Na + -Ca +2 exchanger. Elevated Ca +2 ion concentrations have a cytotoxic impact. After completion of the surgical procedure, when the cross clamp is released, the cardiac tissues are re-perfused with a highly anticoagulated and oxygenated blood, which is affected from the immunological effects of the cardiopulmonary bypass pump. Thus, after cardiac surgery myocardium is exposed to excessive ischemia and reperfusion injury that may manifest themselves as...

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Sodium-Hydrogen Exchange Inhibition by Cariporide to Reduce the Risk of Ischemic Cardiac Events in Patients Undergoing Coronary Artery Bypass Grafting: Results of the EXPEDITION Study

Cited by 246 publications

References 29 publications

Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart

Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart

Why Do We Still Not Have Cardioprotective Drugs?

Ischemia-Reperfusion Injury

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