Oxygen-derived free radical scavengers for amelioration of reperfusion damage in heart transplantation

Jurmann, M.; Schäefers, Hans-Joachim; Dammenhayn, L; Haverich, Axel

doi:10.1016/s0022-5223(19)35755-1

Cited by 42 publications

(3 citation statements)

References 28 publications

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“…The use of antioxidants in cold-storedireperfused organs could be beneficial as shown in laboratory studies with lazeroids [4, 111, DFO, and other antioxidants [2,9,10,12,131. The beneficial effects, however, have been obtained when the antioxidant was used in donor pretreatment or in the recipient.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous antioxidants have been shown to suppress reperfusion injury caused by oxyradicals in livers and other organs and under different stress conditions [2,9,10,12,131. There has been increasing interest in utilization of antioxidants in organ transplantation with clinical trials of some antioxidants (superoxide dismutase, allopurinol) reported [14].…”

Section: Hepatocyte Preservationmentioning

confidence: 99%

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Cold storage sensitizes hepatocytes to oxidative stress injury

Vreugdenhil

Rankin

Southard

1997

Transplant International

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Liver cold storage leads to oxygen free radical production and reperfusion injury. Antioxidants are effective in suppression reperfusion injury in rat livers when used in the reperfusion medium. However, in clinical liver transplantation their effectiveness is not clear, which may be due to the way they are used (in the recipient). In this study we compare the effectiveness of antioxidants when used in the reperfusion medium versus the cold storage solution in isolated hepatocytes and the isolated perfused liver. Hepatocytes were cold stored in UW solution for 24 h. Oxidative stress, induced by t-butyl hydroperoxide (tBHP), was measured in the presence of one of five different antioxidants--deferoxamine (DFO), dithiothreitol (DTT), trolox, tocopherol, dimethylthiourea (DMTU)--in the reperfusion buffer or UW solution. Efficacy was judged by reduction in membrane damage (LDH release) during rewarming. Also, rat livers were cold stored for 48 h in UW solution (+/- antioxidant) and reperfused (+/- antioxidants). Efficacy was judged by the effect on enzyme release and bile production. Cold storage of hepatocytes for 24 h sensitized them to oxidative stress. The concentration of tBHP required to induce maximal cell death (80%-90% LDH release) was reduced from 1.3 mM (fresh cells) to 0.37 mM (LD-50 values). All antioxidants except DMTU suppressed oxyradical-induced LDH release when used in the reperfusion medium, but only DFO was effective when used in the UW solution. In the isolated perfused liver, DFO, DTT, and trolox were effective and suppressed enzyme release when added to the reperfusion buffer, but none were effective when used in the UW solution. We conclude that cold storage sensitizes liver cells to oxidative stress. The most effective antioxidant was the iron chealator, DFO, which was effective in the reperfusion buffer (isolated perfused sliver or hepatocytes) but not in the UW solution when tested in the isolated perfused liver. Suppression of reperfusion injury in liver transplantation could be obtained by antioxidant therapy. However, it is unclear how best to deliver the antioxidants to the site of oxyradical generation.

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Section: Discussionmentioning

confidence: 99%

Section: Hepatocyte Preservationmentioning

confidence: 99%

Cold storage sensitizes hepatocytes to oxidative stress injury

Vreugdenhil

Rankin

Southard

1997

Transplant International

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“…In recent years, the use of free oxygen radical scavengers or antioxidants have become the center of focus in order to remove or decrease the damage caused by free oxygen radicals. [6][7][8][9][10] Calcium dobesilate (DOBE) is a pharmacological agent frequently used in the treatment of pain, edema, paresthesia, and cramps consequent to chronic venous insufficiency, venous stasis ulcers, and superficial thrombophlebitis. This occurs particularly in microangiopathies, such as diabetic retinopathy, hemorrhoids, and microcirculation disorders of arteriovenous origin.…”

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confidence: 99%

The effects of calcium dobesilate and micronized purified flavonoid fractions on myocardial protection

Akgün¹

2011

Turkish J Thorac Cardiovasc Surg

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Kalsiyum dobesilat (DOBE) ve mikronize pürifiye flavanoid fraksiyonlarının (MPFF) iskemi ve reperfüzyon sonrası sıçan kalplerinin fonksiyonları üzerindeki etkileri araştırıldı. Ça lış ma pla nı: On sekiz adet Wistar albino cinsi erkek sıçan randomize olarak üç gruba ayrıldı: DOBE (100 mg/kg/gün), MPFF (100 mg/kg/gün) ve kontrol grubu. On beş dakikalık iskemiden önce ve sonra kalpler iki kez 25 dakika perfüze edildi. Koroner perfüzatlarda kreatin kinaz, laktat dehidrogenaz, troponin I ve miyoglobin seviyeleri, miyokard doku örneklerinde ise malondialdehid ve glutatyon düzeyleri analiz edildi. Ortalama P (koroner arterleri perfüze eden ortalama basınç), PP (pik sistolik basınç), (+)dp/dtmax (kontraksiyon kuvvetinin zamanla değişimi), (-)dp/dtmax (relaksasyon kuvvetinin zamanla değişimi), PP'ye ulaşılana kadar geçen süre, ejeksiyon zamanı ve kontraksiyon zamanı hesaplandı. Bul gu lar: DOBE grubunda reperfüzyonun 1. ve 5. dakikalarındaki ortalama 'p' değerleri kontrol grubundakilerden anlamlı derecede düşük idi; ayrıca 15., 20. ve 25. dakikalarda PP, (+)dp/dtmax ve (-)dp/dtmax ölçümleri ise kontrol grubundakilerden anlamlı derecede yüksek bulundu. MPFF grubunda ise (-)dp/dtmax değeri reperfüzyonun 5. dakikasında kontrol grubundakilere göre anlamlı ölçüde daha yüksek idi. So nuç: DOBE iskemi ve reperfüzyon sonrası miyokard fonksiyonlarını iyileştirmede yararlıdır. Anah tar söz cük ler: Kalsiyum dobesilat; mikronize pürifiye flavanoid fraksiyon; miyokard korunması. Background: We aimed to investigate the effects of calcium dobesilate (DOBE) and micronized purified flavonoid fractions (MPFF) on the functions of rat hearts following ischemia and reperfusion. Methods: Eighteen male Wistar albino rats were randomly divided into three groups: the DOBE group (100 mg/kg/ day), the MPFF group (100 mg/kg/day), and the control group. The hearts were perfused twice for 25 minutes before and after 15 minutes of ischemia. Creatine kinase, lactate dehydrogenase, troponin I and myoglobin levels in the coronary perfusates, and malondialdehyde and glutathione levels in the myocardial tissue samples were analyzed. Mean P (mean pressure perfusing coronary arteries), PP (peak systolic pressure), (+)dp/dtmax (contraction strength change over time), (-)dp/dtmax (relaxation strength change over time), time to reach PP, ejection time, and contraction time were calculated. Results: The mean 'p' values of the DOBE group were significantly lower than those of the control group at the first and fifth minutes of reperfusion; moreover, PP, (+)dp/ dtmax, and (-)dp/dtmax values were found to be significantly higher than the measurements made at the 15 th , 20 th and 25 th minutes in the control group. In the MPFF group, the (-)dp/dtmax value was significantly higher than that of the control group at the fifth minute of reperfusion. Conclusion: DOBE is helpful in improving myocardial functions following ischemia and reperfusion.

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The effects of ischemia on long bone vascular resistance

Davis

Wood²

1991

Journal Orthopaedic Research

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An in vitro canine tibia model was used to assess the effects of 48 h of hypothermic (4 degrees C) ischemia on bone vascular resistance and on responsiveness of intraosseous blood vessels to circulating norepinephrine. Three groups of bones were studied: Group I (n = 11), 48 h hypothermic ischemia; Group II (n = 11), 48 h hypothermic ischemia with pretreatment with allopurinol and oxypurinol; and Group III (n = 10), no ischemia. Resting vascular resistance in both ischemic groups (79 and 74 mmHg/ml/min) was significantly higher (p less than 0.0001) than in the nonischemic group (22 mmHg/ml/min). Effects of norepinephrine on vascular resistance were significantly greater in both ischemic groups (p less than 0.004). In all three groups, acetylcholine infusion attenuated the increases in perfusion pressure caused by norepinephrine. This demonstrates secretion of endothelial-mediated relaxing factors (EDRF) and prostaglandin for up to 48 h of hypothermic ischemia. As no significant differences were detected between the two ischemic groups, this study failed to demonstrate any protective effect of xanthine oxidase inhibitors.

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Oxygen-derived free radical scavengers for amelioration of reperfusion damage in heart transplantation

Cited by 42 publications

References 28 publications

Cold storage sensitizes hepatocytes to oxidative stress injury

Cold storage sensitizes hepatocytes to oxidative stress injury

The effects of calcium dobesilate and micronized purified flavonoid fractions on myocardial protection

The effects of ischemia on long bone vascular resistance

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