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Improvement of functional recovery of donor heart following cold static storage with doxycycline cardioplegia.

Ozcinar E, Okatan EN, Tuncay E, Eryilmaz S, Turan B - Cardiovasc. Toxicol. (2014)

Bottom Line: At the end of the storage period, hearts preserved in DOX cardioplegia had significantly less weight gain than those preserved in the standard cardioplegia.DOX cardioplegia-induced preservation resulted in significantly higher heart rates and better recovery quality during reperfusion in aortic flow compared to the standard cardioplegia group.Recovery in the left ventricular function and Lambeth Convention Arrhythmia scores during 1 h reperfusion were also significantly better in the DOX cardioplegia group.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Ankara Diskapi Training and Research Hospital, Ministry of Health, 06330, Ankara, Turkey.

ABSTRACT
Injury to the donor heart during cold preservation has a negative impact on graft survival before transplantation. This study aims to examine whether doxycycline, known as an MMP-2 inhibitor, has a positive effect on donor heart preservation via its antioxidant action when added to standard preservation solution. Hearts were obtained from 3-month-old male Wistar rats and randomly divided into three groups: hearts stored for 1 h at 4 °C (1) with doxycycline preservation solution (DOX cardioplegia) with low Ca(2+); (2) with standard cardioplegia with low Ca(2+); and (3) unstored hearts. All hearts were perfused in working mode, arrested at 37 °C, removed from the perfusion system, reattached in Langendorff perfusion system, and converted to working mode for 1 h. At the end of the storage period, hearts preserved in DOX cardioplegia had significantly less weight gain than those preserved in the standard cardioplegia. DOX cardioplegia-induced preservation resulted in significantly higher heart rates and better recovery quality during reperfusion in aortic flow compared to the standard cardioplegia group. Recovery in the left ventricular function and Lambeth Convention Arrhythmia scores during 1 h reperfusion were also significantly better in the DOX cardioplegia group. Biochemical data showed that DOX cardioplegia prevented an increase in MMP-2 activity and blocked apoptosis through increased activity of the pro-survival kinase Akt in the donor heart homogenates. DOX cardioplegia also led to a balanced oxidant/antioxidant level in the heart homogenates. This is the first study to report that cardioplegia solution containing doxycycline provides better cardioprotection via the preservation of heart function, through its role in controlling cellular redox status during static cold storage.

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Related in: MedlinePlus

DOX preservation solution during cold static storage of donor hearts preserves total antioxidant capacity of the myocardium. Total antioxidant status measured with respect to Trolox (a) and total oxidant status measured with respect to H2O2 (b) in heart homogenates of unstored hearts (CON), stored hearts with DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C) for 1 h at +4 °C. Bars represent mean ± SEM, n = 5–6 homogenates/group/protocol. *p < 0.05 versus CON group, †p < 0.05 versus Stand-C group by one-way ANOVA
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Fig6: DOX preservation solution during cold static storage of donor hearts preserves total antioxidant capacity of the myocardium. Total antioxidant status measured with respect to Trolox (a) and total oxidant status measured with respect to H2O2 (b) in heart homogenates of unstored hearts (CON), stored hearts with DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C) for 1 h at +4 °C. Bars represent mean ± SEM, n = 5–6 homogenates/group/protocol. *p < 0.05 versus CON group, †p < 0.05 versus Stand-C group by one-way ANOVA

Mentions: A well-established method to demonstrate oxidative stress markers in any tissue is to measure both total oxidant status (TOS) and total antioxidant status (TAS) [16]. To explore the balance between TOS and TAS in donor hearts after 1-h cold static storage, we measured their levels in the heart homogenates of all three groups. While TOS level was higher, TAS level was lower in the donor hearts after 1-h cold static storage with standard preservation solution compared to those of both unstored and the DOX cardioplegia groups (Fig. 6a, b, respectively). Therefore, this suggests that using DOX preservation solution during cold static storage of donor hearts can preserve the balance between TOS and TAS in donor myocardium.Fig. 6


Improvement of functional recovery of donor heart following cold static storage with doxycycline cardioplegia.

Ozcinar E, Okatan EN, Tuncay E, Eryilmaz S, Turan B - Cardiovasc. Toxicol. (2014)

DOX preservation solution during cold static storage of donor hearts preserves total antioxidant capacity of the myocardium. Total antioxidant status measured with respect to Trolox (a) and total oxidant status measured with respect to H2O2 (b) in heart homogenates of unstored hearts (CON), stored hearts with DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C) for 1 h at +4 °C. Bars represent mean ± SEM, n = 5–6 homogenates/group/protocol. *p < 0.05 versus CON group, †p < 0.05 versus Stand-C group by one-way ANOVA
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3936127&req=5

Fig6: DOX preservation solution during cold static storage of donor hearts preserves total antioxidant capacity of the myocardium. Total antioxidant status measured with respect to Trolox (a) and total oxidant status measured with respect to H2O2 (b) in heart homogenates of unstored hearts (CON), stored hearts with DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C) for 1 h at +4 °C. Bars represent mean ± SEM, n = 5–6 homogenates/group/protocol. *p < 0.05 versus CON group, †p < 0.05 versus Stand-C group by one-way ANOVA
Mentions: A well-established method to demonstrate oxidative stress markers in any tissue is to measure both total oxidant status (TOS) and total antioxidant status (TAS) [16]. To explore the balance between TOS and TAS in donor hearts after 1-h cold static storage, we measured their levels in the heart homogenates of all three groups. While TOS level was higher, TAS level was lower in the donor hearts after 1-h cold static storage with standard preservation solution compared to those of both unstored and the DOX cardioplegia groups (Fig. 6a, b, respectively). Therefore, this suggests that using DOX preservation solution during cold static storage of donor hearts can preserve the balance between TOS and TAS in donor myocardium.Fig. 6

Bottom Line: At the end of the storage period, hearts preserved in DOX cardioplegia had significantly less weight gain than those preserved in the standard cardioplegia.DOX cardioplegia-induced preservation resulted in significantly higher heart rates and better recovery quality during reperfusion in aortic flow compared to the standard cardioplegia group.Recovery in the left ventricular function and Lambeth Convention Arrhythmia scores during 1 h reperfusion were also significantly better in the DOX cardioplegia group.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Ankara Diskapi Training and Research Hospital, Ministry of Health, 06330, Ankara, Turkey.

ABSTRACT
Injury to the donor heart during cold preservation has a negative impact on graft survival before transplantation. This study aims to examine whether doxycycline, known as an MMP-2 inhibitor, has a positive effect on donor heart preservation via its antioxidant action when added to standard preservation solution. Hearts were obtained from 3-month-old male Wistar rats and randomly divided into three groups: hearts stored for 1 h at 4 °C (1) with doxycycline preservation solution (DOX cardioplegia) with low Ca(2+); (2) with standard cardioplegia with low Ca(2+); and (3) unstored hearts. All hearts were perfused in working mode, arrested at 37 °C, removed from the perfusion system, reattached in Langendorff perfusion system, and converted to working mode for 1 h. At the end of the storage period, hearts preserved in DOX cardioplegia had significantly less weight gain than those preserved in the standard cardioplegia. DOX cardioplegia-induced preservation resulted in significantly higher heart rates and better recovery quality during reperfusion in aortic flow compared to the standard cardioplegia group. Recovery in the left ventricular function and Lambeth Convention Arrhythmia scores during 1 h reperfusion were also significantly better in the DOX cardioplegia group. Biochemical data showed that DOX cardioplegia prevented an increase in MMP-2 activity and blocked apoptosis through increased activity of the pro-survival kinase Akt in the donor heart homogenates. DOX cardioplegia also led to a balanced oxidant/antioxidant level in the heart homogenates. This is the first study to report that cardioplegia solution containing doxycycline provides better cardioprotection via the preservation of heart function, through its role in controlling cellular redox status during static cold storage.

Show MeSH
Related in: MedlinePlus