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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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Effect of using DOX cardioplegia on heart rate and Lambeth Convention Arrhythmia (LCA) scores during the 1-h reperfusion after 1-h cold static storage. Recovery patterns (in a time-dependent manner) of heart rate (a) and LCA scores (b) during 1-h reperfusion measured every 10 min after 1-h cold static storage of donor hearts. Comparison with the values before the storage with either DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C). The arrythmia scores of the hearts were recorded with bipolar ECG by using two electrodes. Values are mean ± SEM for n = 7–9 rats/protocol. Asterisk indicates significant difference between the values stored with DOX cardioplegia and standard cardioplegia (p < 0.05) by one-way ANOVA (in a) and Mann–Whitney U test (in b)
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Fig3: Effect of using DOX cardioplegia on heart rate and Lambeth Convention Arrhythmia (LCA) scores during the 1-h reperfusion after 1-h cold static storage. Recovery patterns (in a time-dependent manner) of heart rate (a) and LCA scores (b) during 1-h reperfusion measured every 10 min after 1-h cold static storage of donor hearts. Comparison with the values before the storage with either DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C). The arrythmia scores of the hearts were recorded with bipolar ECG by using two electrodes. Values are mean ± SEM for n = 7–9 rats/protocol. Asterisk indicates significant difference between the values stored with DOX cardioplegia and standard cardioplegia (p < 0.05) by one-way ANOVA (in a) and Mann–Whitney U test (in b)

Mentions: The time course of spontaneous heart rates of donor hearts during the 1-h reperfusion period following 1-h cold static storage with or without DOX preservation solution is given in Fig. 3a. The baseline values (or control values without any storage) of the heart rates of donor hearts ranged from 320 to 360 beats/min−1. As shown in Fig. 3a, the recovery in the heart rate during the 1-h reperfusion period was better in the DOX cardioplegia group than the standard preservation solution group, even though the time course of these two groups overlapped during the first 30 min of the reperfusion period.Fig. 3


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)

Effect of using DOX cardioplegia on heart rate and Lambeth Convention Arrhythmia (LCA) scores during the 1-h reperfusion after 1-h cold static storage. Recovery patterns (in a time-dependent manner) of heart rate (a) and LCA scores (b) during 1-h reperfusion measured every 10 min after 1-h cold static storage of donor hearts. Comparison with the values before the storage with either DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C). The arrythmia scores of the hearts were recorded with bipolar ECG by using two electrodes. Values are mean ± SEM for n = 7–9 rats/protocol. Asterisk indicates significant difference between the values stored with DOX cardioplegia and standard cardioplegia (p < 0.05) by one-way ANOVA (in a) and Mann–Whitney U test (in b)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Effect of using DOX cardioplegia on heart rate and Lambeth Convention Arrhythmia (LCA) scores during the 1-h reperfusion after 1-h cold static storage. Recovery patterns (in a time-dependent manner) of heart rate (a) and LCA scores (b) during 1-h reperfusion measured every 10 min after 1-h cold static storage of donor hearts. Comparison with the values before the storage with either DOX cardioplegia (DOX-C) or standard cardioplegia (Stand-C). The arrythmia scores of the hearts were recorded with bipolar ECG by using two electrodes. Values are mean ± SEM for n = 7–9 rats/protocol. Asterisk indicates significant difference between the values stored with DOX cardioplegia and standard cardioplegia (p < 0.05) by one-way ANOVA (in a) and Mann–Whitney U test (in b)
Mentions: The time course of spontaneous heart rates of donor hearts during the 1-h reperfusion period following 1-h cold static storage with or without DOX preservation solution is given in Fig. 3a. The baseline values (or control values without any storage) of the heart rates of donor hearts ranged from 320 to 360 beats/min−1. As shown in Fig. 3a, the recovery in the heart rate during the 1-h reperfusion period was better in the DOX cardioplegia group than the standard preservation solution group, even though the time course of these two groups overlapped during the first 30 min of the reperfusion period.Fig. 3

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