Improvement of Functional Recovery of Donor Heart Following Cold Static Storage with Doxycycline Cardioplegia

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 Ca2+; (2) with standard cardioplegia with low Ca2+; 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.

Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure

“…There are some data in the literature about the antioxidant and scavenging properties of doxycycline [38]. Doxycycline has a multiple-substituted phenol ring which is the key to its ROS-scavenging abilities.…”

Astragalin and dihydromyricetin as adjuncts to histidine‑tryptophan‑ketoglutarate cardioplegia enhances protection during cardioplegic arrest

“…When the amount of ROS available exceeds the capacity of the enzymes (such as GSH and SOD) and cannot be diminished during reperfusion, oxidative stress occurs (26). Oxidative stress-associated alterations in several intracellular signaling pathways have been implicated in the pathophysiology of severe donor heart damage during reperfusion (31). In line with these findings, preventing or at least controlling the increase in the oxidative stress levels of donor hearts during cold storage seems to be a crucial part of heart transplantation in cardiac surgery.…”

High-carbohydrate diet-induced myocardial remodelling in rats

“…Total oxidant status (TOS) and total antioxidant status (TAS) in the serum samples were measured using commercial kits (RL0017 and RL0024, respectively; Rel Assay Diagnostics, Turkey) as previously described (23). TOS or TAS assays were calibrated with H 2 O 2 , and the results were expressed in terms of µmol H 2 O 2 equivalent/L or with Trolox standard (an analogue of vitamin E) and the results were expressed as mmol Trolox equivalent/L, respectively.…”