Impact of Cold Ischemia on Mitochondrial Function in Porcine Hearts and Blood Vessels

Abstract

The effects of cold storage using Custodiol® (Histidine-Tryptophan-Ketoglutarate, HTK) or isotonic saline solution on mitochondrial function in hearts (left and rights ventricles) and various blood vessels of pigs were investigated. Hearts, saphenous veins, internal-mammary-arteries and aortas of male landrace pigs were harvested and exposed to cold ischemia in either saline or Custodiol-HTK solution. Mitochondrial function was measured in situ in permeabilized fibers by high-resolution respirometry. Mitochondrial respiratory capacities (maximal respiration rates) were similar in the right and left ventricle in controls and after 14 h of cold storage were significantly better preserved in Custodiol-HTK than in saline solution. Mitochondrial respiration rates in various blood vessels including aorta, arteries and veins were less than 5% of myocardium rates. In contrast to the pig heart, in some blood vessels, like veins, mitochondrial function remained stable even after 24 h of cold ischemia. HTK-Custodiol protection of mitochondrial function after prolonged cold ischemia was observed in the myocardium but not in blood vessels. HTK-Custodiol solution thus offers significant protection of myocardial mitochondria against cold ischemic injury and can be used as efficient preservation solution in organ transplantation but probably has no benefit for blood vessels preservation. Analysis of mitochondrial function can be used as a valuable approach for the assessment of cold ischemic injury in various tissues including pig heart and various blood vessels.

Acute Myocardial Infarction Reduces Respiration in Rat Cardiac Fibers, despite Adipose Tissue Mesenchymal Stromal Cell Transplant

“…Our data are in general very comparable with the literature [42,43] with respect to the respiratory parameters of oxygen flux (expressed in wet weight (ww)). Similar to previous reports [29,44,45], we also showed that AMI decreased mitochondrial respiration in cardiac cells in different functional states, mainly those associated to ATP synthesis, with ultrastructural modifications in an acute lesion scenario. The feeding by electrons of the ETS in the necrotic phase was more affected through complex I (NADH: ubiquinone oxidoreductase) than that starting from the succinate dehydrogenase (complex II), although both were completely damaged in the fibrotic phase of the IZ (IZ still responded to succinate addition during the necrotic phase).…”

“…Finally, the accentuated increase in respiration after addition of cytochrome c (Figure 3(k)) at the acute phase in IZ-which reveals important damage in the internal mitochondrial membrane and cytochrome c release-could be considered a key and transient event determining the fate of the fibers towards cardiomyocyte death. The increase that doubles the accepted normal values around 15% [56] shows the trigger of the apoptotic cascade [45,57,58], which progressively culminates with late left ventricle dysfunction. The normalized values of cytochrome c found in IZ during fibrotic phase could be justified by the low response to most part of the reagents (Figure 3).…”

The Role of Mitochondria in the Mechanisms of Cardiac Ischemia-Reperfusion Injury

“…The most energy-consuming organ, the heart, containing the biggest mitochondrial content (30% of cell volume), is also most sensitive to IR injury compared with other, less energy-dependent organs [134]. Damage to mitochondrial respiratory chain complexes after ischemia (including also cold ischemia and organ preservation) alone is also significantly different and produces more pronounced injury after reperfusion.…”

Right ventricular mitochondrial respiratory function in a piglet model of chronic pulmonary hypertension

“…They also demonstrated ultrastructural changes of mitochondria in TEM analysis (mitochondria swollen, cristae impairment, and structural anomalies). Using the permeabilized muscle fibers technique, Wiedemann and colleagues 26 showed that cold ischemia storage in saline solution was associated with a decrease of mitochondrial respiratory capacities of complex I (after glutamate þ malate-supported respiration) and complex II (succinate þ rotenone-supported respiration).…”