Background:
Ex situ heart perfusion (ESHP) preserves the donated heart in a perfused, beating condition preventing cold storage–related ischemia and provides a platform to evaluate myocardial viability during preservation. However, myocardial function declines gradually during ESHP. Extracorporeal circulation systems are associated with the induction of systemic inflammatory and stress responses. Our aim was to evaluate the incidence of inflammation and induction of endoplasmic reticulum stress responses during an extended period of ESHP.
Methods:
Cardiac function, myocardial tissue injury, markers of inflammation, oxidative stress, and endoplasmic reticulum stress were assessed in healthy pig hearts, perfused for 12 hours either in nonworking mode (non-WM=7) or working mode (WM, n=6).
Results:
Cardiac function declined during ESHP but was significantly better preserved in the hearts perfused in WM (median 11-hour cardiac index/1-hour cardiac index: WM=27% versus non-WM=9.5%,
P
=0.022). Myocardial markers of endoplasmic reticulum stress were expressed higher in ESHP hearts compared with in vivo samples. The proinflammatory cytokines and oxidized low-density lipoprotein significantly increased in the perfusate throughout the perfusion in both perfusion groups. The left ventricular expression of the cytokines and malondialdehyde was induced in non-WM, whereas it was not different between WM and in vivo.
Conclusions:
Myocardial function declines during ESHP regardless of perfusion mode. However, ESHP in WM may lead to superior preservation of myocardial function and viability. Both inflammation and endoplasmic reticulum stress responses are significantly induced during ESHP and may contribute to the myocardial functional decline, representing a potential therapeutic target to improve the clinical donor heart preservation.
Oxidation of Hexaaquoiron (II) by Chlorine (III) of the reversible Ei/¡ of the FeL2 + + e~-FeL+ step is taken as the potential midway between the peak potentials of the cathodic and anodic peaks. This Ey, value falls on the appropriate line in Figure 4.A linear dependence of Ey, on IP was also reported recently for a series of metalloporphyrins and metallophthalocyanines.16 The linear relationship was observed for the oxidation step, M(II) -e~-* M(III), with the metals Ni, Co, and Fe when the third ionization potentials of the metals were used. It is interesting that with the cyclic amines the linear relationship holds for Cu, Ni, and Co but does not extend to Fe. The =^( ) _ *l[Fe(II)][Cl(III)] + higeggitaq11)! At 25°and 2.0 M ionic strength, ki = (1.89 ± 0.09) X 10s M_1 sec-1 and = 58 ± 10 sec-1. The results are discussed in terms of several possible one-electron-transfer mechanisms.
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