Ultrastructural Findings in Porcine Hearts After Extracorporeal Long‐term Preservation with a Modified Langendorff Perfusion System

Abstract

Preserved ultrastructure is an important precondition for functional regeneration after heart transplantation. We investigated the effectiveness of a newly developed modified Langendorff system in extracorporeal heart perfusion. (Experiment I) Cardioplegia and cold ischaemia were performed in six pigs. Hearts were connected to a modified Langendorff system, and perfused with leucocyte depleted autologous blood. (Experiment II) The untreated hearts of three healthy pigs served as controls. Forty-seven myocardial biopsies at different timepoints (I: n = 29, II: n = 18) were investigated by transmission electronmicroscopy. Cardioplegia/hypothermia (I) induced mild-to-moderate mitochondrial swelling, mild myofibrillar degeneration in cardiomyocytes and moderate endothelial oedema. After 4 h reperfusion cardiomyocytes showed moderate myofibrillar and mild sarcolemmal damage. Moderate endothelial degeneration, mild interstitial oedema and haemorrhages appeared. Untreated hearts (II) showed severely damaged mitochondria and nuclei after 30 min while the myofibrillar structure remained unaffected until 4 h later. This is a promising model for extracorporeal heart perfusion. However, ultrastructural findings indicated that some necessary modifications to prevent cellular damages during reperfusion were needed.

Myocardial calcium overload during graded hypothermia and after rewarming in an in vivo rat model

“…, , Aupperle et al . ) have been reported. Such findings are signs of alterations in mitochondrial function, which again likely affects cardiac contractility.…”

“…Ca 2+ overload may induce cardiac contractile dysfunction through different pathways. In hypothermia and rewarming, an increase in reactive oxygen species (ROS) (Camara et al 2003, Riess et al 2004, decreased ATP synthesis and damaged mitochondrial ultrastructure (Tveita et al 1996a, Aupperle et al 2007) have been reported. Such findings are signs of alterations in mitochondrial function, which again likely affects cardiac contractility.…”

Physiological Impact of Hypothermia: The Good, the Bad, and the Ugly

“…Elevated [Ca 2+ ]cyt increases energy consumption by activating ATP-dependent cross-bridge cycling, and ATP-dependent Ca 2+ pumps in the SR and sarcolemma (14). The hypothermia-induced increase in ATP consumption will eventually cause mitochondrial depolarization, an uncoupling of oxidative phosphorylation, ROS formation, compromised energy production, mitochondrial swelling, and cell death (6,14,30,40,42,70,72,78,88,105,154,155,184,198,199). Using electron microscopy and morphometry, we were able to quantify and categorize myocardial mitochondrial damage after rewarming following a 4-h period at 15-13°C with spontaneous circulation (200).…”

Therapy for Heart Failure: The Leipzig Approach

“…Possible future application could be facilitating donor management and further evaluation of marginal donor hearts. [10][11][12] Immunosuppressive Therapy: Pharmacodynamics Due to Prof. Mohr's initiative, our group showed increased interest in the pharmacodynamics of immunosuppressive therapy. Without proper immunosuppressive therapy, solid organ transplantation is not feasible.…”