gms | German Medical Science

24. Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung

Deutsche Gesellschaft für Arterioskleroseforschung

18.03. - 20.03.2010, Blaubeuren

Predictive value of palmitoylcarnitine in serum of cardiosurgical patients for impaired tissue oxygenation

Meeting Contribution

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  • corresponding author S. Vogt - Biomedical Research Center, Cardiovascular Research Lab, Philipps-University of Marburg, Universitätsklinikum Gießen und Marburg GmbH, Marburg, Germany
  • J. Schäfer - Cardiology, Philipps-University of Marburg, Universitätsklinikum Gießen und Marburg GmbH, Marburg, Germany
  • A. Schulze - Pediatric Hospital, Goethe-University Frankfurt/Main, Germany
  • R. Moosdorf - Heart Surgery, Philipps-University of Marburg, Universitätsklinikum Gießen und Marburg GmbH, Marburg, Germany

Deutsche Gesellschaft für Arterioskleroseforschung e.V.. 24. Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung. Blaubeuren, 18.-20.03.2010. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc10dgaf22

DOI: 10.3205/10dgaf22, URN: urn:nbn:de:0183-10dgaf223

Veröffentlicht: 23. März 2011

© 2011 Vogt et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Abstract

Palmitoylcarnitine is suggested to be involved in the pathological process of cardiac ischemia. Recent experimental data revealed correlation between fatty acid transporter levels and palmitate oxidation rate with ejection fraction in the infarcted heart . Moreover, chronic hypoxia in case of ischemic heart disease alters fatty acid composition in the myocardium.

Palmitate not only reduces blood pressure and heart rate but is only suggested to decrease the enzymatic activities of the mitochondrial respiratory chain. In a pilot study we addressed the perioperative alterations of the plasma fatty acid composition by elevation of acylcarnitines (AC) with special consideration of the palmitoylcarnitine (C16-AC) serum levels.We studied eleven patients choosen consecutively (7 male, 4 female) for elective cardiosurgical procedure. Directly before and after heart arrest, heparinisied blood specimen were taken. The specimen were dried on filter paper strips for further acylcarnitine- analysis by ESI-MS/MS. Results were adjusted to carnitine final concentrations in mmol/l and correlated to clinical data.Independent from gender, age, medication of lipostatins, known CIHD or pulmonary diseases,7 patients found to have a postoperative decrease of C16-AC. Data of C14-AC and C18-AC had no change. These patients had clear lower preoperative ejection fraction. Highest level of C16-AC was found when patients suffered from myocardial infarction within 6 months pre op.These first data indicate further clinical investigations about mitochondrial oxidative capacity as reflection of mitochondrial functional deterioration by palmitoyl carnitine (Ca++ release or ROS production).


Introduction

The production of ATP in the myocardium is dependent on the oxidative decarboxylation of glucose and fatty acids. The type of energy substrate used by the heart during reperfusion will directly influence the contractile recovery. Fatty acid oxidation recovers faster during reperfusion and becomes dominant as a source of oxygen consumption. High rates of fatty acid oxidation influence recovery of postischemic cardiac function, negatively [1].

Increased levels of acylcarnitines have been implicated in the pathology of cardiac ischemia for the last two decades. It is demonstrated that palmitoylcarnitine (PC) was a potent inhibitor of isolated cardiac Na,K-ATPase, and clarified that the palmitoylcarnitine effect on sarcolemmal and sarcoplasmic reticulum membranes is due to the surfactant properties of that amphiphile [2]. The palmitoylcarnitine concentrations in the heart sarcolemma have been reported to increase in cells subjected to hypoxia. In concern of its amphiphile properties it was found that palmitoylcarnitine incorporates into the membranes and this insertion leads to a reduction of the surface negative charge (further references in [2]). Because of this effect the PC induced release of Ca++ from the sarcoplasmatic reticulum and skeletal muscle is suggested. Resulting from increased fatty acid oxidation, the carnitine palmitoyl transferase-1 mediated fatty acid uptake into the mitochondria is accelerated. One of the prominent representative of these fatty acids is palmitate, which is known for attenuation of cardiac recovery after ischemia and reperfusion. When palmitate was added during perfusion in a working heart model, the coronary flow decreased continuously during the hypothermic perfusion and the ventricular pressure development was lower throughout the rewarming reperfusion. The tissue levels of adenosine triphosphate and creatine phosphate decreased in those hearts receiving palmitate [3]. Recent experimental data revealed correlation between fatty acid transporter levels and palmitate oxidation rate with ejection fraction in the infarcted heart [4]. Moreover, chronic hypoxia in case of ischemic heart disease alters fatty acid composition in the myocardium [5].Palmitate reduces blood pressure and heart rate by its own [6] and is suggested to decrease the enzyme activities of the mitochondrial respiratory chain [7]. In a pilot study we addressed the perioperative alterations of the plasma fatty acid composition by elevation of acylcarnitines (AC) with special consideration of the palmitoylcarnitine (C16-AC) serum levels.


Methods

Eleven patients choosen consecutively (7 male, 4 female) underwent elective cardiosurgical procedure (CABG, Aortic Valve replacements). Directly before aortic clamping, heparinisied blood specimen were collected out of the aortic needle vent (point 1). Immediately after aortic declamping first pass blood specimen (point 2) were taken. The specimen were dried on filter paper strips for further acylcarnitine- analysis by ESI-MS/MS [8]. Results were adjusted to carnitine final concentrations in mmol/l and correlated to angiographic, demographic and monitoring data.


Results

Independent from gender, age, medication of lipostatins, known CIHD or pulmonary diseases, 7 patients had an decrease of C16-AC (2.65 ± 1.11 vs. 1.73 ± 0.83 mmol/l, p=0.018 Wilcoxon-test; resulting in group A, Figure 1 [Fig. 1]) in contrast to the others (group B). C14-AC and C18-AC had no change. Group A had clear lower preoperative ejection fraction (47.8 ± 7.7 vs. 75.5 ± 2.1%, p=0.01 Mann-Whitney rank sum test). ECC- time was extended in groupB (103.2 ± 36.1 vs. 83.2 ± 25.7 min, p=0.01 Mann-Whitney-U test) although ischemic time was equal (45.0 ± 8.5 vs. 51.2 ± 22.9 min). Highest level of C16-AC was found when patients suffered from myocardial infarction within 6 months pre op.


Discussion

Accompanying to high rates of fatty acid oxidation in case of postischemic reperfusion the contents of myocardial malonyl-coenzyme A is decreased. Otherwise, malonyl-CoA, which is synthesized by acetyl-CoA carboxylase, is essential in the regulation of fatty acid oxidation. Therefore, the decrease in malonyl-CoA level results in an increase of carnitine palmitoyl transferase-1 mediated fatty acid uptake into the mitochondria [1]. If an increased amount inside the cell promotes myocardial apoptosis by decrease of the mitochondrial membrane potential and release of proapoptotic cytochrome c or if regulatory role of carnitine palmitoyltransferase for β-oxidation determines myocardial postischemic function is under investigation. In concern of the study from Heather et al. [4] where they have found a correlation of fatty acid transporter levels and palmitate oxidation rate with hemodynamic parameters like ejection fraction during cardiac infarction, the blood AC monitoring seems to be clinical relevant because of data elevated during myocardial ischemia, whereas fatty acid metabolism is impaired and tissue carnitine levels are depleted. Carnitine is an essential cofactor for fatty acid metabolism, the predominant source of ATP in the normal aerobic heart. In a study with cardiosurgical patients the incidence of abnormal plasma carnitine concentrations were investigated [9]. They found that total and free carnitine levels were reduced immediately after cardiopulmonary bypass (CPB) and remained depressed until two hours after CPB, while acyl carnitine levels were unchanged over the course of this study. Therefore they considered carnitine supplement might be useful in the intensive care therapy after open heart surgery. Interestingly, data of our evaluation were adjusted to carnitine final concentrations. Hence, the decrease of C16-AC might been enlarged and has to be suggested as clinical relevant in hemodynamic concern (see [3]). Nevertheless, the enhanced recovery of myocardial status after Heat Shock induction [10] is obviously dependent from protection of the myocardial content of high energy phosphates [11] and herein an improved functional status of the tissue associated with an increase in state 3 respiration in the presence of palmitoylcarnitine [12].


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