Extracellular Amino Acids as Markers of Myocardial Ischemia during Cardioplegic Heart Arrest

Kennergren, Charles; Mantovani, Vittorio; Lönnroth, Peter; Nyström, Britta; Berglin, E; Hamberger, Anders

doi:10.1159/000006874

Cited by 26 publications

(20 citation statements)

References 18 publications

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“…Signal transduction through mGluR1b in cardiomyocytes could have physiological and pathological relevance and needs to be investigated further. Indeed, glutamate is the main amino acid known to be released during cardiac ischemia (Kennergren et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Moore-Morris¹,

Varrault²,

Mangoni³

et al. 2009

Mol Pharmacol

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Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functions represents an important issue for the development of new drugs. Indeed, highly targeted receptors represent only a small percentage of known GPCRs. Here, we quantified the expression of 395 endoGPCRs (all GPCRs excluding taste and odorant receptors) in male mouse right and left atria and ventricles by using high-throughput real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and focused on the 135 most highly expressed transcripts. No cardiac functional data are available for almost half of these receptors; therefore, linking GPCR expression patterns to cardiac function has allowed us to provide new insights into the possible function of some of these receptors. Indeed, ventricles and atria are both contractile; however, the latter, and especially the right atrium, are central to the generation and regulation of cardiac rhythm. Accordingly, the right atrium exhibited the most specific signature, whereas the majority of GPCRs found in ventricles were evenly expressed in both the right and left chambers. RT-PCR data were confirmed at the protein level for six selected transcripts. Furthermore, we provide new data showing that, as suggested by our repertoire, the metabotropic glutamate receptor 1b is expressed and is functional in ventricular cardiac myocytes. This is the first report describing GPCRs in the four cardiac chambers and may assist in the identification of therapeutic targets.The four cardiac chambers display morphological and functional differences. They can be distinguished on the basis of contractile properties, rhythm generation, and response to neurohumoral stimulation (Brown et al., 1991;Barth et al., 2005;Narolska et al., 2005). Contractile activity of the heart ensures that blood flow is adapted to the needs of the organism. Left ventricular performance depends on the chamber's capacity to fill up (diastolic property) and to empty (systolic property), and these properties are altered in pathological conditions, the final consequence being heart failure. To trigger the contractile activity, cardiac automaticity is generated by a set of specialized pacemaker cells forming the sinoatrial node (SAN) (Mangoni and Nargeot, 2008). Compared with myocytes of the working myocardium, pacemaker SAN cells are devoted to the generation of an electrical oscillation rather than having a contractile activity. At the molecular level, heart chamber heterogeneity is reflected by the expression patterns of different sets of genes such as transcription factors (Tabibiazar et al., 2003) and ion channels (Marionneau et al., 2005). The heart expresses GPCRs (Regard et al.,

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Moore-Morris¹,

Varrault²,

Mangoni³

et al. 2009

Mol Pharmacol

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“…The microdialysis probes were inserted into the region between the left anterior descending artery and the second diagonal artery immediately after a full median sternotomy (18)(19)(20). Care was taken to avoid vessels and to place the probes at equal depth (i.e., 2-3 mm).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…The microdialysis probes were extracted percutaneously (18,19) no later than 48 h after surgery. With few exceptions, the patients could start intake of fluids and some food on the first postoperative day.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…A key issue is the monitoring of the myocardial metabolism during the cardioplegic period during which relevant plasma sampling cannot be carried out. Sampling of the interstitial fluid of the myocardium by means of microdialysis before, during, and after open-heart surgery is now used also in the clinical situation (18,19). When properly calibrated, the approach offers highprecision data from the myocardial interstitium (26).…”

mentioning

confidence: 99%

“…Myocardial microdialysis has been performed in experimental setups of both the calibrated (25) and the noncalibrated type (20). Noncalibrated microdialysis sampling of the human heart during cardioplegia was recently reported from two different centers (9,18,19).…”

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confidence: 99%

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Myocardial interstitial glucose and lactate before, during, and after cardioplegic heart arrest

Kennergren

Mantovani

Strindberg³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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The interstitial fluid of the human myocardium was monitored in 13 patients undergoing aortic valve and/or bypass surgery before, during, and after hypothermic potassium cardioplegia. The regulation of glucose and lactate was studied after sampling with microdialysis. The following questions were addressed. 1) Is the rate of transcapillary diffusion the limiting step for myocardial uptake of glucose before or after cardioplegia? 2) Does cold potassium cardioplegia induce a critical deprivation of glucose and/or accumulation of lactate in the myocardium? Before cardioplegia, interstitial glucose was ∼50% of the plasma level ( P < 0.001). Interstitial glucose decreased significantly immediately after induction of cardioplegia and remained low (1.25 ± 0.25 mM) throughout cardioplegia. It was restored to precardioplegic levels 1 h after release of the aortic clamp. Interstitial glucose then decreased again at 25 and 35 h postoperatively to the levels observed during cardioplegia. Interstitial lactate decreased immediately after induction of cardioplegia but returned to basal level during the clamping period. At 25 and 35 h, interstitial lactate was significantly lower than before and during cardioplegia. Glucose transport over the capillary endothelium is considered rate limiting for its uptake in the working heart but not during cold potassium cardioplegia despite the glucose deprivation following perfusion of glucose-free cardioplegic solution. Lactate accumulated during cardioplegia but never reached exceedingly high interstitial levels. We conclude that microdialysis provides information that may be relevant for myocardial protection during open-heart surgery.

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Intraperitoneal and intraluminal microdialysis in the detection of experimental regional intestinal ischaemia

Sommer

Larsen

2004

British Journal of Surgery

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Extracellular Amino Acids as Markers of Myocardial Ischemia during Cardioplegic Heart Arrest

Cited by 26 publications

References 18 publications

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

Myocardial interstitial glucose and lactate before, during, and after cardioplegic heart arrest

Intraperitoneal and intraluminal microdialysis in the detection of experimental regional intestinal ischaemia

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