Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model.

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

Effect of Chronic Continuous Normobaric Hypoxia on Functional State of Cardiac Mitochondria and Tolerance of Isolated Rat Heart to Ischemia and Reperfusion: Role of µ and delta2 Opioid Receptors.

Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and delta2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and delta2 ORs and preservation of mitochondrial function. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective delta OR antagonist TIPP(psi) (30 nmol/l), the selective delta1 OR antagonist BNTX (1 nmol/l), the selective delta2 OR antagonist naltriben (1 nmol/l), the selective peptide µ OR antagonist CTAP (100 nmol/l) and the selective delta OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(psi), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and delta2 opioid receptors activation and preservation of mitochondrial function.

Participation of opioid receptors in the cytoprotective effect of chronic normobaric hypoxia.

We studied the role of the delta, micro, and kappa opioid receptor (OR) subtypes in the cardioprotective effect of chronic continuous normobaric hypoxia (CNH) in the model of acute anoxia-reoxygenation of isolated cardiomyocytes. Adaptation of rats to CNH was performed by their exposure to atmosphere containing 12 % of O(2) for 21 days. Anoxia-reoxygenation of cardiomyocytes isolated from normoxic control rats caused the death of 51 % of cells and lactate dehydrogenase (LDH) release. Adaptation of rats to CNH resulted in the anoxia/reoxygenation-induced cardiomyocyte death of only 38 %, and reduced the LDH release by 25 %. Pre-incubation of the cells with either the non-selective OR (opioid receptor) blocker naloxone (300 nM/l), the delta OR antagonist TIPP(psi) (30 nM/l), the selective delta(2) OR antagonist naltriben (1 nM/l) or the micro OR antagonist CTAP (100 nM/l) for 25 minutes before anoxia abolished the reduction of cell death and LDH release afforded by CNH. The antagonist of delta(1) OR BNTX (1 nM/l) or the kappa OR antagonist nor-binaltorphimine (3 nM/l) did not influence the cytoprotective effects of CNH. Taken together, the cytoprotective effect of CNH is associated with the activation of the delta(2) and micro OR localized on cardiomyocytes.

The cardiac proteome in patients with congenital ventricular septal defect: A comparative study between right atria and right ventricles.

Right ventricle (RV) remodelling occurs in neonatal patients born with ventricular septal defect (VSD). The presence of a defect between the two ventricles allows for shunting of blood from the left to right side. The resulting RV hypertrophy leads to molecular remodelling which has thus far been largely investigated using right atrial (RA) tissue. In this study we used proteomic and phosphoproteomic analysis in order to determine any difference between the proteomes for RA and RV. Samples were therefore taken from the RA and RV of five infants (0.34 ±â€¯0.05 years, mean ±â€¯SEM) with VSD who were undergoing cardiac surgery to repair the defect. Significant differences in protein expression between RV and RA were seen. 150 protein accession numbers were identified which were significantly lower in the atria, whereas none were significantly higher in the atria compared to the ventricle. 19 phosphorylation sites (representing 19 phosphoproteins) were also lower in RA. This work has identified differences in the proteome between RA and RV which reflect differences in contractile activity and metabolism. As such, caution should be used when drawing conclusions based on analysis of the RA and extrapolating to the hypertrophied RV. SIGNIFICANCE: RV hypertrophy occurs in neonatal patients born with VSD. Very little is known about how the atria responds to RV hypertrophy, especially at the protein level. Access to tissue from age-matched groups of patients is very rare, and we are in the unique position of being able to get tissue from both the atria and ventricle during reparative surgery of these infants. Our findings will be beneficial to future research into heart chamber malformations in congenital heart defects.

Hypoxic Pulmonary Vasoconstriction in Humans: Tale or Myth.

Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism.

Cellular and molecular basis of RV hypertrophy in congenital heart disease.

RV hypertrophy (RVH) is one of the triggers of RV failure in congenital heart disease (CHD). Therefore, improving our understanding of the cellular and molecular basis of this pathology will help in developing strategic therapeutic interventions to enhance patient benefit in the future. This review describes the potential mechanisms that underlie the transition from RVH to RV failure. In particular, it addresses structural and functional remodelling that encompass contractile dysfunction, metabolic changes, shifts in gene expression and extracellular matrix remodelling. Both ischaemic stress and reactive oxygen species production are implicated in triggering these changes and will be discussed. Finally, RV remodelling in response to various CHDs as well as the potential role of biomarkers will be addressed.

Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery.

Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.

A new methodological sequence to expand and transdifferentiate human umbilical cord blood derived CD133+ cells into a cardiomyocyte-like phenotype.

Transplantation of antigenic-separated stem cells for human cardiovascular diseases such as myocardial infarction needs to be supported by experimental studies that allow refinement of the procedure. In this study we investigated optimising a protocol for the expansion and subsequent differentiation of human umbilical cord blood (HUCB) derived CD133(+) stem cells into a cardiomyocyte-like lineage. CD133(+) cells from HUCB were selected first by immunomagnetic separation and their purity was confirmed by flow cytometry analysis. For expansion and differentiation we developed a novel culture medium recipe that involves sequential signalling factors. Briefly, CD133(+) cells were expanded for 6 days under optimal serum-free conditions in combination with fibronectin and assessed by microscopy and AlamarBlue proliferation assay. Expanded CD133(+) cells were then plated in a cardiac differentiation promoting medium and cultured up to 4 weeks. With this protocol HUCB-CD133(+) cells can be regularly expanded in serum-free medium to obtain recovery and growth in vitro up to 6 folds. The addition of recombinant human thrombopoietin to the remaining factors of the expanding medium was associated with larger cell expansion. Expanded UCB CD133(+) cells showed a cardiomyocyte-like phenotype following differentiation in vitro through expressing intracellular cardiac specific markers including cardiac-specific α-actin, myosin heavy chain and troponin I. This change in phenotype was associated with the expression of cardiac-specific transcription factors Gata-4 and MEF2C. In addition, the change in phenotype was associated with an upregulation of nuclear receptor transcription factors including PPAR α, PPARγ, RXR α and RXRß. We believe our protocol represents a significant advancement and overcome the technical hurdle of deriving cardiomyogenic-like cells from HUCB CD133(+) stem cells. In addition, it has the required attributes of simplicity and consistency. This will permit more robust manipulation of these cells towards better engraftment and repair in patients with myocardial infarction.

Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness.

The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches.

Cardioplegic strategies to protect the hypertrophic heart during cardiac surgery.

Cardioplegic arrest and cardiopulmonary bypass are key triggers of myocardial injury during aortic valve surgery. Cardioplegic ischaemic arrest is associated with disruption to metabolic and ionic homeostasis in cardiomyocytes. These changes predispose the heart to reperfusion injury caused by elevated intracellular reactive oxygen species and calcium. Cardiopulmonary bypass is associated with an inflammatory response that can generate systemic oxidative stress which, in turn, provokes further damage to the heart. Techniques of myocardial protection are routinely applied to all hearts, irrespective of their pathology, although different cardiomypathies respond differently to ischaemia and reperfusion injury. In particular, the efficacy of cardioprotective interventions used to protect the hypertrophic heart in patients with aortic valve disease remains controversial. This review will describe key cellular changes in hypertrophy, response to ischaemia and reperfusion and cardioplegic arrest and highlight the importance of optimising cardioprotective strategies to suit hypertrophic hearts.

The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease.

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 +/- 1.5 vs. 10.9 +/- 1.5), glutamine (20.5 +/- 2.4 vs. 12.1 +/- 1.2), and glutamate (18.3 +/- 2.2 vs. 11.4 +/- 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.

Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics.

Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart). The heart sustains injury triggered by ischaemia and reperfusion and also as a result of the effects of systemic inflammatory mediators. In addition, the heart itself is a source of inflammatory mediators and reactive oxygen species that are likely to contribute to the impairment of cardiac pump function. Formulating strategies to protect the heart during open heart surgery by attenuating reperfusion injury and systemic inflammatory response is essential to reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, the diversity of the proposed mechanisms for protection (e.g. attenuating Ca(2+) overload, anti-inflammatory and antioxidant effects, pre- and post-conditioning-like protection) may have contributed to the slow adoption of anaesthetics as cardioprotective agents during open heart surgery. Clinical trials have suggested at least some cardioprotective effects of volatile anaesthetics. Whether these benefits are relevant in terms of morbidity and mortality is unclear and needs further investigation. This review describes the main mediators of myocardial injury during open heart surgery, explores available evidence of anaesthetics induced cardioprotection and addresses the efforts made to translate bench work into clinical practice.

Apoptosis and the cardiac action of insulin-like growth factor I.

In both cardiac surgical and cardiological settings, clinical interventions used to reperfuse the ischemic heart are associated with myocardial damage that is likely to influence long-term functional recovery. Ischaemia and reperfusion trigger cardiomyocyte death by necrosis and apoptosis. Therefore identifying potent cardioprotective agents remains an important goal in cardiac research. In a variety of tissues, insulin-like growth factor I (IGF-I) stimulates cellular proliferation, somatic growth, and differentiation. In addition, IGF-I inhibits apoptotic cell death and therefore plays an important role as a cell survival factor. This characteristic would provide an opportunity to both protect (rescue) the cardiac myocytes during (after) cardiac insults. In this review, we shall (i) describe the characteristics of apoptotic cell death with particular emphasis on the heart, (ii) discuss the IGF system with emphasis on the cardiac actions of IGF-I under normal and pathological conditions, (iii) elaborate on the potential role of IGF-I in myocardial protection, and finally (iv) describe how an improved understanding of the cardiac actions of IGF-I may lead to better protective clinical strategies in the future. We discuss work by ourselves and others in these areas and also consider recent work describing the cellular signaling associated with the IGF-I receptor (IGF-IR) in the heart and its potential role in regulating excitation-contraction coupling.

Relationship between perioperative troponin elevation and other indicators of myocardial injury in vascular surgery patients.

BACKGROUND: In 2000 the European Society of Cardiology and the American College of Cardiology published a consensus document revising the definition of myocardial infarction. The usefulness of this revised definition has been challenged. It has been suggested that, rather than any release of cardiac troponin being potentially diagnostic of myocardial infarction, a diagnostic threshold consistent with significant myocardial injury should be defined. METHODS: We studied 65 patients undergoing elective major vascular surgery to examine the relationship between the magnitude of cardiac troponin I (cTnI) and creatine kinase MB fraction (CK-MB) release and clinical signs or symptoms of myocardial injury. cTnI and CK-MB concentrations were measured preoperatively and on the first 4 postoperative days using the ACCESS assay (Beckmann). Patients were considered to have suffered a perioperative myocardial infarction if they had either symptoms or ECG changes consistent with this diagnosis, together with cTnI release. RESULTS: Peak postoperative cTnI concentrations above the lower detection limit of the ACCESS assay (0.06 microg litre(-1)) occurred in 26 patients. Eight of these patients displayed symptoms or ECG changes consistent with myocardial injury. A cTnI level greater than 0.68 microg litre(-1) was found to be consistent with the clinical diagnosis of myocardial infarction. The optimal cut-off for the diagnosis of MI using CK-MB was 40.4 microg litre(-1). CONCLUSIONS: These data suggest that further studies are required to define the optimal cardiac troponin diagnostic threshold for the diagnosis of myocardial infarction in the non-cardiac surgery population.

Mechanisms underlying the cardioprotective effect of L-cysteine.

In many tissues the availability of L-cysteine is a rate-limiting factor in glutathione production, though this has yet to be fully tested in heart. This study aimed to test the hypothesis that supplying hearts with 0.5 mM L-cysteine would preserve glutathione levels leading to an increased resistance to ischaemia reperfusion. Left ventricular function was measured in isolated perfused rat hearts before, during and after exposure to 45 min global normothermic ischaemia. Control hearts received Krebs throughout, whilst in treated hearts 0.5 mM L-cysteine was added to the perfusate 10 min before ischaemia, and was then present throughout ischaemia and for the first 10 min of reperfusion. Reperfusion injury was assessed from the appearance of lactate dehydrogenase (LDH) in the effluent. In two separate groups of control and treated hearts, ATP and glutathione (GSH) contents were measured at the beginning and end of ischaemia. Hearts treated with 0.5 mM L-cysteine showed a significantly higher recovery of rate pressure product (16,256+/- 1288 mmHg bpm vs. 10,324+/- 2102 mmHg bpm, p < 0.05) and a significantly lower release of LDH (0.54+/- 0.16 IU/g wet weight vs. 1.44+/- 0.31 IU/g wet weight, p < 0.05) compared to controls. Also, the L-cysteine treated group showed significantly better preservation of ATP and GSH during ischaemia in comparison to control. These results suggest that the mechanisms underlying the cardioprotective effects of 0.5 mM L-cysteine may include: increased anaerobic energy production either directly or through reduced degradation of adenine nucleotides; direct scavenging of free radicals; and/or improved antioxidant capacity through glutathione preservation.

A new method of quantifying glutathione levels in freshly isolated single superfused rat cardiomyocytes.

INTRODUCTION: Glutathione (GSH) is an important antioxidant in the heart whose content changes during cardiac insults. However, there are currently no methods for continuously monitoring free cytoplasmic GSH levels in single isolated and superfused cardiomyocytes exposed to normal and pathological conditions. METHODS: GSH was measured using CellTracker Blue CMAC (Molecular Probes), a member of a new family of thiol-sensitive dyes. The fluorescence of 5 microM CellTracker Blue CMAC was measured in various solutions containing glutathione-S-transferase and in freshly isolated single superfused cardiomyocytes using an inverted fluorescence microscope. The cardiomyocytes were isolated by standard procedures and loaded with either CellTracker Blue CMAC or monochlorobimane by 15 min of shaking incubation in the dark at room temperature followed by centrifugation with resuspension of the cells in dye-free media. Cell volume was calculated from the 3H2O and [14C]sucrose space. RESULTS: CellTracker Blue CMAC fluorescence was linearly proportional to 0-100 microM GSH, as described by the equation: Y = 182.2 (X) + 681.6 (r2 = .99, P < .001). Fluorescence was not affected by changing the glutathione-S-transferase level, the calcium concentration, or the pH, neither was the fluorescence quenched by H2O2 or cyanide. Exposure of freshly isolated single superfused cardiomyocytes to oxidative stress in the presence of 0-1 mM H2O2 caused a progressive decrease in cellular GSH. In contrast, brief exposure to metabolic inhibition in the presence of 2.5 mM NaCN evoked a significant increase in cardiomyocyte GSH followed by a return to control levels during washoff. In comparison to monochlorobimane, cells loaded with CellTracker Blue CMAC gave a stronger signal with better cellular retention of the probe. DISCUSSION: These results suggest that CellTracker Blue CMAC fluorescence will be a good tool for measuring GSH in freshly isolated single superfused cardiomyocytes because it shows the expected changes to oxidative stress and metabolic inhibition, and is reversible.

Paradoxical effects of insulin on cardiac L-type calcium current and on contraction at physiological temperature.

AIMS/HYPOTHESIS: L-type calcium current (I(Ca,L)) is a major determinant of mammalian cardiac contraction, and data from studies performed at room temperature suggest that this current is stimulated by insulin. This investigation aimed to determine whether or not insulin stimulates cardiac I(Ca,L) at 37 degrees C. METHODS: Isolated guinea pig ventricular myocytes were studied at room temperature and at 37 degrees C. Myocytes were either field stimulated or whole-cell voltage clamped, and cell shortening was measured using video edge detection. RESULTS: Insulin stimulated I(Ca,L) at ambient temperature. However, at 37 degrees C the effect of insulin was to decrease rather than to increase I(Ca,L). This action was concentration dependent and was not associated with voltage shifts in steady-state activation or inactivation properties of I(Ca,L). At 37 degrees C, insulin increased the extent of myocyte contraction despite producing a significant decrease in I(Ca,L) amplitude. CONCLUSIONS/INTERPRETATION: The findings of this study indicate that temperature is a key experimental variable in the study of the physiological actions of insulin. Furthermore, the increase in cardiac cell contraction by insulin at physiological temperature is not due to an increase in I(Ca,L), but is probably due to stimulation of excitation-contraction coupling downstream of I(Ca,L).

Myocardial metabolic changes during pediatric cardiac surgery: a randomized study of 3 cardioplegic techniques.

BACKGROUND: Blood cardioplegia and terminal warm blood cardioplegic reperfusion ("hot shot") reduce myocardial injury and improve metabolic recovery in hypoxic but not normoxic experimental models. However, there is little evidence of a benefit of either technique in pediatric clinical practice compared with crystalloid cardioplegia. METHODS: Pediatric patients undergoing cardiac surgery were randomized to receive intermittent antegrade cold crystalloid cardioplegia, cold blood cardioplegia, or cold blood cardioplegia with a hot shot. Right ventricular biopsy specimens were collected before ischemia, at the end of ischemia, and 20 minutes after reperfusion. Cellular metabolites were analyzed. In acyanotic patients postoperative serum troponin I levels were also measured at 1, 4, 12, 24, and 48 hours. RESULTS: Of 103 patients recruited, 32 (22 acyanotic and 10 cyanotic), 36 (24 acyanotic and 12 cyanotic), and 35 (25 acyanotic and 10 cyanotic), respectively, were allocated to the groups receiving cold crystalloid cardioplegia, cold blood cardioplegia, and cold blood cardioplegia with a hot shot. Cyanotic patients were younger, with longer crossclamp times. There were no significant differences in clinical outcomes between cardioplegic methods. The cardioplegic method had no overall effect in terms of adenosine triphosphate, ln(adenosine triphosphate/adenosine diphosphate), or ln(glutamate) in acyanotic patients (P =.11, P =.66, and P =.30, respectively). Also, there was no significant difference between groups in troponin I release. However, in cyanotic patients cold blood cardioplegia with a hot shot significantly reduced the decrease in adenosine triphosphate, ln(adenosine triphosphate/adenosine diphosphate), and glutamate observed at the end of ischemia and after reperfusion compared with the decrease seen in those receiving cold crystalloid cardioplegia (P =.002, P =.003, and P =.008, respectively), with cold blood cardioplegia representing an intermediate. CONCLUSIONS: For cyanotic patients (younger, with longer crossclamp times), cold blood cardioplegia with a hot shot is the best method of myocardial protection. For acyanotic patients (older, with shorter crossclamp times), cardioplegic technique is not critical.

Myocardial taurine, development and vulnerability to ischemia.

Depleting intracellular taurine in heart cells improves their resistance to ischemia and reperfusion injury. The aim of this work was to see whether physiologically low levels of endogenous taurine also reflect a reduced vulnerability of the myocardium to cardiac insults. The myocardial concentration of taurine was measured during different stages of development and compared with vulnerability to ischemia and reperfusion injury in the rat and in pediatric patients undergoing cardiac surgery.Rat hearts with relatively lower levels of taurine were significantly more resistant to an ischemic inult and there was a strong negative correlation between taurine content and recovery. Children's hearts had significantly lower taurine levels compared to infants' hearts which was consistent with their known increased resistance to an ischemic cardioplegic insult (Imura et al., 2001). This work shows that the changes in the concentration of myocardial taurine during development correlate with vulnerability to ischemia where low myocardial taurine is associated with improved recovery upon reperfusion.