Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Orofacial Pain and Toothache as the Sole Symptom of an Acute Myocardial Infarction Entails a Major Risk of Misdiagnosis and Death.

AIMS: To provide an update of knowledge regarding the clinical presentation and neurophysiologic aspects of orofacial pain of cardiac origin in the form of a literature review. METHODS: The peer-reviewed databases Scopus/Embase, NCBI (PubMed), and Science Direct were searched up to December 2018. RESULTS: Patients with myocardial infarction presenting without chest pain run a higher risk of death due to missed diagnosis and subsequently a significantly greater delay between the onset of symptoms and arrival at the hospital. During myocardial ischemia, orofacial pain is reported by 4 in 10 patients and described as oppressive and/or burning. Up to 4% of myocardial infarction patients experience pain solely in the orofacial structures, women more often than men. Orofacial pain during myocardial ischemia is associated with ischemia within the inferior wall of the heart, suggesting the involvement of the vagal system. CONCLUSION: The clinician's awareness of the full spectrum of clinical characteristics of a myocardial infarction constitutes a key factor in accurate diagnosis. Health care professionals and the general public should be aware of the possibility of myocardial infarction presenting with orofacial pain, toothache, or ear/temporomandibular joint pain as the only symptom.

Impact of age and sex on normal left heart structure and function.

BACKGROUND: Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose. METHODS: We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions. RESULTS: Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years. CONCLUSION: Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females.

Craniofacial pain can be the sole prodromal symptom of an acute myocardial infarction: an interdisciplinary study.

We recently found craniofacial pain to be the sole symptom of an acute myocardial infarction (AMI) in 4% of patients. We hypothesized that this scenario is also true for symptoms of prodromal (pre-infarction) angina. We studied 326 consecutive patients who experienced myocardial ischemia. Intra-individual variability analyses with respect to ECG findings and pain characteristics were performed for those 150 patients who experienced at least one recurrent ischemic episode. AMI patients (n=113) were categorized into two subgroups: "abrupt onset" (n=81) and "prodromal angina" (n=32). Age, gender and risk factor comparisons were performed between groups. Craniofacial pain constituted the sole prodromal symptom of an AMI in 5% of patients. In those who experienced two ischemic episodes, women were more likely than men to experience craniofacial pain in both episodes (p<0.01). There was no statistically significant difference between episodes regarding either ECG findings or the use of the two typical pain quality descriptors "pressure" and "burning". This study is to our knowledge the first to report that craniofacial pain can be the only symptom of a pre-infarction angina. Craniofacial pain constitutes the sole prodromal AMI symptom in one out of 20 AMI patients. Recognition of this atypical symptom presentation is low because research on prodromal AMI symptoms has to date studied only patients with chest pain. To avoid a potentially fatal misdiagnosis, awareness of this clinical presentation needs to be brought to the attention of clinicians, researchers and the general public.

En un estudio previo encontramos que un dolor en la región cráneo-facial puede ser el único síntoma de un infarto agudo de miocardio (IAM) en el 4% de los casos. En el presente trabajo la hipótesis fue que este escenario es cierto también para la angina pre-infarto o angina prodrómica. En el estudio se incluyeron 326 pacientes consecutivos con isquemia cardiaca sintomática. Se realizó un análisis intraindividual con respecto a características del dolor y hallazgos electrocardiográficos en los 150 pacientes que presentaron episodios recurrentes de isquemia cardiaca. Los pacientes con infarto agudo se categorizaron en dos grupos: "comienzo abrupto" (n=81) y "angina prodrómica" (n=32). Se realizaron comparaciones entre grupos con respecto a edad, género y factores de riesgo cardiovasculares. El dolor en la región cráneofacial constituyó el único síntoma prodrómico (pre-infarto) de un IAM en el 5% de los casos. En aquellos pacientes que experimentaron dos episodios isquémicos, las mujeres tuvieron una mayor prevalencia de dolor cráneo-facial en los dos episodios (p<0.01). No se detectaron diferencias estadísti cas entre episodios con respecto a hallazgos electrocar dio grá ficos o al empleo de los descriptores verbales del dolor de origen cardíaco "opresivo" y "quemante". Este es el primer estudio de investigación en documentar que el dolor en la región cráneo-facial puede ser el único síntoma de una angina pre-infarto. En efecto, esto ocurre en uno de cada 20 casos de IAM. El reconocimiento de esta presentación clínica es baja debido a que históricamente los criterios de inclusión de los estudios de angina pre-infarto incluyeron únicamente pacientes con dolor de pecho. Para evitar el error diagnóstico con consecuencias fatales para el paciente, es importante que esta información llegue tanto a los clínicos como al público en general.

DNA Content in Extracellular Vesicles Isolated from Porcine Coronary Venous Blood Directly after Myocardial Ischemic Preconditioning.

BACKGROUND: Extracellular vesicles (EV) are nano-sized membranous structures released from most cells. They have the capacity to carry bioactive molecules and gene expression signals between cells, thus mediating intercellular communication. It is believed that EV confer protection after ischemic preconditioning (IPC). We hypothesize that myocardial ischemic preconditioning will lead to rapid alteration of EV DNA content in EV collected from coronary venous effluent. MATERIALS AND METHODS: In a porcine myocardial ischemic preconditioning model, EV were isolated from coronary venous blood before and after IPC by differential centrifugation steps culminating in preparative ultracentrifugation combined with density gradient ultracentrifugation. The EV preparation was validated, the DNA was extracted and further characterized by DNA sequencing followed by bioinformatics analysis. RESULTS: Porcine genomic DNA fragments representing each chromosome, including mitochondrial DNA sequences, were detected in EV isolated before and after IPC. There was no difference detected in the number of sequenced gene fragments (reads) or in the genomic coverage of the sequenced DNA fragments in EV isolated before and after IPC. Gene ontology analysis showed an enrichment of genes coding for ion channels, enzymes and proteins for basal metabolism and vesicle biogenesis and specific cardiac proteins. CONCLUSIONS: This study demonstrates that porcine EV isolated from coronary venous blood plasma contain fragments of DNA from the entire genome, including the mitochondria. In this model we did not find specific qualitative or quantitative changes of the DNA content in EV collected immediately after an in vivo myocardial IPC provocation. This does not rule out the possibility that EV DNA content changes in response to myocardial IPC which could occur in a later time frame.

Craniofacial pain can be the sole prodromal symptom of an acute myocardial infarction: an interdisciplinary study / El dolor cráneo-facial puede ser el único síntoma prodrómico de un infarto agudo de miocárdio: estudio interdisciplinario

We recently found craniofacial pain to be the sole symptom of anacute myocardial infarction (AMI) in 4% of patients. Wehypothesized that this scenario is also true for symptoms ofprodromal (pre-infarction) angina. We studied 326 consecutivepatients who experienced myocardial ischemia. Intra-individualvariability analyses with respect to ECG findings and paincharacteristics were performed for those 150 patients whoexperienced at least one recurrent ischemic episode. AMI patients(n=113) were categorized into two subgroups: “abrupt onset”(n=81) and “prodromal angina” (n=32). Age, gender and riskfactor comparisons were performed between groups. Craniofacialpain constituted the sole prodromal symptom of an AMI in 5% ofpatients. In those who experienced two ischemic episodes, womenwere more likely than men to experience craniofacial pain in bothepisodes (p<0.01). There was no statistically significant differencebetween episodes regarding either ECG findings or the use of thetwo typical pain quality descriptors “pressure” and “burning”. This study is to our knowledge the first to report that craniofacialpain can be the only symptom of a pre-infarction angina.Craniofacial pain constitutes the sole prodromal AMI symptomin one out of 20 AMI patients. Recognition of this atypicalsymptom presentation is low because research on prodromalAMI symptoms has to date studied only patients with chest pain.To avoid a potentially fatal misdiagnosis, awareness of thisclinical presentation needs to be brought to the attention ofclinicians, researchers and the general public.

En un estudio previo encontramos que un dolor en la región cráneo-facial puede ser el único síntoma de un infarto agudo de miocardio (IAM) en el 4 por ciento de los casos. En el presentetrabajo la hipótesis fue que este escenario es cierto también para la angina pre-infarto o angina prodrómica.En el estudio se incluyeron 326 pacientes consecutivos con isquemia cardiaca sintomática. Se realizó un análisis intraindividual con respecto a características del dolor y hallazgoselectrocardiográficos en los 150 pacientes que presentaron episodios recurrentes de isquemia cardiaca. Los pacientes con infarto agudo se categorizaron en dos grupos: “comienzoabrupto” (n=81) y “angina prodrómica” (n=32). Se realizaron comparaciones entre grupos con respecto a edad, género y factores de riesgo cardiovasculares. El dolor en la región cráneofacial constituyó el único síntoma prodrómico (pre-infarto) de un IAM en el 5 por ciento de los casos. En aquellos pacientes que experimentaron dos episodios isquémicos, las mujeres tuvieron una mayor prevalencia de dolor cráneo-facial en los dos episodios (p<0.01). No se detectaron diferencias estadísticas entre episodios con respecto a hallazgos electrocardiográ ficos o al empleo de los descriptores verbales del dolor de origen cardíaco “opresivo” y “quemante”.Este es el primer estudio de investigación en documentar queel dolor en la región cráneo-facial puede ser el único síntoma de una angina pre-infarto. En efecto, esto ocurre en uno decada 20 casos de IAM. El reconocimiento de esta presentación clínica es baja debido a que históricamente los criterios de inclusión de los estudios de angina pre-infarto incluyeron únicamente pacientes con dolor de pecho. Para evitar el error diagnóstico con consecuencias fatales para el paciente, es importante que esta información llegue tanto a los clínicos como al público en general.

Atlas of the clinical genetics of human dilated cardiomyopathy.

AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. CONCLUSION: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.

Craniofacial pain of cardiac origin is associated with inferior wall ischemia.

AIMS: To investigate possible associations between the presence of craniofacial pain of cardiac origin and the location of cardiac ischemia and conventional risk factors. METHODS: A total of 326 consecutive patients with confirmed myocardial ischemia (192 males, 134 females, mean age 64 years) were studied. Demographic details, health history, factors, prodromal symptoms, electrocardiogram (ECG) findings, and pain characteristics during the ischemic episode were assessed. The location of the ischemia according to the ECG findings was categorized as anterior, inferior, or lateral. Univariate chi-square analyses and a multivariate logistic regression model were used for data analysis. Two age subgroups (< 65 and > 65) were established when controlling for covariates. RESULTS: Craniofacial pain of cardiac origin was significantly associated with an inferior localization of cardiac ischemia (P < .001) and was more frequently reported in diabetic patients (P = .014). Thirty-eight patients (12%) did not experience chest pain during the myocardial ischemia. Nine patients (3%) experienced a prodromal angina episode without chest pain. CONCLUSION: The occurrence of craniofacial pain during myocardial ischemia, with or without an acute myocardial infarction, was associated with ischemia within the inferior wall. This result suggests the involvement of the vagal afferent system in the mechanisms of craniofacial pain of cardiac origin.

Role of exosomes in myocardial remodeling.

Exosomes are nanovesicles released from cells through exocytosis and are known to be mediators of proximal as well as distant cell-to-cell signaling. They are surrounded by a classical bilayered membrane with an exceptionally high cholesterol/phospholipid ratio. Exosomes were first described in 1977, then named prostasomes, and in 1987 the name exosome was coined. Exosomes contain surface proteins, some of which can act as labels in order to find their target cells. Exosomes also contain messages in the form of proteins and nucleic acids (RNA and DNA) that are transferable to target cells. Little is known and written about cardiac exosomes, although Gupta and Knowlton described exosomes containing HSP60 in 2007. It is now known that exosomes from cardiomyocytes can transfect other cells and that the metabolic milieu of the parental cell decides the quality of exosomes released such that they induce differential gene expression in transfected cells. Future clinical use of exosomes in diagnosis, monitoring disease progress, and treatment is promising.

The normal impact of age and gender on right heart structure and function.

BACKGROUND: As the proportion of elderly population increases rapidly, it might be difficult to differentiate physiological changes in cardiac function due to age from the pathophysiological ones. In addition, cardiac function variations with gender are well established. The right ventricular (RV) plays an important role in the overall cardiac function, but reference values varying with age and gender are lacking. MATERIAL AND METHODS: We studied 255 healthy individuals from a general population register, mean age of 58 ± 19 (range 22-89) years, 125 were females. We used 2D and M-mode echocardiography to measure RV inflow tract (RVIT) and RV outflow tract (RVOT) dimensions and fractional shortening (fs). Spectral Doppler echocardiography was also used. RESULTS: We found a modest decrease in RVIT dimensions (P < 0.05), but increase in RVOT dimensions with advancing age (P < 0.05). A small decrease in RVOT fs with age was also found (P < 0.05). Estimated pulmonary pressures and pulmonary vascular resistance increased (P < 0.001) as did RVOT wall thickness (P < 0.001), but RV diastolic function was not altered (P < 0.001) with age. Despite correction for the BSA, males showed larger RVIT dimensions (P < 0.001 for both), but RVOT end-diastolic dimension was larger in females (P < 0.05). RVIT and RVOT fractional shortening were increased in females (P < 0.01 for both). CONCLUSION: In a cohort of normal individuals, age has significant impact on RV structure and function, inlet area falls and outflow tract dimensions increase and fractional shortening also increase in females. In addition, RVOT wall thickness significantly increases and Doppler markers of pulmonary vascular resistance show a consistent rise. The age-related changes should carefully be considered when commenting on normality and when using absolute values.

Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes.

Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes. Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-ß2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression. The exosomes were rounded in shape and had an average size of 50-90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-ß2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups. We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system.

Using OPLS-DA to find new hypotheses in vast amounts of gene expression data - studying the progression of cardiac hypertrophy in the heart of aorta ligated rat.

One of the great problems facing science today lies in data mining of the vast amount of data. In this study we explore a new way of using orthogonal partial least squares-discrimination analysis (OPLS-DA) to analyze multidimensional data. Myocardial tissues from aorta ligated and control rats (sacrificed at the acute, the adaptive and the stable phases of hypertrophy) were analyzed with whole genome microarray and OPLS-DA. Five functional gene transcript groups were found to show interesting clusters associated with the aorta ligated or the control animals. Clustering of "ECM and adhesion molecules" confirmed previous results found with traditional statistics. The clustering of "Fatty acid metabolism", "Glucose metabolism", "Mitochondria" and "Atherosclerosis" which are new results is hard to interpret, thereby being possible subject to new hypothesis formation. We propose that OPLS-DA is very useful in finding new results not found with traditional statistics, thereby presenting an easy way of creating new hypotheses.

Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells.

BACKGROUND: Shedding microvesicles are membrane released vesicles derived directly from the plasma membrane. Exosomes are released membrane vesicles of late endosomal origin that share structural and biochemical characteristics with prostasomes. Microvesicles/exosomes can mediate messages between cells and affect various cell-related processes in their target cells. We describe newly detected microvesicles/exosomes from cardiomyocytes and depict some of their biological functions. METHODOLOGY/PRINCIPAL FINDINGS: Microvesicles/exosomes from media of cultured cardiomyocytes derived from adult mouse heart were isolated by differential centrifugation including preparative ultracentrifugation and identified by transmission electron microscopy and flow cytometry. They were surrounded by a bilayered membrane and flow cytometry revealed presence of both caveolin-3 and flotillin-1 while clathrin and annexin-2 were not detected. Microvesicle/exosome mRNA was identified and out of 1520 detected mRNA, 423 could be directly connected in a biological network. Furthermore, by a specific technique involving TDT polymerase, 343 different chromosomal DNA sequences were identified in the microvesicles/exosomes. Microvesicle/exosomal DNA transfer was possible into target fibroblasts, where exosomes stained for DNA were seen in the fibroblast cytosol and even in the nuclei. The gene expression was affected in fibroblasts transfected by microvesicles/exosomes and among 333 gene expression changes there were 175 upregulations and 158 downregulations compared with controls. CONCLUSIONS/SIGNIFICANCE: Our study suggests that microvesicles/exosomes released from cardiomyocytes, where we propose that exosomes derived from cardiomyocytes could be denoted "cardiosomes", can be involved in a metabolic course of events in target cells by facilitating an array of metabolism-related processes including gene expression changes.

Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis.

During ischaemia, ATP depletion leads to insufficient fuelling for Na(+) /K(+) ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca(2+) pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. (45) Ca(2+) was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by (45) Ca(2+) recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca(2+) ionophore and tested for (45) Ca(2+) uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate (45) Ca(2+) recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca(2+) ionophore to increase the intracellular calcium ion pool and subsequently incubated with (45) Ca(2+) , displayed lower (45) Ca(2+) uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate (45) Ca(2+) recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and (45) Ca(2+) inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.

A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM. METHODS AND RESULTS: One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P < 5.0 10(-7)), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p. C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease. CONCLUSION: This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.

Detection of myocardial ischaemia using surface microdialysis on the beating heart.

Microdialysis (MD) can be used to study metabolism of the beating heart. We investigated whether microdialysis results obtained from epicardial (surface) sampling reflect acute changes in the same way as myocardial sampling from within the substance of the ventricular wall. In anaesthetized open-thorax pigs a coronary snare was placed. One microdialysis probe was placed with the sampling membrane intramyocardially (myocardial), and a second probe was placed with the sampling membrane epicardially (surface), both in the area which was made ischaemic. Ten minutes collection intervals were used for microdialysis samples. Samples from 19 pigs were analysed for lactate, glucose, pyruvate and glycerol during equilibration, baseline, ischaemia and reperfusion periods. For both probes (surface and myocardial), a total of 475 paired simultaneous samples were analysed. Results from analyses showed no differences in relative changes for glucose, lactate and glycerol during baseline, ischaemia and reperfusion. Surface microdialysis sampling is a new application of the microdialysis technique that shows promise and should be further studied.