Activity In Myocardial Tissue Research Articles

Patterns stability in cardiac tissue under spatial electromagnetic radiation

The electric activity in myocardial tissue is controlled by the target waves emitted from the sinoatrial node and then the Calcium flow is controlled to regulate the heartbeat. The occurrence of local defects can block the wave propagation in the cardiac tissue and then the heartbeat can be disturbed completely. During the electrophysiological activity including stochastic diffusion of intracellular ions and continuous exchange of extracellular ions along ion channel embedded in the cell membrane, electromagnetic induction occurs in the cardiac tissue and the involvement of external electromagnetic radiation can change the excitability and the neural activities. In this paper, based on a memristive cardiac tissue model by incorporating magnetic flux variable and induction current into the two-variable cardiac model for discerning cardiac excitation, spatial electromagnetic radiation is applied to investigate the stability and propagation of waves in the cardiac tissue. Wave propagation in the reaction-diffusion equations for cardiac tissue is approached by an equivalent diffusive neural network on square array after discretization. Local heterogeneity is produced by introducing diversity in initial value for inducing spiral seed, and stable spiral waves are developed as initial states, which represent tachycardia and arrhythmia in the cardiac tissue. It is found that symmetric spatial patterns can be controlled by the external electromagnetic radiation, in particular, nonlinear resonance is enhanced and specific spatial patterns are developed under noisy radiation.

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury.

Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

A Genotype-Phenotype Analysis of Glutathione Peroxidase 4 in Human Atrial Myocardium and Its Association with Postoperative Atrial Fibrillation.

Heterogeneity in the incidence of postoperative atrial fibrillation (POAF) following heart surgery implies that underlying genetic and/or physiological factors impart a higher risk of this complication to certain patients. Glutathione peroxidase-4 (GPx4) is a vital selenoenzyme responsible for neutralizing lipid peroxides, mediators of oxidative stress known to contribute to postoperative arrhythmogenesis. Here, we sought to determine whether GPX4 single nucleotide variants are associated with POAF, and whether any of these variants are linked with altered GPX4 enzyme content or activity in myocardial tissue. Sequencing analysis was performed across the GPX4 coding region within chromosome 19 from a cohort of patients (N = 189) undergoing elective coronary artery bypass graft (−/+ valve) surgery. GPx4 enzyme content and activity were also analyzed in matching samples of atrial myocardium from these patients. Incidence of POAF was 25% in this cohort. Five GPX4 variants were associated with POAF risk (permutated p ≤ 0.05), and eight variants associated with altered myocardial GPx4 content and activity (p < 0.05). One of these variants (rs713041) is a well-known modifier of cardiovascular disease risk. Collectively, these findings suggest GPX4 variants are potential risk modifiers and/or predictors of POAF. Moreover, they illustrate a genotype–phenotype link with this selenoenzyme, which will inform future mechanistic studies.

The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart

We aimed to explore the impact of ageing on 11C-hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (−)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2–141.9 GBq/μmol) were prepared. 11C-HED (48.7 ± 9.7MBq, ranged 0.2–60.4 μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20–30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11C-HED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.

High-Order Operator Splitting for the Bidomain and Monodomain Models

The bidomain and monodomain models are multiscale reaction-diffusion models that describe the electrical activity in myocardial tissue. Because of the size and specific structure of the system required to produce meaningful data, numerical solutions are often found through the application of operator-splitting (OS) methods. First- and second-order OS methods have been successfully implemented for finding numerical solutions of the bidomain and monodomain models. It is well known that OS methods with order higher than two require backward time integration within each step. Accordingly, one may conclude that splitting methods with order higher than two are not suitable for models that contain deterministic parabolic equations because the necessary backward time integration would cause instabilities. In this paper, we demonstrate that it is indeed possible to obtain stable results from third-order OS methods applied to the bidomain and monodomain models. Furthermore, we demonstrate that the accompanying gain...

Abstract P109: Spiny Mice Are Protected From Myocardial Infarction Induced Cardiac Pathophysiology

Background: Despite the advancement in drug and surgical interventions, myocardial damage and associated cardiac dysfunction lead to heart failure that remains common cause of death following myocardial infarction (MI). Spiny mice (Acomys cahirinus, SM) have been shown to possess regenerating capacity following deep tissue injury without scarring ( Nature 2013 ). This led us to investigate if this regenerative property would also be preserved in the heart. Methods and Results: Adult CD1 and SM were subject to left anterior descending coronary artery ligation or sham surgeries. Proliferative cells were identified by nuclear incorporation of 5-bromodeoxyuridine (BrdU, daily, i.p.) and injection was started from 3d post MI continued to 2wks post MI. Cardiac function was assessed using echocardiography and MRI. SM exhibited 3-fold smaller infarct size (SM-MI 18.6±3.4% vs CD1-MI 76.2±3.4%, p&lt;0.05) and better contractility measured by ejection fraction (SM-MI 77.1±6.5 vs CD1-MI 24.6±4.6, %, p&lt;0.05) than CD1 mice. SM showed 6-fold increase in BrdU + cells in left ventricle after MI while CD1 mice had 4-fold increase (CD1-sham 11±3.5 vs CD1-MI 44±9.1 and SM-sham 16±9.8 vs SM-MI 101.1±30.9, p&lt;0.05). Though basal cardiac ACE2 activity was not different between CD1 and SM, MI resulted in a 16% decrease in cardiac ACE2 activity in CD1-MI mice but 20% elevation of cardiac ACE2 activity in myocardial tissue in SM-MI. Conclusions: SM are protected from ischemia induced cardiac damage and dysfunction. This involves increased proliferating cardiac cells and reduction in infarct size. Thus SM could be an ideal animal model for identification of molecular and genetic circuits involved in preservation/regeneration of cardiac function with translational implication to human MI.

Biochemical and Physiological Studies of Ischemia-Reperfusion in (Doca)-Salt Hypertensive Rat Heart

Abstract Using a (DOCA)-salt arterial hypertension rat model we aimed to test on isolated, ischemised and reperfused rat heart, physiological parameters as well as biochemical markers, both in myocardium and in plasma, in order to characterize modifications induced by DOCA-salt treatment. In our study we used 20 rats of 10 months old divided into two groups of 10 rats each: control and treated. The treated group has received for 4 weeks 2 subcutaneous injections/week with DOCA (20 mg/b.w. in solution of 0.9% NaCl+0.2% KCl) according to the protocol, and 10-14 days since the last dose of treatment, the animals have been sacrificed. Coronary flow (CF), heart rate (HR) and left ventricle developed pressure (LVDP) have been measured on isolated and perfused Langendorff heart system at a constant pressure and total lipids, cholesterol, HDL and LDL, lipid peroxides as well as GGT, LDH, CK have been assessed using standard biochemical methods and Randox and Sigma kits. As results, there was an increase in C.F, H.R. and LVPD in DOCA-salt treated hearts, accounting for an intense mechanic cardiac activity generated by the hypertension following DOCA-salt treatment, accompanied by an increase in lipid peroxide, in CK and LDH as markers of myocardial lesion and a reduction of GGT activity in myocardial tissue probably due to hypoxia generated by the cardiac insufficiency following the increase in arterial blood pressure and a decrease in antioxidant potential . DOCA-salt hypertension is associated with rapid development of high blood pressure, vascular growth, vascular stiffening, and cardiac hypertrophy with increasing in mechanical activity of the heart, and a decrease in GGT activity and in antioxidant potential.

Modeling electrical activity of myocardial cells incorporating the effects of ephaptic coupling.

Existing models of electrical activity in myocardial tissue are unable to easily capture the effects of ephaptic coupling. Homogenized models do not account for cellular geometry, while detailed spatial models are too complicated to simulate in three dimensions. Here we propose a unique model that accurately captures the geometric effects while being computationally efficient. We use this model to provide an initial study of the effects of changes in extracellular geometry, gap junctional coupling, and sodium ion channel distribution on propagation velocity in a single 1D strand of cells. In agreement with previous studies, we find that ephaptic coupling increases propagation velocity at low gap junctional conductivity while it decreases propagation at higher conductivities. We also find that conduction velocity is relatively insensitive to gap junctional coupling when sodium ion channels are located entirely on the cell ends and cleft space is small. The numerical efficiency of this model, verified by comparison with more detailed simulations, allows a thorough study in parameter variation and shows that cellular structure and geometry has a nontrivial impact on propagation velocity. This model can be relatively easily extended to higher dimensions while maintaining numerical efficiency and incorporating ephaptic effects through modeling of complex, irregular cellular geometry.

Improved myocardial perfusion in chronic diabetic mice by the up‐regulation of pLKB1 and AMPK signaling

Previous studies related impaired myocardial microcirculation in diabetes to oxidative stress and endothelial dysfunction. Thus, this study was aimed to determine the effect of up-regulating pAMPK-pAKT signaling on coronary microvascular reactivity in the isolated heart of diabetic mice. We measured coronary resistance in wild-type and streptozotocin (STZ)-treated mice, during perfusion pressure changes. Glucose, insulin, and adiponectin levels in plasma and superoxide formation, NOx levels and heme oxygenase (HO) activity in myocardial tissue were determined. In addition, the expression of HO-1, 3-nitrotyrosine, pLKB1, pAMPK, pAKT, and peNOS proteins in control and diabetic hearts were measured. Coronary response to changes in perfusion pressure diverged from control in a time-dependent manner following STZ administration. The responses observed at 28 weeks of diabetes (the maximum time examined) were mimicked by L-NAME administration to control animals and were associated with a decrease in serum adiponectin and myocardial pLKB1, pAMPK, pAKT, and pGSK-3 expression. Cobalt protoporphyrin treatment to induce HO-1 expression reversed the microvascular reactivity seen in diabetes towards that of controls. Up-regulation of HO-1 was associated with an increase in adiponectin, pLKB1, pAKT, pAMPK, pGSK-3, and peNOS levels and a decrease in myocardial superoxide and 3-nitrotyrosine levels. In the present study we describe the time course of microvascular functional changes during the development of diabetes and the existence of a unique relationship between the levels of serum adiponectin, pLKB1, pAKT, and pAMPK activation in diabetic hearts. The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes.

Cardioprotection with forsythoside B in rat myocardial ischemia-reperfusion injury: Relation to inflammation response

The present study was undertaken to examine the effect of forsythoside B (FB) on rat myocardial ischemia-reperfusion (I/R) model and elucidate the potential mechanism. Left ventricular systolic pressure (LVSP) and +/-dp/dt(max) were detected. Blood samples were collected to determine serum levels of troponin T (Tn-T), TNF-alpha and IL-6. Hearts were harvested to assess histopathological change and infarct size, determine content of MDA, myeloperoxidase (MPO), SOD and GPx activities, analyze expression of high-mobility group box 1 (HMGB1), phosphor-I kappaB-alpha and phosphor-nuclear factor kappaB (NF-kappaB) in ischemic myocardial tissue by Western blot. Compared with control group, rats treatment with FB showed a significant recovery in myocardial function with improvement of LVSP and +/-dp/dt(max). The myocardial infarct volume, serum levels of Tn-T, TNF-alpha and IL-6, content of MDA and MPO activity in myocardial tissue were all reduced, protein expression of HMGB1, phosphor-I kappaB-alpha and phosphor-NF-kappaB were down-regulated, while attenuated the decrease of SOD and GPx activities. Besides, the infiltration of polymorph nuclear leukocytes (PMNs) and histopathological damages in myocardium were decreased in FB treated groups. These findings suggested that FB rescued cardiac function from I/R injury by limiting inflammation response and its antioxidant properties.

Effects of some modulators on purine nucleoside phosphorylase activity in myocardial tissue

Purine nucleoside phosphorylase (PNP) in mammalian tissue is an enzyme responsible for formation of purine bases in DNA. It is also believed that PNP is crucial under energy-deprived conditions for the cell to metabolise adenosine during ATP degradation. This work describes a new method for determination of PNP activity in myocardial tissue using a commercially available substrate, 2-amino-6-mercapto-7-methylpurine riboside (MESG). The method involves the photometric assessment of the reaction between PNP (extracted from myocardial tissue) and MESG. Quantification as well as temperature- and pH-dependency for myocardial PNP activity is described. Also, the effect of some modulators has been studied. We have established the presence of PNP activity in pig myocardial tissue. Further, the results indicate a pH tolerance under slightly acid conditions and a calcium ion dependence of the enzyme.

A multiresolution space‐time adaptive scheme for the bidomain model in electrocardiology

AbstractThe bidomain model of electrical activity of myocardial tissue consists of a possibly degenerate parabolic PDE coupled with an elliptic PDE for the transmembrane and extracellular potentials, respectively. This system of two scalar PDEs is supplemented by a time‐dependent ODE modeling the evolution of the gating variable. In the simpler subcase of the monodomain model, the elliptic PDE reduces to an algebraic equation. Since typical solutions of the bidomain and monodomain models exhibit wavefronts with steep gradients, we propose a finite volume scheme enriched by a fully adaptive multiresolution method, whose basic purpose is to concentrate computational effort on zones of strong variation of the solution. Time adaptivity is achieved by two alternative devices, namely locally varying time stepping and a Runge‐Kutta‐Fehlberg‐type adaptive time integration. A series of numerical examples demonstrates that these methods are efficient and sufficiently accurate to simulate the electrical activity in myocardial tissue with affordable effort. In addition, the optimal choice of the threshold for discarding nonsignificant information in the multiresolution representation of the solution is addressed, and the numerical efficiency and accuracy of the method is measured in terms of CPU time speed‐up, memory compression, and errors in different norms. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2010

Towards a biomechanics-based technique for assessing myocardial contractility: an inverse problem approach

This work presents the initial development and implementation of a novel 3D biomechanics-based approach to measure the mechanical activity of myocardial tissue, as a potential non-invasive tool to assess myocardial function. This technique quantifies the myocardial contraction forces developed within the ventricular myofibers in response to electro-physiological stimuli. We provide a 3D finite element formulation of a contraction force reconstruction algorithm, along with its implementation using magnetic resonance (MR) data. Our algorithm is based on an inverse problem solution governed by the fundamental continuum mechanics principle of conservation of linear momentum, under a first-order approximation of elastic and isotropic material conditions. We implemented our technique using a subject-specific ventricle model obtained by extracting the left ventricular anatomical features from a set of high-resolution cardiac MR images acquired throughout the cardiac cycle using prospective electrocardiographic gating. Cardiac motion information was extracted by non-rigid registration of the mid-diastole reference image to the remaining images of a 4D dataset. Using our technique, we reconstructed dynamic maps that show the contraction force distribution superimposed onto the deformed ventricle model at each acquired frame in the cardiac cycle. Our next objective will consist of validating this technique by showing the correlation between the presence of low contraction force patterns and poor myocardial functionality.

Endotoxin challenge reduces aconitase activity in myocardial tissue

Sepsis impairs mitochondrial respiration but the mechanisms responsible are incompletely understood. We propose that Krebs cycle enzymes are inhibited in sepsis, contributing to reduced rates of oxidative phosphorylation. Hypothesis. The activities of Krebs cycle enzymes are decreased in endotoxemia and contribute to reduced rates of oxidative phosphorylation. Methods. Adult male rats received an intraperitoneal injection of either endotoxin or saline. Cardiac mitochondria were subsequently isolated and measures of mitochondrial respiration and enzyme activities performed. Main results. By 24 h post endotoxin administration, there was a 28% reduction in mitochondrial respiration ( P = 0.0005) and a 24% reduction in aconitase activity ( P = 0.001). Functional activity of the electron transport chain was unaffected. Conclusion. Our data demonstrate that in the heart, the administration of endotoxin significantly and selectively decreased aconitase activity in association with reduced rates of oxidative phosphorylation. We conclude that decreased activity of aconitase contributes to the endotoxin-stimulated reduction in mitochondrial respiration.

Induction of Cardiac Uncoupling Protein-2 Expression and Adenosine 5′-Monophosphate-Activated Protein Kinase Phosphorylation during Early States of Diet-Induced Obesity in Mice

The objective of this work was to characterize the adaptation of cardiac metabolism to a lipid overload in a model of diet-induced obesity (DIO) in mice. After 8 wk dietary treatment, mice receiving a high-fat diet exhibited an increase in the amount of adipose tissue, accompanied by a surge in plasma leptin concentration (from 5.4-16.0 ng/ml). This was associated with: 1) an induction of uncoupling protein-2 (120%), 2) an increase in the phosphorylated form of AMP-activated protein kinase (120%), and 3) a reduction in lactate concentration and lactate dehydrogenase activity in myocardial tissue (40%). Because DIO induces leptin resistance, we analyzed leptin receptor functionality by measuring phospho-signal transducer and activator of transcription 3 in response to acute leptin (1 mg/kg). We observed that leptin receptor signaling remained unaltered within the heart but was fully impaired within the hypothalamus. Taken together, these data show that during DIO development, there is a metabolic shift in the heart aimed at increasing fatty acid oxidation to the detriment of carbohydrates. This effect seems to be leptin-dependent, suggesting that the increased adiposity observed during the onset of obesity might contribute to impairing ectopic lipidic deposition in the heart.

Phase singularities and termination of spiral wave reentry.

Recent defibrillation studies show that electric fields interact with reentrant activity in myocardial tissue through virtual electrode polarization (VEP). This study focuses on determining how VEP relates to the creation and survival of postshock phase singularities in cardiac tissue and demonstrating that interactions between VEP and preshock tissue state engender the probabilistic nature of defibrillation. We constructed a two-dimensional tissue model representing a ventricular cross-section with fiber architecture and surrounding bath. We initiated spiral wave reentry and subjected the tissue to a monophasic shock. We estimated the shock success probability for a given strength by testing 16 coupling intervals throughout a single rotation of the wavefront. Over a range of shock strengths, our model exhibits dose-response behavior similar to experimental defibrillation efficacy curves. At the 50% effective strength (ED50), successful termination of reentry depends upon the interaction between preshock excitable gap and postshock phase singularities. We also found that increasing the stimulus strength toward ED50 increases the number of postshock singularities, whereas further strength increases above ED50 decrease the number of singularities. Our results show for the first time that a computational model can account for the probabilistic nature of defibrillation as VEP interacts with the dynamics of an ongoing reentrant wavefront. Further, we demonstrate that success of a shock depends on the annihilation of the phase singularities that arise after any strong stimulus. Our findings imply that VEP completely overrides the preshock tissue state in shocks that are highly likely to defibrillate (ED95).

Ultrastructural modifications and phosphatidylinositol-3-kinase expression and activity in myocardial tissue deriving from rats in different experimental conditions.

Oxygen supply is essential in the maintenance of the physiological cell metabolism. In fact, both lower and higher O2 concentrations induce modifications of the enzymatic activity of the cell which determine, in turn, morphological changes at nuclear and cytoplasmic level. Among the molecules involved in the maintenance of the cellular homeostasis, the signal transduction pathway PI-3-kinase/AKT-1 should be included. Here we suggest a relationship between the modulation of this pathway and the morphological modifications occurring "in vivo" in myocardial tissue upon hypoxic and hyperoxic stress. In particular, down regulation of this pathway, which when activated is known to deliver an anti-apoptotic signal, is concomitant to the maintenance of the apoptotic events occurring in these cells in response to oxidative stresses.

Dose-response studies with idrapril in the rat heart during acute myocardial ischaemia and reperfusion

We assessed the effects of idrapril, a novel angiotensin-converting enzyme inhibitor, and captopril in the isolated rat heart after ischaemia and reperfusion and measured angiotensin-converting enzyme activity in myocardial tissue. Hearts were perfused and subjected to global ischaemia and reperfusion. Idrapril (0.1, 1, 10, and 50 μg/ml), captopril (80 μg/ml) or vehicle were given before ischaemia and throughout reperfusion. Post-ischaemic recovery of coronary flow was significantly decreased with 50 μg/ml of idrapril (43 ± 9% compared to 64 ± 3% in controls) whereas heart rate was unaffected. Recovery of developed pressure and activity of cardiac angiotenδin-converting enzyme were significantly reduced by idrapril in a dose-dependent manner. This study suggests that protection or lack of protection by idrapril on recovery of contractile function seems to depend on the degree of inhibition of tissue angiotensin-converting enzyme activity in the setting of acute heart ischaemic insult. Our results suggest that while a certain degree of inhibition of angiotensin-converting enzyme in the heart is beneficial, marked tissue inhibition may be deleterious.

Microcalorimetric study of myocardial tissue metabolism in heart failure after experimental myocardial infarction in rats

Abstract Using microcalorimetry and measuring oxygen consumption rate, we have studied metabolic activity in myocardial tissue from rats suffering from congestive heart failure (CHF) after ligation of the left coronary artery followed by myocardial infarction, comprising 30–40% of the endocardial circumference, known to be large enough to induce heart failure and neuroendocrine counter-regulation. The heat production in the preserved part of the left ventricle, harbouring the myocardial infarction, was 0.94 ± 0.05 mW g −1 ( n = 10) and not different from the controls i.e 0.94 ± 0.05 mW g −1 , ( n = 23). The oxygen consumption rate was 1.36 ± 0.20 nmol O 2 s −1 g −1 in CHF myocardium and 1.55 ± 0.24 nmol O 2 s −1 g −1 in the control rats, ( n = 20), n.s. The calculated contribution from aerobic metabolism to total heat production was 71 ± 9% in the CHF rats and 80 ± 6% in the control group, n.s. In tissue samples taken from the region of the border of and into the macroscopically damaged area of the myocardial infarction ( n = 5), the value for heat production was 1.15 ± 0.13 mW g −1 and oxygen uptake 1.79 ± 0.23 nmol O 2 s −1 g −1 . These results show that the contribution from aerobic metabolism to total energy expenditure in preserved left ventricular tissue is not higher than normal and suggest that the effects of left coronary occlusion are not limited to the generation of a myocardial infarction, but may also have a substantial impact on the ability of myocardial cells to increase metabolic activity in macro- and microscopically preserved regions of the left ventricle. In addition, the data demonstrate persistent metabolic activity within the region of ischemically damaged myocardium not different from that found in undamaged myocardium.

Microcalorimetric study of myocardial tissue metabolism in experimental hyperthyroidism in rats

The metabolic consequences in myocardial tissue, specifically concerning the importance of aerobic metabolism, following the stimulatory actions of thyroid hormones were studied in an experimental model for hyperthyrodism in rats, treated with triiodothyronine (T3) for two weeks. The metabolic activity in myocardial tissue was measured by microcalorimetry and related to oxygen consumption and to the ATP content. In myocardial muscle tissue from rats given 10–25 μg T3 daily over two weeks, heat production was 1.53 ± 0.09 mWg −1, compared to 0.94 ± 0.05 mWg −1 in controls, p <0.001. Similarly, oxygen consumption was higher in T3-treated rats, 2.75 ± 0.16 nmol O 2s −1g −1, compared to 1.55 ± 0.14 nmol O 2s −1g −1 in the controls, p < 0.001. There was a significant correlation between heat production and oxygen consumption values when data from controls and T3-treated rats were put together, r = 0.66, p < 0.001. The ATP content in the myocardial tissue was significantly lower in T3-treated rats than in control rats, 2.82 ± 0.53 and 7.91 ± 0.44 μmolg −1 respectively, p < 0.001. The myocardial tissue ATP content was inversely correlated to myocardial heat production, r = −0.54, p < 0.01, and oxygen consumption, r = −0.50, p < 0.05. In conclusion, the present data demonstrate the close relationship between oxygen consumption and metabolic activity in rat myocardial tissue in the euthyroid and hyperthyroid states. Aerobic metabolism was calculated to account for about 80% of the myocardial heat production in the euthyroid state and for about 87% in the hyperthyroid state. In addition, T3 treatment was associated with a significant reduction of the ATP content in the myocardial tissue studied, suggesting that myocardial ATP generation may be insufficient to meet the increased demand on heart performance in hyperthyroidism.