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The aim of this experiment is to study the mechanism of APN in alleviating the Ca2+-overloading in dog model during the process of ischemic reperfusion. In comparison with the sustained ischemic group, the parameters in the ischemic reperfusion group demonstrated: Ca2+ of ischemie region of myocardial cell increased (P

Our aim was to find a simple method of diagnosing the different stages of atrial fibrillation. Using only the time dependence of the action potential of a myocardial cell, an appropriate modified FitzHugh-Nagumo (MFHN) approximation to the electrical function is obtained. A criterion which successfully discerns between healthy patients and patients with different stages of atrial fibrillation (AF) is derived. This method can be used effectively to diagnose AF.

BACKGROUND Troponin-T is one of the contractile proteins of the myocardium. Its release into the circulation indicates various degrees of myocardial cell damage. Troponin-T may be measured in serum with a recently developed enzyme immunoassay. This immunoassay was used to evaluate the preoperative myocardial cell damage in patients with stable and unstable angina undergoing elective coronary artery bypass graft surgery, and it was compared with conventional assays of creatine kinase (CK) MB isoenzyme activity and mass. METHODS Twenty-one patients with unstable angina and 31 with stable angina were studied. Troponin-T, CK-MB activity, and CK-MB mass were measured 24 h before anesthesia and surgery, immediately before induction of anesthesia, before and after cardiopulmonary bypass, at the end of surgery, and 24 h afterward. RESULTS In 90% (19 of 21) of the patients with unstable angina, troponin-T was increased 24 h before anesthesia (median 0.33 microgram/l, range 0.15-5.2 micrograms/l), whereas only 3% (1 of 31) of the patients with stable angina had increased values (median 0.0 microgram/l, range 0.0-0.53 microgram/l). The difference was statistically significant (P < 0.001). The same profile was found in patients with and without unstable angina immediately before induction of anesthesia (86% [18 of 21] and 0%, respectively) and before cardiopulmonary bypass (62% [13 of 21] and 0%, respectively). In contrast to troponin-T, CK-MB activity was increased in only 0-14% of patients with unstable angina, and CK-MB mass was increased in only 9-24%. After bypass troponin-T increased in both groups (P < 0.01), but there was no longer a statistically significant difference between the groups. Twelve percent (4 of 31) of the patients in the stable angina group and 28% (6 of 21) in the unstable group had major cardiac events (P not significant). CONCLUSIONS The study data suggest that many patients with unstable angina undergoing elective coronary artery bypass graft surgery have already increased troponin-T levels preoperatively, although conventional biochemical markers such as CK-MB activity and mass are at a normal range. Increased troponin-T and normal CK-MB concentrations may reflect some degree of ischemic myocardial cell damage. Because of the small number of patients in the study, the influence of preoperative myocardial injury on perioperative outcome could not be clarified.

(1994). Troponin T: A New Marker for Myocardial Cell Injury. Annals of Medicine: Vol. 26, No. 5, pp. 319-320.

Role of Oxidative Damage and Myocardial Cell Injuries in Human Severe Sepsis/Septic Shock after Surgical Correction of Congenital Heart Disease in Infants

Background and aims: Despite advances in pediatric cardiac surgery, perioperative myocardial injury can be the major determinant of postoperative dysfunction after cardiac surgery. The objective was to investigate the pathology-related differences in 29 infants with congenital heart disease that led to death.

Objective To investigate the regulation of microRNAs (generally shorten as miRNAs) on the expression levels of angiotensin-converting enzyme (ACE), which is a key candidate gene in cerebrovascular and cardiovascular diseases. Methods Around 37 miRNAs that may regulate ACE were predicted based on the ‘eed-region’ principle. Among them, miR-27a and miR-27b are two ACE-regulating miRNAs matching 39-UTR regions of both human and rodent origin and thereby were the focus of further tests. Rat myocardial cell line H9c2 (2-1) in culture was subjected to miR-27a and 27b enhancing and inhibiting treatments. MiR-27a and 27b precursor molecules were applied to boost the functional levels, while chemically modified miR-27a and 27b as antagonists were applied to blunt the activities of miR-27a and 27b, respectively. Each test was controlled with the treatment using corresponding negative control molecules. The precursor and inhibitor were introduced into cells using iFect mediated transfection. Cells were harvested for ACE immunoblotting after 48 h of treatments. Results Enhancing of miR-27a or 27b with corresponding precursors significantly down-regulated cellular ACE protein levels, while inhibiting with corresponding antagonists significantly up-regulated ACE levels. According to ANOVA analysis, 48 hours treatments of miR-27a and miR-27b precursors reduced ACE levels by 35.98% (p=0.022) and 41.32% (p=0.009), respectively; meanwhile, 48 h treatments of miR-27a and miR-27b antagonists increased ACE levels by 46.11% (p=0.047) and 75.15% (p=0.002), respectively. Conclusion miR-27a and miR-27b significantly regulate myocardial ACE levels in a negatively correlated pattern.

Results: The mean age of the sample population was 69± 16 years. Male 54%. Forty-one percent had GFR 30%. Of these patients 65% (n= 15) had a discharge diagnosis of ACS, 11 of these underwent coronary angiography, 10 of which required coronary revascularisation; 5% (n= 1) had a discharge diagnosis of other cardiac condition and 30% (n= 7) had a discharge diagnosis of other condition, two of these patients underwent coronary angiography which showed non flow limiting disease. Conclusions: Elevated hs-TnT is not only indicative of ACS but is also representative of other disease states affecting themyocardium.Thereforewhile hs-TnT ismore sensitive in detecting myocardial cell death, it is less specific in isolating the cause of ischemia. doi:10.1016/j.hlc.2011.05.506

Ventricular fibrillation in humans is generally sustained (SVF), but it can be also transient (TVF), reverting spontaneously to sinus rhythm. In previous studies we have shown that: a) TVF appears in all young mammals and varies according to age and species; b) it requires synchronization of myocardial cell activity; c) infusion of certain drugs may change the type of ventricular fibrillation from sustained into transient. We hypothesize that the synchronization required for TVF depends on the electrical conductivity of intercellular structures. These intercellular couplings differ among species and decrease with age. Comparison between the inter- and intra-specific variations of intercellular connective structure described in the literature with the type of ventricular fibrillation found in our previous studies on various animals of different ages showed a clear relationship between these histological variations and the changes in the type of ventricular fibrillation. In this study we examined intercellular connective structures ultrastructurally in 3 groups of cats: a. control, untreated cats exhibiting sustained ventricular fibrillation; b. untreated cats exhibiting transient ventricular fibrillation; c. treated cats exhibiting sustained ventricular fibrillation before infusion of a defibrillating drug and transient ventricular fibrillation thereafter. It was found that the intercellular connective structure in cats exhibiting sustained ventricular fibrillation differs significantly from that in cats exhibiting transient fibrillation. In hearts exhibiting sustained ventricular fibrillation, many intercellular connective structures are widened and the degree of widening is pronounced, forming a continuous line, while in hearts exhibiting transient ventricular fibrillation the widened junctions are rare and isolated and the widening is relatively small. These preliminary results strongly support our above-mentioned hypothesis, providing an explanation for the origin of transient ventricular fibrillation and a tool for the development of new defibrillating drugs.

Respiration is a central factor of metabolism in almost all tissues; thus, all pharmacological effects also concern the energy metabolism in a direct or an indirect manner. A system which allows determination of oxygen consumption and simultaneously application of the methods of light microscopy is therefore of general pharmacological interest, irrespective of the cell type under investigation. We present the application of such a test system to the study of myocardial cell responses after exposition to uremic compounds.

Background The use of halogenated anaesthetics in cardiac surgery is still controversial. Preconditioning and postconditioning are the well described mechanisms that explain the protective myocardial effect of specific drugs in order to prevent the occurrence and/or to reduce the size of a necrotic post-ischemic myocardial area [1]: they play a well recognized role in the “protective effect” of the halogenated anaesthetics. Preconditioning and postconditioning protect the myocardial cell from oxidative stress and take place through the activation of specific receptors and second messengers systems [2]. Desflurane has shown a higher preconditioning and postconditioning power that could be optimal at 6% of Minimum Alveolar Concentration (MAC) [3]. The solubility of the halogenated anaesthetics can be altered during cardiac surgery: Desflurane has shown a rapid wash-in and wash-out profile in cardiac “on pump” surgery [5,6].

Hibernating myocardium refers to the presence of persistent myocardial and left ventricular dysfunction at rest, associated with conditions of severely reduced coronary blood flow. This left ventricular dysfunction probably represents an adaptive mechanism preventing irreversible myocardial cell damage, since myocardial and left ventricular dysfunction in hibernating myocardium improve following the restoration of coronary blood flow. This review examines the evolution of the concept of hibernation from a clinical observation to the potential underlying mechanisms recently proposed.

A floating collagen matrix culture of neonatal rat heart myocardial cells shows rhythmic contractions which are dependent on localization of cells, cell density, and collagen concentration. The rhythmic contractions of the collagen matrix can be registered by a device scanning the optical density at the edge of the gel and have been observed over a temperature range from 9 degrees to 40 degrees C. The results of the present study underline the usefulness of myocardial cell populated collagen matrixes for studies on coherent contractions of heart cell cultures.

To understand pacemaker technology, the knowledge of certain anatomical, physiological and pathophysiological facts is required. The aim of the following chapters is to briefly explain the basic functions of the heart and its control mechanisms such as the autonomic nervous system as a part of the central nervous system. However, the content should not be considered as a complete and detailed description of all anatomical and physiological details. It is recommended that other textbooks on physiology, electrophysiology, pathophysiology as well as cardiology be studied [1–4].

The study of the process and control of the transitional cardiovascular physiology from the fetal to adult condition has brought enormous insight into the diagnosis, natural history and treatment of congenital, as well as acquired, cardiac abnormalities in children. It is now apparent that a remarkable passage also occurs in the metabolic maturation of the myocardium. The myocardial cell undergoes important changes in metabolic operations that include substrate preference, maintenance of cellular integrity, production and delivery of high energy phosphate, replication of the contractile apparatus as well as response to adverse metabolic and hemodynamic conditions. Remarkably, the functional capacity of the heart remains essentially constant throughout this period of differentiation. Indeed, the immature cardiovascular system demonstrates a striking capacity to accommodate severe physiologic burdens and metabolic alterations.

The clinical value of cardiac Troponin T (cTnT) as a marker in assessing myocardial cell damage in the patients undergoing open heart surgery was studied. Serum cTnT and CK-MB levels were measured in serial blood samples from 20 patients undergoing open heart surgery before operation, at aorta clamping, aorta opening, the end of CPB and the operation, and subsequently one h, one day, 3 days and one week after operation respectively. Ten patients receiving thoracic surgery were also subjected to the measurement of cTnT and CK-MB before and 24 h after operation. The results showed that peak concentrations were reached earlier in cTnT than in CK-MB, and the circulation cTnT remained high when CK-MB had already decreased to normal. In 10 patients receiving thoracic surgery, cTnT level was normal and CK-MB was increased in 4 patients after surgery. It was concluded that the sensitivity and specificity of cTnT was more than those of CK-MB and cTnT could be used as a routine indicator for myocardiac protection.

with a history of CHF who present with ACS. This has been associated with an increase in the use of evidence based therapies in this high risk population. doi:10.1016/j.hlc.2009.05.430

Since 1978, the most prevalent drug used in conjunction with cocaine in cocaine-associated myocardial deaths is ethanol. Primary myocardial cell cultures were used to evaluate the acute additive cardiotoxic effects of cocaine and ethanol. The cultures were exposed to 1 × 10 −3 m or 1 × 10 −5 m -cocaine or combinations of both concentrations of cocaine with 600 mg ethanol/100 ml. Alterations in beating activity, morphology, and lactate dehydrogenase (LDH) release were evaluated after 1, 4 and 24 hr of treatment. Although cells exposed to 1 × 10 −5 m -cocaine or to 1 × 10 −5 m -cocaine and ethanol were able to retain some beating activity, no beating activity occurred in cells exposed to 1 × 10 −3 m -cocaine with or without ethanol. Morphologically, pseudopodia and disruption of the monolayer were more extensive in cells treated for 4 or 24 hr with the combinations of cocaine and ethanol in comparison with those treated with cocaine alone. After 24 hr, LDH release in cells exposed to 1 × 10 −3 m -cocaine or 1 × 10 −3 m -cocaine with ethanol was elevated over the level in untreated controls. These data suggest that ethanol enhances cocaine-induced beating abnormalities and morphological alterations in primary myocardial cell cultures.

In neonatal rat ventricular myocytes pretreatment with pertussis toxin did not affect 1 microM (-)-norepinephrine stimulation of inositol phosphates or myocardial cell hypertrophy as measured either by protein radiolabelling or by myocardial cell protein content. Thus guanine nucleotide protein(s) ADP-ribosylated by pertussis toxin do not play a role in two alpha 1-adrenoceptor-mediated processes, phosphatidylinositide turnover and induction of myocardial cell hypertrophy.

It is very much hoped that we might eventually be able to design specific strategies for saving myocardial tissue at different stages of progressive ischemic injury. At the point of irreversible injury, a causal therapeutic approach would have to intervene in the final process in which ischemic cell injury turns into irreversible damage. At present, the causal pathogenetic mechanisms of ischemia and reperfusion are only incompletely understood Today’s clinical therapeutic repertoire already contains a number of remedies applied to the ischemic and reperfused myocardium. For the development of future therapeutic concepts, however, the causal character of these approaches must be scrutinized (see Chapter 2).

The hypothesis that glycolytically produced ATP has a special role in the preservation of myocardial cells is critically examined. Considerable indirect evidence supports this proposal, although the electrophysiological data remain controversial and capable of different interpretations. Thus far the most convincing evidence favoring the concept of compartmentation comes from data relating rates of glycolytic flux to enzyme release from the isolated heart or from isolated myocytes and from the regulation of the onset of ischemic contracture. More direct evidence has now been obtained in isolated cardiac myocytes. The hypothesis formed the basis of a metabolically orientated approach towards decreasing severity of myocardial ischemic injury. Nonetheless, until analytical methods become available for the specific measurement of a membrane-related pool of ATP, the hypothesis will be supported by indirect rather than direct evidence.

Patients with unstable angina represent a heterogeneous group. While in some patients no coronary artery disease is present, in others one finds severe coronary artery narrowing that leads to rather severe myocardial ischemia. In the latter subgroup of patients a release of myocardial cell constituents can be expected due to ischemic cell damage. Diagnostic tools of high sensitivity and specificity must be employed for its detection. This chapter therefore begins with a discussion of the determinants of diagnostic efficacy in serological tests.

In spite of tremendous strides forward in cardiac pathophysiology over the past 30 years, knowledge of the genesis of irreversible ischemic myocardial injury is still limited. Ischemic myocardial heart disease is predominantly caused by the thrombotic occlusion of coronary arteries. After an initial period of ischemia during which restoration of supply conditions still allows structural and functional recovery of the myocardial cell, ischemic injury becomes irreversible or, in other words, reversible ischemia turns into infarction.

We thank Dr Swenne and his colleagues for their interest in our manuscript.1 Transmural dispersion of repolarization (TDR) in the heart has been linked to a variety of arrhythmic manifestations.2 Three electrophysiologically distinct cell types have been identified in the ventricular myocardium: endocardial, epicardial, and M cells. Differences in the time course of repolarization of these three ventricular myocardial cell types contribute prominently to inscription of the electrocardiographic T-wave.3 In isolated ventricular wedge preparations, the …

To the Editor: Okabe et al1 studied the association of hepatitis C virus (HCV) infection with chronic active myocarditis, a variant form of chronic myocarditis characterized by numerous lymphocytic clusters and myocardial cell damage, in 3 patients. Using the so-called genomic analysis to detect positive (genomic) and negative (replicative) strands of HCV RNA, the authors found that all 3 patients had both positive- and negative-strand HCV RNA in their myocardial tissue. They therefore concluded that HCV can replicate in inflamed myocardial tissue and may contribute to the development of chronic active myocarditis. Although their findings are interesting and the association of HCV infection with chronic active myocarditis may be true, controversial issues still exist that should be carefully addressed before drawing a final conclusion. First, the strand-specific polymerase chain reaction (PCR) used by the authors to detect positive- and negative-strand HCV RNA may not be stringent enough, and possible false positivity cannot be excluded. Previous studies2 3 have …

Myocardial contusion (MC) is defined as cellular damage that results from nonpenetrating chest trauma. MC is the most common cause of morbidity and mortality in patients who have had chest trauma. Diagnosis of MC is laborious, and chest pain, dyspnea, and nonspecific electrocardiograph changes are commonly present in patients with chest injury. Although transesophageal echocardiography (TEE) can provide high quality images for diagnosis (1)(2), noninvasive diagnosis of this lesion has been always problematic. Cardiac enzyme activity is not commonly used for MC diagnosis. In recent years, the development of assays using new, highly cardiac-specific proteins has opened new frontiers for the diagnosis of myocardial cell damage. Cardiac troponin I (cTnI) is a small filament-associated regulatory protein of muscle, uniquely specific for the heart (3). cTnI is not expressed by developing or diseased …

Extracorporeal circulation may trigger an extensive inflammatory response and the release of cytokines, which can induce myocardial ischemia.

Backgrounds: It has been well known that Tc-99m sestamibi may have the potential for freezing myocardial perfusion. However, this agent does not freeze myocardial perfusion in a certain situation such as impaired myocardium (JNM 1996:1289–94). The abnormalities of Myocardial blood flow (MBF) and flow reserve have been observed in patients with chronic heart failure (CHF) and MBF reserve may play an important role of the prognosis in these patients. This study was designed to compare myocardial blood flow and flow reserve with washout of Tc-99m sestamibi in CHF patients. Methods: MBF and MBF reserve were measured in 10 patients with CHF due to non-ischemic cardiomyopathy and 10 control subjects by means of O-15 Water PET. Myocardial planar images were also performed using Tc-99m sestamibi in order to measure washout (WO). These parameters were compared to other CHF parameters such as ejection fraction and BNP. Results: The values of MBF reserve in CHF patients significantly decreased compared to control (1.93 + 0.39 versus 3.00 + 0.79, p Conclusions: These results indicated that both myocardial flow reserve and washout of Tc-99m sestamibi were impaired in patients with CHF, reflecting the existence of myocardial cell damage. And in addition, the washout of Tc-99m sestabmibi were closely correlated with myocardial flow reserve and BNP, suggesting the washout of Tc-99m sestamibi might be useful for the risk stratification in patients with CHF.