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Defibrillation electrode configurations developed from cardiac mapping that combine biphasic shocks with sequential timing.

Previous canine mapping studies of the transvenous defibrillation lead configuration of right ventricle (RV) to left R2 patch (P) revealed regions of low potential gradient in the left ventricular apex (A) and the right ventricular outflow tract (O). Thus 16 new lead configurations were tested in eight dogs, which incorporated electrodes in A and O to raise the gradient. When used in conjunction with two sequential biphasic shocks, the average defibrillation threshold energy from these configurations was 57% lower than that produced by a single biphasic shock delivered through RV-->P (phase 1 cathode-->anode, p < 0.001). Of the 16 configurations tested, the most effective was RV-->P followed by A-->O. When the shocking order of this configuration was reversed in another eight dogs, no difference in defibrillation efficacy was noted. In individual configurations of RV-->P and A-->O that used a single biphasic shock, defibrillation was not effective. Finally, when two sequential biphasic shocks were delivered to the same two electrodes in seven other dogs, the defibrillation efficacy was low. Thus configurations that use two sequential biphasic shocks can produce low defibrillation thresholds when the shocks are delivered to two different sets of electrodes. The high efficacy may be caused by one shock increasing the potential gradient in regions of low potential gradient that are produced by the other shock.

Animals↗

Wave-form analysis of intrauterine pressure curves with methods and models developed in cardiac research.

With the Hill model of muscle dynamics and a modified cardiac model, a series of computer programs have been generated which permit the description of certain aspects of uterine contractility and uterine function in human parturition. Patterns of labor relating to delivery outcome, dysfunctional uterine activity, and use of drugs are discussed with reference to the parameters measured in the study. Central tendencies among 70 spontaneous and induced labors (6,302 contractions) are presented and discussed. (Am. J. Obstet. Gynecol.

Cardiology↗

Actin and myosin expression during development of cardiac muscle from cultured embryonal carcinoma cells.

P19 embryonal carcinoma cells are multipotential stem cells that differentiate into striated muscle as well as some other cell types when aggregated and exposed to dimethyl sulfoxide (DMSO). Immunofluorescence experiments using monospecific antibodies indicated that the majority of muscle cells were mononucleate and contained four myosin isoforms normally found in cardiac muscle; atrial and ventricular myosin heavy chains, ventricular myosin light chain 1, and atrial myosin light chain 2. Northern blot analysis of RNA isolated from differentiating cultures indicated that cardiac actin and skeletal actin mRNAs were expressed at similar levels and with identical kinetics during the differentiation of P19-derived myocytes. These results demonstrate that most of the P19-derived myocytes are of the cardiac type and suggest that they closely resemble the cells of the early embryonic myocardium.

Actins↗

[Development of cardiac physiopathological models from cultured cardiomyocytes].

The cultures of neonatal rat cardiomyocytes represent a very useful tool for the observation and the understanding of the cellular aspects of the electrophysiological, contractile, morphological, metabolic and molecular properties of the myocardium. This model is characterized by a homogeneous population of cardiac muscular cells and by vast possibilities of control of the chemical and physical environment of the cells, allowing the in vitro mimicry of a wide range of cardiac pathological situations. The cardiomyocyte cultures are thus suited to very varied experimental protocols, allowing multiparametric analysis of the cardiocellular effects of different stress such as hypoxia-reoxygenation, of ischemia-reperfusion, of the free radical attack and of thermal shock. These investigations can be combined with the study of the effects and of the cytotoxicity of pharmacological agents, not limited to the putatively cardioactive drugs. The present review proposes an outline of the procedures for the isolation, the culture and the use of neonatal cardiomyocytes. To illustrate the potentialities of this preparation, we describe more specifically the protocols and the various consequences at the cellular scale of an in vitro model of myocardial ischemia reperfusion.

Animals↗

Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit.

OBJECTIVE: Myocardial fibrosis contributes to the impairing of cardiac function and characterizes ageing, but is also a consequence of atherosclerotic ischemic disease. Since atherosclerosis is a slow progressive disease, which prevails in elderly populations, the aim of this study was to distinguish the contribution of ageing and atherosclerosis to cardiac fibrosis. METHODS: Coronary atherosclerosis was induced in 5-6-year-old rabbits by a hyperlipemic diet for 9 months. Left ventricular (LV) collagen was quantified by densitometric analysis after Sirius-Red staining; an immunohistochemical investigation of the interstitium was also performed. RESULTS: Atherosclerosis was associated to a marked increase of left ventricular interstitial collagen with the appearance of fibrotic foci and a decrease of coronary vessel endothelial nitric oxide synthase (eNOS) expression. In fibrotic foci, abundant macrophages co-localized with transforming growth factor beta-1 (TGFbeta-1)-positive myofibroblasts and vascular cell adhesion molecule-1 (VCAM-1) positive microvessels (52.3+/-3.9%). In normocholesterolemic rabbits, ageing resulted in a fourfold increase of myocardial interstitial collagen, with alpha-smooth muscle actin and TGFbeta-1 negative fibroblasts and VCAM-1 positive microvessels (19.4+/-1.2%) without macrophages, suggesting a role of endothelial dysfunction in age-related fibrosis. CONCLUSIONS: There is a distinct difference between ageing and coronary atherosclerosis-induced cardiac fibrosis, although the effects may be cumulative. In the cascade of events leading to myocardial remodeling, reparative fibrosis with TGFbeta-1-positive myofibroblasts and interstitial inflammation were the major findings in atherosclerotic old rabbits, whereas with ageing alone, interstitial fibrosis with TGFbeta-1 negative fibroblasts and VCAM-1 positive microvessels prevailed.

Actins↗

The cumulative effect of acute rejection on development of cardiac allograft vasculopathy.

BACKGROUND: Acute rejection increases the inflammatory burden of the transplanted organ and predisposes to cardiac allograft vasculopathy (CAV). In this study we aim to determine the magnitude of the association, and to differentiate between the effects of mild vs severe rejection episodes. METHODS: Between 1988 and 2003, 489 1-year survivors of heart transplantation underwent 1,435 angiograms. These patients were classified as having no CAV (0% stenosis), mild/moderate CAV (<70%) or severe CAV (>70%). Acute rejection was considered either mild (Grades 1A, 1B and 2 untreated) or moderate/severe (Grade 2 treated on a clinical basis and Grades 3A, 3B and 4). We used multi-state Markov models to examine risk factors for the onset of CAV. RESULTS: Expressed as relative risk, the onset of CAV was significantly increased by donor age (1.26 per 10 years, 95% confidence interval [CI] 1.12 to 1.42), male recipient (1.72, 95% CI 1.01 to 2.94), pre-transplant recipient ischemic disease (1.53, 95% CI 1.14 to 2.06) and cumulative number of moderate/severe rejections (1.10 per episode, 95% CI 1.03 to 1.18). Human leukocyte antigen (HLA) and cytomegalovirus (CMV) matching, donor gender, recipient age, smoking, cumulative CMV infections and mild rejections were not significant risk factors. Estimated annual onset rate of CAV was 11.3% for patients with no moderate/severe rejection, rising to 13.6% for those with two and 18.0% for those with five such rejections. CONCLUSIONS: Acute moderate/severe cellular rejection has a cumulative impact on CAV onset, whereas mild, untreated rejection is not associated with CAV.

Acute Disease↗

Effects of ACE inhibition during fetal development on cardiac microvasculature in adult spontaneously hypertensive rats.

BACKGROUND: Early angiotensin-converting enzyme (ACE) inhibition is able to re-program spontaneously hypertensive rats (SHR) to express an attenuated form of disease in adulthood. METHODS: Three groups of animals (n=5 each) were studied: Wistar male rats, SHR males, and SHR males obtained from dams treated with enalapril maleate (15 mg/kg/day) during gestation. Animals were sacrificed 180 days after birth, and hearts were removed for stereological quantification. Volume [Vv] (myocytes, cardiac interstitium and intramyocardial vessels), length [Lv] (intramyocardial vessels), surface [Sv] densities (myocyte and intramyocardial vessels), and the mean cross-sectional area [a] (myocyte) were estimated. RESULTS: Blood pressure (BP) was lower in Wistar group, higher in SHR group, and intermediate in SHR-enalapril group (respectively: 122+/-8.4, 194+/-11.4, and 158+/-7.6 mm Hg, p<0.0001). Increased Vv (p=0.016), Lv (p<0.01), and Sv (p<0.01) of intramyocardial vessels were observed in SHR-enalapril group when compared to untreated SHR. A small but significant reduction was observed in a of myocytes (p=0.045). CONCLUSION: Prenatal ACE inhibition resulted in partial hypertension attenuation as well as left ventricular hypertrophy (LVH). The positive impact on the vascular compartment came along with little or no difference in myocytes and interstitium, suggesting the involvement of a direct mechanism.

Angiotensin-Converting Enzyme Inhibitors↗