Cardiac MRI of the normal and hypertrophied mouse heart

With the development of recent transgenic techniques, studies involving mice offer opportunities to increase understanding of cardiac disease. This provides motivation for the current study to perform noninvasive evaluation of the normal and hypertrophied mouse heart with MRI. By acquiring ECG and respiratory signals, the MR image acquisition was gated to both the cardiac and respiratory cycles. Combining a spin-warp imaging sequence with an RF surface coil resulted in short-axis images that allowed quantification of in vivo cardiac mass. Excellent agreement between MRI-determined (y) and postmortem heart weight (x) was obtained: y = 0.991x + 1.43 (r = 0.996). Isoproterenol, at 282 micromol/kg body weight (BW) and 573 micromol/kg BW, induced a dose-dependent increase in the ratio of heart weight to BW of 16.8 +/- 1.09% and 24.1 +/- 1.71%, respectively, which was accurately measured by MRI. These results demonstrate the ability of MRI to noninvasively monitor cardiac anatomy in the mouse.     

Potassium metabolism in the normal and ischemic heart cell

Potassium is an important electrolyte in heart cells and has the greatest membrane permeability in the unexcited state. Hence it is responsible for th generation of the resting membrane potential. Clinical disorders of conduction and impulse formation occur within physiological values of serum potassium. Potassium is indirectly involved in excitation-contraction coupling, and its relation to intracellular calcium metabolism is reviewed. While potassium movements within the cell are metabolic-dependent, it is also true that the activity of metabolic pathways is affected by changes in potassium concentration. During anoxia and ischemia, sodium and calcium are gained by the myocyte, and potassium and magnesium are lost by the cell. At the same time, the action potential duration is abbreviated, the slope of the action potential downstroke (phase 2) is increased, and the resting membrane potential may be reduced. A relationship between disturbances in intracellular potassium and ischemic arrhythmias appears likely.     

Surgical repair of the congenitally malformed mitral valve in infants and children

BACKGROUND: Mitral valve remodeling techniques were applied to 26 infants and children (mean age, 6.0 years, range, 0.4 to 15.9 years) with various forms of congenital mitral valve disease over a 7-year period. Patients with atrioventricular canal, L-transposition and single ventricle were excluded. Intraoperative transesophageal echocardiography (TEE) was utilized to assess the repair and guide the need for immediate intervention. METHODS: Twenty-one patients had mitral regurgitation: 10 with cleft anterior mitral leaflet, 7 with annular dilatation, 1 with normal leaflets with an obstructing cord, 2 with prolapsed leaflets and elongated cords, and 1 with restricted leaflet motion, normal papillary muscles, and shortened cords. Of the 5 mitral stenosis patients, 3 had supravalvular mitral ring, 1 had midvalvular mitral ring, and 1 had a parachute valve. Three of the mitral stenosis patients had additional stenotic lesions. Concurrent repair of associated lesions was performed in 21 patients (78%). RESULTS: Operative mortality was 3.8% (n = 1). There were no late deaths. Immediate rerepair in 4 patients resulted in improved function. All mitral stenosis patients improved. A total of 20 mitral regurgitation patients (95%) improved; 1 required mitral valve replacement. Mean follow-up is 31 months (range, 2 to 81 months). All patients are in New York Heart Association functional class I or II. CONCLUSIONS: Mitral valve repair can be successfully performed in infants and children with excellent short- and midterm results. Assessment using transesophageal echocardiography can guide the necessity for immediate rerepair to achieve improved function.     

Effect of enalapril treatment on the heart of normal rats

Previous experiments showed that enalapril (EN) treatment as well as enalaprilic acid, when added to the perfusion bath, diminish the inotropic response of the papillary muscles to isoproterenol (ISO). The main objective of this study was to evaluate, in normal rats, the effect of EN on basal contractility and inotropic response to ISO on the whole perfused ventricles (Langendorff preparation). Blood pressure (BP), increase in body weight (IBW), ventricular weight/body weight ratio (R) and concentration of ventricular proteins and DNA were also analyzed. Five groups were studied: EN10: 5 mg/kg/day, 10 days; EN21(L): 5mg/kg/day, 21 days; EN21(H): 15 mg/kg/day, 21 days. C10 and C21 were untreated controls. Cardiac contractility was evaluated by the maximal developed pressure, maximal rate of rise of pressure and maximal velocity of relaxation; no changes were found due to EN treatments either on basal conditions or on ISO stimulation. Significant differences (p<0.05 vs C21) were: lower BP and R in EN21(L) and EN21(H), slower IBW in EN21(H), decreased ventricular DNA in EN21(H). In conclusion, daily treatment for ten or twenty one days with enalapril does not change either basal cardiac contractile performance or inotropic response to ISO in the Langendorff preparation. Longterm treatment with EN seems to modify nuclear processes involved in cardiomyocite DNA content.     

Angiocardiographic findings and morphogenesis of criss-cross heart with situs solitus, concordant artrioventricular relationships and L-transposition

A case of so-called criss-cross heart is presented. The right atrium drained to the left-sided morphologic right ventricle from which the aorta originated anteriorly and leftward. The left atrium drained to the right-sided morphologic left ventricle, from which the pulmonary artey originated posteriorly and rightward. These angiographic findings are morphogenetically interpreted as a clockwise rotation of approximate 90 degrees looking toward the base (from the inferior view) of d-bulboventricular loop following the truncal septation.     

Troponin I phosphorylation in the normal and failing adult human heart

BACKGROUND: In the failing human heart myofibrillar calcium sensitivity of tension development is greater and maximal myofibrillar ATPase activity is less than in the normal heart. Phosphorylation of the cardiac troponin I (cTnI)-specific NH2-terminus decreases myofilament sensitivity to calcium, while phosphorylation of other cTnI sites decreases maximal myofibrillar ATPase activity. METHODS AND RESULTS: We examined cTnI phosphorylation in left ventricular myocardium collected from failing hearts at the time of transplant (n=20) and normal hearts from trauma victims (n=24). The relative amounts of actin, tropomyosin, and TnI did not differ between failing and normal myocardium. Using Western blot analysis with a monoclonal antibody (MAb) that recognizes the striated muscle TnI isoforms, we confirmed that the adult human heart expresses only cTnI. A cTnI-specific MAb recognized two bands of cTnI, designated cTnI1 and cTnI2, while a MAb whose epitope is located in the cTnI-specific NH2-terminus recognized only cTnI1. Alkaline phosphatase decreased the relative amount of cTnl1, while protein kinase A and protein kinase C increased cTnI1. The percentage of cTnI made up of cTnI1, the phosphorylated form of TnI, is greater in the normal than the failing human heart (P<.00). CONCLUSIONS: This phosphorylation difference could underlie the reported greater myofibrillar calcium sensitivity of failing myocardium. The functional consequence of this difference may be an adaptive or maladaptive response to the lower and longer calcium concentration transient of the failing heart, eg, enhancing force development or producing ventricular diastolic dysfunction.     

On the analytic description of normal grain growth

The main analytic theories of grain growth driven by capillarity are reviewed. When grain growth is pictured as a grain drift process, the major problem is to derive the drift velocity equation. The simplest possible choice is based on a one-grain model and thus neglects some of the topological requirements of the system. When grain growth on the other hand is pictured as a diffusion process in grain size-time-space there are problems with the physical interpretation of the diffusion coefficient. The previous treatments of grain growth along this line are shown to contain some fundamental shortcomings.     

Neurocardiogenic syncope in children with a normal heart

OBJECTIVES: The purpose of this study was to review the results of investigation and management of children with syncope and a structurally normal heart. BACKGROUND: Syncope is a common clinical problem and has many etiologies. Autonomic testing and, in particular, the tilt/orthostatic test have helped to positively diagnose neurocardiogenic syncope in a high proportion of such patients. METHODS: Patient case notes and autonomic test charts were reviewed in 162 children aged 1 to 20 years (mean age 12.8 years) with syncope. The autonomic test consisted of orthostatic maneuver, carotid sinus massage, diving reflex, Valsalva maneuver and dose response to intravenous boluses of isoproterenol and phenylephrine. Serum levels of epinephrine and norepinephrine were drawn during the orthostatic test. After confirmation of neurocardiogenic syncope, treatment was begun with fludrocortisone and salt, and beta-adrenergic blocking agents were used as a second line of therapy when indicated. RESULTS: The orthostatic test was positive for neurocardiogenic syncope in 100 patients (62%) and negative in 62 (38%). Patients in the former group were older, were more often female and had a diminished response to carotid sinus massage, a higher Valsalva ratio and a higher supine epinephrine level. Both groups showed an increase in epinephrine and norepinephrine levels at 5 min of standing. In the orthostatic positive group at the time of syncope, norepinephrine levels decreased, whereas epinephrine levels increased. Patients in this group were also more sensitive to the vasodilating effect of isoproterenol but not to its chronotropic effects. Eleven patients had cardioinhibitory syncope (asystole > or = 3 s). Of these, three had pacemaker implantation. Fludrocortisone and salt used in 84 patients in the orthostatic positive group produced resolution of symptoms in 55 patients (65%) and improvement in 14 (17%). Ten patients received beta-blockers, with resolution in four and improvement in four. CONCLUSIONS: Patients with orthostatic test-proved neurocardiogenic syncope show evidence of autonomic dysfunction. They also show beta-adrenergic hypersensitivity. Treatment initiated on the basis of the protocol was associated with amelioration of symptoms in the majority of patients.     

A flat decelerative fetal heart rate tracing with normal fetal heart rate variability

We report two cases for which computer interpretation of nonstress test indicated a flat decelerative trace in spite of normal fetal heart rate variability. Fetal behavioral state in the first case and signal loss in the second case were possibly responsible for this computerized interpretation of the tracings in the absence of fetal distress.     

Comparative effects of rapid and normal smoking on heart rate and carboxyhemoglobin.

Compared a rapid smoking procedure closely approximating that found in clinical and research practice to normal smoking and a rapid breathing/sham-smoking control. Ss were 3 male and 3 female undergraduates who had smoked for an average of 4.4 yrs with a mean baseline of 24.2 cigarettes/day. Nicotine concentration of cigarettes was systematically varied. Major dependent variables included heart rate (HR) and estimates of blood carboxyhemoglobin (COHb) based on expired respiratory air carbon monoxide. Results show rapid smoking produced significantly greater rise in HR than normal smoking. No carbon monoxide differences were found across the smoking conditions. Individual data indicated that no S exceeded estimated danger levels of COHb or HR increases. Although replication and extension of these findings are necessary, results indicate that rapid smoking is not unduly hazardous to nonsymptomatic young adults. A suggested screening procedure for rapid smoking is presented. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integrins in morphogenesis and signaling

Integrins are a family of heterodimeric transmembrane receptors that provide a physical and biochemical bridge between components of the extracellular matrix and the intracellular physiological environment. Binding of integrins to their ligands results in the formation of cytoplasmic multi-protein assemblies composed of both cytoskeletal and signaling molecules. The composition and activity of these assemblies is regulated by the nature of integrin-ligand interactions, as well as by intracellular regulators that include tyrosine kinases and phosphatases, PKC, and small GTPases. Integrin-mediated cellular physiological responses include the activation of signal transduction, cytoskeletal rearrangements, and co-regulation of growth factor activities. These responses, combined with integrin-mediated cell adhesion, play a major role in tissue morphogenesis and developmental processes.     

Does autopsy of antenatally diagnosed malformed foetuses aid genetic counselling?

BACKGROUND: Many pregnancies are terminated because of ultrasonographic diagnosis of malformation in the foetus. A detailed foetal autopsy is needed to arrive at a definite diagnosis on the basis of which genetic counselling can be provided. METHODS: Sixty-one foetuses, terminated because of antenatal diagnosis of congenital malformations by ultrasound, were autopsied. The ultrasound diagnosis was compared with the diagnosis reached after autopsy. RESULTS: In 31 cases (51%) the autopsy provided additional findings. In 21 cases (34.4%), the autopsy changed the primary diagnosis. The revised diagnosis led to a change in the risk of recurrence in 18 cases (29.5%). CONCLUSION: Genetic counselling depending solely on ultrasonographic foetal diagnosis may be erroneous. For appropriate genetic counselling, a detailed foetal examination should be carried out after termination in cases with ultrasonographically detected congenital malformations.     

Epithelial/mesenchymal interactions and branching morphogenesis of the lung

The establishment of the permissible levels for the use of additives in foods must be based on the Acceptable Daily Intake (ADI). A method that may be applied for this purpose is the Danish Budget Method which estimates the maximum amount of the additive that may be added to the food based on the functional properties of the additive, and on the categories of the food in which the additive will be used. Based on the latest information B?r and Würtzen propose some modifications to the original Budget Method, one of which is the addition of a correction factor which takes into account the competition between different food additives with the same functional properties. In the present paper, both the Budget Method and the B?r and Würtzen-modified method were applied to evaluate whether the maximum levels of food colours use exceeded their ADI or not. Applying the original Budget Method, the results showed that the colours Sunset Yellow, Amaranth, Erythrosine, Ponceau 4R and Cochineal possibly exceeded the ADI; while applying the modified method only the colours Erythrosine and Cochineal would exceed the ADI. Brazilian regulatory authorities should be advised to establish maximum limits of use for the following categories of colours: Caramel, Inorganic, Natural and Artificial Colours Identical to the Natural Ones, where ADIs have been evaluated by JECFA.     

Ultrastructure and morphogenesis of human immunodeficiency virus

The ultrastructure and morphogenesis of human immunodeficiency virus (HIV) were elucidated by observation with several techniques including immunoelectron microscopy and cryo-microscopy. The virus particle consists of an envelope, a core and matrix. The virus particles were observed extracellularly as having one of three profiles: (1) a centric or an eccentric electron-dense core, (2) rod-shaped electron-dense core, and (3) doughnut-shaped. HIV-1 particles in the hydrated state were observed by high resolution electron cryo-microscopy to be globular, and the lipid membrane was clearly resolved as a bilayer. Many projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially head parts, were found to vary in each projection. By isolation with Nonidet P40 and glutaraldehyde, HIV-1 cores were confirmed to consist of p24 protein by immunogold labeling. When the virus enters the cell, two entry modes were found: membrane fusion and endocytosis. No structures resembling virus particles could be seen in the cytoplasm after viral entry. In HIV-1-infected cells, positive reactions by immuno-labeling suggest that HIV-1 Gag may be produced in membrane-bound structures and transported to the cell surface by cytoskeletons. Then a crescent electron-dense layer was first formed underneath the cell membrane. Finally, the virus particle was released from the cell surface. Several cell clones producing defective particles were isolated from MT-4/HIV-1 cells. Among them, doughnut-shaped or teardrop-shaped particles were seen to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins faced each other against the inner electron dense ring, suggesting that the inner ring consists of a precursor Gag protein.