Relationship between Myocardial Extracellular Space Expansion Estimated with Post-Contrast T1 Mapping MRI and Left Ventricular Remodeling and Neurohormonal Activation in Patients with Dilated Cardiomyopathy

OBJECTIVE: Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: Fifty-nine patients with DCM (mean age, 55 +/- 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. RESULTS: The mean LV ejection fraction was 24 +/- 9% and the post-T1 value was 254.5 +/- 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (beta = -0.351, p = 0.016) and the LV mass/volume ratio (beta = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (beta = -0.339, p = 0.017). CONCLUSION: Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.

Extra and intracelular activities of carbonic anhydrase of the marine microalga Tetraselmis gracilis (Chlorophyta)

As atividades da Anidrase Carbônica (AC) extra e intracelular foram estudadas na microalga marinha Tetraselmis gracilis (Kylin) Butcher (Chlorophyta, Prasinophyceae) crescendo em cultivos laboratoriais. Durante dez dias de cultivo, determinacões diárias do pH, número de células, atividades enzimáticas, carbono inorgânico total dissolvido (CID) e suas principais espécies CO2 e HCO3- foram feitas. A atividade enzimática aumentou na medida em que a populacão celular em crescimento retirava carbono inorgânico do meio de cultivo. A concentracão de dióxido de carbono decresceu rapidamente, especialmente no terceiro dia do cultivo, quando um significante aumento na atividade enzimática intracelular foi observado. A concentracão de bicarbonato teve seu maior decréscimo no meio de cultivo no quarto dia, quando a atividade da enzima extracelular teve seu maior aumento, sugerindo seu uso pela alga através da atividade da AC. Após o quarto dia de cultivo, metade das culturas passou a ser aerada com ar atmosférico sem CO2, o que causou um aumento na atividade total e externa da enzima, fazendo com que esses cultivos entrassem na fase estacionária do crescimento antes que aqueles aerados com ar atmosférico normal. O pH do meio foi medido diariamente, aumentando desde o primeiro até o quarto dia e permanecendo quase constante até o fim do cultivo. Material algal transferido para o escuro perdeu toda a atividade enzimática.

Cell swelling and ion redistribution assessed with intrinsic optical signals

Cell volume changes are associated with alterations of intrinsic optical signals (IOS). In submerged brain slices in vitro, afferent stimulation induces an increase in light transmission. As assessed by measurement of the largely membrane impermeant ion tetramethylammonium (TMA) in the extracellular space, these IOS correlate with the extent and time course of the change of the extracellular space size. They have a high signal to noise ratio and allow measurements of IOS changes in the order of a few percent. Under conditions of reduced net KCl uptake (low Cl solution) a directed spatial buffer mechanism (K syphoning) can be demonstrated in the neocortex with widening of the extracellular space in superficial layers associated with a reduced light transmission and an increase of extracellular K concentration. The nature of the IOS under pathophysiological conditions is less clear. Spreading depressions first cause an increase of light transmission, then a decrease. Such a decrease has also been observed following application of NMDA where it was associated with structural damage. Pharmacological analyses suggest that under physiological conditions changes of extracellular space size are mainly caused by astrocytic volume changes while with strong stimuli and under pathophysiological conditions also neuronal swelling occurs. With reflected light usually signals opposite to those observed with transmitted light are seen. Recording of IOS from interface slices gives very complex signals since under these conditions an increase of light transmission has been reported to be superimposed by a decrease of the signal due to mechanical lensing effects of the slice surface. Depending on the method of measurement and the exact conditions, several mechanisms may contribute to IOS. Under well defined conditions IOS are a useful supplementary tool to monitor changes of extracellular volume both in space and time

Regulation of the renal proximal tubule second sodium pump by angiotensins

For several years it was believed that angiotensin II (Ang II) alone mediated the effects of the renin-angiotensin system. However, it has been observed that other peptides of this system, such as angiotensin-(1-7) (Ang-(1-7)), present biological activity. The effect of Ang II and Ang-(1-7) on renal sodium excretion has been associated, at least in part, with modulation of proximal tubule sodium reabsorption. In the present review, we discuss the evidence for the involvement of Na+-ATPase, called the second sodium pump, as a target for the actions of these compounds in the regulation of proximal tubule sodium reabsorption

Biochemistry below 0§C: nature's frozen vertebrates

Although alien to man, the ability to endure the freezing of extracellular body fluids during the winter has developed in several species of terrestrially hibernating frogs and turtles as well as in many species of insects and other invertebrates. Wood frogs, for example, can endure freezing for at least 2 weeks with no breathing, no heart beat or blood circulation, and with up to 65 per cent of their total body water as ice. Our studies are providing a comprehensive view of the requirements for natural freezing survival and of the physical and metabolic protection that must be offered for effective cryopreservation of vertebrate organs. Molecular mechanisms of natural freeze tolerance in lower vertebrates include: 1) control over ice crystal growth in plasma by ice nucleating proteins, 2) the accumulation of low molecular weight cryoprotectants to minimize intracellular dehydration and stabilize macromolecular components, and 3) good ischemia tolerance by all organs that may include metabolic arrest mechanisms to reduce organ energy requirements while frozen. Cryomicroscopy of tissue slices and magnetic resonance imaging (MRI) of whole animals is revealing the natural mode of ice propagation through an organism. MRI has also revealed that thawing is non-uniform; core organs (with high cryoprotectant levels) melt first, facilitating the early resumption of heart beat and blood circulation. Studies of the production and actions of the natural cryoprotectant, glucose, in frogs have shown its importance in maintaining a critical minimum cell volume in frozen organs and new work on the metabolic effects of whole body dehydration in 3 species of frogs has indicated that adaptations supporting freeze tolerance grew out of mechanisms that deal with desiccation resistance in amphibians. Studies of the regulation of cryoprotectant glucose synthesis by wood frog liver have shown the role of protein kinases and of (alpha and beta adrenergic receptors in regulating the glycemic response, and of changes in membrane glucose transporter proteins to facilitate cryoprotectant distribution.

Frequency-dependent excitability enhancement in isolated ventricular myocardial cells

The understanding of the mechanisms underling the frquency-dependent slow response ecitability enhancement has been hndered by the problem inhyerent in multicellular preparations. These include ion acdcumulation/depletion in intercellular space and difficulties in the spatial control of transmembrane voltage. In the present communication we show that isolated ventricular cells exposed to a depolarizing (high potassium-barium containing) solution present electrophysiological properties similar to those of mulcellular preparations: stable resting potential of -45.2 ñ 0.7 mV (mean ñ SEM, N = 57) in 75% of the cells and spontaneous activity in the remaining 25% (maximum diatolic potential of -41.9 ñ 1.2 mV, N=19)ñ high input resistance and slow response, under current clamp conditions. Under whole cell voltage clamp conditions with -45 mV holding potential, transient outward and delayed potassium currents as well as typical L type calcium channel are present. These cells also present thye frequency-dependent excitability enhancement of the slow response, with the threshold stimulus at 1 Hz corresponding to about 50% of that obtained at 0.1 Hz. Thus, isolated ventricular cells constitute a suitable model for the study of frequency-dependent exitability enhancement of the slow response

Post-rest contractions of amphibian cardiac muscle

Post-rest potentiated contractions have been reported to be more dependent on Ca2+ stored in intracellular sites than on transmembrana Ca2+ influx. The phenomenon was examined using toad ventricular strips contracting isometrically and superfused with Ringer solution. Toad ventricular strips did not present post-rest potentiation, a fact that may be explained be the reduced volume of the sarcoplasmic reticulum in the amphibian myocardium. Potentiated post-res contractins were obtained after calcium influx blockade with 10 µM verapamil or 2mM Mn2+ and the slow reduction of extracellular Ca2+ concentration obtained by slowly exchanging the bath fluid was accompanied by a progressive decrease of both steady-state and post-rest contractions. These data suggestion of the dependende of post-rest potentiation on activator calcium liberated from intracellular stores

Aspectos ultraestructurales de la penetracion de lantano en vesicula biliar de cobayo en funcion del flujo de absorción de agua / Ultrastructural aspects of the lanthanum penetration in guinea gallbladder in function of the absorption flow water

Hay controversias sobre si el agua atraviesa la vía paracelular en epitelios de baja resistencia (por ejemplo, vesícula biliar). El objetivo de este trabajo es por tanto, estudiar una posible correlación entre el flujo de absorción de volumen (Jv) y la penetración del ión La3+ usando fluidos de diferentes osmolalidades, lo cual permite variar Jv. Vesículas biliares de cobayo se perfundieron in vitro a pH y temperatura fisiológicos con fluidos oxigenados a dos osmolalidades: 300 mOsm/Kg (isosmótico) y 100 mOsm/Kg (hiposmótico) que contenían dos concentraciones de La3+1 y 10mM para cada osmolalidad y se prepararon para estudios de microscopía electrónica de transmisión. Después se procedió a evaluar el grado de pentración del La3+ cuantificando el número de uniones penetradas por el marcador y la longitud de su recorrido dentro del espacio intercelular (en *m), el trayecto se midió comenzando en el borde apical y en dirección latero-basal. Jv se duplica en la condición hiposmótica y en las micrografías se aprecia mayor grado de penetración del La3+ por las vías paracelulares en las vesículas con mayor flujo de volumen. Hay ausencia de precipitados de La3+ en el citoplasma, el cual está satisfactoriamente preservado, aun a 100 mOsm/Kg, lo que muestra que la integridad de la membrana plasmática se mantiene. Esto indica que la penetración del La3+ varía con Jv. Los resultados obtenidos constituyen una evidencia para afirmar que la penetración de La3+ varía con Jv y que una fracción de este último se cumple a través de las vías paracelulares

Effects of acute volemic changes on jejunal compliance in dogs

1. Jejunal compliance (deltaV/deltaP) was calculated from the intraluminal pressures measured in anesthetized dogs in an in situ upper jejunal pouch (40-50-ml capcity) with intraluminal volumes of 10, 20, 30, 40 and 50 ml of fisotonic saline. 2. Measurements were made in the same animal during and after acute sequential alterations of the extracellular fluid (ECF) volume obtained by: a) acute intravenous (iv) infusion of isotonic saline, b) acute hemorrhage, and c) reinfusion of isotonic saline. 3. Expansion of the ECF volume caused a significant, reversible downward shift of the compliance curve, i.e., the jejunal pouch became less receptive to liquid distension. After saline infusion was discontinued, complicance gradually returned to control levels. 4. Acute loss a substantial volume of blood after ECF expansion gradually shifted the complicance curve upwards to levels significantly diferent from control, indicating that retraction of the ECF volume made the jejunal pouch more receptive to liquid distension. 5. Reinfusion of bled animals with saline rather than autologous blood also induced a significant decrease in jejunal complicance to below control levels. 6. The jejunal pouch as a suitable preparation for monitoring in vivo modifications of compliance induced by acute changes in ECF volume, especially when it was nearly "half-full" (i.e., filled with 20 ml), suggesting a critical relationship between the volume capacity of the pouch and its fluid content. 7. These results suggest that the modulation of the jejunal portion os small intestine compliance is involved in the processes that balance the ECF volume during acute life-threatening situations such as accidental hyperhydration or hemorrhage

Acute changes in extracellular fluid volume modify the antroduodenal flow of saline in dogs: a possible physiological role

The antroduodenal (AD) flow of saline was measured in anesthetized dogs following two different protocols of acute changes in extracellular fluid (ECF) volume, ECF expansion by in infusion of saline before or after hemorrhage decreased the AD flow; conversely, hemorrhage before or after expansion increased flow. These alternating modifications in the AD flow are independent of the sequence of volemic changes and may constitue part of the homeostatic responses of the gut to confront life-thratening situations such as accidental hyperhydration or hemorrhage

Organ fluid compartments in rats exposed to high altitude.

Rats were exposed to acute hypobaric hypoxia corresponding to an altitude of 6,100 m for 5 hours and 24 hours and were studied for organ fluid changes. Total water and extracellular water content of various organs, i.e. lung, liver, spleen, heart, kidney, muscle, brain testis and subcutaneous tissue were determined by the difference of dry and wet weights and using radiobromide-82 respectively. Lung and liver were found to be significantly hydrated with lower water contents in subcutaneous tissue, spleen and muscle on prolonged exposure. The data indicated a shift of fluids from extracellular to intracellular compartment.