Lipoprotein oxidation in chronic renal failure

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Characteristics of Intracellular Ca2+ Waves in Equine Cardiac Myocytes

No abstract available

Comparison of Ca2+ release and uptake characteristics of the sarcoplasmic reticulum in isolated horse and rabbit cardiomyocytes

Both the cardiac action potential duration (APD) (0.6–1 s) and resting heart rate (30–40 beats/min) in the horse are significantly different from humans and smaller mammals, including the rabbit. This would be anticipated to have consequences for excitation-contraction (EC) coupling and require adaptation of the individual processes involved. The sarcoplasmic reticulum (SR) is one of the main components involved in EC coupling. This study examines and compares the activity of this organelle in the horse with that of the rabbit. In particular, the study focuses on SR Ca2+ release via the Ca2+ release channel/ryanodine receptor (RyR2) and Ca2+ uptake via the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump. Isolated cardiomyocytes from both horse and rabbit hearts were permeabilized, bathed in a mock intracellular solution, and exposed to a specified [Ca2+]. Rabbit cardiomyocytes exposed to 260 nM [Ca2+] produced spontaneous Ca2+ release and propagated Ca2+ waves. Horse cells failed to produce Ca2+ waves; instead, only local release in the form of Ca2+ sparks was evident. However, at 550 nM [Ca2+], Ca2+ waves were produced in both species. Ca2+ waves were four times less frequent yet ~1.5 times greater in amplitude in the horse compared with the rabbit. Ca2+ wave velocity was comparable between the species. The reason for this disparity in Ca2+ wave characteristics is unknown. Separate measurements of oxalate-supported Ca2+ uptake into the SR suggest that both horse and rabbit cardiomyocytes have comparable levels SERCA activity. The possible reasons for the observed differences in SR Ca2+ release between the horse and rabbit are discussed

Intracellular Calcium Waves in Heart Muscle: Source of Triggered Arrhythmias

No abstract available

Characteristics of Intracellular Ca2+ Waves in Equine Cardiac Myocytes

No abstract available

Measurement of the dissociation constant of Fluo-3 for Ca2+ in isolated rabbit cardiomyocytes using Ca2+ wave characteristics

The Ca2+ dissociation constant (Kd) of Fluo-3 was determined using confocal fluorescence microscopy in two different situations: (i) within the cytosol of a permeabilised cardiomyocyte; and (ii) in an intact cardiomyocyte after incubation with the acetoxymethyl ester form of Fluo-3 (AM). Measurements were made on isolated rabbit ventricular cardiomyocytes after permeabilisation by a brief treatment with β-escin (0.1 mg/ml) and equilibration with 10 μM Fluo-3. The Kd of Fluo-3 within the cytosol was not significantly different from that in free solution (558±15 nM, n=6). Over a range of cytoplasmic [Ca2+], the minimum [Ca2+] values between Ca2+ waves was relatively constant despite changes in wave frequency. After loading intact cardiomyocytes with Fluo-3 by incubation with the −AM, spontaneous Ca2+ waves were produced by incubation with strophanthidin (10 μM). By assuming a common minimum [Ca2+] in permeabilised and intact cells, the intracellular Kd of Fluo-3 in intact myocytes was estimated to be 898±64 nM (n=6). Application of this Kd to fluorescence records shows that Ca2+ waves in intact cells have similar amplitudes to those in permeabilised cells. Stimulation of cardiac myocytes at 0.5 Hz in the absence of strophanthidin (room temperature) resulted in a Ca2+ transient with a maximum and minimum [Ca2+] of 1190±200 and 158±30 nM (n=11), respectively

Isolated rabbit working heart function during progressive inhibition of myocardial SERCA activity

<p>Rationale: The extent to which sarcoplasmic reticulum Ca2+ATPase (SERCA) activity alone determines left ventricular (LV) pump function is unknown.</p> <p>Objective: To correlate SERCA activity with hemodynamic function of rabbit LV during thapsigargin perfusion.</p> <p>Methods and Results: Isolated rabbit hearts were perfused in working heart configuration, and LV pump function was assessed using a pressure-volume catheter. Rapid and complete (>95%) inhibition of SERCA was associated with a moderate decrease in cardiac function (to 70%–85% of control). Further decrease in cardiac function to 50%–75% of control occurred over the next ≈30 minutes despite no detectable further inhibition of SERCA activity. Analysis of the 20 seconds prior to pump failure revealed a rapid decrease in end diastolic volume. Intermediate levels of SERCA function (≈50% of control) had only minor hemodynamic effects. Parallel experiments in field-stimulated isolated ventricular cardiomyocytes monitored intracellular Ca2+ and cell shortening. On perfusion with thapsigargin, Ca2+ transient amplitude and cell shortening fell to ≈70% of control followed by increased diastolic Ca2+ concentration and diastolic cell shortening to achieve a new steady state.</p> <p>Conclusions: The relationship between SERCA activity and LV function in the rabbit is highly nonlinear. In the short term, only moderate effects on LV pump function were observed despite almost complete (>95%) reduction in SERCA activity. The terminal decline of function was associated with sudden sustained increase in diastolic tone comparable to the sustained contraction observed in isolated cardiomyocytes. Secondary increases of intracellular Ca2+ and Na+ following complete SERCA inhibition eventually limit contractile function and precipitate LV pump failure.</p&gt

Relationship Between Extracellular [Ca2+] and Intracellular Ca2+ Wave Characteristics in β-escin-permeabilised Single Cardiac Myocytes (Rabbit)

No abstract available

The Quandaries of Shelter Reform: An Appraisal of Efforts to Manage Homelessness

In this article, I describe efforts to manage the capacity of homeless shelter programs in Philadelphia and assess the impact of those efforts on providers and consumers of homeless services. Most reforms have focused on reducing the capacity of the shelter system by reducing the average length of stay of persons in shelter and by providing housing relocation assistance. However, these reforms have been compromised by an inability to contol the demand for shelter, particularly the rate of new admissions , and by the extent of need for housing assistance among homeless and near-homeless people in Philadelphia. Alternative methods of financing shelters are described, as are attempts to create a system of specialty shelter providers. The contradictions of shelter reform and the need for a more comprehensive homelessness prevention strategy are discussed