Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic myocardial infarction even when the absolute atrioventricular plane displacement is decreased.

BACKGROUND: The majority (60%) of left ventricular (LV) stroke volume (SV) is generated by longitudinal shortening causing apical atrioventricular plane displacement (AVPD) in systole. The remaining SV is caused by radial inward motion of the epicardium both in the septal and the lateral wall. We aimed to determine if these longitudinal, septal and lateral contributions to LVSV are changed in patients with chronic myocardial infarction (MI). METHODS: Patients with a chronic (>3 months) ST-elevation MI in the left anterior descending (LAD, n = 20) or right coronary artery (RCA, n = 16) and healthy controls (n = 20) were examined with cardiovascular magnetic resonance (CMR). AVPD was quantified in long axis cine CMR images and LV volumes and dimensions in short axis cine images. RESULTS: AVPD was decreased both in patients with LAD-MI (11 ± 1 mm, p < 0.001) and RCA-MI (13 ± 1 mm, p < 0.05) compared to controls (15 ± 0 mm). However, the longitudinal contribution to SV was unchanged for both LAD-MI (58 ± 3%, p = 0.08) and RCA-MI (59 ± 3%, p = 0.09) compared to controls (64 ± 2%). The preserved longitudinal contribution despite decreased absolute AVPD was a results of increased epicardial dimensions (p < 0.01 for LAD-MI and p = 0.06 for RCA-MI). In LAD-MI the septal contribution to LVSV was decreased (5 ± 1%) compared to both controls (10 ± 1%, p < 0.01) and patients with RCA-MIs (10 ± 1%, p < 0.01). The lateral contribution was increased in LAD-MI patients (44 ± 3%) compared to both RCA-MI (35 ± 2%, p < 0.05) and controls (29 ± 2%, p < 0.001). CONCLUSION: Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic MI even when the absolute AVPD is decreased.

Acute reactive oxygen species (ROS)-dependent effects of IL-1ß, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo.

This study was performed to investigate the immediate actions of the proinflammatory cytokines IL-1ß, TNF-α, and IL-6 on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously with either IL-1ß (0.4 and 2 µg·kg(-1)·h(-1)), TNF-α (0.4 and 2 µg·kg(-1)·h(-1)), or IL-6 (4 and 8 µg·kg(-1)·h(-1)), together with polydisperse FITC-Ficoll-70/400 and inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ). The glomerular filtration rate (GFR) was also assessed (51Cr-EDTA). In separate experiments, the superoxide scavenger tempol (30 mg·kg(-1)·h(-1)) was given before and during cytokine infusions. IL-1ß and TNF-α caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll50-80Å), peaking at 5-30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1ß, TNF-α, and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger tempol, suggesting an important role of ROS in acute cytokine-induced permeability changes in the GFB.

Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo.

The proteinuric actions of protamine sulfate (PS) have classically been, at least partly, attributed to alterations of the negatively charged glomerular endothelial glycocalyx. To investigate whether the charge-selective properties of the glomerular filtration barrier (GFB) would be altered by PS, we assessed the glomerular sieving of conventional, uncharged, polydispersed Ficoll (n-Ficoll) compared with charge modified, conformationally intact, anionic (carboxymethylated) Ficoll (a-Ficoll) before and after systemic infusions of PS in rats. For comparison, we also investigated the impact of hyaluronidase (hyase), which partially degrades the glycocalyx, on GFB permeability. In anaesthetized Wistar rats, blood access was achieved, and the left ureter was cannulated for urine collection. Rats were infused with either n-Ficoll or a-Ficoll before and during systemic infusions with either PS or hyase. Plasma and urine samples were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients (θ) for Ficoll (radius 10-80 Å). The GFB showed a significant glomerular charge selectivity for Ficoll molecules of radius 20-35 Å. PS and hyase infusions reversibly increased θ for large Ficoll molecules (Ficoll molecules of radius 50-80 Å). Thus, for PS, θ for a-Ficoll molecules of radius 70 Å increased from 2.47 × 10(-5) ± 1.1(-5) to 7.25 × 10(-5) ± 1.1(-5) (P < 0.05) at 15 min. For hyase, changes in a-Ficoll molecules of radius 50-80 Å were, however, not statistically significant. Neither PS nor hyase had any effect on θ for n-Ficoll molecules of radius 20-45 Å or a-Ficoll molecules of radius 20-45 Å. It is concluded that systemically administered PS and hyase in moderate doses dynamically decreased the size selectivity of the rat GFB without affecting its charge selective properties.

Non-contrast-enhanced magnetic resonance imaging can be used to assess renal cortical and medullary volumes-A validation study.

BACKGROUND: Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing. PURPOSE: To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents. MATERIALS AND METHODS: Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13-16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5-97.5 percentiles. RESULTS: Agreement between MRI and ex-vivo quantification were -7 mL (-10-0 mL) for total parenchyma, -4 mL (-9-3 mL) for cortex, and -2 mL (-7-2 mL) for medulla. Intraobserver variability for pig and human kidneys were <5% for total parenchyma, cortex, and medulla. Interobserver variability for both pig and human kidneys were ≤4% for total parenchyma and cortex, and 6% and 12% for medulla. Reference ranges indexed for body surface area and sex were 54-103 mL/m2 (boys) and 56-103 mL/m2 (girls) for total parenchyma, 39-62 mL/m2 and 36-68 mL/m2 for cortex, and 16-45 mL/m2 and 17-42 mL/m2 for medulla. CONCLUSION: The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.

Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats.

It is established that the glomerular filter sieves macromolecules based on their size, shape, and charge. Anionic proteins are thus retarded compared with their neutral or cationic counterparts. However, recent studies have indicated that charge effects are small, or even "anomalous," for polysaccharides. We therefore investigated the impact of charge on the glomerular permeability to polysaccharides by comparing sieving coefficients (theta; primary urine-to-plasma concentration ratio) for negatively charged, carboxymethylated (CM) FITC-Ficoll and FITC-dextran with their neutral counterparts. For these probes, theta were determined in anesthetized Wistar rats [269 +/- 2.7 g (+/-SE; n = 36)], whose ureters were cannulated for urine sampling. The glomerular filtration rate was assessed using FITC-inulin. Polysaccharides were constantly infused, and after equilibration, urine was collected and a midpoint plasma sample was taken. Size and concentration determinations of the FITC-labeled polysaccharides were achieved by size-exclusion HPLC (HPSEC). For CM-Ficoll, theta was significantly increased (32 times at 55 A) compared with that of uncharged Ficoll. A small increase in theta for CM-dextran compared with neutral dextran was also observed (1.8 times at 55 A). In conclusion, negatively charged Ficoll relative to neutral Ficoll was found to be markedly hyperpermeable across the glomerular filter. Furthermore, negatively charged Ficoll was observed to be larger on HPSEC compared with its neutral counterpart of the same molecular weight. It is proposed that the introduction of negative charges in the "dendrimeric," cross-linked Ficoll molecule may alter its configuration, so as to make it more extended, and conceivably, more flexible, thereby increasing its glomerular permeability.

Nature of glomerular capillary permeability changes following acute renal ischemia-reperfusion injury in rats.

This study was performed to evaluate the alterations of glomerular filtration barrier characteristics following acute renal ischemia-reperfusion (I/R). Ischemia was induced in anesthetized rats by unilateral renal artery occlusion for either 20 or 60 min, followed by reperfusion during 20 or 60 min, respectively, with the contralateral kidney serving as control. Sieving coefficients (theta) were obtained by analyzing Ficoll [mol.radius (a(e)) 13-85 A] in urine and plasma after 20 and 60 min I/R. Furthermore, theta for human serum albumin (HSA) was estimated using a tissue uptake technique after 20 and 60 min of I/R, while clearance of HSA compared with that for neutralized HSA (nHSA) was assessed after 20 min of I/R only. Glomerular filtration rate (GFR) was measured by [51Cr]EDTA and inulin. I/R reduced GFR and increased theta for Ficoll molecules of a(e) >55 A and theta for albumin. theta for Ficoll vs. a(e), analysed using a two-pore model, demonstrated that, despite increases in theta, the large-pore fractional ultrafiltration coefficient (alpha(L)) was unchanged after 20 min of I/R, owing to the decline in GFR, but increased after 60 min of I/R. However, the apparent alpha(L) for albumin increased already after 20 min of I/R (P < 0.005) and the nHSA/HSA clearance ratio was slightly reduced, possibly reflecting a diminished negative charge barrier. In conclusion, after 20 min of I/R, indications of a reduced charge selectivity were noted, while after 60 min of I/R, there was mainly a reduction in size selectivity, compatible with an increased formation of large pores.