Serial changes in cardiovascular and renal function of rabbits ingesting a high-fat, high-calorie diet

To explore the mechanisms of obesity-induced hypertension we analyzed the sequential changes in cardiovascular and renal function in adult rabbits switched to high-fat diet (HFD) for 8 weeks. Animals were housed in metabolic cages for continuous 24-h recording of arterial pressure by telemetry and daily urine collection. High-fat diet induced a progressive increase in body weight (+47%) and a rapid rise in mean arterial pressure, heart rate, and glomerular filtration rate that stabilized, respectively, at 14%, 31% and 68% greater than control values. Time-course analysis of changes in blood pressure may reveal two components of obesity-induced hypertension, an early phase related to HFD itself and a later phase related to weight gain. Am J Hypertens 1999;12:826-829 © 1999 American Journal of Hypertension, Lt

Regulation of blood pressure during long-term ouabain infusion in Long-Evans rats

We tested whether ouabain, an inhibitor of the sodium pump, can lead to chronic hypertension in Long-Evans rats using sensitive 24-h measurements of blood pressure. After a control week of vehicle isotonic saline infusion (14.4 mL/day), ouabain was infused intravenously at 30 μg/kg/day in intact (2K) and uninephrectomized (1K) Long-Evans rats for a total of 4 weeks. Although plasma ouabain concentration rose to 0.97 ± 0.15 nmol/L with ouabain infusion, mean arterial pressure did not change in either 2K (Δ = −0.6 ± 1.3 mm Hg) or 1K (Δ = −1.2 ± 0.7 mm Hg) rats. These data suggest that Long-Evans rats are insensitive to the hypertensive effects of ouabain. Am J Hypertens 1999;12:423-426 © 1999 American Journal of Hypertension, Lt

Role of the sympathetic nervous system during the development of obesity-induced hypertension in rabbits

We have previously reported that weight gain induced by high-fat diet (HFD) leads to an increase in mean arterial pressure (MAP, +14%) and heart rate (HR, +31%) in the adult rabbit. In the present study, we tested the hypothesis that an increased activity of the sympathetic nervous system may contribute to the development of obesity-induced hypertension. A combination of α- and β-adrenergic blockers (terazosin + propranolol) was chronically administered to rabbits housed in metabolic cages for continuous monitoring of arterial pressure by telemetry, 24 h a day. After 2 weeks of adrenergic blockade under control diet, animals were switched to HFD for the next 6 weeks. HFD induced a progressive increase in body weight, but no increase in mean arterial pressure (+0.2 ± 2.5%) and a slight increase in heart rate (+14 ± 3%). Time-control animals fed normal diet showed no changes in MAP or HR with long-term α- and β-adrenergic blockade. Our results indicate that the activation of the sympathetic nervous system may play an important role in the pathogenesis of obesity-induced hypertensio

Impact of cortical and subcortical atrophy in the diagnosis and prognosis of bvFTD: A multicenter longitudinal study

AbstractBackgroundThe behavioral variant of frontotemporal dementia (bvFTD) presents with variable patterns of cortical and subcortical atrophy on Magnetic Resonance Imaging (MRI). We aimed to assess the clinical utility of two reproducible measurements of cerebral atrophy (Harper's visual atrophy scale [HVAS], and the Magnetic Resonance Parkinsonism Index [MRPI]) in a large multicenter sample of bvFTD with longitudinal follow‐up.MethodsWe included 466 participants from three centers: 241 bvFTD (according to the International bvFTD Criteria Consortium), and 225 healthy controls (HC). Clinical deterioration was assessed with Mini‐Mental State Examination (MMSE) and the Clinical Deterioration Scale Sum‐of‐boxes (CDR‐sb). bvFTD participants were considered to have an increased certainty of underlying Frontotemporal Lobar Degeneration (+FTLD) when: (i) FTLD was confirmed at autopsy (n=72); (ii) a secondary FTLD‐related phenotype was identified during follow‐up (n=47) or (iii) a FTLD‐related mutation was found (n=49). Six raters blinded to clinical data were first asked to dichotomize participants according to the presence of "a clear pattern of atrophy suggestive of probable bvFTD", and then applied the HVAS (ICC(2,k)=.86 to .96). The MRPI was calculated with a fully automated algorithm.ResultsMean age of bvFTD participants was 63.3 ± 10, 68% were male (MMSE=23 ± 7 and CDR‐sb=6.7 ± 3.5). Blinded raters had 52% sensitivity and 97% specificity for the identification of bvFTD participants (AUC=.74, p=.001). All HVAS measures with the exception of posterior atrophy discriminated between bvFTD and HC (AUC=.77 to .83, p<.001). The composite bvFTD score (average score of orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe and frontal insula regions) showed the best diagnostic accuracy for the differentiation of bvFTD from HC (AUC=.91, p<.001 in +FTLD). This composite score also differentiated between bvFTD participants that were not considered to have a clear pattern of atrophy suggestive of probable bvFTD (blinded raters) and HC (p<.001). We hypothesized that HVAS and MRPI scores may be independent predictors of clinical deterioration and survival in bvFTD (definitive results pending).ConclusionThe combination of HVAS and MRPI may provide valuable diagnostic and prognostic information in the behavioral syndromes verifying bvFTD criteria. These measures represent reliable, reproducible and affordable imaging biomarkers

Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration

Can widely available measures of atrophy on magnetic resonance imaging increase diagnostic certainty of underlying frontotemporal lobar degeneration (FTLD) and estimate clinical deterioration in the behavioral variant of frontotemporal dementia (bvFTD)? This diagnostic/prognostic study investigated the clinical utility of 5 validated visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index. When combined, VAS showed excellent diagnostic performance for differentiating between bvFTD with high and low confidence of FTLD and for the estimation of longitudinal clinical deterioration, whereas the Magnetic Resonance Parkinsonism Index was increased in bvFTD with underlying 4-repeat tauopathies. These findings suggest that, in bvFTD, VAS can be used to increase diagnostic certainty of underlying FTLD and estimate longitudinal clinical deterioration. This diagnostic/prognostic study assesses the utility of 6 visual atrophy scales and the Magnetic Resonance Parkinsonism Index in patients with behavioral variant frontotemporal dementia to distinguish those with high vs low confidence of frontotemporal lobar degeneration. The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration