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Variability in integration of mechanisms associated with high tolerance to progressive reductions in central blood volume: the compensatory reserve.

ABSTRACT: High tolerance to progressive reductions in central blood volume has been associated with higher heart rate (HR), peripheral vascular resistance (PVR), sympathetic nerve activity (SNA), and vagally mediated cardiac baroreflex sensitivity (BRS). Using a database of 116 subjects classified as high tolerance to presyncopal-limited lower body negative pressure (LBNP), we tested the hypothesis that subjects with greater cardiac baroreflex withdrawal (i.e., BRS > 1.0) would demonstrate greater LBNP tolerance associated with higher HR, PVR, and SNA. Subjects underwent LBNP to presyncope. Mean and diastolic arterial pressure (MAP; DAP) was measured by finger photoplethysmography and BRS (down sequence) was autocalculated (WinCPRS) as ∆R-R Interval/∆DAP. DownBRS : ms/mmHg) was used to dichotomize subjects into two groups (Group 1 = DownBRS > 1.0, N = 49, and Group 2 = DownBRS < 1.0, N = 67) at the time of presyncope. Muscle SNA was measured directly from the peroneal nerve via microneurography (N = 19) in subjects from Groups 1 (n = 9) and 2 (n = 10). Group 1 (DownBRS > 1.0) had lower HR (107 ± 19 vs. 131 ± 20 bpm), higher stroke volume (45 ± 15 vs. 36 ± 15 mL), less SNA (45 ± 13 vs. 53 ± 7 bursts/min), and less increase in PVR (4.1 ± 1.3 vs. 4.5 ± 2.6) compared to Group 2 (DownBRS < 1.0). Both groups had similar tolerance times (1849 ± 260 vs. 1839 ± 253 sec), MAP (78 ± 11 vs. 79 ± 12 mmHg), compensatory reserve index (CRI) (0.10 ± 0.03 vs. 0.09 ± 0.01), and cardiac output (4.5 ± 1.2 vs. 4.7 ± 1.1 L/min) at presyncope. Contrary to our hypothesis, higher HR, PVR, SNA, and BRS were not associated with greater tolerance to reduced central blood volume. These data are the first to demonstrate the variability and uniqueness of individual human physiological strategies designed to compensate for progressive reductions in central blood volume. The sum total of these integrated strategies is accurately reflected by the measurement of the compensatory reserve.

SUBMITTER: Carter R

PROVIDER: S-EPMC4759043 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Project description:There is burgeoning evidence that, among HIV+ adults, exposure to high levels of early life stress (ELS) is associated with increased cognitive impairment as well as brain volume abnormalities and elevated neuropsychiatric symptoms. Currently, we have a limited understanding of the degree to which cognitive difficulties observed in HIV+ High-ELS samples reflect underlying neural abnormalities rather than increases in neuropsychiatric symptoms. Here, we utilized a behavioral marker of cognitive function, reaction time intra-individual variability (RT-IIV), which is sensitive to both brain volume reductions and neuropsychiatric symptoms, to elucidate the unique contributions of brain volume abnormalities and neuropsychiatric symptoms to cognitive difficulties in HIV+ High-ELS adults. We assessed the relation of RT-IIV to neuropsychiatric symptom levels and total gray and white matter volumes in 44 HIV+ adults (26 with high ELS). RT-IIV was examined during a working memory task. Self-report measures assessed current neuropsychiatric symptoms (depression, stress, post-traumatic stress disorder). Magnetic resonance imaging was used to quantify total gray and white matter volumes. Compared to Low-ELS participants, High-ELS participants exhibited elevated RT-IIV, elevated neuropsychiatric symptoms, and reduced gray and white matter volumes. Across the entire sample, RT-IIV was significantly associated with gray and white matter volumes, whereas significant associations with neuropsychiatric symptoms were not observed. In the High-ELS group, despite the presence of elevated neuropsychiatric symptom levels, brain volume reductions explained more than 13% of the variance in RT-IIV, whereas neuropsychiatric symptoms explained less than 1%. Collectively, these data provide evidence that, in HIV+ High-ELS adults, ELS-related cognitive difficulties (as indexed by RT-IIV) exhibit strong associations with global brain volumes, whereas ELS-related elevations in neuropsychiatric symptoms appear to contribute minimally to these cognitive difficulties. Such findings support a growing body of evidence indicating that high ELS exposure is a significant risk factor for neurocognitive dysfunction in HIV+ adults. Further, these data highlight the need to better understand how ELS-related pathophysiological mechanisms contribute to volumetric and other neural abnormalities in HIV+ individuals.

Project description:BackgroundEnlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.MethodsWe obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse.ResultsWe found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.LimitationsThis study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.ConclusionReductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.

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Variability in integration of mechanisms associated with high tolerance to progressive reductions in central blood volume: the compensatory reserve.

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