Cerebrovascular Response during Acute Exercise in Kidney Transplant Recipients

Ward, Jaimie L.; Ramakrishnan, Madhuri; Jurgensen, Andrew; Billinger, Sandra A.; Gupta, Aditi

doi:10.2215/cjn.08410621

Cited by 4 publications

(6 citation statements)

References 6 publications

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“…We have previously shown that CVR is blunted in KT recipients. 14 Low CVR is associated with lower cognitive function. 33 Aging, stroke, and dementia are all associated with low CVR.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, lower CBF is associated with faster cognitive decline. 12 We have previously shown that CBF decreases after KT, 13 CVR to exercise is impaired in KT recipients, 14 and there is a high prevalence of cognitive impairment in KT recipients. 15 Furthermore, liver transplant recipients on CNI-sparing regimens have better cognitive function than patients who are on CNIs.…”

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confidence: 99%

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The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function

Mahaparn,

Lepping,

Montgomery

et al. 2023

Transplantation Direct

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Background. Calcineurin inhibitors are inherent vasoconstrictors. Cerebral vasoconstriction can reduce cerebral blood flow (CBF), and negatively impact cerebrovascular response (CVR) to exercise, and cognitive function. The once-daily extended-release (LCP) tacrolimus has fewer side effects than the immediate-release (IR) tacrolimus. The role of calcineurin inhibitors on CBF and the impact of specific formulations of tacrolimus on CBF, CVR, and cognitive function are unknown. In this pilot study, we evaluated whether changing from IR tacrolimus to LCP tacrolimus modulates CBF, CVR, or cognitive function in kidney transplant (KT) recipients. Methods. We randomized (2:1) 30 stable KT recipients on IR tacrolimus to intervention (switch to LCP tacrolimus) and control (continue IR tacrolimus) arms. We measured CBF, CVR, and cognitive function at baseline and at 12 wk. We used ANCOVA to evaluate changes in outcome variables, with baseline values and study arm as covariates. We used descriptive statistics with mean changes in outcome variables to compare the 2 groups. Results. Participants were 51 ± 13 y old. There was no difference in plasma tacrolimus levels at baseline and at 12 wk in the 2 arms. The changes in CBF, resting middle cerebral artery velocity, CVR, and cognitive function were more favorable in the intervention arm than in the control group. Conclusions. Changing IR tacrolimus to LCP tacrolimus may improve CBF, cerebrovascular dynamics, and cognitive function in KT recipients. Larger studies are needed to confirm these results.

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“…We have previously shown that CVR is blunted in KT recipients. 14 Low CVR is associated with lower cognitive function. 33 Aging, stroke, and dementia are all associated with low CVR.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function

Mahaparn,

Lepping,

Montgomery

et al. 2023

Transplantation Direct

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“…It is important to also consider the stimulus and the actual CVR outcome, as study in kidney transplant patient used exercise as the stimulus had different outcomes of change in velocity of middle cerebral artery and the kinetics of the change in velocity as the cerebrovascular response. 39 The differences in outcomes may lead to different inconsistent results if not interpreted carefully.…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular Function is Altered in Hemodialysis Patients

Richerson,

Meier,

Cohen

et al. 2023

Kidney360

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Introduction: Hemodialysis (HD) patients have declines in cerebral blood flow (CBF) and cerebral oxygenation during HD that may lead to ischemic brain injury. Cerebrovascular reactivity (CVR) may indicate which individuals are more susceptible to intradialytic hypoperfusion and ischemia. We hypothesized that HD patients would have decreased CVR and increased CBF relative to controls and deficits in CVR would be related to brain structural deficits. Methods: We measured cortical thickness and white matter hyperintensity (WMH) volume from T1 and T2 FLAIR images respectively, CVR from a breath hold BOLD CVR fMRI and arterial transit time (ATT) and CBF from ASL. Cerebrovascular and structural deficits in gray and white matter (GM and WM) were tested by averaging across the tissue and with a pothole analysis. Finally, we correlated cortical thickness and WMH volume with GM and WM cerebrovascular variables to assess the relationship between brain structure and cerebrovascular health. Results: In ten HD patients, cortical thickness was found to be decreased (p= 0.002), WMH volume increased (p=0.004), and WM CBF increased (p=0.02) relative to ten controls. Pothole analysis indicated a higher number of increased GM and WM CBF voxels (p=0.03, p=0.02) and a higher number of decreased GM and WM CVR voxels (p=0.02, p=0.01). Conclusions: This pilot study demonstrates that HD patients have decreased CVR and increased CBF relative to controls, along with reduced brain integrity. Further investigation is required to fully understand if these cerebrovascular deficits may lead to structural changes.

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“…Recently, a monoexponential model has been applied to analyze middle cerebral artery blood velocity (MCAv) data from a rest‐to‐exercise transition using various large muscle mass exercise protocols (Billinger et al, 2017 ; Weston et al, 2022 ). Since then, several studies published using this analysis technique comparing various populations suggest differences exist with time delay (TD) in health and disease (Kaufman et al, 2019 ; Ward et al, 2018 , 2022 ; Weston et al, 2022 ; Witte et al, 2019 ). These data are important to gain a greater understanding of the dynamic adjustment of MCAv.…”

Section: Introductionmentioning

confidence: 99%

Cerebral blood flow dynamics: Is there more to the story at exercise onset?

Ashley

Shelley

Song

et al. 2023

Physiological Reports

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A monoexponential model characterizing cerebral blood velocity dynamics at the onset of exercise may mask dynamic responses by the cerebrovasculature countering large fluctuations of middle cerebral artery blood velocity (MCAv) and cerebral perfusion pressure (CPP) oscillations. Therefore, the purpose of this study was to determine whether the use of a monoexponential model attributes initial fluctuations of MCAv at the start of exercise as a time delay (TD). Twenty-three adults (10 women, 23.9 ± 3.3 yrs; 23.7 ± 2.4 kg/m 2 ) completed 2 min of rest followed by 3 mins of recumbent cycling at 50 W. MCAv, CPP, and Cerebrovascular Conductance index (CVCi), calculated as CVCi = MCAv/MAP × 100 mmHg, were collected, a lowpass filter (0.2 Hz) was applied, and averaged into 3-second bins. MCAv data were then fit to a monoexponential model [ΔMCAv(t) = Amp(1 -e −(t−TD)/τ )]. TD, tau (τ), and mean response time (MRT = TD + τ) were obtained from the model.Subjects exhibited a TD of 20.2 ± 18.1 s. TD was directly correlated with MCAv nadir (MCAv N ), r = −0.560, p = 0.007, which occurred at similar times (16.5 ± 15.3 vs. 20.2 ± 18.1 s, p = 0.967). Regressions indicated CPP as the strongest predictor of MCAv N (R 2 a = 0.36). Fluctuations in MCAv were masked using a monoexponential model. To adequately understand cerebrovascular mechanisms during the transition from rest to exercise, CPP and CVCi must also be analyzed. A concurrent drop in cerebral perfusion pressure and middle cerebral artery blood velocity at the start of exercise forces the cerebrovasculature to respond to maintain cerebral blood flow. The use of a monoexponential model characterizes this initial phase as a time delay and masks this large important response.

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Cerebrovascular Response during Acute Exercise in Kidney Transplant Recipients

Cited by 4 publications

References 6 publications

The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function

The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function

Cerebrovascular Function is Altered in Hemodialysis Patients

Cerebral blood flow dynamics: Is there more to the story at exercise onset?

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