Cardiac and peripheral vasomotor factors contribute to the rapid pressor response at the onset of isometric handgrip exercise. We tested the hypothesis that age enhances the sympathetic and vasoconstrictor response at the onset of isometric handgrip exercise so that the pressor response is maintained, despite a diminished cardiac function. Twelve young and twelve older (24 ± 3 and 63 ± 8 yr) individuals performed 20-s isometric handgrip exercise at 30, 40, or 50% of maximal voluntary contraction force. Muscle sympathetic nerve activity (MSNA) was measured using microneurography. Mean arterial pressure (MAP) and cardiac output (Q) were assessed continuously by finger plethysmography and total peripheral resistance was calculated. MAP increased with the onset of handgrip; this increase was associated with handgrip intensity and was similar in both groups. Heart rate and Q increased with increasing handgrip intensity in both groups, but increases were greater in young vs. older individuals (age × handgrip intensity interaction, P < 0.05). MSNA burst frequency increased (P < 0.01), while MSNA burst incidence tended to increase (P = 0.06) with increasing handgrip intensity in both groups. The change in MSNA between baseline and handgrip, for both frequency and incidence, increased with increasing handgrip intensity for both groups. There was no effect of handgrip intensity or age on total peripheral resistance. The smaller heart rate and Q response during the first 20 s of handgrip exercise in older individuals was not accompanied by a greater sympathetic activation or vasoconstrictor response. However, increases in MAP were similar between groups, indicating that the pressor response at the onset of handgrip exercise is preserved with aging.
BackgroundAutonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise‐based cardiac rehabilitation (CR) on autonomic function and neuro‐cardiovascular stress reactivity in CAD patients.Methods and ResultsTwenty‐two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic‐ and resistance‐training–based CR. Twenty‐two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro‐cardiovascular reactivity during short‐duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P<0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P<0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P<0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P<0.01). Heart rate variability (all P>0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre‐CR from CTRL (all P>0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P<0.05); yet, responses were reduced following CR (all P<0.05) to levels observed in CTRL.ConclusionsSix months of exercise‐based CR was associated with marked improvement in baseline autonomic function and neuro‐cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training.
Progressive multifocal leukoencephalopathy (pml) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (jcv), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of pml was established with gadolinium-enhanced magnetic resonance imaging (mri) and by detection of jcv in the cerebrospinal fluid. Despite cessation of chemotherapy and treatment with mirtazapine, he had an inexorable neurological decline and died two months after presenting to hospital. Multiple myeloma and its treatments can predispose patients to opportunistic infections including pml. Although there have been case reports of pml in patients with multiple myeloma treated with bortezomib (a different proteosome inhibitor), this is, to our knowledge, the first documented case of pml in a patient treated with a regimen that includes ixazomib.
Further research is required to establish the validity of scales that specifically address aggression for use in the adult TBI population which could be used to support rehabilitation and social reintegration strategies.
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