Physiological Targets for Orthostatic Hypotension: Improving Nonpharmacological Interventions in Patients with Orthostatic Cerebral Hypoperfusion.

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.

Cardiovascular Autonomic Regulation, ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance.

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of ≥ 30 bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO2 and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N = 108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO2 during 10 min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO2 show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

Cardiovascular disease risks in adult Native and Mexican Americans with a history of alcohol use disorders: association with cardiovascular autonomic control.

Hypertension and obesity are serious health problems that have been associated with an increased risk of cardiovascular disease (CVD). We recently showed a relationship between hypertension, obesity and cardiovagal control in a sample of Native and Mexican Americans at high risk of alcohol use disorders (AUD). While studies have shown that Native and Mexican Americans exhibit high rates of AUD, the consequences of AUD on CVD risk factors and their relationship with cardiovascular autonomic control is not well understood in these ethnic groups. This study investigated whether an association could be demonstrated between cardiovascular autonomic control and several CVD risk factors in Native and Mexican American men and women (n = 228) who are literate in English and are residing legally in San Diego County. Participants with lifetime history of AUD showed higher rates of systolic and diastolic hypertension and obesity than participants without lifetime AUD. Lifetime AUD was significantly associated with reduced HR response to deep breathing (HRDB) measure of cardiovagal control, higher current drinking quantity, and obesity. Reduced HRDB was also associated with increased systolic pre-hypertension or hypertension (pre-/hypertension) and with higher diastolic blood pressure in a linear regression model that included several diagnostic and demographic variables. HRDB and time- and frequency-domain measures of cardiovagal control were significantly reduced in participants with diastolic pre-/hypertension. These data suggest that lower cardiovagal control may play a role in the prevalence of systolic and diastolic pre-/hypertension in a community sample with a history of alcohol and substance use disorders.

Obesity in american Indian and mexican american men and women: associations with blood pressure and cardiovascular autonomic control.

Obesity is a serious public health problem, especially in some minority communities, and it has been associated with an increased risk of cardiovascular diseases. While obesity is a serious health concern in both American Indian and Mexican American populations, the relationship between obesity and cardiac autonomic control in these two populations is not well understood. The present study in a selected sample of American Indians and Mexican Americans assessed associations between obesity, blood pressure (BP), and cardiovascular autonomic control. Cardiovascular autonomic control, systolic and diastolic mean BP, and body mass index were obtained from one hundred thirty-two American Indian and Mexican American men and women who are literate in English and are residing legally in San Diego County. Men had a significant greater systolic and diastolic BP and were more likely to develop systolic prehypertension and hypertension than women. Obese participants showed greater mean heart rate (HR) and systolic and diastolic BP than nonobese participants. Obese men also exhibited greater cardiac sympathetic activity and lower cardiovagal control than obese women. These results suggest that obesity and gender differences in cardiovascular autonomic control may contribute to risk for cardiovascular disorders in this sample of American Indians and Mexican Americans.

Loss of medial septal modulation of dentate gyrus physiology in young mice overexpressing human beta-amyloid precursor protein.

Mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show deficits in hippocampal-dependent spatial learning and hippocampal short- and long-term plasticity at ages preceding Abeta plaque deposition. We determined whether young PDAPP mice also exhibit alterations in septohippocampal function in vivo, which plays an important role in cognitive function. Electrical stimulation of the medial septum significantly increased neuronal excitability and reduced paired-pulse facilitation in the dentate gyrus. Medial septal-induced facilitation of dentate neuronal excitability was reduced in PDAPP mice. The inhibitory effects of medial septum stimulation on dentate paired-pulse facilitation were also attenuated in PDAPP mice. Young mice overexpressing hbetaAPP exhibit early abnormalities in neural circuits implicated in cognitive function that may play an important role in the more profound deficits observed in aged PDAPP mice.