Cardiovascular and cerebrovascular responses to lower body negative pressure in type 2 diabetic patients

Abstract

In diabetic patients, vascular disease and autonomic dysfunction might compromise cerebral autoregulation and contribute to orthostatic intolerance. The aim of our study was to determine whether impaired cerebral autoregulation contributes to orthostatic intolerance during lower body negative pressure in diabetic patients.Thirteen patients with early-stage type 2 diabetes were studied. We continuously recorded RR-interval, mean blood pressure and mean middle cerebral artery blood flow velocity at rest and during lower body negative pressure applied at −20 and −40 mm Hg. Spectral powers of RR-interval, blood pressure and cerebral blood flow velocity were analyzed in the sympathetically mediated low (LF: 0.04-0.15 Hz) and the high (HF: 0.15-0.5 Hz) frequency ranges. Cerebral autoregulation was assessed from the transfer function gain and phase shift between LF oscillations of blood pressure and cerebral blood flow velocity. In the diabetic patients, lower body negative pressure decreased the RRinterval, i.e. increased heart rate, while blood pressure and cerebral blood flow velocity decreased. Transfer function gain and phase shift remained stable.Lower body negative pressure did not induce the normal increase in sympathetically mediated LF-powers of blood pressure and cerebral blood flow velocity in our patients indicating sympathetic dysfunction. The stable phase shift, however, suggests intact cerebral autoregulation. The dying back pathology in diabetic neuropathy may explain an earlier and greater impairment of peripheral vasomotor than cerebrovascular control, thus maintaining cerebral blood flow constant and protecting patients from symptoms of presyncope.

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations

“…The above mentioned variability of BP and CBFV changes upon orthostatic challenge [21,25,50,51,53,54], with no change or a decrease in one or both signals, or even diametrical changes,…”

“…Marple [45] and applied in many previous studies assessing PA as a parameter of cerebral autoregulation [10,24,25,29,30,40,43,46].…”

“…The high-pass filter characteristics of autoregulation shift CBFV-oscillations to the left of corresponding BP-oscillations [20,22,[24][25][26]. Therefore, buffered maxima or minima of CBFVoscillations occur prior to maxima or minima of corresponding BP-oscillations [1,20,22].…”

Dynamic cerebral autoregulation assessed by respiratory manoeuvres in non‐insulin‐treated Type 2 diabetes mellitus

“…This may reflect the small size of studies. The development of impaired dynamic cerebral autoregulation may also relate to disease duration, although studies of similardisease duration have [4,5] and have not [7,8] reported impaired dynamic cerebral autoregulation. However, we did not find an increased likelihood of impaired dynamic cerebral autoregulation in patients with a diseasedurationgreaterthan5 years.Anothercontributormaybe disease severity, although the present study excluded insulintreated patients, and only approximately 30% of patients had evidence of macro-or microvascular complications.…”

“…People with diabetes may be particularly susceptible to the consequences of impaired cerebral autoregulation, being at increased risk of cerebral hypoperfusion secondary to autonomic neuropathic‐related orthostatic hypotension, and cerebral atherothromboembolism as a result of accelerated atherosclerosis. However, the few previous cerebral autoregulation studies in diabetes have produced conflicting results, showing impaired dynamic cerebral autoregulation [4–6] or no difference compared with control subjects [7,8]. These differences may be a consequence of small study size and the different methodologies and indices used to assess cerebral autoregulation.…”