Cerebrovascular Compliance during Progressive Hypotension in Patients with Autonomic Failure

Abstract

Background: Cerebral perfusion during reductions in arterial pressure (AP) can be supported transiently by a Windkessel mechanism that increases cerebrovascular compliance (Ci). This defense mechanism exists in healthy participants during rapid standing and in patients during vasovagal syncope. However, it remains unknown whether the rise in Ci with falling AP exhibits a threshold effect. Thus, we tested the hypothesis that increased Ci is passive to a reduction in AP and starts to increase only after a threshold has been reached. To test this hypothesis, it was necessary to study a population that tolerates progressive large reductions in BP without a loss of consciousness. Therefore, we analyzed Ci changes during a graded head-up tilt (HUT) from patients with autonomic failure (AF). Methods: Finger AP and right middle cerebral artery blood velocity (MCAv) were recorded from 5 AF patients (n = 5 male, 61 ± 23 years, 25 ± 5 kg/m2) at supine rest and during graded-HUT (30, 45, 60 degrees). Tilt gradients increased incrementally every 5 minutes until AP reached a critically low value prompting termination of HUT. The total time in HUT was 11 ± 4 min. Individual AP and MCAv waveforms during supine rest and graded HUT (one waveform every 5 s) were assessed with a modified Windkessel model to calculate Ci and cerebrovascular resistance (CVR). Pulse pressure (PP) was calculated as systolic AP − diastolic AP. A threshold value for the increase in Ci was determined as five consecutive cardiac cycles greater than the average supine Ci plus 2 standard deviations. Results: Graded HUT resulted in an overall reduction in AP (85 ± 18 to 50 ± 7 mmHg), PP (72 ± 22 to 32 ± 19 mmHg), mean MCAv (62 ± 12 to 35 ± 7 cm/s), and CVR (1.4 ± 0.1 to 1.0 ± 0.3 mmHg/cm/s; all p < 0.05 vs supine). Ci increased by 905 ± 756% (p = 0.04 vs supine). The threshold effect was evident as Ci began to increase progressively after PP fell by 15 ± 3 mmHg and AP fell by 12 ± 2 mmHg. Conclusions: Our results provide evidence that Ci increases after a threshold reduction in PP and AP in the apparent absence of autonomic support. These data support the idea that increasing Ci during reductions in AP represents a pressure-dependent Windkessel mechanism. Of interest, our findings provide clinical insight into how AF patients compensate for such large reductions in pressure without the assistance of CVR as a defense mechanism. NSERC USRA — Western University, Natural Sciences and Engineering Research Council of Canada (NSERC, Grant No. RGPIN-2018-06255). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.