Authors: Tan CO.

Reliable assessment of cerebrovascular effectiveness in buffering against pressure fluctuations may have important implications for the timing and the outcome of therapy after adverse cerebrovascular events. Though linear approaches may indicate the presence or absence of cerebral autoregulation, they are inadequate to describe its characteristics and its effectiveness. Establishing a simple yet robust methodology to reliably measure the effectiveness of cerebral autoregulation could provide a tool to guide screening and clinical options to characterize and treat adverse cerebrovascular events associated with alterations in cerebral perfusion. To test the utility of one such methodology, an oscillatory lower body negative pressure of 30 - 40 mmHg was used at 6 frequencies from 0.03 to 0.08 Hz in 43 healthy volunteers, and the pressure - flow relation and the effectiveness of autoregulation was quantified using projection pursuit regression. Projection pursuit regression explained the majority of the relationship between pressure and cerebral blood flow fluctuations, and revealed its nature consistently across individuals and across separate study days. The nature of this relationship entailed an autoregulatory region wherein slow arterial pressure fluctuations are effectively counter-regulated and two passive regions wherein pressure fluctuations resulted in parallel changes in flow. The effectiveness of autoregulation was significantly reduced as pressure fluctuations become faster. These results demonstrate the characteristic relationship between arterial pressure and cerebral blood flow. Furthermore, the methodology utilized in this study provides a tool that can provide unique insight to integrated cerebrovascular control, and that may allow diagnosis of physiological alterations underlying impaired cerebral autoregulation.

Authors: Cipolla MJ, Bishop N, Chan SL.

Severe preeclampsia and eclampsia are associated with brain edema that forms preferentially in the posterior cerebral cortex possibly because of decreased sympathetic innervation of posterior cerebral arteries and less effective autoregulation during acute hypertension. In the present study, we examined the effect of pregnancy on the effectiveness of cerebral blood flow autoregulation using laser Doppler flowmetry and edema formation by wet:dry weight in acute hypertension induced by phenylephrine infusion in the anterior and posterior cerebrum from nonpregnant (n=8) and late-pregnant (n=6) Sprague-Dawley rats. In addition, we compared the effect of pregnancy on sympathetic innervation by tyrosine hydroxylase staining of posterior and middle cerebral arteries (n=5-6 per group) and endothelial and neuronal NO synthase expression using quantitative PCR (n=3 per group). In nonpregnant animals, there was no difference in autoregulation between the anterior and posterior cerebrum. However, in late-pregnant animals, the threshold of cerebral blood flow autoregulation was shifted to lower pressures in the posterior cerebrum, which was associated with increased neuronal NO synthase expression in the posterior cerebral cortex versus anterior. Compared with the nonpregnant state, pregnancy increased the threshold of autoregulation in both brain regions that was related to decreased expression of endothelial NO synthase. Lastly, acute hypertension during pregnancy caused greater edema formation in both brain cortices that was not attributed to changes in sympathetic innervation. These findings suggest that, although pregnancy shifted the cerebral blood flow autoregulatory curve to higher pressures in both the anterior and posterior cortices, it did not protect from edema during acute hypertension.

Authors: Peterson EC, Tozer K, Cohen W, Lam AM, Chesnut RM.

INTRODUCTION: It is widely accepted that pressure autoregulation is often disrupted after traumatic brain injury, based on studies using dynamic testing. The response to cerebral blood flow augmentation in such patients has not been evaluated. We hypothesized that augmenting systemic blood pressure with pressors would not change cerebral blood flow in patients that had disrupted dynamic autoregulation by TCD.
METHODS: We conducted autoregulation testing on a consecutive series of severe TBI patients treated at Harborview Medical Center from 2009 to 2010. All patients nderwent placement of a Licox intracranial pressure monitor and brain tissue oxygen probe. Each patient underwent dynamic testing with TCD (thigh-cuff method) and static autoregulation testing with CT perfusion. A CTP was performed at a baseline CPP and then repeated at an elevated CPP of 20mmHg above baseline. The two CTP blood flow maps were compared to assess the cerebrovascular response to the CPP challenge.
RESULTS: Autoregulation testing was performed in 81 patients. Eighty-four percent were performed in the first 48 hours, and 56% in the first 24 hours. Three patterns of CPA disruption emerged: 48% had intact static CPA but disrupted dynamic CPA, 40% had disrupted static and dynamic CPA, and 12% had intact static and dynamic CPA. The pattern of disrupted static and intact dynamic CPA was not seen.
CONCLUSION: Testing both static and dynamic CPA in the same patient suggests that the global CPA reflex has separate components and that dynamic CPA testing can demonstrate an impaired latency while static CPA testing may show that the overall capacity of CPA is intact. The majority of patients with disrupted dynamic autoregulation by TCD testing do not demonstrate improved perfusion when CPP was increased. This suggests the traditional concept of autoregulation in TBI needs to be reconsidered in light of at least two underlying mechanisms.

Authors: Lind-Holst M, Cotter JD, Helge JW, Boushel R, Augustesen H, Van Lieshout JJ, Pott FC.

Aerobic fitness may be associated with reduced orthostatic tolerance. To investigate whether trained individuals have less effective regulation of cerebral vascular resistance, we studied the middle cerebral artery (MCA) mean blood velocity (V(mean)) response to a sudden drop in mean arterial pressure (MAP) after 2.5 min of leg ischemia in endurance athletes and untrained subjects (maximal O(2) uptake: 69 ± 7 vs. 42 ± 5 ml O(2)·min(-1)·kg(-1); n = 9 for both, means ± SE). After cuff release when seated, endurance athletes had larger drops in MAP (94 ± 6 to 62 ± 5 mmHg, -39%, vs. 99 ± 5 to 73 ± 4 mmHg, -26%) and MCA V(mean) (53 ± 3 to 37 ± 2 cm/s, -30%, vs. 58 ± 3 to 43 ± 2 cm/s, -25%). The athletes also had a slower recovery to baseline of both MAP (25 ± 2 vs. 16 ± 1 s, P < 0.01) and MCA V(mean) (15 ± 1 vs. 11 ± 1 s, P < 0.05). The onset of autoregulation, determined by the time point of increase in the cerebrovascular conductance index (CVCi = MCA V(mean)/MAP) appeared later in the athletes (3.9 ± 0.4 vs. 2.7 ± 0.4s, P = 0.01). Spectral analysis revealed a normal MAP-to-MCA V(mean) phase in both groups but ~40% higher normalized MAP to MCA V(mean) low-frequency transfer function gain in the trained subjects. No significant differences were detected in the rates of recovery of MAP and MCA V(mean) and the rate of CVCi regulation (18 ± 4 vs. 24 ± 7%/s, P = 0.2). In highly trained endurance athletes, a drop in blood pressure after the release of resting leg ischemia was more pronounced than in untrained subjects and was associated with parallel changes in indexes of cerebral blood flow. Once initiated, the autoregulatory response was similar between the groups. A delayed onset of autoregulation with a larger normalized transfer gain conforms with a less effective dampening of MAP oscillations, indicating that athletes may be more prone to instances of symptomatic cerebral hypoperfusion when MAP declines.