Background: Acute ischaemic stroke (AIS) patients often show impaired cerebral autoregulation (CA). We tested the hypothesis that CA impairment and other alterations in cerebral haemodynamics are associated with stroke subtype and severity. Methods: AIS patients (n = 143) were amalgamated from similar studies. Data from baseline (< 48 h stroke onset) physiological recordings (beat-to-beat blood pressure [BP], cerebral blood flow velocity (CBFV) from bilateral insonation of the middle cerebral arteries) were calculated for mean values and autoregulation index (ARI). Differences were assessed between stroke subtype (Oxfordshire Community Stroke Project [OCSP] classification) and severity (National Institutes of Health Stroke Scale [NIHSS] score < 5 and 5–25). Correlation coefficients assessed associations between NIHSS and physiological measurements. Results: Thirty-two percent of AIS patients had impaired CA (ARI < 4) in affected hemisphere (AH) that was similar between stroke subtypes and severity. CBFV in AH was comparable between stroke subtype and severity. In unaffected hemisphere (UH), differences existed in mean CBFV between lacunar and total anterior circulation OCSP subtypes (42 vs. 56 cm•s^–1, p < 0.01), and mild and moderate-to-severe stroke severity (45 vs. 51 cm•s^–1, p = 0.04). NIHSS was associated with peripheral (diastolic and mean arterial BP) and cerebral haemodynamic parameters (CBFV and ARI) in the UH. Conclusions: AIS patients with different OCSP subtypes and severity have homogeneity in CA capability. Cerebral haemodynamic measurements in the UH were distinguishable between stroke subtype and severity, including the association between deteriorating ARI in UH with stroke severity. More studies are needed to determine their clinical significance and to understand the determinants of CA impairment in AIS patients.

No abstract

We hypothesized that knowledge of cerebral autoregulation (CA) status during recanalization therapies could guide further studies aimed at neuroprotection targeting penumbral tissue, especially in patients that do not respond to therapy. Thus, we assessed CA status of patients with acute ischemic stroke (AIS) during intravenous r-tPA therapy and associated CA with response to therapy. AIS patients eligible for intravenous r-tPA therapy were recruited. Cerebral blood flow velocities (transcranial Doppler) from middle cerebral artery and blood pressure (Finometer) were recorded to calculate the autoregulation index (ARI, as surrogate for CA). National Institute of Health Stroke Score was assessed and used to define responders to therapy (improvement of ≥ 4 points on NIHSS measured 24-48 h after therapy). CA was considered impaired if ARI < 4. In 38 patients studied, compared to responders, non-responders had significantly lower ARI values (affected hemisphere: 5.0 vs. 3.6; unaffected hemisphere: 5.4 vs. 4.4, p = 0.03) and more likely to have impaired CA (32% vs. 62%, p = 0.02) during thrombolysis. In conclusion, CA during thrombolysis was impaired in patients who did not respond to therapy. this variable should be investigated as a predictor of the response to therapy and to subsequent neurological outcome. The key objective of current acute ischemic stroke (AIS) treatment is based on rapid blood flow restoration by thrombolysis, using intravenous recombinant tissue plasminogen activator (r-tPA), and/or mechanical arterial recanalization techniques 1-3. Several factors predict stroke outcome including age, initial stroke severity, arterial blood pressure (BP), site of occlusion, collaterals, and others 4,5. Nevertheless, complete or partial successful recanalization may not necessarily result in favorable outcome, with a number of predictors hypothesized 6,7. In particular, BP control may affect penumbral lesion size, with an optimal strategy still lacking evidence 8-10. Therapeutic BP manipulation may further impact on microvascular autoregulatory failure, as a consequence of an increase in lactate and free oxygen radicals in the occluded and/or reperfused tissues 11. Cerebral autoregulation (CA) refers to a set of physiological mechanisms that maintain the constancy of cerebral blood flow (CBF) despite wide variations in arterial BP. CA can be impaired within the first hours of ischemic stroke onset 11 ; as a consequence, BP control may be important for improving both the ischemic area in the brain and clinical outcome. Therefore, assessment of CA during recanalization therapy for AIS is relevant, and may influence future strategies for personalized BP control and associated neuroprotection. The aims of the present study were to assess CA status of responder and non-responder AIS patients to intravenous r-tPA during the therapy and after 24-48 h, and to test the hypothesis that CA during thrombolysis is associated with early response to therapy.

Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). r In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. r Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. r During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. r Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia.

BackgroundExercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development.Methods df was measured in 24 healthy individuals prior to, after 5 min of submaximal exercise, following maximal exercise, 45 min of passive recovery and following 60 min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. ResultsSignificantly increased df was observed following exercise, returning to resting values following 60 min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. ConclusionThis study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.

Both manoeuvres can be used to evoke similar bilateral MCA responses in assessing NVC. This finding should lead to more efficient protocols when using passive arm movement for NVC studies in healthy subjects.

Instantaneous arterial pressure-flow (or velocity) relationships indicate the existence of a cerebral critical closing pressure (CrCP), with the slope of the relationship expressed by the resistance-area product (RAP). In 194 healthy subjects (20–82 years, 90 female), cerebral blood flow velocity (CBFV, transcranial Doppler), arterial blood pressure (BP, Finapres) and end-tidal CO2 (EtCO2, capnography) were measured continuously for five minutes during spontaneous fluctuations of BP at rest. The dynamic cerebral autoregulation (CA) index (ARI) was extracted with transfer function analysis from the CBFV step response to the BP input and step responses were also obtained for the BP-CrCP and BP-RAP relationships. ARI was shown to decrease with age at a rate of −0.025 units/year in men (p = 0.022), but not in women (p = 0.40). The temporal patterns of the BP-CBFV, BP-CrCP and BP-RAP step responses were strongly influenced by the ARI (p < 0.0001), but not by sex. Age was also a significant determinant of the peak of the CBFV step response and the tail of the RAP response. Whilst the RAP step response pattern is consistent with a myogenic mechanism controlling dynamic CA, further work is needed to explore the potential association of the CrCP step response with the flow-mediated component of autoregulation.

Squat‐stand maneuvers (SSMs) are a popular method of inducing blood pressure (BP) oscillations to reliably assess dynamic cerebral autoregulation (dCA), but their effects on the cerebral circulation remain controversial. We designed a protocol whereby participants would perform SSMs under hypercapnic conditions. Alarmingly high values of cerebral blood flow velocity (CBFV) were recorded, leading to early study termination after the recruitment of a single participant. One healthy subject underwent recordings at rest (5 min sitting, 5 min standing) and during two SSMs (fixed and random frequency). Two sets of recordings were collected; one while breathing room air, one while breathing 5% CO 2 . Continuous recordings of bilateral CBFV (transcranial Doppler), heart rate (ECG), BP (Finometer), and end‐tidal CO 2 (capnography) were collected. Peak values of systolic CBFV were significantly higher during hypercapnia ( p < 0.01), and maximal values exceeded 200 cm.s −1 . Estimates of dCA (ARI) during hypercapnia were impaired relative to poikilocapnia ( p = 0.03). The phase was significantly reduced under hypercapnic conditions ( p = 0.03). Here we report extremely high values of CBFV in response to repeated SSMs during induced hypercapnia, in an otherwise healthy subject. Our findings suggest that protocols performing hypercapnic SSMs are potentially dangerous. We, therefore, urge caution if other research groups plan to undertake similar protocols.