The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke.

BACKGROUND - Increased flow velocities, and combinations of low mean flow velocity (MFV) and a high pulsatility index (PI) are associated with intracranial arterial disease. We investigated the association of MFV and the ratio of PI and MFV (PI-MFV ratio) in the middle cerebral artery (MCA) with recurrence of vascular events in patients with a transient ischemic attack (TIA) or minor ischemic stroke. METHODS - Five hundred and ninety-eight consecutive patients underwent TCD investigation. Outcome events were fatal or non-fatal stroke and the composite of stroke, myocardial infarction, or vascular death (major vascular events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple regression method, adjusted for age, gender, and vascular risk factors. RESULTS - TCD registration was successful in 489 patients. Mean follow-up was 2.1 years. Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV over 60.5 cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3-6.0) and major vascular events (HR 2.6; 95% CI: 1.3-5.0). Each unit increase in PI-MFV ratio was associated with a HR 2.8 (95% CI: 1.7-4.8) for stroke and HR 2.2 (95% CI: 1.3-3.6) for major vascular events. CONCLUSION - In patients with a TIA or non-disabling ischemic stroke, MFV and the PI-MFV ratio in the MCA are independent prognostic factors for recurrent vascular events.

Cerebral hemodynamics before and after shunting in normal pressure hydrocephalus.

OBJECTIVE: To study the relationship between cerebral hemodynamics and clinical performance in normal pressure hydrocephalus (NPH), before and after surgery. MATERIAL AND METHODS: Ten patients were studied prospectively before and 3 months after shunt surgery by means of transcranial Doppler (TCD). Clinical performance was scored by means of an NPH scale and the modified Rankin scale. RESULTS: Peak systolic and mean cerebral blood flow velocity (MCV) were lower and cerebrovascular CO2 reactivity was higher after shunt surgery. The three patients with clinical improvement had higher preoperative end diastolic cerebral blood flow velocity and MCV. All postoperative cerebral blood flow velocities were higher in patients with clinical improvement. CONCLUSION: Our data suggest that higher cerebral blood flow velocity before surgery in patients with NPH is related to clinical improvement after shunt surgery. Cerebral hemodynamic parameters may develop into predictors of successful shunt surgery in patients with normal pressure hydrocephalus.

Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke.

BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin.

Effect of diaspirin cross-linked hemoglobin on endothelin-1 and blood pressure in acute ischemic stroke in man.

OBJECTIVE: For almost 50 years it has been known that hemolysed blood can increase blood pressure. Although preclinical studies suggest that this pressor response is due to an interaction of hemoglobin with endothelium-derived vasoactive substances, its mechanism in humans is unknown. We investigated the involvement of endothelin-1 in the blood pressure response to the oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in stroke patients. DESIGN: In a randomized phase II study, increasing doses of DCLHb (25, 50 and 100 mg/kg, n=8, 8 and 11, respectively) or placebo (n=26) were infused intravenously every 6 h for 72 h to patients with an acute ischemic stroke. Blood pressure and heart rate were measured every 15 min and plasma concentrations of endothelin-1, catecholamines, renin, vasopressin and atrial natriuretic peptide were measured before and 24 and 66 h after the start of the infusions. RESULTS: In the placebo group, mean arterial pressure (MAP) was 112 (109-115) mmHg (mean and 95% confidence interval) at baseline and decreased spontaneously by 11.4 (5.4-17.5) and 12.5 (5.4-19.5) mmHg after 24 and 66 h, respectively. This decrease in MAP was attenuated in patients treated with DCLHb, reaching statistical significance in the highest dose group. The plasma endothelin-1 concentration decreased slightly in the placebo group, from 4.2 (3.1-5.3) pg/ml (median and range) at baseline to 2.4 (1.9-3.7) pg/ml after 24 h (P=0.0044) and 2.8 (1.9-3.7) pg/ml after 66 h (P=0.0042), but increased dose-dependently in response to DCLHb infusion. With the highest dose of DCLHb, the plasma endothelin-1 concentration rose from 4.8 (0.1-7.8) pg/ml at baseline to 21.2 (13.4-53.2) pg/ml after 24 h (P< 0.001) and to 27.6 (11.9-47.8) pg/ml after 66 h (P< 0.001). The increases in the plasma endothelin-1 concentration and in MAP were correlated (r=0.30, P=0.02). Other vasoactive hormones were not affected by the DCLHb infusion. CONCLUSIONS: Infusion of DCLHb in patients with acute ischemic stroke was associated with a dose-dependent increase in plasma endothelin-1 concentration. This may underlie the attenuation by DCLHb of the natural decrease in blood pressure that we observed in these patients.