BACKGROUND AND AIMS: Regional blood-flow dynamics play an important role in thrombus formation and dissolution. Local intravascular conditions in the environment surrounding a thrombus contribute to its composition and susceptibility to lysis. Currently, approved treatment methods for acute ischemic stroke attempt to limit tissue injury by thrombolytic recanalization of the occluded vessel. However, vascular patency is achieved in only 30% of patients. Thus, there is a need for ancillary measures to enhance the efficacy of thrombolytic therapy. Human albumin therapy is highly neuroprotective in rodent models of focal cerebral ischemia and reperfusion. The results of a recently completed pilot-phase clinical trial suggest that albumin therapy appeared to be particularly beneficial in stroke patients who also underwent thrombolysis. To study further the role of albumin on microvascular hemodynamics in thrombotic stroke, we employed two-photon laser scanning microscopy to assess laser-induced thrombosis of superficial neocortical arterioles in the rat. METHODS: Male Sprague-Dawley rats were anesthetized with isoflurane/nitrous oxide, intubated, and mechanically ventilated. Arterial blood pressure and acid-base status were maintained within normal limits. A cranial window was created over the fronto-parietal cortex; the dura was kept intact. The animal was then transferred to a specially constructed stereotaxic frame attached to the stage of a two-photon microscope. The cranial defect was filled with artificial CSF and the skull defect sealed within a circulating chamber that maintained cranial temperature at 36.5oC. Arterioles of interest were identified at 20x magnification via z-scans performed at 1·m intervals after plasma labeling with fluorescein isothiocyanate-dextran (∼0.7 mg/kg i.v). Baseline blood flow velocities and diameters were measured in the selected microvessels by the method of Kleinfeld et al. In brief, RBC flow velocity was determined by repeated line-scans along a vessel's longitudinal (y) axis. Computer stacking of these scans revealed oblique shadows, from whose slopes with respect to time (dy/dt) flow velocity was computed. To produce vascular injury, a segment of an arteriole of interest was selected at the maximal optical zoom setting for laser-irradiation at the two-photon wavelength of 840 nm. With the laser shutter in the off position, irradiation intensity (W/cm2) was set according to the vessel diameter. The vessel was then irradiated for ∼5 min. Animals were allocated to albumin or isotonic saline treatment groups by coin toss. Treatment was carried out 25 min following vascular injury, and flow velocities determined over a 90 min period. RESULTS: Average baseline blood flow velocity was 24.5 ± 12.5 mm/s (n=6). Following injury, flow velocity decreased to 9.2 ± 2.8 mm/s (p< 0.05 by ANOVA vs. baseline). After saline infusion, blood flow velocity remained unchanged at 9.9 ± 2.4 mm/s. By contrast, after albumin infusion, blood flow velocity increased to 20.7 ± 4.0 mm/s (p< 0.05 by ANOVA vs. post-injury flow). CONCLUSIONS: Albumin administration following laser-induced microvascular thrombosis improves local hemodynamics; this may be an important component of its therapeutic effect.
|Original language||English (US)|
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|State||Published - Nov 13 2007|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine