Quantification of dynamic blood flow autoregulation in optic nerve head of rhesus monkeys Yi Liang, Brad Fortune, Grant Cull, George A. Cioffi, Lin Wang * Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health System,1225 NE 2nd Avenue, Portland, OR 97232, USA article info Article history: Received 8 July 2009 Accepted in revised form 13 October 2009 Available online 22 October 2009 Keywords: optic nerve head dynamic blood flow autoregulation static blood flow autoregulation intraocular pressure abstract Autoregulation capacity has been classically assessed with a ‘two-point’ measurement or static autor- egulation (sAR). In such an approach, stabilized hemodynamic parameters are determined before and after a perfusion pressure challenge. Analysis of dynamic autoregulation (dAR), an early phase of blood flow response to a sudden perfusion pressure change is emerging as a preferred approach to assess the capacity of autoregulation in many non-ocular tissues and has developed rapidly in the last decade. The purpose of this study was to develop a method to quantify dAR in the optic nerve head (ONH). In six pentobarbital (6e9 mg/kg/h, IV) anesthetized rhesus monkeys, dAR was elicited by increasing intraocular pressure (IOP) from 10 to 30 or 40 mmHg (IOP 10e30 /IOP 10e40 ) manometrically via switch between reservoirs connected to the anterior chamber. Relative blood flow changes during dAR in the ONH, estimated with a laser speckle flowgraph (LSFG), were continuously measured for 1 min. Time-domain parameters of dAR response, including: BF Dmax (maximal blood flow decrease, %), K r (descending slope of blood flow from baseline to BF Dmax ) and T r (descending time of blood flow from baseline to BF Dmax ) were extracted and analyzed offline. For each monkey, same procedure was repeated three times during three different visits. The test-retest repeatability and inter-ocular difference of the parameters was statistically evaluated. During IOP 10e30 and IOP 10e40 , the mean arterial BP was 89  7 and 85  6 mmHg, respectively. Immediately after the reservoir was switched, the blood flow started to decline and reached maximal in w4 s. The blood flow then returned back toward baseline despite continuous IOP increase, which took 8e11 s to reach the level of the raised reservoir. The general pattern of blood flow responses was similar between IOP 10e30 and IOP 10e40 and there was no statistically significant difference for T r (P > 0.05). However, IOP 10e40 caused greater BF Dmax and deeper K r than IOP 10e30 (P < 0.0001 and P < 0.05, respectively). The blood flow during steady state, 5 min after IOP elevation, showed no statistically significant difference from baseline (P > 0.05). All dAR parameters (T r , K r and BF Dmax ) showed no significant difference across the 3 visits (Repeat measures ANOVA, P ¼ 0.7, 0.2 and 0.2, respectively); the corresponding coefficients of variance were 24%, 43% and 34% during IOP 10e30 and 11.8%, 30.3% and 19.0% during IOP 10e40 . The mean dAR parameters between the eyes showed no statistically differences (P ¼ 0.6) during both IOP 10e30 and IOP 10e40 . The current study showed that a rapid ocular perfusion pressure decrease induced by a sudden IOP step increase evoked a transient and reproducible dAR response in the ONH of non-human primates measured with LSFG. Quantitative analysis of dAR may provide a direct view of vasomotorial activity in the resistant vessels and thus a new approach to assess the autor- egulatory capacity in the ONH. Ó 2009 Elsevier Ltd. All rights reserved. Autoregulation is the intrinsic ability of retina and optic nerve head (ONH), among many other tissues in the body, to maintain a constant level of blood flow (BF) in response to variations in perfusion pressure and metabolic demand (Anderson, 1999; Bill and Sperber, 1990). This capability, involving multiple mechanisms including both myogenic and metabolic regulation, may fail as a part of pathogenetic processes in diseases, such as diabetes (Rassam et al., 1995) and glaucoma (Anderson, 1999; Cioffi, 1998; Spaeth, 1975). Thus, assessment of autoregulation capacity in ocular tissues is important to understand the mechanisms of these diseases and to investigate potential therapeutic target. Autoregulation capacity in the ocular tissues of both human and experimental animals is assessed conventionally by a ‘two-point’ BF measurement. In brief, BF or other hemodynamic parameters, * Corresponding author. E-mail address: lwang@deverseye.org (L. Wang). Contents lists available at ScienceDirect Experimental Eye Research journal homepage: www.elsevier.com/locate/yexer 0014-4835/$ e see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.exer.2009.10.009 Experimental Eye Research 90 (2010) 203e209