Arteriolar Red Blood Cell Velocity Research Articles

Frequency selective neuronal modulation triggers spreading depolarizations in the rat endothelin-1 model of stroke

Ischemia is one of the most common causes of acquired brain injury. Central to its noxious sequelae are spreading depolarizations (SDs), waves of persistent depolarizations which start at the location of the flow obstruction and expand outwards leading to excitotoxic damage. The majority of acute stage of stroke studies to date have focused on the phenomenology of SDs and their association with brain damage. In the current work, we investigated the role of peri-injection zone pyramidal neurons in triggering SDs by optogenetic stimulation in an endothelin-1 rat model of focal ischemia. Our concurrent two photon fluorescence microscopy data and local field potential recordings indicated that a ≥ 60% drop in cortical arteriolar red blood cell velocity was associated with SDs at the ET-1 injection site. SDs were also observed in the peri-injection zone, which subsequently exhibited elevated neuronal activity in the low-frequency bands. Critically, SDs were triggered by low- but not high-frequency optogenetic stimulation of peri-injection zone pyramidal neurons. Our findings depict a complex etiology of SDs post focal ischemia and reveal that effects of neuronal modulation exhibit spectral and spatial selectivity.

Ozagrel attenuates early streptozotocin-induced constriction of arterioles in the mouse retina

Retinal blood flow in human diabetics has been reported to follow a biphasic time course in which an initial period of reduced flow and ischemia is often followed by a hyperemic and angiogenic phase in which flow can exceed normal levels. The purpose of the present study is to investigate the mechanisms of the initial decrease in flow, since early interventions could provide the most effective treatment strategies. C57BL/6 mice were injected with streptozotocin (STZ) at 12weeks of age and remained hyperglycemic until data were gathered 4 or 8weeks later. Experimental measurements included retinal arteriolar red blood cell velocity and arteriolar diameters, with the diameters measured prior to and following an intravenous injection of the thromboxane synthase inhibitor ozagrel (100mg/kg). Arterioles leading out of the optic disk constricted significantly at 4weeks post-STZ (p<0.001) compared to age-matched controls, but not at 8weeks post-STZ. Calculations of retinal blood flow indicated a 45% decrease at 4weeks post-STZ, but only a 26% decrease by 8weeks. Not all arterioles constricted equally in response to STZ; the most substantial constrictions were present in arterioles that were more closely arranged with countercurrent venules leading back into the optic disk. Injection of ozagrel provided significant dilation of constricted retinal arterioles. In addition, the pattern of dilation was consistent with the sites of the most severe constriction, i.e., ozagrel-induced dilation in the STZ mice occurred to the greatest extent in the arterioles more closely paired with the venules draining the microvascular bed. In summary, STZ induces a biphasic alteration in retinal blood flow in mice, in which thromboxane contributes to the initial reduction in blood flow at 4weeks. Moreover, the thromboxane-induced arteriolar constriction is dependent on the proximity of the retinal arterioles to countercurrent venules.

Inhibition of CD18-dependent leukocyte adherence by mAb 6.5 E does not prevent ischemia-reperfusion injury as seen in grafted kidneys.

The present study was designed to determine whether beta-2 integrin-mediated leukocyte adherence to the endothelium is involved in renal ischemia-reperfusion damage and to evaluate the therapeutic intervention potency of monoclonal antibody (mAb) 6.5 E, directed against the leukocyte CD18 adhesion molecule. To answer these questions, we used a clinically relevant canine model for the autotransplantation of kidneys that had been subjected to 30 min of normothermic ischemia, followed by 24 h of cold storage preservation. Intravital fluorescence microscopy of capsular microvessels showed that substantial leukocyte adherence occurred after renal ischemia and reperfusion. Leukocyte adherence was observed in both arterioles and venules, but predominantly in the latter. Reperfusion of the graft resulted in a statistically significant reduction of the venular red blood cell velocity (RBCV). Moreover, the venular diameter increased. No significant changes in the arteriolar RBCV or in the arteriolar diameter were observed. Administration of mAb 6.5 E, 1 h before reperfusion, inhibited leukocyte adherence to the renal microvascular endothelium, resulting in an improved venular flow 2 h after reperfusion. However, we observed no beneficial effect of mAb 6.5 E pretreatment on post-transplant graft function and survival. We conclude that leukocyte adherence does not play a critical role in the development of renal injury following reperfusion of kidneys that have been subjected to prolonged warm and cold ischemia.

Arteriolar vasoconstriction in rat cremaster muscle induced by local heat stress.

The effect of moderate local heat stress on arteriolar tone in the cremaster muscle of anesthetized rats was investigated by direct microscopic observation. Muscle temperature was raised from the in vivo temperature of 34.5 to 38 degrees C, over a 5-min period, by elevating bath temperature. Muscle temperature, arteriolar lumen diameter, and arteriolar red blood cell velocity were continuously recorded. A number of the smallest arterioles studied (approximately 30 micrometers lumen diam) underwent a rapid and significant vasoconstriction near 36 degrees C. Denervation of the muscle eliminated the constrictor response. Addition of an alpha-blocking agent (dibenzyline to the denervated muscle unmasked the constriction, but the percent of arterioles demonstrating thermal reactivity remained decreased. We conclude that in some skeletal muscle beds a local thermoregulatory mechanism may exist whereby blood is shunted away from the tissue during heat stress at rest.