Middle Cerebral Artery Diameter Research Articles

Flow-induced responses in piglet isolated cerebral arteries.

Although cerebral hemorrhage is a widely occurring neurologic disorder thought to be caused by fluctuating blood flow, the response to flow in the neonatal cerebrovasculature has not been characterized. In the present study, we examined the effect of changing flow on middle cerebral artery diameter and pathways by which flow modulates cerebrovascular tone. Arteries from 2-14-d-old piglets were mounted on cannulas and bathed in and perfused with physiologic saline solution. An electronic system controlled pressure and a syringe pump provided constant flow. The transmural pressure was held constant at 20 mm Hg, and changes in vessel diameter were measured as flow was increased in steps from 0 to 1.60 mL/min (flow/diameter curves). Increasing flow at constant pressure resulted in constriction at flows from 0.077 to 0.152 mL/min and dilation at flows from 0.212 to 1.60 mL/min. The flow/diameter curves were repeated in arteries bathed in Na(+)-reduced or Ca(2+)-free physiologic saline solution; denervated with 6-hydroxydopamine; or treated with indomethacin, N-nitro-L-arginine methyl ester, N omega-nitro-L-arginine (NLA), and L-arginine), ryanodine, or glutaraldehyde. In Na(+)-reduced and in Ca(2+)-free physiologic saline solution, flow constriction was eliminated. Neither indomethacin nor 6-hydroxydopamine affected the biphasic response. N-Nitro-L-arginineL, NLA, and ryanodine blocked dilation, whereas L-arginine restored dilation in NLA-treated arteries. These data suggest that neither prostaglandins nor adrenergic nerve endings participate in flow-induced responses in piglet cerebral arteries. Elimination of flow-constriction by Na+ reduction or Ca2+ removal is consistent with findings in other artery types. The elimination of dilation by N-nitro-L-arginine methyl ester, NLA, and ryanodine suggests that dilation is mediated by nitric oxide and intracellular Ca2+. Whereas the contractile and dilatory responses to agonists remained intact after glutaraldehyde perfusion, both flow-induced constriction and dilation were eliminated, indicating that both types of flow responses result from endothelial cell deformation.

Characterization of an anterior circulation rat subarachnoid hemorrhage model.

Our aim was to demonstrate the feasibility of an angiographically controlled rat model for the study of macrocirculatory and microcirculatory changes of the anterior intracranial circulation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by transorbital injection of 0.3 mL of nonheparinized autologous arterial blood into the chiasmatic cistern. Changes in regional cerebral blood flow were continuously recorded with the use of laser-Doppler flowmetry over the parietal cortex. Angiographic verification of middle cerebral artery diameter was performed by carotid catheterization at baseline and 2 days after injection of blood or artificial cerebrospinal fluid. We monitored intracranial and systemic blood pressure during and after injections. Injection of artificial cerebrospinal fluid in the control group did not change the diameter of the middle cerebral artery. Injection of blood caused a significant arterial narrowing of 17.5%, from 0.37 +/- 0.04 mm to 0.31 +/- 0.04 mm after 2 days (P = .0001). In the control group regional cerebral blood flow decreased to 75.9 +/- 16.8% of preinjection control but quickly recovered to 99.7 +/- 19.4%. Intracranial pressure increased for 5 minutes after the injection to a maximum of 27.3 +/- 8.9 mm Hg, accompanied by a 10% decrease in mean arterial pressure. A fall in cerebral blood flow to 53.1 +/- 26.3% in blood-injected animals that recovered to only 80.7 +/- 16.9% of baseline values during the observation period of 30 minutes was noted. A peak intracranial pressure of 45.7 +/- 11.5 mm Hg occurred 2 minutes after injection with a decrease in mean arterial pressure of 13%, resulting in a markedly lower cerebral perfusion pressure than in the control group. An angiographically controlled model of subarachnoid hemorrhage primarily involving the anterior circulation is feasible in the rat. The resulting narrowing of the middle cerebral artery reflects moderate vasospasm and will allow further microcirculatory studies with cranial windows.

Effect of Ketanserin on Global Cerebral Blood Flow and Middle Cerebral Artery Flow Velocity

The aim of this study was to examine the influence of ketanserin, a 5-hydroxytryptamine antagonist antihypertensive agent, on the relationship between cerebral blood flow (CBF) and middle cerebral artery flow velocity (Vmean MCA) and to compare Doppler-sonographic indices of downstream resistance (pulsatility index, PI; resistance index, RI) with calculations of cerebrovascular resistance (CVR) in 17 male patients under fentanyl/midazolam anesthesia. CBF was measured with the Kety-Schmidt technique using argon as a tracer. Cerebral perfusion pressure (CPP) was calculated as the difference between mean arterial pressure (MAP) and jugular bulb pressure. Measurements of Vmean MCA and determinations of PI and RI were performed by use of a 2-MHz transcranial Doppler ultrasound device. All variables were measured at normo- and moderate hypocapnia before and after intravenous (i.v.) bolus administration of 0.3 mg/kg ketanserin followed by an infusion of 0.06 mg.kg-1.h-1. Ketanserin changed neither average CBF nor Vmean MCA. The CO2 reactivity of Vmean MCA was significantly lower than the CO2 reactivity of CBF (P < 0.01); however, ketanserin did not change the relationship between CBF and Vmean MCA. During hypocapnia, CVR as well as PI and RI significantly increased (P < or = 0.01), indicating consistent directional changes in arteriolar resistance and flow velocity pulsatility. In contrast, after i.v. administration of ketanserin, CVR decreased (P < 0.05), whereas both Doppler-derived indices increased (P < 0.01). These results suggest that ketanserin in a clinically relevant dose does not alter the validity of serial Vmean MCA measurements as an index of global CBF and that ketanserin does not change the diameter of middle cerebral arteries (MCAs). Doppler-derived indices of pulsatility and resistance, which are supposed to estimate changes in downstream resistance, reflect changes, after administration of ketanserin, in systemic hemodynamics rather than changes in CVR.

Angiographic and Doppler diagnosis of cerebral artery vasospasm following subarachnoid haemorrhage

Angiographic middle and anterior cerebral artery diameter and transcranial ultrasound flow velocity measurements were performed within 24 h of each other in 102 patients with recent aneurysmal subarachnoid haemorrhage. There was a significant inverse correlation between middle cerebral artery diameter and flow velocity (r = -0.54, p < 0.001). No such correlation was seen for anterior cerebral arteries (r = -0.25). The ratio of middle cerebral artery to extracranial internal carotid artery velocities, which is an index of vasospasm, did not show improved correlation with arteriographic diameters, compared with uncorrected middle cerebral artery readings. Middle and anterior cerebral artery velocities and diameters both began to show significant changes indicative of vasospasm from day 4-5 onwards, suggesting that an increase in Doppler velocity is a good indicator of middle cerebral artery diameter, as shown by angiography. These studies indicate that transcranial Doppler is a useful non-invasive monitor for the development of delayed vasospasm following subarachnoid haemorrhage.

Neuropeptide Y in the primate model of subarachnoid hemorrhage.

The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.

Sex and side differences of cerebral arterial caliber

The diameter of 261 middle cerebral and 225 anterior cerebral arteries was measured on half axial antero-posterior (ap) view, and the diameter of 217 internal carotid arteries on side view angiograms. Mean diameter was significantly larger by 9.3%, 8.8% and 9.7% respectively in males than in females. In the females the vessels of the left hemisphere were wider but not significantly so than those of the right hemisphere, and the contrary was true for the males. In both sexes the side difference was reversed in the eighth decennium. There was no correlation of vessel diameter with age except for a statistically significant increase by 7.8% of right middle cerebral artery diameter in males from the fifth to the sixth decennium.

Endothelium-independent contractions of human cerebral arteries in response to vasopressin.

We studied the effects of vasopressin in isolated segments from branches (500-700 micrograms in external diameter) of human middle cerebral arteries obtained during autopsy of 15 patients who had died 3-8 hours before. Paired segments, one normal and the other de-endothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. In 11 normal segments, vasopressin produced concentration-dependent contractions with an EC50 of 7.0 X 10(-10) M. Removal of the endothelium from 12 segments did not significantly affect vasopressin-induced contractions. Vasopressin produced further contractions in arterial segments with (n = 4) or without (n = 5) endothelium precontracted with KCl. In segments precontracted with prostaglandin F2 alpha, acetylcholine choline caused relaxation only of those with endothelium. At 10(-8) M (n = 11), the vasopressin V-1 receptor antagonist d(CH2)5Tyr(Me)AVP produced a 60-fold shift to the right of the control response curve for vasopressin. Increasing the concentration of the receptor antagonist to 10(-6) M (n = 7) further displaced the control curve in a parallel manner. These results indicate that vasopressin exerts a powerful constrictor action on isolated human cerebral arteries by direct stimulation of V-1 receptors located predominantly on smooth muscle cells. It appears that this contractile response is not modulated by the presence of an intact endothelial cell layer.

On the postjunctional alpha-adrenoreceptors in rat cerebral and mesenteric arteries.

The contractile response to exogenously applied noradrenaline (NA) was examined in vitro in tubal segments (0.2-0.1 mm in diameter) of rat middle cerebral (MCA), basilar (BA) and mesenteric (MA) arteries. In the MCA, the maximum contractile response to NA (10(-4)M) was considerably smaller than that induced by K+ (124 mM) or 5-hydroxytryptamine (10(-5)M), whereas the inverse relationship was found in the MA. NA usually failed to elicit contraction in the BA even in the presence of propranolol and cocaine. In the MCA, propranolol (3 X 10(-7)M) enhanced the maximum contractile response to NA by approximately 100% without affecting the potency of the agonist. In the MA, propranolol had no effect on the concentration-response relationship for NA. Cocaine (10(-5)M) or 6-hydroxydopamine pretreatment increased the NA sensitivity of the MA by a factor of three, whereas these procedures failed to influence the NA sensitivity of the MCA. A marked stereoselectivity was found in the MCA, as (-)-NA was more than 100 times more potent than (+)-NA as a contractile agent. The order of potency of a series of alpha-adrenoreceptor agonists was (-)-adrenaline greater than oxymetazoline greater than (+/-)-NA approximately (-)-phenylephrine greater than methoxamine in the MCA and (+/-)-NA greater than (-)-phenylephrine in the MA. Clonidine failed to elicit contraction in concentrations lower than 3 X 10(-4)M in both types of artery. Prazosin was between three and four orders of magnitude more potent than rauwolscine in inhibiting NA-induced contractions in the MCA and MA. The pA2 values for, respectively, prazosin and rauwolscine were 9.3 and 5.4 in the MCA and 9.7 and 6.8 in the MA. The slope of the Schild plot deviated significantly from unity only for rauwolscine in the MA (0.64). It is concluded that the contractile response to exogenous NA in the MCA and MA is mediated mainly by stimulation of alpha 1-adrenoreceptors, although a small contribution of postjunctional alpha 2-adrenoreceptors in the MA cannot be excluded. In contrast to the MCA, the BA appears to lack contraction-mediating alpha-adrenoreceptors, indicating regional differences in the alpha-adrenoreceptor distribution in the rat cerebrovascular bed.