Faculty Bibliography

UNLABELLED:In this study we sought to determine the acute cerebrovascular effects of intracarotid adenosine by using real-time cerebral blood flow (CBF) measurements in nonhuman primates. The internal carotid arteries of healthy anesthetized baboons were transfemorally cannulated. Changes in CBF were continuously measured at baseline and with 6 increasing doses of adenosine (0.002 to 1.5 mg/min) by use of an intraparenchymal thermal diffusion (TD) probe. Each infusion lasted 5 min. At baseline and at the largest dose of adenosine, CBF was also determined by the intraarterial (133)Xe technique. TD measurements revealed a dose-dependent increase in CBF from 32 +/- 6 mL x l00 g(-1) x min(-1) at baseline to 90 +/- 38 mL x l00 g(-1) x min(-1) with the largest dose of adenosine (n = 5; P < 0.0001). A similar magnitude of increase in CBF was also observed with (133)Xe CBF measurements. No significant increases in intracranial pressure or adverse systemic hemodynamic side effects were observed during adenosine infusion. The increase in CBF after adenosine lasted only for the duration of drug infusion. In conclusion, the transient cerebrovascular effects of intracarotid adenosine make it suitable for a trial of intraarterial vasodilator therapy and for controlled manipulation of cerebrovascular resistance. IMPLICATIONS/CONCLUSIONS:Using a real-time cerebral blood flow (CBF) measurement technique, we evaluated the acute cerebrovascular effects of intracarotid adenosine in anesthetized baboons. The increase in CBF lasted only for the duration of the adenosine infusion. Adenosine might be a suitable drug for trial as an intraarterial vasodilator for the treatment of cerebral vasospasm.

Over the last two decades, interventional neuroradiologists have developed powerful techniques for the treatment of cerebrovascular disorders and brain tumors. Current interventional neuroradiological procedures are performed under X-ray fluoroscopy, which has allowed for high temporal and spatial resolution. However, these imaging techniques do not provide the treating physician with vital anatomic and functional information regarding vessel walls and the surrounding brain tissue. Better visualization of vessel structures and real-time information about the state of perfusion and metabolism of the surrounding brain tissue (real-time magnetic resonance arteriography, diffusion and perfusion-weighted imaging, apparent diffusion coefficient maps) would enhance safety and efficacy of neuroendovascular procedures available currently. Recent advances in magnetic resonance hardware and software have permitted significant enhancements in temporal and spatial resolution, which have resulted in the capability of visualizing anatomic structures with real-time fluoroscopy and angiography. This review outlines how real-time magnetic resonance procedures may replace conventional X-ray fluoroscopy in diagnostic and interventional neuroradiology during the next decade.

BACKGROUND:Intracranial atherosclerosis accounts for 8% to 10% of all ischemic strokes, and intracranial angioplasty is increasingly performed to treat stenotic lesions. We report an autopsy case and discuss the effects of intracranial angioplasty for atherosclerotic arteries. CASE DESCRIPTION/METHODS:A 77-year-old patient died 9 days after angioplasty of the left middle cerebral artery as a result of cardiorespiratory failure. The patient was anticoagulated before, during, and after the procedure with heparin, aspirin, and clopidogrel. At the site of angioplasty, the densely fibrotic eccentric plaque was displaced from the adjacent media into the lumen, distorting it and forming elongated projections. No local thrombosis, plaque compression, or inflammation was observed. Additionally, an intramural hemorrhage extended from the site of angioplasty into the stenotic proximal inferior division of the left middle cerebral artery. CONCLUSIONS:Histopathological findings after intracranial angioplasty parallel those in other arterial territories. The implications of these pathological findings on the medical and endovascular treatment of intracranial atherosclerosis are discussed.

BACKGROUND:Obtaining viable informed consent from stroke patients for participation in clinical trials of acute stroke therapies is often problematic because of patients' neurological deficits. Furthermore, obtaining permission from surrogates is often not possible or not legally permissible. SUMMARY OF REVIEW/RESULTS:In 1996 the Food and Drug Administration and Department of Health and Human Services published regulations that allow investigators to conduct emergency research without patient consent under a narrowly defined set of circumstances. We review requirements of these regulations, paying particular attention to how they may be applied in a clinical trial of an acute stroke therapy. CONCLUSIONS:Acute stroke researchers should consider conducting clinical trials with an exception from the informed consent requirement permitted by this law.

OBJECTIVE AND IMPORTANCE/OBJECTIVE:To describe the clinical presentation and endovascular management of peripheral aneurysms of the lateral posterior choroidal artery. Aneurysms in this location are exceptionally rare and optimal treatment may be difficult. CLINICAL PRESENTATION/METHODS:Two patients with peripheral aneurysms of the distal portion of the lateral posterior choroidal artery presented with headaches from extensive intraventricular hemorrhage. INTERVENTION/METHODS:Endovascular surgical therapy by use of superselective n-butylcyanoacrylate embolization of the aneurysm and adjacent distal parent artery was successful in both patients. CONCLUSION/CONCLUSIONS:Patients with peripheral aneurysms of the lateral posterior choroidal artery usually present with intraventricular hemorrhage. They may be difficult to treat by open surgical techniques owing to their intraventricular location and the frequent inability to preserve the parent artery by aneurysm clipping. Instead, it is typical that either proximal parent artery occlusion or aneurysm trapping must be used. An equivalent endovascular surgical technique may be an attractive alternative method of management.

Intra-arterial vasodilators, such as papaverine, have been used to treat cerebrovascular insufficiency. The short biologic half-life, and the vasodilating and neuroprotective properties of adenosine could be useful during the treatment of cerebral ischemia. However, in human subjects a proposed intracarotid dose of 1 mg/min adenosine was ineffective in augmenting cerebral blood flow (CBF). The object of this experiment was to determine the dose-CBF response characteristics of intracarotid adenosine in nonhuman primates. Studies were conducted on five male baboons under isoflurane anesthesia. After transfemoral internal carotid artery cannulation, changes in CBF (intra-arterial 133Xe technique) were determined after intracarotid infusion of saline and three increasing doses of adenosine (0.5, 1.0, and 1.5 mg/min). Each infusion lasted 5 minutes. Data (mean +/- standard deviation) were analyzed by repeated-measure analysis of variance and the post hoc Tukey test. Intracarotid adenosine (0.5, 1.0, and 1.5 mg/min) resulted in a dose-dependent increase in CBF from 22.6 +/- 4 mL/100 g/min at baseline to 50 +/- 15, 65 +/- 22, and 83 +/- 31 mL/100 g/min respectively (n = 5, P < .05 each). No adverse hemodynamic side effects were noted, and animals recovered promptly from anesthesia. The authors conclude that intracarotid adenosine in the range of 0.5 to 1.5 mg/min results in a robust increase in CBF. Based on body weight, intracarotid adenosine in a dose range of 2.5 to 7.5 mg/min may be required to augment CBF in human subjects.

UNLABELLED:Intracarotid infusion of short-acting vasodilators, such as adenosine and nitroprusside, in doses that lack significant systemic side effects, may permit controlled manipulation of cerebrovascular resistance. In this experiment we assessed changes in cerebral blood flow (CBF) after intracarotid infusion of nitroprusside and adenosine. The study was conducted on six adult baboons under isoflurane anesthesia and controlled ventilation. Intracarotid drug infusion protocol avoided hypotension during nitroprusside infusion and tested for autoregulatory vasoconstriction. CBF (intraarterial (133)Xe technique) was measured four times during infusions of 1) intracarotid saline, 2) IV phenylephrine (0.2 microg x kg(-1) x min(-1)) aimed to increase mean arterial pressure by 10-15 mm Hg, 3) IV phenylephrine and intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and 4) intracarotid adenosine (1 mg/min). IV phenylephrine increased mean arterial pressure (69 +/- 8 to 91 +/- 9 mm Hg, P < 0.0001, n = 6), and concurrent infusion of intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with IV phenylephrine or with concurrent infusion of IV phenylephrine and intracarotid nitroprusside. Intracarotid adenosine profoundly increased CBF (from 29 +/- 8 to 75 +/- 32 mL x 100 g(-1) x min(-1); P < 0.0001). In nonhuman primates, intracarotid adenosine increases CBF in doses that lack significant systemic side effects, whereas intracarotid nitroprusside has no effect. Intracarotid adenosine may be useful for manipulating cerebrovascular resistance and augmenting CBF during cerebral ischemia. IMPLICATIONS/CONCLUSIONS:Intraarterial (133)Xe cerebral blood flow (CBF) measurements suggest that intracarotid adenosine, in a dose that lacks significant systemic side effects, profoundly increases CBF, whereas nitroprusside has no effect.(5-12)