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David G. Piepgras, Michael K. Morgan, Thoralf M. Sundt Jr., Takehiko Yanagihara and Lynn M. Mussman

✓ A series of 14 patients with intracerebral hemorrhage after carotid endarterectomy is reviewed. This complication occurred in 0.6% of 2362 consecutive carotid endarterectomies performed at the Mayo Clinic from 1972 through 1986. All hemorrhages occurred within the first 2 weeks after operation and were ipsilateral to the side of the operation. Eight patients died, and only two made a good recovery. Significant risk factors are hypertension and chronic hemispheric hypoperfusion with impaired autoregulation. The “normal pressure-hyperperfusion breakthrough” syndrome was considered to be operative in 12 of the 14 patients. Nine patients had documented hyperperfusion (at least 100% increase of baseline cerebral blood flow) at the time of surgery. In an additional three patients, normal perfusion-pressure breakthrough was inferred by the clinical course and radiological findings, as well as by the absence of alternative explanations. Patients at risk for postendarterectomy intracerebral hemorrhage include those who have a clinical history suggestive of hemodynamic cerebral ischemia, severe carotid stenosis with limited hemispheric collateral flow, and postendarterectomy hyperperfusion, as measured by intraoperative cerebral blood flow. To minimize the risk of hemorrhage in these patients, strict maintenance of blood pressure at normotensive or even relatively hypotensive levels during the intraoperative and early postoperative periods is advised.

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Max E. Ots, Tony L. Yaksh, Robert E. Anderson and Thoralf M. Sundt Jr.

✓ Nimodipine, a dihydropyridine that interacts with a Ca++ channel-associated binding site, when delivered (30 to 150 µg/kg) intra-arterially (ia) to enflurane-anesthetized cats, produced a dose-dependent suppression of seizures evoked by pentylenetetrazol. A comparable suppression was produced by clonazepam (1 to 30 µg/kg, ia). Phenytoin was maximally effective only at nearly lethal doses (90 mg/kg, ia). Verapamil, a diphenyl-alkylamine that interacts with a separate Ca++ channel-associated site, at the maximum nonlethal dose (6 mg/kg, ia) resulted in a mild facilitation of seizure activity. The drug vehicle used in these studies (50% polyethylene glycol-400) had no effect when given alone. Regional cerebral blood flow (rCBF) as measured by the clearance of xenon-133 was markedly elevated immediately after the onset of seizure activity (89 ± 3 to 168 ± 4 ml/100 gm/min). Concurrent with their resolution of the seizure activity, both nimodipine and clonazepam reduced rCBF to near preseizure levels and preserved the rCBF response to hypercarbia which would otherwise have been abolished following prolonged seizure activity. Moreover, the effect of nimodipine on rCBF and seizures occurred without any prominent alterations in mean arterial blood pressure as compared to preseizure levels. These data support the proposition that a dihydropyridine Ca++ channel binding site may play a role in modulating paroxysmal neuronal activity, and suggest that this class of agents may reflect a novel group of antiepileptic drugs.

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Thoralf M. Sundt III and Thoralf M. Sundt Jr.

✓ Experience in cardiovascular and peripheral vascular surgery with saphenous vein bypass conduits is reviewed. It is clear that meticulous technique and graft preparation are crucial to short-term and long-term patency. The risk of early thrombosis is related to damage to the graft 's native intima, graft flow, and coagulability of the patient 's blood. Attention to atraumatic harvesting techniques and perfection of anastomoses are crucial to minimizing intimal damage. Graft inflow and outflow are fundamental principles. The use of vitamin K antagonists and platelet inhibitors may improve graft survival. Subacute occlusion is related to structural alterations in the grafts themselves. These include intimal hyperplasia and medial fibrosis as the grafts become “arterialized,” valve fibrosis, aneurysmal dilatation, clamp stenosis, and suture stenosis. Long-term patency is threatened primarily by atherosclerosis in the graft itself. There is some evidence that care in vein harvesting and implantation as well as the use of anticoagulant agents affect the development of this complication.

A technique for graft preparation is presented that is based on the experience of the authors in harvesting grafts for both cerebral and coronary bypass conduits.

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David O. Wiebers, Jack P. Whisnant, Thoralf M. Sundt Jr. and W. Michael O'Fallon

✓ The authors report the results of a long-term follow-up study of 130 patients with 161 unruptured intracranial saccular aneurysms. Their findings suggest that unruptured saccular aneurysms less than 10 mm in diameter have a very low probability of subsequent rupture; The mean diameter of the aneurysms that subsequently ruptured was 21.3 mm, compared with a diameter of 7.5 mm for aneurysms defined after rupture at the same institution. Part of the explanation for this discrepancy may be that the size of the filling compartment of the aneurysm decreases after rupture. There is also evidence from the present study that intracranial saccular aneurysms develop with increasing age of the patient and stabilize over a relatively short period, if they do not initially rupture, and that the likelihood of subsequent rupture decreases considerably if the initial stabilized size is less than 10 mm in diameter. Consequently, the critical size for aneurysm rupture is likely to be smaller if rupture occurs at the time of or soon after aneurysm formation. There seems to be a substantial difference in potential for growth and rupture between previously ruptured and unruptured aneurysms.

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Treatment of experimental focal cerebral ischemia with mannitol

Assessment by intracellular brain pH, cortical blood flow, and electroencephalography

Fredric B. Meyer, Robert E. Anderson, Thoralf M. Sundt Jr. and Tony L. Yaksh

✓ Intracellular brain pH, cortical blood flow (CBF), and electrocorticograms were recorded in regions of severe and moderate ischemia in 10 control rabbits and 10 rabbits given mannitol, 1 gm/kg, after occlusion of a major branch of the middle cerebral artery. Pooling the data from all 20 animals, preocclusion CBF was 46.4 ±3.6 ml/100 gm/min and intracellular brain pH was 7.01 ± 0.04 (means ± standard error of the means). Although mannitol administration mildly improved CBF in regions of severe ischemia, this increase was not sufficient to prevent metabolic deterioration as assessed by brain pH. However, in regions of moderate ischemia, CBF improved significantly with mannitol and the gradual decline in brain pH observed in control animals was prevented. For example, in the treated moderate ischemia sites 4-hour postocclusion CBF and pH values were 31.8 ml/100 gm/min and 6.89 ± 0.09, respectively, as compared to control values of 14.3 ml/ 100 gm/min and 6.75 ± 0.06. These results suggest that mannitol may be of benefit in stabilizing regions of moderate, but not severe, ischemia after vessel occlusion.

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W. Richard Marsh, Robert E. Anderson and Thoralf M. Sundt Jr.

✓ The adverse effect of a minimal cerebral blood flow (CBF) in models of global ischemia has been noted by many investigators. One factor believed important in this situation is the level of blood glucose, since a continued supply of this metabolite results in increased tissue lactate, decreased brain pH, and increased cell damage. The authors have extended these observations to a model of focal incomplete ischemia. Brain pH was measured in fasted squirrel monkeys in regions of focal incomplete ischemia after transorbital occlusion of the middle cerebral artery (MCA). In both control and hyperglycemic animals, CBF was reduced to less than 30% of baseline. At 3 hours after MCA occlusion, brain pH in the control group was 6.66 ± 0.68 as compared to 6.27 ± 0.26 in the glucose-treated group. This difference was statistically significant by Student's unpaired t-test (p < 0.05). Thus, hyperglycemia results in decreased tissue pH in regions of focal incomplete cerebral ischemia in monkeys.

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Thoralf M. Sundt Jr., David G. Piepgras, W. Richard Marsh and Nicolee C. Fode

✓ The authors report their experience with the use of saphenous vein bypass grafts for treating advanced occlusive disease in the posterior circulation (77 patients, all of whom had failed medical management and showed severe ischemic symptoms), deteriorating patients with giant aneurysms of the posterior circulation (nine patients), progressive ischemia in the anterior circulation (26 patients, none of whom had a normal examination), and giant aneurysms in the anterior circulation (20 patients, all of whom presented with mass effect or subarachnoid hemorrhage). Graft patency in the first 65 cases treated was 74%. However, after significant technical changes of vein-graft preparation and construction of the proximal anastomosis, patency in the following 67 cases was 94%. Excellent or good results (including relief of deficits existing prior to surgery) were achieved in 71% of patients with advanced occlusive disease in the posterior circulation, 44% of those with giant aneurysms of the posterior circulation, 58% of those with ischemia of the anterior circulation, and 80% of those with giant aneurysms of the anterior circulation. Mean graft blood flow at surgery in the series was 100 ml/min for posterior circulation grafts and 110 ml/min for anterior circulation grafts. Experience to date indicates that this is a useful operation, and is particularly applicable to patients who are neurologically unstable from advanced intracranial occlusive disease in the posterior circulation or with giant aneurysms in the anterior circulation. The risk of hyperperfusion breakthrough with intracerebral hematoma restricts the technique in patients with progressing ischemic symptoms in the anterior circulation, and the intolerance of patients with fusiform aneurysms in the posterior circulation to the iatrogenic vertebrobasilar occlusion limits the applicability of this approach to otherwise inoperable lesions in that system.

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Thoralf M. Sundt Jr. and George Kees Jr.

✓ The authors have designed a miniclip and a microclip for occlusion of small perforating vessels deep in the operative wound. These clips are intended for permanent occlusion but may be used for temporary hemostasis.