Biomedical subjects

T M Sundt

Publications and source records attributed to T M Sundt.

At least 127 records · Page 7Linked to original sources

PubMed1987

Focal cerebral ischemia: pathophysiologic mechanisms and rationale for future avenues of treatment.

Although approximately 500,000 patients suffer from a stroke each year in the United States, treatment of these patients to date has consisted primarily of prevention, supportive measures, and rehabilitation. The modification of experimental cerebral infarction by new pharmacologic agents, along with encouraging results from the restoration of blood flow to areas of focal ischemia in both laboratory and clinical trials, suggests that a more aggressive approach might be considered in selected patients with acute stroke.

Anticoagulants↗

PubMed1987

Regional cerebral blood flow and focal cortical perfusion: a comparative study of 133Xe, 85Kr, and umbelliferone as diffusible indicators.

We report that regional CBF determined by the initial slope technique using 133Xe and 85Kr in cats and rabbits can be significantly influenced by the size of the field of measurement. The clearance curves of umbelliferone, a lipid-soluble intracellular pH fluorescent indicator, from a visually avascular 80-micron field were used to cross-correlate rCBF with focal cortical perfusion. Our findings indicate that in the cat, as the gamma or beta detector's field of volume was reduced, regional CBF (rCBF) measured by intraarterially injected 133Xe or 85Kr decreased in value by 33% and 28%, respectively, and the slope of the rCBF-PaCO2 response curve became less steep by 56% and 45%, respectively. Umbelliferone, measuring a much smaller volume of tissue, showed a lower normocapnic flow and a more oblique PaCO2 response curve. In the rabbits studied, the normocarbic rCBFs and the rCBF-PaCO2 response curves measured with the three techniques corresponded to those measured in the cat. These results suggest that large field/volume measurements assess a measure of flow that is a weighted average of several distinct flow compartments and that these compartments differ in their response to changes in PaCO2.

Animals↗

PubMed1987

Correlation of regional cerebral blood flow (rCBF) with EEG changes during isoflurane anesthesia for carotid endarterectomy: critical rCBF.

A prospective evaluation of regional cerebral blood flow (rCBF) (ipsilateral middle cerebral artery distribution) was determined using a 133Xe clearance technique in 31 ASA P.S. II-III patients anesthetized with isoflurane-50% N2O in O2 for carotid endarterectomy. Each patient was monitored with 16-channel EEG throughout anesthesia and surgery. Critical rCBF was defined as that flow below which EEG signs of ischemia occurred. Critical rCBF (T1/2 method of analysis) was less than 10 ml X 100 g-1 X min-1 (mean +/- SE 5.9 +/- 1.2) in the six patients in whom transient EEG changes occurred at the time of temporary surgical carotid artery occlusion. No EEG changes occurred with occlusion in the other 25 patients; mean (+/- SE) occlusion rCBF in this group was 18.9 +/- 1.3 ml X 100 g-1 X min-1 (P less than 0.001). Preocclusion flows were not significantly different in the two groups. Critical rCBF during isoflurane anesthesia was less than that previously determined during halothane anesthesia (18-20 ml X 100 g-1 X min-1), and is compatible with the effects of isoflurane on CMRO2 and CBF.

Aged↗

PubMed1987

Isoflurane when compared to enflurane and halothane decreases the frequency of cerebral ischemia during carotid endarterectomy.

Data from the records of patients who underwent 2223 carotid endarterectomies at the Mayo Clinic between January 1, 1972, and December 31, 1985, were abstracted to compare the effects of isoflurane, enflurane, and halothane on the critical cerebral blood flow (CBF) (i.e., the CBF below which the majority of patients develop EEG ischemic changes within 3 min of carotid occlusion), the incidence of EEG ischemic changes, and the neurologic outcome. In a total of 2196 of these procedures, the patient received one of the three volatile anesthetics and, in 2010 of these, both the EEG and the CBF were monitored. Chronologically, halothane was the primary agent from 1972-1974; enflurane progressively replaced halothane during 1975-1981; and isoflurane was used almost exclusively since 1982. This analysis confirmed a previous study that the critical CBF during isoflurane anesthesia (703 procedures) was approximately 10 ml X 100 g-1 X min-1, as contrasted to that of approximately 20 ml X 100 g-1 X min-1 during halothane anesthesia (467 procedures). This analysis also established that the critical CBF during enflurane anesthesia (840 procedures) was approximately 15 ml X 100 g-1 X min-1. The incidence of EEG ischemic changes was significantly less (P less than 0.001) during isoflurane anesthesia (18%) than during either enflurane (26%) or halothane (25%) anesthesia. This difference occurred despite the fact that the preoperative risk status was greater in the patients given isoflurane. There was no difference in neurologic outcome between the three anesthetics, and none was expected, since all patients with EEG changes were immediately shunted, if possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1987

Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: investigation of the possible role of xanthine oxidase in chronic vasospasm.

Based on accumulating evidence of the role of xanthine oxidase (XO) in generating oxygen free radicals and causing tissue damage during ischemia, we examined the possible role of XO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). After inducing SAH in dogs by two autologous blood injections 2 days apart, chronic vasospasm of the basilar artery was reliably produced. There was a 3.5-fold elevation in uric acid (UA), the product of XO, in the cerebrospinal fluid (CSF) of these animals. Parenteral administration of allopurinol (i.v., 25 mg/kg, every 6 hours), a specific blocker of XO, successfully abolished the elevation in CSF uric acid levels due to SAH. However, angiographic vasospasm measured on Day 7, morphological changes observed by electron microscope, and elevated CSF prostaglandin levels were not altered by the treatment. It can be concluded that the observed activation of the enzyme XO, which is a well-known source of oxygen free radicals in ischemia in various organs, is not playing a major role in the pathogenesis of chronic cerebral vasospasm in this animal.

Allopurinol↗

PubMed1987

Preliminary report: effects of high dose methylprednisolone on delayed cerebral ischemia in patients at high risk for vasospasm after aneurysmal subarachnoid hemorrhage.

Mounting evidence suggests that chronic cerebral vasospasm may be linked to the inflammatory response that follows subarachnoid hemorrhage. Twenty-one patients judged to be at high risk for vasospasm because of either poor admitting grade or a large amount of subarachnoid blood shown by computed tomography were treated with a course of high dose methylprednisolone, and management results were compared to those of a cohort of contemporary control patients matched for grade, number of hemorrhages, time from hemorrhage to admission, time from hemorrhage to operation, aneurysm location, age, and sex. Patients treated with high dose methylprednisolone were twice as likely to have an excellent result and half as likely to die as those who were not treated. The incidence and severity of delayed cerebral ischemia were reduced in treated patients when compared to control patients. None of the treated patients developed a serious side effect that could be attributed to steroid treatment. These findings are consistent with the conclusion that chronic vasospasm is an inflammatory vasculopathy and suggest that early treatment with high dose methylprednisolone may benefit this high risk group of patients.

Adult↗

PubMed1987

The significance of unruptured intracranial saccular aneurysms.

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.

Adolescent↗

PubMed1987

Treatment of experimental focal cerebral ischemia with mannitol. Assessment by intracellular brain pH, cortical blood flow, and electroencephalography.

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.

Animals↗

PubMed1987

Principles of preparation of vein bypass grafts to maximize patency.

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.

Graft Occlusion, Vascular↗

PubMed1987

Effect of dihydropyridines and diphenylalkylamines on pentylenetetrazol-induced seizures and cerebral blood flow in cats.

Nimodipine, a dihydropyridine that interacts with a Ca++ channel-associated binding site, when delivered (30 to 150 micrograms/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 micrograms/kg, ia). Phenytoin was maximally effective only at nearly lethal doses (90 mg/kg, ia). Verapamil, a diphenylalkylamine 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.

Animals↗

PubMed1987

Cerebral hyperperfusion syndrome: a cause of neurologic dysfunction after carotid endarterectomy.

Neurologic deficits evident when patients initially awaken from surgery are generally due to intraoperative embolization or inadequate cerebral protection in patients with marginal cerebral perfusion; neurologic deficits occurring in the immediate postoperative period are usually related to acute carotid occlusion or embolization. However, in a small subset of patients, transient postoperative neurologic dysfunction seems to be related to a syndrome of cerebral hyperperfusion rather than a lack of adequate cerebral blood flow. This study describes the courses of 10 patients with classic findings of cerebral hyperperfusion syndrome. Typically, this syndrome occurred in patients with longstanding severe chronic cerebral ischemia and occurred after correction of a very high-grade carotid stenosis. Intraoperatively, there was often a dramatic increase in xenon-labeled cerebral blood flows, with postocclusion flows sometimes attaining three to four times baseline levels. Postoperatively, the patients initially did well. However, over the next several days, many of them began to complain of unilateral headache on the operated side and subsequently had seizures. Electroencephalography obtained during this period uniformly revealed periodic lateralizing epileptiform discharges on the side of the brain ipsilateral to the endarterectomy. Although neurologic dysfunction fully resolved in all of the patients in this group, it is possible that intracerebral hemorrhage may occur in some patients with hyperperfusion syndrome. The pathophysiology of this syndrome is believed to be related to preoperative loss of cerebral autoregulatory mechanisms caused by chronic cerebral ischemia.

Adult↗

PubMed1986

Inhibition of electrically induced seizures by a dihydropyridine calcium channel blocker.

Nimodipine, a calcium channel blocker with high affinity for central dihydropyridine Ca2+ channels, produced a dose-dependent suppression of electrically induced seizures in the rabbit. Verapamil, a diphenylalkylamine which acts at peripheral Ca2+ channels, was ineffective. Phenytoin was less effective than nimodipine. These results suggest that calcium flux into neurons may be a biochemical precipitant for seizure genesis. Centrally acting calcium channel blockers may prove to be a new class of anticonvulsants.

Animals↗

PubMed1986

Effect in cat of locus coeruleus lesions on the response of cerebral blood flow and cardiac output to altered paCO2.

In pentobarbital-anesthetized cats, over arterial paCO2 values of 20-60 mm Hg, cerebral blood flow (CBF, Xenon) and cardiac output (CO, thermal dilution) show positively inflicted curves with slopes significantly greater than zero. To examine the role of the locus coeruleus (LC) in these responses, bilateral stereotactic thermo-coagulation lesions of the LC were made. The effect of lesions confirmed to involve the LC bilaterally (n = 10), were compared with the effects of misdirected lesions placed in the cerebellum and lateral to the LC (n = 10) and sham lesions (n = 10). Ten days after the lesioning procedure, the animals were re-anesthetized with pentobarbital and paCO2 response curves were determined for CBF and CO prior to and following intravenous administration of propranolol (1 mg/kg, i.v.). The results obtained with the sham-operated animals and the animals with lesions outside of the LC were indistinguishable. Bilateral LC lesions had no significant effect on normocapnic CBF as compared to control animals. They did, however, significantly reduce the slope of the CBF paCO2 response curve. Propranolol produced a significant reduction in CBF in lesioned and non-lesioned animals measured at all levels of pCO2 and did not alter the slope of the pCO2 response curve for any group as compared to predrug values. Bilateral lesions of the LC did not significantly alter either normocapnic CO or the slope of the CO-paCO2 relationship, but did reduce the elevation in mean arterial blood pressure otherwise observed during hypercarbia. Measurement of norepinephrine levels in cortex indicate a close correlation between the ability of the lesion to reduce norepinephrine content and produce the observed physiological effects. The results of these experiments suggest that the hypercapnic response of CBF, but not CO to arterial paCO2 is modulated by systems which traverse the dorsal brainstem. The role of the locus coeruleus-catecholamine cell bodies in this effect, however, must be considered speculative until further transmitter-selective interventions are carried out.

Animals↗

PubMed1986

Minimal oculomotor nerve paresis secondary to unruptured intracranial aneurysm.

In 12 patients with minimal oculomotor nerve deficits due to unruptured intracranial aneurysm, the nerve-related findings were incomplete and at least one element (ptosis, mydriasis, or extraocular muscle weakness) was spared in every patient. Although symptomatic, the affected cranial nerve III functions were only partially lost. Six patients had ptosis and mydriasis, three had ptosis and diplopia, two had mydriasis and diplopia, and one had mydriasis alone. Eleven patients had accompanying headaches that were remarkably variable and difficult to categorize. Cerebral angiography showed the aneurysms, but computed tomography missed one third of them. The symptomatic aneurysm arose from the internal carotid artery in six patients, and from the distal basilar artery in six. Fragments of a cranial nerve III palsy associated with recent onset and ipsilateral headache suggest an enlarging internal carotid or distal basilar artery aneurysm.

Adult↗

PubMed1986

Spontaneous dissection of the cervical internal carotid artery.

We studied 36 patients (21 women and 15 men) with spontaneous dissection of the internal carotid arteries. The ages of these patients ranged from 21 to 63 years. Focal unilateral headache was the most common symptom. Other common clinical manifestations (in decreasing order of frequency) included focal cerebral ischemic symptoms, oculosympathetic paresis, bruits, light-headedness, and neck pain. Less common symptoms were syncope, amaurosis fugax, scalp tenderness, swelling in the neck, and dysgeusia. Common angiographic manifestations (in decreasing order of frequency) were elongated, irregular, and frequently tapered narrowing of the lumen; abrupt luminal reconstitution (often at the carotid canal); aneurysms; intimal flaps; slow internal carotid artery--middle cerebral artery flow; tapered occlusion; and distal branch occlusions. The incidence of hypertension in these patients was considerably higher than that in the general population. Angiographic evidence of fibromuscular dysplasia was found in 14% of the patients, but atherosclerotic changes were uncommon. Follow-up ranged from 14 to 140 months (mean, 58.5 months). Twenty-three patients with 29 dissected internal carotid arteries were also restudied angiographically. The stenosis of the internal carotid artery either completely resolved or substantially improved in more than 85% of the dissected vessels. About two-thirds of the dissecting aneurysms either resolved or decreased in size. Clinically more than 85% of the patients had an excellent or complete recovery. Recurrence of the dissection or rupture of a dissecting aneurysm was not noted. Despite their disconcerting appearance on angiography, spontaneous dissections of the internal carotid arteries are often associated with a good prognosis.

Adult↗

PubMed1986

Selective central nervous system calcium channel blockers--a new class of anticonvulsant agents.

Current research suggests that Ca2+ flux into the neuron may be a critical factor in the genesis of seizures. We report herein the influence of nimodipine, a selective central nervous system calcium channel blocker, in 60 rabbits with seizures that had been induced through ischemia, postischemia reperfusion, pentylenetetrazol, and bicuculline. In 30 animals subjected to 4 hours of ischemia, 9 of the 15 control animals had seizures in comparison with 1 of the 15 treated animals (P less than 0.005). Five animals with reperfusion seizures demonstrated similar results. In 10 animals in which a convulsant was applied topically to both cerebral hemispheres, unilateral intracarotid injection of nimodipine arrested seizures in that hemisphere alone, whereas the control contralateral hemisphere continued to have electrical seizure activity (P less than 0.001). Both placebo and verapamil were ineffective. These results suggest that Ca2+ influx is a common biochemical precipitant for various types of experimental seizures. Selective central nervous system calcium channel blockers may prove to be a new class of anticonvulsant agents.

Animals↗

PubMed1986

Intracellular brain pH, indicator tissue perfusion, electroencephalography, and histology in severe and moderate focal cortical ischemia in the rabbit.

Intracellular brain pH and indicator tissue perfusion were measured with a lipid-soluble, pH-sensitive fluorescent indicator in 10 rabbits who had either severe or moderate focal ischemia depending on whether the middle cerebral artery was occluded at its main trunk or bifurcation. Preocclusion tissue indicator perfusion was 50.1 ml/100 g/min and intracellular brain pH was 7.03. In severe focal ischemia, immediate postocclusion tissue perfusion was 12.7 ml/100 g/min and intracellular brain pH was 6.64. Four hours after occlusion, the perfusion was 5.2 ml/100 g/min and intracellular brain pH was 6.08. There was EEG and histological confirmation of infarction. In the moderate focal ischemia group, immediate postocclusion flow was 20.0 ml/100 g/min and intracellular brain pH was 6.92. At 3 h, postocclusion tissue perfusion was 22.6 ml/100 g/min and intracellular brain pH was 6.86. Therefore, for the first 3 h, this ischemic penumbra was stable. At the fourth hour, both cerebral tissue perfusion and intracellular brain pH worsened. This suggests that the ischemic penumbra is a dynamic state. The rabbit is a good experimental model for the production of both severe and moderate focal ischemia.

Animals↗

PubMed1986

Emergency carotid endarterectomy for patients with acute carotid occlusion and profound neurological deficits.

Emergency revascularization procedures for patients with acute stroke are controversial. Thirty-four patients with acute internal carotid artery occlusion documented at the time of emergency endarterectomy were analyzed. Before operation, all these patients had profound neurological deficits including hemiplegia and aphasia. There was a 94% success rate in restoring patency. In follow-up, nine patients (26.5%) had a normal neurological exam, four (11.8%) had a minimal deficit, 10 (29.4%) had a moderate hemiparesis, which was improved over their preoperative deficit, 4 (11.8%) remained hemiplegic, and seven (20.6%) died. The natural history of patients with acute carotid occlusion and profound neurological deficits is dismal. In comparison, 13 patients (38%) made a dramatic recovery. The surgical mortality rate compares favorably with the natural history. Good collateral flow was a good prognostic factor, while a simultaneous middle cerebral artery embolus was associated with a poorer prognosis. An emergency carotid endarterectomy may be indicated in selected patients with acute internal carotid artery occlusion with profound neurological deficits. Full preoperative angiography may identify those patients who would benefit from surgical intervention and reduce the operative mortality rate.

Aged↗