Biomedical subjects

C E Gross

Publications and source records attributed to C E Gross.

At least 19 recordsLinked to original sources

PubMed1995

U83836E reduces secondary brain injury in a rabbit model of cryogenic trauma.

Oxygen-derived free radicals have been implicated in secondary brain injury after head trauma. Although oxygen-free radicals may be derived from multiple sources, the activation and accumulation of neutrophils in areas of brain injury is a potential source of deleterious inflammatory mediators, including free radicals, which may exacerbate the primary insult. Neutrophils may also impede the cerebral microcirculation by congestion and occlusion of postcapillary venules. The lazaroid U83836E is a potent-free radical scavenger that inhibits lipid peroxidation. U83836E was studied in a cryogenic model of cerebral injury in pretreatment paradigm. Fifteen rabbits received a unilateral cryogenic brain lesion. Six animals received U83836E, and nine animals received vehicle only. Arterial blood gases, hematocrit, temperature, and mean arterial pressure were controlled in physiologic range throughout the experiment. Intracranial pressure was continuously monitored. Lesion size was determined by triphenyltertrazolium chloride staining and planimetric image analysis. Neutrophil aggregation and oxygen-free radical generation was assessed in whole blood by impedance aggregometry and simultaneous luminol-mediated chemiluminescence, respectively. Myeloperoxidase assay was used to determine neutrophil accumulation within the brain. Elevations in intracranial pressure from baseline values were significantly greater in the untreated (control) animals at all time points (p < 0.0001). Mean lesion size (% hemisphere +/- SEM) was significantly reduced in animals receiving U83836E (4.41 +/- 0.64, n = 6) when compared with controls (15.09 +/- 2.28, n = 9, p < 0.001). A reduction in both the release of oxygen-free radicals and in neutrophil aggregation following the cryogenic injury in the U83836E animals correlated with a smaller lesion volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Intravenous aspirin causes a paradoxical attenuation of cerebrovascular thrombolysis.

BACKGROUND AND PURPOSE: Aspirin treatment is recognized as an advantageous adjunct to thrombolytic agents in myocardial infarct patients. In this study we examined the effects of aspirin on the rate of clot lysis and on the frequency and extent of hemorrhagic transformations in rabbit models of embolic stroke. METHODS: Rabbit models of ex vivo platelet aggregation and cutaneous template bleeding times were used to show the anticoagulant effects of aspirin in our experimental paradigm. We monitored tissue-type plasminogen activator (TPA)-induced clot lysis in two rabbit models of embolic stroke by (1) scintigraphically following the dissolution of a 99mTc-tagged clot or (2) using roentgenography to follow the disappearance of an Sn-tagged clot. RESULTS: In animals pretreated (18 hours) with a single administration of aspirin (1, 5, or 20 mg/kg IV) or 1 mg/kg per day for 3 days, the aggregation response of platelets to collagen (3.3 micrograms/mL) or arachidonic acid (0.5 mmol/L) was attenuated. High-dose aspirin also increased ear template bleeding time from 1.6 to 2.6 minutes. When aspirin (20 mg/kg) was administered 18 hours before embolism and subsequent lysis with TPA (0.3 mg/kg bolus; 3 mg/kg per hour IV), the pretreatment significantly antagonized the rate and extent of TPA-induced clot lysis by up to 70%. This was confirmed in a second embolic stroke model. The suppression of TPA-induced lysis was reversed by administration of the prostacyclin analogue iloprost (10 micrograms/kg per hour) directly into the cerebral circulation. CONCLUSIONS: We conclude that aspirin reduces the effects of TPA in embolic stroke models. This effect may be the result of a loss of endothelial prostacyclin production since the effect is reversed by iloprost.

Animals↗

PubMed1995

Delayed tissue-plasminogen activator therapy in a rabbit model of thromboembolic stroke.

This study investigated the efficacy and safety of delayed therapy with tissue-plasminogen activator (t-PA) in a rabbit model of thromboembolic stroke. The t-PA therapy was started 3, 4, or 5 hours after autologous clot embolization. New Zealand rabbits were randomized to receive a 2-hour intravenous infusion of either t-PA (6.3 mg/kg) or a saline solution (0.9% saline) after an autologous clot had embolized the anterior cerebral circulation. Regional cerebral blood flow (rCBF), intracranial pressure (ICP), and infarct size were measured to determine the effects of the delayed administration of the t-PA after intracranial embolization. Additionally, the following physiological parameters were monitored throughout the protocol: mean arterial pressure, hematocrit, arterial blood gases, glucose, and core and brain temperatures. All animals were studied for 4 hours after the administration of the t-PA or control solution; thus, the duration of each experiment was 7, 8, or 9 hours after autologous clot embolization. In control animals, brain infarct size and final ICP values were directly related to the length of time studied after clot embolization; among control animals, the largest infarct size and greatest rise in ICP were seen 9 hours after embolization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Detection of circle of Willis aneurysms in patients with acute subarachnoid hemorrhage: a comparison of CT angiography and digital subtraction angiography.

OBJECTIVE: The purpose of this study was to compare CT angiography with digital subtraction angiography (DSA) in the detection and measurement of intracranial aneurysms in patients with acute subarachnoid hemorrhage. SUBJECTS AND METHODS: Thirty consecutive patients with recent subarachnoid hemorrhage shown by unenhanced CT scanning or lumbar puncture were studied with CT angiography and DSA. Using a shaded surface display format and source images, two reviewers working independently blindly interpreted CT angiograms for presence and size of aneurysms. Sensitivity and specificity for aneurysm detection were calculated for each reviewer. Aneurysm size measurements were compared between reviewers and between the two imaging techniques. RESULTS: Thirty aneurysms were found in 22 patients with DSA; eight patients had no aneurysms. The sensitivity and specificity of CT angiography for reviewer A were 0.97 and 1.0, respectively. For reviewer B, the sensitivity and specificity were 0.77 and 0.87, respectively. All cases with single aneurysms on DSA (18 patients) had surgical confirmation of aneurysm location and rupture. In each case with multiple aneurysms (four patients), the aneurysm thought responsible for the hemorrhage was surgically confirmed. In those cases with no aneurysms found on DSA, follow-up DSA studies did not reveal additional findings. Differences between reviewers in aneurysm size measurements made with CT angiography were not significant (p = .10). Mean aneurysm measurements for reviewer A, reviewer B, and DSA were 6.6 mm, 7.0 mm, and 6.9 mm, respectively. CONCLUSION: CT angiography shows potential in the detection and measurement of aneurysms in patients with acute subarachnoid hemorrhage when compared with DSA.

Acute Disease↗

PubMed1994

Comparison of triphenyltetrazolium dye with light microscopic evaluation in a rabbit model of acute cerebral ischaemia.

The present study was performed to compare brain infarct size assessment by routine histology (haematoxylin and eosin) and by 2,3,5-triphenyltetrazolium chloride staining techniques. New Zealand white rabbits were subjected to autologous clot embolization to the anterior circulation of the brain. After a study period of 7-8 h the brains were harvested and serially sectioned in the coronal plane. Brain slices were then immersed in a 1% triphenyltetrazolium chloride dye. Following visualization of the infarcted region, the brains were immediately placed in 10% formalin and later prepared for histologic evaluation by routine haematoxylin and eosin. The two methods were compared for their ability to estimate infarct size by an independent observer. There was excellent correlation between the two methodologies; infarct sizes of 57.4 +/- 5.0% versus 55.9 +/- 5.4% (mean +/- SEM, p < 0.007, r = 0.73, n = 12; expressed as percentage of the hemisphere infarcted) were noted for light microscopic evaluation versus triphenyltetrazolium chloride staining, respectively. It is concluded that triphenyltetrazolium chloride staining is an acceptable method for delineating brain infarct size in this rabbit model of thromboembolic stroke. The relative ease of infarct size determination with this technique suggests its more widespread use in similar models.

Animals↗

PubMed1994

TGF-beta 1 post-treatment in a rabbit model of cerebral ischaemia.

Transforming growth factor-beta 1 (TGF-beta 1), suggested in some studies to suppress astrocyte and neutrophil function, has also reduced ischaemic brain injury when administered immediately prior to clot embolization in models of thromboembolic stroke. The effect of TGF-beta 1 as a post-treatment paradigm was investigated in a rabbit model of thromboembolic stroke. Following clot embolization, regional cerebral blood flow fell to < 10 cc 100 g-1 min-1 in all animals. TGF-beta 1 (10 micrograms) or vehicle (n = 5 each group) was infused via the contralateral carotid artery. TGF-beta 1 administration resulted in a rapid and selective reduction in the peripheral neutrophil count as compared to a significant (p < 0.05) increase in control values (2336 +/- 817 vs 4320 +/- 928 neutrophils mm3, mean +/- SEM). Neutrophil aggregation was increased within 30 min of TGF-beta 1 infusion when compared to control (2.07 +/- 0.70 vs 1.09 +/- 0.17 ohms, p < 0.05); neutrophil chemiluminescence, an index of the oxygen respiratory burst was not significantly affected by TGF-beta 1 administration. No difference in platelet counts or aggregation was noted. There was no significant difference between the two groups regarding brain infarct size (47.5 +/- 10.9 vs 56.5 +/- 10.4, n = 4, TGF-beta vs control, mean +/- SEM), intracranial pressure, or brain excitatory amino acid levels (aspartate and glutamate) within ischaemic regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

Tissue plasminogen activator: comparison of dose and route of administration in a rabbit model of thromboembolic stroke.

The thrombolytic activity of tissue plasminogen activator was evaluated in a rabbit model of thromboembolic stroke using both various concentrations (3, 5, and 10 mg/kg; 20% bolus with the remaining 80% given over 30 min.) and routes of administration (intravenous versus regional intra-arterial). An autologous tin-tagged clot was embolized to the brain via the carotid artery. Tissue plasminogen activator was then given at the doses and routes noted (n = 3 in all groups). Thrombolytic activity was followed by serial x-rays of the tin-laden clot over a four-hour period. The brains were then removed and subjected to gross inspection. Only the intravenous dose of 5 mg/kg tissue plasminogen activator produced greater than 50% clot lysis in all animals. Doses of t-PA higher (10 mg/kg) or lower (3 mg/kg) than this were less effective in producing thrombolysis, demonstrating greater than 50% clot lysis in only one animal of each group. We conclude that in this model of thromboembolic stroke the intravenous administration of tissue plasminogen activator is more effective than intra-arterial, and that the optimal dose is in the range of 5 mg/kg.

Animals↗

PubMed1993

Transforming growth factor-beta 1 reduces infarct size after experimental cerebral ischemia in a rabbit model.

BACKGROUND AND PURPOSE: The aim of this study was to examine the effect of transforming growth factor-beta 1, a cytokine shown to amelioriate cardiac ischemia, in a rabbit model of thromboembolic stroke. METHODS: An autologous clot embolus was introduced intracranially through the right internal carotid artery in 21 New Zealand White rabbits, with seven in each group receiving either vehicle control (albumin) or 10 or 50 micrograms transforming growth factor-beta 1 administered as an intracarotid bolus immediately before autologous clot embolization. Multiple physiological parameters were monitored, including regional cerebral blood flow, arterial blood gases, hematocrit, glucose, core temperature, and mean arterial pressure. The brain was harvested 4 hours after embolization, and infarct size was determined planimetrically as a percentage of the entire hemisphere. RESULTS: Brain infarct size was reduced in both the 10-microgram (16.7 +/- 4.0% [mean +/- SEM], p < 0.05) and 50-microgram (21.7 +/- 4.5%) transforming growth factor-beta 1-treated groups when compared with the control group (31.9 +/- 6.6%). Regional cerebral blood flow did not show any significant intergroup or intragroup variation over time, although the 10-microgram transforming growth factor-beta 1 group experienced a greater return of cerebral blood flow in the first 2 hours after embolization. CONCLUSIONS: Transforming growth factor-beta 1 reduced brain infarct size in a rabbit model of thromboembolic stroke. This effect was not related to a direct effect on blood flow. Studies are ongoing to determine the mechanism by which transforming growth factor-beta 1 salvages ischemic brain.

Animals↗

PubMed1992

In vitro evidence supporting two mechanisms of action for the anion transport inhibitor L-644,711 in cerebral ischaemia.

L-644,711 is a novel anion channel inhibitor which has previously been shown to decrease brain injury in two related rabbit models of cerebral ischaemia. We hypothesize two mechanisms of action of L-644,711 for its salutary effects on cerebral ischaemia: inhibition of neutrophil function and prevention of excitotoxin release from astrocytes. We present in vitro evidence supporting these two mechanisms of action. L-644,711 demonstrated a dose dependent inhibition of fMLP-induced neutrophil aggregation and superoxide anion release. In addition, L-644,711 demonstrated a dose dependent inhibition of glutamate release from swollen astrocytes in primary culture. We conclude that L-644,711 may prevent brain injury in cerebral ischaemia by inhibiting neutrophil function and preventing release of glutamate from swollen astrocytes.

Animals↗

PubMed1992

A non-linear haemodynamic model for the arterial pulsatile component of the intracranial pulse wave.

An indication that pressure pulses in cerebral arteries may play a role in the configuration of intracranial pressure pulsations is given by the observation that vasospasm of cerebral arteries narrows the amplitude of the intracranial pressure wave. The present work develops a mathematical model for the transmission of arterial pressure pulses across the compliant arterial wall to the surrounding intracranial space. Compliance of both the arterial segment and the intracranial space are considered. So as to retain accuracy at higher values of the mean intracranial pressure, a physiological range in which pulse transmission is enhanced due to lower pressure gradients but intracranial compliance is not necessarily decreased, a logistic fit is used to model the intracranial pressure-volume relationship. A sequence of approximations (with error bounds) is obtained for the induced intracranial pressure pulse amplitude as a function of arterial pulse amplitude, mean transmural pressure, and mean intracranial pressure. It is found that at higher mean intracranial pressures, where the usual exponential assumption for the intracranial pressure-volume curve loses validity, the amplitude of the transmitted arterial pressure pulse depends non-linearly on the mean intracranial pressure.

Animals↗

PubMed1992

Orbital paraganglioma: case report and review of the literature.

Paragangliomas of the orbit are extremely rare. A case of an orbital paraganglioma, including the first magnetic resonance imaging description of this tumour is described here. The patient underwent surgery with gross total removal of the tumour and relief of his initial chief complaint of visual blurring. The differential diagnosis and therapeutic options for the management of this tumour are discussed.

Humans↗

PubMed1992

Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711.

BACKGROUND AND PURPOSE: We studied the anion transport inhibitor L-644,711, which is known to reduce astrocyte swelling and excitotoxin release in primary astrocyte culture, in two models of thromboembolic stroke to assess its capacity to influence ischemic brain injury. METHODS: New Zealand White rabbits were used in this study. The two models include autologous clot embolized to the brain via the carotid artery, with one model using a transient period of systemic hypotension. Cerebral blood flow was determined by the hydrogen clearance method, intracranial pressure was measured with a fiberoptic transducer, and infarct size was assessed with triphenyltetrazolium chloride staining of the coronally sectioned brain. Both models received a 2-hour infusion of L-644,711 (total dose, 12 mg/kg) beginning 20 minutes before embolization. RESULTS: In both the normotensive (p less than 0.01) and the hypotensive (p less than 0.05) model, treatment with L-644,711 resulted in a significant reduction in infarct size and a significant improvement in regional cerebral blood flow (p less than 0.03, normotensive model, and p less than 0.05, hypotensive model). Raised intracranial pressure, unique to the hypotensive model, was abolished by the administration of L-644,711 (p less than 0.05). A hyperglycemic response associated with embolization, also unique to the hypotensive model, was significantly reduced by the administration of L-644,711 (p less than 0.05). CONCLUSIONS: The ability of L-644,711 to limit brain injury in two related models of thromboembolic stroke suggests a potential therapeutic role for anion channel blockers in cerebral ischemia.

Animals↗

PubMed1992

The effect of the 21-aminosteroid U74006F in a rabbit model of thromboembolic stroke.

U74006F, a novel 21-aminosteroid, is an inhibitor of iron-dependent lipid peroxidation that is devoid of glucocorticoid and mineralocorticoid side effects. The efficacy of U74006F in reducing cerebral infarct size was investigated in a rabbit model of thromboembolic stroke. Each animal received either U74006F (3.0 mg/kg immediately before and 2 hr after embolization, n = 8) or vehicle control (n = 10). Hematocrit, mean arterial pressure, PCO2, PO2, and pH were measured and controlled both before and after the administration of an autologous clot into one internal carotid artery. Regional cerebral blood flow (in ml/100 g/min, mean +/- SEM) measured by hydrogen clearance was similar in both groups, being reduced from 68.2 +/- 9.6 to 5.2 +/- 1.9 in the control group immediately after clot embolization and from 73.3 +/- 14.9 to 7.0 +/- 1.7 in the U74006F group. Four hours after embolization the brain was harvested and cerebral infarct size was determined using the triphenyl-tetrazolium chloride technique (% hemisphere, mean +/- SEM). In the U74006F-treated group, the infarct size was significantly reduced (P < 0.05) to 14.8 +/- 6.4 from a control value of 36.0 +/- 6.4. Additionally, cerebral blood flow values after embolization were consistently higher in the U74006F group, although the differences were not statistically significant. This data suggests that the 21-aminosteroid U74006F may have a protective effect in cerebral ischemia.

Animals↗

PubMed1991

The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.

Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.

Animals↗

PubMed1990

Increased cerebral blood flow in idiopathic pseudotumour cerebri.

Cerebral blood flow was studied in nine patients with idiopathic pseudotumour and one patient with cortical vein thrombosis in Denver, Colorado using the 133Xe inhalation method. Globally elevated blood flows were found in all of the idiopathic pseudotumour patients averaging 149% of control values generated in the same setting. The patient with the cortical vein thrombosis demonstrated normal global flows. Possible pathophysiological mechanisms for these findings are discussed.

Adult↗

PubMed1990

Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke.

Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.

Animals↗

PubMed1988

Colloidal volume expansion during acute cerebral ischaemia: assessed by local cerebral blood flow and computerized power ratio index.

Colloidal volume expansion during acute cerebral ischaemia was assessed by local cerebral blood flow (CBF) and the power ratio index (PRI) in 8 anaesthetized Macaque monkeys. Focal cerebral ischaemia was produced by right middle cerebral artery occlusion. The animals were then volume expanded (to maximum cardiac output) with 6% hetastarch and then exsanguinated to baseline cardiac output. During volume expansion, local CBF in the ischaemic hemisphere increased from 25 +/- 12 to 39 +/- 23 cc/100 g/min (p less than 0.01) and during exsanguination decreased to 32 +/- 18 cc/100 g/min. Local CBF did not change significantly in the nonischaemic hemisphere. EEG power data, as assessed by PRI [(delta + theta power/alpha + beta power) x 100] changed significantly during blood volume manipulation. The mean PRI value in the right hemisphere deteriorated by increasing from 65 +/- 22 to 94 +/- 25 (p less than 0.01) following vessel occlusion but improved by decreasing to 81 +/- 23 (p less than 0.05) following volume expansion. Following exsanguination, the PRI value increased to 87 +/- 21. These data demonstrate the benefits of volume expansion during acute cerebral ischaemia. Changes in local CBF were consistently associated with changes in the PRI maps and values.

Animals↗

PubMed1986

Acute middle cerebral artery occlusion: experience with volume expansion therapy.

Five consecutive patients with acute neurological deficits after middle cerebral artery (MCA) occlusion were given emergency treatment with colloidal volume expansion. In each case, the diagnosis was confirmed promptly by computed tomography and cerebral angiography. Aggressive volume expansion therapy was started 2 to 18 hours (mean, 11 hr) after the onset of the neurological deficit. The mean colloidal volume used was 920 ml/day for an average of 4 days. During volume expansion, the mean cardiac output increased 57% from 4.6 +/- 0.6 to 7.2 +/- 1.9 litres/min (P less than 0.05). The mean hematocrit decreased 19% from 46 +/- 3% to 37 +/- 4% (P less than 0.01). The mean arterial blood pressure remained stable, and the pulmonary artery wedge pressure was maintained at less than 15 mm Hg. Three patients improved dramatically with volume expansion therapy and have returned to their previous life-styles. Two patients made partial recoveries and manage at home with nursing care. The three patients who improved dramatically were young (aged less than 34) and, when compared to the older patients, they had greater increases in cardiac output (67% vs. 19%). No major complications or deaths were attributed to the volume expansion therapy. We propose that intravascular volume expansion and its concomitant augmentation of the cardiovascular dynamics may be effective in the treatment of acute neurological deficits after acute MCA occlusion.

Acute Disease↗