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M Chopp

Publications and source records attributed to M Chopp.

At least 181 records · Page 10Linked to original sources
PubMed1991

Effect of mild hyperthermia on the ischemic infarct volume after middle cerebral artery occlusion in the rat.

We investigated the effect of mild whole-body hyperthermia (40 degrees C) on a permanent middle cerebral artery occlusion (MCAo) model in Fisher rats by subjecting them to MCAo under the following conditions: (1) normothermia (n = 20); (2) hyperthermia (n = 14) before (1 hour), during, and after (1 hour) MCAo; and (3) post-MCAo hyperthermia (n = 14) for 1 hour. We measured brain and body temperatures during the experiment using micro-thermocouples and blood-brain-barrier (BBB) permeability using Evans blue staining of the brain. We measured the volume of the infarcted brain tissue 4 days after MCAo. We detected no differences in BBB permeability among three groups. The volume of infarcted tissue was significantly greater (p less than 0.05) for the two groups of hyperthermic animals than the normothermic animals. Our data suggest that mild hyperthermia, both during and after induction of ischemia, has a detrimental effect on the ischemic infarct volume in this model.

Animals↗
PubMed1991

Dose-dependent thermal response of tumor pH and energy metabolism evaluated by in vivo 31P NMR spectroscopy and microelectrodes.

In vivo 31P NMR spectroscopy and pH microelectrodes were employed to measure the energy metabolism and pH of a mammary carcinoma in the flank of the C3H mouse before and serially up to a week after various hyperthermia treatments. Water bath hyperthermia was used to treat the tumor at 43.5 degrees C for 30 min (TCD0/30, NMR measurement only), 1 h (TCD10/30), and 2 h (TCD60/30), respectively. The data indicate that, except at 4 h after TCD60/30 treatment, all pH values measured by NMR (pHn) were significantly higher (P less than or equal to 0.001) compared to pH values measured by microelectrodes (pHe) at all treatment levels and times. The magnitude of the difference between pHn and pHe (delta pH) was significantly decreased from the pretreatment level only at 4 h after hyperthermia treatment (0.51 pH units for TCD60/30 and 0.21 pH units for TCD10/30). The ratio of beta-nucleoside triphosphate to inorganic phosphate (beta-NTP/Pi) and pHn were more sensitive to hyperthermia treatment than pHe. The beta-NTP/Pi ratio failed to recover to the pretreatment ratio after 1 or 2 h hyperthermia treatment, while a total recovery was observed within 72 h for 30 min hyperthermia treatment. Our data suggest that the temporal profile of beta-NTP/Pi, pHn, and delta pH may be indicative of the biological outcome of hyperthermia treatment.

Animals↗
PubMed1990

Time course of postischemic intracellular alkalosis reflects the duration of ischemia.

We investigated the long-term (up to 1 week) relationships between the duration of cerebral ischemia and postischemic energy metabolic profile, pH, and tissue edema in the rat. Ten rats each were subjected to 8 or 12 min of forebrain ischemia induced by bicarotid occlusion concurrent with systemic hypotension, and the results were compared with those of 10 sham-operated rat controls. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to ischemia and at intervals up to 168 h after ischemia. Cerebral edema (measured by specific gravity) was assessed prior to ischemia and at 24, 72, and 168 h after ischemia. The data revealed significant differences in the brain tissue pH profile over time between the ischemic groups (p less than 0.03). The 12-min ischemic animals exhibited brain tissue alkalosis (pH = 7.27 +/- 0.12) at 24 h compared with both sham (pH = 7.09 +/- 0.08) at 24 h and preischemic (pH = 7.06 +/- 0.04) pH values. The pH remained alkalotic (pH = 7.23 +/- 0.15) through the 48-h time period. In contrast, in the 8-min group, the onset of alkalosis was delayed until 48 h after ischemia (pH = 7.24 +/- 0.15), and pH remained alkalotic for only 24 h. No difference in high-energy phosphate metabolism was detected between groups. A different time dependence of tissue pH and specific gravity changes after 12 min of ischemia was detected. The present study suggests that the duration of an ischemic event marks the time of onset of brain tissue alkalosis and its duration and that cerebral edema alone cannot explain the pH changes.

Alkalosis↗
PubMed1990

Chronic metabolic measurements of normal brain tissue response to photodynamic therapy.

The metabolic response of normal rat brain to photodynamic therapy (PDT) was studied over a 1 week interval using in vivo 31P-NMR spectroscopy. Rats injected with 12.5 mg/kg Photofrin II were submitted to brain photoactivation 48 h after drug administration with either 140 or 70 J/cm2 light (630 +/- 1 nm) from an Argon dye laser. Control studies, animals not given drug or light, animals submitted only to brain illumination without drug, and animals given drug but no light, were also performed. The data revealed a transient metabolic degradation; a decrease in the ratio of beta-nucleotriphosphate to inorganic phosphate (P less than 0.001) at 24 h after PDT treatment was followed by a return to pretreatment spectral values. Brain tissue alkalosis was also noted, with significant (P less than 0.05) differences in brain tissue pH detected at 72 h post treatment between 70 J/cm2 PDT vs control studies and at 1 week post treatment between 140 J/cm2 vs 70 J/cm2, 140 J/cm2 vs no light-no drug and 140 J/cm2 vs drug only. The data suggest that there is no difinitive metabolic marker from 31P-NMR spectroscopy that can identify necrotic brain tissue caused by PDT. Phosphorus-31 NMR data are also presented which suggest that PDT damage to brain is not solely the result of microvascular occlusion causing ischemic necrosis.

Animals↗
PubMed1990

Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats.

We measured cerebral intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during 1 week after forebrain ischemia or sham operation in eight and seven rats, respectively. Mean maximum pH was significantly higher (p less than 0.003) in the ischemic group than in the sham-operated group (7.34 +/- 0.03 and 7.19 +/- 0.02, respectively). The difference between mean maximum pH and baseline pH (7.08 +/- 0.01 in each group) was significantly greater (p less than 0.02) in the ischemic group than in the sham-operated group. In the ischemic group, alkalosis occurred primarily after 48-72 hours of recirculation. We speculate that brain tissue alkalosis occurring chronically after ischemia is associated with delayed ischemic neuronal death.

Alkalosis↗
PubMed1990

Dose-dependent metabolic response of mammary carcinoma to photodynamic therapy.

The metabolic response of mammary carcinoma in the C3H mouse to photodynamic therapy (PDT) was measured using in vivo 31P nuclear magnetic resonance (31P-NMR) spectroscopy and pH microelectrodes. Twenty-four hours after administration of Photofrin II (12.5 mg/kg), the tumor was subjected to photoactivation using an argon dye laser. Optical treatment doses were 200, 400, and 600 J/cm2 and corresponded to the following tumor control doses: TCD10/30, TCD50/30, and TCD90/30, respectively. In vivo 31P-NMR spectra and pH micro-electrode measurements were obtained prior to treatment and at 4, 24, 48, and 72 h and 1 week post-treatment. The data revealed a significant (P less than 0.0002) alkalosis as indicated by the pH measured by NMR compared to pH measured by microelectrodes at all treatment levels and time points. Spectral differences between treatment groups were apparent as early as 4 h after treatment. The ratio of beta-nucleoside triphosphate to inorganic phosphate at 4 h after treatment was significantly (P less than 0.01) smaller for 600 J/cm2 treatment than for 200 J/cm2 treatment. At curative (600 J/cm2) levels, from 48 h on, no phosphate resonances were detected in the spectra. The pH measured by NMR transiently decreased from pretreatment levels after 200 and 400 J/cm2 treatment (P less than 0.002, P less than 0.009, respectively), while no change in pH from pretreatment values was found after 600 J/cm2 treatment. The data suggest that the early metabolic response of mammary carcinoma to PDT, as indicated by 31P-NMR spectroscopy, is dose dependent, and may be a sensitive indicator of biological outcome to treatment.

Animals↗
PubMed1990

Changes in muscle pH following hyperthermia.

Considerable attention has been paid to the modification of intratumor pH in response to hyperthermia. It has been hypothesized that observed reductions in intralesional pH are involved in the ultimate response of tissue to hyperthermia treatment. Further, it has been shown that significant differences exist in hyperthermia-induced changes in blood flow between tumor and normal tissue in many systems. Changes in blood flow are hypothesized to be related to observed changes in pH. Since reduced blood flow is not observed in normal tissue under normal treatment conditions, changes in pH in normal tissue have not been considered significant in their response to hyperthermia treatment. However, this conclusion has not been verified or documented experimentally. The purpose of this study was to examine the distribution of pH in normal tissue (muscle) as a function of time following hyperthermia treatments which in the same animal system resulted in subcurative (TCD 10/30) or curative (TCD 90/30) tumor (mammary adenocarcinoma) responses. The observed distribution of pH in normal tissue was compared with that obtained in tumors under identical conditions. The results indicate that some post-treatment changes in muscle pH do occur following hyperthermia, but that these changes are small compared to those observed in tumors. More importantly, unlike the response observed in tumors, no hyperthermia dose dependency is observed in the muscle response. From these studies it can be concluded that changes in normal muscle pH are probably not associated with normal tissue response to hyperthermia.

Adenocarcinoma↗
PubMed1989

Hyperthermic "dose" dependent changes in intralesional pH.

Following hyperthermia a dramatic drop in intra-lesional pH has occurred in a variety of experimental tumor systems. To date, no direct observations have been made that document the time course of such changes or the recovery from such changes over prolonged periods of time. These experiments were designed to measure intralesional pH as a function of time following "doses" of hyperthermia related to specific biological end points. All studies were conducted in the C3H-mammary carcinoma tumor model system. Intralesional temperature was continuously monitored throughout treatment and post treatment pH was measured with microelectrodes at several specific time points ranging from 4 hrs to 7 days. The pretreatment control value of mean pH was 6.73. At the TCD90 "dose" level the mean value of pH dropped to a level of 6.22 +/- .095 while following the TCD10 "dose" the value obtained was 6.55 +/- .148. Recovery of the pH to higher values followed similar time courses returning to maximum values approximately 3 days post treatment. The recovery, plateau levels of pH were however, separated by approximately .3 pH units with the higher "dose" curve always at lower values than that achieved following the lower "dose".

Adenocarcinoma↗
PubMed1989

The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia.

The metabolic effects of graded whole body hypothermia on complete global cerebral ischemia and recirculation was investigated in the cat. Hypothermia was induced to one of three levels prior to ischemia; T = 26.8 degrees +/- 0.5 degrees C (n = 4), T = 32.1 degrees +/- 0.2 degrees C (n = 5), and T = 34.6 degrees +/- 0.3 degrees C (n = 6), and maintained constant throughout 16 min of ischemia and 1.5-2 h of recirculation. Intracellular cerebral pH and relative concentrations of high-energy phosphate metabolites were continuously monitored, using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Except for the first 4 min of ischemia, no significant differences were detected in the response of adenylate intensities and intracellular pH to ischemia and recirculation between the hypothermic groups. The three hypothermic groups were then pooled into one group, and the data compared to previously published data from a normothermic group, T = 38.4 degrees +/- 0.6 degrees C (n = 14), and a hyperthermic group, T = 40.6 degrees +/- 0.2 degrees C (n = 9), subjected to the identical ischemic and NMR measurement protocols. The hypothermic animals exhibited a statistically significant reduction of cerebral intracellular acidosis, both during ischemia and recirculation, as well as a more rapid return of adenylate intensities during recirculation, compared to the normothermic or hyperthermic groups. The data thus suggest that mild hypothermia has an ameliorative affect on brain energy metabolism and intracellular pH under conditions of complete global cerebral ischemia and recirculation.

Animals↗
PubMed1989

Normal brain tissue response to photodynamic therapy: histology, vascular permeability and specific gravity.

The response of photodynamic therapy on normal brain was investigated in 140 Fisher rats. The rats were injected i.p. with Photofrin II (12.5 mg/kg) and 48 h later the dural area over the frontal cortex was photoactivated with red light (630 +/- 1 nm) from an argon dye laser. Treatment was performed with optical energy densities of 140 and 70 J/cm2. Histopathology, vascular permeability and specific gravity measurements were conducted on different populations of rats at 4 h, 24 h, 72 h and 1 week after photodynamic therapy (PDT). Histopathology revealed similar gross and microscopic pathology associated with light energies of 70 and 140 J/cm2 after all time points. A large cerebral infarct approximately the size of the brain surface area treated, evolved 24 h following treatment. Evans blue extravasation indicated a small area of vascular permeability evident as early as 4 h following PDT treatment at both energy levels, with increasing permeability evident at later time points. Specific gravity measurements taken on a representative area of the lesion indicated a significant (P less than 0.01) amount of edema present at 24 h post treatment with a gradual reduction approaching control values over the time period of 1 week. The data indicate a significant amount of damage to normal brain from low PDT treatment doses.

Animals↗
PubMed1989

Reduction of hyperthermic ischemic acidosis by a conditioning event in cats.

We investigated the effects of multiple episodes of cerebral ischemia on intracellular brain pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Four cats were subjected to two 16-minute episodes of complete global cerebral ischemia 6 hours apart; the second episode occurred under hyperthermic conditions (mean +/- SD body temperature 40.8 +/- 0.4 degrees C). Intracellular pH in these four cats was compared with that in nine cats subjected to a single 16-minute episode of complete global cerebral ischemia under hyperthermic conditions (mean +/- SD body temperature 40.6 +/- 0.2 degrees C). Intracellular pH during hyperthermic recirculation was significantly (p less than 0.03) greater in cats subjected to a previous ischemic event than that in cats subjected to only a single hyperthermic ischemic event. We speculate that the induction of heat shock proteins by an initial ischemic event may protect brain tissue from further ischemic insult.

Acidosis↗
PubMed1989

Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat.

We heated Wistar rats (n = 10) to 41.5 +/- 0.2 degrees C for 15 minutes, 24 hours before the induction of forebrain cerebral ischemia. We subjected 23 rats to forebrain ischemia without prior heating. Ischemic cell damage in the medial, lateral, and overall CA 1/2 hippocampus, inferior frontal cortex, and dorsal-lateral striatum was significantly (p less than 0.05) less severe in heated animals than in nonheated animals.

Animals↗
PubMed1988

Prolonged deterioration of ischemic brain energy metabolism and acidosis associated with hyperglycemia: human cerebral infarction studied by serial 31P NMR spectroscopy.

We report on a patient with a large ischemic hemispherical stroke studied serially by 31P nuclear magnetic resonance spectroscopy. Persistent hyperglycemia was associated with prolonged acidosis in ischemic brain and failure of high-energy phosphate metabolism to recover. These in vivo human data support the concept that hyperglycemia adversely affects ischemic brain metabolism, pH, and clinical outcome.

Acidosis↗
PubMed1988

Global cerebral ischemia and intracellular pH during hyperglycemia and hypoglycemia in cats.

In 27 cats treated to vary arterial serum glucose concentrations, we measured cerebral high-energy phosphate metabolite concentration and intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during transient global cerebral ischemia and reperfusion. Hypoglycemia was induced with 4 units/kg i.v. insulin in six cats before ischemia; hyperglycemia was induced with 1.5 g/kg i.v. glucose in six cats before and in six cats during ischemia. Nine untreated cats subjected to ischemia without manipulation of blood glucose concentration served as controls. During ischemia, intracellular pH fell to similar levels in the control and both hyperglycemic groups. During reperfusion, the hyperglycemic before ischemia group initially exhibited a severe further decline in intracellular pH (p less than 0.003); this further decline was not observed in the control or the hyperglycemic during ischemia groups. Intracellular acidosis was attenuated both during ischemia and early after reperfusion in the hypoglycemic before ischemia group. In all groups, cerebral high-energy phosphate metabolite concentrations were depleted during ischemia and then recovered to the same degree during reperfusion. Our data suggest that brain glucose stores before ischemia determine the severity and time course of intracellular acidosis during ischemia and reperfusion.

Animals↗
PubMed1988

Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats.

We investigated the effect of mild whole-body hyperthermia before and after 16 minutes of global cerebral ischemia on metabolic recovery during recirculation in cats using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Hyperthermia (temperature 40.6 +/- 0.2 degrees C) was induced greater than or equal to 1 hour before ischemia and was maintained during 1.5-2 hours of recirculation in nine cats; four cats were subjected to hyperthermia without cerebral ischemia, six to hyperthermia during recirculation (after return of intracellular pH to preischemic values), and 14 to normothermic ischemia and recirculation. Our data indicate that preischemic hyperthermia results in an intracellular cerebral pH during recirculation significantly lower than that in normothermic cats. In hyperthermic cats beta-ATP and phosphocreatine (PCr) concentrations and the ratio of PCr to inorganic phosphate failed to return to preischemic levels during recirculation in contrast to normothermic cats. Hyperthermia without ischemia and hyperthermia during recirculation had no significant effect on intracellular pH. Thus, preischemic hyperthermia has a detrimental effect on metabolic recovery after transient global cerebral ischemia.

Acidosis↗
PubMed1987

Photodynamic therapy of normal cerebral tissue in the cat: a noninvasive model for cerebrovascular thrombosis.

The early neuropathological response of normal cat brain to photodynamic therapy was investigated. Photofrin II was injected (IV) into a cat and photoactivated with red light from a filtered incandescent lamp. Animals were subjected to phototherapy either through the intact skull or with energy deposition onto the intact dura. Following photoactivation the animals were maintained for 6 h after which time the brain was removed and sections submitted for electron microscopic and or light microscopic study. Gross anatomical analysis of the photoactivated brain revealed hemorrhagic dusky discoloration limited to the area of the tissue illuminated. Animals that failed to show a lesion were cats characterized by low Photofrin II dosage and low photoactivation intensity. The microscopic cortical features of cats with lesions included prominent capillary congestion and regions of marked vacuolization and rarefaction. Blood vessels were structurally altered and the lumen of many vessels was completely filled with tightly packed erythrocytes. Our study suggests that the acute neuropathological response of cerebral tissue to photoactivation resembles that of microvascular thrombosis. It is thus reasonable to explore PDT of normal tissue as a non invasive model of cerebrovascular thrombosis in the cat.

Animals↗