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M Chopp

Publications and source records attributed to M Chopp.

196 records · Page 11Linked to original sources

In vivo evaluation of intracellular pH and high-energy phosphate metabolites during regional myocardial ischemia in cats using 31P nuclear magnetic resonance.

Phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) was used to assess the temporal changes of high-energy phosphate metabolites in the region of acute myocardial ischemia of open-chest cats. Eight anesthetized cats were studied following ligation of the left anterior descending coronary artery. Creatine phosphate showed a 79 +/- 16% (mean +/- SD) reduction by 4 min after the onset of ischemia. Prominent qualitative reductions of the spectral peak of creatine phosphate occurred by 40 s after ischemia. Adenosine triphosphate measured under the beta spectral peak (beta-ATP) decreased 37 +/- 9% by 20-25 min after ligation of the left anterior descending coronary artery. These reductions developed more slowly and were of smaller magnitude than those of creatine phosphate. Intracellular pH decreased from 7.39 +/- 0.07 to 7.13 +/- 0.09 units by 40 s after ischemia. By 30 min, pH decreased to 6.07 +/- 0.40 units. The study shows, therefore, the temporal changes of high-energy phosphate metabolites during ischemia in localized regions of the myocardium of open-chest animals.

Adenosine Triphosphate↗

The CSF pulse wave in hydrocephalus.

Twenty-one dogs were rendered hydrocephalic by the intracisternal injection of kaolin. After various intervals between 1 and 44 days the animals were anesthetized for the measurement of arterial (lingual), ventricular, and sagittal sinus pressures. Following the recordings the animals were sacrificed by formalin infusion, the brains sectioned serially, and ventricular size measured. In general, the longer the period of incubation the larger the ventricles. There was no correlation between the degree of hydrocephalus and mean or pulsatile ventricular pressure. All animals with a pressure of less than 9 torr demonstrated non-linear transmission of the arterial wave into the CSF (which is the same as the pulse in the venous bed). All animals with a pressure greater than 12 torr had linear transmission of the wave. These findings in the hydrocephalic animals are the same as those found in nonhydrocephalic animals with similar pressures. It is concluded that the CSF pulse wave seen in hydrocephalic dogs is a result of how the cerebrovascular bed processes the cardiac pulse wave and is independent of the hydrocephalic process. There is no evidence that the pulse wave produces hydrocephalus.

Animals↗

Anoxia followed by hyperoxia: in vivo 31-P NMR of cat brain.

In vivo 31P NMR spectroscopy was performed on a cat brain subjected to an extended period of anoxia followed by restoration of oxygen. High energy phosphate spectra were continuously obtained and pH measured. Following the onset of anoxia, phosphocreatine and ATP peaks decreased with a concomitant increase in inorganic phosphate. Following 34 min ventilation on 100% N2, the animal was ventilated on 100% O2. The spectral content progressively changed, inorganic phosphate decreased and ATP increased with the spectrum closely resembling that of control. Our results suggest that the absence of NMR detectable ATP signal cannot be interpreted as an irreversable change in cellular metabolic function.

Adenosine Triphosphate↗

Hydraulic model of the cerebrovascular bed: an aid to understanding the volume-pressure test.

A hydraulic model of the cerebrovascular bed is presented. The model consists of a Starling resistor in series with an upstream resistance. Volume-pressure tests were performed on the model by injecting fluid into the rigid shell of the Starling resistor. An exponential pressure response to the increase in fluid volume was observed, which supports the hypothesis that the origin of the in vivo exponential pressure response to a transient increase in cerebrospinal fluid (CSF) volume can be attributed to compression of the cerebral vessels, most probably the veins. Mathematical expressions for the dependence of pressure on volume change were derived from the model and applied to in vivo volume-pressure data. The correlation between the model and in vivo experiments suggests that the CSF pressure is coupled to cerebral venous pressure and that the volume-pressure test is an indirect measure of the cerebral venous volume and is not a measure of intracranial elastance. The physical basis for the volume-pressure test is clarified, and expressions are derived to improve the utility of the test.

Blood Pressure↗

Hydraulic model of myogenic autoregulation and the cerebrovascular bed: the effects of altering systemic arterial pressure.

Systemic arterial (Ps), cerebrospinal fluid (Pcsf), and sagittal sinus (Pss) pressures were measured in 39 dogs divided into eight groups in which Ps was altered pharmacologically or by bleeding. The pharmaceuticals used were norepinephrine (N-EP), dopamine (DOP), sodium nitroprusside (SNP), and nitroglycerin (NTG). SNP and NTG were examined with and without methohexital (MHX) anesthesia and during chronic infusion and bolus injection. The various pressures were subjected to systems analysis in accordance with a previously published model of myogenic autoregulation. Myogenic autoregulation seemed to be impaired only during infusions of N-EP, DOP, and SNP without MHX and during hypovolemic hypotension. The various observed changes in Pcsf are explained by using a hydraulic model of the cerebrovascular bed in which Pcsf represents the pressure drop across the outflow resistance of the bridging veins and lateral lacunae and myogenic autoregulation at the arteries and arterioles represents the major inflow resistance. Impaired myogenic autoregulation is associated with a rise in Pcsf. In addition, variation in pulse pressure is demonstrated to be related to the arterial pulse pressure and the degree of arterial and arteriolar vasodilation.

Animals↗

Cerebrospinal fluid pulse waveform as an indicator of cerebral autoregulation.

Systems analysis of the systemic arterial (SAPW), cerebrospinal fluid (CSFPW), and sagittal sinus (SSPW) pulse waves was carried out in 13 dogs during hypercapnia (5% CO2), intracranial normotension (inhalation of 100% O2), and intracranial hypertension (inhalation of 100% O2 plus an intraventricular infusion). Power amplitude and phase spectra were determined for each wave, and the power amplitude and phase transfer functions calculated between the cerebrospinal fluid (CSF) pressure and systemic arterial pressures, and between the sagittal sinus pressure and CSF pressure. The study indicates that the CSFPW and SSPW were virtually identical when impedance between the cerebral veins and sagittal sinus was minimal, which argues that the CSF pulse was derived from the cerebral venous bed. During inhalation of 100% O2, transmission of the SAPW across the precapillary resistance vessels into the cerebral venous pulse (as represented by the CSFPW) was nonlinear, while transmission across the lateral lacunae into the sagittal sinus was linear. During intracranial hypertension, wave transmission across the precapillary resistance vessels was linear, and across the lateral lacunae was nonlinear. During hypercapnia, wave transmission across the precapillary resistance vessels and the lateral lacunae was linear. When the wave transmission was nonlinear, there was also suppression in transmission of the lower harmonics, particularly the fundamental frequency, and a more positive phase transfer function, suggesting an inertial effect or decrease in acceleration of the pulse. Conversion from a nonlinear to linear transmission across the precapillary resistance vessels is evidence of loss of vasomotor tone, and is accompanied by rounding of the CSFPW. A vascular model which encompasses the above data and is based on flow in collapsible tubes and changes in vasomotor tone is posited to explain control of pulsatile flow and pulse waveform changes in the cerebrovascular bed. The model helps to clarify the strong interrelationship between intracranial pressure, cerebral blood flow, and cerebral autoregulation.

Animals↗

The contribution of internal scatter to radiation dose during CT scan of the head.

An acrylic head phantom was irradiated during a computed tomographic scan with four commercial scanners. Measurements of the spatial distribution of the radiation dose on the surface and internal to the phantom were performed for the scan plane and the scattered beam at various distances from the scan plane. The surface scatter dose was found to be considerably smaller than that for internal scatter. A significant increase in radiation exposure within the head phantom due to internal radiation scatter, and an asymmetrical primary beam profile for dual slice scanners were also noted.

Head↗

Cerebrospinal fluid pulse wave form analysis during hypercapnia and hypoxia.

Systems analysis of cerebrospinal fluid pulse wave forms (CSFPWs) was carried out in 19 cats during the inhalation of 5% CO2 + 95% O2. 10% CO2 + 90% O2 and 10% O2 + 90% N2. The results were compared to CSFPWs obtained during the inhalation of 100% O2 and during an intraventricular infusion to the same level of cerebrospinal fluid (CSF) pressure (CSFP) as produced by the test gas. The systemic arterial pressure pulse was utilized as the system input, and the CSFP pulse was used as the output. The harmonic amplitudes of the two pulses and the amplitude transfer function (XFRa) between the pulses were calculated. Hypercapnia and and hypoxia produced an increase in CSF pulse pressure (delta Pcsf), an increase in primarily the XFRa of the fundamental frequency, and as a result, an increase in amplitude of the fundamental frequency of the CSFPW with rounding of the pulse wave. The changes are greater than those noted during an intraventricular infusion (IVI) to the same level of CSFP. In addition, the volume-pressure test was performed on the hypercapnic animals. The volume-pressure response was less during hypercapnia than during the IVI at the same mean level of CSFP. The result suggest that the increase in deltaP csf is related to cerebral arteriolar vasodilation and not to a steepening of the volume-pressure curve and that rounding of the CSFPW is related to a decrease in cerebrovascular tone.

Animals↗

Clinical dosimetry during cerebral arteriography.

Radiation dosimetry measurements on angiographer, X-ray technician and patient were performed during 18 femerocerebral angiograms. Lithium fluoride (LiF) thermoluminescent dosimeters were placed on various body areas to measure X-ray exposure. The results of this study indicate that radiation exposure received by medical personnel are well within the maximum permissible dose range established by the National Council of Radiation Protection. However, radiation exposure levels to radiosensitive areas of the patient are significant. A method to reduce patient exposure during femerocerebral arteriograms is suggested.

Cerebral Angiography↗

Systems analysis of intracranial pressure. Comparison with volume-pressure test and CSF-pulse amplitude analysis.

Systems analysis is explored as a method of evaluating intracranial pressure (ICP). The intracranial cavity is characterized by a transfer function that is evaluated by the blood pressure pulse acting as the system input and the ICP pulse acting as the output. A comparison is made of the ability of systems analysis, volume-pressure test (VPT), and cerebrospinal fluid-pulse amplitude analysis (CSFPAA) to distinguish between an epidural balloon inflation (EBI) and an intraventricular infusion (IVI) at various steady state levels of ICP. The VPT could not distinguish between EBI and IVI at any level of ICP, and above 30 mm Hg the volume-pressure response decreased. Spectral analysis was able to distinguish EBI from IVI above 30 mm Hg, and CSFPAA was demonstrated to be a simplified spectral analysis. Changes in ICP waveform generated during each cardiac cycle appear to be related to changes in vasomotor reactivity and may have value in the clinical monitoring of ICP.

Animals↗

The role of protein kinase Calpha in U-87 glioma invasion.

To investigate the hypothesis that protein kinase Calpha (PKCalpha) is functional glial tumor cell invasion, stable PKCalpha sense and antisense transfected U-87 cell lines were established and PKCalpha expression characterized by Western blot and PKC activity assays. Invasion assays including barrier migration (Koochekpour et al., Extracellular matrix proteins inhibit proliferation, upregulate migration and induce morphological changes in human glioma lines. Eur. J. Cancer, 1995, 31, 375-380; Merzak et al., CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res., 1994, 54, 3988-3992; Merzak et al., Cell surface gangliosides are involved in the control of human glioma cell invasion in vitro. Neurosci. Lett., 1994, 177, 11-16), and spheroid confrontation were used to study the relationship between PKCalpha expression and invasiveness. PKCalpha overexpressing clones show increased barrier migration (1.5x) relative to the control transfected clones. PKCalpha inhibited clones exhibited reduced invasiveness, to < 50%. In coculture with PKCalpha overexpressing clones, the remaining normal fetal rat brain aggregate volume was significantly decreased (up to 200%) but 90% of the initial brain volume was left in PKCalpha inhibited clone in the rat brain aggregate tumor spheroid confrontation. This effect was not associated with significant growth inhibition. We conclude that expression of PKCalpha in glioma-derived cell lines appears to be central to glioma invasion in vitro.

Animals↗

In vivo 31-P NMR of photoactivated hematoporphyrin derivative in cat brain.

In vivo 31-P nuclear magnetic resonance (NMR) spectroscopy was performed on cat brains injected with hematoporphyrin derivative (HpD). A 2-cm-diam region of the right parietal lobe was photoactivated with red light. The 31-P NMR spectra of the photoactivated hemisphere revealed increased inorganic phosphate and decreased phosphocreatine and adenosine triphosphate (ATP) levels, compared to spectra obtained from the control hemisphere. In the absence of drug, no difference in spectra was observed between the photoradiated and control lobes. Our studies suggest that in vivo 31-P NMR spectroscopy may be used to monitor the effects of phototherapy on tissue high-energy phosphate metabolism.

Animals↗

Intracellular acidosis during and after cerebral ischemia: in vivo nuclear magnetic resonance study of hyperglycemia in cats.

In vivo 31P nuclear magnetic resonance spectroscopy was used to monitor the time course of intracellular pH in cat cerebral cortex subjected to global cerebral ischemia under control and hyperglycemic pretreatment conditions. Transient (16 minutes) global cerebral ischemia was induced in 14 cats using an inflatable cervical cuff combined with systemic arterial hypotension. Six cats were pretreated with infusion of 1.5 g/kg glucose prior to ischemia. Relative concentrations of high-energy phosphate metabolites and intracellular pH were continuously monitored before, during, and for 2 hours after cerebral reperfusion. During ischemia, intracellular pH fell to the same level and followed a similar time course in both groups. However, during initial reperfusion in the hyperglycemic group, there was a severe further decline (p less than 0.003) in intracellular pH. We suggest that the increased neurologic deficit and mortality found in hyperglycemic animals subjected to cerebral ischemia may be attributed to this transient severe tissue acidosis.

Acidosis↗

Adult bone marrow transplantation after stroke in adult rats.

We transplanted adult whole bone marrow prelabeled with bromodeoxyuridine (BrdU) into the ischemic boundary zone of the adult rat brain at 1 day after 2 h of middle cerebral artery occlusion (MCAo). Approximately 3.3% of 10(6) transplanted bone marrow cells were BrdU reactive at 14 days after MCAo. BrdU-reactive cells expressed neuronal and astrocytic proteins, neuronal nuclei protein (NeuN, 1%), and glial fibrillary acidic protein (GFAP, 5%) immunoreactivities, respectively. In addition, bone marrow transplantation promoted proliferation of ependymal and subependymal cells, identified by nestin (a neuroepithelial stem cell marker), within the ventricular zone and subventricular zone (VZ/SVZ). These data suggest that intracerebral transplantation of bone marrow could potentially be used to induce plasticity in ischemic brain.

Animals↗