Biomedical subjects

J A Helpern

Publications and source records attributed to J A Helpern.

At least 55 records · Page 3Linked to original sources

PubMed1990

Fluorocarbon-23 measure of cat cerebral blood flow by nuclear magnetic resonance.

We employed fluorocarbon-23 (trifluoromethane) as a nuclear magnetic resonance gaseous indicator of cerebral blood flow in seven cats. Pulsed inhalation of this indicator and switching between two coils allowed the acquisition of both an arterial input and a cerebral response function, making possible multicompartmental curve fits to cerebral uptake and clearance data. The brain:blood partition coefficient for trifluoromethane was 0.9 for both gray and white matter. Fast-compartment blood flows were normal and showed appropriate CO2 reactivity. Slow-compartment blood flows did not demonstrate CO2 reactivity, probably because cranial as well as white-matter blood flows were lumped together in the slow compartment. Although cerebral blood flow was stable during administration of 60% trifluoromethane, the compound did prove to be a mild cardiac sensitizer to epinephrine in five cats.

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↗

PubMed1989

Interleaved 31P NMR with transcutaneous nerve stimulation (TNS): a method of monitoring compliance-independent skeletal muscle metabolic response to exercise.

31P NMR spectroscopy was used to monitor the metabolic response of the tibialis anterior muscle group to transcutaneous nerve stimulation of the peroneal nerve at a rate of 4 Hz for 5 min in human volunteers (n = 8). It is demonstrated that this technique can be used as a method of investigating effort-free and compensation-independent skeletal muscle exercise.

Adult↗

PubMed1989

Rubidium transport in human erythrocyte suspensions monitored by 87Rb NMR with aqueous chemical shift reagents.

Dysprosium(III) triethylenetraamine-N,N,N',N",N"',N"'-hexaacetic acid (DyTTHA3-) was used as an aqueous chemical shift reagent in conjunction with high-resolution nuclear magnetic resonance (NMR) spectroscopy to monitor 87-rubidium (87Rb+) transport in human erythrocyte suspensions. NMR spectra demonstrated two resonances which were assigned to the intra- and extracellular compartments of the erythrocyte suspension. Uptake of 87Rb+ was shown to proceed via the [Na,K]-ATPase dependent pump as evidenced by the inhibition of uptake in the presence of ouabain. The steady state intra- to extracellular concentration ratio of 87Rb was 3.00 and 1.13 in the absence and presence of ouabain, respectively. The rate of uptake of 87Rb+ in the absence and presence of ouabain was found to be 1.3 and 0.5 mmol Rb+/L erythrocytes/h at 18 mM Rb+, respectively. Data are also presented which indicate that the intracellular component of 87Rb is less than 100% NMR visible.

Biological Transport↗

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

Low brain magnesium in migraine.

Brain magnesium was measured in migraine patients and control subjects using in vivo 31-Phosphorus Nuclear Magnetic Resonance Spectroscopy. pMg and pH were calculated from the chemical shifts between Pi, PCr and ATP signals. Magnesium levels were low during a migraine attack without changes in pH. We hypothesize that low brain magnesium is an important factor in the mechanism of the migraine attack.

Adult↗

PubMed1989

Low brain magnesium in migraine.

Adult↗

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

Cerebral blood flow measured by NMR indicator dilution in cats.

We developed techniques to assess the utility of a nuclear magnetic resonance (NMR) indicator for cerebral blood flow studies in cats, using Freon-22 for the first candidate. A PIN-diode-switched NMR experiment allowed the acquisition of an arterial as well as a cerebral fluorine-19 signal proportional to concentration vs. time in a 1.89 T magnet. Mean +/- SD blood:brain partition coefficients for Freon-22 were estimated at 0.93 +/- 0.08 for gray matter and 0.77 +/- 0.12 for white matter. Using maximum-likelihood curve fitting, estimates of mean +/- SD resting cerebral blood flow were 50 +/- 19 ml/100 g-min for gray matter and 5.0 +/- 2.0 ml/100 g-min for white matter. Hypercapnia produced the expected increases in gray and white matter blood flow. The physiologic effects of Freon-22, including an increase in cerebral blood flow itself with administration of 40% by volume, may limit its use as an indicator. Nevertheless, the NMR techniques described demonstrate the feasibility of fluorine-19-labeled compounds as cerebral blood flow indicators and the promise for their use in humans.

Animals↗

PubMed1989

In vivo 31P NMR profiles of Alzheimer's disease and multiple subcortical infarct dementia.

We used in vivo phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy to study regional high-energy phosphate and phospholipid metabolism in brains of patients with dementia associated with probable Alzheimer's disease (AD) and multiple subcortical cerebral infarctions (MSID). The MSID patients demonstrated elevations of the phosphocreatine (PCr)/inorganic orthophosphate (Pi) ratio in both the temporoparietal and frontal regions. Phosphomonoesters (PME) and the ratio of PME to phosphodiesters were elevated in the temporoparietal region of AD. Pi was also elevated in the frontal and temporoparietal regions of AD. Findings from 31P NMR were accurate in distinguishing MSID from AD. Values of PCr/Pi accurately classified 100% of the MSID patients and 92% of AD. Pi and PME, considered jointly, also accurately classified all MSID and all but 1 AD. Findings from in vivo 31P NMR spectroscopy appear to yield metabolic profiles useful in distinguishing AD from MSID.

Aged↗

PubMed1989

Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy.

We measured brain energy phosphate metabolism and intracellular pH (pHi) in a cross-sectional study of migraine patients by in vivo phosphorus 31 NMR spectroscopy. During a migraine attack the ratio ATP/total phosphate signal (mole % ATP) was preserved, but there was a decrease in mole % phosphocreatine (PCr) and an increase in mole % inorganic phosphate (Pi) resulting in a decrease of the PCr/Pi ratio, an index of brain phosphorylation potential. This was found in classic but not common migraine. Mole % Pi was also increased in combined brain regions between attacks. There was no alteration in brain pHi during or between attacks. Energy phosphate metabolism but not pHi appears disordered during a migraine attack.

Adenosine Triphosphate↗

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

Brain pH in migraine: an in vivo phosphorus-31 magnetic resonance spectroscopy study.

The intracellular pH (pHi) of cerebral cortex was measured in migraine patients by use of in vivo phosphorus-31 NMR spectroscopy. No changes in pHi were measured during a migraine attack. The long-standing concept that the headache of migraine is due to cerebral vasodilation induced by prodromal vasospasm-induced ischemic acidosis is not substantiated.

Adult↗

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

The development of a pH-sensitive contrast agent for NMR 1H imaging.

Fe(III)meso-tetra(4-sulfonatophenyl)porphine (Fe-TPPS4) has been investigated as a potential pH-sensitive nuclear magnetic resonance (NMR) proton image contrast agent. Relaxation rates (1/T1 and 1/T2) of water protons were measured as a function of pH and concentration of Fe-TPPS4 in phosphate-buffered isotonic saline. Transverse relaxation rates (1/T2) did not change appreciably with pH above 6.0. Longitudinal relaxation rates (1/T1) increased significantly between pH 7.75 and 5.75. This effect was more pronounced with the increasing concentration of Fe-TPPS4 from 0.1 to 1.5 mM and is attributed to a pH-dependent equilibrium between the high-spin (S = 5/2) Fe-TPPS4 monomer at low pH and the antiferromagnetically coupled mu-oxodimer O-(FeTPPS4)2 at high pH. The efficacy of this pH-dependent contrast agent is demonstrated in vitro.

Contrast Media↗

PubMed1986

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↗

PubMed1985

Biochemical effects of cerebral ischemia: relevance to migraine.

Although decreased CBF has now been reported during the prodrome of migraine, the cause of the decreased flow is still unknown. It is particularly unclear whether these phenomena are related to vasospasm and "steal" between the extracranial and intracranial circulation or to the spreading depression of Leao and the accompanying metabolic depression. In the present paper, metabolic changes in the brain during ischemia and reperfusion are reviewed and compared with CNS biochemical changes during migraine attack. In addition, the technique of Topical Magnetic Resonance (TMR) as applied to the in vivo study of energy phosphate metabolism in extracranial tissues and brain is described and the potential of this technique to evaluate shifts in energy metabolism and pH in stroke and migraine is discussed.

5-Hydroxytryptophan↗