Biomedical subjects
Publications and source records attributed to V H Subramanian.
A new pulse sequence which edits proton spectra of lactate with full signal return and gives good suppression of water and fat signals is described. This sequence exploits longitudinal spin-order from lactate to edit lactate from fat. Experimental results from phantoms and excised pig heart are presented.
Cerebral blood flow (CBF) was measured in cat brain in vivo at 2.7 T using 2H NMR to monitor the washout of deuterated saline injected into both carotid arteries via the lingual arteries. In anesthetized cats, global CBF varied directly with PaCO2 over a range of 20-50 mm Hg, and the corresponding global CBF values ranged from 25 to 125 ml.100 g-1.min-1. Regional CBF was measured in a 1-cm axial section of cat brain using intracarotid deuterated saline and gradient-echo 2H NMR imaging. Blood flow images with a maximum pixel resolution of 0.3 x 0.3 x 1.0 cm were generated from the deuterium signal washout at each pixel. Image derived values for CBF agreed well with other determinations, and decreased significantly with hypocapnia.
A new NMR technique for nondestructive, noninvasive, nonradioactive concurrent measurements of blood flow and several energy-dependent metabolites were applied to in situ cat brain during high cerebral blood flow states (seizures) and low flow states (carotid occlusion plus hemorrhagic shock). An inductively coupled, quadruple-tuned surface coil with a 50-ohm match at all relevant frequencies was used for both excitation and receiving. A broadband spectometer was used to measure the 31P spectrum (PCr, ATP, Pi, and pH), a water-suppressed 1H spectrum (lactate), 23Na, and 19F (blood flow via CHF3 washout). Each nucleus was excited at an independently determined rate. Sodium, with a short T1, was excited more frequently than phosphorus. The results qualitatively agreed with other techniques. Blood flow greatly increased during seizures with a 10% decrease in the Na signal, minimal lactate accumulation, no pH shift, and a change in the PCr-to-Pi ratio from 3.4 to 1.7. During carotid occlusion plus hypotension blood flow, PCr and ATP decreased to less than 10% of baseline values. Changes in PCr and Pi preceded parallel changes in Na and ATP. These experiments demonstrated the feasibility of concurrent measurements of physiologically induced changes in high-energy phosphates, lactate, sodium, and blood flow from the same volume of brain, in a nondestructive manner using NMR spectroscopy.
The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)
The energy metabolism of the brain has been measured in a middle cerebral artery (MCA) occlusion model in the cat utilizing 31P-nuclear magnetic resonance (NMR). 31P-NMR spectra were serially obtained during 2 h of ischemia and a subsequent 4-h recovery period. The ratio of creatine phosphate (PCr) to inorganic phosphate (Pi) (PCr/Pi) showed a precipitous decrease in parallel with changes in electroencephalographic (EEG) amplitude in severe strokes during ischemia as well as during recirculation. Animals with mild strokes, as determined by EEG criteria, exhibited a much smaller decrease in PCr/Pi during ischemia. In the severe strokes, there was a splitting and significant shift of the Pi peak immediately after occlusion. In addition, the shifted Pi peak rapidly increased and remained elevated throughout the study. In the mild strokes, Pi also increased, but not as markedly. Intracellular pH determination by chemical shift of the Pi peak revealed a decrease from 7.1 to 6.2-6.3 during ischemia and the subsequent recovery period in the animals with severe strokes, whereas the pH in the animals with mild strokes did not show a significant change. A gradual decrease in adenosine triphosphate (ATP) to 57-79% of the control was exhibited in severely stroked animals during both the ischemia and the recovery period, whereas there was no change in ATP in the mild stroked animals. These results suggest that the dynamic process of pathophysiological changes in an MCA occlusion model in the cat leads to significant differences in cerebral metabolism between animals with mild and severe strokes.
With the use of specially designed multiple-tuned probes for magnetic resonance (MR) imaging, data collection schemes can be developed for obtaining images of different nuclei simultaneously. Both phantom and in vivo MR images of two nuclei (either hydrogen-1, phosphorus-31, lithium-7, or fluorine-19) were obtained in the time span necessary to collect the image of the less sensitive nuclei. This technique offers a means by which physiologic and anatomic information can be gathered in a highly efficient fashion.
The in vivo dog brain 31P NMR spectrum has a large peak in the phosphodiester region accounting for more than 35% of the total observable phosphorus metabolites. It is possible to reduce the intensity of this peak by off-resonance saturation. To characterize the nature of this peak, extracts of dog brain frozen in situ were analyzed by high resolution 31P NMR. ATP, phosphocreatine, inorganic phosphate, and phosphomonoesters were recovered in appropriate amounts in the methanol:HCl extract. However, acid soluble phosphodiesters accounted for only 8% of the observable phosphorus. More NMR observable phosphodiesters were selectively recovered following CHCl3:methanol extraction of phospholipids. These results suggest that the in vivo phosphodiester resonance has substantial contributions from a fraction of mobile brain phospholipids.
The regulation of the energy metabolism in contracting skeletal muscle is under close control, and several regulating factors have been reported. The aim of this study was to investigate the importance of the oxygen supply as a limiting factor for muscle performance during contractions and recovery from contractions. To perform well-controlled standardized experiments on contracting skeletal muscle, the perfused rat hind limb model was developed. The 31P NMR technique was adapted to the rat hind limb model. This enabled continuous nondestructive monitoring of the energy state at various levels of muscular activity. Significant correlations were found between oxygen delivery and oxygen consumption, lactate release, and glucose uptake, respectively. An increased degree of fatigue was observed at lower oxygen deliveries. In both soleus and gastrocnemius muscles, oxygen delivery correlated with the intramuscular concentrations of phosphocreatine (PCr), lactate, and glycogen. The 31P NMR experiments showed a correlation between oxygen delivery and the steady-state level of PCr/inorganic phosphate (Pi) during the contraction period. The rate of recovery in PCr/Pi after the contraction was also dependent on oxygen delivery. The results demonstrate a causal relationship between oxygen supply and energy state in contracting as well as recovering skeletal muscles.
Magnetic resonance (MR) is a technique that permits the noninvasive evaluation of morphologic features and function based on the distribution of protons and other selected elements. We present a basic description of MR and illustrate both 31P-MR spectroscopy and proton imaging applications in pediatric patients. The applications of these techniques are diverse, and are presented concisely in an attempt to give pediatricians an overview of this new technology and its potential role in patient management.
The relationship between the oxygen supply and the energy metabolism in perfused rat hindlimb muscles was evaluated both during contractions and during recovery from contractions. The 31P-nuclear magnetic resonance (NMR) technique and conventional biochemical methods were used. Significant correlations were found between the oxygen delivery and the oxygen consumption, lactate release and glucose uptake, respectively. An increased degree of fatigue was observed at the lower oxygen deliveries. In both the soleus and gastrocnemius muscles the oxygen delivery correlated with the intramuscular concentrations of phosphocreatine, lactate, and glycogen. The 31P-NMR experiments showed a correlation between the oxygen delivery and the steady-state level of the phosphocreatine-to-inorganic phosphate (PCr+Pi) ratio during the contraction period. The rate of recovery in PCr/Pi after the contractions was also dependent on the oxygen delivery. The results demonstrate a causal relationship between the oxygen supply and the energy state in contracting as well as recovering skeletal muscles.
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