Noninvasive assessment of pharmaceutical intervention during myocardial ischemia-reperfusion in a canine model using two-dimensional 31P chemical shift imaging

1998 ◽  
Vol 76 (2-3) ◽  
pp. 522-531 ◽  
Author(s):  
Constance M Campbell ◽  
Gerald Wisenberg ◽  
Jane Sykes ◽  
R Terry Thompson

The metabolic effects during myocardial ischemia and sustained reperfusion of the antianginal agents diltiazem (n = 10) and propranolol (n = 10) were monitored with noninvasive phosphorus nuclear magnetic resonance spectroscopy to establish any correlation between metabolic changes and infarct size. Spectroscopy followed changes in high-energy phosphate concentrations and myocardial intracellular pH during 2 h of left anterior descending coronary artery occlusion and 3 subsequent weeks of reperfusion, in a closed chest canine infarct model. Gadolinium-DTPA enhanced magnetic resonance imaging was used to assess the extent of myocardial injury (infarct size). Microspheres were used to document the zone at risk and the success of reperfusion. Whereas diltiazem appeared to reduce the derangement in high-energy phosphates during coronary occlusion, there was no significant change in infarct size when compared with a previously studied control group. Propranolol, which produced a lesser decline in pH during occlusion and smaller pH changes during early reperfusion, was associated with a significant reduction in the degree of tissue necrosis (compared with controls). There was an inverse correlation (r = -0.51) between the change in myocardial pH (occlusion end to immediate reperfusion) and the recovery index (an index of myocardial salvage). By 1 h into reperfusion, there was a stronger inverse correlation between pH and infarct size (r = -0.75), implying a protective effect of delaying pH recovery during early reperfusion and indicating the potential use of this parameter as a predictor of tissue viability.Key words: diltiazem, propranolol, magnetic resonance spectroscopy, myocardial infarction.

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 328-333 ◽  
Author(s):  
D NF Harris ◽  
J A Wilson ◽  
S D Taylor-Robinson ◽  
K M Taylor

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 ± 0.86 vs after: 2.57 ± 1.31; mean ± 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 ± 0.04 vs 7.16 ± 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 ± 0.37 vs 6.39 ± 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.


1988 ◽  
Vol 8 (6) ◽  
pp. 816-821 ◽  
Author(s):  
Kathryn Allen ◽  
Albert L. Busza ◽  
H. Alan Crockard ◽  
Richard S. J. Frackowiak ◽  
David G. Gadian ◽  
...  

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. At the same time, intracellular pH and the concentrations of lactate and high-energy phosphates were measured in the brain using 1H and 31P nuclear magnetic resonance spectroscopy. Flow and metabolism have been followed during either a 15- or a 30-min ischaemic period (induced by bilateral carotid occlusion) and for up to 1 h of recovery. There was no significant difference between the flow characteristics of the two experimental groups. High-energy phosphate levels and pH returned to control within ∼20 min of the end of the ischaemic period. Lactate clearance, following a 30-min occlusion, was slower than the recovery of pH. The concentration of free ADP, calculated from the creatine kinase equilibrium, was lower during the recovery phase than under control conditions.


1999 ◽  
Vol 58 (4) ◽  
pp. 841-850 ◽  
Author(s):  
Chris Boesch ◽  
Jacques Décombaz ◽  
Johannes Slotboom ◽  
Roland Kreis

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.


1998 ◽  
Vol 85 (4) ◽  
pp. 1457-1463 ◽  
Author(s):  
Luke J. Haseler ◽  
Russell S. Richardson ◽  
John S. Videen ◽  
Michael C. Hogan

There is evidence that the concentration of the high-energy phosphate metabolites may be altered during steady-state submaximal exercise by the breathing of different fractions of inspired O2([Formula: see text]). Whereas it has been suggested that these changes may be the result of differences in time taken to achieve steady-state O2 uptake (V˙o 2) at different[Formula: see text] values, we postulated that they are due to a direct effect of O2 tension. We used31P-magnetic resonance spectroscopy during constant-load, steady-state submaximal exercise to determine 1) whether changes in high-energy phosphates do occur at the sameV˙o 2 with varied[Formula: see text] and 2) that these changes are not due to differences in V˙o 2onset kinetics. Six male subjects performed steady-state submaximal plantar flexion exercise [7.2 ± 0.6 (SE) W] for 10 min while lying supine in a 1.5-T clinical scanner. Magnetic resonance spectroscopy data were collected continuously for 2 min before exercise, 10 min during exercise, and 6 min during recovery. Subjects performed three different exercise bouts at constant load with the[Formula: see text] switched after 5 min of the 10-min exercise bout. The three exercise treatments were 1)[Formula: see text] of 0.1 switched to 0.21, 2)[Formula: see text] of 0.1 switched to 1.00, and 3)[Formula: see text] of 1.00 switched to 0.1. For all three treatments, the[Formula: see text] switch significantly ( P ≤ 0.05) altered phosphocreatine: 1) 55.5 ± 4.8 to 67.8 ± 4.9% (%rest); 2) 59.0 ± 4.3 to 72.3 ± 5.1%; and 3) 72.6 ± 3.1 to 64.2 ± 3.4%, respectively. There were no significant differences in intracellular pH for the three treatments. The results demonstrate that the differences in phosphocreatine concentration with varied [Formula: see text] are not the result of different V˙o 2onset kinetics, as this was eliminated by the experimental design. These data also demonstrate that changes in intracellular oxygenation, at the same work intensity, result in significant changes in cell homeostasis and thereby suggest a role for metabolic control by O2 even during submaximal exercise.


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