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Biomedical subjects

G Bloch

Publications and source records attributed to G Bloch.

At least 37 records · Page 2Linked to original sources

Field-frequency locked in vivo proton MRS on a whole-body spectrometer.

The stability of the main magnetic field is critical for prolonged in vivo magnetic resonance spectroscopy (MRS) acquisitions, especially for difference spectroscopy. This study was focused on the implementation and optimization of a field-frequency lock (FFL) on a whole body spectrometer, to correct the main field drift during localized proton MRS of the human brain. The FFL was achieved through a negative feed-back applied in real time on the Z0 shim coil current, after calculation of the frequency shift from a reference signal. This signal was obtained from the whole head with a small flip angle acquisition interleaved with the PRESS acquisition of interest. To avoid propagation of the important short-term time-correlated fluctuations of the head water frequency (mainly due to respiratory motion) onto Z0 correction, the sampling rate of the reference frequency and the smoothing window for the Z0 correction were carefully optimized. Thus, an effective FFL was demonstrated in vivo with no significant increase of the short-term variance of the water frequency. Magn Reson Med 1999 42:636-642, 1999.

Brain↗

Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid.

Previous studies in primates have shown that chronic systemic administration of the succinate dehydrogenase (SDH) inhibitor, 3-nitropropionic acid (3NP), replicates most of the motor, cognitive, and histopathological features of Huntington's disease. In the present study, serial 1H-NMR spectroscopy (1H-MRS) assessment of striatal and occipital cortex concentrations of N-acetylaspartate, phosphocreatine/creatine, choline, and lactate, were obtained every 2-weeks during the entire course of a chronic 3NP treatment in baboons. A region-selective increase in lactate was detected in the striatum of the 3NP-treated animals, either immediately before or in conjunction with a lesion in the dorsolateral putamen detected by T2-MR imaging. Absolute 1H-MRS quantitation demonstrated a progressive and region-specific decrease in striatal N-acetylaspartate, creatine, and choline, occuring as early as 3 weeks before the first detection of lactate. These results demonstrate that 1H-MRS can be used to monitor early stages of brain metabolic impairment. In addition, given that 3NP-induced SDH inhibition following systemic injection similarly affects all brain regions, the striatal selective decreases in N-acetylaspartate or creatine concentrations are not simply related to the level of mitochondrial impairment but to a preferential vulnerability of the striatum to 3NP-induced toxicity.

Animals↗

Simultaneous surgical treatment of atrial septal defect and atrial flutter using a simple modification of the atrial incision.

The reentrant circuit of common atrial flutter is known to be located in the right atrium between two anatomical barriers. Recent electrophysiologic studies have defined the tricuspid annulus as the anterior barrier, and the terminal crest and its continuation as the eustachian ridge as the posterior barrier. Construction of a bidirectional block to conduction between these two barriers by means of lesions created with radiofrequency current have been shown to be effective in ablating the flutter. We now find that surgical creation of such a block to conduction between the barriers by a simple modification of the atrial incision line is equally effective. In a 6-year-old boy, who was admitted to our hospital for closure of an atrial septal defect and treatment of sustained atrial flutter, the atriotomy was performed perpendicular to the terminal groove and extended towards the tricuspid annulus, placing some cryothermal lesions between the end of the incision and the annulus. The septal defect was closed using a Dacron patch. The child was free of arrhythmia both during the postoperative stay and over the initial three months of follow-up. We conclude that this simple modification of the atrial incision line provides cure of atrial flutter in children who require atriotomy for repair of congenital cardiac anomalies. It may also be beneficial in preventing 'incisional' reentrant tachycardia.

Atrial Flutter↗

Effect of chronic magnesium supplementation on magnesium distribution in healthy volunteers evaluated by 31P-NMRS and ion selective electrodes.

AIMS: The role of magnesium (Mg) intake in the prevention and treatment of diseases is greatly debated. Mg biodistribution after chronic Mg supplementation was investigated, using state-of-the-art technology to detect changes in free ionized Mg, both at extra- and intracellular levels. METHODS: Thirty young healthy male volunteers participated in a randomised, placebo (P)-controlled, double-blind trial. The treated group (MgS) took 12 mmol magnesium lactate daily for 1 month. Subjects underwent in vivo 31P-NMR spectroscopy and complete clinical and biological examinations, on the first and last day of the trial. Total Mg was measured in plasma, red blood cells and 24 h urine ([Mg]U ). Plasma ionized Mg was measured by ion-selective electrodes. Intracellular free Mg concentrations of skeletal muscle and brain tissues were determined noninvasively by in vivo 31P-NMR at 3T. NMR data were automatically processed with the dedicated software MAGAN. RESULTS: Only [Mg]U changed significantly after treatment (in mmol/24 h, for P, from 4.2+/-1.4 before to 4.1+/-1.3 after and, for MgS, from 3.9+/-1.1 before to 5. 1+/-1.1 after, t=2.15, P=0.04). The two groups did not differ, either before or after the trial, in any other parameter, whether clinical, biological or in relation with the Mg status. CONCLUSIONS: Chronic oral administration of Mg tablets to young healthy male volunteers at usual pharmaceutical doses does not alter Mg biodistribution. This study shows that an adequate and very complete noninvasive methodology is now available and compatible with the organization of clinical protocols which aim at a thorough evaluation of Mg biodistribution.

Adult↗

13C/31P NMR studies of glucose transport in human skeletal muscle.

The muscle intracellular (IC) free glucose concentration and the rate of muscle glycogen synthesis were measured by using in vivo 13C and 31P NMR spectroscopy in normal volunteers under hyperinsulinemic ( approximately 300 pM) clamp conditions at the following three plasma glucose levels: euglycemia ( approximately 6 mM), mild ( approximately 10 mM), and high ( approximately 16 mM) hyperglycemia. In keeping with biopsy studies, muscle IC free glucose concentration at euglycemia (-0.03 +/- 0.03 mmol/kg of muscle, mean +/- SEM, n = 10) was not statistically different from zero. A small but statistically significant amount of IC free glucose was observed during mild and high hyperglycemia: 0.15 +/- 0.08 (n = 5) and 0.43 +/- 0.20 mmol/kg of muscle (n = 5), respectively. Muscle glycogen synthesis rate, in mmol per kg of muscle per min, was 111 +/- 11 at euglycemia (n = 10), 263 +/- 29 during mild hyperglycemia (n = 5), and 338 +/- 42 during high hyperglycemia (n = 5), these three rates being significantly different from each other. As previous in vitro and in vivo studies, these rates suggest a Km (concentration at which unidirectional glucose transport reaches half-maximal rate) of the muscle glucose transport system in the 15-25 mM range under hyperinsulinemic conditions. The low concentrations of muscle IC free glucose observed under hyperinsulinemic conditions were interpreted, with this estimate and in the framework of metabolic control theory, as glucose transport being the predominant step controlling muscle glucose flux not only at euglycemia but also during hyperglycemia.

Biological Transport↗

Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient-echo NMRI and myoglobin NMRS during leg ischemia.

The purpose of this work was to investigate the temporal relationship between intensity changes in T2*-weighted NMR images and tissue oxygen content, measured by myoglobin proton NMR spectroscopy, in the skeletal muscle. During an ischemic stress test, the calf muscles of five healthy volunteers were studied at 3 Tesla. An interleaved NMRI-NMRS sequence was used, which made it possible to record T2*-weighted images and myoglobin spectra simultaneously. During ischemia, rapid changes in muscle signal intensity were observed on T2*-weighted images, which immediately preceded myoglobin desaturation. Bearing in mind the respective P50 of hemoglobin and myoglobin, this observation clearly favored the hypothesis that hemoglobin desaturation was responsible for the changes in T2*. This interpretation was further supported by the temporal coincidence between the experimental NMR data and a model of hemoglobin desaturation solely derived from physiological considerations.

Adult↗

Surgical ablation of a cardiac rhabdomyoma in an infant with tuberous sclerosis.

Cardiac rhabdomyoma is a rare tumor. Because of its rate of regression, mainly in the first year of life, conservative therapy is generally suggested when diagnosis occurs in infancy. We report surgical ablation of a rhabdomyoma in a 2-month-old boy in whom the tumor extended into the subaortic outflow tract. The tumor, which had a dual attachment to the aortic and mitral valves, was safely removed without any valvar damage. We suggest immediate surgical intervention for those rhabdomyomas which are life-threatening because of their size, location, or arrhythmogenicity.

Heart Neoplasms↗

[Coronary surgery on the beating heart under extracorporeal circulation in high-risk patients. An acceptable compromise?].

Coronary artery surgery with cardioplegia in high risk patients carries a risk of myocardial ischaemia and, without cardiopulmonary bypass, is not always technically feasible. The authors assessed an alternative, surgery on the beating heart with haemodynamic assist by cardiopulmonary bypass in 43 consecutive patients with poor left ventricular function (mean ejection fraction: 0.26), evolving myocardial ischaemia or acute myocardial infarction, old age (mean: 79.5 years) and comorbid conditions. Results were assessed mainly on clinical criteria. In addition, 9 patients had pre- and post-cardiopulmonary bypass measurements of markers of myocardial ischaemia (troponine Ic) and systemic inflammation (interleukines 6 and 10, elastase). In 6 cases, right atrial biopsy was analysed for expression of messenger ribonucleic acid coding for heat shock protein (HSP) 70; the data were compared with those of patients operated under warm blood cardioplegia. There was one cardiac death and one myocardial infarction. Myocardial conservation was confirmed by the minimal increase in troponine Ic levels and the significant increase in HSP 70 in RNA suggesting myocardial adaptation to stress. On the other hand, the minimal concentrations of mediators of inflammation were not significantly changed. In selected high risk patients, coronary revascularisation on the beating heart under cardiopulmonary bypass could be a valuable alternative. It conserves the potentially deleterious effects of cardiopulmonary bypass but peroperative global myocardial ischaemia, an important factor in the aggressivity of cardiac surgery, is eliminated.

Adult↗

Simultaneous determination of muscle perfusion and oxygenation by interleaved NMR plethysmography and deoxymyoglobin spectroscopy.

A novel approach is presented that combines NMR-plethysmography and NMRS of deoxymyoglobin in real-time, using line-by-line interleaved acquisitions of both gradient echo images during venous occlusion and of the N-delta proton signal of myoglobin's proximal F8 histidine. This method allowed simultaneous measurement of peripheral regional perfusion and skeletal muscle oxygen content. During reactive hyperaemia, using our combined NMRI-NMRS protocol, we explored the relationship between muscle reoxygenation (myoglobin resaturation half-time, y in s) and reperfusion (x in ml/100 g tissue/min) and found it to be highly significant (y = 70.83x-0.94; r2 = 0.70; F = 64.40; p = 9.73 x 10(-9). We also demonstrated that at low flow, muscle perfusion was a rate-limiting factor to reoxygenation. Making certain hypotheses, muscle oxygen extraction was derived from perfusion and myoglobin resaturation rate. Muscle oxygen extraction during early post-ischemic recovery (0.78 +/- 0.11, 0.79 +/- 0.09 and 0.72 +/- 0.05 at 0, 60 and 100 Torr counter-pressure, respectively) was shown to be independent of perfusion and maximum at each step of the protocol in most volunteers but also to display significant variability among subjects in this supposedly normal population sample.

Adult↗

Evidence for 100% 13C NMR visibility of glucose in human skeletal muscle.

The accuracy of the measurement of total muscle glucose by in vivo 13C NMR spectroscopy was tested in five normal volunteers during a euglycemic [1-13C]glucose infusion. The NMR visible concentration calibrated using an external reference was compared with that calculated from plasma glucose concentration, assuming that glucose remained extracellular. The NMR measurement always provided higher values than the calculation from plasma glucose: 0.51 +/- 0.035 (mean +/- SE) versus 0.38 +/- 0.005 mmol/liter of muscle on average. This systematic difference was interpreted as reflecting the presence of muscle glucose-6-phosphate, co-resonating with free glucose. Thus, glucose appeared to be virtually 100% NMR visible in human skeletal muscle.

Adult↗

Low visibility of lactate in excised rat muscle using double quantum proton spectroscopy.

Lactate NMR visibility was investigated in excised rat muscle at 3 T by comparing the concentration determined in situ by double quantum (DQ) proton spectroscopy (150 ms effective echo time) to the concentration measured in vitro from perchloric acid extracts of the same muscle samples. After 1-2 h of ischemia, lactate NMR visibility was 32 +/- 3% (+/- SE, n = 9), and was only 21 +/- 1% (n = 6) after 10-12 h. Muscle lactate T2 was 140 +/- 11 ms and 184 +/- 6 ms, respectively. All potential mechanisms of DQ lactate signal attenuation (B0 and B1 inhomogeneity, DQ transverse relaxation, diffusion) were examined, and accounted for when necessary. A significant increase in lactate NMR visibility was demonstrated using a shorter effective echo time (79 ms) DQ editing sequence. These results are interpreted as reflecting muscle lactate compartmentation between a long T2 pool predominantly detected by DQ spectroscopy, and a short T2 pool virtually invisible with longer echo time NMR techniques.

Animals↗

On-pump, beating-heart coronary artery operations in high-risk patients: an acceptable trade-off?

BACKGROUND: Current cardioplegic techniques do not consistently avoid myocardial ischemic damage in high-risk patients undergoing coronary artery bypass grafting. Alternatively, revascularization without cardiopulmonary bypass is not always technically feasible. We investigated whether an intermediary approach based on maintenance of a beating heart with cardiopulmonary bypass support but without aortic cross-clamping might be an acceptable trade-off. METHODS: Thirty-seven consecutive patients underwent coronary artery bypass grafting (with an average of two grafts per patient) in a pump-supported, non-cross-clamped beating heart. Inclusion criteria were poor left ventricular function (18 patients; mean ejection fraction, 0.25), evolving myocardial ischemia or infarction (11 patients, 5 of whom were in cardiogenic shock), and advanced age (3 patients; mean age 79.5 years) with comorbidities. Results were assessed primarily on the basis of clinical outcome. In addition, measurements of plasma levels of markers of myocardial damage (troponin Ic) and systemic inflammation (interleukin-6, interleukin-10, elastase) were done in 9 patients before and after bypass. In 6 patients, right atrial biopsy specimens were taken before and after bypass and processed by Northern blotting for the expression of messenger ribonucleic acid coding for the cardioprotective heat-shock protein 70. These biologic data were compared with those from control patients who underwent warm cardioplegic arrest within the same time span. RESULTS: There was one cardiac-related death (2.7%), one Q-wave myocardial infarction, and no strokes. Four other deaths occurred from noncardiac causes, yielding an overall mortality rate of 13.5%. Limitation of myocardial injury was demonstrated by the minimal increase in postoperative troponin Ic levels (3.3 +/- 1.0 micrograms/L versus 6.6 +/- 1.5 micrograms/L in controls; p < 0.05) and the finding that heat-shock protein 70 messenger ribonucleic acid levels (expressed as a percentage of an internal standard) were significantly increased after bypass compared with pre-bypass values (279% +/- 80% versus 97% +/- 21%; p < 0.05). In the control group (cardioplegia), end-arrest values of heat-shock protein 70 messenger ribonucleic acid were not significantly changed from baseline (148% +/- 49% versus 91% +/- 29%), a finding suggesting a defective adaptive response to surgical stress. Conversely, peak levels of inflammatory mediators were not significantly different between the two groups. The eight grafts to the left anterior descending coronary artery that were assessed angiographically, by transthoracic Doppler echocardiography, or both methods were patent with satisfactory anastomoses. CONCLUSIONS: In select high-risk patients, on-pump, beating-heart coronary artery bypass grafting may be an acceptable trade-off between conventional cardioplegia and off-pump operations. It is still associated with the potentially detrimental effects of cardiopulmonary bypass but eliminates intraoperative global myocardial ischemia.

Adult↗

[Valvular homografts].

Renewed interest in heart valve homografts is related to recent advances in viability. Increased viability is achieved by collecting explanted hearts from multi-organ donors and cryopreservation. Right access is usually used in case of hereditary cardiopathy to resect or repair the aortic, mitral and tricuspid valves. Life-long anticoagulant treatment can thus be avoided. Current mid-term and long-term results are very promising.

Heart Valve Diseases↗

An interleaved heteronuclear NMRI-NMRS approach to non-invasive investigation of exercising human skeletal muscle.

Novel tools are presented that aim at more comprehensive NMR investigations of human skeletal muscle metabolism, in particular during exercise protocols. They integrate imaging (NMRI) and spectroscopy (NMRS) experiments in a single dynamic examination. The first sequence that we propose combine NMR-plethysmography, 1H-NMRS of deoxymyoglobin and 31P-NMRS. This allows simultaneous determination of skeletal muscle perfusion, oxygenation and high-energy phosphates status. It is very well suited to the study of interplay between blood supply and energy metabolism during the recovery period from aerobic or anaerobic exercise. In a second sequence, the same spectroscopic measurements are associated to a 1H double quantum coherence (DQC) edition of lactate. It is, this time, possible to estimate muscle lactate production concurrently with oxygen content, high-energy phosphates distribution and intracellular pH. This sequence is intended mainly for metabolic investigations of ischemic bouts. Examples are given of the use of these sequences in normal adult volunteers. They demonstrate the technical feasibility of these new approaches and illustrate their potential for future applications, particularly non-invasive of regulatory mechanisms of muscle metabolism in situ.

Adult↗

Metabolic investigations in humans by in vivo nuclear magnetic resonance. Recommendations of ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic Diseases).

Although nuclear magnetic resonance (NMR) is well-established as a routine clinical imaging technique (magnetic resonance imaging or MRI), its application as a tool for metabolic investigations in humans is much less widespread in the medical community. To date, very few laboratories have combined the scientific interest, technical expertise (especially in vivo NMR spectroscopy), and facilities required to perform meaningful NMR studies of human metabolism. Among the few published reports of studies using in vivo NMR spectroscopy, diabetes mellitus, or more generally the physiology and pathophysiology of glucose homeostasis, is the dominant topic. This situation is related to the historical role of the Yale MR Center (R.G. Shulman, D.L. Rothman) in the development of in vivo NMR, and to the collaboration of NMR methodologists with the Endocrinology Section of the Yale Medical School (G.I. Shulman). Thus, in the field of diabetes and metabolism, in vivo NMR has already contributed significantly to increasing our understanding of basic physiology as well as of pathophysiological mechanisms. This "practical research note" first describes the basic principles of in vivo NMR and provides practical information about the use of this technique in metabolic investigations. The metabolic parameters accessible through in vivo NMR are then reviewed and illustrated by a few examples from the literature.

Biological Transport↗

Practical implementation of single-voxel double-quantum editing on a whole-body NMR spectrometer: localized monitoring of lactate in the human leg during and after exercise.

The classical double-quantum editing sequence 90 degrees,x-tau-180 degrees y-tau-90 degrees x-t1-90 degrees x-tau-180 degrees y-tau-AQ (tau = 1/4J) was rendered volume selective, by making slice selective the first 90 degrees pulse and the two 180 degrees pulses. Using simple rules to ensure optimum radio frequency phase coherence, this single-voxel editing sequence, reminiscent of a basic PRESS localization technique, was implemented on a whole-body 3 T spectrometer, and in vitro editing of lactate methyl protons was demonstrated without any significant loss in intrinsic sensitivity. The effectiveness of the proposed approach in vivo was also illustrated through the localized monitoring of lactate in the human leg during and after exercise.

Exercise↗

Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations.

BACKGROUND: Improvements in myocardial protection may include the continuous delivery of normothermic blood cardioplegia. Technical aids are required for optimal visualization of the operative field during the performance of coronary anastomoses if cardioplegia is to be given continuously or during minimally invasive operations. However, the effects of the different hemostatic devices on coronary endothelial function are unknown. METHODS: We compared the effects on endothelial function of two commonly used hemostatic techniques, coronary clamping and gas jet insufflation, with those of a technique using extravascular balloon occlusion to mimic systolic luminal closure by the surrounding myocardium. The three techniques were applied for 15 minutes on porcine epicardial coronary arteries from explanted hearts. For coronary clamping, standard bulldog clamps were used. Gas jet insufflation was applied by blowing oxygen (12 L/min) tangentially at a 45-degree angle 1 cm away from a 3-mm arteriotomy. Extravascular balloon occlusion was achieved with a needle-tipped silicone loop, the midportion of which, once positioned beneath the coronary artery, was inflated to push a myocardial "cushion" against the back of the vessel until its occlusion. Control rings were taken from the same coronary artery. The endothelial function of control and instrumented arterial rings was then studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. RESULTS: Contractions to potassium chloride and prostaglandin F2 alpha and endothelium-independent relaxation to sin-1, a nitric oxide donor, were unaffected in all groups. Endothelium-dependent relaxation to serotonin was impaired after clamping and preserved after gas jet insufflation and extravascular balloon occlusion. Maximal endothelium-dependent relaxation to serotonin was as follows: for coronary clamping, 63% +/- 6% versus 87% +/- 3% in controls; for gas jet insufflation, 67% +/- 12% versus 88% +/- 7%; and for extraluminal balloon occlusion, 79% +/- 6% versus 85% +/- 5%. CONCLUSIONS: Whereas commonly used hemostatic devices may impair endothelial function, extravascular balloon occlusion appears to achieve effective hemostasis while preserving endothelial integrity.

Animals↗