PubMed HealthSearch

Biomedical subjects

R Deslauriers

Publications and source records attributed to R Deslauriers.

At least 19 recordsLinked to original sources

A 31p-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs.

To evaluate the effect of hypothermic circulatory arrest on brain metabolism, we used 31P-magnetic resonance spectroscopy to monitor brain metabolites in pigs during 2 hours of ischemia and 1 hour of reperfusion. Twenty-eight pigs were divided into five groups. Anesthesia (n = 5) and hypothermic cardiopulmonary bypass groups (n = 5) served as controls. In the circulatory arrest (n = 6), antegrade perfusion (n = 6), and retrograde (n = 6) brain perfusion groups, the bypass flow rate was 60 to 100 ml.kg-1.min-1. In the antegrade group, the brain was perfused via the carotid arteries at a blood flow rate of 180 to 200 ml.min-1 during circulatory arrest at 15 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml.min-1 during circulatory arrest at 15 degrees C. The intracellular pH was 7.1 +/- 0.1 and 7.3 +/- 0.1 in the anesthesia and hypothermic cardiopulmonary bypass groups, respectively. In the circulatory arrest group, the intracellular pH decreased to 6.2 +/- 0.1 and did not recover to its initial value (7.0 +/- 0.1) during reperfusion (p < 0.05 compared with the value obtained from the control groups at the corresponding time). Inorganic phosphate did not return to its initial level during reperfusion. In three animals in this group, levels of high-energy phosphates, adenosine triphosphate and phosphocreatine, recovered partially but did not reach the levels observed before arrest. In the group receiving antegrade perfusion, cerebral metabolites and intracellular pH were unchanged throughout the protocol. During circulatory arrest in the retrograde perfusion group the intracellular pH decreased to 6.4 +/- 0.1 and recovered fully during reperfusion (7.1 +/- 0.1). High-energy phosphates also returned to their initial levels during reperfusion. These studies show that deep hypothermic circulatory arrest with antegrade brain perfusion provides the best brain protection of the options investigated.

Adenosine Triphosphate

A 31P-nuclear magnetic resonance study of intermittent warm blood cardioplegia.

This study was designed to assess the effects of intermittent warm blood cardioplegia on myocardial energy metabolites, intracellular pH, and contractile function. The isolated blood-perfused pig hearts were divided into three groups. After 30 minutes of control perfusion, the hearts in group 1 (n = 10) received 90 minutes of continuous warm (37 degrees C) blood cardioplegia; the hearts in group 2 (n = 9) received six 5-minute periods of warm blood cardioplegia, interrupted by six 10-minute episodes of ischemia (37 degrees C). The hearts were then reperfused for 30 minutes. The hearts in group 3 underwent 150 minutes of control perfusion without cardioplegia or ischemic episodes. Phosphorus 31-nuclear magnetic resonance spectra showed that a 10-minute interruption of warm blood cardioplegia decreased phosphocreatine levels and intracellular pH by approximately 47% (p < 0.01) and 0.12 unit (p < 0.05), respectively, and increased inorganic phosphate levels by approximately 87%, whereas resumption of cardioplegia for 5 minutes resulted in almost 100% recovery of phosphocreatine and inorganic phosphate levels and intracellular pH. More important, subsequent interruptions did not result in any cumulative changes in phosphocreatine level, inorganic phosphate level, or intracellular pH beyond those changes observed after the initial cardioplegic interruption. Moreover, during reperfusion there were no significant differences in adenosine triphosphate and phosphocreatine levels among the three groups of hearts. Furthermore, hearts from groups 1 and 2 showed comparable recovery of contractile function. These results indicate that six 10-minute interruptions and six 5-minute restorations of warm blood cardioplegia caused only mild and reversible changes in myocardial energy metabolites and intracellular pH and these changes were not cumulative. This study suggests that antegrade intermittent warm blood cardioplegia may provide as much myocardial protection as does antegrade continuous warm blood cardioplegia in the normal heart.

Adenosine Triphosphate

Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium.

The aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia.

Aged

Pathways of Rb+ influx and their relation to intracellular [Na+] in the perfused rat heart. A 87Rb and 23Na NMR study.

The aims of this study were to characterize the routes of influx of the K+ congener, Rb+, into cardiac cells in the perfused rat heart and to evaluate their links to the intracellular Na+ concentration ([Na+]i) using 87Rb and 23Na nuclear magnetic resonance (NMR) spectroscopy. The rate constant for Rb+ equilibration in the extracellular space was 8.5 times higher than that for the intracellular space. The sensitivity of the rate of Rb+ accumulation in the intracellular space of the perfused rat heart to the inhibitors of the K+ and Na+ transport systems has been analyzed. The Rb+ influx rates were measured in both beating and arrested hearts: both procaine (5 mmol/L) and lidocaine (1 mmol/L) halved the Rb+ influx rate. In procaine-arrested hearts, the Na+,K(+)-ATPase inhibitor ouabain (0.6 mmol/L) decreased Rb+ influx by 76 +/- 24% relative to that observed in untreated but arrested hearts. Rb+ uptake was insensitive to the K+ channel blocker 4-aminopyridine (1 mmol/L). The inhibitor of Na+/K+/2 Cl- cotransport bumetanide (30 mumol/L) decreased Rb+ uptake only slightly (by 9 +/- 8%). Rb+ uptake was dependent on [Na+]i: it increased by 58 +/- 34% when [Na+]i was increased with the Na+ ionophore monensin (1 mumol/L) and decreased by 48 +/- 9% when [Na+]i was decreased by the Na+ channel blockers procaine and lidocaine. Dimethylamiloride (15 to 20 mumol/L), an inhibitor of the Na+/H+ exchanger, slightly reduced [Na+]i and Rb+ entry into the cardiomyocytes (by 15 +/- 5%). 31P NMR spectroscopy was used to monitor the energetic state and intracellular pH (pHi) in a parallel series of hearts. Treatment of the hearts with lidocaine, 4-aminopyridine, dimethylamiloride, or bumetanide for 15 to 20 minutes at the same concentrations as used for the Rb+ and Na+ experiments did not markedly affect the levels of the phosphate metabolites or pHi. These data show that under normal physiological conditions, Rb+ influx occurs mainly through Na+,K(+)-ATPase; the contribution of the Na+/K+/2 Cl- cotransporter and K+ channels to Rb+ influx is small. The correlation between Rb+ influx and [Na+bdi during infusion of drugs that affect [Na+]i indicates that, in rat hearts at 37 degrees C, Rb+ influx can serve as a measure of Na+ influx. We estimate that, at normothermia, at least 50% of the Na+ entry into beating cardiac cells is provided by the Na+ channels, with only minor contributions (< 15%) from the Na+/K+/2 Cl- cotransporter and the Na+/H+ exchanger.

Animals

The role of magnesium in myocardial preservation.

The purpose of this review is to look at the role of magnesium in the formation of preservation and reperfusion solutions for the ischaemic heart. Preservation of the heart during cardiac surgery procedures, including cardiac transplantation, can be divided into distinct phases: arrest, cold storage in the case of transplantation, global ischaemia during implantation or cardiac surgery procedures, followed by reperfusion when the heart is rewarmed and restarted. Although the magnesium ion can play a significant role in myocardial protection, it is important to recognize the different types of protection required during these different phases of surgical procedures. The rationale for the inclusion of magnesium in cardioplegic solutions is threefold: (i) for its negative inotropic effect; (ii) to prevent ischaemia-induced magnesium loss; (iii) to influence cellular ionic movements. Preservation temperature as well as the concentration of other ionic constituents present in the preservation solution alter the effects of magnesium. Results obtained from animal models suggest that elevated magnesium (16 mM) is beneficial to the hypothermic preservation of hearts with extracellular type solutions, especially when calcium is elevated in the solution formulation. Research has shown that the amplitude of the inotropic effect of magnesium varies from one species to another so that the beneficial effect of magnesium is inferior in the less sensitive species. Using the human atrial trabecular preparation as a model for myocardial preservation, we have assessed the effects of elevated magnesium on the recovery of developed force, both for long-term preservation (24 h) during hypothermic arrest (4 degrees C) and for reperfusion during rewarming of the trabeculae. No clear pattern emerged when the ratio of calcium to magnesium was altered in St Thomas' I and II solutions used for the storage. However, when the atrial trabecular preparation was rewarmed in a Krebs Henseleit buffer containing an elevated level of magnesium (16 mM), a greater number of trabeculae reached a greater developed force and had higher levels of energetic metabolites than when the magnesium in the Krebs Henseleit buffer was 1.2 mM. Several studies have suggested that an elevated magnesium prevents calcium overload by competing with this ion at the membrane, and reduces the workload, while ATP reserves and ion homoeostasis are re-established. The role of the magnesium ion in hypothermic preservation of the human myocardium is still not clear after many clinical and experimental studies and requires further investigation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Phasing spin-echo-acquired 31P spectroscopic images using complex conjugate data reversal.

A simple method has been developed for phasing 31P spectroscopic images acquired with short echo-time (1-2 ms) spin-echo sequences. The technique is based on reconstructing complete echoes in the time domain by the reversal of the complex conjugate of the data. After Fourier analysis, a magnitude reconstruction is used, which no longer broadens the lines. Advantages of the method compared to other phasing procedures are discussed.

Animals

An NMR probe to study function and metabolism simultaneously in isolated human cardiac tissue.

Trabeculae isolated from human atrial appendages have been used to study preservation of donor hearts for cardiac transplantation. We have developed a perifusion system equipped with a fiber optic strain gauge to study mechanical performance of human atrial trabeculae (10-20 mg) while simultaneously observing the energetic compounds by 31P NMR spectroscopy. The NMR probe consists of an eight-turn solenoid coil (2.3 mm i.d. x 5 mm length, 24-gauge wire) double tuned to allow observation of 1H and 31P nuclei. The probe and the perifusion system are temperature regulated and permit preservation studies using a variety of small muscles at low temperatures (down to 4 degrees C) as well as at physiological temperature (37 degrees C). 31P NMR spectra suitable for quantification can be obtained from approximately 10 mg of human atrial trabeculae in 15 min. Spectra of 8- to 12-mg mouse extensor digitalis longus or soleus muscle can be obtained in less than 10 min.

Animals

23Na and flame photometric studies of the NMR visibility of sodium in rat muscle.

23Na nuclear magnetic resonance spectroscopy (NMR) is increasingly being used to study Na+ gradients and fluxes in biological tissues. However, the quantitative aspects of 23Na NMR applied to living systems remain controversial. This paper compares sodium concentrations determined by 23Na NMR in intact rat hindlimb (n = 8) and excised rat gastrocnemius muscle (n = 4) with those obtained by flame photometric methods. In both types of samples, 90% of the sodium measured by flame photometry was found to be NMR-visible. This is much higher than previously reported values. The NMR measurements for intact hindlimb correlated linearly with the flame photometric measurements, implying that one pool of sodium, predominantly extracellular, is 100% visible. From measurements on excised muscle, in which extracellular space is more clearly defined, the NMR visibility of intracellular Na+ was calculated to be 70%, assuming an extracellular space of 12% of the total tissue water volume and an extracellular NMR visibility of 100%. 23Na transverse relaxation measurements were carried out using a Hahn spin echo on both intact hindlimb (n = 1) and excised muscle (n = 2) samples. These showed relaxation curves that could each be described adequately using two relaxation times. The rapidly relaxing component showed a T2 value of 3-4 ms and the slowly relaxing component a T2 of 21-37 ms. A spin lattice relaxation (T1) measurement on intact hindlimb yielded a value of 51 ms. These relatively long relaxation times show that the quadrupolar relaxation effect of Na+ complexing to large macromolecules or being otherwise motionally restricted is relatively weak. This is consistent with the high NMR visibilities reported here.

Animals

Cardiac hypothermia: 31P and 1H NMR spectroscopic studies of the effect of buffer on preservation of human heart atrial appendages.

31P and 1H nuclear magnetic resonance spectroscopy has been used to follow noninvasively the time course of energetic metabolite levels in human heart atrial appendages preserved under various temperatures and buffer conditions. From sample harvest up to the normal 5-h time limit for heart preservation, ATP levels in human atrial appendages are much better maintained in 0.9% saline and PIPES-buffered preservation solutions at 12 degrees C than at 4 degrees C. Furthermore, preservation at 12 degrees C can be improved considerably by using high extracellular buffer concentrations. The increased buffer concentration allows better maintenance of the intracellular pH and leads to a faster glycolytic rate as measured by lactate production. At 4 degrees C, ATP levels decline rapidly during the first 5 h but reached a stable plateau, which is well maintained over 15-20 h. At this temperature, the rate of lactate production is similar at all buffer concentrations (20, 60, and 100 mM PIPES). As a consequence of these observations, we postulate that the mechanisms of ATP production and utilization at 4 degrees C and at 12 degrees C are different. At 4 degrees C, the rate of glycolysis is temperature limited whereas at 12 degrees C, low intracellular pH inhibits glycolysis.

Adenosine Triphosphate

The effect of high buffer cardioplegia and secondary cardioplegia on cardiac preservation and postischemic functional recovery: a 31P NMR and functional study in Langendorff perfused pig hearts.

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.

Adenosine Triphosphate

Optimization of magnetization transfer measurements: statistical analysis by stochastic simulation. Application to creatine kinase kinetics.

A systematic study was performed to optimize the accuracy of kinetic parameters derived from magnetization transfer measurements. Three techniques were investigated: time-dependent saturation transfer (TDST), saturation recovery (SRS), and inversion recovery (IRS). In the last two methods, one of the resonances undergoing exchange is saturated throughout the experiment. The three techniques were compared with respect to the accuracy of the kinetic parameters derived from experiments performed in a given, fixed, amount of time. Stochastic simulation of magnetization transfer experiments was performed to optimize experimental design. General formulas for the relative accuracies of the unidirectional rate constant (k) were derived for each of the three experimental methods. It was calculated that for k values between 0.1 and 1.0 s-1, T1 values between 1 and 10 s, and relaxation delays appropriate for the creatine kinase reaction, the SRS method yields more accurate values of k than does the IRS method. The TDST method is more accurate than the SRS method for reactions where T1 is long and k is large, within the range of k and T1 values examined. Experimental verification of the method was carried out on a solution in which the forward (PCr----ATP) rate constant (kf) of the creatine kinase reaction was measured.

Adenosine Diphosphate

A high-sensitivity, high-B1 homogeneity probe for quantitation of metabolites.

Accurate quantitation of metabolites in biological samples of irregular shape and inhomogeneous composition is generally acknowledged to be difficult. The difficulties are less pronounced with a probe having excellent B1 field homogeneity, high sensitivity, and a resonant frequency independent of sample size and composition. A prototype probe that aims to fulfill these requirements in wide-bore horizontal magnets is described. It comprises four separate tuned rings on a spherical surface which give a B1 field that is flat to +/- 1% over the design volume. Inter-ring coupling, and to a fifth ring used for matching, is by induction, and the mathematics of the tuning of the system are derived. It is shown that resonant frequency variation with sample size is negligible, and that the sensitivity closely approaches the theoretical limit.

Animals

Elimination of signal strength dependency upon coil loading--an aid to metabolite quantitation when the sample volume changes.

The phase, height, and width of NMR spectral lines from a constant number of nuclei are frequently dependent upon changes in probe Q factor and tuning, caused by motion of the sample and/or changes in its electrical conductivity and size. Thus quantitation of metabolites in biological samples can be difficult. When probe tuning and matching are rendered independent by the use of a tuned coupling coil for matching, use of a very low input impedance preamplifier can virtually eliminate such dependencies in the received signal. Likewise, by reciprocity, the use of a low output impedance transmitter greatly reduces the dependence of pulse flip angle upon sample characteristics. Experimental results verifying these statements are presented, and the time course of signals from a swelling, perfused pig heart and an external reference are plotted.

Animals

1H magnetic resonance of human tumours. Analysis of the transverse relaxation of the methylene protons using continuous distributions of relaxation times.

In tumours, the decay of 1H transverse magnetization (relaxation profile) of the methylene resonances is usually not a single exponential. The conventional sum-of-exponentials approximation often leads to several solutions which fit the experimental data; choosing one solution over another is highly subjective. We have therefore analyzed transverse relaxation data for the methylene resonance of lipids in human tumours, assuming a continuous distribution of relaxation times. We have studied 89 colon tumours (27 with metastasis), 12 'normal' colon tissues, 40 breast tumours (24 with metastasis) and 13 malignant lymph nodes. All were primary tumours and the patients had received no previous treatment. Two continuous distribution approximations were tested. The two-parameter lognormal distribution provides a simple representation of the relaxation profile. The constrained regularization method (Contin) complements and extends the lognormal approach. The average T2 values, mean value of T2, whether derived from the lognormal or the Contin approximations, are consistent and comparable. Tumour and 'normal' colon tissue taken from the same patient show important differences in relaxation behaviour. A considerable broadening of the lognormal distribution, with mean value of T2 shifted to shorter values, is observed for the colon tumours. This is verified by the constrained regularization method. The 'normal' colon tissues are usually characterized by a single, relatively narrow distribution, while tumours show one or more broad peaks. A substantial broadening of the distribution of relaxation times is observed in colon tumours, whether metastasized or not. A similar broadening is noted for breast tumours and malignant lymph nodes, although the range is slightly less than for colon tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms

31P NMR studies of the metabolic status of pig hearts preserved for transplantation.

31P NMR spectroscopy has been used to evaluate the metabolic status of cardioplegically arrested pig hearts. Hearts were stored with Plegisol for up to 12 hours at either 5 degrees C or 12 degrees C. Results indicated that the ATP content of hearts could be maintained (greater than 70% of initial values) for up to 5 hours in the ischemic storage state. The ATP loss was greater at 12 degrees C. PCr was lost exponentially under the same conditions. Functional testing by reperfusing the stored hearts in vitro indicated a good correlation between the ATP content and survivability of the preparations. Twenty-four hour preservation of pig hearts using slow perfusion with a modified cardioplegic solution (Wicomb) allowed for preservation of both PCr and ATP, in all cases, reperfusion of hearts revealed a loss of NMR- visible ATP and PCr.

Adenosine Triphosphate

The effects of temperature and buffer concentration on the metabolism of human atrial appendages measured by 31P and 1H NMR.

In this study we measured changes in intracellular ATP and pH together with lactate production in isolated ischemic human atrial tissue. The measurements were made using 31P and 1H NMR. ATP preservation is improved as temperature is reduced from 20 degrees C to 1 degree C because of a progressive decrease in energy demand. At a constant temperature (12 degrees C), ATP preservation is improved by increasing the extracellular buffer capacity with PIPES buffer at concentrations up to 100 mM. Under these conditions, energy demand appears to increase but the ATP level is kept relatively constant for periods of 10 hours or longer. This appears to be due to a tighter regulation between supply and demand in which glycolysis is driven faster at relatively lower ADP and Pi levels. This tight regulation may be attributed to the better maintenance of intracellular pH.

Adenosine Triphosphate

Preservation of high-energy phosphates in human myocardium. A phosphorus 31-nuclear magnetic resonance study of the effect of temperature on atrial appendages.

After prolonged exposure to low temperatures (1 degree and 4 degrees C), human atrial trabeculae show poor recovery of contraction. At somewhat higher temperatures (12 degrees and 20 degrees C), recovery is much better (Keon and associates. Ann Thorac Surg 1988;46:337-41). Although better preservation of adenosine triphosphate and therefore improved contractile recovery might be expected after exposure to lower temperatures, it remained possible that, below a certain temperature, adenosine triphosphate-generating mechanisms could be slowed more than adenosine triphosphate utilization. To investigate this phenomenon further, we followed the time course of metabolic changes in human atrial appendages, harvested during cardiac bypass operations, at 1 degree, 4 degrees, 12 degrees, and 20 degrees C using high-resolution 31P and 1H nuclear magnetic resonance spectroscopy. The results are quantitated by correlation with data obtained from biochemical assays on quick-frozen tissues. Initial adenosine triphosphate levels in myocytes of human atrial appendages are 3.3 to 4.3 mumol.gm-1 tissue wet weight. At 20 degrees C, adenosine triphosphate disappears after 6 hours; at 12 degrees C, about half the initial adenosine triphosphate is still observable at this time; at 4 degrees C or 1 degree C, the decline is still slower. Only a small contribution toward adenosine triphosphate maintenance comes from creatine phosphate, since creatine phosphate, inorganic phosphate, and total creatine levels in the appendage are low (less than 2 mumol.gm-1 tissue wet weight). Glycolysis is active at all temperatures; the rate of glycolysis correlates positively with increasing temperature. Adenosine triphosphate generated by glycolysis falls just short of demand at all temperatures, but the difference is small at 1 degree and 4 degrees C. These studies lead us to conclude that the relatively poor recovery of contractile response of human atrial trabeculae, together with contracture reported previously at lower temperatures (1 degree and 4 degrees C), is not due to a failure to maintain adenosine triphosphate levels.

Adenosine Triphosphate