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Subcortical structures involved in pain processing: evidence from single-trial fMRI.

Pain is processed in multiple cortical and subcortical brain areas. Subcortical structures are substantially involved in different processes that are closely linked to pain processing, e.g. motor preparation, autonomic responses, affective components and learning. However, it is unclear to which extent nociceptive information is relayed to and processed in subcortical structures. We used single-trial functional magnetic resonance imaging (fMRI) to identify subcortical regions displaying hemodynamic responses to painful stimulation. Thulium-YAG (yttrium-aluminum-granate) laser evoked pain stimuli, which have no concomitant tactile component, were applied to either hand of healthy volunteers in a randomized order. This procedure allowed identification of areas displaying differential fMRI responses to right- and left-sided stimuli. Hippocampal complex, amygdala, red nucleus, brainstem and cerebellum were activated in response to painful stimuli. Structures related to the affective processing of pain showed bilateral activation, whereas structures involved in the generation of withdrawal behavior, namely red nucleus, putamen and cerebellum displayed differential (i.e. asymmetric) responses according to the side of stimulation. This suggests that spatial information about the nociceptive stimulus is made available in these structures for the guidance of defensive and withdrawal behavior.

Adult↗

Histologic analysis of thermal effects of laser thermokeratoplasty and corneal ablation using Sirius-red polarization microscopy.

PURPOSE: To evaluate how well several histologic techniques differentiate degrees of thermally induced changes in corneal tissue after laser thermokeratoplasty (LTK) or corneal ablation. SETTING: Medical Laser Center Lübeck, Germany. METHODS: Corneas of freshly enucleated porcine eyes were treated with a continuous wave laser diode (1.86 microns) and a pulsed chromium-thulium-holmium: YAG laser (2.1 microns) to produce LTK lesions or ablated with a Q-switched and a free-running chromium-erbium: YSGG laser (2.70 microns), a free-running erbium: YAG laser (2.94 microns), and an argon-fluoride excimer laser (193 nm). The lesions were evaluated by light microscopy (LM) (hematoxylin and eosin, Azan, van Gieson's, and Masson-Goldner's trichrome stains), transmission electron microscopy (TEM), and polarization microscopy after Sirius-red staining. Sirius-red, a strongly elongated, birefringent molecule binding parallel to collagen molecules, was used to enhance corneal birefringence. RESULTS: With routine LM, it was difficult to discriminate the degrees of thermal alterations in LTK lesions. Combined Sirius-red staining and polarization microscopy distinguished between a strongly coagulated central zone and the transition zone to normal tissue. Sirius-red uptake was increased in both zones, reflecting the availability of new binding sites. The central zone appeared darker under polarization than normal collagen because of a loss of birefringence. Intrinsic birefringence was greatly reduced; however, form birefringence partly remained as long as some collagen fibrils were intact. In the center of very strong lesions, where the collagen was hyalinized, birefringence was completely lost because of the complete disintegration of the fibrillar structure, which was visible under TEM. The transition zone toward normal cornea showed increased birefringence because the natural birefringence was largely preserved and enhanced by the increased Sirius-red uptake. Mechanical stretching between neighboring LTK lesions was manifested by increased birefringence. CONCLUSION: Sirius red offered an improved and simple histologic method for analyzing thermal collagen changes. It may contribute to a better understanding of the working mechanisms of LTK and improve analysis of thermal effects in corneal ablation.

Animals↗

Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices.

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.

Adult↗

Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis.

OBJECTIVE: Somatosensory evoked potentials (SEPs) play a less important role in the diagnosis of multiple sclerosis (MS) than visually evoked potentials. Since standard SEPs only reflect the dorsal column function, we now investigated spinothalamic tract function in patients with MS using laser-evoked potentials (LEPs). METHODS: LEPs to thulium laser stimuli (3ms, 540 mJ, 5mm diameter) were recorded from 3 midline positions (Fz, Cz, Pz) in 20 patients with MS, and 6 patients with possible but unconfirmed MS. Peak latencies and peak-to-peak amplitude of the vertex potential negativity (N2) and positivity (P2) were evaluated and compared with normative values from 22 healthy control subjects. Median and tibial nerve SEPs were recorded with standard methods. Depending on the results of sensory testing, two skin areas (both hands, both feet, or one hand and foot of the same body side) were assessed in each patient. RESULTS: In group comparisons, LEPs in patients with MS were significantly delayed and reduced in amplitude compared with healthy subjects (P<0.001) or patients with suspected but unconfirmed MS (P<0.05). In intraindividual comparisons within the patients with MS, LEP amplitude was significantly lower (P<0.01) and latencies were significantly longer (N2: P<0.01; P2: P<0.05) for a clinically hypoalgesic skin area than an unaffected control area. On a single case basis, LEPs were abnormal in 12 (60%) and SEPs in 8 (40%) of the patients with MS; combined analysis of LEPs and SEPs raised sensitivity to 75% (15 patients). LEPs were also abnormal for 7 skin areas with clinically normal nociception and thermal sensitivity, indicating subclinical lesions. Standard SEPs detected subclinical lesions in 5 areas with normal tactile sensitivity. CONCLUSIONS: In patients with multiple sclerosis, spinothalamic tract function and LEPs were impaired more often than dorsal column function and SEPs. LEPs also detected subclinical lesions. Combined assessment of LEPs and SEPs can help to document dissemination of demyelinating CNS lesions and thus contribute to the diagnosis of multiple sclerosis.

Adult↗

Effect of rare-earth component of the RE/Ni catalyst on the formation and nanostructure of single-walled carbon nanotubes.

A systematic experimental study has been carried out on the efficiency of bimetallic catalysts based on Ni and the rare-earth elements Y, La, Ce, Nd, Gd, Tb, Dy, Ho, Er, and Lu (group A) and Eu, Sm, Yb, and Tm (group B) in the synthesis of single-walled carbon nanotubes (SWNTs). The two groups give quite different results when analyzed by a combination of SEM/TEM and Raman and UV-NIR spectroscopies. The elements in group A have an obvious catalytic effect and increase the yield of SWNTs dramatically, whereas those in group B are not efficient catalysts. The diameter distribution of the synthesized SWNTs was also affected by the rare-earth element used. For group A metals, there is a tendency that the fraction of small-diameter tubes decreases with decreasing ionic radius of the rare-earth element used. EDX and X-ray analyses indicate that group A metals deposit on the cathode deposits and form rare-earth carbides, whereas no group B metals are found in cathode deposits, except for a small amount of Tm present in the form of thulium carbide. Further analysis indicates that there is a very strong correlation between the ability to form rare-earth carbides and the catalytic efficiency for the formation of SWNTs.

Journal Article↗

7Li nuclear magnetic resonance study for the determination of Li+ properties in neuroblastoma SH-SY5Y cells.

Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel 7Li NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane-N,N',N'',N'''-tetramethylene phosphonate (HTmDOTP4-). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 mM HTmDOTP4- were 0.055 +/- 0.006 (n = 4) and -0.025 +/- 0.006 min(-1) (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Na+ channel-mediated Li+ transport in SH-SY5Y cells. 7Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Retention time of feed particles and liquids in the stomachs and intestines of dairy cows. Direct measurement and calculations based on faecal collection.

To validate a method for analysing indigestible marker excretion patterns in terms of digesta passage, the mean retention time (MRT) of long hay, ground hay and concentrate, marked, respectively, with thulium, ytterbium and dysprosium was measured in the total digestive tract (TMRT) and in the stomachs (SMRT) of four cows fed on a diet of hay in the long form (17.7 kg DM/day). The MRT of the particulate and liquid phases in the intestines was obtained after faecal particles labelled by Europium and Chromium EDTA were pulse dosed through the duodenal cannula. Following test meals, total faecal collection and spot sampling of duodenal digesta were performed at fixed intervals. TMRT were 51.7, 45.6, 40.6 h and SMRT were 39.5, 31.9 and 28.0 h, respectively, for hay, ground hay and concentrate. The MRT of the liquids in the rumen (8.7 h) was shorter than the SMRT of particles but there was no differential passage between liquids and particles after the duodenum. Intestinal MRT averaged 11 h and was partitioned into 7.5 and 3.5, respectively, for MRT in the tubular sections and the caecum-proximal colon. The compartmental analysis of the faecal patterns of markers given during a test meal gives the following results. The time associated with the descending part of faecal kinetics (respectively, 25.3 and 22.9 h for hay and concentrate) is directly related to the escape of feed particles from the rumen. The delay of first appearance of markers mostly reflects transit in the post duodenal tubular sections for the concentrate. The time associated with the ascending part (respectively, 16.9 and 9.4 h for hay and concentrate) represents the time required to reduce the size of the forage particles (7 h according to the difference between TMRT of long and ground hay direct measurements) and caecal mixing (3.5 h) as well as other compartments or processes that are not clearly identified.

Animal Feed↗

Long-term expression of transforming growth factor TGF beta 1 in mouse skin after localized beta-irradiation.

The long-term expression of TGF beta 1 in mouse skin after localized irradiation with a beta-emitting source is reported. The skin of CBA/ca mice was exposed to 50 Gy superficial beta radiation from an 11 mm strontium-90 source. Such a dose produced an acute moist desquamation reaction in 100% of the animals, which was macroscopically resolved within 30 days. The acute response was followed by progressive remodelling of dermal tissues as characterized by histological means. The expression of TGF beta 1 was followed for 12 months after irradiation and showed three distinct waves of expression at the RNA level. Levels of expression initially rose to 230% above controls at 6 h before returning to control levels around 24-48 h. Expression then rose again to 169 and 234% above controls at 14 and 28 days post-irradiation respectively. Levels then declined to those of the controls by 2 months. A progressive increase in expression was then noted after 3 months, which peaked around 9 months and was resolved by 12 months. In a parallel study the skin of 144 CBA/ca mice was exposed to 50 Gy superficial beta radiation from 2 x 4 cm Thulium-170 source and compared with a similar group of sham-irradiated controls. The irradiated group showed a cumulative tumour incidence of 54.3% compared with 0% incidence in the sham-irradiated group. Of the 45 radiation-induced tumours a representative sample of 16 (nine malignant fibrous histiocytomas; three fibrosarcomas; two fibromas; one squamous cell carcinoma; one rhabdomyosarcoma) were selected for further study. Semiquantitative PCR on all these tumours showed elevated levels of TGF beta 1 expression ranging from 1.8 to 87-fold above the levels found in normal skin. This study is part of ongoing investigations into the long-term effects of single accidental exposures. The 50 Gy dose used is comparable with the surface doses obtained by some of the victims of the Chernobyl accident.

Animals↗

Cause of upper urinary-tract essential hematuria: Veno-caliceal fistula or contralateral coexistent upper-tract transitional-cell carcinoma? Case report.

A 65-year-old woman was admitted with intermittent gross hematuria of 6 months' duration without other significant urinary-tract symptoms. At bilateral ureterorenoscopy under general anesthesia, a connection from an upper calix to the main left renal vein through a small venous channel was apparent, but there was no evidence of bleeding. In the right upper calix, a bleeding small papillary lesion was seen and ablated with low-power thulium laser coagulation. The histologic examination revealed a grade 3 stage pT1 TCC. Where no definite bleeding is seen from a veno-caliceal fistulous opening at ureterorenoscopy, it is imperative to inspect the entire contralateral upper urinary tract to exclude other causes of bleeding.

Aged↗

THC:YAG laser sclerostomy with mitomycin subconjunctival injection in rabbits.

We performed sclerostomy using THC:YAG laser (thulium, holmium, chromium doped YAG crystal) and subconjunctival injection of mitomycin soon after the filtering process in rabbits to observe the lowering effect of intraocular pressure(IOP) and filtering bleb formation. A 1-mm conjunctiva wound was made 12 mm away from the sclerostomy site to allow the entry of the optic probe for delivering energy. Forty-eight rabbits were divided into 3 groups. After sclerostomy, Group I received 0.2 ml normal saline subconjunctival injection and Group II and III received 0.2 ml mitomycin injection of 0.1 and 0.2 mg/ml respectively. One eye of each rabbit was randomly selected for the experiment while the fellow eye served as control. The bleb lasted 1.4 +/- 0.5 days (or 1 to 2 days) in Group I, 8.5 +/- 4.5 days (or 4 to 17 days) in Group II and 15.4 +/- 10.9 days (or 4 to 37 days) in Group III. The IOP lowering effect was significantly enhanced in Group III. The postoperative complication was minimal corneal punctate erosion in the mitomycin group, but all of them, however, resolved within one week. The results demonstrated that mitomycin is effective in prolonging the filtering effect produced by the THC:YAG laser.

Animals↗

Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study.

Only recently have neuroimaging studies moved away from describing regions activated by noxious stimuli and started to disentangle subprocesses within the nociceptive system. One approach to characterizing the role of individual regions is to record brain responses evoked by different stimulus intensities. We used such a parametric single-trial functional MRI design in combination with a thulium:yttrium-aluminium-granate infrared laser and investigated pain, stimulus intensity and stimulus awareness (i.e. pain-unrelated) responses in nine healthy volunteers. Four stimulus intensities, ranging from warm to painful (300-600 mJ), were applied in a randomized order and rated by the subjects on a five-point scale (P0-4). Regions in the dorsolateral prefrontal cortex and the intraparietal sulcus differentiated between P0 (not perceived) and P1 but exhibited no further signal increase with P2, and were related to stimulus perception and subsequent cognitive processing. Signal changes in the primary somatosensory cortex discriminated between non-painful trials (P0 and P1), linking this region to basic sensory processing. Pain-related regions in the secondary somatosensory cortex and insular cortex showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with signal changes for painful trials (P2-4). This was also true for the amygdala, with the exception that, in P0 trials in which the stimulus was not perceived (i.e. 'uncertain' trials), the evoked signal changes were as great as in P3 trials, indicating that the amygdala is involved in coding 'uncertainty', as has been suggested previously in relation to classical conditioning.

Adult↗

Somatotopic representation of nociceptive information in the putamen: an event-related fMRI study.

The ability to locate pain plays a pivotal role in immediate defence and withdrawal behaviour. However, it is unclear to what extent nociceptive information is relayed to and processed in subcortical structures relevant for motor preparation and possibly the generation of withdrawal behaviour. We used single-trial functional magnetic resonance imaging (fMRI) to assess whether nociceptive information is represented in the putamen in a somatotopic manner. We therefore applied thulium-YAG laser-evoked pain stimuli, which had no concomitant tactile component, to the dorsum of the left hand and foot to 15 healthy subjects in a randomized order. In addition, 11 subjects were stimulated on the right body side. Differential representations of hand- and foot-related blood oxygen level dependent (BOLD) responses within the putamen were assessed using a single subject approach. Nociceptive stimuli significantly activated the putamen bilaterally. However, a somatotopic organization for hand- and foot-related responses was only present in the contralateral putamen. Here the foot was located anteriorly and medially to the hand, which parallels results from anatomical and microstimulation studies in monkeys and also human imaging data on the arrangement of movement related activity in the putamen. This result provides evidence for the hypothesis that behaviourally relevant nociceptive information without additional information from the tactile system is represented in the putamen and made available for pain related motor responses.

Adult↗

Sequence-specific and hydrolytic scission of DNA and RNA by lanthanide complex-oligoDNA hybrids.

Totally synthetic and sequence-specific nucleases and ribonucleases, which hydrolyze DNAs and RNAs selectively at target sites, have been prepared. Lanthanide ions, which efficiently hydrolyze the phosphodiester linkages in nucleic acids, are attached to the 5'-end of synthetic DNA oligomers (sequence-recognizing sites) by use of an iminodiacetate ligand. Under physiological conditions, the hybrids selectively hydrolyze substrate DNA or RNA at the 3'-side of the sequence which is complementary with the DNA oligomers in the hybrids. The cerium(IV) ion is the most active as to DNA scission, whereas the europium(III), thulium(III), and lutetium(III) ions are the most effective for RNA scission. All the scissions proceed totally via hydrolysis of the phosphodiester linkages, in the same way as the scissions by natural nucleases and ribonucleases do. The artificial enzymes, which show far greater sequence-specificities than natural ones, exhibit high potential for application to molecular biology, biotechnology, and therapy.

Animals↗

Effects of interstimulus interval on cortical responses to painful laser stimulation.

Short laser pulses applied to the skin are used increasingly in both clinical and basic assessment of nociceptive brain mechanisms. The authors aimed to characterize further the cortical responses to noxious laser stimuli and to define the interstimulus interval (ISI) for the optimum signal-to-noise ratio during a fixed measurement time. Three hundred six-channel whole-scalp magnetoencephalographic (MEG) and midline EEG signals were recorded from nine healthy adults during painful thulium laser stimulation. The stimuli were delivered on the dorsum of the left hand at ISIs of 0.5, 1, 2, 4, 8, and 16 seconds. The MEG responses peaked at 160 to 195 msec around the contralateral primary somatosensory (SI) cortex, at 150 to 190 msec in the contralateral secondary somatosensory (SII) cortex, and at 160 to 205 msec in the ipsilateral SII cortex. The simultaneously measured electrical vertex potentials peaked at 190 to 230 msec and 310 to 330 msec (N200-P300). All these responses showed rather similar refractory times: The amplitudes increased strongly from 0.5 to 4-second ISIs and thereafter saturated at ISIs of 8 to 16 seconds. On the basis of the time constants of the recovery cycles, the optimum ISI for obtaining the best signal-to-noise ratio for laser-evoked MEG and EEG responses during a fixed measurement interval is 4 to 5 seconds.

Adult↗

In vivo 23Na nuclear magnetic resonance study of maintenance of a sodium gradient in the ruminal bacterium Fibrobacter succinogenes S85.

Sodium gradients (DeltapNa) were measured in resting cells of Fibrobacter succinogenes by in vivo 23Na nuclear magnetic resonance using Tm(DOTP)5- [thulium(III) 1,4,7,10-tetraazacyclododecane-N',N",N"'-tetramethylenephosphonate] as the shift reagent. This bacterium was able to maintain a DeltapNa of -55 to -40 mV for extracellular sodium concentrations ranging from 30 to 200 mM. Depletion of Na+ ions during the washing steps led to irreversible damage (modification of glucose metabolism and inability to maintain a sodium gradient).

Animals↗

Effect of lidocaine on contracture, intracellular sodium, and pH in ischemic rat hearts.

The relationships among intracellular Na concentration ([Na+]i), intracellular pH, [ATP], and contracture during global ischemia were studied in isolated, perfused rat hearts. Intracellular Na was monitored by 23Na nuclear magnetic resonance (NMR) spectroscopy using thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonate) (TmDOTP5-) as the paramagnetic shift reagent. High-energy phosphates and pH were monitored under the same conditions using 31P-NMR spectroscopy. Lidocaine (130 microM), a class IB fast Na channel blocker known to protect ischemic myocardium, prolonged the time to contracture in both unpaced and paced hearts (240 beats/min). After 10 min of global ischemia in paced hearts, [Na+]i was lower in the lidocaine-treated group compared with untreated hearts. The addition of lidocaine also significantly attenuated the depletion of ATP as well as development of intracellular acidosis. At the time of contracture, however, there was no difference in [Na+]i or pH between the two groups. Interestingly, the effect of lidocaine on Na+i accumulation during ischemia was manifested during the first 5-10 min of ischemia, while its effect on pH occurred after 9 min. This finding suggests that a mechanism other than the Na-H exchanger may play a role in the accumulation of Na+i early in the course of ischemia.

Animals↗

Effects of ischemia on intracellular sodium and phosphates in the in vivo rat liver.

Metabolic factors that influence the transition form reversible to irreversible ischemic injury were studied in the rat liver in vivo with 31P-nuclear magnetic resonance (NMR) spectroscopy. Hepatic ischemia for 15, 35, or 65 min was produced by occlusion of the hepatic artery and portal vein in rats. Ischemia caused a rapid decrease in the ATP concentration ([ATP])-to-P(i) concentration ratio and pH within 5 min, but there was little change in these variables detectable by 31P-NMR with longer periods of ischemia. After reperfusion, the [ATP] and P(i) concentration returned toward normal values in livers exposed to 15 or 35 min of ischemia, but 65 min of ischemia were associated with only modest recovery in [ATP], and the [ATP] later decreased. Because the 31P-NMR spectrum was similar after brief compared with prolonged ischemia, it appears that neither ATP depletion, P(i) accumulation, nor acidosis predicts metabolic recovery. Hepatic intracellular NA+ was also measured in separate groups of animals by 23Na-NMR in the presence of a shift agent, thulium (III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene-phosphonate) (TmDOTP5-), and by atomic absorption spectroscopy. Under baseline conditions, the concentration of intracellular Na+ was 15.2 mM by atomic absorption spectroscopy and 16.5 mM by 23Na-NMR. Although the 31P-NMR spectrum responded very rapidly to the onset of ischemia, intracellular Na+ concentration measured by 23Na-NMR increased gradually but steadily at approximately 1.0 mM/min during early (up to 15 min) ischemia. These observations demonstrate that a rise in intracellular Na+ does occur early ischemia, that TmDOTP5- can be applied in vivo for analysis of intracellular Na+ in the ischemic liver, and that 31P-NMR spectroscopy is very sensitive to early ischemic injury.

Adenosine Triphosphate↗

Time course of myocardial sodium accumulation after burn trauma: a (31)P- and (23)Na-NMR study.

In this study, (23)Na- and (31)P- nuclear magnetic resonance (NMR) spectra were examined in perfused rat hearts harvested 1, 2, 4, and 24 h after 40% total body surface area burn trauma and lactated Ringer resuscitation, 4 ml. kg(-1). %(-1) burn. (23)Na-NMR spectroscopy monitored myocardial intracellular Na+ using the paramagnetic shift reagent thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonic acid). Left ventricular function, cardiac high-energy phosphates (ATP/PCr), and myocyte intracellular pH were studied by using (31)P NMR spectroscopy to examine the hypothesis that burn-mediated acidification of cardiomyocytes contributes to subsequent Na+ accumulation by this cell population. Intracellular Na+ accumulation was confirmed by sodium-binding benzofuran isophthalate loading and fluorescence spectroscopy in cardiomyocytes isolated 1, 2, 4, 8, 12, 18, and 24 h postburn. This myocyte Na+ accumulation as early as 2 h postburn occurred despite no changes in cardiac ATP/PCr and intracellular pH. Left ventricular function progressively decreased after burn trauma. Cardiomyocyte Na+ accumulation paralleled cardiac contractile dysfunction, suggesting that myocardial Na+ overload contributes, in part, to the progressive postburn decrease in ventricular performance.

Acidosis↗