Effect of brain,body, and magnet bore temperatures on energy metabolism during global cerebral ischemia and reperfusion monitored by magnetic resonance spectroscopy in rats

To record brain temperature for comparison with rectal and temporalis muscle temperatures in preliminary studies before MR spectroscopy experiments, a thermistor was inserted into the basal ganglia in eight anesthetized, ventilated, and physiologically monitored rats. The rats were placed in an MR spectrometer and subjected to 60 min of global cerebral ischemia and 2 h of reperfusion without radiofrequency (RF) pulsing. Body temperature was maintained at 37.5–38.0°C (normothermia) or 36.5–37.0°C (mild hypothermia). Brain temperature during ischemia, which dropped to 31.9 ± 0.3 (hypothermia) and 33.6 ± 0.5±C (normothermia), correlated with temporalis muscle temperature (r² = 0.92) but not with body or magnet bore temperature measurements. Ischemia reduced brain temperature approximately 1.7°C in rats subjected to mild hypothermia (1° reduction of body temperature). Parallel MR spectroscopy experiments showed no significant difference in energy metabolites between normothermic and hypothermic rats during ischemia. However, the metabolic recovery was more extensive 20–60 min after the onset of reperfusion in hypothermia rats, although not thereafter (P < 0.05). Mild hypothermia speeds metabolic recovery temporarily during reperfusion but does not retard energy failure during global ischemia in rats.     

Myocardial infarction in a canine model monitored by two-dimensional 31p chemical shift spectroscopic imaging

We have developed a closed chest animal model that allows noninvasive monitoring of cardiac high energy phosphate metabolism before, during, and for at least 3 weeks after a myocardial infarction. Ten beagles underwent 2 h of coronary occlusion followed by 3 weeks of reperfusion. Myocardial high energy phosphates from 12-ml voxels were noninvasively tracked using ³¹P two-dimensional chemical shift imaging. Gadolinium enhanced ¹H MRI identified the zone at risk, and radioactive microspheres assessed regional blood flow and partition coefficients. Occlusion of the left anterior descending coronary artery produced infarcts that were 13.7 ± 8.8% (mean ± SD) of the left ventricular volume. Rapid changes in the phosphocreatine and inorganic phosphate levels were observed during occlusion, whereas adenosine triphosphate levels decreased more slowly. All metabolites recovered to base-line levels 2 weeks after occluder release. Multiple inorganic phosphate peaks in the infarct voxel spectra indicated that more than one metabolically compromised tissue zone developed during occlusion and reperfusion. Microsphere data indicating three distinct blood flow zones during ischemia and reperfusion (<0.3, 0.3-0.75, and >0.75 ml/min/g) supported the grouping of pH values into three distinct metabolic distributions.     

Proton transfer ratio,lactate, and intracellular pH in acute cerebral ischemia

The amide proton transfer ratio (APTR) from the asymmetry of the Z‐spectrum was determined in rat brain tissue during and after unilateral middle cerebral artery occlusion (MCAo). Cerebral lactate (Lac) as determined by ¹H NMR spectroscopy, water diffusion, and T_1ρ were quantified as well. Lac concentrations were used to estimate intracellular pH (pH_i) in the brain during the MCA occlusion. A decrease in APTR during occlusion indicated acidification from 7.1 to 6.79 ± 0.19 (a drop by 0.3 ± 0.2 pH units), whereas pH_i computed from Lac concentration was 6.3 ± 0.2 (a drop by 0.8 ± 0.2 pH units). Despite the disagreement between the two methods in terms of the size of the change in the absolute pH_i during ischemia, ΔAPTR and pH_i (and Lac concentration) displayed a strong correlation during the MCAo. Diffusion and T_1ρ indicated cytotoxic edema following MCA occlusion; however, APTR returned slowly toward the values determined in the contralateral hemisphere post‐ischemia. These data argue that the APTR during ischemia is affected not only by pH_i but by other physicochemical factors as well, and indicates different aspects of pathology in the post‐ischemic brain compared to those that influence water diffusion and T_1ρ. Magn Reson Med 57:647–653, 2007. © 2007 Wiley‐Liss, Inc.     

Measurement of lactate accumulation by in vivo proton NMR spectroscopy during global cerebral ischemia in rats

In vivo 1H NMR spectral editing techniques were used to monitor cerebral lactate production during remotely controlled temporary forebrain ischemia in rats. The lactate/N-acetylaspartate (NAA) ratio correlated with survival after ischemia and subsequent reperfusion. The lactate/NAA ratio that predicted death after ischemia in rats was estimated to be approximately 1.3.     

Cerebral metabolite dynamics during temporary complete ischemia in rats monitored by time-shared 1H and 31P NMR spectroscopy

The changes in cerebral phosphorus metabolites, intracellular pH, and lactate during 30 min of complete global ischemia and 2 h of reperfusion were monitored by time-shared 1H and 31P in vivo NMR spectroscopy in rats. After the induction of ischemia, intracellular pH decreased from 7.14 +/- 0.01 to 6.32 +/- 0.10, and lactate concentration increased from 1.6 +/- 0.4 to 15.8 +/- 2.5 mumol/g; ATP and phosphocreatine were totally depleted, while inorganic phosphate increased 715 +/- 47%. Within 1 h after blood flow was restored, high-energy phosphates and lactate levels had recovered close to baseline levels. The changes in intracellular pH and lactate levels during ischemia and reperfusion correlated well.     

Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging

The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 ± 4.2% (mean ± SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 ± 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH³ signal of N-acetylaspartate (NAA) to 67 ± 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 ± 40 ms, considering a J-cou-pling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T₂ of the CH₃ signal of creatine/phosphocre-atine (Cr/PCr) was observed in the lesion, from 163 ± 22 ms during control to 211 ± 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.     

AKT信号通路通过亚低温对大鼠局脑缺血再灌注损伤神经元的保护作用

目的通过检测AKT及Bcl-2蛋白的表达,探讨亚低温对局脑缺血再灌注后神经元存活的影响。方法用线拴法制作大鼠大脑中动脉闭塞（MCAO）局脑缺血再灌注模型,将36只SD大鼠随机分成假手术组、常温缺血再灌注组和亚低温缺血再灌注组,缺血组分别缺血6h再灌注4h、24h、72h、1w（n=4）后处死,亚低温组于缺血后13~14min实施病灶侧亚低温持续4h。免疫组织化学法检测AKT、Bcl-2蛋白的表达,电镜检测自噬小体。结果不同缺血时间再灌注4h,亚低温组比常温组缺血侧半暗带AKT表达水平显著增高（P〈0.05）,Bcl-2表达明显降低（P〈0.01）;亚低温组自噬小体明显减少。结论病灶侧亚低温通过促进缺血半暗带脑组织AKT表达,抑制Bcl-2表达,从而抑制神经元凋亡,抑制自噬的产生,从而对神经元起保护作用,促进脑缺血后神经功能恢复。     

Serial MR Analysis of Early Permanent and Transient Ischemia in Rats: Diffusion Tensor Imaging and High b Value Diffusion Weighted Imaging

Objective

To evaluate the temporal evolution and diagnostic values of the diffusion tensor imaging (DTI) and the high b value diffusion weighted imaging (DWI) in the early permanent and transient cerebral ischemia.

Materials and Methods

For permanent or 30-minute transient-ischemia induced 30 rats, DTI and DWIs at both high b (b = 3000 s/mm²) and standard b value (b = 1000 s/mm²) were obtained at the following conditions: at 15, 30, 45, 60 minutes after the occlusion of what for hyperacute permanent ischemia; at 1, 3, 5, 7, 9 hours after the occlusion for acute permanent ischemia; and at 15 minutes before reperfusion, 0.5, 2.5, and 24 hours after reperfusion for transient ischemia. The diffusion parameters and their ratios were obtained and compared between different b values, and among different time points and groups, respectively.

Results

For both b values, the apparent diffusion coefficient (ADC) ratio decreased for first three hours, and then slightly increased until 9 hours after the occlusion during a gradual continuous increase of DWI signal intensity (SI) ratio, with excellent correlation between ADC ratios and DWI SI ratios. The DWI showed a higher contrast ratio, but the ADC map showed a lower contrast ratio for permanent ischemia at high b value than at standard b value. Fractional anisotropy (FA) increased for 1 hour, then gradually decreased until 9 hours after the occlusion in permanent ischemia and showed transient normalization and secondary decay along with change in ADC in transient ischemia.

Conclusion

This study presents characteristic initial elevation and secondary decay of FA, higher contrast ratio of DWI, and lower contrast ratio of ADC map at high b value, in addition to the time evolutions of diffusion parameters in early permanent and transient ischemia.     

Continuous assessment of relative cerebral blood volume in transient ischemia using steady state susceptibility-contrast MRI

The utility of a noninvasive steady state susceptibility-contrast MRI technique for continuous measurement of relative cerebral blood volume (rCBV) during global transient ischemia and subsequent hyperemia in a feline ischemia model is demonstrated. The measurements were obtained during a 10-min period of occlusion and 1-h period of reperfusion. Maximal hyperemic responses in gray matter, basal ganglia, and white matter (observed at 7,7, and 5 min, respectively) were 1.9 ± 0.5,1.8 ± 0.3, and 1.7 ± 0.6 times greater than baseline CBV (mean ± SEM). Thirty to forty minutes after onset of reperfusion, CBV returned to normal. Thereafter, it decreased below baseline, nearing the control level by 1 h after onset of reperfusion. Steady state susceptibility-contrast MRI permits continuous, in vivo mapping of alterations in CBV.     

Cerebral metabolic changes in patients with a symptomatic occlusion of the internal carotid artery: a longitudinal 1H magnetic resonance spectroscopy study

The objective of this 1H magnetic resonance spectroscopy study was to investigate the time course of the brain metabolites N-acetyl-aspartate (NAA), choline, and lactate in patients with transient or minor disabling neurological deficits associated with an occlusion of the internal carotid artery (ICA). Fifty patients had had symptoms of hemispheric ischemia, and 16 had suffered symptoms of retinal ischemia. Single-voxel proton spectra were obtained from uninfarcted cerebral regions on three occasions: 0-6, 6-12, and 12-18 months after symptoms. Reference values were obtained from 29 control subjects. In the 0-6 month period, patients with hemispheric ischemia showed a significantly lower NAA/creatine ratio in the hemisphere ipsilateral to the ICA occlusion, compared with control subjects and patients with retinal ischemia, and a significantly higher choline/creatine ratio, compared with control subjects. The prevalence of lactate did not differ significantly between patient groups. In the following time periods, the NAA/creatine ratio in patients with hemispheric ischemia tended to return to control values and no longer differed from that in patients with retinal ischemia; the choline/creatine ratio decreased significantly and returned to control values. These results demonstrate that cerebral metabolism is altered in patients with an ICA occlusion who have had a hemispheric ischemic event, but returns (choline) or tends to return (NAA) to control values over time. The metabolic changes occur primarily in the hemisphere ipsilateral to the symptomatic ICA occlusion and are related to the occurrence of the hemispheric ischemic event.     

Usefulness of MRI to Differentiate Between Temporary and Long-Term Coronary Artery Occlusion in a Minimally Invasive Model of Experimental Myocardial Infarction

The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 ± 4.4%; p = 0.008) and group 2 (9.4 ± 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 ± 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 ± 0.3, 5.9 ± 0.7, and 6.1 ± 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 ± 2.1%) compared to group 1 (5.3 ± 5.4%; p = 0.003) and group 2 (9.7 ± 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development.     

Diffusion of metabolites in normal and ischemic rat brain measured by localized 1H MRS

The apparent diffusion coefficient (ADC) of choline-containing compounds (Cho), creatine and phosphocreatine (Cre), N-acetyl-aspartate (NAA), lactate, and water was measured in normal rat brain, and in the ischemic and contralateral region of rat brain approximately 3 and 24 h after induction of focal cerebral ischemia. After 3 h of ischemia, the ADC of Cre and NAA in the ischemic region had significantly decreased by 29% and 19%, respectively (P < 0.05). Lactate ADC was also obtained in the ischemic region. After 24 h of focal ischemia, no ADC values could be measured for NAA, Cre and Cho in the ischemic region because their concentrations had become too low. The ADCs of lactate and water in the ischemic volume were virtually identical at 3 and 24 h after occlusion. The experiments suggest that the ADC decrease of water after induction of ischemia is partly caused by changes in the diffusion characteristics of the intracellular compartment.     

Intracellular Volume Measurement and Detection of Edema: Multinuclear NMR Studies of Intact Rat Hearts during Normothermic Ischemia

The present study describes the cell volume dynamics in intact rat hearts, during ischemia and after reperfusion. Cell volumes were measured in isolated hearts by either ¹³C or ⁵⁹Co NMR of mannitol or cobalticyanide, respectively, as extracellular markers and ¹H NMR of water as the aqueous space marker. A constant volume chamber was built inside a 15-mm NMR tube; the contents of the chamber were measured with and without a heart. The intracellular volume of isolated rat hearts was estimated to be 2.45 ± 0.13 ml/g dry weight. In the perfused heart, adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations were calculated to be 12.2 ± 0.7 and 16.1 ± 1.0 mM, respectively. Consecutive volume measurements showed cell swelling of 16% during 30 min of ischemia, which was reduced at reperfusion to 7%. After 30 min of reperfusion, ATP and PCr concentrations were 4.5 ± 0.8 and 8.1 ± 0.9 mM. It is concluded that: (1) cell swelling is an ischemic event, which is partially reversed by reperfusion; and (2) continuous measurement of cell volumes provides intracellular molar concentrations of metabolites, which are the physiologically significant parameters.     

Effects of severe global ischemia on N-acetylaspartate and other metabolites in the rat brain

N-acetylaspartate (NAA) is found exclusively in neurons and their processes in the adult brain. Since the regional distribution of NAA may be imaged using magnetic resonance spectroscopic imaging (¹H-MRSI), a regional measure of neuronal density may be noninvasively obtained. The technique may be particularly useful in the diagnosis of diseases where neurons are selectively injured, since these diseases do not result in definitive changes on conventional imaging studies. The goal of this study was to determine whether ¹H-MRSI measurement of NAA detects neuronal loss following global ischemia. ¹H-MRSI was performed in rats 24 h after global ischemia was induced by bilateral carotid occlusion plus hypotension. ¹H-MRSI showed that NAA was decreased by 29–74% in vulnerable regions, including the cortex, striatum, hippocampus, and, to a lesser extent, the thalamus. No change was observed in the brain stem or cerebellum. Regions where ¹H-MRSI observed NAA was decreased also had histological evidence of selective neuronal necrosis and showed marked increase of lactate and alanine. These results show that ¹H-MRSI detected loss of NAA in brain regions with selective neuronal loss, suggesting that ¹H-MRSI measurements of NAA could detect neuronal loss in a variety of disease states where there is selective neuronal necrosis.     

31P NMR and triple quantum filtered 23Na NMR studies of the effects of inhibition of Na+/H+ exchange on intracellular sodium and pH in working and ischemic hearts

The triple quantum filtered ²³Na NMR method is applied here to measure the effects of EIPA, a specific inhibitor of the Na⁺/H⁺antiporter, on relative intracellular sodium concentrations in isolated working hearts at baseline, during ischemia, and at subsequent reperfusion. In analogy to the spectrophotometric isosbestic point, an approach is developed that defines a value of τ at which the effect of the relaxation times on the TQF signal intensities is minimized, and the signals are proportional to the sodium concentration for both ischemic and working hearts. EIPA at 1.5 μ significantly inhibited (P < 0.01) the influx of intracellular Na⁺ during 20 min of ischemia at 36.2°C in this rat heart model. In parallel³¹P NMR studies, EIPA had no effect on either the development of acidosis during ischemia or on the recovery of pH, during reperfusion despite its profound effect on intracellular Na⁺ influx. Thus, under our conditions the Na⁺/H⁺ antiporter did not play a critical role in the maintenance of intracellular pH. EIPA treatment resulted in improved recovery (P < 0.005) of mechanical function after 20 min of ischemia. [ATP] was higher in treated hearts during ischemia and reperfusion.     

Sodium time course using 23Na MRI in reversible focal brain ischemia in the monkey

Purpose

To demonstrate the use of sodium MRI for measuring the time course of tissue sodium concentration (TSC) in a nonhuman primate model of reversible focal brain ischemia.

Materials and Methods

Reversible endovascular focal brain ischemia was induced in nonhuman primates (n = 4), and sodium MRI was performed on a 3 Tesla scanner for monitoring changes in TSC during both the middle cerebral artery (MCA) occlusion and MCA reperfusion portions of the experiment.

Results

The TSC increased linearly in the ischemic tissue during MCA occlusion (ranging from a mean TSC increase of 5.44%/h to 7.15%/h across the four subjects), and then there was a statistically significant change from a positive TSC slope during MCA occlusion to a TSC slope after MCA reperfusion that was not statistically different from zero. The linear increase in sodium MRI during brain ischemia was used to estimate the stroke onset time to within 0.45 h in each of the four subjects (with a maximum 95% confidence interval of ± 1.147 h).

Conclusion

The data indicate that sodium MRI increases linearly during brain ischemia, and that this increase is stopped by tissue reperfusion within 5.4 h after stroke onset. J. Magn. Reson. Imaging 2009;30:219–223. © 2009 Wiley‐Liss, Inc.     

Changes in metabolites and tissue water status after focal ischemia in cat brain assessed with localized proton MR spectroscopy

Localized proton spectroscopy was used to monitor changes in metabolism and the biophysical status of tissue water in cat brain induced by occlusion of the middle cerebral artery. Changes in the intensity of N-acetyl-aspartate (NAA), total creatine (tCr), and lactate (Lac) signals in localized volumes of interest in the ischemic hemisphere were quantified relative to the preischemic signal. Changes in the apparent diffusion coefficient (ADC), T₁- and T₂-relaxation times of water in those volumes were also quantified. Lactate was shown to increase rapidly in the first 0.5?2.0 h of ischemia and stabilized afterwards. The ADC of water started to decrease from 0.64 × 10^?9 m2/s to 0.54 × 10^?9 m2/s in the first minutes following occlusion, as was shown in two cases where ADC was measured with high temporal resolution, and stabilized after approximately 3 h at 0.38 × 10^?9 m2/s (n = 6). NAA and tCr decreased by 35% (P< 0.0001) and 30% (P< 0.005), respectively, in the first 8 h of ischemia in comparison with the preischemic control levels. T₁ and T₂ gradually increased with 0.3 s (P< 0.0001) and 5.2 ms (P< 0.0001), respectively, during the same time span.     

The effect of cardiopulmonary bypass on brain and heart metabolism: a 31P NMR study

The development of a large animal preparation using 31P nuclear magnetic resonance (NMR) spectroscopy for the study of cerebral and myocardial metabolism during cardiopulmonary bypass (CPB) is reported. The effect of normothermic CPB on myocardial and cerebral metabolism was evaluated. Adolescent sheep were used which have low levels of 2,3-diphosphoglycerate, a compound which can interfere with the calculation of intracellular pH and inorganic phosphate content. CPB was performed using standard procedures modified for the presence of a high magnetic field and limited access to the animal. High quality 31P NMR data were obtained from the brains and hearts of these animals before and during normothermic CPB. These results demonstrate that the initiation of normothermic CPB does not change high energy phosphate levels or intracellular pH. In particular, the decreased myocardial oxygen demand associated with CPB is not associated with improvement in the levels of adenosine triphosphate or phosphocreatine. The measurements of energy metabolism and intracellular pH of the brain and heart during CPB were possible within the constraints of the NMR experiment without compromising the CPB procedure. Combining NMR and CPB techniques permits future studies of cerebral and myocardial metabolism, especially those relating to ischemia.     

Late stimulation of the sphenopalatine‐ganglion in ischemic rats: Improvement in N‐acetyl‐aspartate levels and diffusion weighted imaging characteristics as seen by MR

Purpose:

To assess, by MR spectroscopy (MRS) and diffusion weighted imaging (DWI), the ability of electrical stimulation of the sphenopalatine ganglion (SPG) to augment stroke recovery in transient middle cerebral artery occluded (t‐MCAO) rats, when treatment is started 18 ± 2 h post‐occlusion.

Materials and Methods:

¹H‐MRS imaging (¹H‐MRSI) and DWI were used to evaluate ischemic brain tissue after SPG stimulation in rats subjected to 2 h of t‐MCAO. Rats were examined by ¹H‐MRSI, DWI, and behavioral tests at 16 ± 2 h, 8 days, and 28 days post‐MCAO.

Results:

N‐Acetyl‐aspartate (NAA) levels of the stimulated and control rats were the same 16 ± 2 h post‐MCAO (0.52 ± 0.03, 0.54 ± 0.03). At 28 days post‐occlusion, NAA levels were significantly higher in the treated group (0.60 ± 0.04) compared with those of the untreated animals (0.50 ± 0.04; P < 0.05). This effect was more pronounced for regions with low NAA values (0.16 ± 0.03) that changed to 0.32 ± 0.03 (P = 0.04) for the treated group and to 0.10 ± 0.03 (P = 0.20) for the controls. DWI data showed better ischemic tissue condition for the treated rats, but the measured parameters showed only a trend of improvement. The MR results were corroborated by behavioral examinations.

Conclusion:

Our findings suggest that SPG stimulation may ameliorate MR tissue characteristics following t‐MCAO even if treatment is started 18 h post‐occlusion. J. Magn. Reson. Imaging 2010;31:1355–1363. © 2010 Wiley‐Liss, Inc.     

心脑通口服液对全脑缺血再灌注损伤大鼠的保护作用

目的探讨心脑通口服液抗脑缺血的作用。方法用四动脉结扎法建立大鼠全脑缺血再灌注模型,观察心脑通口服液对脑缺血再灌注过程中脑电图及翻正反射恢复时间、脑含水量、脑指数的影响;对全脑缺血再灌注后脑组织匀浆丙二醛含量,超氧化物歧化酶、乳酸脱氢酶活性的影响。结果在全脑缺血再灌注大鼠模型上,心脑通口服液可以缩短翻正反射恢复时间,促进脑电的恢复;降低脑含水量和脑指数;提高脑组织超氧化物歧化酶、乳酸脱氢酶活性,降低丙二醛含量。结论心脑通口服液对缺血性脑损伤有一定的保护作用。