TNF-alpha as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload

TNF-alpha has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-alpha production in myocardial injury due to intracellular Ca2+-overload is available in the literature. The intracellular Ca2+-overload was induced in the isolated rat hearts subjected to 5 min Ca2+-depletion and 30 min Ca2+-repletion (Ca2+-paradox). The Ca2+-paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-alpha content. The ratio of cytosolic to homogenate nuclear factor-kappaB (NFkappaB) was decreased whereas the ratio of phospho-NFkappaB to total NFkappaB was increased in the Ca2+-paradox hearts. All these changes due to Ca2+-paradox were significantly attenuated upon treating the hearts with 100 microM pentoxifylline. These results suggest that activation of NFkappaB and increased production of TNF-alpha may play an important role in cardiac injury due to intracellular Ca2+-overload.     

Effects of ouabain on calcium paradox in rat hearts

The effects of ouabain (10(-7) to 10(-5) M) on the interrelationship between cell-cell contacts, resting tension, and creatine phosphokinase (CK) leakage owing to myocardial cell injury during Ca2+ paradox were studied in isolated perfused rat heart preparations. After perfusing for 15 min with Ca2+ -containing medium, hearts were perfused for 5 min with Ca2+ -free medium followed by a reperfusion with Ca2+ -containing medium for 5 min. This resulted in a transient increase in resting tension and a substantial release of CK into the perfusate during the calcium reperfusion period. These changes were accompanied by extensive structural damage in the myocardial cell, including formation of contraction bands, swelling of the mitochondria, and cell-cell separation. Inclusion of 10(-5) M ouabain for 5 min in the Ca2+ -containing perfusion medium prior to the start of Ca2+ -free perfusion resulted in a higher and sustained resting tension that was accompanied by a reduced loss of CK from the heart during Ca2+ reperfusion. In a histological examination of these ouabain exposed hearts, most of the structural changes owing to calcium paradox were apparent, but the cell-cell contacts were maintained. The results are consistent with the hypothesis that the loss of cell-cell contacts in the intercalated disc during the occurrence of Ca2+ paradox may be the cause of the delayed decline in the resting tension and is only partially responsible for the loss of CK. These differences in myocardial changes during Ca2+ paradox with or without ouabain may be due to the retention of calcium at certain crucial sites under the influence of ouabain.     

Factors affecting the post-ischemic recuperation of isolated perfused rat heart

A number of cardioplegic solutions have been described for the reduction of cellular damage during ischemic cardiac arrest. Using an isolated working rat heart model, we have attempted to precise some of the factors affecting the post-ischemic recovery of myocardial tissue after a 30-min period of total ischemia at 37 degrees C. The results indicate that procaine (1 mM) is able to afford some protective against normothermic ischemia while this protective effect remains consistently lower than that of the St. Thomas' Hospital solution (procaine + high K+ + high Mg2+; JYNGE et al., 1977). On the other hand, hearts from rats of the Wistar strain consistently exhibit a significantly better degree of recovery than do hearts from rats of the Shermann strain. When hearts were perfused at different levels of preload (1 or 2 kPa) and afterload (8 or 10 kPa), post-ischemic recovery was better in hearts with lower levels of cardiac work. Glucose, insulin and DL-propranolol which have been shown to exert a protective effect in isolated rat hearts with regional ischemia failed to protect the heart in the present experimental conditions. No clear correlation does exist between the post-ischemic recovery and the enzymatic assessment of myocardial cell damage.     

17beta-estradiol attenuates cardiac dysfunction and decreases NF-kappaB binding activity in mechanically stretched rat hearts

This study was to examine the effect of estrogen on mechanical stretching-induced cardiac dysfunction in an isolated heart model. The isolated rat hearts were perfused via the Langendorff system and exposed to left ventricular stretching. One group hearts (n=6) were perfused with 17beta-estradiol (100nM) and the other group hearts (n=6) were perfused with estrogen plus its receptor antagonist ICI182,780 (1microM) before myocardial stretching was performed. Control hearts (n=6) were perfused with perfusion buffer. Cardiac functions were recorded. At the end of perfusion, the hearts were harvested and the levels of tumor necrosis factor-alpha (TNF-alpha), phospho-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) binding activity were examined. Acute ventricular stretching resulted in significantly decrease in left ventricular developed pressure (LVDP) by 42.7%, maximal positive and negative values of the first derivative of pressure (+dP/dt and -dP/dt) by 43.2%, and 43.5%, respectively. The levels of TNF-alpha, phospho-p38 MAPK and NF-kappaB DNA binding activity were significantly increased following myocardial stretching. In 17beta-estradiol treated hearts, the myocardial functions were significantly improved. The levels of TNF-alpha, phospho-p38 MAPK, and NF-kappaB binding activity in myocardium were also significantly reduced by 35.7%, 56.9%, and 50%, respectively, compared with untreated stretched hearts. The beneficial effects of 17beta-estradiol on the stretched hearts were abolished by ICI182,780. The results suggest that pharmacological dose of 17beta-estradiol will attenuate stretching-induced cardiac dysfunction in an isolated heart model. The mechanisms could involve in blunting p38 MAPK and NF-kappaB signaling.     

Myocardium in hypertrophy: Oxygen consumption by isolated cardiac myocytes and working hearts from spontaneously hypertensive rats

Oxygen consumption was measured on suspensions of calcium tolerant myocytes obtained from hearts of Spontaneously Hypertensive Rats (SHR) and normotensive Wistar Kyoto Rats (WKY). Oxygen consumptions of the isolated cells were not significantly different from each other either in the presence or absence of added calcium (1.5 mM). Additionally, there was excellent agreement between the oxygen consumption of the isolated cells and estimates of basal oxygen consumption obtained from linear regression analysis of the relationship between work and myocardial oxygen utilization in isolated perfused working hearts. At any given workload there was no significant difference in oxygen consumption between SHR hearts and WKY hearts. The mechanical performance of the SHR hearts was lower compared to that of the WKY hearts at low preloads. At high preloads and high afterloads the SHR hearts developed higher pressures than did hearts obtained from WKY rats. The data suggest that: (a) basal oxygen consumption of the two hearts are similar and (b) the contractile defects in the SHR heart are not the result of hypoxia.     

Cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats

Hypertension is the risk factor of serious cardiovascular diseases, such as ischemic heart disease and atherosclerosis. The aim of the present study was to analyze the development of cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats (SHR) and possible protective effect of ischemic preconditioning (IP) or adaptation to intermittent high-altitude hypoxia (IHAH). For this purpose we used 1- and 10-day-old pups of SHR and their normotensive control Wistar Kyoto rats (WKY). Isolated hearts were perfused in the Langendorff mode with Krebs-Henseleit solution at constant pressure, temperature and rate. Cardiac tolerance to ischemia was expressed as a percentage of baseline values of developed force (DF) after global ischemia. IP was induced by three 3-min periods of global ischemia, each separated by 5-min periods of reperfusion. IHAH was simulated in barochamber (8 h/day, 5000 m) from postnatal day 1 to 10. Cardiac tolerance to ischemia in 1-day-old SHR was higher than in WKY. In both strains tolerance decreased after birth, and the difference disappeared. The high cardiac resistance in 1- and 10-day-old SHR and WKY could not be further increased by both IP and adaptation to IHAH. It may be concluded that hearts from newborn SHR are more tolerant to ischemia/reperfusion injury as compared to age-matched WKY; cardiac resistance decreased in both strains during the first ten days, similarly as in Wistar rats.     

Reduction of asymmetric dimethylarginine involved in the cardioprotective effect of losartan in spontaneously hypertensive rats

Previous studies have indicated that nitric oxide synthase (NOS) inhibitors can induce an increase of blood pressure and exacerbate myocardial injury induced by ischemia and reperfusion, whereas angiotensin II receptor antagonists protect the myocardium against injury induced by ischemia and reperfusion. Isolated hearts from male spontaneously hypertensive rats (SHR) or male Wistar-Kyoto rats (WKY) were subjected to 20 min global ischemia and 30 min reperfusion. Heart rate, coronary flow, left ventricular pressure, and its first derivatives (+/-dP/dt(max)) were recorded, and serum concentrations of asymmetric dimethylarginine (ADMA) and NO and the release of creatine kinase in coronary effluent were measured. The level of ADMA was significantly increased and the concentration of NO was decreased in SHR. Ischemia and reperfusion significantly inhibited the recovery of cardiac function and increased the release of creatine kinase, and ischemia and reperfusion-induced myocardial injury in SHR was aggravated compared with WKY. Vasodilation responses to acetylcholine of aortic rings were decreased in SHR. Treatment with losartan (30 mg/kg) for 14 days significantly lowered blood pressure, elevated the plasma level of NO, and decreased the plasma concentration of ADMA in SHR. Treatment with losartan significantly improved endothelium-dependent relaxation and cardiac function during ischemia and reperfusion in SHR. Exogenous ADMA also aggravated myocardial injury induced by ischemia and reperfusion in isolated perfused heart of WKY, as shown by increasing creatine kinase release and decreasing cardiac function. The present results suggest that the protective effect of losartan on myocardial injury induced by ischemia and reperfusion is related to the reduction of ADMA levels.     

Metabolic phenotyping of the diseased rat heart using 13C-substrates and ex vivo perfusion in the working mode

The objective of the present study was to compare energy substrate fluxes through metabolic pathways leading to mitochondrial citrate synthesis and release in normal and diseased rat hearts using ¹³C-substrates and mass isotopomer analysis by gas chromatography-mass spectrometry (GCMS). This study was prompted by our previous finding of a modulated citrate release by perfused rat hearts and by the possibility that a dysregulated myocardial citrate release represents a specific chronic alteration of energy metabolism in cardiac patients. The 15-week-old spontaneously hypertensive rat (SHR) was chosen as our animal model of disease and the Wistar-Kyoto (WKY) rat as its matched control. Ex vivo work-performing hearts were perfused with a semi-recirculating buffer containing physiological concentrations of unlabeled (glucose) and ¹³C-labeled ([U-¹³C₃](lactate + pyruvate) and/or [1-¹³C]oleate) substrates. In parallel to the continuous monitoring of indices of the heart's functional and physiological status, the following metabolic parameters were documented: (i) citrate release rates and citric acid cycle intermediate tissue levels, (ii) the contribution of fatty acids as well as pyruvate decarboxylation and carboxylation to citrate synthesis, and (iii) lactate and pyruvate uptake and efflux rates. Working hearts from both rat species showed a similar percent contribution of carbohydrates for citrate synthesis through decarboxylation (70%) and carboxylation (10%). SHR hearts showed the following metabolic alterations: a higher citrate release rate, which was associated with a parallel increase in its tissue level, a lower contribution of oleate -oxidation to citrate synthesis, and an accelerated efflux rate of unlabeled lactate from glycolysis. These metabolic changes were not explained by differences in myocardial oxygen consumption, cardiac performance or efficiency, nor correlated with indices of tissue necrosis or ischemia. This study demonstrates how the alliance between ex vivo semi-recirculating working perfused rat hearts with ¹³C-substrates and mass isotopomer analysis by GCMS, can provide an unprecedented insight into the metabolic phenotype of normal and diseased rat hearts. The clinical relevance of metabolic alterations herein documented in the SHR heart is suggested by its resemblance to those reported in cardiac patients. Taken altogether, our results raise the possibility that the increased citrate release of diseased hearts results from an imbalance between citrate synthesis and utilization rates, which becomes more apparent under conditions of substrate abundance.     

缺血-再灌注过程中心肌肌浆网钙摄取和Ca~(2 )-ATPase活性的变化

本实验用离体大鼠心脏Langendorff灌流模型,观察缺血及缺血——再灌注对大鼠心肌肌浆网[SR]钙转运功能的影响。结果表明:缺血25min引起SR钙摄取初速率下降,摄取量降低;缺血40min,使其进一步加重。缺血25min后再灌注15min,SR的钙转运功能进一步降低,与缺血40min后果类似;同时SR上的Ca~(2 )-ATPase活性也显著降低。用不同pH的灌流液进行再灌注,对SR钙转运功能的障碍无显著影响。这提示:心肌缺血可引起SR的钙转运功能障碍,并随缺血时间的延长而加重;再灌注加重缺血造成的SR功能的损伤。偏酸或偏碱的K-H液再灌注均不能改善SR钙转运功能的抑制,表明pH变化不是缺血-再灌注时引起SR功能障碍的重要因素。     

Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction

Bilirubin is a potent antioxidant generated intracellularly during the degradation of heme by the enzyme heme oxygenase. The purpose of this study was to determine the role of increased cardiac bilirubin in protection against postischemic myocardial dysfunction. Rat hearts were isolated and perfused according to the Langendorff technique to evaluate the recovery of myocardial function after 30 min of global ischemia and 60 min of reperfusion. We found that upregulation of the inducible isoform of heme oxygenase (HO-1) by treatment of animals with hemin 24 h before ischemia ameliorated myocardial function and reduced infarct size (tetrazolium staining) on reperfusion of isolated hearts. Tin protoporphyrin IX, an inhibitor of heme oxygenase activity, completely abolished the improved postischemic myocardial performance observed after hemin-mediated HO-1 induction. Likewise, cardiac tissue injury was exacerbated by treatment with tin protoporphyrin IX. Increased cardiac HO-1 expression and heme oxygenase activity were associated with enhanced tissue bilirubin content and an increased rate of bilirubin release into the perfusion buffer. Furthermore, exogenously administered bilirubin at concentrations as low as 100 nanomolar significantly restored myocardial function and minimized both infarct size and mitochondrial damage on reperfusion. Our data provide strong evidence for a primary role of HO-1-derived bilirubin in cardioprotection against reperfusion injury.     

Nitrate tolerance aggravates postischemic myocardial apoptosis and impairs cardiac functional recovery after ischemia

Objectives: This study examined the effects of nitrate tolerance (NT) on myocardial ischemia reperfusion (MI/R) injury and elucidated the potential mechanisms involved. Furthermore, the effects of GSH on postischemic myocardial apoptosis in NT rats were investigated. Methods and results: Male Sprague–Dawley rats were randomized to receive nitroglycerin (60 μg/kg/h) or saline for 12 h followed by 40 min of MI and 4 h of reperfusion. Myocardial apoptosis, infarct size, nitrotyrosine formation, plasma CK and LDH activity, and cardiac function were determined. MI/R resulted in significant apoptotic cell death, which was further increased in animals with NT. In addition, NT further increased plasma CK and LDH activity, enlarged infarct size, and impaired cardiac functional recovery after ischemia. Myocardial nitrotyrosine, a footprint for cytotoxic reactive nitrogen species formation, was further enhanced in the NT heart after MI/R. Treatment of NT animals with exogenous GSH inhibited nitrotyrosine formation, reduced apoptosis, decreased infarct size, and improved cardiac functional recovery. Conclusion: Our results demonstrate that nitrate tolerance markedly enhances MI/R injury and that increased peroxynitrite formation likely plays a role in this pathologic process. In addition, our results suggest that GSH could decrease peroxynitrite formation and reduce MI/R injury in nitrate tolerant hearts.     

Release of fatty acid-binding protein from isolated rat heart subjected to ischemia and reperfusion or to the calcium paradox

The release of cardiac fatty acid-binding protein (cFABP) and of fatty acids from isolated rat hearts was measured during both reperfusion following 60 min of ischemia and the calcium paradox (readmission of Ca2+ after a period of Ca2+-free perfusion). Total cFABP release was much more pronounced after Ca2+ readmission (over 50% of tissue content) than during post-ischemic reperfusion (on average, 3% of tissue content), but in both cases, it closely paralleled the release of lactate dehydrogenase. Only minor amounts of long-chain fatty acids, if any, were released from the heart. These observations are challenging the idea that cFABP plays a fatty acid-buffering role under the pathophysiological conditions studied.     

Insulin inhibits β-adrenergic action in ischemic/reperfused heart: a novel mechanism of insulin in cardioprotection

Objective Sympathetic overactivity is closely connected with cell injury and contractile dysfunction during myocardial ischemia/reperfusion (MI/R). Insulin exerts protection for the I/R heart and the underlying mechanisms remain unclear. This study aimed to investigate the ability of insulin to modulate β-adrenergic actions on myocardial contraction and post-ischemic injury in acute MI/R and the underlying mechanism. Methods Isolated hearts from adult SD rats were subjected to MI/R (30 min/2 h) and treated with isoproterenol (ISO) or/and insulin. Myocardial contraction, cardiomyocyte apoptosis, myocardial injury and infarction were assessed. In a separate study, isolated ventricular myocytes were subjected to simulated I/R (15/30 min) and myocyte shortening and intracellular Ca²⁺ transient in response to ISO during reperfusion were assessed with presence or absence of insulin. Results In isolated I/R hearts, insulin largely reversed the ISO-associated contractile functional impairment at 2 h after MI/R, inhibiting ISO-induced declines in heart rate and left ventricular systolic pressure by 34.0% and 23.0% and preventing ISO-induced elevation in left ventricular end-diastolic pressure by 28.7% respectively (all P < 0.05). In addition, ISO alone resulted in enlarged infarct size, elevated CK and LDH activity and increased apoptotic index in I/R hearts compared with vehicle, which were inhibited by treatment of insulin (all P < 0.05). Interestingly, in SI/R cardiomyocytes, insulin alone at 10⁻⁷ mol/l increased cell contraction whereas attenuated the positive inotropic response to ISO (10⁻⁹ mol/l) during R as evidenced by a 18.7% reduction in peak twitch amplitude and a 23.9% reduction in calcium transient amplitude (both P < 0.05). Moreover, insulin blunted ISO-mediated increase in PKA activity, enhanced the PKA-dependent phosphorylation of phospholamban (PLB), resulting in increased sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) activity. Conclusion Insulin attenuated the contractile response to β-AR stimulation and suppressed ISO-elicited cardiac dysfunction and cell injury in MI/R. The inhibitory effect of insulin on the β-adrenergic action involved the inhibition of PKA-mediated Ca²⁺ transient and promotion of post-ischemic Ca²⁺ handling.     

缺血—再灌注过程中心肌肌浆网钙摄取和...

Using Langendorff's perfusion model of isolated rat heart, the effect of period of ischemia, ischemia-reperfusion and changes in perfusate pH on the function of calcium uptake of cardiac sarcoplasmic reticulum (SR) was observed. The initial rate and capacity of calcium uptake by SR decreased significantly after 25 min ischemia, and were further worsened when ischemia was prolonged to 40 min. When hearts were subjected to 15 min reperfusion after 25 min ischemia, calcium uptake capacity and initial rate decreased even more in comparison with that of 40 min ischemia. In addition, the calcium dependent ATPase activity of SR was also markedly inhibited. Reperfusion with acid (pH 6.8) or alkaline (pH 8.0) made no significant difference on the aforementioned reperfusion induced changes. The results indicated that myocardial ischemia depressed the calcium transport activity of SR, and this depression was further aggravated with prolonging ischemia. Reperfusion after ischemia exacerbated the ischemic injury. Reperfusion with either acid or alkaline Krebs-Henseleit solution could not improve the calcium uptake function of SR, implying that the pH change does not seem to be an important factor in inducing the SR dysfunction during ischemia-reperfusion.     

Preservation of ischemic myocardial tissue with an antagonist of vasoconstrictor eicosanoids

A new antagonist of the vasoconstrictor eicosanoids, L-640,035, was studied in a standardized model of myocardial ischemia (MI) in anesthetized cats. This eicosanoid antagonist was not found to exert any overt hemodynamic action in cats subjected to a sham myocardial ischemia protocol. However, the antagonist markedly reduced the S-T segment of the electrocardiogram when administered 30 min after permanent occlusion of the left coronary artery. Moreover, circulating activities of the marker enzyme creatine kinase (CK) were markedly attenuated by L-640,035 3-5 h after the onset of MI. This was verified by cardiac biopsies 5 h post-MI since myocardial CK activities decreased much less in treated MI cats than in MI cats receiving only the vehicle for L-640,035 (i.e., ethanol). The active metabolite of the antagonist in biological fluids (i.e., L-636,499) markedly antagonized the vasoconstrictor actions of endoperoxide and thromboxane analogs, but not of noneicosanoids in isolated perfused coronary arteries.     

α-Lipoic Acid Reduces Infarct Size and Preserves Cardiac Function in Rat Myocardial Ischemia/Reperfusion Injury through Activation of PI3K/Akt/Nrf2 Pathway

Background

The present study investigates the effects and mechanisms of α-Lipoic acid (LA) on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in rat hearts subjected to in vivo myocardial ischemia/reperfusion (MI/R) injury.

Methodology/Principal Findings

Male adult rats underwent 30 minutes of ischemia followed by 3, 24, or 72 h of reperfusion. Animals were pretreated with LA or vehicle before coronary artery ligation. The level of MI/R- induced LDH and CK release, infarct size, cardiomyocyte apoptosis and cardiac functional impairment were examined and compared. Western blot analysis was performed to elucidate the mechanism of LA pretreatment. The level of inflammatory cytokine TNF-α released to serum and accumulated in injured myocardium as well as neutrophil accumulation in injured myocardium were also examined after MI/R injury. Our results reveal that LA administration significantly reduced LDH and CK release, attenuated myocardial infarct size, decreased cardiomyocytes apoptosis, and partially preserved heart function. Western blot analysis showed that LA pretreatment up-regulated Akt phosphorylation and Nrf2 nuclear translocation while producing no impact on p38MAPK activation or nitric oxide (NO) production. LA pretreatment also increased expression of HO-1, a major target of Nrf2. LA treatment inhibited neutrophil accumulation and release of TNF-α. Moreover, PI3K inhibition abolished the beneficial effects of LA.

Conclusions/Significance

This study indicates that LA attenuates cardiac dysfunction by reducing cardiomyoctyes necrosis, apoptosis and inflammation after MI/R. LA exerts its action by activating the PI3K/Akt pathway as well as subsequent Nrf2 nuclear translocation and induction of cytoprotective genes such as HO-1.     

Energy dependence of enzyme release from hypoxic isolated perfused rat heart tissue

There is a sudden release of intracellular constituents upon reoxygenation of isolated perfused hypoxic heart tissue (O2 paradox) or on perfusion with calcium-free medium after a period of hypoxia. Rat hearts were perfused by the method of Langendorff (Pfluegers Arch. 61: 291-332, 1895) with Krebs-Henseleit medium containing 10 mM glucose. Hearts were equilibrated for 30 min, followed by 90 min of hypoxia or 60 min of hypoxia and 30 min of reoxygenation. The massive enzyme release observed upon reoxygenation after 60 min of hypoxia was prevented by infusing 0.5 or 5 mM cyanide 5 min before reoxygenation. Lactate dehydrogenase (LDH) release commenced immediately upon withdrawal of cyanide. Hearts perfused with calcium-free medium throughout hypoxia did not release increased amounts of LDH at reoxygenation. Perfusing heart tissue with medium containing 0 or 25 microM calcium, but not 0.25 or 2.5 mM, after 50 min of hypoxia initiated a release of cardiac LDH, which was not further enhanced by reoxygenation. Enzyme release was significantly inhibited when the calcium-free perfusion medium included 10 mM 2-deoxyglucose (replacing glucose), 0.5 mM dinitrophenol, or 2.5 mM cyanide. Histologically, hearts perfused with calcium-free medium after 50 min of hypoxia showed areas of severe necrosis and contracture without any evidence of the contraction bands that were seen in hearts reoxygenated in the presence of calcium. Cardiac ATP and creatine phosphate (PCr) levels were significantly decreased after 50-60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of membrane protection by 31P-NMR effects of lidocaine on calcium-paradox in myocardium

In studying calcium paradox, perfused rat hearts were used to investigate the myocardial protective effects of lidocaine. Intracellular contents of phosphates were measured using the 31P-NMR method. In hearts reexposed to calcium, following 3 minute calcium-free perfusion, a rapid contracture occurred, followed by rapid and complete disappearance of intracellular phosphates with no resumption of cardiac function. In hearts where lidocaine was administered from the onset of the calcium-free perfusion until 2 minutes following the onset of reexposure to calcium, both intracellular phosphates and cardiac contractility were maintained. Therefore, it can be said that cell membranes were protected by lidocaine.     

Taurine's possible protective role in age-dependent response to calcium paradox

When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the "calcium paradox". Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. The taurine (2-aminoethanesulfonic acid) content of hearts in the newborn animal is high, and decreases rapidly during the first few days of life. The present experiments were performed to test whether the myocardial taurine content was closely linked to an age-dependent response in the calcium paradox model, using post-hatched chicks. The mechanical dysfunction of the heart was much more severe in 9-day-old post-hatched chicks than in 2-day-old chicks when the hearts were subjected to the calcium paradox. Myocardial taurine content was lower in the 9-day-old chicks than in the 2-day-old chicks. The age-related response to the calcium paradox was partially protected by oral pretreatment with taurine, and there was a small increase in myocardial taurine level. It is proposed that myocardial taurine is one factor in the protection against the calcium paradox phenomenon.