Myocardial Oxidative Damage Research Articles

Metallothionein-I/II null cardiomyocytes are sensitive to Fusarium mycotoxin butenolide-induced cytotoxicity and oxidative DNA damage

Previous studies revealed butenolide (BUT), a Fusarium mycotoxin distributes extensively, induced myocardial oxidative damage, which could be abated by antioxidants such as glutathione. Metallothionein (MT) has proved to attenuate several oxidative cardiomyopathies via its potent antioxidant property. The present study is therefore undertaken to investigate the protective potential of the endogenous expression of MT against BUT-induced myocardial toxicity. Primary cultures of neonatal cardiomyocytes from MT-I/II null mice along with the corresponding wild-type mice will be utilized to determine the possible mechanistic properties of MT. BUT treatment to the cardiomyocytes evoked significant cytotoxicity as evidenced by morphological changes and concentration- and time-dependent reductions in cell viability. Additionally, BUT treatment remarkably increased reactive oxygen species (ROS) production in the cardiomyocytes of both MT-I/II null and wild-type mice. As a result, noticeable DNA damage in both cardiomyocytes was detected by alkaline comet assay. Furthermore, the comparison between the MT-I/II null and wild-type cardiomyocytes indicated that ROS production in the cardiomyocytes from the MT-I/II null mice was higher than from wild-type mice. DNA damage as evaluated by percentage of comet tail DNA, tail length and tail moment was more severe in the MT-l/II null cardiomyocytes than in wild-type myocytes. And in agreement with those results mentioned above, the MT-l/II null cardiomyocytes were more sensitive to BUT-induced cytotoxicity than wild-type cardiomyocytes. Taken together, these findings clearly show that basal MT can efficiently attenuate BUT-induced cytotoxic injuries in cardiomyocytes via the inhibition of intracellular ROS production, and associated DNA damage.

Cardiac and metabolic effects of hypothermia and inhaled hydrogen sulfide in anesthetized and ventilated mice*

To test the hypothesis whether inhaled hydrogen sulfide amplifies the effects of deliberate hypothermia during anesthesia and mechanical ventilation as hypothermia is used to provide organ protection after brain trauma or circulatory arrest. Awake mice inhaling hydrogen sulfide exhibit reduced energy expenditure, hypothermia, and bradycardia despite unchanged systolic heart function. In rodents, anesthesia alone causes decreased metabolic rate and thus hypothermia and bradycardia. Prospective, controlled, randomized study. University animal research laboratory. Male C57/B6 mice. After surgical instrumentation (central venous, left ventricular pressure-conductance catheters, ultrasound flow probes on the portal vein and superior mesenteric artery), normo- or hypothermic animals (core temperature = 38 degrees C and 27 degrees C) received either 100 ppm hydrogen sulfide or vehicle over 5 hrs (3 hrs hydrogen sulfide during normothermia). During normothermia, hydrogen sulfide had no hemodynamic or metabolic effect. With or without hydrogen sulfide, hypothermia decreased blood pressure, heart rate, and cardiac output, whereas stroke volume, ejection fraction, and end-diastolic pressure remained unaffected. Myocardial and hepatic oxidative deoxyribonucleic acid damage (comet assay) and endogenous glucose production (rate of appearance of 1,2,3,4,5,6-13C6-glucose) were similar in all groups. Hypothermia comparably decreased CO2 production with or without inhaled hydrogen sulfide. During hypothermia, inhaled hydrogen sulfide increased the glucose oxidation rate (derived from the expiratory 13CO2/12CO2 ratio). This shift toward preferential carbohydrate utilization coincided with a significantly attenuated responsiveness of hepatic mitochondrial respiration to stimulation with exogenous cytochrome-c-oxidase (high-resolution respirometry). In anesthetized and mechanically ventilated mice, inhaled hydrogen sulfide did not amplify the systemic hemodynamic and cardiac effects of hypothermia alone. The increased aerobic glucose oxidation together with the reduced responsiveness of cellular respiration to exogenous cytochrome-c stimulation suggest that, during hypothermia, inhaled hydrogen sulfide improved the yield of mitochondrial respiration, possibly via the maintenance of mitochondrial integrity. Hence, inhaled hydrogen sulfide may offer metabolic benefit during therapeutic hypothermia.

Increased resistance to hydrogen peroxide‐induced cardiac contracture is associated with decreased myocardial oxidative stress in hypothyroid rats

The purpose of this study was to determine whether decreased oxidative stress would increase the resistance to cardiac contracture induced by H(2)O(2) in hypothyroid rats. Male Wistar rats were divided into two groups: control and hypothyroid. Hypothyroidism was induced via thyroidectomy. Four weeks post surgery, blood samples were collected to perform thyroid hormone assessments, and excised hearts were perfused at a constant flow with or without H(2)O(2) (1 mmol/L), being divided into two sub-groups: control, hypothyroid, control + H(2)O(2), hypothyroid + H(2)O(2). Lipid peroxidation (LPO) was evaluated by chemiluminescence (CL) and thiobarbituric acid reactive substances (TBARS) methods, and protein oxidation by carbonyls assay in heart homogenates. Cardiac tissue was also screened for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and for total radical-trapping antioxidant potential (TRAP). Analyses of SOD and glutathione-S-transferase (GST) protein expression were also performed in heart homogenates. Hypothyroid hearts were found to be more resistant to H(2)O(2)-induced contracture (60% elevation in LVEDP) as compared to control. CL, TBARS, carbonyl, as well as SOD, CAT, GPx activities and TRAP levels were reduced (35, 30, 40, 30, 16, 25, and 33%, respectively) in the cardiac homogenates of the hypothyroid group as compared to controls. A decrease in SOD and GST protein levels by 20 and 16%, respectively, was also observed in the hypothyroid group. These results suggest that a hypometabolic state caused by thyroid hormone deficiency can lead to an improved response to H(2)O(2) challenge and is associated with decreased oxidative myocardial damage.

The antioxidant tempol attenuates pressure overload-induced cardiac hypertrophy and contractile dysfunction in mice fed a high-fructose diet

We have previously shown that high-sugar diets increase mortality and left ventricular (LV) dysfunction during pressure overload. The mechanisms behind these diet-induced alterations are unclear but may involve increased oxidative stress in the myocardium. The present study examined whether high-fructose feeding increased myocardial oxidative damage and exacerbated systolic dysfunction after transverse aortic constriction (TAC) and if this effect could be attenuated by treatment with the antioxidant tempol. Immediately after surgery, TAC and sham mice were assigned to a high-starch diet (58% of total energy intake as cornstarch and 10% fat) or high-fructose diet (61% fructose and 10% fat) with or without the addition of tempol [0.1% (wt/wt) in the chow] and maintained on the treatment for 8 wk. In response to TAC, fructose-fed mice had greater cardiac hypertrophy (55.1% increase in the heart weight-to-tibia length ratio) than starch-fed mice (22.3% increase in the heart weight-to-tibia length ratio). Treatment with tempol significantly attenuated cardiac hypertrophy in fructose-fed TAC mice (18.3% increase in the heart weight-to-tibia ratio). Similarly, fructose-fed TAC mice had a decreased LV area of fractional shortening (from 38+/-2% in sham to 22+/-4% in TAC), which was prevented by tempol treatment (33+/-3%). Markers of lipid peroxidation in fructose-fed TAC hearts were also blunted by tempol. In conclusion, tempol significantly blunted markers of cardiac hypertrophy, LV remodeling, contractile dysfunction, and oxidative stress in fructose-fed TAC mice.

Diet with isolated soy protein reduces oxidative stress and preserves ventricular function in rats with myocardial infarction

We investigated the effects of an isolated soy protein (ISP) diet offered over a 9-week period to rats in whom myocardial infarction (MI) had been induced, and a casein diet given as a control. Male Wistar rats were assigned to six groups after infarct size determination ( n = 8/group): Sham Casein (SC); Infarct Casein < 25% (IC < 25%); Infarct Casein > 25% (IC > 25%); Sham Soy (SS); Infarct Soy < 25% (IS < 25%); and Infarct Soy > 25% (IS > 25%). MI surgery was performed at the fifth week, and one month later, the animals were hemodynamically assessed to evaluate left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), contractility and relaxation indexes (±d P/d t). Lung and liver specimens were also collected for the estimation of organ congestion. Oxidative stress was evaluated in heart homogenates through chemiluminescence (CL), carbonyl groups, and antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Infarcted groups treated with casein showed cardiac hypertrophy, lung and liver congestion, increased LVEDP and decreased LVSP and ±dP/dt, all typical signals of heart failure. Ventricular dysfunction was correlated with increased myocardial oxidative damage as seen by CL and carbonyl groups data in the groups IC < 25% and IC > 25% (3 and 10-fold increase, respectively). The ISP diet was able to improve ventricular systolic and diastolic function in the groups IS < 25% and IS > 25% (LVEDP was reduced by 44% and 24%, respectively) and to decrease myocardial oxidative stress. The overall results confirm the preventive role of soy-derived products in terms of post-MI myocardial dysfunction probably by an antioxidant action.

Protective role of curcumin in myocardial oxidative damage induced by isoproterenol in rats

This study was designed to investigate the effect of oral curcumin pretreatment (200 mg/kg) on isoproterenol-induced myocardial injury in rats. Isoproterenol (85 mg/kg, s.c., in two divided doses at 24 h intervals) administration induced a statistically significant increase (P < 0.01) in serum lactate dehydrogenase, creatine kinase, aspartate transaminase, and alanine transaminase activities and significant increase (P < 0.01) in myocardial lipid peroxides levels as compared to vehicle control rats. Furthermore, significant depletion (P < 0.01) of myocardial endogenous antioxidants viz. superoxide dismutase, catalase, and tissue glutathione levels were also found in the pathogenic control group, that is, isoproterenol only treated animals. Curcumin (200 mg/kg) pretreatment for 20 days in isoproterenol treated rats significantly lowered (P < 0.01) the serum lactate dehydrogenase, creatine kinase, aspartate transaminase, alanine transaminase, and myocardial lipid peroxides levels and increased the levels of myocardial endogenous antioxidants (superoxide dismutase, catalase, and tissue glutathione) as compared to pathogenic control rats. Furthermore, histological examination of rat's heart section confirmed myocardial injury with isoproterenol administration and near normal pattern with curcumin pretreatment. The results of our study provide clear evidence that the curcumin pretreatment enhances the antioxidant defense against isoproterenol-induced oxidative myocardial injury in rats and exhibit cardioprotective property.

Antioxidant and cardioprotective effect of Leptadenia reticulata against adriamycin-induced myocardial oxidative damage in rat experiments

Antioxidant and cardioprotective effect of Leptadenia reticulata against adriamycin-induced myocardial oxidative damage in rat experiments

Increased oxidative stress is correlated with mitochondrial dysfunction in chagasic patients

Previously, we have shown in an experimental model of Trypanosoma cruzi infection that increased oxidative stress and antioxidant insufficiency are associated with myocardial (cellular and mitochondrial) oxidative damage and mitochondrial functional decline and might be of pathological significance in Chagas disease. In the present study, we investigated whether enhanced oxidative stress and mitochondrial functional decline are found in human chagasic patients. Our data show substantially higher plasma (two-four-fold) and mitochondrial (67%) malonylaldehyde (MDA) levels in chagasic ( n = 80, group 2) compared to healthy ( n = 50, group 1) subjects. Moreover, antioxidant defense was compromised in chagasic patients. Hence, we noted a 50% decline in glutathione content and losses of 31, 60, and 68% in glutathione peroxidase, superoxide dismutase (SOD), and MnSOD activities, respectively, relative to the findings in healthy controls. Further, chagasic subjects exhibited decreased mitochondrial respiratory complex (CI: 72%; CIII: 71%) activities. Nonchagasic cardiomyopathy subjects ( n = 20, group 3) exhibited marginally higher plasma MDA levels compared to gp1 subjects and were not compromised in plasma antioxidant defense capacity. These data suggest that human chagasic patients sustain an antioxidant/oxidant imbalance and a mitochondrial decline of respiratory complex activities in the circulatory system. A positive correlation between increased MDA levels, MnSOD decline, and inhibition of respiratory complexes suggests that oxidative stress may contribute to mitochondrial dysfunction in chagasic patients.

Oxidative stress-induced ischemic heart disease: protection by antioxidants.

Heart disease is one of the major health problems of advanced as well as developing countries of the world. Extensive research through the last decade has shown beyond doubt that free radicals, particularly, reactive oxygen species play a cardinal role in the pathogenesis of oxidative myocardial damage with consequential cardiac malfunction. This review presents a comprehensive account of the present day knowledge regarding the oxygen free radicals involved in the genesis of ischemic heart disease, the mechanism(s) of oxidative myocardial damage and the endogenous as well as exogenous antioxidant defense systems. Furthermore, the role of ischemic pre-conditioning, some antioxidants and the ability of some cardioprotective drugs in providing protection against the ischemic myocardial damage are also discussed. The text of the article comes to an end with a commentary on the future research perspective in the concerned area, which throws a light on the development of combinatorial therapeutics in the treatment of ischemic myocardial disease.

2,2,5,5-Tetramethylpyrroline-based compounds in prevention of oxyradical-induced myocardial damage.

Reactive oxygen species have been known to play a major role in a wide variety of pathophysiologic processes. A new compound, H-2545, based on a 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide structure, has been reported to exhibit antiarrhythmic function as well as favorable antioxidant properties. Studies were performed in an isolated rat heart model to measure the efficacy of H-2545 and its metabolite, H-2954, in preventing ischemia-reperfusion and hydrogen peroxide-induced oxidative myocardial damage: lipid peroxidation, protein oxidation, activity of respiratory complexes, NAD, and high-energy phosphate metabolism. The cardioprotective effects of examined compounds were compared with that of a well-known water-soluble vitamin E analog, Trolox. To determine whether the antioxidant property of H-2545 is due to the pyrroline ring, the scavenger effects of mexiletine and HO-2434 (mexiletine substituted with a pyrroline group) were compared. The results showed that H-2545 decreased significantly the ischemia-reperfusion-induced thiobarbituric acid reactive substance (TBARS) formation, the protein oxidation and ssDNA break formation in perfused rat hearts. H-2545 decreased the NAD loss in postischemic hearts. The activity of respiratory complexes, myocardial energy metabolism, and functional myocardial recovery were also improved during reperfusion by adding H-2545 to the perfusion medium. H-2954 exerted significantly lower protection against ischemia-reperfusion-induced myocardial injury than H-2545, and it was comparable to that of Trolox. Both H-2545 and H-2954 are highly effective against H O -induced oxidative myocardial cell damage. The findings show that substitution of mexiletine with a 2,2,5,5-tetramethyl-pyrroline group (HO-2434) increased its antioxidant and cardioprotective effects. In conclusion, these results suggest that sterically hindered pyrroline derivatives accumulating in membranes can be highly effective at preventing oxidative myocardial cell damage.

Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo: role of glutathione

The current study tested the hypothesis that ischemia-reperfusion (I-R) can cause more severe myocardial dysfunction and oxidative damage in senescent rats than young adult rats. Male Fischer 344 rats at the age of 6 (adult) and 24 (old) months were subjected to an open-chest heart surgery and randomly assigned to one of the following treatments: ischemia only (I), with the occlusion of the main descending branch of the left coronary artery (LCA) for 30 min; I-R, with the release of LCA occlusion for 20 min; or sham (S) operation. Heart mechanical performance was monitored using a fluid-filled catheter inserted in the right carotid artery and advanced to the left ventricle. Ischemia caused similar reductions of left ventricle systolic pressure (LVSP) and contractility (±d P/d t) in adult and aged hearts. After I-R, adult hearts regained 82% ( P<0.05) of the pre-ischemic LVSP, whereas the aged hearts regained 91% ( P>0.05) of LVSP. There was no significant difference in the reduction of ±d P/d t with I-R between adult and aged hearts. Old rats had lower pre-ischemic heart rate than adult rats, however, I-R caused no reduction of heart rate, and a smaller reduction of pressure-rate double product in the aged rats (10%, P>0.05) than the adult rats (23%, P<0.01). Aged rats demonstrated greater myocardial and plasma glutathione (GSH) concentrations prior to surgery, and maintained higher GSH levels and GSH:glutathione disulfide (GSSG) ratio with I-R. Aged hearts also had higher GSH peroxidase, GSH reductase and GSH sulfur-transferase activities than adult hearts, while I-R induced lipid peroxidation was similar. It is concluded that senescent hearts with intact circulatory and neural inputs are not more susceptible to I-R injury than adult hearts during myocardial I-R, partly because they have a greater GSH antioxidant protection.

The Left Atrial Appendage

The Left Atrial Appendage

Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult

Objective: Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult. This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide. Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy (normoxic cardiopulmonary bypass). Methods: During elective coronary artery bypass grafting, 40 consecutive patients underwent either hyperoxic (oxygen tension = 400 mm Hg) or normoxic (oxygen tension = 140 mm Hg) cardiopulmonary bypass. At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase, nitrate, creatine kinase, and lactic dehydrogenase, antioxidant levels, and malondialdehyde in coronary sinus blood. Cardiac index was measured before and after cardiopulmonary bypass. Results: There was no difference between groups with regard to age, sex, severity of disease, ejection fraction, number of grafts, duration of cardiopulmonary bypass, or ischemic time. Hyperoxic bypass resulted in higher levels of polymorphonuclear leukocyte elastase (377 ± 34 vs 171 ± 32 ng/ml, p = 0.0001), creatine kinase 672 ± 130 vs 293 ± 21 U/L, p = 0.002), lactic dehydrogenase (553 ± 48 vs 301 ± 12 U/L, p = 0.003), antioxidants (1.97 ± 0.10 vs 1.41 ± 0.11 mmol/L, p = 0.01), malondialdehyde (1.36 ± 0.1 μmol/L, p = 0.005), and nitrate (19.3 ± 2.9 vs 10.1 ± 2.1 μmol/L, p = 0.002), as well as reduction in lung vital capacity (66% ± 2% vs 81% ± 1%, p = 0.01) and forced 1-second expiratory volume (63% ± 10% vs 93% ± 4%, p = 0.005) compared with normoxic management. Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups (3.1 ± 0.2 vs 3.3 ± 0.3 L/min per square meter). [Data are mean ± standard error (analysis of variance), with p values compared with an oxygen tension of 400 mm Hg. Conclusions: Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. These adverse effects can be markedly limited by reduced oxygen tension management. The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations. (J Thorac Cardiovasc Surg 1998;116:327-34)

Effects of adriamycin on heart mitochondrial function in rested and exercised rats

The effect of Adriamycin ® (ADM) administration on heart mitochondria was investigated in rats at rest and after an acute bout of maximal exercise. ADM was given intravenously at a dosage of 8 mg/kg body weight 24 and 1 hr before rats were decapitated. Respiratory functions of the isolated heart mitochondria were measured polarographically with both site 1 (pyruvate-malate and 2-oxoglutarate) and site 2 (succinate) substrates. State 4 (basal) respiration was increased using all substrates in ADM-treated rat hearts compared with non-drug control hearts. The mitochondrial respiratory control index was decreased with ADM, but the reduction was due to an increase in state 4 rather than a decrease of state 3 (ADP-stimulated) respiration. ADM administration abolished an exercise-induced elevation of state 3 respiration using all substrates. There was no significant myocardial oxidative damage of dysfunction as evaluated by lipid peroxidation and antioxidant enzyme activity. Addition of exogenous free radicals to the respiratory medium using hypoxanthine and xanthine oxidase resulted in significant deterioration of mitochondrial function in all parameters measured, but no drug- or exercise-specific patterns of damage were revealed. It is concluded that the current dose of ADM (20% of the established cumulative toxic dose) administered within 24 hr can interfere with normal heart mitochondrial function both at rest and during heavy exercise, but does not elicit overwhelming oxidative damage to the myocardium.

Lisinopril increases the recovery during reoxygenation and resistance to oxidative damage in cardiomyocytes

The action of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the consequences of myocardial reoxygenation and oxidative damage was assessed in cultured chick embryonic ventricular cardiomyocytes. Lisinopril, 10 −8 M to 10 −6 M, produced a significant (P < 0.05) dose-dependent enhancement of the restoration of contractile frequency occurring during myocardial reoxygenation but did not alter the depression in contractile frequency during hypoxia. Lisinopril significantly (P < 0.05) shifted the dose-response relationship of ammonium persulfate-induced reduction in cardiac contractile frequency. Lisinopril significantly (P < 0.05) reduced the effect of another oxidative agent, tertbutylhydroperoxide which produced a time-dependent reduction in cardiac contractile frequency. Lisinopril did not alter cardiac contractile frequency in the absence of hypoxia or ammonium persulfate or tertbutylhydroperoxide. The viability of cardiomyocytes, assessed by trypan blue exclusion, paralleled the changes in cardiac contractile frequency. Lisinopril significantly (P < 0.05) improved viability of cardiomyocytes exposed to either ammonium persulfate or tertbutylhydroperoxide. Lisinopril did not display any antioxidant properties against the free radical α,α-diphenyl-β-picrylhydrazyl. These data suggest that lisinopril accelerates the recovery of cardiomyocytes during reoxygenation and blunts the effects of oxidative agents through mechanisms involving the endogenous renin angiotensin system and/or a direct cellular action.

Improvement in contractile recovery of isolated rat heart after cardioplegic ischaemic arrest with endogenous phosphocreatine: involvement of antiperoxidative effect?

The aim was to attempt to get further insight into the mechanism of the cardioprotective action of phosphocreatine (PCr). Three experimental protocols were used: (1) The effect was examined of exogenous PCr (10 mmol.litre-1) on myocardial oxidative damage produced by H2O2 perfusion (90 mumol.litre-1) of isolated rat heart. (2) Isolated rat hearts were subjected to 35 min cardioplegic ischaemia followed by reperfusion. A control group was studied along with two PCr groups, one corrected for Ca2+ to compensate its binding with PCr (1.4 mmol.litre-1 CaCl2 in St Thomas's Hospital cardioplegic solution), and the other not (1.2 mmol.litre-1). (3) The effect was studied of PCr alone and in combination with the antioxidant tocopherol phosphate (0.1 mumol.litre-1) on contractile and metabolic recovery of isolated rat heart reperfused after 40 min cardioplegic ischaemia. Studies were performed on hearts of 84 male Wistar rats, weighing 250-300 g. (1) Oxidative stress resulted in irreversible contracture and impairment of sarcolemmal integrity revealed by using the transmembrane tracer ionic lanthanum. These effects coincided with the decrease of developed pressure from 116 (SEM 3) to 38(3) mm Hg and rate-pressure product from 498(13) to 165(16) mm Hg.s-1. The Ca2+ binding property of PCr was estimated experimentally and the stability constant of the complex CaPCr was found to be 35.4(0.7) mmol; from this the Ca2+ bound by PCr was calculated to be 14% in the experimental conditions used. Ca2+ concentration in K-H buffer containing PCr was increased to compensate its binding with PCr. PCr prevented H2O2 induced contracture, preserved sarcolemmal integrity, and attenuated H2O2 induced decrease in developed pressure and rate-pressure product [73(6) mm Hg and 340(28) mm H.s-1, respectively, p less than 0.05 compared with control]. (2) PCr reduced the diastolic pressure [29(10) v 68(10) mm Hg in control group at 30 min of reperfusion, p less than 0.05] and enhanced the developed pressure [81(10) v 46(10) mm Hg in controls, p less than 0.05] and rate-pressure product [325(44) v 158(40) mm Hg.s-1 in controls, p less than 0.05]. When CaCl2 was increased to 1.4 mmol.litre-1 the protective effect of PCr was not abolished. (3) PCr resulted in improvement of developed pressure [49(7) v 18(5) mm Hg in controls at 40 min of reperfusion, p less than 0.05] and rate-pressure product [184(27) v 71(20) mm Hg.s-1 in controls, p less than 0.05]. The degree of contractile recovery in the tocopherol group was almost the same as in the PCr group. Combined addition of PCr and tocopherol further increased the developed pressure and rate-pressure product to 72(4) mm Hg and 284(23) mm Hg.s-1, respectively. Similarly, PCr and tocopherol in combination provided substantial inhibition of creatine kinase release into perfusate, at 3.8(0.4) v 10.9(2.5) IU in controls, p less than 0.05. PCr decreases the vulnerability of myocardium to oxidative stress and ischaemic damage. These effects cannot be explained by PCr induced shifts in Ca2+ concentration. Protective effects of PCr and tocopherol are quantitatively additive, most probably due to their different mechanisms of action, and tocopherol may be effective in extending the ability of PCr to stabilise cell membrane structure.

Oxidative myocardial damage: Protective action of exogenous phosphocreatine

Oxidative myocardial damage: Protective action of exogenous phosphocreatine