![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARDIOVASCULAR
Experimental Cardiology, Thoraxcenter, Cardiovascular Research School (COEUR), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (D.A.L., B.C.G., S.K., O.C.M., P.D.V., D.J.D.); and GHO Pharma, Maastricht, The Netherlands (C.C.G., S.K.)
Received November 5, 2003; accepted February 25, 2004.
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionReferences |
|---|
; Vahlhaus et al., 1998; Fryer et al., 1999), which is the most potent endogenous mechanism to limit myocardial infarct size. There is evidence that increased tyrosine residue phosphorylation, produced by a shift in the balance between tyrosine kinase and tyrosine phosphatase, increases white blood cell survival by inhibiting apoptosis (Bergamaschi et al., 1993; LaVoie and Witorsch, 1995; Brown et al., 1996). Vanadate enhances tyrosine residue phosphorylation by inhibition of tyrosine phosphatase (Simons, 1979; Palmer et al., 1996), suggesting that vanadate may be of therapeutic benefit in myocardial infarction, which may involve both apoptosis and necrosis (Kajstura et al., 1996; Weiss et al., 2003). In support of this concept, Armstrong et al. (1998) reported that serine threonine phosphatase inhibitors are highly effective in protecting isolated cardiomyocytes subjected to ischemia (without reperfusion), even when administered late (75 min) after onset of ischemia, suggesting that vanadate may not require administration before the onset of ischemia and might also act against reperfusion injury. However, to date, in vivo studies on the cardioprotective effects of tyrosine phosphatase inhibitors are lacking.
The mechanism by which tyrosine phosphatase inhibitors exert their cardioprotective effects is incompletely understood. However, since K+ATP channels have been reported to be downstream targets of tyrosine kinase in the signaling pathway of ischemic preconditioning (Przyklenk and Kloner, 1998; Fryer et al., 1999), we hypothesized that K+ATP channels contribute to the cardioprotection by vanadate. Finally, several studies, including from our own laboratory, have reported that a brief period of ischemia (Gho et al., 1996) or local intra-arterial infusion of adenosine (Liem et al., 2002b) and bradykinin (Schoemaker and van Heijningen, 2000) in remote organs such as small intestine and kidneys can protect the myocardium by stimulation of afferent nerves in the remote ischemic organ that results in activation of a neurogenic pathway (Gho et al., 1996; Liem et al., 2002b). We hypothesized that activation of this neurogenic pathway (which implies that compounds are not required to reach the area at risk) might also contribute to the cardioprotection by vanadate administered intravenously just before reperfusion.
In view of these considerations, the present study was designed to investigate 1) whether pretreatment with bis(maltolato)-oxovanadium (BMOV) is cardioprotective; 2) whether BMOV treatment after the onset of occlusion, but just before reperfusion is still cardioprotective; and 3) the mechanism of protection by BMOV, including the involvement of K+ATP channel opening and a neurogenic pathway. All studies were performed in anesthetized open-chest rats subjected to a 60-min coronary artery occlusion.
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
300 g) in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health publication no. 86-23, revised 1996) and with approval of the Animal Care Committee of the University.
Surgical and Experimental Procedures. Pentobarbital-anesthetized (60 mg/kg) rats were intubated for positive pressure ventilation (Servo ventilator) with oxygen-enriched room air (Liem et al., 2001, 2002b). Through the carotid artery, a PE-50 catheter was positioned in the thoracic aorta for measurement of arterial blood pressure and heart rate. In the inferior caval vein, a PE-50 catheter was placed for infusion of physiological saline to maintain fluid balance. Following thoracotomy, via the left third intercostal space, the pericardium was opened, and a silk 6-0 suture was looped under the left anterior descending coronary artery for later coronary artery occlusion (CAO). A catheter was positioned in the abdominal cavity to allow intraperitoneal administration of pentobarbital for maintenance of anesthesia. Rectal temperature was continuously measured and maintained at 36.5° to 37.5°C (Van den Doel et al., 1998). To prevent local heat loss from the thorax, the thoracotomy site was covered with aluminum foil. After completion of surgery, a 30-min stabilization period was allowed before experimental protocols were carried out.
All rats were subjected to a 60-min CAO followed by 180 min of reperfusion. At the end of reperfusion, the left anterior descending coronary artery was re-occluded and the area at risk determined with negative trypan blue staining, after which the heart was excised and infarct size determined with negative nitroblue tetrazolium staining (Gho et al., 1996; Van den Doel et al., 1998; Liem et al., 2001, 2002b).
Rats that fibrillated were allowed to complete the protocol, provided that conversion to normal sinus rhythm occurred spontaneously within 1 min or that defibrillation by gently thumping on the thorax or with a 9-V battery was successful within 2 min after onset of fibrillation. Occlusion and reperfusion were visually verified (Liem et al., 2001).
Effect of BMOV on Infarct Size. To determine whether BMOV had any effect on infarct size 3 doses of BMOV (3.3, 7.5, and 15 mg/kg) or its vehicle [up to 2.5 ml of phosphate-buffered saline (PBS)] were administered over 10 min, starting 20 min before the 60-min CAO. We subsequently investigated whether attenuation of reperfusion injury contributed to the limitation of infarct size. Since the former experiments established a dose-dependent limitation of infarct size by BMOV, the same doses of BMOV or its vehicle were again administered over 10 min but now starting 10 min before reperfusion.
Mode of Action of BMOV. To establish whether the limitation of infarct size/reperfusion injury by BMOV required an increased state of tyrosine phosphorylation during reperfusion, we investigated whether the cardioprotection by BMOV, in a dose of 7.5 mg/kg i.v. administered either before occlusion or before reperfusion, was affected by the presence of the tyrosine kinase inhibitor genistein (Fryer et al., 1999; Tanno et al., 2000). Genistein was administered intravenously in doses of either 5 or 10 mg/kg over 5 min, starting 15 min before reperfusion. To investigate the involvement of K+ATP channel opening in the protection by BMOV, we determined whether the K+ATP channel blocker glibenclamide affected the cardioprotection by BMOV (7.5 mg/kg) administered before reperfusion. Glibenclamide was administered in two doses of 3 mg/kg each and infused over a 5-min period, the first infusion starting 20 min before occlusion (to ensure sufficient incubation time for glibenclamide in the area at risk; Schultz et al., 1997) and the second infusion starting at 45 min after the onset of occlusion.
The involvement of indirect protection of the heart by stimulation of afferent nerves in a remote organ and subsequent activation of a neurogenic pathway was investigated by studying the effect of intravenous BMOV (7.5 mg/kg before reperfusion) in the presence of the ganglion blocker hexamethonium (20 mg/kg i.v.) administered over 15 min starting 35 min after the onset of occlusion.
Materials. BMOV (GHO-1; GHO-Pharma, Maastricht, The Netherlands) was dissolved in 1 ml (3.3 and 7.5 mg/kg) or 2.5 ml (15 mg/kg) of PBS (modified Sörensen). Genistein (5 and 10 mg/kg, Sigma-Aldrich, St. Louis, MO) was dissolved in 0.3 ml of 95% ethanol and alkamuls EL-620 (Rhodia, Lyon, France) to which 0.3 ml of physiologic saline was added. Glibenclamide (6 mg/kg, Sigma-Aldrich) was dissolved in 1 ml of deionized H2O at a pH of 10. Hexamethonium (20 mg/kg, Sigma-Aldrich) was dissolved in 1 ml of physiologic saline. Fresh drug solutions were prepared each day.
Data Analysis and Presentation. Infarct size was analyzed by one-way analysis of variance (ANOVA) followed by Dunnett's test. The importance of timing of administration of BMOV (preischemia versus prereperfusion) was analyzed by using two-way (timing x dose) ANOVA. Hemodynamic variables were compared by two-way ANOVA for repeated measures followed by paired or unpaired Student's t testing. Statistical significance was accepted when P < 0.05. Data are presented as mean ± S.E.M.
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Effect of BMOV on Infarct Size. There were no differences (P = 0.22) between the areas at risk of the various experimental groups (40 ± 1%, n = 112). Infarct size, which was 70 ± 2% in vehicle-treated rats, was limited in a dose-dependent manner to 41 ± 5% by administration of BMOV before the 60-min CAO (P < 0.05; Fig. 1, left). When administered just before reperfusion, BMOV in the dose of 3.3 mg/kg was ineffective, but the doses of 7.5 and 15 mg/kg were equally cardioprotective (both P > 0.30) as the corresponding doses administered before the 60-min CAO (Fig. 1, right).
|
Mode of Action of BMOV. The cardioprotection by BMOV in a dose of 7.5 mg/kg was abolished when rats were treated with genistein, independent of whether BMOV was administered before the 60-min CAO (Fig. 2, left) or just before the 180-min reperfusion period (Fig. 2, right). The inhibition by genistein of the infarct size limitation by BMOV occurred in a dose-dependent fashion because 5 mg/kg only partly blocked the protection by BMOV administered just before reperfusion [infarct size 60 ± 4% (n = 5; data not shown in Fig. 2); P < 0.05 versus both BMOV-treated (44 ± 3%) and PBS-treated (70 ± 2%) rats]. The cardioprotection by BMOV, administered before reperfusion, was also abolished by glibenclamide but not by hexamethonium (Fig. 3). Genistein (10 mg/kg; Fig. 2), glibenclamide (Fig. 3), and hexamethonium (Fig. 3) had no effect on infarct per se, which is in agreement with previous observations (Gho et al., 1996; Mei et al., 1996; Fryer et al., 1999; Tanno et al., 2000).
|
|
Hemodynamic Effects of BMOV. There were no differences in baseline values of heart rate (P = 0.37) and mean arterial blood pressure (P = 0.25) between any of the experimental groups (Table 1). In the PBS-treated groups, heart rate and mean aortic blood pressure remained virtually unchanged throughout the 60-min CAO. During the subsequent 180-min reperfusion period, blood pressure slightly decreased, and heart rate slightly increased. BMOV, administered either before occlusion or before reperfusion, produced a transient and dose-dependent increase in mean arterial pressure, which was accompanied by a decrease in heart rate. Apart from these transient effects, the hemodynamic responses to occlusion and reperfusion were not different from those in the vehicle-treated animals.
|
Pretreatment with 10 mg/kg genistein markedly attenuated the pressor response induced by 7.5 mg/kg BMOV (14 ± 5 compared with 31 ± 4 mm Hg, P < 0.05; Table 1). In contrast, the BMOV-induced increase in blood pressure was not altered by pretreatment with either glibenclamide (25 ± 9 mm Hg) or hexamethonium (53 ± 12 mm Hg).
Infarct size limitation by preocclusion treatment with BMOV was not related to alterations in the product of heart rate and mean arterial blood pressure at the onset of occlusion (Fig. 4, left), which is in line with previous observations that infarct size is not correlated with oxygen demand at the onset of occlusion (Miura et al., 1992; Koning et al., 1994; Gho et al., 1996; Van den Doel et al., 1998). In addition, the cardioprotection by BMOV administered before reperfusion was also not correlated with the rate-pressure product at the onset of reperfusion (Fig. 4, right). Together, these findings indicate that the infarct size limitation by BMOV cannot be explained by a decrease in global left ventricular energy demands.
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Importance of Dosage and Timing of Administration of BMOV. Previous in vitro studies have indicated that vanadate possesses cardioprotective properties (Geraldes et al., 1997; Takeuchi et al., 1998). For example, vanadate limited acidosis and lactate accumulation during global ischemia in isolated buffer-perfused rat hearts, although postischemic recovery of left ventricular-developed pressure was only minimally improved (Geraldes et al., 1997). The results from this study are difficult to interpret, because vanadate was administered in a high dose of 40 µM that produced marked cardiodepression at baseline, as reflected in the more than 50% reduction in left ventricular-developed pressure (Geraldes et al., 1997). Furthermore, ischemia lasted up to 15 min, which in buffer-perfused rodent hearts may already result in significant necrosis (Borgers et al., 1987). As a consequence, without measurement of infarct size, no distinction can be made between a vanadate-induced attenuation of reversible contractile dysfunction (stunning) versus limitation of myocardial infarct size.
Takeuchi et al. (1998) administered vanadate for a period of 3 to 4 weeks in a dose of 7.5 mg/kg p.o. per day to rabbits with pressure overload-induced left ventricular hypertrophy. When isolated hearts were then subjected to a 40-min period of global ischemia, vanadate-treated hearts showed reduced lactate release and improved postischemic recovery of left ventricular-developed pressure compared with vehicle-treated hypertrophied hearts. However, since in these experiments the duration of ischemia exceeded 15 to 20 min, again no distinction can be made between a vanadate-induced attenuation of reversible contractile dysfunction (stunning) versus limitation of myocardial infarct size (Duncker et al., 1998).
The present study is the first to demonstrate that BMOV, in a dose-dependent manner, limits myocardial infarct size in vivo. At a low dose of 3.3 mg/kg, only preischemia treatment was effective in limiting infarct size, suggesting either that the compound exerts principally anti-ischemic actions or that tissue concentrations were too low at the onset of reperfusion. Rats lack a significant collateral circulation in the coronary vascular bed, so that administration of BMOV may not have reached the jeopardized myocardium in sufficient concentrations before the onset of reperfusion. However, at sufficiently high doses, BMOV was equally effective when administered before reperfusion as compared with administration before coronary artery occlusion. It could be argued that BMOV exerted at least part of its protective action by reducing ischemia injury during the last 10 min of the 60-min CAO. This is highly unlikely, in view of previous observations in our laboratory in the identical experimental model in which a 45-min CAO followed by 180 min of reperfusion already resulted in an infarct size of 61 ± 7%, which was not significantly different from the infarct size of 70 ± 2% produced by a 60-min CAO (Van den Doel et al., 1998). As a consequence, any limitation of ischemia damage by BMOV, administered after 50 min of CAO, cannot explain the BMOV-induced limitation of infarct size to 43 ± 5%. Taken together, these findings suggest that BMOV exerts its effects principally during reperfusion but that sufficiently high concentrations need to be present in the blood at the onset of reperfusion.
Mechanism of Cardioprotection by BMOV. The cardioprotective effect of vanadate in isolated buffer-perfused rat hearts has been proposed to be in part mediated by its apparent free radical scavenging properties. Thus, vanadate has been reported to inhibit the generation of superoxide, resulting in a blunting of the superoxide-induced loss of sarcolemmal Ca2+ pump activity and Na+-dependent Ca2+ uptake in isolated rat hearts (Matsubara et al., 1995). In contrast, under certain conditions in vitro, vanadate has been shown to be capable of generating free radicals (Kalyani et al., 1992). However, this does not account for all its actions because other investigators failed to observe any action of reductants or antioxidants on vanadate-induced expression of actin and c-Ha-ras (Yin et al., 1992). Importantly, the role of reactive oxygen species in lethal reperfusion injury in vivo is still poorly understood because studies on efficacy of scavengers of reactive oxygen species against reperfusion injury have been highly equivocal (Jeroudi et al., 1994; Black, 2000).
In the present in vivo study, the tyrosine kinase inhibitor genistein dose-dependently attenuated the cardioprotection by BMOV even when BMOV was administered before ischemia and genistein was administered after 45 min of ischemia (i.e., just before reperfusion). These findings are consistent with the concept that BMOV is dependent on an intact tyrosine kinase activity during reperfusion and also suggest that the tyrosine phosphorylation status is an important determinant of ischemia reperfusion damage. An increased phosphorylation of tyrosine residues has been proposed to afford protection against ischemia reperfusion damage via a number of subcellular actions. First, vanadate exerts insulin-like effects including enhanced stimulation of glucose transport and oxidation in the isolated rat heart, which might be due to its tyrosine phosphatase inhibitory actions (Takeuchi et al., 1998). Recent clinical trials indicate that a combination of glucose and insulin might increase the salvage of cardiomyocytes during early reperfusion (Wang et al., 2002). The mechanism by which enhanced glucose utilization produces protection might be related to increased ATP production at the site of the sarcolemma (and perhaps the mitochondria) during the first few minutes of reperfusion (at a time when mitochondria have not yet resumed ATP production), thereby maintaining ion homeostasis and chaperoning the vulnerable cardiomyocytes into a phase in which the mitochondria resume ATP generation (Jeremy et al., 1993). Another mechanism by which an increase in tyrosine phosphorylation may exert cardioprotection could involve opening of K+ATP channels, which is suggested by studies showing that ischemic preconditioning involves activation of tyrosine kinase and protein kinase C (Vahlhaus et al., 1998; Fryer et al., 1999) and opening of K+ATP channels (Schultz et al., 1997). Although the sequence of involvement is still controversial (Pain et al., 2000), studies in the rat heart suggest that kinases are principally involved early in preconditioning and act upstream of the K+ATP channels (Fryer et al., 1999, 2001; Nozawa et al., 2003). In accordance with this concept, we observed that the K+ATP channel blocker glibenclamide, which had no effect on infarct size per se, abolished the cardioprotection by BMOV, suggesting that opening of K+ATP channels is involved in the actions of BMOV. However, one could argue that glibenclamide antagonized the effects of BMOV by increasing myocardial susceptibility to ischemia (i.e., in a BMOV-independent manner), but that this went undetected in the control infarct group because infarct size reaches a plateau at 60 min of coronary artery occlusion (Van den Doel et al., 1998). This scenario is, however, highly unlikely in view of a preliminary study from our laboratory in which we observed that the reduction in infarct size by ischemic preconditioning with three cycles of 3 min of coronary artery occlusion and interspersed by 5 min of reperfusion from 70 ± 1% (in sham rats) to 25 ± 4% (P < 0.05) was not affected by glibenclamide (infarct size 28 ± 8%; Liem et al., 2002a). Taken together, the findings in the present study are consistent with the concept that K+ATP channel activation during early reperfusion contributes to the protection by BMOV. Since glibenclamide blocks both the sarcolemmal and mitochondrial K+ATP channels (Sargent et al., 1991; Gross and Peart, 2003), future studies are needed to determine the involvement of mitochondrial versus sarcolemmal K+ATP channels in the protection against reperfusion injury by BMOV.
We have previously shown that a brief episode of intestinal ischemia can elicit remote preconditioning of the heart via a neurogenic pathway that induces protection via myocardial adenosine release and consequent receptor stimulation in the rat heart (Gho et al., 1996; Liem et al., 2002b). Because BMOV, when administered intravenously after a total coronary artery occlusion, cannot easily reach the jeopardized myocardium before reperfusion has been reinstated (rats lack a significant coronary collateral circulation), we hypothesized that activation of a neurogenic pathway could have contributed to the protective actions of BMOV. However, in the present study, we observed that the ganglion blocker hexamethonium had no effect on the cardioprotection by BMOV, suggesting that a neurogenic pathway is not involved in the cardioprotection by BMOV.
Clinical Relevance. In patients with an impending myocardial infarction, early restoration of blood flow to jeopardized ischemic myocardium is compulsory for limiting infarct size. Despite its necessity, several investigators (Braunwald and Kloner, 1985; Park and Lucchesi, 1999; Rezkalla and Kloner, 2002) have suggested that reperfusion causes irreversible myocardial damage by itself, beyond that inflicted by ischemia alone. This "lethal reperfusion injury" implies the death of cardiomyocytes (which are still viable at the onset of reperfusion) as a direct result of sequelae initiated by reperfusion itself, thereby resulting in extension of myocardial infarction. Since in patients that encounter a myocardial infarction as the first symptom of ischemic heart disease pharmacotherapy can only be applied after the coronary artery has become occluded, there is a need for agents that are protective even when given after the onset of ischemia or just before reperfusion. Most cardioprotective agents developed to date require administration before the onset of ischemia to be effective (Black, 2000). The present study shows that BMOV, administered in a sufficiently high dose, is still highly cardioprotective when administered just before reperfusion.
|
Acknowledgements |
|---|
|
Footnotes |
|---|
ABBREVIATIONS: K+ATP, ATP-sensitive potassium; BMOV, bis(maltolato)-oxovanadium; CAO, coronary artery occlusion; PBS, phosphate-buffered saline; ANOVA, analysis of variance.
Address correspondence to: Dirk J. Duncker, Experimental Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: d.duncker{at}erasmusmc.nl
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Armstrong SC, Gao W, Lane JR, and Ganote CE (1998) Protein phosphatase inhibitors calyculin A and fostriecin protect rabbit cardiomyocytes in late ischemia. J Mol Cell Cardiol 30: 61-73.[CrossRef][Medline]
Bergamaschi G, Rosti V, Danova M, Ponchio L, Lucotti C, and Cazzola M (1993) Inhibitors of tyrosine phosphorylation induce apoptosis in human leukemic cell lines. Leukemia 7: 2012-2018.[Medline]
Black SC (2000) In vivo models of myocardial ischemia and reperfusion injury: application to drug discovery and evaluation. J Pharmacol Toxicol Methods 43: 153-167.[CrossRef][Medline]
Borgers M, Shu LG, Xhonneux R, Thone F, and Van Overloop P (1987) Changes in ultrastructure and Ca2+ distribution in the isolated working rabbit heart after ischemia. A time-related study. Am J Pathol 126: 92-102.[Abstract]
Braunwald E and Kloner RA (1985) Myocardial reperfusion: a double-edged sword? J Clin Investig 76: 1713-1719.
Brown TJ, Shuford WW, Wang WC, Nadler SG, Bailey TS, Marquardt H, and Mittler RS (1996) Characterization of a CD43/leukosialin-mediated pathway for inducing apoptosis in human T-lymphoblastoid cells. J Biol Chem 271: 27686-27695.
Duncker DJ, Schulz R, Ferrari R, Garcia-Dorado D, Guarnieri C, Heusch G, and Verdouw PD (1998) "Myocardial stunning" remaining questions. Cardiovasc Res 38: 549-558.
Fryer RM, Hsu AK, and Gross GJ (2001) Mitochondrial K(ATP) channel opening is important during index ischemia and following myocardial reperfusion in ischemic preconditioned rat hearts. J Mol Cell Cardiol 33: 831-834.[CrossRef][Medline]
Fryer RM, Schultz JE, Hsu AK, and Gross GJ (1999) Importance of PKC and tyrosine kinase in single or multiple cycles of preconditioning in rat hearts. Am J Physiol 276: H1229-1235.
Geraldes CF, Castro MM, Sherry AD, and Ramasamy R (1997) Influence of vanadate on glycolysis, intracellular sodium and pH in perfused rat hearts. Mol Cell Biochem 170: 53-63.[CrossRef][Medline]
Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, and Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94: 2193-2200.
Gross GJ and Peart JN (2003) KATP channels and myocardial preconditioning: an update. Am J Physiol Heart Circ Physiol 285: H921-930.
Jeremy RW, Ambrosio G, Pike MM, Jacobus WE, and Becker LC (1993) The functional recovery of post-ischemic myocardium requires glycolysis during early reperfusion. J Mol Cell Cardiol 25: 261-276.[CrossRef][Medline]
Jeroudi MO, Hartley CJ, and Bolli R (1994) Myocardial reperfusion injury: role of oxygen radicals and potential therapy with antioxidants. Am J Cardiol 73: 2B-7B.[CrossRef][Medline]
Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajwski S, Reed JC, Olivetti G, and Anversa P (1996) Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Investig 74: 86-107.[Medline]
Kalyani P, Vijaya S, and Ramasarma T (1992) Characterization of oxygen free radicals generated during vanadate-stimulated NADH oxidation. Mol Cell Biochem 111: 33-40.[CrossRef][Medline]
Koning MM, Simonis LA, de Zeeuw S, Nieukoop S, Post S, and Verdouw PD (1994) Ischaemic preconditioning by partial occlusion without intermittent reperfusion. Cardiovasc Res 28: 1146-1151.
LaVoie HA and Witorsch RJ (1995) Investigation of intracellular signals mediating the anti-apoptotic action of prolactin in Nb2 lymphoma cells. Proc Soc Exp Biol Med 209: 257-269.[CrossRef][Medline]
Liem DA, van den Doel MA, de Zeeuw S, Verdouw PD, and Duncker DJ (2001) Role of adenosine in ischemic preconditioning in rats depends critically on the duration of the stimulus and involves both A1 and A3 receptors. Cardiovasc Res 51: 701-708.
Liem DA, Verdouw PD, Mies R, Te Lintel Hekkert M, and Duncker DJ (2002a) Mechanism of ischemic preconditioning depends critically on the stimulus (Abstract). Circulation 106: II-133.
Liem DA, Verdouw PD, Ploeg H, Kazim S, and Duncker DJ (2002b) Sites of action of adenosine in interorgan preconditioning of the heart. Am J Physiol Heart Circ Physiol 283: H29-37.
Matsubara T, Musat-Marcu S, Misra HP, and Dhalla NS (1995) Protective effect of vanadate on oxyradical-induced changes in isolated perfused heart. Mol Cell Biochem 153: 79-85.[CrossRef][Medline]
Mei DA, Elliott GT, and Gross GJ (1996) KATP channels mediate late preconditioning against infarction produced by monophosphoryl lipid A. Am J Physiol 271: H2723-2729.
Miura T, Ogawa T, Iwamoto T, Shimamoto K, and Iimura O (1992) Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic preconditioning. Circulation 86: 979-985.
Nozawa Y, Miura T, Miki T, Ohnuma Y, Yano T, and Shimamoto K (2003) Mitochondrial K+ATP channel-dependent and -independent phases of ischemic preconditioning against myocardial infarction in the rat. Basic Res Cardiol 98: 50-58.[CrossRef][Medline]
Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusch G, Cohen MV, and Downey JM (2000) Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res 87: 460-466.
Palmer G, Bonjour JP, and Caverzasio J (1996) Stimulation of inorganic phosphate transport by insulin-like growth factor I and vanadate in opossum kidney cells is mediated by distinct protein tyrosine phosphorylation processes. Endocrinology 137: 4699-4705.[Abstract]
Park JL and Lucchesi BR (1999) Mechanisms of myocardial reperfusion injury. Ann Thorac Surg 68: 1905-1912.
Przyklenk K and Kloner RA (1998) Ischemic preconditioning: exploring the paradox. Prog Cardiovasc Dis 40: 517-547.[CrossRef][Medline]
Rezkalla SH and Kloner RA (2002) No-reflow phenomenon. Circulation 105: 656-662.
Sargent CA, Smith MA, Dzwonczyk S, Sleph PG, and Grover GJ (1991) Effect of potassium channel blockade on the anti-ischemic actions of mechanistically diverse agents. J Pharmacol Exp Ther 259: 97-103.
Schoemaker RG and van Heijningen CL (2000) Bradykinin mediates cardiac preconditioning at a distance. Am J Physiol Heart Circ Physiol 278: H1571-H1576.
Schultz JE, Yao Z, Cavero I, and Gross GJ (1997) Glibenclamide-induced blockade of ischemic preconditioning is time dependent in intact rat heart. Am J Physiol Heart Circ Physiol 272: H2607-H2615.
Simons TJ (1979) Vanadate: a new tool for biologists. Nature (Lond) 281: 337-338.[CrossRef][Medline]
Takeuchi K, McGowan FX Jr, Glynn P, Moran AM, Rader CM, Cao-Danh H, and del Nido PJ (1998) Glucose transporter upregulation improves ischemic tolerance in hypertrophied failing heart. Circulation 98: II234-239.
Tanno M, Tsuchida A, Nozawa Y, Matsumoto T, Hasegawa T, Miura T, and Shimamoto K (2000) Roles of tyrosine kinase and protein kinase C in infarct size limitation by repetitive ischemic preconditioning in the rat. J Cardiovasc Pharmacol 35: 345-352.[CrossRef][Medline]
Vahlhaus C, Schulz R, Post H, Rose J, and Heusch G (1998) Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs. J Mol Cell Cardiol 30: 197-209.[CrossRef][Medline]
Van den Doel MA, Gho BC, Duval SY, Schoemaker RG, Duncker DJ, and Verdouw PD (1998) Hypothermia extends the cardioprotection by ischaemic preconditioning to coronary artery occlusions of longer duration. Cardiovasc Res 37: 76-81.
Wang QD, Pernow J, Sjoquist PO, and Ryden L (2002) Pharmacological possibilities for protection against myocardial reperfusion injury. Cardiovasc Res 55: 25-37.
Weiss JN, Korge P, Honda HM, and Ping P (2003) Role of the mitochondrial permeability transition in myocardial disease. Circ Res 93: 292-301.
Yin X, Davison AJ, and Tsang SS (1992) Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species. Mol Cell Biochem 115: 85-96.[Medline]
This article has been cited by other articles:
|
|
 |
|
  Md. S. Bhuiyan, N. Shioda, M. Shibuya, Y. Iwabuchi, and K. Fukunaga Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats Hypertension, January 1, 2009; 53(1): 57 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Przyklenk, M. Maynard, C. E. Darling, and P. Whittaker Aging Mouse Hearts Are Refractory to Infarct Size Reduction With Post-Conditioning J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1393 - 1398. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|
 |
 |
 |
, P < 0.05 BMOV prereperfusion versus BMOV pre-CAO.
