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Am J Physiol Heart Circ Physiol 293: H1007-H1012, 2007. First published March 30, 2007; doi:10.1152/ajpheart.00051.2007
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Cardioprotective effects of stretch are mediated by activation of sarcolemmal, not mitochondrial, ATP-sensitive potassium channels

Susana M. Mosca

Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina

Submitted 15 January 2007 ; accepted in final form 26 March 2007


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
To determine whether sarcolemmal and/or mitochondrial ATP-sensitive potassium (KATP) channels (sarcKATP, mitoKATP) are involved in stretch-induced protection, isolated isovolumic rat hearts were assigned to the following protocols: nonstretched hearts were subjected to 20 min of global ischemia (Is) and 30 min of reperfusion, and before Is stretched hearts received 5 min of stretch + 10 min of no intervention. Stretch was induced by a transient increase in left ventricular end-diastolic pressure (LVEDP) from 10 to 40 mmHg. Other hearts received 5-hydroxydecanoate (5-HD; 100 µM), a selective inhibitor of mitoKATP, or HMR-1098 (20 µM), a selective inhibitor of sarcKATP, before the stretch protocol. Systolic function was assessed through left ventricular developed pressure (LVDP) and maximal rise in velocity of left ventricular pressure (+dP/dtmax) and diastolic function through maximal decrease in velocity of left ventricular pressure (–dP/dtmax) and LVEDP. Lactate dehydrogenase (LDH) release and ATP content were also measured. Stretch resulted in a significant increase of postischemic recovery and attenuation of diastolic stiffness. At 30 min of reperfusion LVDP and +dP/dtmax were 87 ± 4% and 92 ± 6% and –dP/dtmax and LVEDP were 95 ± 9% and 10 ± 4 mmHg vs. 57 ± 6%, 53 ± 6%, 57 ± 10%, and 28 ± 5 mmHg, respectively, in nonstretched hearts. Stretch increased ATP content and did not produce LDH release. 5-HD did not modify and HMR-1098 prevented the protection achieved by stretch. Our results show that the beneficial effects of stretch on postischemic myocardial dysfunction, cellular damage, and energetic state involve the participation of sarcKATP but not mitoKATP.

ischemia; reperfusion

ONE OR MORE BRIEF EPISODES of coronary artery occlusion render the myocardium more resistant to a subsequent sustained ischemic insult (18). Numerous studies have shown that this protection, termed ischemic preconditioning, can be mimicked by pharmacological stimulation of various plasma membrane receptors or ion channels (1, 2, 24). Moreover, it has been demonstrated that this enhanced tolerance toward subsequent ischemia may also be triggered by transient mechanical deformation of the heart (11, 19, 23). A recent paper (10) showed that a brief pressure overload of the left ventricle preconditioned rabbit myocardium against infarction and the underlying mechanism might be related to the activation of stretch-activated ion channels. In accordance with these results, it was also demonstrated that gadolinium, a blocker of stretch-activated ion channels, was able to prevent stretch-induced protection (20, 23). However, the mechanism by which activation of these mechanosensors may protect the heart from a subsequent ischemic insult is still an unresolved issue. A previous study demonstrated that glibenclamide, a blocker of ATP-sensitive potassium (KATP) channels, prevented infarct size reduction due to transient myocardial stretch, suggesting that stretch-activated ion channels may activate KATP channels (8). Sarcolemmal and/or mitochondrial KATP channels (sarcKATP, mitoKATP) have been involved in the protection by ischemic preconditioning (17, 27, 29) and other pharmacological interventions (26). However, it is not clearly defined whether both KATP channels are end effectors of the protection by stretching.

The objectives of the present study were 1) to examine the effects of transient stretch on postischemic myocardial dysfunction, lactate dehydrogenase (LDH) release, and ATP levels in isolated rat heart submitted to 20 min of global ischemia and 30 min of reperfusion and 2) to determine whether the effects of stretch are mediated through sarcKATP and/or mitoKATP activation.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Isolated heart preparation. The investigation conformed to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Pub. No. 85-23, revised 1996). The protocol was approved by the Ethics Committee of Centro de Investigaciones Cardiovasculares, National Council of Technological and Scientist Research (CONICET).

Male Wistar rats 6 mo of age were anesthetized with an intraperitoneal injection of pentobarbital sodium (60 mg/kg body wt). The heart was rapidly excised and perfused by the nonrecirculating Langendorff technique with Ringer solution containing (in mM) 118 NaCl, 5.9 KCl, 1.2 MgSO4, 1.35 CaCl2, 20 NaHCO3, and 11.1 dextrose. The buffer was saturated with a mixture of 95% O2-5% CO2, had a pH of 7.4, and was maintained at 37°C. The conductive tissue in the atrial septum was damaged with a fine needle to achieve atrioventricular block, and the right ventricle was paced at 280 ± 10 beats/min. A latex balloon tied to the end of a polyethylene tube was passed into the left ventricle through the mitral valve; the opposite end of the tube was then connected to a Statham P23XL pressure transducer. The balloon was filled with water to provide a left ventricular end-diastolic pressure (LVEDP) of 8–12 mmHg, and this volume remained unchanged for the rest of the experiment. Coronary perfusion pressure (CPP) was monitored at the point of aorta cannulation and adjusted to ~60–70 mmHg. Coronary flow (CF), controlled with a peristaltic pump, was 11 ± 2 ml/min. Left ventricular pressure (LVP) and its first derivative (dP/dt) were recorded with a direct writing recorder.

Experimental protocols. After 10 min of stabilization, the following experimental protocols were performed.

Nonstretched hearts (n = 10) were subjected to 20 min of normothermic global ischemia followed by 30 min of reperfusion. Global ischemia was induced by stopping the perfusate inflow line, and the heart was placed in a saline bath held at 37°C.

In stretched hearts (n = 7), the balloon volume was increased until LVEDP values of ~40 mmHg were reached. The hearts remained in this condition for 5 min and then were released, returning LVEDP to an initial value over 10 min. Hearts were then submitted to the protocol of ischemia and reperfusion described above for nonstretched hearts.

Other hearts were treated 10 min before ischemia (in the absence of stretch) or before stretching with 100 µM 5-hydroxydecanoate (5-HD; Sigma-Aldrich, St. Louis, MO), a selective blocker of mitoKATP, or with 20 µM 1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea (HMR-1098, a gift of Aventis Pharma Deutschland), a selective blocker of sarcKATP.

Systolic and diastolic function. Myocardial contractility was assessed by left ventricular developed pressure (LVDP), obtained by subtracting LVEDP values from LVP peak values, and maximal rise velocity of LVP (+dP/dtmax) values. Data were expressed as a percentage of their respective preischemic values. Diastolic function was evaluated by –dP/dtmax values and LVEDP.

LDH measurement. LDH release—an indicator of cellular damage—was measured in samples collected from the coronary effluent during preischemic and reperfusion periods for all groups and assayed by a spectrometric technique with a commercial kit at 340 nm. The amount of LDH released during reperfusion was obtained by subtracting from the total enzyme release the LDH leakage observed before the ischemic period and expressed in international units per gram of heart wet weight.

ATP content. Before ischemia and at the end of reperfusion hearts were frozen and stored in an ultra low-temperature freezer (–70°C) until ATP extraction. The hearts were crushed with a nitrogen-cooled mortar and pestle, and neutralized perchloric acid extracts were assayed for ATP levels by a standard enzymatic procedure (14).

Statistical analysis. Data are given as means ± SE and were analyzed with repeated-measures one-way analysis of variance (ANOVA) with the Newman-Keuls test for multiple comparisons among groups. Values of P < 0.05 were considered to be significant.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Figure 1 shows the effects in our preparation of 20 min of global ischemia followed by 30 min of reperfusion. In nonstretched hearts, a decrease of LVDP and +dP/dtmax to values of 57 ± 6% and 53 ± 6%, respectively, from baseline was detected at the end of the reperfusion period. At the end of reperfusion LVDP and +dP/dtmax were 87 ± 4% and 92 ± 6%, respectively.


Figure 1
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  		Fig. 1. Time course of left ventricular developed pressure (LVDP, top) and maximal rise velocity of left ventricular pressure (+dP/dtmax, bottom) during ischemia and reperfusion in nonstretched and stretched hearts. Note that both parameters were significantly improved by stretching. *P < 0.05 compared with nonstretched hearts. Is, ischemia.

 
The protection of LVDP and +dP/dtmax observed in stretched hearts (Fig. 2) was not modified when hearts were treated 10 min before stretching with 5-HD, a selective mitoKATP blocker. Figure 2 also shows that the protection of postischemic systolic function induced by stretch was lost by sarcKATP blockade with HMR-1098 applied 10 min before stretching (LVDP 53 ± 11%, +dP/dtmax 54 ± 11%). Neither HMR-1098 nor 5-HD modified preischemic myocardial function and postischemic recovery of nonstretched hearts. At the end of reperfusion LVDP and +dP/dtmax recovered ~50%.


Figure 2
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  		Fig. 2. Effects of HMR-1098 [sarcolemmal ATP-sensitive potassium (KATP) channel blocker] and 5-hydroxydecanoate (5-HD; mitochondrial KATP channel blocker) on LVDP (top) and +dP/dtmax (bottom) during ischemia and reperfusion in stretched hearts. Note that 5-HD did not modify whereas HMR-1098 abolished the improvement of both parameters afforded in stretched hearts.

 
Figure 3 shows the improvement of diastolic dysfunction (LVEDP) by stretch, diminishing the increase of stiffness during reperfusion observed in nonstretched hearts (at 30 min of reperfusion LVEDP was 10 ± 4 mmHg vs. 28 ± 5 mmHg in nonstretched hearts). In stretched hearts an increase of –dP/dtmax recovery during reperfusion (95 ± 9% vs. 57 ± 10% in nonstretched hearts) was also detected. Ischemic contracture was significantly diminished by stretching (at 20 min of ischemia LVEDP was 19 ± 6 mmHg vs. 44 ± 4 mmHg in nonstretched hearts). This diastolic protection was maintained when mitoKATP were blocked, but it was not abolished when sarcKATP were blocked (Fig. 4).


Figure 3
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  		Fig. 3. Changes of left ventricular end-diastolic pressure (LVEDP, top) and maximal decrease velocity of left ventricular pressure (–dP/dtmax, bottom) during ischemia and reperfusion in nonstretched and stretched hearts. Stretching performed before ischemia attenuated the increase of diastolic stiffness and increased relaxation velocity during reperfusion. A decrease in ischemic contracture was also detected in stretched hearts. *P < 0.05 compared with nonstretched hearts.

 

Figure 4
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  		Fig. 4. Effects of HMR-1098 (sarcolemmal KATP channel blocker) and 5-HD (mitochondrial KATP channel blocker) on LVEDP (top) and –dP/dtmax (bottom) during ischemia and reperfusion in stretched hearts. Note that 5-HD did not modify whereas HMR-1098 abolished the effects of stretch.

 
Absolute values of LVDP, +dP/dtmax, and –dP/dtmax during prestretch, stretch, and preischemia and at 5, 15, and 30 min of reperfusion in all experimental groups are shown in Table 1.


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  		Table 1. Absolute values of LVDP, +dP/dtmax, and +dP/dtmax in nonstretched, stretched, stretched + HMR-1098, and stretched +5-HD hearts

 
Since CF was maintained constant, during stretch CPP increased to 76 ± 1.8 mmHg from a value of 65 ± 0.8 mmHg. This increase probably took place to counteract the mechanical overpressure on the endocardium due to the increase of balloon volume. This would maintain an adequate perfusion of the myocardial tissue and would avoid possible ischemia by demand. Furthermore, LDH release did not change during prestretch and stretch, indicating that stretch per se did not result in significant myocardial necrotic injury.

Figure 5 shows the extent of LDH release into the coronary effluent during reperfusion, measured to assess the degree of cell damage in all experimental groups. The release of LDH detected during the reperfusion period in nonstretched hearts was completely absent when hearts were protected by stretch. Figure 5 also shows that when 5-HD was administered before stretching LDH leakage similar to that obtained in stretched hearts was detected. Treatment with HMR-1098 before stretch restored the LDH release of nonstretched hearts.


Figure 5
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  		Fig. 5. Values of lactate dehydrogenase (LDH) release during the reperfusion period in nonstretched and stretched hearts with and without HMR-1098 (sarcolemmal KATP channel blocker) or 5-HD (mitochondrial KATP channel blocker). Note that stretching annulled the LDH release detected in nonstretched hearts and this effect was lost by HMR-1098 treatment. NS, not significant. *P < 0.05 with respect to 0.

 
Preischemic ATP content in nonstretched hearts was 20.2 ± 0.8 µmol/g and did not differ significantly among all experimental groups. Figure 6 shows ATP content of myocardial tissue at the end of the reperfusion period. In stretched hearts a higher ATP concentration was obtained compared with nonstretched hearts (9.6 ± 1.1 vs. 5.4 ± 0.8 µmol/g). This improvement of energetic reserve was maintained in the presence of 5-HD, but it was abolished when sarcKATP were blocked.


Figure 6
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  		Fig. 6. Myocardial ATP values in nonstretched and stretched hearts with and without HMR-1098 (sarcolemmal KATP channel blocker) or 5-HD (mitochondrial KATP channel blocker). Stretching improved ATP content compared with nonstretched hearts, and this improvement was lost when sarcolemmal KATP channels were blocked. *P < 0.05 compared with nonstretched hearts; #P < 0.05 compared with stretched hearts.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The present study shows that mechanical stretch improves postischemic recovery of contractility, energetic state, and cellular damage of isovolumically isolated rat hearts submitted to 20 min of global ischemia and 30 min of reperfusion. These results are in close agreement with previous studies performed in other species and experimental models (6, 10, 11, 20, 23, 28).

Experiments were performed to induce a short ischemia, selected because it resulted in a transient myocardial dysfunction, characterized as "myocardial stunning" (4). Although in this model there are no significant irreversible changes we cannot exclude the presence of patchy infarcts, which were estimated by LDH release. Since stretch annulled LDH leakage and preserved ATP levels, we could conclude that this mechanical maneuver protects the myocardium against stunning and against cell death, both effects being dependent and/or simultaneous. These two protective actions afforded by stretch do not coexist in all cardioprotective interventions. Thus a previous study performed by Ovize et al. (22) showed that ischemic preconditioning reduced infarct size but was unable to preserve contractile function, both actions appearing to be independent. Given that the increase in balloon volume does not produce ischemia, we suggest that the stretch per se is responsible for the observed cardioprotective effects.

The underlying mechanism of this stretch-induced preconditioning remains unclear. Previous studies using gadolinium showed that nonselective cationic stretch-activated channels (SAC) are involved in the protective effect achieved by stretch (20, 23). However, the interpretation of results with gadolinium is difficult because this drug blocks many types of ion channels and exchangers and binds to anions such as HCO3– (5, 13). Considering that cell swelling taking place during ischemia-reperfusion affects other osmotically modulated channels and transporters (30), other mechanisms than SAC could be participating in the beneficial effects of stretch. There is evidence from the use of glibenclamide as blocker that KATP channels, apart from participation in ischemic preconditioning, are involved in the favorable effects of stretch (21). In this sense, one important finding of our study is that sarcKATP but not mitoKATP are involved in the protective effects achieved by stretch, taking into account that the stretch protection was not modified by treatment with 5-HD but was abolished when HMR-1098 was added to the perfusion line. Therefore, although many studies support a role for both KATP channels in ischemic preconditioning (7) we observed that only sarcKATP are involved in stretch-induced protection. What is the mechanism of sarcKATP activation by stretch? Considering that ATP levels were improved by stretch, the energy state would not be the cause of the opening of sarcKATP. One possibility to be considered is that mechanical deformation of the myocyte might directly activate sarcKATP, an hypothesis supported by a previous study performed by Van Wagoner (31) in isolated atrial myocytes. Van Wagoner demonstrated that stretch can directly activate sarcKATP in the absence of variation in ATP content. Alternatively, one can hypothesize that the mechanosensitive protection would be indirect, with the intervention of biochemical steps between the initial mechanical event (activation of SAC) and the end effector (sarcKATP). Another hypothesis could be that activation of sarcKATP is an initial event that modulates gating of stretch-activated channels. However, at present, there is no evidence that the stretch-induced protection for channels is activated before mechanogated sensors are stimulated.

Komuro et al. (12) demonstrated in a primary culture of rat ventricular myocytes that stretch activates both phospholipases C and D and increases the production of diacylglycerol, the natural activator of PKC. A previous paper suggested activation of PKC as a mechanism involved in the protection induced by stretch (21). One may speculate about the link between stretch-activated ion channels, PKC, and sarcKATP. Previous papers reported that PKC may regulate KATP channels, increasing ATP-sensitive K+ currents (9, 15, 16). Our data are consistent with the activation of sarcKATP by stretching in the presence of higher ATP levels than in nonstretched hearts. Moreover, these two effects of stretching appear to be independent mechanisms of protection. Although we do not have experimental evidence, a sequential activation of mechanosensitive ion channels, PKC, and sarcKATP would be possible. However, further work is needed to clarify the link between these mediators.

Because Ca2+ overload appears to play a negative role in postischemic recovery of contractility (3), the opening of sarcKATP could cause hyperpolarization-induced decrease of Ca2+ influx. The diminution of intracellular Ca2+ could avoid the mitochondrial Ca2+ overload, thus preserving the mitochondrial function. This mechanism would explain the better energy state detected in stretched compared with nonstretched hearts. Both events, a decrease in Ca2+ influx and ATP preservation, would also explain the low ischemic contracture obtained after stretching.

It has also been proposed that cyclic mechanical stretch increases myocyte reactive oxygen species (ROS) production (25). Although the stretch applied in our experiments was transient, the possibility of an activation of survival enzymes by ROS cannot be rule out and needs further investigation.

In conclusion, the present study demonstrates that stretch improves postischemic myocardial dysfunction and energy stores and decreases cellular damage in the isolated rat heart through activation of sarcolemmal KATP channels.


   FOOTNOTES
 

Address for reprint requests and other correspondence: Susana M. Mosca, Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina (e-mail: smosca{at}atlas.med.unlp.edu.ar)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Auchampach JA, Maruyama M, Gross GJ. Cardioprotective actions of potassium channel openers. Eur Heart J 15: 89–94, 1994.[Abstract/Free Full Text]
  2. Banerjee A, Locke-Winter C, Rogers KB, Mitchell MB, Brew EC, Cairns CB, Bensard DD, Harken AH. Preconditioning against myocardial dysfunction after ischemia and reperfusion by an alpha1-adrenergic mechanism. Circ Res 73: 656–670, 1993.[Abstract/Free Full Text]
  3. Bolli R, Marban E. Molecular and cellular mechanisms of myocardial stunning. Physiol Rev 79: 609–634, 1999.[Abstract/Free Full Text]
  4. Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 66: 1146–1149, 1982.[Abstract/Free Full Text]
  5. Caldwell RA, Clemo HF, Baumgarten CM. Using gadolinium to identify stretch-activated channels: technical considerations. Am J Physiol Cell Physiol 275: C619–C621, 1998.[Abstract/Free Full Text]
  6. Christensen O. Mediation of cell volume regulation by Ca2+ influx through stretch-activated channels. Nature 330: 66–68, 1987.[CrossRef][Medline]
  7. Gross GJ, Peart JN. KATP channels and myocardial preconditioning: an update. Am J Physiol Heart Circ Physiol 285: H921–H930, 2003.[Abstract/Free Full Text]
  8. Gysembergh A, Margonari H, Loufoua J, Ovize A, André-Fouët X, Minaire Y, Ovize M. Stretch-induced protection shares a common mechanism with ischemic preconditioning in rabbit heart. Am J Physiol Heart Circ Physiol 274: H955–H964, 1998.[Abstract/Free Full Text]
  9. Hu K, Duan D, Li GR, Nattel S. Protein kinase C activates ATP-sensitive K+ current in human and rabbit ventricular myocytes. Circ Res 78: 492–498, 1996.[Abstract/Free Full Text]
  10. Huang CH, Wang JS, Chiang SC, Wang YY, Lai ST, Weng ZC. Brief pressure overload of the left ventricle preconditions rabbit myocardium against infarction. Ann Thorac Surg 78: 628–633, 2004.[Abstract/Free Full Text]
  11. Iliodromitis EK, Vlahakos DV, Bofilis E, Karavolias GK, Tasouli A, Kremastinos DT. Angiotensin II fails to induce preconditioning in vivo-the protective role of myocardial stretch due to pressure overload. Can J Cardiol 18: 34–42, 2002.[ISI][Medline]
  12. Komuro I, Katoh H, Kaida T, Shibazaki Y, Kurabayashi M, Hoh E, Takaku F, Yazaki Y. Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role for protein kinase C activation. J Biol Chem 266: 1265–1268, 1991.[Abstract/Free Full Text]
  13. Lamberts RR, Van Rijen MH, Sipkema P, Fransen P, Sys SU, Westerhof N. Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms. Am J Physiol Heart Circ Physiol 283: H1515–H1522, 2002.[Abstract/Free Full Text]
  14. Lamprecht W, Stein P, Heinz F, Weisser H. Creatine phosphate. In: Methods of Enzymatic Analysis, edited by Bergmeyer HU. New York: Academic, 1974, p. 1777–1781.
  15. Light PE, Sabir AA, Allen BG, Walsh MP, French RJ. Protein kinase C-induced changes in the stoichiometry of ATP binding activate cardiac ATP-sensitive K+ channels. Circ Res 79: 399–406, 1996.[Abstract/Free Full Text]
  16. Liu Y, Gao WD, O'Rourke B, Marbán E. Synergistic modulation of ATP-sensitive K+ currents by protein kinase C and adenosine. Implications for ischemic preconditioning. Circ Res 78: 443–454, 1996.[Abstract/Free Full Text]
  17. Liu Y, Sato T, O'Rouke B, Marbán E. Mitochondrial ATP-sensitive potassium channels: novel effectors of cardioprotection? Circulation 97: 2463–2469, 1998.[Abstract/Free Full Text]
  18. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 5: 1124–1136, 1986.
  19. Nakagawa C, Asayama J, Katamura M, Matoba S, Keira N, Kawahara A, Tsuruyama K, Tanaka T, Kobara M, Akashi K, Ohta B, Tatsumi T, Nakagawa M. Myocardial stretch induced by increased left ventricular diastolic pressure preconditions isolated perfused hearts of normotensive and spontaneously hypertensive rats. Basic Res Cardiol 92: 410–416, 1997.[ISI][Medline]
  20. Nicolosi AC, West G, Markley JG, Logan B, Olinger GN. Gadolinium attenuates regional stunning in the canine heart in vivo. J Thorac Cardiovasc Surg 124: 57–62, 2002.[Abstract/Free Full Text]
  21. Obadia JF, Ovize M, Maupoil V, Terrand J, Abadie C, Ovize A, Andre-Fouet X, Minaire Y, Rochette L. Beneficial actions of preconditioning and stretch on postischemic contractile function of isolated working rat heart: effects of staurosporine. J Cardiovasc Pharmacol 30: 191–196, 1997.[CrossRef][ISI][Medline]
  22. Ovize M, Przyklenk K, Hale SL, Kloner RA. Preconditioning does not attenuate myocardial stunning. Circulation 85: 2247–2254, 1992.[Abstract/Free Full Text]
  23. Ovize M, Przyklenk K, Kloner RA. Stretch preconditions the canine myocardium. Am J Physiol Heart Circ Physiol 266: H137–H146, 1994.[Abstract/Free Full Text]
  24. Peart JN, Gross GJ. Cardioprotective effects of acute and chronic opioid treatment are mediated via different signaling pathways. Am J Physiol Heart Circ Physiol 291: H1746–H1753, 2006.[Abstract/Free Full Text]
  25. Pimentel DR, Amin JK, Xiao L, Miller T, Viereck J, Oliver-Krasinski J, Baliga R, Wang J, Siwik DA, Singh K, Pagano P, Colucci WS, Sawyer DB. Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res 89: 453–460, 2001.[Abstract/Free Full Text]
  26. Piriou V, Chiari P, Knezynski S, Bastien O, Loufoua J, Lehot JJ, Foex P, Annat G, Ovize M. Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium: possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels. Anesthesiology 93: 756–764, 2000.[CrossRef][ISI][Medline]
  27. Schulz R, Rose J, Heusch G. Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine. Am J Physiol Heart Circ Physiol 267: H1341–H1352, 1994.[Abstract/Free Full Text]
  28. Suleymanian MA, Clemo HF, Cohen NM, Baumgarten CM. Stretch-activated channel blockers modulate cell volume in cardiac ventricular myocytes. J Mol Cell Cardiol 27: 721–728, 1995.[ISI][Medline]
  29. Suzuki M, Sasaki N, Miki T, Sakamoto N, Ohmoto-Sekine Y, Tamagawa M, Seino S, Marban E, Nakaya H. Role of sarcolemmal KATP channels in cardioprotection against ischemia/reperfusion injury in mice. J Clin Invest 109: 509–516, 2002.[CrossRef][ISI][Medline]
  30. Vandenberg J, Rees SA, Wright AR, Powell T. Cell swelling and ion transport pathways in cardiac myocytes. Cardiovasc Res 32: 85–97, 1996.[CrossRef][ISI][Medline]
  31. Van Wagoner DR. Mechanosensitive gating of atrial ATP-sensitive potassium channels. Circ Res 72: 973–983, 1993.[Abstract/Free Full Text]




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