| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2004;78:961-969
© 2004 The Society of Thoracic Surgeons
a Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Crawford Long Hospital, Emory University School of Medicine, Atlanta, Georgia, USA
Accepted for publication March 8, 2004.
* Address reprint requests to Dr Zhao, Cardiothoracic Research Laboratory, Crawford Long Hospital, Emory University School of Medicine, 550 Peachtree St, NE, Atlanta, GA 30308-2225, USA
zzhao{at}emory.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
METHODS: Four groups of open-chest canines endured 60 minutes coronary occlusion followed by 3 hours reperfusion: control (n = 10), no intervention; IPC (n = 9), 5 minutes left anterior descending coronary artery occlusion preceded 10 minutes of reperfusion before prolonged occlusion; postcon (n = 10), 3 cycles of 30 seconds reperfusion-30 seconds reocclusion were imposed immediately upon reperfusion; IPC+postcon (n = 8), IPC and postcon algorithms were combined.
RESULTS: Collateral blood flow during ischemia was similar in all groups. Compared to control (24% ± 2%), infarct size was comparably reduced in IPC (13% ± 2%* [* denotes p less than 0.05 compared with control]), and postcon (10% ± 1%*), consistent with a reduction in plasma creative kinase activity in these groups; infarct size was not further reduced by IPC+postcon (12% ± 3%*). Tissue water content in ischemic myocardium was comparably reduced in IPC, postcon, and IPC+postcon compared to control. Superoxide anion generation detected by dihydroethidium staining in area at risk myocardium was comparably reduced in all intervention groups relative to control. Plasma malondialdehyde (µM), a lipid peroxidation byproduct of oxidant injury, was less at 1 hour of reperfusion in IPC (2.2 ± 0.2*), postcon (2.1 ± 0.2*), and IPC+postcon (2.5 ± 0.2*) relative to control (3.3 ± 0.2). Ventricular fibrillation occurred less often in all intervention groups.
CONCLUSIONS: No additive cardioprotective effects by IPC and postcon were observed in a canine model of regional ischemia and reperfusion. The potent attenuation of myocardial injury by postcon may suggest a clinically applicable strategy during some surgical revascularization procedures (ie, OPCAB).
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Perfusion-assisted direct coronary artery bypass surgery (PADCAB) strategies have been reported to improve postreperfusion outcomes [6, 7]. However, PADCAB requires delivery devices for perfusion of vessel conduits, therefore increasing the complexity of the procedure. We have recently shown that postconditioning (postcon), a brief period of repetitive coronary artery occlusion and reperfusion applied at the onset of reperfusion, significantly reduced infarct size, preserved endothelial function, and inhibited inflammatory and endothelial cell-cell interactions [8]. Postconditioning has been reproduced in independent laboratories [9] and in cell culture systems [10]. These data demonstrate a novel endogenous cardioprotective mechanism that can be applied to OPCAB procedures in which brief periods of ischemia are introduced during reperfusion.
Both preconditioning and postconditioning have demonstrated powerful cardioprotection in the laboratory setting. However, preconditioning and postconditioning intervene at opposite ends of the ischemic event. The present study tested the hypothesis that coapplication of ischemic preconditioning and postconditioning in a canine model of regional ischemia and reperfusion would provide additive protection compared to either intervention alone.
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Adult canines weighing 25 to 35 kg were premedicated with an intramuscular injection of morphine sulfate (4 mg/kg) followed by continuous inhalation of isoflurane (1%) after endotracheal intubation. Exposure of the left anterior descending artery and instrumentation for measuring left ventricular pressure and regional contractile function was achieved, as reported previously [8]. A catheter was inserted into the left atrium for injection of neutron-activated microspheres (BioPal Laboratories, Worcester, MA) to measure regional myocardial blood flow. All dogs were systemically heparinized with 300 U/kg sodium heparin before starting the experiment.
Experimental protocol
In all animals, the left anterior descending coronary artery (LAD) was reversibly occluded by gently pulling up on an occluding silk ligature for 60 minutes followed by 3 hours of reperfusion. The animals were randomly assigned to 1 of 4 groups (Fig 1): (1) control (n = 10), no intervention before ischemia or reperfusion; (2) IPC (n = 9), the LAD was occluded for 5 minutes followed by 10 minutes reperfusion before 60 minutes occlusion; (3) postcon (n = 10), after 60 minutes LAD occlusion, reperfusion was initiated for 30 seconds followed by 30 seconds of reocclusion, repeated for 3 cycles (3 minutes total intervention); (4) IPC+postcon (n = 8), the above IPC and postcon protocols were combined. After ligature release, the ischemic myocardium was reperfused for a total of 3 hours in all groups, inclusive of postcon interventions. At the end of reperfusion, the heart was excised to evaluate infarct size, tissue edema, regional myocardial blood flow, and superoxide anion generation in the area at risk.
|
|
Regional myocardial blood flow
Regional myocardial blood flow in the subepicardial and subendocardial regions of the AR and nonischemic LV free wall was determined by neutron-activated microspheres at baseline, ischemia, and at 15 minutes and 3 hours of reperfusion using the reference sampling method as previously described [8]. Results are expressed as mL/min/g tissue.
Determination of plasma creatine kinase (CK) and malondialdehyde (MDA)
Arterial blood samples were withdrawn at baseline, at the end of ischemia, and at 1, 2, and 3 hours of reperfusion to measure CK activity (Sigma Diagnostic, St. Louis, MO), an index of morphologic injury, and MDA (lipid peroxidation assay, Calbiochem, San Diego, CA), an index of lipid peroxidation reflecting oxygen free radical mediated membrane damage [11, 12]. Plasma CK and MDA were analyzed spectrophotometrically (SPECTRAmax, Molecular Devices, Sunnyvale, CA) at 340 nm and 586 nm absorbance, respectively. Creatine kinase activity was expressed as U/g protein, and plasma MDA values were given as µM.
Tissue edema in area at risk myocardium
Tissue samples (0.3 g) were taken from subepicardial and subendocardial regions of the area at risk, and from the contralateral nonischemic left ventricular free wall, quickly blotted of surface moisture, and weighed. The samples were desiccated in an 80°C oven for 48 hours and reweighed. Tissue water content was calculated as 100*[1-(dry weight/wet weight)].
In situ detection of superoxide anion generation in myocardium
Ischemic and nonischemic myocardium was stained with dihydroethidium (DHE, Molecular Probes, Eugene, OR) to identify superoxide anions, as previously described [8]. Dihydroethidium reacts with superoxide anions to form ethidium (Eth) bromide, which in turn intercalates into DNA to provide nuclear fluorescence as a marker of superoxide anion generation. Briefly, transmural tissue samples from nonischemic and ischemic myocardium were harvested at the end of the experiment, placed in cold saline, and embedded in optimal cutting temperature (OCT) compound for cryosectioning. The tissue sections (20 µm) were cut using a Hacker-Bright cryostat, thaw-mounted on Fisher-Plus (Fisher Scientific) slides, and stained with 10 µmol/L DHE at 37°C for 30 minutes. The image of ethidium staining, as well as a quantitative assessment of fluorescent intensity was obtained using an imaging system (Image-Pro Plus, Media Cybemetics, Silver Spring, MD) with a 585 nm long-pass filter. Generation of superoxide anions in tissue after 3 hours of reperfusion, demonstrated by red fluorescent labeling, represents the phase of sustained production of reactive oxygen species (ROS) after the initial reperfusion burst [13, 14]. The enhanced Eth-DNA fluorescence is an indicator of superoxide generation within cells [15]. The fluorescent intensity of the cells was expressed as arbitrary units of per millimeter square field.
Ventricular fibrillation
The incidence of ventricular fibrillation (VF) was recorded in all experiments. Ventricular fibrillation did not occur during ischemia in any of the animals. If VF occurred upon reperfusion, the heart was quickly defibrillated. Ventricular fibrillation was deemed intractable if sinus rhythm could not be restored with 2 countershocks or if hemodynamic instability resulted in cardiac arrest. Although animals with intractable VF and/or cardiac arrest were excluded from the final analysis, the occurrence of all VF in animals requiring defibrillation was documented and compared in all groups.
Statistical analysis
A one-way analysis of variance (ANOVA) followed by Student-Newman-Keuls test was used to analyze group differences in a single point data such as infarct size and tissue water content. Hemodynamic data and other time-dependent determinations were analyzed by repeated measures ANOVA followed by posthoc analysis with Student-Newman-Keuls multiple comparisons. A 
2 analysis was used to test differences in the incidence of VF. A p value less than 0.05 was considered significant. Results are reported as mean ± standard error of the mean.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Hemodynamics and regional contractile function
Baseline function was similar in all groups (Table 1). In all groups, LAD occlusion caused paradoxical bulging in the area at risk. Contractile dysfunction in the area at risk, quantified as percent systolic shortening and segment work, persisted during the 3 hours of reperfusion without any significant return of regional function, and with no statistically significant group differences.
Regional myocardial blood flow
Regional myocardial blood flow was equivalent in the nonischemic myocardium at baseline in all groups studied, and remained unchanged during the experiment. The LAD occlusion reduced regional myocardial blood flow in the AR subepicardium and subendocardium (data not shown) comparably in all groups by approximately 94% (Fig 2). Release of the coronary ligature resulted in a marked increase in subepicardial regional myocardial blood flow in the AR at 15 minutes of reperfusion that was significantly less in IPC, postcon, and IPC+postcon compared to control (p = 0.04, Fig 2). There were no significant differences in subendocardial flow during ischemia among the four groups (control 0.05 ± 0.02, IPC 0.04 ± 0.01, postcon 0.05 ± 0.01, and IPC+postcon 0.02 ± 0.01 [mL/min/g of tissue]), suggesting that changes in infarct size were independent of collateral flow. Similarly, there were no significant group differences in subendocardial blood flow during any of the other time points during reperfusion.
|
|
|
|
|
|
|
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
In the present study, we demonstrate a novel strategy that can potentially be used in OPCAB surgery to protect the revascularized segment from reperfusion injury. Postconditioning with a rapid sequence of repetitive reperfusions and reocclusions at the onset of reperfusion provides potent cardioprotection comparable to that of ischemic preconditioning. The protective effects of ischemic preconditioning and postconditioning were independent of changes in collateral blood flow in the area at risk during ischemia, which is a known determinant of infarct size after coronary occlusion [22]. The cardioprotection of postconditioning may be related to the observed inhibition of superoxide anion generation and oxidant-mediated cellular membrane damage expressed as lipid peroxidation. However, there were no additive protective effects when both preconditioning and postconditioning were sequentially applied. None of the strategies improved regional postischemic contractile function at 3 hours of reperfusion. However, there was a tendency for the combination to reduce the incidence of reperfusion ventricular fibrillation.
In this study, the generation of reactive oxygen species (ROS) during reperfusion, was comparably reduced by both ischemic preconditioning and postconditioning. Although free radical generation occurs during prolonged ischemia [23], a larger oxidative "burst" occurs with reperfusion [13, 24], which contributes to the development of postischemic injury [14, 25]. In addition, there is a sustained elevated level of ROS observed during later reperfusion [13]. In a study by Kevin and colleagues [14], ROS generation was reduced during the first 10 minutes of reperfusion in preconditioned hearts. Others have confirmed the effects of ischemic preconditioning in decreasing ROS production during reperfusion [11, 25]. In contrast to ischemic preconditioning, postconditioning can only reduce ROS generation during early reperfusion by mechanisms other than those engaged by preconditioning. Our results show similar reductions in DHE fluorescence after 3 hours of reperfusion with both preconditioning and postconditioning; lipid peroxidation products were also reduced at 1 hour of reperfusion, consistent with a reduction in ROS and ROS-derived products during the earlier stages of reperfusion. The observation by Vinten-Johansen and colleagues [26] that the cardioprotection by postconditioning is abrogated if the algorithm is delayed and the initial minutes of reperfusion are uncontrolled, is consistent with the hypothesis that postconditioning attenuates the large burst of ROS generated during the early moments of reperfusion, as well as the sustained generation during late reperfusion. However, whether postconditioning reduces ROS generation and during which time point of reperfusion this reduction takes place must still be elucidated. Although we cannot directly correlate the reduction of infarct size with the reduction of ROS in this study, a reduction of oxygen radicals is strongly associated with a reduction of postischemic injury [14, 25]. However, we cannot exclude the possibility that postconditioning reduces postischemic injury by mechanisms unrelated to ROS generation.
Several studies have documented the antiarrhythmic effects of ischemic preconditioning [27, 28]. In the present study, we found that VF occurred less often in the treatment groups compared to the control group. Ventricular fibrillation occurred in only 10% of the combined ischemic preconditioning and postconditioning cases. In addition, ventricular tachyarrhythmias that usually occurred with the initiation of reperfusion promptly resolved with reocclusion during the period of postconditioning. However, the study was not sufficiently powered to show statistical differences for this variable by nonparametric techniques, so we cannot claim attenuation of reperfusion arrhythmias as a benefit of postconditioning.
Limitations
As has been previously reported [29], both morphine sulfate and isoflurane used in the present study for premedication and anesthesia have preconditioning-mimetic effects. This may help to explain why the average infarct size in the control group was smaller than that reported by others who used different premedication and anesthesia regimens in canine models of regional ischemia-reperfusion [30]. However, the animals in all groups were premedicated and anesthetized in the same manner, and myocardial injury was significantly reduced by ischemic preconditioning and postconditioning. Therefore, we can exclude the possibility that changes in the reduction of infarct size and inhibition of ROS in the IPC and postconditioning groups were related to the anesthetic drugs used to some extent. In addition, either ischemic preconditioning or postconditioning alone may exert the maximum protection relative to the combination in our coronary occlusion model. We cannot exclude the possibility that a longer occlusion time or a more proximal LAD ligation would have unmasked additive cardioprotective effects of preconditioning and postconditioning, but a study with prolonged ischemic times should be performed. Finally, although we have implied that postconditioning could be applied during OPCAB, a model more closely resembling the surgical conditions during off-pump surgery would be needed to demonstrate protection. Furthermore, a prospective clinical trial would be required to document the safety and efficacy of this intervention in the clinical OPCAB setting.
In conclusion, the present study demonstrated the cardioprotective effects of postconditioning in the setting of acute myocardial infarction. However, the study failed to demonstrate enhanced cardioprotection when both preconditioning and postconditioning were combined. A preliminary report by Yang and colleagues [9] in a rabbit model of coronary occlusion-reperfusion suggests that preconditioning and postconditioning are additive during more prolonged ischemia than tested in the present study. Therefore, an additive effect may be expressed if coronary occlusion times exceed those used in the present study. The data from the present study suggest that the area at risk myocardium can be salvaged by manipulating the dynamics of the immediate onset of reperfusion. Even a short period of full reperfusion preceding the cyclical postconditioning algorithm can abrogate its cardioprotection [26]. Postconditioning offers a practical alternative to preconditioning in that foreknowledge of ischemia is not required. Postconditioning would be simple to apply in the OPCAB setting in which full reperfusion after completion of the distal anastomosis is preceded by cyclical interruptions of reflow according to a specific algorithm. Postconditioning may also be applied after completion of vascular grafts in surgical revascularization using cardiopulmonary bypass, or as a final procedure before release of aortic cross clamp. In addition, this procedure may also be suitable for other clinical settings such as percutaneous transluminal coronary angioplasty and organ transplantation.
|
Acknowledgments |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Related Article
This article has been cited by other articles:
|
|
 |
|
  E. K. Iliodromitis, J. M. Downey, G. Heusch, and D. T. Kremastinos What Is the Optimal Postconditioning Algorithm? Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2009; 14(4): 269 - 273. [Abstract] [PDF]
|
|
|
|
 |
|
 O. C. Manintveld, M. t. L. Hekkert, N. T. van der Ploeg, P. D. Verdouw, and D. J. Duncker Interaction Between Pre- and Postconditioning in the In Vivo Rat Heart Experimental Biology and Medicine, November 1, 2009; 234(11): 1345 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Granfeldt, D. J. Lefer, and J. Vinten-Johansen Protective ischaemia in patients: preconditioning and postconditioning Cardiovasc Res, July 15, 2009; 83(2): 234 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hecht, J. Rong, A. L. F. Sampaio, C. Hermesh, C. Rutledge, R. Shemesh, A. Toporik, M. Beiman, L. Dassa, H. Niv, et al. A Novel Peptide Agonist of Formyl-Peptide Receptor-Like 1 (ALX) Displays Anti-Inflammatory and Cardioprotective Effects J. Pharmacol. Exp. Ther., February 1, 2009; 328(2): 426 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nishino, I. G. Webb, S. M. Davidson, A. I. Ahmed, J. E. Clark, S. Jacquet, A. M. Shah, T. Miura, D. M. Yellon, M. Avkiran, et al. Glycogen Synthase Kinase-3 Inactivation Is Not Required for Ischemic Preconditioning or Postconditioning in the Mouse Circ. Res., August 1, 2008; 103(3): 307 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ferdinandy, R. Schulz, and G. F. Baxter Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning Pharmacol. Rev., December 1, 2007; 59(4): 418 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vinten-Johansen, Z.-Q. Zhao, R. Jiang, A. J. Zatta, and G. P. Dobson Preconditioning and postconditioning: innate cardioprotection from ischemia-reperfusion injury J Appl Physiol, October 1, 2007; 103(4): 1441 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sato, R. Bolli, G. D. Rokosh, Q. Bi, S. Dai, G. Shirk, and X.-L. Tang The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2557 - H2564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Loukogeorgakis, R. Williams, A. T. Panagiotidou, S. K. Kolvekar, A. Donald, T. J. Cole, D. M. Yellon, J. E. Deanfield, and R. J. MacAllister Transient Limb Ischemia Induces Remote Preconditioning and Remote Postconditioning in Humans by a KATP Channel Dependent Mechanism Circulation, September 18, 2007; 116(12): 1386 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gomez, H. Thibault, A. Gharib, J.-M. Dumont, G. Vuagniaux, P. Scalfaro, G. Derumeaux, and M. Ovize Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1654 - H1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Deyhimy, N. W. Fleming, I. G. Brodkin, and H. Liu Anesthetic Preconditioning Combined with Postconditioning Offers No Additional Benefit Over Preconditioning or Postconditioning Alone Anesth. Analg., August 1, 2007; 105(2): 316 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-X. Jin, J.-J. Zhou, M. Xin, D.-R. Peng, X.-M. Wang, S.-H. Bi, X.-F. Wei, and D.-H. Yi Postconditioning the Human Heart with Adenosine in Heart Valve Replacement Surgery Ann. Thorac. Surg., June 1, 2007; 83(6): 2066 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. C. Manintveld, M. te Lintel Hekkert, E. J. van den Bos, G. M. Suurenbroek, D. H. Dekkers, P. D. Verdouw, J. M. Lamers, and D. J. Duncker Cardiac effects of postconditioning depend critically on the duration of index ischemia Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1551 - H1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Tang, H. Sato, S. Tiwari, B. Dawn, Q. Bi, Q. Li, G. Shirk, and R. Bolli Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2308 - H2317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ramzy, V. Rao, and R. D. Weisel Clinical applicability of preconditioning and postconditioning: The cardiothoracic surgeons's view Cardiovasc Res, May 1, 2006; 70(2): 174 - 180. [Full Text] [PDF]
|
|
|
|
|
|
Z.-Q. Zhao and J. Vinten-Johansen Postconditioning: Reduction of reperfusion-induced injury Cardiovasc Res, May 1, 2006; 70(2): 200 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Gateau-Roesch, L. Argaud, and M. Ovize Mitochondrial permeability transition pore and postconditioning Cardiovasc Res, May 1, 2006; 70(2): 264 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kloner and S. H. Rezkalla Preconditioning, postconditioning and their application to clinical cardiology Cardiovasc Res, May 1, 2006; 70(2): 297 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Zatta, H. Kin, G. Lee, N. Wang, R. Jiang, R. Lust, J. G. Reeves, J. Mykytenko, R. A. Guyton, Z.-Q. Zhao, et al. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling Cardiovasc Res, May 1, 2006; 70(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Schwartz and C. J. Lagranha Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1011 - H1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Loukogeorgakis, A. T. Panagiotidou, D. M. Yellon, J. E. Deanfield, and R. J. MacAllister Postconditioning Protects Against Endothelial Ischemia-Reperfusion Injury in the Human Forearm Circulation, February 21, 2006; 113(7): 1015 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Staat, G. Rioufol, C. Piot, Y. Cottin, T. T. Cung, I. L'Huillier, J.-F. Aupetit, E. Bonnefoy, G. Finet, X. Andre-Fouet, et al. Postconditioning the Human Heart Circulation, October 4, 2005; 112(14): 2143 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Darling, R. Jiang, M. Maynard, P. Whittaker, J. Vinten-Johansen, and K. Przyklenk Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2 Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1618 - H1626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Lucchinetti, R. da Silva, T. Pasch, M. C. Schaub, and M. Zaugg Anaesthetic preconditioning but not postconditioning prevents early activation of the deleterious cardiac remodelling programme: evidence of opposing genomic responses in cardioprotection by pre- and postconditioning Br. J. Anaesth., August 1, 2005; 95(2): 140 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tsang, D. J. Hausenloy, and D. M. Yellon Myocardial postconditioning: reperfusion injury revisited Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H2 - H7. [Full Text] [PDF]
|
|
|
|
|
|
H. Kin, A. J. Zatta, M. T. Lofye, B. S. Amerson, M. E. Halkos, F. Kerendi, Z.-Q. Zhao, R. A. Guyton, J. P. Headrick, and J. Vinten-Johansen Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine Cardiovasc Res, July 1, 2005; 67(1): 124 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Sun, N.-P. Wang, F. Kerendi, M. Halkos, H. Kin, R. A. Guyton, J. Vinten-Johansen, and Z.-Q. Zhao Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1900 - H1908. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
= ischemic preconditioning (IPC); 
= postcon; 
= IPC+postcon.
= IPC, 
= postcon; 
= IPC+postcon.
with solid line = ischemic preconditioning (IPC); 
with long dashed line = IPC+postcon. (AN = area of necrosis; AR = area at risk.)
= IPC; 
p less than 0.05 versus control.