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Roberto Bolli - One of the best experts on this subject based on the ideXlab platform.
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IV. Heterogeneity of Myocardial Stunning 611
2016Co-Authors: Roberto Bolli, Eduardo MarbánAbstract:A. Myocardial Stunning after a single, completely reversible ischemic episode 61
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Nitric oxide donors attenuate Myocardial Stunning in conscious rabbits.
The American journal of physiology, 1999Co-Authors: Ken Shinmura, Xian-liang Tang, Hitoshi Takano, Michael F. Hill, Roberto BolliAbstract:Although previous studies suggested that the protection of late preconditioning (PC) against Myocardial Stunning is mediated by nitric oxide (NO), direct evidence that exogenous administration of N...
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Molecular and Cellular Mechanisms of Myocardial Stunning
Physiological reviews, 1999Co-Authors: Roberto Bolli, Eduardo MarbánAbstract:The past two decades have witnessed an explosive growth of knowledge regarding postischemic Myocardial dysfunction or Myocardial “Stunning.” The purpose of this review is to summarize current infor...
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Gene Therapy With Extracellular Superoxide Dismutase Attenuates Myocardial Stunning in Conscious Rabbits
Circulation, 1998Co-Authors: Roberto Bolli, Xian-liang Tang, Yumin Qiu, Sidney S. Murphree, Brent A. FrenchAbstract:Background —Administration of Cu/Zn superoxide dismutase (SOD) without catalase fails to alleviate Myocardial Stunning, but extracellular SOD (Ec-SOD) may be more effective because it binds to heparan sulfate proteoglycans on the cellular glycocalyx. We therefore used in vivo gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy protects against Myocardial Stunning. Methods and Results —The cDNA for human Ec-SOD was cloned behind the cytomegalovirus (CMV) promoter and incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus (2×108 pfu/kg IV) produced high levels of Ec-SOD in the liver, which could be redistributed to the heart and other organs by injection of heparin. Conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days starting 3 days after intravenous injection of Ad5/CMV/Ec-SOD or Ad5/CMV/nls/LacZ (negative control). Both groups were given heparin (2000 U/kg IV) 2 hours before the first sequence of occlusions. The severity of Myocardial Stunning was measured as the total deficit of LV wall thickening after the last reperfusion. On day 1, the total deficit of wall thickening was markedly decreased in Ad5/CMV/Ec-SOD rabbits versus controls and similar to that seen on days 2 and 3 in controls. Conclusions —The results demonstrate that in vivo gene transfer of the cDNA encoding Ec-SOD provides the heart with substantial protection against Myocardial Stunning without the need for concomitant administration of catalase. The present observations provide the basis for controlling gene therapy at the posttranslational level and for simultaneously protecting multiple organs from oxidant stress.
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Basic and clinical aspects of Myocardial Stunning.
Progress in cardiovascular diseases, 1998Co-Authors: Roberto BolliAbstract:Although the pathogenesis of Myocardial Stunning has not been definitively established, the two major hypotheses are that it is caused by the generation of oxygen-derived free radicals on reperfusion and by a loss of sensitivity of contractile filaments to calcium. These hypotheses are not mutually exclusive and are likely to represent different facets of the same pathophysiological cascade. For example, a burst of free radical generation after reperfusion could alter contractile filaments in a manner that renders them less responsive to calcium. Increased free radical formation could also cause cellular calcium overload, which would damage the contractile apparatus of the myocytes. There is now considerable evidence that Myocardial Stunning occurs clinically in various situations in which the heart is exposed to transient ischemia, such as unstable angina, acute Myocardial infarction with early reperfusion, exercise-induced ischemia, cardiac surgery, and cardiac transplantation. Recognition of Myocardial Stunning is clinically important and may impact patient treatment. Although no ideal diagnostic technique for Myocardial Stunning has yet been developed, thallium-201 scintigraphy or dobutamine echocardiography are available and can be useful to identify viable myocardium with reversible wall motion abnormalities. An intriguing possibility is that so-called chronic hibernation may in fact be the result of repetitive episodes of Stunning, which have a cumulative effect and cause protracted postischemic left ventricular dysfunction. A better understanding of Myocardial Stunning will expand our knowledge of the pathophysiology of Myocardial ischemia and provide a rationale for developing new therapeutic strategies designed to prevent postischemic dysfunction.
Xian-liang Tang - One of the best experts on this subject based on the ideXlab platform.
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Nitric oxide donors attenuate Myocardial Stunning in conscious rabbits.
The American journal of physiology, 1999Co-Authors: Ken Shinmura, Xian-liang Tang, Hitoshi Takano, Michael F. Hill, Roberto BolliAbstract:Although previous studies suggested that the protection of late preconditioning (PC) against Myocardial Stunning is mediated by nitric oxide (NO), direct evidence that exogenous administration of N...
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Gene Therapy With Extracellular Superoxide Dismutase Attenuates Myocardial Stunning in Conscious Rabbits
Circulation, 1998Co-Authors: Roberto Bolli, Xian-liang Tang, Yumin Qiu, Sidney S. Murphree, Brent A. FrenchAbstract:Background —Administration of Cu/Zn superoxide dismutase (SOD) without catalase fails to alleviate Myocardial Stunning, but extracellular SOD (Ec-SOD) may be more effective because it binds to heparan sulfate proteoglycans on the cellular glycocalyx. We therefore used in vivo gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy protects against Myocardial Stunning. Methods and Results —The cDNA for human Ec-SOD was cloned behind the cytomegalovirus (CMV) promoter and incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus (2×108 pfu/kg IV) produced high levels of Ec-SOD in the liver, which could be redistributed to the heart and other organs by injection of heparin. Conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days starting 3 days after intravenous injection of Ad5/CMV/Ec-SOD or Ad5/CMV/nls/LacZ (negative control). Both groups were given heparin (2000 U/kg IV) 2 hours before the first sequence of occlusions. The severity of Myocardial Stunning was measured as the total deficit of LV wall thickening after the last reperfusion. On day 1, the total deficit of wall thickening was markedly decreased in Ad5/CMV/Ec-SOD rabbits versus controls and similar to that seen on days 2 and 3 in controls. Conclusions —The results demonstrate that in vivo gene transfer of the cDNA encoding Ec-SOD provides the heart with substantial protection against Myocardial Stunning without the need for concomitant administration of catalase. The present observations provide the basis for controlling gene therapy at the posttranslational level and for simultaneously protecting multiple organs from oxidant stress.
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Early and Late Preconditioning Against Myocardial Stunning: Pathogenesis and Pathophysiology
Advances in Organ Biology, 1998Co-Authors: John A. Auchampach, Xian-liang Tang, Yumin Qiu, Peipei Ping, Roberto BolliAbstract:Publisher Summary This chapter reviews the current knowledge regarding the influence of ischemic preconditioning on Myocardial Stunning. Similar to Myocardial infarction, it has become apparent that preconditioning against Myocardial Stunning includes an early phase (which becomes manifest within minutes) and a late phase (which becomes manifest approximately 12 hours after the preconditioning ischemia). The mechanisms of cardioprotection probably differ between the two phases. Ischemic preconditioning is the phenomenon, whereby, brief periods of ischemia protect the myocardium during subsequent ischemic insults. Early attempts to observe a preconditioning effect against Myocardial Stunning were made in models of Stunning induced by a single coronary artery occlusion. Brief ischemia induces a late phase of preconditioning against Stunning—that is long lasting (at least 72 hours) and powerful (resulting in approximately 50% reduction in total dysfunction). This late phase is triggered by the generation of reactive oxygen species (ROS) during the preconditioning ischemia-reperfusion cycles, and is mediated by a mechanism that involves a protein kinase C-mediated pathway. Based on the time-course of late preconditioning, it is likely that the synthesis of protective proteins contributes to the protection.
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The Late Phase of Preconditioning Against Myocardial Stunning
Developments in Cardiovascular Medicine, 1997Co-Authors: Roberto Bolli, Xian-liang Tang, Yumin Qiu, Seong-wook ParkAbstract:It has recently become apparent that there are two phases of ischemic preconditioning against Myocardial Stunning: an early phase, which begins within minutes, and a late phase, which begins after >6 h.1 These two phases have different pathophysiology and probably different mechanisms. Although the early phase is somewhat controversial, most of the discrepancies can be explained by differences in the duration of the ischemic insult, as detailed in ref. 1; that is, the available evidence indicates that an episode of ischemia protects against the Stunning induced by a second ischemic episode when the second episode lasts ≤, 5 min but not when it lasts ≥ 10 min. When early preconditioning does take place, the protection is limited to only a few ischemic episodes (probably less than five).1 In addition to this early phase of protection, brief ischemia induces a late phase of preconditioning against Stunning. This late phase lasts much longer and therefore is likely to be more important from a clinical standpoint.1 The purpose of this essay is to succinctly review the existing knowledge regarding the pathophysiology and pathogenesis of late preconditioning against Myocardial Stunning.
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Role of adenosine receptors in late preconditioning against Myocardial Stunning in conscious rabbits.
The American journal of physiology, 1997Co-Authors: C Maldonado, Xian-liang Tang, Y Qiu, M V Cohen, J Auchampach, R BolliAbstract:Conscious rabbits underwent six 4-min coronary occlusions interspersed with 4-min periods of reperfusion for 2 consecutive days (days 1 and 2 of stage I); 2 wk later, they underwent the same protocol (days 1 and 2 of stage II) except that they received either 8-(p-sulfophenyl)theophylline (SPT) on day 1 (group I, n = 5) or 2-chloro-N6-cyclopentyl-adenosine (CCPA) on the day before day 1 (group II, n = 6). In both groups I and II, on day 1 of stage I, systolic wall thickening (WTh) remained significantly depressed for several hours, indicating Myocardial Stunning; on day 2, however, the total deficit of WTh was approximately 50% less than on day 1 (P < 0.01), indicating the development of late preconditioning (PC) against Myocardial Stunning. Despite administration of SPT, in group I the deficit of WTh during stage II was 55% less on day 2 than on day 1 (P < 0.05). Similar results were obtained in three other rabbits treated with PD-115199 on day 1. In group II, pretreatment with CCPA during stage II failed to decrease the deficit of WTh on day 1. This study presents a new conscious rabbit model for studying Myocardial Stunning that is relatively inexpensive and technically less demanding than larger animal models. In this model, the development of late PC against Myocardial Stunning is not blocked by nonselective blockade of adenosine receptors with either SPT or PD-115199, nor is it induced by activation of adenosine A1 receptors with CCPA, indicating that adenosine receptors are not involved in the pathogenesis of this phenomenon.
Koji Sumikawa - One of the best experts on this subject based on the ideXlab platform.
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Milrinone Administered Before Ischemia or Just After Reperfusion, Attenuates Myocardial Stunning in Anesthetized Swine
Cardiovascular Drugs and Therapy, 2006Co-Authors: Tetsuji Makita, Hiroyuki Ureshino, Osamu Yoshitomi, Daiji Akiyama, Motoko Oshibuchi, Tetsuya Hara, Koji SumikawaAbstract:Purpose We assessed the dose or timing effect of milrinone administered against Myocardial Stunning in 37 anesthetized open-chest swine. Methods All swine were subjected to 12-min ischemia followed by reperfusion to produce Myocardial Stunning. Group A ( n = 12) received saline in place of milrinone both before and after ischemia. Group B ( n = 9) and C ( n = 9) received intravenous milrinone at a rate of 5 μg/kg/min for 10 min followed by 0.5 μg/kg/min for 10 min and 10 μg/kg/min for 10 min followed by 1 μg/kg/min for 10 min, respectively, until 30 min before coronary occlusion. Group D ( n = 7) received the same dose of milrinone as group B starting 1 min after reperfusion. Myocardial contractility was assessed by percentage segment shortening (%SS). Results Five swine in group A and two swine in groups B and C each had ventricular fibrillation or tachycardia after reperfusion, and were thus excluded from further analysis. The percentage changes of %SS from the baseline 90 min after reperfusion in groups B, C, and D were 78 ± 9%, 82 ± 13%, and 79 ± 7%, respectively, which were significantly higher than those in group A (43 ± 13%). Conclusion We conclude that milrinone administered before ischemia or just after reperfusion attenuates Myocardial Stunning.
Robert A. Kloner - One of the best experts on this subject based on the ideXlab platform.
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Acetaminophen and Myocardial Stunning after transient ischemia in rabbit hearts.
Journal of cardiovascular pharmacology and therapeutics, 2005Co-Authors: Sharon L. Hale, Robert A. KlonerAbstract:Background: Myocardial Stunning is a lingering contractile dysfunction that occurs after brief ischemia, even in the absence of necrosis. Recent studies have shown that acetaminophen may have some benefit on the return ofleft ventricular function after brief global ischemia in an in vitro model. This study was conducted to determine whether treatment with acetaminophen results in enhanced Myocardial tolerance to transient ischemia-reperfusion by improving left ventricular function and decreasing Stunning in an in vivo model. Methods: Anesthetized, open-chest rabbits were randomized to receive acetaminophen (37 mg/kg, n = 13) or saline (n = 11) 15 minutes before a series of transient coronary artery occlusions followed by reperfusion (three 10-minute periods of ischemia with 5 minutes reperfusion between). Hemodynamics and maximal and minimal values of developed pressure velocity (dP/dt) were measured at baseline, during ischemia, and throughout 2 hours of reperfusion. To assess Myocardial Stunning, echocardiography was used to determine regional systolic wall thickening fractions and global indices of function such as LV cavity dimensions and ejection fraction. Results: Hemodynamic variables, including left ventricular systolic pressure and positive and negative dP/dt, were similar in both groups throughout the study. Left ventricular end-diastolic pressure was significantly lower in the acetaminophen group during occlusion and early reperfusion. The repeated short periods of ischemia in the free wall of the heart caused Myocardial Stunning in both groups. During ischemia, contractile function in the free wall was severely reduced, and although it improved during reperfusion, dysfunction persisted in the postischemic free wall after 2 hours of reflow, recovering to less than 52% of preischemic values (P
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Therapy for Myocardial Stunning.
Basic research in cardiology, 1995Co-Authors: Y. Birnbaum, Robert A. KlonerAbstract:Myocardial Stunning, or postischemic dysfunction, is defined as delayed recovery of systolic and/or diastolic function of viable myocardium despite restoration of coronary flow after an ischemic insult (4). The severity and duration of Myocardial Stunning is highly dependent on the duration and severity of the previous ischemic insult (2). Thus, clinically significant Myocardial Stunning can be seen only after severe ischemic insult, especially after reperfusion therapy for acute Myocardial infarction and during the recovery period after coronary artery bypass surgery (2). However, in the former condition some of the cases of delayed recovery of function may be attributed to delayed improvement of perfusion by either delayed recanalization or recuitment of collaterals, and in the latter condition a delayed recovery from hibernation or new ischemic insult due to acute occlusion of the bypass grafts may be the reason for the continuous Myocardial dysfunction (2). Thus, in the clinical setting pure Myocardial Stunning should be diagnosed only after simultaneous demonstration of persistent mechanical dysfunction despite restoration of normal coronary perfusion. Myocardial Stunning has also been described following less severe ischemia induced by partial coronary stenosis following exercise in both animals and humans (2). This form of Myocardial Stunning following exercise treadmill testing may serve as a marker of severe multivessel coronary artery disease (2). It might be that in daily life uncontrolled effort induced ischemia may result in prolonged and clinically relevant Myocardial Stunning in patients with severe coronary artery disease.
Takenobu Kamada - One of the best experts on this subject based on the ideXlab platform.
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Staged reperfusion attenuates Myocardial Stunning in dogs. Role of transient acidosis during early reperfusion.
Circulation, 1991Co-Authors: M. Hori, M Kitakaze, Hiroshi Sato, Seiji Takashima, Katsuomi Iwakura, Michitoshi Inoue, Akira Kitabatake, Takenobu KamadaAbstract:BACKGROUND Acidosis during early reperfusion is reported to be beneficial for Myocardial Stunning. We tested in 31 dogs the hypothesis that staged reperfusion is beneficial to Myocardial Stunning. METHODS AND RESULTS Contractile dysfunction was observed 3 hours after the onset of reperfusion after 15 minutes of occlusion of the coronary artery. In the staged reperfusion, pH of the coronary venous blood was lower for 20 minutes and fractional shortening was significantly improved compared with the control reperfusion group. When we increased pH of the reperfused myocardium by an intracoronary infusion of sodium bicarbonate, beneficial effects of the staged reperfusion were abolished. Furthermore, an intracoronary infusion of hydrogen chloride, which mimicked the changes in pH in coronary venous blood of the staged reperfusion, attenuated Myocardial Stunning. CONCLUSIONS These results indicate that acidosis during staged reperfusion primarily attenuates Myocardial Stunning. This procedure is clinically applicable for attenuation of reperfusion injury.
