Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine
Tóm tắt
It seems controversial whether or not neutrophil elastase inhibitors are effective in attenuating myocardial ischemia/reperfusion injury. We thus investigated possible protective effects of sivelestat, a neutrophil elastase inhibitor, against myocardial stunning i.e., prolonged myocardial dysfunction following a brief episode of ischemia. Swine were divided into control group (group C), low-dose sivelestat group (group L), and high-dose sivelestat group (group H) (n = 7 for each group). All the swine were subjected to myocardial ischemia through ligation of the left anterior descending (LAD) coronary artery for 12-min, followed by 90-min reperfusion. Sivelestat was infused intracoronally at concentrations of 6 and 60 mg/ml throughout the reperfusion period in groups L and H, respectively, while saline was infused in the group C. Heart rate (HR), left ventricular developed pressure (LVdP), maximum rate of LVdP (LVdP/dt
max), LV end-diastolic pressure (LVEDP), percentage of segment shortening (%SS, an index of regional myocardial contractility), and coronary venous interleukin-6 concentration in the LAD perfusion area were measured before ischemic induction and during reperfusion. The ischemia/reperfusion insult did not cause any significant changes in HR, LVdP, LVdP/dt
max, and LVEDP in all groups. However, it significantly reduced %SS in the LAD perfusion area and increased the interleukin-6 concentration in group C. Those changes in %SS and the interleukin-6 concentration were both greatly attenuated, but not prevented, in groups L and H. Sivelestat presumably attenuates myocardial contractile dysfunction due to myocardial stunning by inhibiting neutrophil-derived elastase, thereby suppressing the production of interleukin-6 in activated neutrophils.
Tài liệu tham khảo
Yu X, Kennedy RH, Liu SJ. JAK2/STAT3, not ERK1/2, mediates interleukin-6-induced activation of inducible nitric-oxide synthase and decrease in contractility of adult ventricular myocytes. J Biol Chem. 2003;278:16304–9.
Nicolini FA, Mehta JL, Nichols WW, Donnelly WH, Luostarinen R, Saldeen TGP. Leukocyte elastase inhibition and t-PA induced coronary artery thrombolysis in dogs: beneficial effects on myocardial histology. Am Heart J. 1991;122:1245–51.
Dinerman JL, Mehta JL, Saldeen TGP, Emerson S, Wallin R, Davda R, Davidson A. Increased neutrophil elastase release in unstable angina pectoris and acute myocardial infarction. J Am Coll Cardiol. 1990;15:1559–63.
Bidouard JP, Duval N, Kapui Z, Herbert JM, O’Connor SE, Janiak P. SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia–reperfusion injury. Eur J Pharmacol. 2003;461:49–52.
Braunwald E, Kloner RA. The stunned myocardium. Prolonged post-ischemic ventricular dysfunction. Circulation. 1982;66:1146–9.
Nixon JV, Brown CN, Smitherman TC. Identification of transient and persistent segmental wall motion abnormalities in patients with unstable angina by two-dimensional echocardiography. Circulation. 1982;65:1497–503.
Kloner RA, Allen J, Cox TA, Zheng Y, Ruiz CE. Stunned left ventricular myocardium following exercise treadmill testing in coronary artery disease. Am J Cardiol. 1991;68:329–34.
Wijns W, Serruys PW, Slager CJ, Grimm J, Kragenbuehl HP, Hugenholtz PG, Hess OM. Effect of coronary occlusion during percutaneous transluminal angioplasty in humans on left ventricular chamber stiffness and regional diastolic pressure radius relations. J Am Coll Cardiol. 1986;7:455–61.
Breisblatt WM, Stein KL, Wolfe CJ, Follansbee WP, Capozzi J, Armitage JM, Hardesty RL. Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery. J Am Coll Cardiol. 1990;15:1261–9.
Kloner RA, Bolli R, Marban E, Reinlib L, Braunwald E. Medical and cellular implication of stunning, hibernation, and preconditioning; an NHLBI work shop. Circulation. 1998;97:1848–67.
Lo Go, Murry CE, Richard VJ, Jennings RB, Weischedel GR, Reimer KA. Myocardial neutrophil accumulation during reperfusion after reversible or irreversible ischaemia injury. Am J Physiol. 1988;255:H1188–98.
Harlan JM, Killen PD, Harker LA, Striker GE. Neutrophil-mediated endothelial injury in vitro. Mechanisms of cell detachment. J Clin Invest. 1981;68:1394–403.
Juneau CF, Ito BR, Balzo U, Engler RL. Severe neutrophil depletion by leucocyte filters or cytotoxic drug does not improve recovery of contractile function in stunned porcine myocardium. Cardiovasc Res. 1993;27:720–7.
Tiefenbacher CP, Ebert M, Niroomand F, Batkai S, Tillmanns H, Zimmermann R, Kubler W. Inhibition of elastase improves myocardial function after repetitive ischaemia and myocardial infarction in the rat heart. Pflugers Arch. 1997;433:563–70.
Kawabata K, Suzuki M, Sugitani M, Imaki K, Toda M, Miyamoto T. ONO-5046, a novel inhibitor of human neutrophil elastase. Biochem Biophys Res Commun. 1991;177:814–20.
Soejima Y, Yamada K, Nishizaki T, Yosizumi T, Uchiyama H, Sugimachi K. Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation. J Surg Res. 1999;86:150–4.
Ohwada S, Tomizawa N, Takahasi T, Ichikawa H, Kamosita N, Kobayasi J, Ogawa T, Izumi M, Nakamura S, Iino Y, Morisita Y. Effects of a specific neutrophil elastase inhibitor (ONO-5046 Na) and neutrophil elastase depletion using a G-1 column on lung reperfusion. Transplant Proc. 1996;28:1826–7.
Ueno M, Moriyama Y, Toda R, Yotsumoto G, Yamamoto H, Fukumoto Y, Sakasegawa K, Nakamura K, Sakata R. Effect of neutrophil elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using the left-sided Heterotopic canine heart transportation model. J Heart Lung Transplant. 2001;20:889–96.
Miura M, Ito S, Baba E, Endo S, Katsuya H. A clinical pharmacological study of a neutrophil elastase inhibitor; ONO-5046 Na in SIRS patients. J Clin Ther Med. 1998;14:379.
Hara T, Tomiyasu S, Cho S, Fukusaki M, Sumikawa K. Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels. Anesth Analg. 2001;92:1139–45.
Use T, Makita T, Ureshino H, Cho S, Yoshitomi O, Akiyama D, Oshibuchi M, Hara T, Sumikawa K. Milrinone administered before ischemia or just after reperfusion, attenuates myocardial stunning in anesthetized swine. Cardiovasc Drugs Ther. 2006;20:327–34.
Kersten JR, Lowe D, Hettrick DA, Pagel PS, Gross GJ, Warltier DC. Glyburide, a KATP channel antagonist, attenuates the cardioprotective effects of isoflurane in stunned myocardium. Anesth Analg. 1996;83:27–33.
Jordan JE, Zhao ZQ, Vinten-Johansen J. The role of neutrophils in myocardial ischemia–reperfusion injury. Cardiovasc Res. 1999;43:860–78.
Aoshiba K, Yasuda K, Yasui S, Tamaoki J, Nagai A. Serine proteases increase oxidative stress in lung cells. Am J Physiol Lung Cell Mol Physiol. 2001;281:L556–64.
Ohta K, Nakajima T, Cheah AY, Zaidi SH, Kaviani N, Dawood F, You XM, Liu P, Husain M, Rabinovitch M. Elafin overexpressing mice have improved cardiac function after myocardial infarction. Am J Physiol Heart Circ Physiol. 2004;287:H286–92.
Nian M, Lee P, Khaper N, Liu P. Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 2004;94:1543–53.
Kukielka GL, Smith CW, Manning AM, Youker KA, Michael LH, Entman ML. Induction of interleukin-6 synthesis in the myocardium. Potential role in postreperfusion inflammatory injury. Circulation. 1995;92:1866–75.
Haga Y, Ogawa M. Neutrophil elastase inhibitor (ONO-5046.Na) decreases production of proinflammatory cytokines by lipopolysaccharide-stimulated human monocytes. Res Commun Mol Pathol Pharmacol. 1997;98:243–8.
Toyoda Y, Di Gregorio V, Parker RA, Levitsky S, McCully JD. Anti-stunning and anti-infarct effects of adenosine-enhanced ischemic preconditioning. Circulation. 2000;102:III326–31.
Kusuoka H. Theoretical analysis of the relationship between regional and global measures of myocardial contractility. Jpn Circ J. 1993;57:904–11.
Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Garcia C, Schaub MC. Differential effects of anesthetics on mitochondrial KATP channel activity and cardiomyocyte protection. Anesthesiology. 2002;97:15–23.
Kato R, Foex P. Fentanyl reduces infarction but not stunning via delta-opioid receptors and protein kinase C in rats. Br J Anaesth. 2000;84:608–14.