Effects of Doxycycline on Left Ventricular Remodeling in Patients With Acute Anterior Myocardial Infarction Uundergoing Primary Angioplasty: A Randomized Clinical Trial

Document Type: Original Article

Authors

1 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

2 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

3 Cardio-Oncology Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

Abstract

Background: Inflammatory mechanisms can cause left ventricular (LV) remodeling. These mechanisms include increased matrix metalloproteinases and the tissue inhibitors of metalloproteinases. Doxycycline is an antibiotic (macrolide) and a broad inhibitor of matrix metalloproteinases. This study evaluated the effects of early short-term doxycycline treatment on LV remodeling in patients suffering from ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).
Methods: In the present double-blinded randomized control trial, 68 post-MI patients who underwent primary PCI for STEMI were assigned to 2 groups, each consisting of 34 volunteers. Over a 7- day period, all these volunteers took 100 mg of Doxycycline twice a day. A placebo with the same order was prescribed for the control group. The cardiac function, the LV diameter, the left atrial diameter, and the LV torsion were measured at baseline and 40 days afterward.
Results: The mean age of the control and experimental groups was 53.7 years and 56.1 years, respectively. The averages of the left atrial volume (P = 0.03), the LV end-diastolic volume (P = 0.03), and the LV end-systolic volume (P = 0.01) in the experimental group rose less significantly than those in the control group. However, the LV torsion such as basal rotation (P = 0.03), apical rotation (P = 0.02), twist (P = 0.02), and torsion (P = 0.002) increased more substantially in the experimental group than in the control group.
Conclusions: Early administration of doxycycline attenuated LV remodeling measured by speckletracking echocardiography in our patients with anterior STEMI after primary PCI, vs. our control group subjects, who were on a placebo diet. 

Keywords


1. Braunwald's heart disease: a textbook of
cardiovascular medicine DL Mann, DP Zipes, P
Libby, RO Bonow- Elsevier Health Sciences:
2016:1063-1114.
2. Gajarsa JJ, Kloner RA. Left ventricular
remodeling in the post infarction heart: a review
of cellular, molecular mechanisms, and
therapeutic modalities. Heart Fail Rev. 2011;
16:13–21.
3. Hayashi M, Tsutamoto T, Wada A, et al.
Immediate administration of mineralocorticoid
receptor antagonist spironolactone prevents
post-infarct left ventricular remodeling
associated with suppression of a marker of
myocardial collagen synthesis in patients with
first anterior acute myocardial infarction.
Circulation. 2003; 107: 2559–2565.
4. Martin G. John Sutton, Norman Sharpe, Left
Ventricular Remodeling After Myocardial
Infarction Pathophysiology and Therapy,
Circulation. 2000; 101: 2981-2988.
5. French BA, Kramer CM. Mechanisms of post
infarct left ventricular remodeling. Drug Discov
Today Dis Mech. 2007;4: 185–196.
6. Jhund PS, McMurray JJV. Heart failure after
acute myocardial infarction: a lost battle in the
war on heart failure? Circulation 2008:118,
2019–2021.
7. Torina AG, Reichert K, Lima F, de Souza
Vilarinho KA, de Oliveira PP, do Carmo HR, de
Carvalho DD, Saad MJ, Sposito AC, Petrucci O,
Diacerein improves left ventricular remodeling
and cardiac function by reducing the
inflammatory response after myocardial
infarction, PLoS One. 2015 Mar 27; 10(3): e
0121842.
8. Seropian IM, Toldo S, van Tassell BW, Abbate
A. Anti-inflammatory strategies for ventricular
remodeling following St-segment elevation
acute myocardial infarction. J Am Coll Cardiol
2014;63:1593–1603.
9. Curci, J., D. Mao, D. Bohner, B. Allen, B.
Rubin, J. Reilly, G. Sicard, and R. Thompson.
Preoperative treatment with doxycycline reduces
aortic wall expression and activation of matrix
metalloproteinases in patients with abdominal
aortic aneurysms. J. Vasc. Surg. 2000, 31:325-
342.
10. Geerling G, Tauber J, Baudouin C, et al. The
International Workshop on Meibomian Gland
Dysfunction: report of the Subcommittee on
Management and Treatment of Meibomian
Gland Dysfunction. Invest Ophthalmol Vis
Sci 2011; 52: 2050–64.
11. Halade, G. V., Jin, Y. F. & Lindsey, M. L.
Matrix metalloproteinase (MMP)-9: a proximal

biomarker for cardiac remodeling and a distal
biomarker for inflammation. Pharmacol. Ther.
2013, 139, 32–40.
12. Fan G.C., Zhou X., Wang X., Song G., Qian J.,
Nicolaou P., Chen G., Ren X., Kranias E.G.
Heat shock protein 20 interacting with
phosphorylated akt reduces doxorubicintriggered oxidative stress and
cardiotoxicity. Circ. Res. 2008; 103: 1270–1279.
13. Sitia S, Tomasoni L, Turiel M. Speckle tracking
echocardiography: A new approach to
myocardial function. World J Cardiol. 2010;
2:1–5.
14. Abduch MC, Alencar AM, Mathias W, Jr,
Vieira ML. Cardiac mechanics evaluated by
speckle tracking echocardiography. Arq Bras
Cardiol. 2014; 4: 403–412.
15. Opdahl, T. Helle-Valle, H. Skulstad, and O.
Smiseth, “Strain, strain rate, torsion, and twist:
echocardiographic evaluation,” Curr Cardiol
Rep, 2015, vol. 17(3):15.
16. Cerisano G, Buonamici P, Valenti R, Sciagrà R,
Raspanti S, Santini A, Carrabba N, Dovellini
EV, Romito R, Pupi A, Colonna P, Antoniucci
D. Early short-term doxycycline therapy in
patients with acute myocardial infarction and
left ventricular dysfunction to prevent the
ominous progression to adverse remodelling: the
TIPTOP trial. Eur Heart J. 2014 Jan; 35(3):184–
191.
17. Kormi I, Alfakry H, Tervahartiala T, Pussinen
PJ, Sinisalo J, Sorsa T. The effect of prolonged
systemic doxycycline therapy on serum tissue
degrading proteinases in coronary bypass
patients: a randomized, double-masked,
placebo-controlled clinical trial. Inflamm Res.
2014 May; 63(5):329-34.
18. Dong M, et al. Doxycycline stabilizes
vulnerable plaque via inhibiting matrix
metalloproteinases and attenuating inflammation
in rabbits. PLoS One. 2012; 7(6).
19. Nucifora G., Ajmone Marsan N., Bertini
M.; Reduced left ventricular torsion early after
myocardial infarction is related to left
ventricular remodeling. Circ Cardiovasc
Imaging. 2010(3):433-442.
20. Jang JY, et al. Serial assessment of left
ventricular remodeling by measurement of left
ventricular torsion using speckle tracking
echocardiography in patients with acute
myocardial infarction. Cardiol. 2010 Oct
1;106(7):917-23.
21. Cerisano, G., Buonamici, P., Gori, et al, Matrix
metalloproteinases and their tissue inhibitor after
reperfused ST-elevation myocardial infarction
treated with doxycycline. Insights from the
TIPTOP trial (2015) International Journal of
Cardiology, 197, 147-153.
22. Yaghoubi, A., Safaie, N., Azarfarin, R.,
Alizadehasl, Azin., Golzari, S.E. valuation of
cardiovascular diseases and their risk factors in
hospitalized patients in East Azerbaijan
province, Northwest Iran: A review of 18323
cases . Journal of Tehran University Heart
Center, 2013, 8(2):101-105
23. Mirinejad, M., Azarfarin, R., Azin Alizadehasl. .
Cisatracurium in cardiac surgery - Continuous
infusion vs. bolus administration; Middle East
Journal of Anesthesiology; 2007, 19(3):563-
572.
24. Azarfarin, R., Sheikhzadeh, D., Mirinazhad, M.,
Bilehjani, E., Alizadehasl, Azin. Do nondiabetic
patients undergoing coronary artery bypass
grafting surgery require intraoperative
management of hyperglycemia? Acta
Anaesthesiol Taiwan. 2011 Jun;49(2):41-5. doi:
10.1016/j.aat.2011.05.009. Epub 2011 Jun 24.
25. Joyce E, Leong DP, Hoogslag GE, van Herck
PL, Debonnaire P, Abate E, et al. Left
ventricular twist during dobutamine stress
echocardiography after acute myocardial
infarction: association with reverse
remodeling. Int J Cardiovasc Imaging. 2014; 30:
313–322.