Myocardial Infarction

PLoS One. 2014 Jul 3;9(7):e101270. doi: 10.1371/journal.pone.0101270. eCollection 2014.

Amelioration of Cardiac Function and Activation of Anti-Inflammatory Vasoactive Peptides Expression in the Rat Myocardium by Low Level Laser Therapy.

Manchini MT1, Serra AJ1, Feliciano RD1, Santana ET1, Antônio EL2, de Tarso Camillo de Carvalho P1, Montemor J2, Crajoinas RO3, Girardi AC3, Tucci PJ2,Silva JA Jr1.

Author information

  • 1Universidade Nove de Julho, UNINOVE, São Paulo, SP, Brasil.
  • 2Universidade Federal de São Paulo, UNIFESP, São Paulo, SP, Brasil.
  • 3Heart Institute (InCor), Universidade de São Paulo, USP, São Paulo, SP, Brasil.


Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation.

Photomed Laser Surg.  2013 Sep;31(9):447-52. doi: 10.1089/pho.2013.3481.

Effect of low-level laser irradiation on oxygen free radicals and ventricular remodeling in the infarcted rat heart.

Yang J, Huang Z, Zhou Y, Sai S, Zhu F, Lv R, Fa X.


1 Department of Cardiovascular Surgery, the Second Affiliated Hospital of Zhengzhou University , Zhengzhou, People's Republic of China .


Abstract Objective: The purpose of this study was to assess the effects of low-level laser irradiation (LLLI) on the expression of oxygen free radicals (OFR) and ventricular remodeling (VR) in the model of rat myocardial infarction (RMMI).

Background data: LLLI reduces the infarct size and formation of scar tissue in the rat heart after myocardial infarction (MI). However, the exact mechanism has not been demonstrated so far.

Methods: RMMI was induced by ligating the left anterior descending coronary artery (LAD). After 3 weeks, LLLI (635?nm, 6?mW laser, 7.64?mW/cm(2), 125?sec, 0.96?J/cm(2)) was applied to the surface of heart directly. Four to six rats were euthanized at 1?h, 24?h, 48?h, 72?h, and 1 week after LLLI, and the infarcted myocardia were excised for the measurement of the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA). At the end of 4 weeks after MI, the hearts were harvested for histological analysis.

Results: Myocardial SOD activity with LLLI was lower compared with control (p<0.05), and myocardial MDA content with LLLI was higher compared with control (p<0.05), at all the time points. In all rats, the activity of SOD was down to the minimum and the content of MDA was up to the peak at 48?h after laser irradiation. The infarct size was reduced (35±10% vs. 18±9%, p<0.05), the left ventricular wall thickness was increased (0.31±0.03 vs. 0.84±0.02?mm, p<0.05) and the percentage of collagen fibers in the infarcted area was attenuated (64.34±2.20% vs. 30.97±2.60%) by LLLI.

Conclusions: LLLI could cause OFR accumulation, reduce infarct size, increase ventricular wall thickness, and attenuate the formation of collagen fibers, suggesting the beneficial effects of LLLI on improvement of VR after MI.

Photomed Laser Surg.  2011 Jun;29(6):391-8. Epub 2011 Feb 24.

Low-level laser irradiation alters cardiac cytokine expression following acute myocardial infarction: a potential mechanism for laser therapy.

Yang Z, Wu Y, Zhang H, Jin P, Wang W, Hou J, Wei Y, Hu S.


Department of Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.



Low-level laser irradiation (LLLI) has the potential of exerting cardioprotective effect following myocardial infarction (MI). The authors hypothesized that LLLI could influence the expression of cardiac cytokines and contribute to the reversal of ventricular remodeling.


LLLI regulates the expression of cytokines after tissue damage. However, little is known concerning the alteration of the cardiac cytokine expression profile after LLLI.


MI was created by coronary ligation. The surviving rats were divided randomly into laser and control groups. 33 rats were exposed to a diode laser (635 ?nm, 5? mW, CW, laser, beam spot size 0.8? cm(2), 6? mW/cm(2), 150? sec, 0.8? J, 1J/cm(2)) as laser group. Another 33 rats received only coronary ligation and served as control group. 28 rats received a thoracotomy without coronary ligation (sham group). One day after laser irradiation, 5 rats from each group were sacrificed and the heart tissues were analyzed by cytokine antibody arrays. Enzyme-linked immunosorbent assay (ELISA) was performed to confirm its reliability. Two weeks after MI, cardiac function and structure were evaluated by echocardiography and histological study.


Cytokine antibody array indicated 4 cytokines were significantly changed after laser therapy. ELISA confirmed that granulocyte-macrophage colony stimulating factor and fractalkine were the cytokines involved in the response to therapeutic laser irradiation. However, there was no difference in cytokine release between various groups at 2 weeks after MI. Although LLLI did not improve the damaged heart function, it did reduce the infarct area expansion.


The antibody-based protein array technology was applied for screening the cytokine expression profile following MI, with or without laser irradiation. The expression of multiple cytokines was regulated in the acute phase after LLLI. Our results revealed a potential novel mechanism for applying laser therapy to the treatment of heart disease.

J Cell Mol Med. 2009 Sep 1. [Epub ahead of print]

Low Level Laser Irradiation Precondition to Create Friendly Milieu of Infarcted Myocardium and Enhance Early Survival of Transplanted Bone Marrow Cells.


Zhang H, Hou JF, Shen Y, Wang W, Wei YJ, Hu S.

Department of Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

We hypothesized that low-level laser irradiation (LLLI) precondition prior to cell transplantation might remodel the hostile milieu of infarcted myocardium and subsequently enhance early survival and therapeutic potential of implanted bone-marrow mesenchymal stem cells (BMSCs). Therefore, in this study we wanted to address: (1) whether LLLI pretreatment change the local cardiac micro-environment after MI; and (2) whether the LLLI preconditions enhance early cell survival and thus improve therapeutic angiogenesis and heart function. Myocardial infarction was induced by left anterior descending artery ligation in female rats. A 635 nm, 5 mW diode laser was performed with energy density of 0.96 J/cm(2) for 150 seconds for the purpose of myocardial precondition. Three weeks later, qualified rats were randomly received with LLLI precondition (n=26) or without LLLI precondition (n=27) for LLLI precondition study. Rats received thoracotomy without coronary ligation were served as sham group (n=24). For the following cell survival study, rats were randomly received serum-free culture media injection (n=8), LLLI precondition and culture media injection (n=8), 2 millions male BMSCs transplantation without LLLI pretreatment (n=26) and 2 millions male BMSCs transplantation with LLLI precondition (n=25). Vascular endothelial growth factor (VEGF), glucose-regulated protein 78 (GRP78), superoxide dismutase (SOD) and malondialdehyde (MDA) in the infarcted myocardium were evaluated by Western blotting, real-time polymerase chain reaction (real-time PCR) and colorimetry, respectively, at 1 hour, 1 day and 1 week after laser irradiation. Cell survival was assayed with quantitative real-time PCR to identify Y chromosome gene and apoptosis was assayed with TUNEL staining. Capillary density, myogenic differentiation and left ventricular function were tested by immunohistochemistry and echocardiography, respectively, at 1 week. After LLLI precondition, increased VEGF and GRP78 expression, as well as the enhanced SOD activity and inhibited MDA production, was observed. Compared with BMSCs transplantation and culture media injection group, although there was no difference in the improved heart function and myogenic differentiation, LLLI precondition significantly enhanced early cell survival rate by 2-fold, decreased the apoptotic percentage of implanted BMSCs in infarcted myocardium and thus increased the number of newly formed capillaries. Taking together, LLLI precondition could be a novel non-invasive approach for intraoperative cell transplantation to enhance cell early survival and therapeutic potential.

Photomed Laser Surg. 2009 Apr;27(2):227-33.

Implantation of low-level laser irradiated mesenchymal stem cells into the infarcted rat heart is associated with reduction in infarct size and enhanced angiogenesis.

Tuby H, Maltz L, Oron U.

Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.

OBJECTIVE: The aim of the present study was to evaluate the possible beneficial effects of implantation of laser-irradiated mesenchymal stem cells (MSCs) into the infarcted rat heart. BACKGROUND DATA: It was demonstrated that low-level laser therapy (LLLT) upregulates cytoprotective factors in ischemic tissues. MATERIALS AND METHODS: MSCs were isolated from rat bone marrow and grown in culture. The cells were laser irradiated with a Ga-Al-As laser (810 nm wavelength), labeled with 5-bromo-2'deoxyuridine (BrdU), and then implanted into infarcted rat hearts. Non-irradiated cells were similarly labeled and acted as controls. Hearts were excised 3 wk later and cells were stained for BrdU and c-kit immunoreactivity. RESULTS: Infarcted hearts that were implanted with laser-treated cells showed a significant reduction of 53% in infarct size compared to hearts that were implanted with non-laser-treated cells. The hearts implanted with laser-treated cells prior to implantation demonstrated a 5- and 6.3-fold significant increase in cell density that positively immunoreacted to BrdU and c-kit, respectively, as compared to hearts implanted with non-laser-treated cells. A significantly 1.4- and 2-fold higher level of angiogenesis and vascular endothelial growth factor, respectively, were observed in infarcted hearts that were implanted with laser-treated cells compared to non-laser-treated implanted cells. CONCLUSION: The findings of the present study provide the first evidence that LLLT can significantly increase survival and/or proliferation of MSCs post-implantation into the ischemic/infarcted heart, followed by a marked reduction of scarring and enhanced angiogenesis. The mechanisms associated with this phenomenon remain to be elucidated in further studies.

Vopr Kurortol Fizioter Lech Fiz Kult. 2007 Jul-Aug;(4):12-5.

Therapeutic effects of laser therapy in patients with silent myocardial ischemia.

[Article in Russian]

Krysiuk OB, Ponomarenko GN, Obrezan AG.

The technique of registration of pain and vibration sensitivity providing early diagnosis of painless ischemic heart disease is described. Basing on evident pathogenetic direction of a therapeutic action of laser therapy to different links of pathogenesis of arterial hypertension and ischemic heart disease, therapeutic effects of laser therapy in patients with painless myocardial ischemia in combination with essential hypertension were studied.

Vopr Kurortol Fizioter Lech Fiz Kult. 2006 Mar-Apr;(2):6-8.

Effect of low-intensity laser radiation on lipid metabolism and hemostasis in patients with myocardial infarction.

[Article in Russian]

Kemalov RF.

Progression of coronary atherosclerosis often causes complications resulting in myocardial infarction, early disability and death of patients with coronary heart disease. Low efficacy of medicines against coronary atherosclerosis progression after myocardial infarction gave rise to investigations of nonpharmacological methods, laser radiation, in particular. Our study shows a noticeable positive effect of low-intensity laser radiation on blood lipid spectrum and hemostasis. This makes laser therapy promising in combined rehabilitation of postmyocardial infarction patients.

J Clin Laser Med Surg. 2003 Aug;21(4):231-5.

A preliminary investigation into light-modulated replication of nanobacteria and heart disease.

Sommer AP, Oron U, Pretorius AM, McKay DS, Ciftcioglu N, Mester AR, Kajander EO, Whelan HT.

Central Institute of Biomedical Engineering, University of Ulm, 89081 Ulm, Germany.

OBJECTIVE: The purpose of this preliminary study is to evaluate the effect of various wavelengths of light on nanobacteria (NB). BACKGROUND DATA: NB and mitochondria use light for biological processes. NB have been described as multifunctional primordial nanovesicles with the potential to utilize solar energy for replication. NB produce slime, a process common to living bacteria. Slime release is an evolutionary important stress-dependent phenomenon increasing the survival chance of individual bacteria in a colony. In the cardiovascular system, stress-induced bacterial colony formation may lead to a deposition of plaque. METHODS: Cultured NB were irradiated with NASA-LEDs at different wavelengths of light: 670, 728 and 880 nm. Light intensities were about 500k Wm(-2), and energy density was 1 x 10(4) J m(-2). RESULTS: Monochromatic light clearly affected replication of NB. Maximum replication was achieved at 670 nm. CONCLUSIONS: The results indicate that suitable wavelengths of light could be instrumental in elevating the vitality level of NB, preventing the production of NB-mediated slime, and simultaneously increasing the vitality level of mitochondria. The finding could stimulate the design of cooperative therapy concepts that could reduce death caused by myocardial infarcts.

Ross Fiziol Zh Im I M Sechenova. 2003 Dec;89(12):1496-502.  


Effect of the He-Ne irradiation on resistance of the isolated heart to the ischemic and reperfusion injury.

[Article in Russian]

Kolpakova ME, Vlasov TD, Petrishchev NN, Vislobokov AI.

St.-Petersburg Acad. I. P. Pavlov State Medical University, 197089, Russia, St.-Petersburg, L. Tolstoy st., 6/8.

The aim of this work was to investigate the myocardial protection against ischemia/reperfusion using low level laser irradiation (LLLI). It has been shown that pulse pressure was higher in the period of post-ischemic reperfusion as compared with the control group. It provided a better restoration of myocardial contractility as well as increasing of coronary flow in the reperfusion period. The amount of ventricular rhythm disorder episodes decreased. These effects of laser application were registered in conditions of coronary flow reduction less than 50%. One of the suggested mechanisms of laser effect is an ATP-sensitive channel activation.

Vopr Kurortol Fizioter Lech Fiz Kult. 1995 Nov-Dec;(6):14-6.  

The use of laser therapy and physical exercises in myocardial infarct patients at the hospital stage.

[Article in Russian]

Kuimov AD, Beliavskaia NV, Barbarich VB, Potanina LM, Metelkina NV.

89 postmyocardial infarction patients were exposed to low-intensity laser radiation combined with muscular training. The treatment improved clinical condition of the patients, myocardial contractility, exercise tolerance.


 K.G.Khutchumova, V.A.Lyusov

Moscow State University, Russia

The article deals with hemorheological and clinical aspects of therapeutic effects of low-laser therapy in patients with acute myocardial infarction. 20 patients were investigated by laser therapy together with traditional treatment (1), and 20 patients – only by traditional treatment (2). The treatment was carried out by means of infrared laser 'Vector' in persistent regime. The region of projection of carotid sinuses and heart, expositions 3 min. The levels of fibrinogen, platelet aggregation, blood viscosity, anti-thrombin III, fibrinogen fragments were investigated before applying laser light and on the 5th and the 10th day after the treatment. Laser therapy lessened cardiac pain and arrhythmias. The improvement of the clinical state of the patients was accompanied with improvement of hemorheological properties. The impact of laser therapy on fibronectin level which rose from 245±19,4 to 310±21,2 on the 10th day and on antithrombin III level wich changed from 56,3±3,5 to 75,8±6,2 was statistically significant. The amount of fibrinogen fragments decreased on 16% (p<0,05). Normal data of blood viscosity, fibrinogen, platelet aggregation was obtained on the 10th day. Each of these factors reflects its positive effect on the disseminated intravascular coagulation. The results showed, that laser therapy improved hemorheological properties of blood, which can be compared with the improving of clinical state of the patients with acute myocardial infarction.

Longterm experience of endovascular laser irradiation in myocardial infarction.

Maximov N I et al.

HeNe intravenous laser irradiation is reported to decrease the reinfarction rate in patients with a story of myocardial infarction. A 2 mW HeNe laser was used, 40 min. duration each session

Int J Cardiol. 2001; 80:109-116

Impace of low level laser irradiation on infarct size in the rat following myocardial infarction.

 Ad N, Oron U.

The effect of LLLI on the development of acute myocardial infarction (MI) was investigated following chronic ligation of the left anterior descending (LAD) coronary artery in laboratory rats. The hearts of 22 rats were laser irradiated (LI) using a diode laser (804 nm, 38 mW power output) through the intercostal muscles in the chest following MI and on day 3 post MI. In the control non laser irradiated (NLI) group (19 rats) MI was induced experimentally and laser irradiation was not applied. All rats were sacrificed 21 days post MI. Size, thickness and relative circumferential length of the infarct, as well as other parameters, were determined from histological sections stained with Masson's trichrome and hearts stained with triphenyl tetrazolium chloride (TTC) using histomorphometric methods. The infarct size (expressed as percent of total left ventricle area) of the LI rats was 10.1+/-5.8, which was significantly lower (65%; P<0.01) than the infarct size of NLI rats which was 28.7+/-9.6. Correlatively, the ratio of circumferential length of the infarcted area was significantly lower (2-fold; P<0.01) in the LI rats as compared to the NLI rats. LLLI of the infarcted area in the myocardium of experimentally induced MI rats, at the correct energy, duration and timing, markedly reduces the loss of myocardial tissue. This phenomenon may have an important beneficial effect on patients after acute MI or ischemic heart disease.

Sov Med. 1990;(3):9-12.

[Effectiveness of blood irradiation using a helium-neon laser in the acute period of myocardial infarction]

[Article in Russian]

Kipshidze NN, Chapidze GE, Bokhua MR, Marsagishvili LA.

The efficacy of endovascular irradiation of the blood with He-Ne laser by the method developed by the authors was examined in 295 patients with primary acute transmural myocardial infarction. Laser therapy was conducive to effective alleviation of the pain syndrome and prevention of anginous status. Twenty-four-hour Holter monitoring, carried out before and after irradiation, has detected high antiarrhythmic activity in respect of complex ventricular arrhythmias and a preventive possibility of fibrillations. Studies of precardial ECG parameters and measurements of the blood enzymic activities (creatine phosphokinase and MB creatine phosphokinase) have shown that irradiation carried out within the first hours of myocardial infarction is conducive to limitation of the infarction area, i.e. that endovascular laser therapy is a highly effective and pathogenetic method for acute myocardial infarction treatment.