Myocardial Protective Effect

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.

J Mol Cell Cardiol. 2009 Jan;46(1):4-14. Epub 2008 Sep 30.

Near infrared light protects cardiomyocytes from hypoxia and reoxygenation injury by a nitric oxide dependent mechanism.

Zhang R, Mio Y, Pratt PF, Lohr N, Warltier DC, Whelan HT, Zhu D, Jacobs ER, Medhora M, Bienengraeber M.

Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53326, USA.

Photobiomodulation with near infrared light (NIR) provides cellular protection in various disease models. Previously, infrared light emitted by a low-energy laser has been shown to significantly improve recovery from ischemic injury of the canine heart. The goal of this investigation was to test the hypothesis that NIR (670 nm) from light emitting diodes produces cellular protection against hypoxia and reoxygenation-induced cardiomyocyte injury. Additionally, nitric oxide (NO) was investigated as a potential cellular mediator of NIR. Our results demonstrate that exposure to NIR at the time of reoxygenation protects neonatal rat cardiomyocytes and HL-1 cells from injury, as assessed by lactate dehydrogenase release and MTT assay. Similarly, indices of apoptosis, including caspase 3 activity, annexin binding and the release of cytochrome c from mitochondria into the cytosol, were decreased after NIR treatment. NIR increased NO in cardiomyocytes, and the protective effect of NIR was completely reversed by the NO scavengers carboxy-PTIO and oxyhemoglobin, but only partially blocked by the NO synthase (NOS) inhibitor L-NMMA. Mitochondrial metabolism, measured by ATP synthase activity, was increased by NIR, and NO-induced inhibition of oxygen consumption with substrates for complex I or complex IV was reversed by exposure to NIR. Taken together these data provide evidence for protection against hypoxia and reoxygenation injury in cardiomyocytes by NIR in a manner that is dependent upon NO derived from NOS and non-NOS sources.

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.

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


Effect of the He-Ne laser 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.

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.