Effects of Electronic Cigarette Vaping on Cardiac and Vascular Function, and Post-myocardial Infarction Remodeling in Rats.

The effect of electronic cigarette (E-cig) vaping on cardiac and vascular function during the healing phase of myocardial infarction (MI), and post-MI remodeling was investigated. Sprague Dawley rats were subjected to left coronary artery ligation to induce MI. One week later, rats were randomized to receive either 12 weeks of exposure to purified air (n = 37) or E-cig vapor (15 mg/ml of nicotine) (n = 32). At 12 weeks, cardiac and vascular function, and post-MI remodeling were assessed. Baseline blood flow in the femoral artery did not differ between groups, but peak reperfusion blood flow was blunted in the E-cig group (1.59 ± 0.15 ml/min) vs. the air group (2.11 ± 0.18 ml/min; p = 0.034). Femoral artery diameter after reperfusion was narrower in the E-cig group (0.54 ± 0.02 mm) compared to the air group (0.60 ± 0.02 mm; p = 0.023). Postmortem left ventricular (LV) volumes were similar in the E-cig (0.69 ± 0.04 ml) and air groups (0.73 ± 0.04 ml; p = NS); and myocardial infarct expansion index did not differ between groups (1.4 ± 0.1 in E-cig group versus 1.3 ± 0.1 in air group; p = NS). LV fractional shortening by echo did not differ between groups at 12 weeks (E-cig at 29 ± 2% and air at 27 ± 1%; p = NS). Exposure to E-cig during the healing phase of MI was associated with altered vascular function with reduced femoral artery blood flow and diameter at reperfusion, but not with worsened LV dilation or worsened cardiac function.

Flavoring Agents in E-cigarette Liquids: A Comprehensive Analysis of Multiple Health Risks.

The availability of a wide range of flavored e-cigarettes is one of the primary reasons for vaping initiation and persistent use among adolescents and young people. This plethora of flavors available on the market are crafted using different flavoring agents such as cinnamaldehyde, vanillin, benzaldehyde, ethyl maltol, menthol, and dimethylpyrazine. Recent studies have brought to light the potential risks associated with e-cigarette flavoring agents and their effects on various organ systems, both with and without nicotine. Research has demonstrated that flavoring agents can induce inflammation, endothelial dysfunction, epithelial barrier disruption, oxidative stress, DNA damage, electrophysiological alterations, immunomodulatory effects, and behavioral changes, even independently of nicotine. Notably, these negative outcomes adversely affect cardiovascular system by reducing cell viability, decreasing endothelial nitric oxide synthase, nitric oxide bioavailability, soluble guanylyl cyclase activity and cyclic guanosine monophosphate accumulation, impairing endothelial proliferation and tube formation, and altering vasoreactivity resulting in vascular dysfunction. In the heart, these agents decrease parasympathetic activity, induce depolarization of resting membrane potential, loss of rhythmicity, increase isovolumic relaxation time, and change in ventricular repolarization and ventricular tachyarrhythmias. It is found that the specific response elicited by flavoring agents in different organ systems varies depending on the flavor used, the concentration of the flavoring agent, and the duration of exposure. However, the literature on the effects of flavoring agents is currently limited, emphasizing the need for more preclinical and randomized clinical trials to gain a deeper understanding and provide further evidence of the harmful effects of flavored e-cigarette use. In summary, recent research suggests that flavoring agents themselves can have detrimental effects on the body. To fully comprehend these effects, additional preclinical and clinical studies are needed to explore the risks associated with flavored e-cigarette usage.

Effects of Electronic Cigarette Exposure on Myocardial Infarction and No-Reflow, and Cardiac Function in a Rat Model.

PURPOSE: We investigated the effects of exposure to electronic cigarettes (E-cig) vapor on the sizes of the no-reflow and myocardial infarction regions, and cardiovascular function compared to exposure to purified air and standard cigarette smoke. METHODS AND RESULTS: Sprague Dawley rats (both male and female, 6 weeks old) were successfully exposed to filtered air (n = 32), E-cig with nicotine (E-cig Nic+, n = 26), E-cig without nicotine (E-cig Nic-, n = 26), or standard cigarette smoke (1R6F reference, n = 31). All rats were exposed to inhalation exposure for 8 weeks, prior to being subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Exposure to E-cig vapor with or without nicotine or exposure to standard cigarettes did not increase myocardial infarct size or worsen the no-reflow phenomenon. Exposure to E-cig Nic+ reduced the body weight gain, and increased the LV weight normalized to body weight and LV wall thickness and enhanced the collagen deposition within the LV wall. E-cig exposure led to cardiovascular dysfunction, such as reductions in cardiac output, LV positive and negative dp/dt, suggesting a reduction in contractility and relaxation, and increased systemic arterial resistance after coronary artery occlusion and reperfusion in rats compared to air or cigarette exposure. CONCLUSIONS: E-cig exposure did not increase myocardial infarct size or worsen the no-reflow phenomenon, but induced deleterious changes in LV structure leading to cardiovascular dysfunction and increased systemic arterial resistance after coronary artery occlusion followed by reperfusion.

One Acute Exposure to E-Cigarette Smoke Using Various Heating Elements and Power Levels Induces Pulmonary Inflammation.

Background: Electronic cigarettes (eC) may not be entirely benign. There is a lack of data on the effect of a single acute exposure of eC vapor using various heating sources and power settings upon lung injury. The purpose of this study was to determine if an acute exposure with eC vapor heated with different heating elements and power levels induced inflammatory changes in the lungs and heart. Methods: Rats were exposed to pure air or received a single, 4-h exposure to eC vapor. The devices used either a stainless steel (SS) or nichrome (NC) heating element randomized to a low or high atomization power (45 versus 70 W). Rats were euthanized within 48 h of exposure. Results: The eC groups showed accumulation of inflammatory cells in bronchial lumen, near the pleura, and within the alveolar spaces. The numbers of inflammatory cells per field in the lung parenchyma were significantly greater in the rats exposed to eC groups vs. the air group. There were significantly higher inflammatory gene expression changes in the lungs of animals assigned to 70 W power. We observed that eC vapor generated using burnt coils were toxic and could cause acute respiratory distress and myocarditis. Conclusion: In conclusion, one 4-h exposure to eC vapor, in the absence of vitamin E oil or nicotine, significantly increased lung inflammation. Effects were seen after exposures to vapor generated using SS and NC heating elements at either high or low power. Vapor from devices with burnt coils can negatively affect the heart and lung.

Impact of Regional Green Development Strategy on Environmental Total Factor Productivity: Evidence from the Yangtze River Economic Belt, China.

Chinese government policy officially identify the Yangtze River Economic Belt (YREB) as one of regional green development strategies firstly in 2014. This strategy can be regarded as quasi-natural experiment, this paper aims to test its impact on regional environmental total factor productivity (TFP). First, slack-based measure model is used to calculate the environmental TFP from 2005 to 2017 at provincial level. Second, based on Chinese official statistics, differences-in-differences (DID) method is applied to construct an evaluation model of policy effect, combining with the kernel matching in propensity score matching (PSM) method. The results show that environmental TFP of YREB has significant spatial differences, with characteristic of high-east and low-west, its average level is 11.69 percentage points higher than the national average. YREB strategy promotes regional economic growth, but it does no effect on the regional environmental TFP yet. Modelling suggests that YREB strategy may play a role in the short term. From the significance of the control variables, infrastructure construction level is positively correlated with environmental TFP, while per capita GDP, financial development and energy consumption intensity have negative effect on environmental TFP. Based on this, policymakers should focus on green development, promoting industrial transformation, and enhancing environmental protection.

Acute administration of nicotine induces transient elevation of blood pressure and increases myocardial infarct size in rats.

AIMS: We investigated the acute effects of nicotine on myocardial infarct size, no reflow, hemodynamics and cardiac function in an acute myocardial ischemia and reperfusion infarction rat model. MAIN METHODS: Female Sprague-Dawley rats (n = 23/group) received an intravenous loading dose of nicotine at 2.0 µg/kg/min or saline control for 30 min before starting coronary artery occlusion, then followed by a maintenance dose 0.35 µg/kg/min of nicotine to the end of 30 min occlusion and 3 h reperfusion. KEY FINDINGS: At baseline, there was no difference in systolic blood pressure (BP in mmHg) (nicotine, 69.0 ± 2.7; control, 69.3 ± 4.4; p = NS) or diastolic BP (nicotine, 45.7 ± 3.2; control, 48.2 ± 4.2; p = NS) between groups. Nicotine administration initially increased systolic BP (nicotine, 97.0 ± 8.6; control, 69.2 ± 3.3, p < 0.0001) and diastolic BP (nicotine, 65.6 ± 6.4; control, 47.4 ± 3.1, p = 0.0003) at 10 min after starting injection of the loading dose; BP dropped to control levels in both groups at 30 min. During occlusion and reperfusion, the BP and heart rate were not altered by nicotine. Nicotine significantly increased myocardial infarct size as a percentage of the ischemic risk zone compared to the controls (nicotine, 54.9 ± 1.9; control, 48.6 ± 2.7, p < 0.05), but nicotine did not affect the no-reflow size and heart function. SIGNIFICANCE: While acute nicotine only transiently elevated blood pressure, it did not affect hemodynamic parameters during coronary artery occlusion. Nicotine increased myocardial infarct size, suggesting that the increase in infarct size was not simply due to an increase in oxygen demand due to altered afterload, heart rate, or contractility, but may have been due to a more direct effect on the myocardium.

E-cigarette or Vaping Product Use-Associated Lung Injury Produced in an Animal Model From Electronic Cigarette Vapor Exposure Without Tetrahydrocannabinol or Vitamin E Oil.

E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested that E-cigarette or vaping product use-associated lung injury was due to tetrahydrocannabinol or vitamin E acetate oil mixed with the electronic cigarette liquid. In experimental rodent studies initially designed to study the effect of electronic cigarette use on the cardiovascular system, we observed an E-cigarette or vaping product use-associated lung injury-like condition that occurred acutely after use of a nichrome heating element at high power, without the use of tetrahydrocannabinol, vitamin E, or nicotine. Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs. Electronic cigarette users should be cautioned about the potential danger of operating electronic cigarette units at high settings; the possibility that certain heating elements may be deleterious; and that E-cigarette or vaping product use-associated lung injury may not be dependent upon tetrahydrocannabinol, vitamin E, or nicotine.

Environmental Kuznets Curve: Empirical Relationship between Energy Consumption and Economic Growth in Upper-Middle-Income Regions of China.

This paper examines the environmental Kuznets curve (EKC) relationship between energy consumption and economic growth in upper-middle-income regions of China with the panel data of 21 provinces from 2000 to 2017. The influence mechanism of socio-economic factors on the EKC of these regions is also detected. The results show that the energy consumption EKC fitting map in these regions conforms to the classical environmental Kuznets curve, which is an inverted "N" type, and the inflection point is ahead and more accurate after adding spatial effects. The direct effect of energy consumption has delayed the inflection point, indicating that the level of industrialization, urbanization, and population density have a significant impact on EKC. At the same time, it is found that the level of industrialization and population density have a positive relationship with energy consumption, while the level of urbanization has a negative correlation with energy consumption. The spatial spillover effect of the indirect effects of total energy consumption, coal consumption, and crude oil consumption shows that the level of industrialization has a significant and negative link with EKC. The increase in the level of industrialization will affect the total energy consumption of neighboring areas and the consumption of coal and crude oil.

Therapeutic Hypothermia Improves Long-Term Survival and Blunts Inflammation in Rats During Resuscitation of Hemorrhagic Shock.

We tested the hypothesis that therapeutic hypothermia (TH) improves survival and blunts inflammation in rats undergoing experimental hemorrhagic shock. Rats were randomized to TH (n = 16) or normothermia (n = 15). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure (MBP) of 30 mmHg for 30 minutes followed by reinfusion of shed blood for the next 30 minutes. TH (target 32°C) was started at 5 minutes after MBP reached 30 mmHg and was maintained throughout blood volume resuscitation. In the normothermic control group, body temperature was maintained at 37°C during the procedure. Rats were allowed to recover for 6 weeks. TH significantly improved survival: 4 of 15 (26.7%) rats in the normothermic group and 11 of 16 (68.8%; p = 0.032) rats in the TH group survived 6 weeks. Recovery of MBP during the resuscitation phase was significantly improved and left ventricular fractional shortening was markedly increased in the TH group compared with the normothermic group. Brain infarction was observed in 3 of 4 surviving rats (75%) in normothermic group, and in only 1 of the 11 surviving rats (9%) in TH group. The neutrophil-to-lymphocyte ratio was lower in TH group (0.20 ± 0.02) compared with the normothermic group (0.32 ± 0.03; p = 0.003). TH influenced the levels of blood gases and blood counts, favoring hypothermia over control. TH significantly improved long-term survival and blunted the inflammatory response in experimental hemorrhagic shock.

Different Effects of Volatile and Nonvolatile Anesthetic Agents on Long-Term Survival in an Experimental Model of Hemorrhagic Shock.

BACKGROUND: We investigated whether the cardioprotective, volatile gas anesthetic agent, isoflurane, could improve survival and organ function from hemorrhagic shock in an experimental rat model, compared to standard nonvolatile anesthetic agent ketamine/xylazine. METHODS: Sprague Dawley rats (both genders) were randomized to receive either intraperitoneal ketamine/xylazine (K/X, 90 and 10 mg/kg; n = 12) or isoflurane (5% isoflurane induction and 2% maintenance in room air; n = 12) for anesthesia. Blood was withdrawn to maintain mean arterial blood pressure at 30 mm Hg for 1 hour, followed by 30 minutes of resuscitation with shed blood. Rats were allowed to recover and survive for 6 weeks. RESULTS: During the shock phase, the total withdrawn blood volume (expressed as % of estimated total blood volume) to maintain a level of hypotension of 30 mm Hg was significantly higher in the isoflurane group (51.0% ± 1.5%) than in the K/X group (45.3% ± 1.8%; P = .023). Recovery of blood pressure during the resuscitation phase was significantly improved in the isoflurane group compared to the K/X group. The survival rate at 6 weeks was 1 (8.3%) of 12 in rats receiving K/X and 10 (83.3%) of 12 in rats receiving isoflurane (P < .001). Histology performed at 6 weeks demonstrated brain infarction in the 1 surviving rat receiving K/X; no brain infarction occurred in the 10 surviving rats that received isoflurane. No infarction was detected in heart, lung, liver, or kidneys among the surviving rats. CONCLUSIONS: Isoflurane improved blood pressure response to resuscitation and resulted in significantly higher long-term survival rate.

Remote Ischemic Conditioning in Acute Myocardial Infarction and Shock States.

Remote ischemic conditioning is the phenomenon whereby brief, nonlethal episodes of ischemia in one organ (such as a limb) protect a remote organ from ischemic necrosis induced by a longer duration of severe ischemia followed by reperfusion. This phenomenon has been reproduced by dozens of experimental laboratories and was shown to reduce the size of myocardial infarction in many but not all clinical studies. In one recent large clinical trial, remote ischemic conditioning induced by repetitive blood pressure cuff inflations on the arm did not reduce infarct size or improve clinical outcomes. This negative result may have been related in part to the overall success of early reperfusion and current adjunctive therapies, such as antiplatelet therapy, antiremodeling therapies, and low-risk patients, that may make it difficult to show any advantage of newer adjunctive therapies on top of existing therapies. One relevant area in which current outcomes are not as positive as in the treatment of heart attack is the treatment of shock, where mortality rates remain high. Recent experimental studies show that remote ischemic conditioning may improve survival and organ function in shock states, especially hemorrhagic shock and septic shock. In this study, we review the preclinical studies that have explored the potential benefit of this therapy for shock states and describe an ongoing clinical study.

Myocardial hypothermia induced after reperfusion does not prevent adverse left ventricular remodeling nor improve cardiac function.

AIMS: The purpose of the study was to determine whether late therapeutic hypothermia (LTH), administered after reperfusion, could prevent adverse left ventricular (LV) remodeling and improve cardiac function in the rat myocardial ischemia/reperfusion model. MAIN METHODS: Rats were randomized to normothermia (n = 10) or LTH (initiated at 1 min after coronary artery reperfusion, n = 10) and subjected to 30 min of coronary occlusion followed by 6 weeks of reperfusion. Hypothermia was induced by pumping cold saline over the anterior surface of the LV until the temperature cooled to <32 °C. In the normothermic group, the heart was bathed in saline at 38 °C. KEY FINDINGS: After 6 weeks of recovery, fractional shortening of the LV was comparable in the LTH (20.2 ±â€¯0.6%) and normothermic group (20.0 ±â€¯2.1%; p = 0.918). Postmortem LV volume (0.47 ±â€¯0.04 ml in LTH and 0.44 ±â€¯0.05 ml in normothermic group) and lung wet/dry weight ratio were similar in both groups. There were no significant differences in scar size, scar thickness, infarct expansion index, LV cavity or transmurality (%) between groups. This data contrasts with our previous study showing that hypothermia administered during the ischemic phase significantly reduced the scar size; decreased LV cavity, infarct expansion index and transmurality (%), and improved the scar thickness. SIGNIFICANCE: LTH did not prevent adverse LV remodeling nor improve cardiac function in the rat myocardial ischemia/reperfusion model. To have a long term benefit on remodeling, hypothermia must be administered during the ischemic phase and not just the reperfusion phase.

Improved Long-term Survival with Remote Limb Ischemic Preconditioning in a Rat Fixed-Pressure Hemorrhagic Shock Model.

PURPOSE: We investigated whether bilateral, lower limb remote ischemic preconditioning (RIPC) improved long-term survival using a rat model of hemorrhagic shock/resuscitation. METHODS: Rats were anesthetized, intubated and ventilated, and randomly assigned to RIPC, induced by inflating bilateral pressure cuffs around the femoral arteries to 200 mmHg for 5 min, followed by 5-min release of the cuffs (repeated for 4 cycles), or control group (cuffs were inflated to 30 mmHg). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure of 30 mmHg for 30 min, followed by 30 min of resuscitation with shed blood. Rats remained anesthetized for 1 h during which hemodynamics were monitored then they were allowed to survive for 6 weeks. RESULTS: The percentage of estimated total blood volume withdrawn to maintain a level of 30 mmHg was similar in both groups. RIPC significantly increased survival at 6 weeks: 5 of 27 (19%) rats in the control group and 13 of 26 (50%; p = 0.02) rats in the RIPC group survived. Blood pressure was higher in the RIPC group. The diastolic internal dimension of the left ventricle, an indicator of circulating intravascular blood volume, was significantly larger in the RIPC group at 1 h after initiation of resuscitation compared to the control group (p = 0.04). Left ventricular function assessed by fractional shortening was comparable in both groups at 1 h after initiation of resuscitation. Blood urea nitrogen (BUN) was within normal range in the RIPC group (17.3 ± 1.2 mg/dl) but elevated in the control group (22.0 ± 1.7 mg/dl) at 48 h after shock. CONCLUSIONS: RIPC significantly improved short-term survival in rats that were subjected to hemorrhagic shock, and this benefit was maintained long term. RIPC led to greater circulating intravascular blood volume in the early phase of resuscitation and improved BUN.

New and revisited approaches to preserving the reperfused myocardium.

Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.

Therapeutic Hypothermia Reduces the Inflammatory Response Following Ischemia/Reperfusion Injury in Rat Hearts.

Therapeutic hypothermia (TH) is known to protect against ischemia/reperfusion (I/R) injury. One mechanism of I/R injury includes secondary injury due to the inflammatory cascade. We hypothesized that TH reduces the inflammatory response following I/R injury. Rats were randomized to sham, normothermic, or hypothermic groups and subjected to 1 hour of coronary artery occlusion and 48 hours of reperfusion. Hypothermia was initiated, using the ThermoSuit® device, 2 minutes after the onset of coronary artery occlusion to a core temperature of 32°C, and then the rats were allowed to rewarm. After 48 hours, rats in the hypothermia group demonstrated a preserved left ventricular fractional shortening by echocardiography. TH decreased the inflammatory cytokines in the risk zone of the heart, which included monocyte chemoattractant protein-1, interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthase gene expression, and altered expression of the remodeling genes of matrix metalloproteinase and tissue inhibitor of metalloproteinase. Furthermore, rat inflammatory cytokines & receptors PCR array was performed and the data showed that 71 out of 84 genes were upregulated in the risk zone of normothermia hearts versus shams. The upregulation was largely reversed in the risk zone of hypothermia hearts compared to normothermia. TH preserves cardiac function, decreases excessive inflammatory gene expression, and regulates myocardial matrix remodeling related genes.

Cardioprotection: Where to from here?

The size of the myocardial infarction remains an important therapeutic target, because heart attack size correlates with mortality and heart failure. In this era, myocardial infarct size is reduced primarily by timely reperfusion of the infarct related coronary artery. Whereas numerous pre-clinical studies have shown that certain pharmacologic agents and therapeutic maneuvers reduce myocardial infarction size greater than reperfusion alone, very few of these therapies have translated to successful clinical trials or standard clinical use. In this review we discuss both the recent successes as well as recent disappointments, and describe some of the newer potential therapies from the preclinical literature that have not yet been tested in clinical trials.

Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function.

Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart.

AIMS: We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondrial biogenesis and gene expression, suppresses cardiac fibrosis, and preserves sarco/endoplasmic reticulum (SERCA2a) level in the noninfarcted border zone of infarcted hearts. MAIN METHODS: Starting 2h after left coronary artery ligation, rats were randomized to receive Bendavia (3mg/kg/day), water or sham operation. At 6weeks, PCR array and qRT-PCR was performed to detect gene expression. Picrosirius red staining was used to analyze collagen deposition. KEY FINDINGS: There was decreased expression of 70 out of 84 genes related to mitochondrial energy metabolism in the border zone of untreated hearts. This down-regulation was largely reversed by Bendavia treatment. Downregulated mitochondrial biogenesis and glucose & fatty acid (FA) oxidation related genes were restored by administration of Bendavia. Matrix metalloproteinase (MMP9) and tissue inhibitor of metalloproteinase (TIMP1) gene expression were significantly increased in the border zone of untreated hearts. Bendavia completely prevented up-regulation of MMP9, but maintained TIMP1 gene expression. Picrosirius red staining demonstrated that Bendavia suppressed collagen deposition within border zone. In addition, Bendavia showed a trend toward restoring SERCA2a expression. SIGNIFICANCE: Bendavia restored expression of mitochondrial energy metabolism related genes, prevented myocardial matrix remodeling and preserved SERCA2a expression in the noninfarcted border, which may have contributed to the preservation of cardiac structure and function.