Search Results (35)

Cardiovascular diseases remain the leading cause of death worldwide, highlighting the urgent need for novel therapeutic strategies. The Mediterranean diet is renowned for its cardiovascular benefits, largely attributed to extra virgin olive oil (EVOO) and its phenolic compounds, particularly hydroxytyrosol (HT). HT, a potent antioxidant and anti-inflammatory agent, has demonstrated significant therapeutic potential in mitigating myocardial damage following acute myocardial infarction (AMI). However, there is a notable lack of published evidence regarding the effects of HT administration in the context of acute ischemia/reperfusion (I/R) injury, making this study a novel contribution to the field. This study aimed to evaluate the cardioprotective effects of HT using the Langendorff technique in an isolated mouse heart ischemia/reperfusion (I/R) model. Mice were administered a single intraperitoneal dose of HT (10 mg/kg) 24 h prior to the I/R protocols, and parameters such as the infarct size, mitochondrial function, and redox balance were assessed. The results revealed a remarkable 57% reduction in infarct size in HT-treated mice compared to untreated controls. HT treatment also improved mitochondrial bioenergetics, as evidenced by the increased membrane potential (ΔΨm), enhanced oxygen consumption, and reduced hydrogen peroxide (H₂O₂) production. Furthermore, HT restored the activity of the mitochondrial respiratory complexes, notably Complex I, even under I/R conditions. These findings highlight the efficacy of HT in reducing oxidative stress and preserving mitochondrial function, critical factors in cardiac disease. In conclusion, HT emerges as a promising therapeutic agent for ischemic heart disease, demonstrating both preventive and restorative potential. Future research should explore its clinical applicability to advance cardiovascular disease management. Full article

Background: A significant proportion of post-myocardial infarction (MI) patients do not reach target low-density lipoprotein cholesterol (LDL-C) levels. Suboptimal LDL-C reduction is often attributed to poor adherence to pharmacological therapy and lifestyle recommendations. Methods: In a prospective registry of 179 post-MI patients who completed a Phase 2 Cardiac Rehabilitation Program (CRP), we evaluated the characteristics and predictors of suboptimal LDL-C reduction. Key indicators were assessed before and after CRP: adherence to the Mediterranean diet (using the PREDIMED questionnaire), weekly physical activity (via the IPAQ questionnaire), therapeutic adherence (using the Morisky–Green questionnaire), and peak oxygen consumption (VO₂) on exercise testing. Lipid-lowering therapy (LLT) and LDL-C were recorded prior to MI and both before and after Phase 2 CRP. At the end of Phase 2, we analyzed the difference between measured and theoretical LDL-C (basal LDL-C minus expected LDL-C reduction by LLT), which was defined as “residual difference in LDL-C” (RD-LDL-C). We analyzed the predictors of positive RD-LDL-C (lower than theoretically expected). Results: After CRP, 54 (30.2%) patients exhibited positive RD-LDL-C. Within this subgroup, LLT was uptitrated, and patients received more potent LLT at the conclusion of CRP (theoretical potency: 69.81 ± 7.07 vs. 66.41 ± 7.48%, p = 0.005). However, they were less likely to reach the target LDL-C level <55 mg/dL (66.7% vs. 93.6%, p < 0.001). Male sex (HR 17.96 [2.15, 149.92], p = 0.008) and higher lipoprotein (a) levels (HR 1.02 [1.01, 1.03] per mg/dL, p = 0.001) were associated with a positive RD-LDL-C. Conversely, diabetes mellitus (HR 0.17 [0.06, 0.51], p = 0.002), higher corrected basal LDL-C levels (HR 0.98 [0.97, 0.99] per mg/dL, p = 0.001), and supervised in-hospital training during CRP (HR 0.28 [0.09, 0.86], p = 0.03) were associated with a reduced probability of positive RD-LDL-C. No association was found with adherence to the Mediterranean diet (88.1%), therapeutic adherence (89.1%), reported weekly physical activity (median 3545 [1980, 6132] metabolic equivalents per week), or change in peak VO₂. Conclusions: More than one-third of post-MI patients demonstrated lower than expected LDL-C reduction (positive RD-LDL-C) following CRP, a finding that could not be attributed to poor adherence to pharmacological therapy or lifestyle recommendations. These findings suggest that a personalized approach to prescribing and uptitrating LLT may help achieve LDL-C targets, particularly in MI patients with healthy lifestyle habits who exhibit a lower response to LLT. Full article

Introduction: Vascular aging is associated with a loss of aortic compliance (C_A), which results in increased left ventricular pressure–volume area (PVA), stroke work (SW) and myocardial oxygen consumption (MVO₂). Myocardial efficiency (MyoEff) is derived from the PVA and MVO₂ construct, which includes potential energy (PE). However, the SW/MVO₂ ratio does not include PE and provides a more accurate physiologic measure. Methods: We used a modified computational model (CM) to assess PVA and SW and calculate MVO₂ using a pressure-work index (e MVO₂), to derive MyoEff–PVA and MyoEff–SW metrics. Phase I evaluated five levels of human C_A from normal (N) to stiff (S) at 80 bpm, and Phase II evaluated two levels of C_A (N and S) at three heart rates (60, 100, and 140 bpm). Results: During Phase I, MyoEff–PVA increased from 20.7 to 31.2%, and MyoEff–SW increased from 14.8 to 18.9%. In Phase II, during the N setting coupled with increases in the heart rate, the MyoEff–PVA decreased from 29.4 to 14.8 to 9.5%; the MyoEff–SW also decreased from 22.5 to 10.3 to 5.9%. As expected, during the S setting, MyoEff–PVA decreased from 45.5 to 22.9 to 14.8; a similar effect occurred with the MyoEff–SW, demonstrating a decrease from 29.9 to 13.9 to 7.9%, respectively. Conclusions: The CM provided insights into a simple and clinically relevant calculation for assessing MyoEff. The agreement on the CM metrics aligns with studies conducted previously in the clinical setting. Full article

Background: The systemic stress response to surgery is a complex physiological process characterized by neuroendocrine, sympathetic, and inflammatory activation. While necessary for survival, this response can lead to adverse outcomes such as hyperglycemia, immune suppression, cardiovascular complications, and delayed recovery. Regional anesthesia (RA) has been shown to modulate this stress response more effectively than general anesthesia (GA) by blocking nociceptive signaling and attenuating the release of stress mediators. Objectives: This review aims to elucidate how RA influences the systemic stress response, highlighting its clinical benefits in reducing postoperative pain, improving hemodynamic stability, minimizing inflammatory responses, and preserving immune function. Additionally, this review examines evidence from clinical trials supporting using RA to improve surgical outcomes, particularly in high-risk populations. Methods: A comprehensive narrative review of the literature was conducted to explore the physiological impact of RA on the systemic stress response and its associated clinical outcomes. Studies comparing RA to GA across various surgical procedures were evaluated, focusing on neuroendocrine modulation, sympathetic inhibition, inflammatory attenuation, and the implications for pain management, cardiovascular and pulmonary function, and immune preservation. Results: RA significantly attenuates the neuroendocrine response by reducing the release of cortisol and catecholamines, thereby improving hemodynamic stability and reducing myocardial oxygen consumption. RA also inhibits the sympathetic nervous system, leading to improved cardiovascular outcomes. Furthermore, RA mitigates the inflammatory response by reducing pro-inflammatory cytokine levels, reducing the risk of systemic inflammatory response syndrome (SIRS), sepsis, and pulmonary complications. Clinical studies and meta-analyses consistently demonstrate that RA reduces postoperative pain, opioid consumption, and the incidence of cardiovascular and pulmonary complications, particularly in elderly and high-risk patients. Conclusions: RA offers a significant advantage in modulating the systemic stress response to surgery, improving postoperative outcomes by reducing pain, enhancing cardiovascular stability, and preserving immune function. Its benefits are particularly pronounced in high-risk populations such as the elderly or those with pre-existing comorbidities. Given the growing evidence supporting its efficacy, RA should be considered a critical component of multimodal perioperative care strategies aimed at minimizing the systemic stress response and improving recovery. Future research should optimize RA techniques and identify patient-specific factors to enhance therapeutic benefits. Full article

Background: A knee injury in an athlete leads to periods of forced exercise interruption. Myocardial work (MW) assessed by echocardiographic and cardiopulmonary exercise testing (CPET) are two essential methods for evaluating athletes during the period following injury. However, compared to pre-surgery evaluations, the variations in cardiovascular parameters and functional capacity assessed by these methods after surgery remain unclear. Methods: We evaluated 22 non-professional athletes aged 18–52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, who were affected by a knee pathology requiring surgical treatment. The evaluation was performed at rest using transthoracic echocardiography, including MW assessment, and during exercise using CPET. Each athlete underwent the following two evaluations: the first before surgery and the second after surgery (specifically at the end of the deconditioning period). Results: Resting heart rate (HR) increased significantly (from 63.3 ± 10.85 to 71.2 ± 12.52 beats per minute, p = 0.041), while resting diastolic and systolic blood pressure, forced vital capacity, and forced expiratory volume in the first second did not show significant changes. Regarding the echocardiographic data, global longitudinal strain decreased from −18.9 ± 1.8 to −19.3 ± 1.75; however, this reduction was not statistically significant (p = 0.161). However, the global work efficiency (GWE) increased significantly (from 93.0% ± 2.9 to 94.8% ± 2.6, p = 0.006) and global wasted work (GWW) reduced significantly (from 141.4 ± 74.07 to 98.0 ± 50.9, p = 0.007). Additionally, the patients were able to perform maximal CPET at both pre- and post-surgery evaluations, as demonstrated by the peak respiratory exchange ratio and HR. However, the improved myocardial contractility (increased GWE and decreased GWW) observed at rest did not translate into significant changes in exercise parameters, such as peak oxygen consumption and the mean ventilation/carbon dioxide slope. Conclusions: After surgery, the athletes were more deconditioned (as indicated by a higher resting HR) but exhibited better resting myocardial contractility (increased GWE and reduced GWW). Interestingly, no significant changes in exercise capacity parameters, as evaluated by CPET, were found after surgery, suggesting that the improved myocardial contractility was offset by a greater degree of muscular deconditioning. Full article

Background: Despite the effectiveness of cardiac rehabilitation (CR), the actual participation rate in CR is low. While home-based CR offers a viable alternative, it faces challenges in participation due to factors such as a lack of self-motivation and fear of exercising without supervision. Utilizing a mobile healthcare application (app) during counseling may be an effective strategy for patients. Therefore, the aim of this study was to assess whether 6 weeks of home-based CR with exercise readjustment using a mobile app is an effective therapy for patients with acute myocardial infarction (AMI). Methods: Post-AMI patients eligible for home-based CR were randomized into the intervention group (CR-Mobile) and the control group, which followed the usual home-based CR protocol (CR-Usual). Both groups participated in a 6-week home-based CR program, with exercise readjustment and encouragement carried out every 2 weeks. The CR-Mobile group was supervised using data recorded in the mobile app, while the CR-Usual group was supervised via phone consultations. The primary outcome measured was maximal oxygen consumption (VO_2max). Results: Within-group comparisons showed significant improvements in VO_2max (P_CR-Mobile = 0.011 vs. P_CR-Usual = 0.020) and METs (P_CR-Mobile = 0.011 vs. P_CR-Usual = 0.011) for both groups. Conclusions: These findings suggest that a 6-week home-based CR program with exercise readjustment using a mobile app can potentially enhance exercise capacity as effectively as verbal supervision. Full article

Health care is currently showing a fall in heart failure (HF) incidence and prevalence, particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF remain unidentified, which would help in choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique which is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated the clinical application and accuracy of STE in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption. Furthermore, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS), which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. However, STE is known for its limitations; despite these, it has been shown to explain symptoms and signs and also to be an accurate prognosticator. The aim of this review is to examine the advantages of STE in the early evaluation of myocardial dysfunction and its correlation with right heart catheterization (RHC) parameters, which should have significant clinical relevance in the management of HF patients. Full article

Atrial fibrillation (AF), characterized by structural remodeling involving atrial myocardial degradation and fibrosis, is linked with obesity and transforming growth factor beta 1 (TGF-β1). Aldehyde dehydrogenase 2 (ALDH2) deficiency, highly prevalent in East Asian people, is paradoxically associated with a lower AF risk. This study investigated the impact of ALDH2 deficiency on diet-induced obesity and AF vulnerability in mice, exploring potential compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1). Wild-type (WT) and ALDH2*2 knock-in (KI) mice were administered a high-fat diet (HFD) for 16 weeks. Despite heightened levels of reactive oxygen species (ROS) post HFD, the ALDH2*2 KI mice did not exhibit a greater propensity for AF compared to the WT controls. The ALDH2*2 KI mice showed equivalent myofibril degradation in cardiomyocytes compared to WT after chronic HFD consumption, indicating suppressed ALDH2 production in the WT mice. Atrial fibrosis did not proportionally increase with TGF-β1 expression in ALDH2*2 KI mice, suggesting compensatory upregulation of the Nrf2 and HO-1 pathway, attenuating fibrosis. In summary, ALDH2 deficiency did not heighten AF susceptibility in obesity, highlighting Nrf2/HO-1 pathway activation as an adaptive mechanism. Despite limitations, these findings reveal a complex molecular interplay, providing insights into the paradoxical AF–ALDH2 relationship in the setting of obesity. Full article

Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium’s ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge. Full article

The application of doxorubicin (DOX) is hampered by cardiotoxicity, with diastolic dysfunction as the earliest manifestation. Fibrosis leads to impaired relaxation, but the mechanisms that operate shortly after DOX exposure are not clear. We asked whether the activation of cardiac fibroblasts (CFs) anticipates myocardial dysfunction and evaluated the effects of DOX on CF metabolism. CFs were isolated from the hearts of rats after the first injection of DOX. In another experiment, CFs were exposed to DOX in vitro. Cell phenotype and metabolism were determined. Early effects of DOX consisted of diastolic dysfunction and unchanged ejection fraction. Markers of pro-fibrotic remodeling and evidence of CF transformation were present immediately after treatment completion. Oxygen consumption rate and extracellular acidification revealed an increased metabolic activity of CFs and a switch to glycolytic energy production. These effects were consistent in CFs isolated from the hearts of DOX-treated animals and in naïve CFs exposed to DOX in vitro. The metabolic switch was paralleled with the phenotype change of CFs that upregulated markers of myofibroblast differentiation and the activation of pro-fibrotic signaling. In conclusion, the metabolic switch and activation of CFs anticipate DOX-induced damage and represent a novel target in the early phase of anthracycline cardiomyopathy. Full article

About half a century ago, Eugene Braunwald, a father of modern cardiology, shared a revolutionary belief that “time is muscle”, which predetermined never-ending effort to preserve the unaffected myocardium. In connection to that, researchers are constantly trying to better comprehend the ongoing changes of the ischemic myocardium. As the latest studies show, metabolic changes after acute myocardial infarction (AMI) are inconsistent and depend on many constituents, which leads to many limitations and lack of unification. Nevertheless, one of the promising novel mechanistic approaches related to iron metabolism now plays an invaluable role in the ischemic heart research field. The heart, because of its high levels of oxygen consumption, is one of the most susceptible organs to iron-induced damage. In the past few years, a relatively new form of programmed cell death, called ferroptosis, has been gaining much attention in the context of myocardial infarction. This review will try to summarize the main novel metabolic pathways and show the pivotal limitations of the affected myocardium metabolomics. Full article

Connexin 43 (Cx43) is expressed in the left and right ventricles and is primarily responsible for conducting physiological responses in microvasculature. Studies have demonstrated that NADPH oxidase (NOX) enzymes are essential in cardiac redox biology and are responsible for the generation of reactive oxygen species (ROS). NOX2 is linked to left ventricular remodeling following myocardial infarction (MI). It was hypothesized that conjugated linoleic acid (cLA) treatment increases NOX-2 levels in heart tissue and disrupts connexins between the myocytes in the ventricle. Data herein demonstrate that cLA treatment significantly decreases survival in a murine model of MI. The observance of cLA-induced ventricular tachyarrhythmia’s (VT) led to the subsequent investigation of the underlying mechanism in this MI model. Mice were treated with cLA for 12 h, 24 h, 48 h, or 72 h to determine possible time-dependent changes in NOX and Cx43 signaling pathways in isolated left ventricles (LV) extracted from cardiac tissue. The results suggest that ROS generation, through the stimulation of NOX2 in the LV, triggers a decrease in Cx43 levels, causing dysfunction of the gap junctions following treatment with cLA. This cascade of events may initiate VT and subsequent death during MI. Taken together, individuals at risk of MI should use caution regarding cLA consumption. Full article

Background: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). Methods: We measured eosinophils in 64 patients with HF (50% females), 55 (51–63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO₂) with a treadmill test. Results: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1–0.3] to 0.3 [0.1–0.4] × 10³ cells/µL (p < 0.001) and from 0.3 [0.2–0.5] to 0.2 [0.1–0.3] × 10³ cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO₂ (Spearman’s Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4–0.6] vs. 0.2 [0.1–0.4] × 10³ cells/µL, p = 0.023), who also showed a greater increase in peak VO₂ (3.0 [0.9–4.3] vs. 0.3 [−0.6–1.8] mLO₂·kg⁻¹·min⁻¹, p = 0.015). Conclusion: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO₂. Full article

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study. Full article

The prevalence of acute coronary syndrome in Korea has steadily increased, however, the understanding of and participation rate in cardiac rehabilitation (CR) is very low. There are few studies have been conducted in myocardial infarction (MI) patients with reduced heart function, a so-called high-risk group. Therefore, it is necessary to compare the effects of CR on the degree of improvement in cardiopulmonary fitness (CPF), whether MI patients participate or not, especially in the patients that are at a high risk of MI. Three hundred and ninety-four patients that were commissioned for CR between January 2016 and December 2020 were screened for risk stratification based on the American Association of Cardiovascular and Pulmonary Rehabilitation guidelines, and 115 were classified as high-risk patients. We retrospectively reviewed the patients who underwent both an exercise tolerance test (ETT) during the initial visit and 3 months after the onset of the study. During this period, 42 subjects were included, of which, 26 underwent at least one CR session and 16 did not. The baseline characteristics of the patients showed no significant differences. The results of the CPF improvement were measured as peak oxygen consumption (VO_{2 peak}) and metabolic equivalent of tasks (METs) values which were derived through the ETT. Prior to the ETT, all of the demographic features, including ejection fraction, showed that there were no significant differences between the two groups. The initial CPF values were the same. However, after three months, the VO_{2 peak} and METs values showed that there were significant differences between the two groups (p < 0.01). Additionally, the exercise time differed significantly between the two groups. The CPF values and exercise time showed a significant increase after 3 months in the CR participants. Therefore, it is necessary to initiate cardiac rehabilitation especially in high-risk patients as soon as the patient’s vital signs are stable to improve their cardiopulmonary function. Full article