Search

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal.

Background Estimated pulse wave velocity (ePWV) calculated by equations using age and blood pressure has been suggested as a new marker of mortality and cardiovascular risk. However, the prognostic potential of ePWV during long‐term follow‐up in patients with symptoms of stable angina remains unknown. Methods and Results In this study, ePWV was calculated in 25 066 patients without diabetes, previous myocardial infarction (MI), stroke, heart failure, or valvular disease (mean age 63.7±10.5 years, 58% male) with stable angina pectoris undergoing elective coronary angiography during 2003 to 2016. Multivariable Cox models were used to assess the association with incident all‐cause mortality, MI, and stroke. Discrimination was assessed using Harrell´s C‐index. During a median follow‐up period of 8.5 years (interquartile range 5.5–11.3 years), 779 strokes, 1233 MIs, and 4112 deaths were recorded. ePWV was associated with all‐cause mortality (hazard ratio [HR] per 1 m/s, 1.13; 95% CI, 1.05–1.21) and MI (HR per 1 m/s 1.23, 95% CI, 1.09–1.39) after adjusting for age, systolic blood pressure, body mass index, smoking, estimated glomerular filtration rate, Charlson Comorbidity Index score, antihypertensive treatment, statins, aspirin, and number of diseased coronary arteries. Compared with traditional risk factors, the adjusted model with ePWV was associated with a minor but likely not clinically relevant increase in discrimination for mortality, 76.63% with ePWV versus 76.56% without ePWV, P

ObjectiveInvestigating the cardiovascular system is challenging due to its complex regulation by humoral and neuronal factors. Despite this complexity, many existing research methods are limited to the assessment of a few parameters leading to an incomplete characterization of cardiovascular function. Thus, we aim to establish a murine in vivo model for integrated assessment of the cardiovascular system under conditions of controlled heart rate. Utilizing this model, we assessed blood pressure, cardiac output, stroke volume, total peripheral resistance, and electrocardiogram (ECG).HypothesisWe hypothesize that (i) our in vivo model can be utilized to investigate cardiac and vascular responses to pharmacological intervention with the α1-agonist phenylephrine, and (ii) we can study cardiovascular function during artificial pacing of the heart, modulating cardiac function without a direct vascular effect.MethodsWe included 12 mice that were randomly assigned to either vehicle or phenylephrine intervention through intraperitoneal administration. Mice were anesthetized with isoflurane and intubated endotracheally for mechanical ventilation. We measured blood pressure via a solid-state catheter in the aortic arch, blood flow via a probe on the ascending aorta, and ECG from needle electrodes on the extremities. Right atrium was electrically paced at a frequency ranging from 10 to 11.3 Hz before and after either vehicle or phenylephrine administration.ResultsPhenylephrine significantly increased blood pressure, stroke volume, and total peripheral resistance compared to the vehicle group. Moreover, heart rate was significantly decreased following phenylephrine administration. Pacing significantly decreased stroke volume and cardiac output both prior to and after drug administration. However, phenylephrine-induced changes in blood pressure and total peripheral resistance were maintained with increasing pacing frequencies compared to the vehicle group. Total peripheral resistance was not significantly altered with increasing pacing frequencies suggesting that the effect of phenylephrine is primarily of vascular origin.ConclusionIn conclusion, this in vivo murine model is capable of distinguishing between changes in peripheral vascular and cardiac functions. This study underlines the primary effect of phenylephrine on vascular function with secondary changes to cardiac function. Hence, this in vivo model is useful for the integrated assessment of the cardiovascular system.