Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.

Mitochondria and Pharmacologic Cardiac Conditioning—At the Heart of Ischemic Injury

Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.

The athletic ECG

The electrocardiogram (ECG) is the most frequently performed basic cardiology investigation. Correct interpretation of the ECG is vital, both to confirm acute diagnoses such as myocardial infarction, and in the elective setting to diagnose previous or underlying cardiac abnormalities. Normal electrocardiographic parameters for the multiple components of the ECG have been identified and are applied to the general population, but it is acknowledged that cardiac conditioning occurs with frequent and sustained aerobic exercise, in turn leading to physiological changes in the ECG. Service personnel may perform exercise at a level that leads to cardiac conditioning with associated ECG changes. This clinical review will briefly address the normal ECG and consider changes associated with aerobic cardiac conditioning. By identifying what constitutes physiological non-pathological changes in the athletic ECG, this clinical review aims to assist those who interpret ECGs in Service personnel.

Distance exercised during submaximal training on race winnings for Thoroughbred racehorses

Evaluations of the physical fitness of Thoroughbred racehorses have been correlated with race earnings, but few reports exist about the influence of the distance exercised during training on both physical conditioning indices and financial productivity. During one training season sixteen claiming Thoroughbred horses were subjected to submaximal training and monitored by a global positioning system (GPS) coupled to a heart rate monitor. After initial and single monitoring, the horses were distributed into two groups of eight individuals each; one group exercised short distances (SD) between 1600 and 1900m, while the other exercised long distances (LD) between 2000 and 2350m. The duration (min) and mean and maximal velocities (ms-1)attained during each session were determined, as well as the difference in distances exercised (m) between official races and each training session. Blood lactate concentration ([LA]) during recovery was also determined. Student's t-test was used for a non-paired analysis, with P≤0.05 considered significant. The winnings (USD) of each horse were correlated with the peak heart rate (HRpeak) attained during the training session. The distances exercised in the training sessions were greater in relation to the official races distances by 24.7% and 40% for SD and LD, respectively. Lactatemia did not differ between the groups. The HRpeak obtained during the training session was lower in LD group. The velocity at which the heart rate reached 200 bpm (V200) was higher in LD group. There was a moderate correlation (r= 0.42) between the highest winnings and lowest HRpeak. The horses that ran longer distances during their submaximal training session had better cardiac conditioning and tendency to increase financial productivity