Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Spontaneous baroreflex control of heart rate during exercise and muscle metaboreflex activation in heart failure

In heart failure (HF), there is a reduced baroreflex sensitivity at rest, and during dynamic exercise there is enhanced muscle metaboreflex activation (MRA). However, how the arterial baroreflex modulates HR during exercise is unknown. We tested the hypothesis that spontaneous baroreflex sensitivity (SBRS) is attenuated during exercise in HF and that MRA further depresses SBRS. In seven conscious dogs we measured heart rate (HR), cardiac output, and left ventricular systolic pressure at rest and during mild and moderate dynamic exercise, before and during MRA (via imposed reductions of hindlimb blood flow), and before and after induction of HF (by rapid ventricular pacing). SBRS was assessed by the sequences method. In control, SBRS was reduced from rest with a progressive resetting of the baroreflex stimulus-response relationship in proportion to exercise intensity and magnitude of MRA. In HF, SBRS was significantly depressed in all settings; however, the changes with exercise and MRA occurred with a pattern similar to the control state. As in control, the baroreflex stimulus-response relationship showed an intensity- and muscle metaboreflex (MMR)-dependent rightward and upward shift. The results of this study indicate that HF induces an impairment in baroreflex control of HR at rest and during exercise, although the effects of exercise and MRA on SBRS occur with a similar pattern as in control, indicating the persistence of some vagal activity.     

Phrenic nerve injury after catheter ablation of atrial fibrillation

Phrenic Nerve Injury (PNI) has been well studied by cardiac surgeons. More recently it has been recognized as a potential complication of catheter ablation with a prevalence of 0.11 to 0.48 % after atrial fibrillation (AF) ablation. This review will focus on PNI after AF ablation. Anatomical studies have shown a close relationship between the right phrenic nerve and it's proximity to the superior vena cava (SVC), and the antero-inferior part of the right superior pulmonary vein (RSPV). In addition, the proximity of the left phrenic nerve to the left atrial appendage has been well established. Independent of the type of ablation catheter (4 mm, 8 mm, irrigated tip, balloon) or energy source used (radiofrequency (RF), ultrasound, cryothermia, and laser); the risk of PNI exists during ablation at the critical areas listed above. Although up to thirty-one percent of patients with PNI after AF ablation remain asymptomatic, dyspnea remain the cardinal symptom and is present in all symptomatic patients. Despite the theoretical risk for significant adverse effect on functional status and quality of life, short-term outcomes from published studies appear favorable with 81% of patients with PNI having a complete recovery after 7 +/- 7 months. CONCLUSION: Existing studies have described PNI as an uncommon but avoidable complication in patients undergoing pulmonary vein isolation for AF. Prior to ablation at the SVC, antero-inferior RSPV ostium or the left atrial appendage, pacing should be performed before energy delivery. If phrenic nerve capture is documented, energy delivery should be avoided at this site. Electrophysiologist's vigilance as well as pacing prior to ablation at high risk sites in close proximity to the phrenic nerve are the currently available tools to avoid the complication of PNI.     

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability

Mammalian skeletal muscles generate marked amounts of superoxide (O₂·^–) at 37°C, but it is not well understood which is the main source of O₂·^– production in the muscle fibers and how this interferes with muscle function. To answer these questions, O₂·^– production and twitch force responses were measured at 37°C in mechanically skinned muscle fibers of rat extensor digitorum longus (EDL) muscle. In mechanically skinned fibers, the sarcolemma is removed avoiding potential sources of O₂·^– production that are not intrinsically part of the muscle fibers, such as nerve terminals, blood cells, capillaries and other blood vessels in the whole muscle. O₂·^– production was also measured in split single EDL muscle fibers, where part of the sarcolemma remained attached, and small bundles of intact isolated EDL muscle fibers at rest, in the presence and absence of modifiers of mitochondrial function. The results lead to the conclusion that mitochondrial production of O₂·^– accounts for most of the O₂·^– measured intracellularly or extracellularly in skeletal muscle fibers at rest and at 37°C. Muscle fiber excitability at 37°C was greatly improved in the presence of a membrane permeant O₂·^– dismutase mimetic (Tempol), demonstrating a direct link between O₂·^– production in the mitochondria and muscle fiber performance. This implicates mitochondrial O₂·^– production in the down-regulation of skeletal muscle function, thus providing a feedback pathway for communication between mitochondria and plasma membranes that is not directly related to the main function of mitochondria as the power plant of the mammalian muscle cell. excitation-contraction coupling; mechanically skinned fiber; physiological temperature     

Heart failure attenuates muscle metaboreflex control of ventricular contractility during dynamic exercise

Underperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex (MMR). In normal dogs during mild exercise, MMR activation causes large increases in cardiac output (CO) and mean arterial pressure (MAP); however, in heart failure (HF) although MAP increases, the rise in CO is virtually abolished, which may be due to an impaired ability to increase left ventricular contractility (LVC). The objective of the present study was to determine whether the increases in LVC seen with MMR activation during dynamic exercise in normal animals are abolished in HF. Conscious dogs were chronically instrumented to measure CO, MAP, and left ventricular (LV) pressure and volume. LVC was calculated from pressure-volume loop analysis [LV maximal elastance (E(max)) and preload-recruitable stroke work (PRSW)] at rest and during mild and moderate exercise under free-flow conditions and with MMR activation (via partial occlusion of hindlimb blood flow) before and after rapid ventricular pacing-induced HF. In control experiments, MMR activation at both workloads [mild exercise (3.2 km/h) and moderate exercise (6.4 km/h at 10% grade)] significantly increased CO, E(max), and PRSW. In contrast, after HF was induced, CO, E(max), and PRSW were significantly lower at rest. Although CO increased significantly from rest to exercise, E(max) and PRSW did not change. In addition, MMR activation caused no significant change in CO, E(max), or PRSW at either workload. We conclude that MMR causes large increases in LVC in normal animals but that this ability is abolished in HF.     

Effects of helicopter net-gunning on survival of bighorn sheep

Wildlife capture, and the data collection associated with it, has led to major advancements in ecology that are integral to decision making pertaining to wildlife conservation. Capturing wildlife, however, can cause lethal and non-lethal risks to animals. Understanding the factors that contribute to the level of risk involved in wildlife capture is therefore important for the development and implementation of the safest and most effective methodologies. We used data from 736 animal captures of 389 individuals for 2 subspecies of female bighorn sheep (Rocky Mountain bighorn [Ovis canadensis canadensis], Sierra Nevada bighorn sheep [O. c. sierrae]) in Wyoming and California, USA, in 2002–2020 to evaluate the degree and extent of time that capture via helicopter net-gunning affects survival. We compared pre- and post-capture survival during a 10-week window centered on a capture event, and post-capture survival between captured animals and animals that were monitored but not captured during the 10-week window. Additionally, we evaluated the effects of handling techniques (number of times captured, season of capture event, handling time, chase time, and body temp) and biological factors (age and nutritional condition) on probability of capture mortality. Mean daily survival was 0.9992 during a 5-week pre-capture window, dropped to 0.9864 on the day of capture, and rebounded within 3 days of capture to pre-capture levels and that of sheep that were not captured. Overall, direct mortality resulting from capture was 1.36%, with 0.54% mortality occurring within the 3 days following a capture event for an overall 1.90% capture-related mortality. The only handling and biological metrics that influenced the probability of capture mortality were rectal temperature and nutritional condition; high initial rectal temperatures and poor body condition were associated with increased risk of mortality in the days following capture. Overall, helicopter net-gunning imposed low and short-term risk to survival of female bighorn sheep. To reduce bias in survival estimates, we recommend using a 3-day censorship window for post-capture mortalities as opposed to the common practice of a 2–5-week censor window. Helicopter net-gunning, including annual or seasonal recaptures, remains an effective and comparatively safe technique for capture and associated data collection of bighorn sheep.     

Multiple antibacterial histone H2B proteins are expressed in tissues of American oyster

We have previously identified a histone H2B isomer (cvH2B-1) from tissue extracts of the bivalve mollusk, the American oyster (Crassostrea virginica). In this paper, we isolate an additional three antibacterial proteins from acidified gill extract by preparative acid-urea-polyacrylamide gel electrophoresis and reversed-phase high performance liquid chromatography. Extraction of these proteins from tissue was best accomplished by briefly boiling the tissues in a weak acetic acid solution. Addition of protease inhibitors while boiling resulted in somewhat lower yields, with one protein being totally absent with this method. Via mass spectrometry, the masses of one of these purified proteins was 13607.0Da (peak 2), which is consistent with the molecular weight of histone H2B. In addition, via western-blotting using anti-calf histone H2B antibody, all three proteins were positive and were thus named cvH2B-2, cvH2B-3 and cvH2B-4. The antibacterial activity of cvH2B-2 was similar to that of cvH2B-1, with activity against a Gram-positive bacterium (Lactococcus lactis subsp. lactis; minimum effective concentration [MEC] 52-57μg/mL) but inactive against Staphylococcus aureus (MEC>250μg/mL). However, both proteins had relatively potent activity against the Gram-negative oyster pathogen Vibrio parahemolyticus (MEC 11.5-14μg/mL) as well as the human pathogen Vibrio vulnificus (MEC 21.3-25.3μg/mL). cvH2B-3 and cvH2B-4 also had similarly strong activity against Vibrio vulnificus. These data provide further evidence for the antimicrobial function of histone H2B isomers in modulating bacterial populations in oyster tissues. The combined estimated concentrations of these histone H2B isomers were far above the inhibitory concentrations for the tested vibrios, including human pathogens. Our results indicate that the highly conserved histone proteins might be important components not only of immune defenses in oysters but have the potential to influence the abundance of a ubiquitous microbial resident of oyster tissues that is the major source of seafood-borne illness in humans.     

Macroecology of high-elevation myxomycete assemblages in the northern Neotropics

A number of recent studies have been directed towards developing a more complete understanding of myxomycete ecology throughout the world. However, the lack of comparative data obtained using standard methodologies makes the results of these studies somewhat speculative. The objective of this investigation was to examine the evidence of macroecological patterns in myxomycete assemblages in high-elevation areas of the northern Neotropics. For this, a series of study areas in Mexico, Guatemala, and Costa Rica, as well as two external study areas (one in the United States and the other in Thailand), were selected to compare the diversity-environment relationships exhibited by myxomycetes. Altogether, the 2592 moist chamber cultures prepared yielded a total of 1377 myxomycete records, representing 89 different species. A trend of decreasing species richness with decreasing latitude was observed for the species assemblages associated with the study areas in the Neotropics. As latitude increased, species assemblages in the Neotropical study areas became increasingly similar to the temperate study area. The difference in species richness between study areas in Mexico and Thailand, along with the results obtained for a series of macroclimatic patterns evaluated in the study areas of the Neotropical region, suggests that forest structure plays an important role in the structure of myxomycete assemblages. In contrast, soil chemical characteristics and the pH of the substrates present seem to be indirectly related to the diversity estimators used for analysis, suggesting that they are probably more important at a smaller ecological scale.