Glenn M. Stewart

The impact of an experimentally induced increase in arterial blood pressure on left ventricular twist mechanics

What is the central question of this study? Increases in blood pressure elicited by isometric hand‐grip exercise (IHG) have been shown to impair ventricular twist mechanics. However, the utility of the IHG model is confounded by a concurrent increase in heart rate, which independently influences ventricular mechanics. What is the main finding and its importance? We show that a period of post‐IHG circulatory occlusion isolates the effect of an arterial blood pressure increase from heart rate and magnifies the impairment of left ventricular twist when compared with IHG alone. A protocol using IHG followed by brief circulatory occlusion may serve as a useful tool in examining and understanding the relationships between afterload and cardiac function in various disease states.

Influence of exercise intensity and duration on functional and biochemical perturbations in the human heart.

Strenuous endurance exercise induces transient functional and biochemical cardiac perturbations that persist for 24–48 h. The magnitude and time‐course of exercise‐induced reductions in ventricular function and increases in cardiac injury markers are influenced by the intensity and duration of exercise. In a human experimental model, exercise‐induced reductions in ventricular strain and increases in cardiac troponin are greater, and persist for longer, when exercise is performed within the heavy‐ compared to moderate‐intensity exercise domain, despite matching for total mechanical work. The results of the present study help us better understand the dose–response relationship between endurance exercise and acute cardiac stress/injury, a finding that has implications for the prescription of day‐to‐day endurance exercise regimes.

Altered ventricular mechanics after 60 min of high-intensity endurance exercise: insights from exercise speckle-tracking echocardiography.

Transient reductions in myocardial strain coupled with cardiac-specific biomarker release have been reported after prolonged exercise (>180 min). However, it is unknown if 1) shorter-duration exercise (60 min) can perturb cardiac function or 2) if exercise-induced reductions in strain are masked by hemodynamic changes that are associated with passive recovery from exercise. Left ventricular (LV) and right ventricular global longitudinal strain (GLS), LV torsion, and high-sensitivity cardiac troponin T were measured in 15 competitive cyclists (age: 28 ± 3 yr, peak O2 uptake: 4.8 ± 0.6 l/min) before and after a 60-min high-intensity cycling race intervention (CRIT60). At both time points (pre- and post-CRIT60), strain and torsion were assessed at rest and during a standardized low-intensity exercise challenge (power output: 96 ± 8 W) in a semirecumbent position using echocardiography. During rest, hemodynamic conditions were different from pre- to post-CRIT60 (mean arterial pressure: 96 ± 1 vs. 86 ± 2 mmHg, P < 0.001), and there were no changes in strain or torsion. In contrast, during the standardized low-intensity exercise challenge, hemodynamic conditions were unchanged from pre- to post-CRIT60 (mean arterial pressure: 98 ± 1 vs. 97 ± 1 mmHg, not significant), but strain decreased (left ventricular GLS: -20.3 ± 0.5% vs. -18.5 ± 0.4%, P < 0.01; right ventricular GLS: -26.4 ± 1.6% vs. -22.4 ± 1.5%, P < 0.05), whereas LV torsion remained unchanged. Serum high-sensitivity cardiac troponin T increased by 345% after the CRIT60 (6.0 ± 0.6 vs. 20.7 ± 6.9 ng/l, P < 0.05). This study demonstrates that exercise-induced functional and biochemical cardiac perturbations are not confined to ultraendurance sporting events and transpire during exercise that is typical of day-to-day training undertaken by endurance athletes. The clinical significance of cumulative exposure to endurance exercise warrants further study.

Altered thermoregulatory responses in heart failure patients exercising in the heat

Heart failure (HF) patients appear to exhibit impaired thermoregulatory capacity during passive heating, as evidenced by diminished vascular conductance. Although some preliminary studies have described the thermoregulatory response to passive heating in HF, responses during exercise in the heat remain to be described. Therefore, the aim of this study was to compare thermoregulatory responses in HF and controls (CON) during exercise in the heat. Ten HF (NYHA classes I–II) and eight CON were included. Core temperature (Tc), skin temperature (Tsk), and cutaneous vascular conductance (CVC) were assessed at rest and during 1 h of exercise at 60% of maximal oxygen uptake. Metabolic heat production (Hprod) and the evaporative requirements for heat balance (Ereq) were also calculated. Whole‐body sweat rate was determined from pre–post nude body mass corrected for fluid intake. While Hprod (HF: 3.9 ± 0.9; CON: 6.4 ± 1.5 W/kg) and Ereq (HF: 3.3 ± 0.9; CON: 5.6 ± 1.4 W/kg) were lower (P < 0.01) for HF compared to CON, both groups demonstrated a similar rise in Tc (HF: 0.9 ± 0.4; CON: 1.0 ± 0.3°C). Despite this similar rise in Tc, Tsk (HF: 1.6 ± 0.7; CON: 2.7 ± 1.2°C), and the elevation in CVC (HF: 1.4 ± 1.0; CON: 3.0 ± 1.2 au/mmHg) was lower (P < 0.05) in HF compared to CON. Additionally, whole‐body sweat rate (HF: 0.36 ± 0.15; CON: 0.81 ± 0.39 L/h) was lower (P = 0.02) in HF compared to CON. Patients with HF appear to be limited in their ability to manage a thermal load and distribute heat content to the body surface (i.e., skin), secondary to impaired circulation to the periphery.

Heart Failure and Thermoregulatory Control: Can Patients With Heart Failure Handle the Heat?

Upon heat exposure, the thermoregulatory system evokes reflex increases in sweating and skin blood flow responses to facilitate heat dissipation and maintain heat balance to prevent the continuing rise in core temperature. These heat dissipating responses are mediated primarily by autonomic and cardiovascular adjustments; which, if attenuated, may compromise thermoregulatory control. In patients with heart failure (HF), the neurohumoral and cardiovascular dysfunction that underpins this condition may potentially impair thermoregulatory responses and, consequently, place these patients at a greater risk of heat-related illness. The aim of this review is to describe thermoregulatory mechanisms and the factors that may increase the risk of heat-related illness in patients with HF. An understanding of the mechanisms responsible for impaired thermoregulatory control in HF patients is of particular importance, given the current and projected increase in frequency and intensity of heat waves, as well as the promotion of regular exercise as a therapeutic modality. Furthermore, novel therapeutic strategies that may improve thermoregulatory control in HF, and the clinical relevance of this work in this population will be discussed.

Reproducibility of Echocardiograph‐Derived Multilevel Left Ventricular Apical Twist Mechanics

Left ventricular (LV) twist mechanics are routinely assessed via echocardiography in clinical and research trials investigating the function of obliquely oriented myocardial fibers. However, echocardiograph‐derived measures of LV twist may be compromised by nonstandardized acquisition of the apical image. This study examined the reproducibility of echocardiograph‐derived parameters of apical twist mechanics at multiple levels of the apical myocardium. Two sets of 2D LV parasternal short‐axis images were obtained in 30 healthy subjects (24 men; 19–57 year) via echocardiography. Images were acquired immediately distal to the papillary muscles (apical image 1), immediately above the point of LV cavity obliteration at end systole (apical image 3), and midway between apical image 1 and apical image 3 (apical image 2). Repeat scans were performed within 1 hour, and twist mechanics (rotation and rotation rate) were calculated via frame‐by‐frame tracking of natural acoustic echocardiographic markers (speckle tracking). The magnitude of apical rotation increased progressively toward the apex (apical image 1: 4.2 ± 2.1°, apical image 2: 7.2 ± 3.9°, apical image 3: 11.8 ± 4.6°). apical images 1, 2, and 3 each had moderate to good correlations between repeat scans (ICC: 0.531–0.856). When apical images 1, 2, and 3 were averaged, rotation was 7.7 ± 2.7° and between‐scan correlation was excellent (ICC: 0.910). Similar results were observed for systolic and diastolic rotation rates. Averaging multiple standardized apical images, tending progressively toward the apex, generated the most reproducible rotation indices and may be optimal for the assessment of LV twist mechanics across therapeutic, interventional, and research studies; however, care should be taken given the influence of acquisition level on the magnitude of apical rotation.

Thermoeffector Responses at a Fixed Rate of Heat Production in Heart Failure Patients

PurposeHeart failure (HF) patients seem to exhibit altered thermoregulatory responses during exercise in the heat. However, the extent to which these responses are altered due to physiological impairments independently of biophysical factors associated with differences in metabolic heat production (Hprod), evaporative heat balance requirements (Ereq), and/or body size is presently unclear. Therefore, we examined thermoregulatory responses in 10 HF patients and 10 age-matched controls (CON) similar in body size during exercise at a fixed rate of Hprod and therefore Ereq in a 30°C environment. MethodsRectal temperature, local sweat rate, and cutaneous vascular conductance were measured throughout 60 min of cycle ergometry. Whole-body sweat rate was estimated from pre–post nude body weight corrected for fluid intake. ResultsDespite exercising at the same rate of Hprod (HF, 338 ± 43 W; CON, 323 ± 31 W; P = 0.25), the rise in rectal temperature was greater (P < 0.01) in HF (0.81°C ± 0.16°C) than in CON (0.49°C ± 0.27°C). In keeping with a similar Ereq (HF, 285 ± 40 W; CON, 274 ± 28 W; P = 0.35), no differences in whole-body sweat rate (HF, 0.45 ± 0.11 L·h−1; CON, 0.41 ± 0.07 L·h−1; P = 0.38) or local sweat rate (HF, 0.96 ± 0.17 mg·cm−2·min−1; CON, 0.79 ± 0.15 mg·cm−2·min−1; P = 0.50) were observed between groups. However, the rise in cutaneous vascular conductance was lower in HF than in CON (HF, 0.83 ± 0.42 au·mm Hg−1; CON, 2.10 ± 0.79 au·mm Hg−1; P < 0.01). In addition, the cumulative body heat storage estimated from partitional calorimetry was similar between groups (HF, 154 ± 106 kJ; CON, 196 ± 174 kJ; P = 0.44). ConclusionsCollectively, these findings demonstrate that HF patients exhibit a blunted skin blood flow response, but no differences in sweating. Given that HF patients had similar body heat storage to that of CON at the same Hprod, their greater rise in core temperature can be attributed to a less uniform internal distribution of heat between the body core and periphery.

Impact of high-intensity endurance exercise on regional left and right ventricular myocardial mechanics.

Aims Strenuous endurance exercise acutely increases myocardial wall stress and evokes transient functional cardiac perturbations. However, it is unclear whether exercise-induced functional cardiac disturbances are ubiquitous throughout the myocardium or are segment specific. The aim of this study was to examine the influence of high-intensity endurance exercise on global and segmental left (LV) and right (RV) ventricular tissue deformation (strain). Methods and results Echocardiography was used to measure strain in 23 active men (age: 28 ± 2 years; VO2 peak: 4.5 ± 0.7 L min−1) at rest and during a standardized low-intensity exercise challenge, before and after a 90-min high-intensity endurance cycling intervention. Following the cycling intervention, LV and RV global strain decreased at rest (LV: −18.4 ± 0.4% vs. −17.7 ± 0.4%, P < 0.05; RV: −27.6 ± 0.7% vs. −26.4 ± 0.6%, P < 0.05) and by a greater extent during the low-intensity exercise challenge (LV: −21.3 ± 0.4% vs. −19.2 ± 0.5%, P < 0.01; RV: −28.4 ± 0.8% vs. −23.5 ± 0.9%, P < 0.01). Reductions in LV strain were unique to regions of RV attachment (e.g. LV septum: −24.4 ± 0.5% vs. −21.4 ± 0.6%, P < 0.01) with lateral (−18.9 ± 0.4% vs. −18.4 ± 0.5%) and posterior segments (−19.5 ± 0.4% vs. −18.8 ± 0.7%) unaffected. Similarly, augmentation of strain from rest to exercise was abolished in the RV free wall (−1.1 ± 1.0% vs. 2.9 ± 1.2%, P < 0.01), reduced in the septum (−4.6 ± 0.4% vs. −2.4 ± 0.5%, P < 0.01), and unchanged in the lateral (−1.2 ± 0.6% vs. −0.9 ± 0.6%) and posterior walls (−1.7 ± 0.6% vs. −1.3 ± 0.7%). Conclusion Changes in ventricular strain following high-intensity exercise are more profound in the right ventricle than in the left ventricle. Reductions in LV strain were unique to the septal myocardium and may reflect ventricular interactions secondary to exercise-induced RV dysfunction.

The influence of thoracic gas compression and airflow density dependence on the assessment of pulmonary function at high altitude

The purpose of this report was to illustrate how thoracic gas compression (TGC) artifact, and differences in air density, may together conflate the interpretation of changes in the forced expiratory flows (FEFs) at high altitude (>2400 m). Twenty‐four adults (10 women; 44 ± 15 year) with normal baseline pulmonary function (>90% predicted) completed a 12‐day sojourn at Mt. Kilimanjaro. Participants were assessed at Moshi (Day 0, 853 m) and at Barafu Camp (Day 9, 4837 m). Typical maximal expiratory flow‐volume (MEFV) curves were obtained in accordance with ATS/ERS guidelines, and were either: (1) left unadjusted; (2) adjusted for TGC by constructing a “maximal perimeter” MEFV curve; or (3) adjusted for both TGC and differences in air density between altitudes. Forced vital capacity (FVC) was lower at Barafu compared with Moshi camp (5.19 ± 1.29 L vs. 5.40 ± 1.45 L, P < 0.05). Unadjusted data indicated no difference in the mid‐expiratory flows (FEF25–75%) between altitudes (∆ + 0.03 ± 0.53 L sec−1; ∆ + 1.2 ± 11.9%). Conversely, TGC‐adjusted data revealed that FEF25–75% was significantly improved by sojourning at high altitude (∆ + 0.58 ± 0.78 L sec−1; ∆ + 12.9 ± 16.5%, P < 0.05). Finally, when data were adjusted for TGC and air density, FEFs were “less than expected” due to the lower air density at Barafu compared with Moshi camp (∆–0.54 ± 0.68 L sec−1; ∆–10.9 ± 13.0%, P < 0.05), indicating a mild obstructive defect had developed on ascent to high altitude. These findings clearly demonstrate the influence that TGC artifact, and differences in air density, bear on flow‐volume data; consequently, it is imperative that future investigators adjust for, or at least acknowledge, these confounding factors when comparing FEFs between altitudes.

Folic acid supplementation improves vascular endothelial function, yet not skin blood flow during exercise in the heat, in patients with heart failure

Heart failure (HF) patients are susceptible to heat strain during exercise, secondary to blunted skin blood flow (SkBF) responses, which may be explained by impaired nitric oxide (NO)-dependent vasodilation. Folic acid improves vascular endothelial function and SkBF through NO-dependent mechanisms in healthy older individuals and patients with cardiovascular disease. We examined the effect of folic acid supplementation (5 mg/day for 6 wk) on vascular function [brachial artery flow-mediated dilation (FMD)] and SkBF responses [cutaneous vascular conductance (CVC)] during 60 min of exercise at a fixed metabolic heat production (300 ẆHprod) in a 30°C environment in 10 patients with HF (New York Heart Association Class I-II) and 10 healthy controls (CON). Serum folic acid concentration increased in HF [preintervention (pre): 1.4 ± 0.2; postintervention (post): 8.9 ± 6.7 ng/ml, P = 0.01] and CON (pre: 1.3 ± 0.6; post: 5.2 ± 4.9 ng/ml, P = 0.03). FMD improved by 2.1 ± 1.3% in HF ( P < 0.01), but no change was observed in CON postintervention ( P = 0.20). During exercise, the external workload performed on the cycle ergometer to attain the fixed level of heat production for exercise was similar between groups (HF: 60 ± 13; CON: 65 ± 20 external workload, P = 0.52). Increases in CVC during exercise were similar in HF (pre: 0.89 ± 0.43; post: 0.83 ± 0.45 au/mmHg, P = 0.80) and CON (pre: 2.01 ± 0.79; post: 2.03 ± 0.72 au/mmHg, P = 0.73), although the values were consistently lower in HF for both pre- and postintervention measurement intervals ( P < 0.05). These findings demonstrate that folic acid improves vascular endothelial function in patients with HF but does not enhance SkBF during exercise at a fixed metabolic heat production in a warm environment.