Echocardiographic assessments of longitudinal left ventricular function in healthy English springer spaniels

OBJECTIVES: To establish reference intervals for echocardiographic measures of longitudinal left ventricular function in adult English springer spaniel dogs. ANIMALS: Forty-two healthy adult English springer spaniels. METHODS: Animals were prospectively recruited from a general practice population in the United Kingdom. Dogs were examined twice, at least 12 months apart, to exclude dogs with progressive cardiac disease. Mitral annular plane systolic excursion, tissue Doppler imaging (TDI) mitral annular velocities and two-dimensional speckle-tracking echocardiographic (2DSTE) left ventricular longitudinal strain and strain rate were measured. Intraoperator and intraobserver variability were examined and reference intervals were calculated. The potential effects of body weight, age and heart rate on these variables were examined. RESULTS: Intraoperator and intraobserver variability was <10% for all parameters except TDI E’ and 2DSTE variables, which were all <20%. Thirty-nine dogs were used to create reference intervals. Significant (but mostly weak) effects of age, heart rate and body weight on were detected. Reference intervals were similar to previously published values In different breeds. CLINICAL SIGNIFICANCE: Breed specific reference intervals for measures of longitudinal left ventricular function in the English springer spaniel are presented

Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise

PURPOSE: To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist and untwisting rate ('LV mechanics'). METHODS: LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double leg press exercise at two intensities (30% and 60% of maximum strength, 1-repetition-maximum, 1RM). Speckle tracking analysis generated LV strain, twist and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. RESULTS: Responses in both exercise trials were statistically similar (P > 0.05). During effort, stroke volume decreased while SVR and LV wall stress increased (P 0.05). Immediately following exercise, systolic LV mechanics returned to baseline levels (P < 0.05) but LV untwisting rate increased significantly (P < 0.05). CONCLUSIONS: A single, acute bout of double leg-press resistance exercise transiently reduces systolic LV mechanics, but increases diastolic mechanics following exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. exposure to high altitude (HA) challenges the cardiovascular system to meet the metabolic demand for oxygen (O2) in an environment where arterial O2 content is markedly reduced. The drop in arterial O2 has both direct and indirect consequences for the heart, including depressed inotropy of cardiac muscle (40, 44), changes in blood volume and viscosity, and vasoconstriction of the pulmonary arteries (33). Despite these broad physiological changes, which have been reviewed previously (28, 49), there is evidence that the heart copes relatively well at HA (29, 34). Short-term HA exposure in lowland natives is characterized by a decreased plasma volume (PV), an increased sympathetic nerve activity, and pulmonary vasoconstriction (17, 30, 37), all of which have considerable impact on cardiac function and in time, could stimulate cardiac remodeling. Himalayan native Sherpa, who are of Tibetan lineage and have resided at HA for ∼25,000 yr (2), are well adapted to life at HA, demonstrating greater lung-diffusing capacity (11) and an absence of polycythemia compared with acclimatized lowlanders (4). Previous studies have also reported Sherpa to have higher maximal heart rates (HRs) and only moderate pulmonary hypertension compared with lowlanders at HA (11, 25). Due to their longevity at HA, Sherpa provide an excellent model to investigate the effects of chronic hypoxic exposure. Despite this, neither the acute nor lifelong effects of HA on right- and left-ventricular (RV and LV, respectively) structure and function have been fully assessed in lowlanders or the unique Sherpa population. Due to the unique arrangement of myofibers, cardiac form and function are intrinsically linked, as reflected in the cardiac mechanics (LV twist and rotation and ventricular strain) that underpin ventricular function. In response to altered physiological demand, ventricular mechanics acutely change (16, 41) and chronically remodel (31, 42) to reduce myofiber stress and achieve efficient ejection (5, 47). Therefore, concomitant examination of myocardial mechanics and ventricular structure in both the acute and chronic HA setting will provide novel insight into human adaptation to hypoxia. To investigate the effects of chronic hypoxic exposure, we compared ventricular volumes and mechanics in Sherpa at 5,050 m with lowlanders at sea level (SL). In addition, to reveal potential stimuli for remodeling and to examine the time course of adaptation, we compared Sherpa with lowlanders after short-term HA exposure. We hypothesized that: 1) Sherpa would exhibit smaller LV volumes and a higher RV/LV ratio than lowlanders at SL, 2) LV mechanics in Sherpa will closely resemble those of lowlanders at SL, and 3) following partial acclimatization to HA, LV volumes would be reduced in lowlanders and LV mechanics acutely increased

The effect of an acute bout of resistance exercise on carotid artery strain and strain rate

Arterial wall mechanics likely play an integral role in arterial responses to acute physiological stress. Therefore, this study aimed to determine the impact of low and moderate intensity double-leg press exercise on common carotid artery (CCA) wall mechanics using 2D vascular strain imaging. Short-axis CCA ultrasound images were collected in 15 healthy men (age: 21 ± 3 years; stature: 176.5 ± 6.2 cm; body mass; 80.6 ± 15.3 kg) before, during, and immediately after short-duration isometric double-leg press exercise at 30% and 60% of participants’ one-repetition maximum (1RM: 317 ± 72 kg). Images were analyzed for peak circumferential strain (PCS), peak systolic and diastolic strain rate (S-SR and D-SR) and arterial diameter. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were simultaneously assessed and arterial stiffness indices were calculated post hoc. A two-way repeated measures ANOVA revealed that during isometric contraction, PCS and S-SR decreased significantly (P < 0.01) before increasing significantly above resting levels post-exercise (P < 0.05 and P < 0.01 respectively). Conversely, D-SR was unaltered throughout the protocol (P = 0.25). No significant differences were observed between the 30% and 60% 1RM trials. Multiple regression analysis highlighted that HR, BP and arterial diameter did not fully explain the total variance in PCS, S-SR and D-SR. Acute double-leg press exercise is therefore associated with similar transient changes in CCA wall mechanics at low and moderate intensities. CCA wall mechanics likely provide additional insight into localized intrinsic vascular wall properties beyond current measures of arterial stiffness

The independent effects of hypovolemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800 m

We aimed to determine the isolated and combined contribution of hypovolemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxemia at high altitude. In a double‐blinded, randomized and placebo‐controlled design, twelve healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5–10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of Sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values; high altitude (HA), Plasma Volume Expansion (HA‐PVX), Sildenafil (HA‐SIL) and Plasma Volume Expansion with Sildenafil (HA‐PVX‐SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end‐diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA‐PVX. LV EDV and SV were also elevated in the HA‐SIL and HA‐PVX‐SIL trials compared to HA, but to a lesser extent. Neither PVX or SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, however, restoring LV filling does not confer an improvement in maximal exercise performance

Impaired myocardial function does not explain reduced left ventricular filling and stroke volume at rest or during exercise at high altitude

Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end-diastolic volume was ∼19% lower at rest (P = 0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (∼17%; 60 ± 10 vs. 70 ± 8 ml) despite higher LV twist (43%), apical rotation (115%), and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely because of the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, although hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted. during initial exposure to hypobaric hypoxia at high altitude (HA), cardiac output for a given absolute workload is increased to compensate for a lower arterial oxygen content before returning to baseline levels with acclimatization (8). However, after 2-5 days of acclimatization, the required cardiac output is generated through a lower stroke volume (SV) and higher heart rate (38). The reduced SV is suggestive of either lower ventricular filling, potentially caused in part by an impaired myocardial relaxation, or impaired ejection secondary to systolic contractile dysfunction. There is, however, a paucity of data in humans supporting a direct effect of hypoxia on myocardial function at HA (25, 41). The suggestion that hypoxia may impair myocardial systolic function during exercise was proposed nearly 50 years ago (3) and has been revisited more recently (27–29). Negative inotropic effects of hypoxia (arterial oxygen tension of 44 mmHg) have been shown in intact animal models (39) and isolated myocardial fibers under severe hypoxia (1% O2) (33). Exercise training under hypobaric hypoxia is also associated with altered mechanical properties at a cellular level in rodents (9), although chronic hypoxia alone did not decrease myofilament sensitivity to calcium. However, in contrast to animal studies, data in humans indicate that systolic function is maintained or enhanced at HA. For example, Suarez et al. (37) reported the maintenance of systolic function after gradual decompression to a barometric pressure of 282 mmHg, a finding that was subsequently confirmed by numerous investigations during acute and prolonged hypoxic exposure (6, 10, 12, 23, 31). However, of these studies, only Suarez et al. (37) investigated systolic function during light exercise (60 W), where function appeared to be maintained. It is not known whether systolic function is maintained at higher exercise intensities. It has also been speculated that reduced oxygen availability may impair diastolic relaxation at HA (15, 18) and thus explain the decreased left ventricular (LV) end-diastolic volume (EDV) commonly observed (2, 6, 18). However, despite numerous studies reporting a decrease in plasma volume and altered transmitral filling patterns (2, 6, 20), myocardial relaxation was only previously investigated during hypoxia in dogs (15), and no data exist examining LV relaxation during exercise at high altitude. By using sensitive, noninvasive imaging techniques (two-dimensional speckle tracking), it is now possible to examine the LV deformation mechanics (strain, twist, and untwist velocity) that underpin LV systolic and diastolic function. LV strain and twist have been shown to be sensitive measures of global and regional myocardial function, and reveal subclinical dysfunction in patients where ejection fraction is unchanged (16, 22). In addition, diastolic LV untwist velocity correlates well with invasive measures of LV stiffness and provides a temporal link between relaxation and the development of intraventricular pressure gradients (30, 43). Therefore, examination of LV mechanics at HA may determine whether the decreased SV observed at HA is dependent on impaired myocardial relaxation and/or myocardial contractile dysfunction or confirm previous findings of preserved ventricular function during exercise (37). We therefore assessed systolic and diastolic ventricular mechanics during incremental exercise at sea level and HA to examine whether impaired myocardial relaxation or systolic dysfunction explains the previously reported reduction in SV at HA. We hypothesized that at HA, 1) ventricular filling would be lower at rest and during exercise and would be accompanied by a reduction in untwist velocity and 2) systolic mechanics would be impaired during exercise at HA

Carotid artery wall mechanics in young males with high cardiorespiratory fitness

The influence of cardiorespiratory fitness (CRF) on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, 2D strain imaging of the common carotid artery (CCA) provides novel information related to the intrinsic properties of the arterial wall. Therefore, this study aimed to assess the effect of CRF on both conventional indices of CCA stiffness and 2D strain parameters, at rest and following a bout of aerobic exercise in young healthy males. Short‐axis ultrasound images of the CCA were recorded in 34 healthy men [22 years (95%CI, 19–22)] before, and immediately after 5‐minutes of aerobic exercise (40% VO2max). Images were analysed for arterial diameter, peak circumferential strain (PCS), and peak systolic and diastolic strain rates (S‐SR, D‐SR). Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were simultaneously assessed and Petersons' elastic modulus (Ep) and Beta stiffness (β1) were calculated. Participants were separated post hoc into moderate and high fitness groups [VO2max: 48.9 ml.kg‐1 min‐1 (95%CI, 44.7–53.2) vs. 65.6 ml.kg‐1 min‐1 (95%CI, 63.1–68.1); P 0.13) but were elevated in the moderate‐fitness group post‐exercise (P 0.05). High‐fit individuals exhibit elevated CCA PCS and S‐SR, which may reflect training‐induced adaptations that help to buffer the rise in pulse‐pressure and stroke volume during exercise

The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives

In contrast to Andean natives, high altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e. no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also elevated in Sherpa compared to lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and towards a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude

P194: Cardiovascular Responses to Increased Pressure During Healthy Pregnancy

A long-standing question is whether pregnant females, who bear an increased biological stress, experience exacerbated cardiovascular responses during physiological challenge. At rest, pregnant females have reduced blood pressure, increased cardiac output, heart rate and stroke volume (1), with reported reductions in cardiac contraction and relaxation (2). Increased cardiac work may potentially exasperate impairments in function observed at rest. The aim of this study was to investigate the cardiovascular responses to an isolated increase in pressure in healthy nulliparous non-pregnant, primiparous pregnant (22–26 weeks gestation; n = 14) and primiparous postpartum (12–16 weeks after delivery; n = 13) females. The pressure challenge was elicited through a sustained isometric hold for approximately 5 minutes at 30% of maximum using an externally loaded handgrip dynamometer. Echocardiographic images were collected to measure cardiac volumes and mechanics. Blood pressure was monitored continuously using finger photoplethysmography. Analyses of covariance, with baseline measures as covariate, were completed to determine differences between groups (P = <0.05). Post hoc analyses were performed with a Bonferroni adjustment. There were no significant differences between groups in cardiac volumes or blood pressure during the challenge however; pregnant females had a greater heart rate (68 ± 2 versus 62 ± 2 beats min−1) and longitudinal strain (−20.6 ± 1.0% versus −17.1 ± 0.7%) than non-pregnant females. Increased longitudinal strain and heart rate are likely result of increased contractility mediated by greater myocardial sympathetic innervation (3). In healthy pregnant females, increased pressure does not result in impaired cardiovascular function, however dysfunctional responses may predict hypertensive disorders of pregnancy

Cardiac structure and function in adolescent Sherpa; effect of habitual altitude and developmental stage

The purpose of this study was to examine ventricular structure and function in Sherpa adolescents to determine whether age-specific differences in oxygen saturation (S