Michinari Hieda

Effect of increases in cardiac contractility on cerebral blood flow in humans

The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine [first a low dose (5 μg·kg-1·min-1) and then a high dose (15 μg·kg-1·min-1)] for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA, and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output, and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low- and high-dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low- and high-dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect overperfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion attributable to dobutamine administration does not cause cerebral overperfusion or an associated risk of cerebral vascular damage.NEW & NOTEWORTHY A dobutamine-induced increase in cardiac contractility did not increase internal carotid artery blood flow despite an increase in cardiac output and arterial blood pressure. In contrast, external carotid artery blood flow and conductance increased. This external cerebral blood flow response may assist with protecting from overperfusion of intracranial blood flow.

Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether the LVEDP-SV relationship remained impaired in heart failure with preserved ejection fraction (HFpEF) patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower-body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls ( n = 12) (HFpEF vs. CONTROLS 10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m-2·mmHg-1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

Effects of Sedentary Aging and Lifelong Exercise on Left Ventricular Systolic Function

PurposeThe current study examined whether age-related changes in left ventricular (LV) longitudinal systolic function is an adaptation to a more sedentary lifestyle and can be preserved by lifelong exercise training. MethodsA cross-sectional examination of 18 sedentary young (37 ± 6 yr), 29 sedentary seniors (71 ± 5 yr, 0–3 exercise sessions per week), and 26 seniors (68 ± 5 yr) who had performed a committed level (four to seven exercise sessions per week) of lifelong (>25 yr) exercise. Invasive right heart catheterization (pulmonary capillary wedge pressure) and noninvasive measures of LV function were collected at the following conditions: 1) supine rest, 2) during LV unloading (lower body negative pressure), and 3) LV loading (saline infusion). Ejection fraction and preload-recruitable stroke work (PRSW) were used to describe global LV systolic function, while peak systolic tissue velocity and longitudinal strain (LS) indicate LV longitudinal systolic function. To adjust LS for aging and training-related differences in LV preload and afterload, LV end-diastolic volume and end-systolic pressure (ESP) were included as covariates in ANCOVA models. ResultsEjection fraction and PRSW were unaffected by aging or lifelong exercise (P = 0.22, P = 0.08, respectively). Peak systolic tissue velocities decreased with aging (P < 0.001) and sedentary seniors had a smaller LS compared with young (P = 0.023) and lifelong exercisers (P = 0.046). Preload-recruitable stroke work, ESP as a covariate did not alter group differences; however, LV end-diastolic volume eliminated group differences between senior groups. Longitudinal strain was preload dependent (P < 0.001), which was independent of aging and lifelong exercise. ConclusionsSedentary aging leads to a reduction in systolic LS, which is attenuated by committed lifelong exercise due to improved LV diastolic filling.

Left ventricular remodeling and arterial afterload in older women with uncontrolled and controlled hypertension

Objective: The prevalence of hypertension increases with advancing age in women. Blood pressure control is more difficult to achieve in older women, and despite well-controlled blood pressure, the cardiovascular mortality remains high. However, the underlying mechanisms are not understood. Methods: Nineteen women with uncontrolled hypertension on drug treatment (70 ± 2 [SE] years, ambulatory awake blood pressure; 152 ± 2/84 ± 2 mm Hg), 19 with controlled hypertension (68 ± 1 years, 128 ± 2/71 ± 2 mm Hg), and 31 healthy normotensive women (68 ± 1 years, 127 ± 1/73 ± 1 mm Hg) were recruited. Participants were weaned from antihypertensive drugs and underwent 3 weeks of run-in before cardiac-vascular assessments. Left ventricular morphology was evaluated with cardiac magnetic resonance imaging. Arterial load and vascular stiffness were measured via ultrasound and applanation tonometry. Results: Left ventricular mass normalized by body surface area was not different between hypertension groups (uncontrolled vs controlled: 50.0 ± 1.7 vs 51.8 ± 2.3 g/m2), but it was lower in the normotensive group (41.7 ± 0.9 g/m2; one-way analysis of variance [ANOVA] P = 0.004). Likewise, central pulse wave velocity was not different between hypertension groups (11.5 ± 0.6 vs 11.1 ± 0.5 m/s) and lower in the normotensive group (9.1 ± 0.3 m/s; 1-way ANOVA P = 0.0001). Total peripheral resistance was greater in uncontrolled hypertension (HTN) compared with normotensive group (2051 ± 323 vs 1719 ± 380 dyn*s/cm5), whereas controlled HTN group (1925 ± 527 dyn*s/cm5) was not different to either groups. Conclusion: Regardless of current blood pressure control, hypertensive older women exhibited increased cardiac mass and arterial stiffness compared with normotensives. Future large-scale longitudinal studies are warranted to directly investigate the mechanisms for the high cardiovascular mortality among older hypertensive women with well-controlled blood pressure.

Left Ventricular Volume-Time Relation in Patients With Heart Failure With Preserved Ejection Fraction

Elevated left ventricular (LV) filling pressures are commonly reported in patients with heart failure with preserved ejection fraction (HFpEF) and are associated with impaired relaxation in diastole. Relaxation has been assessed by Doppler, but the methods for doing so are indirect and heavily influenced by loading conditions. The aim of this study is to assess LV volume-time relation in patients with HFpEF, when correcting for left atrial driving pressure and chamber size, using cardiac magnetic resonance imaging (cMRI). Cine short-axis views by cMRI (1.5T-magnet) at 26 Hz were used for measurement of LV volume. We compared the following diastolic parameters: peak filling rate/end-diastolic volume (PFR/EDV); PFR/EDV/pulmonary capillary wedge pressure (PFR/EDV/PCWP); time to PFR (TPFR); and %TPFR for cardiac cycle calculated by cMRI between patients with HFpEF (n = 10, 73 ± 7 years) and age-matched controls (n = 12, 70 ± 3 years). PCWP was significantly greater in the HFpEF group than in controls (HFpEF vs controls: 15.6 ± 5.2 vs 11.2 ± 1.3 mmHg, p = 0.0092). PFR/EDV was significantly slower in the HFpEF group than in controls (2.68 ± 0.85 vs 3.59 ± 0.87/s, p = 0.03), and was nearly 50% slower when corrected for left atrial driving pressure: PFR/EDV/PCWP (0.18 ± 0.07 vs 0.33 ± 0.10/s/mmHg, p = 0.002). In addition, TPFR (246 ± 17.2 vs 188 ± 15.7 ms, p = 0.04) and %TPFR of cardiac cycle (36.4 ± 10.4 vs 25.6 ± 5.9%, p = 0.012) were significantly longer in the HFpEF group than in controls. Patients with HFpEF have an abnormal volume-time relation, including lower PFR/EDV (PFR/EDV/PCWP) and prolonged TPFR, due to the impairment of active relaxation during early diastole.