Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.

Background: Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI.

Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction.

Background: The PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity.

Objectives: The aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies.

Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial.

Background: Abnormalities in cardiac structure and function in heart failure with preserved ejection fraction may help identify patients at particularly high risk for cardiovascular morbidity and mortality.

Methods And Results: Cardiac structure and function were assessed by echocardiography in a blinded core laboratory at baseline in 935 patients with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial and related to the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest, and its components. At a median follow-up of 2.

Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial.

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggest significant heterogeneity in this population.

Methods And Results: Echocardiograms were obtained from 935 patients with HFpEF (left ventricular ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial before initiation of randomized therapy.

Enhanced hemeoxygenase activity in the rostral ventrolateral medulla mediates exaggerated hemin-evoked hypotension in the spontaneously hypertensive rat.

In anesthetized normotensive rats, activation of brainstem hemeoxygenase (HO) elicits sympathoinhibition and hypotension. Accordingly, we tested the hypothesis that attenuated basal or induced HO activity in the rostral ventrolateral medulla (RVLM) contributes to hypertension in the spontaneously hypertensive rat (SHR). We measured basal RVLM HO expression and catalytic activity and investigated the effects of intra-RVLM HO activation (hemin) or selective HO isoform 1 (HO-1) inhibition [zinc protoporphyrin IX (ZnPPIX)] on mean arterial pressure (MAP), heart rate, and RVLM neuronal norepinephrine (NE) level (index of sympathetic activity) in conscious SHRs and Wistar Kyoto rats.

Estrogen-dependent enhancement of NO production in the nucleus tractus solitarius contributes to ethanol-induced hypotension in conscious female rats.

Background: Our previous pharmacological and cellular studies showed that peripheral (cardiac and vascular) nitric oxide synthase (NOS)-derived NO is implicated in the estrogen (E(2))-dependent hypotensive action of ethanol in female rats. The objective of this study was to test the hypothesis that enhanced NO production in the nucleus tractus solitarius (NTS) is implicated in the E(2)-dependent hypotensive action of ethanol.

Methods: To achieve this goal, we utilized in vivo electrochemistry to measure real time changes in neuronal NO to investigate the acute effects of intragastric ethanol (0, 0.

Direct evidence for imidazoline (I1) receptor modulation of ethanol action on norepinephrine-containing neurons in the rostral ventrolateral medulla in conscious spontaneously hypertensive rats.

Background: Enhancement of the rostral ventrolateral medulla (RVLM) presympathetic (norepinephrine, NE) neuronal activity represents a neurochemical mechanism for the pressor effect of ethanol. In this study, we tested the hypothesis that ethanol action on RVLM presympathetic neurons is selectively influenced by the signaling of the local imidazoline (I1) receptor. To support a neuroanatomical and an I1-signaling selectivity of ethanol, and to circumvent the confounding effects of anesthesia, the dose-related neurochemical and blood pressure effects of ethanol were investigated in the presence of selective pharmacological interventions that cause reduction in the activity of RVLM or nucleus tractus solitarius (NTS) NE neurons via local activation of the I1 or the alpha2-adrenergic receptor in conscious spontaneously hypertensive rats.

Neuronal norepinephrine responses of the rostral ventrolateral medulla and nucleus tractus solitarius neurons distinguish the I1- from the alpha2-receptor-mediated hypotension in conscious SHRs.

We tested the hypothesis that the I1 receptor mediates the reduction in rostral ventrolateral medulla (RVLM) neuronal norepinephrine (NE; index of sympathetic activity) that leads to hypotension independent of other brainstem areas or the alpha2-adrenergic receptor. To this end, we developed a model that permitted measurement of real-time changes in neuronal NE in the RVLM or nucleus tractus solitarius (NTS) along with blood pressure and heart rate in the conscious SHR in response to localized microinjections of selective I1 (rilmenidine) or alpha2-adrenergic (alpha-methylnorepinephrine; alpha-MNE) agonist versus the mixed I1/alpha2 agonist clonidine. To further support the hypothesis, we investigated the effects of localized selective alpha2- (SK&F86466) or I1 (efaroxan) blockade on the reductions in neuronal NE and blood pressure elicited by intra-RVLM rilmenidine.

Site-dependent inhibition of neuronal c-jun in the brainstem elicited by imidazoline I1 receptor activation: role in rilmenidine-evoked hypotension.

Clonidine (a mixed alpha2-adrenoceptor and imidazoline I1 receptor agonist)-evoked hypotension was associated with dissimilar reductions in c-jun gene expression in the rostral ventrolateral medulla (RVLM) and the nucleus tractus solitarius (NTS) in normotensive rats. In the present study, we investigated the relative contribution of the alpha2-adrenoceptor vs. the imidazoline I1 receptor to the reduction in c-jun gene expression in these two brainstem areas.

Brainstem norepinephrine neurons mediate ethanol-evoked pressor response but not baroreflex dysfunction.

Background: Ethanol elicits strain-dependent blood pressure and baroreflex sensitivity responses in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats; the mechanisms underlying these divergent effects are not clear. The authors tested the hypothesis that differential neuronal actions of ethanol may account for these strain-dependent responses. To this end, the authors investigated the direct effects of ethanol on norepinephrine (NE)-containing neurons in the rostral ventrolateral medulla (RVLM), which modulate sympathetic neuronal activity, and on c-Jun-expressing neurons in the nucleus tractus solitarius (NTS), whose activity is inversely correlated with baroreflex sensitivity.

Effect of ethanol on reductions in norepinephrine electrochemical signal in the rostral ventrolateral medulla and hypotension elicited by I1-receptor activation in spontaneously hypertensive rats.

The mechanism of the antagonistic hemodynamic interaction between ethanol and centrally acting sympatholytics is not known. In this study, we tested the hypothesis that the imidazoline (I1)-receptor modulation of norepinephrine (NE) release within the rostral ventrolateral medulla (RVLM) plays a pivotal role in this clinically relevant hemodynamic interaction. METHOD In anesthetized spontaneously hypertensive rats, the effects of centrally acting sympatholytics on RVLM NE electrochemical signal were investigated by in vivo electrochemistry along with cardiovascular responses in the absence and presence of ethanol.