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May 4, 2018AJP Heart and Circulatory Physiology

Acute stimulation of the soluble guanylate cyclase does not impact on left ventricular capacitance in normal and hypertrophied porcine hearts in vivo

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Why the study?

Does acute pharmacological sGC stimulation with BAY 41-8543 increase LV capacitance via titin phosphorylation in healthy and DOCA-induced hypertensive pigs?

Population

9 healthy Landrace pigs and 7 pigs with deoxycorticosteroneacetate-induced hypertension and LV concentric…

Comparison

Intravenous infusion of BAY 41-8543 vs Baseline (before infusion)

Design

Preclinical

Follow-up

30 min

Key result

Acute pharmacological stimulation of soluble guanylate cyclase with BAY 41-8543 did not increase left ventricular compliance in normal and hypertrophied porcine hearts.

Authors

AAAlessio AlognaMSMichael SchwarzlMMMartin Manninger

Discussion

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Member takes

Overview

Does not support acute sGC stimulation to improve LV compliance; leaves open whether titin phosphorylation affects capacitance in other models or species.

Structured PICO

Does acute pharmacological sGC stimulation with BAY 41-8543 increase LV capacitance via titin phosphorylation in healthy and DOCA-induced hypertensive pigs?

P
Population
9 healthy Landrace pigs and 7 pigs with deoxycorticosteroneacetate (DOCA)-induced hypertension and LV concentric hypertrophy (for EDPVRs); separately 7 healthy and 6 DOCA pigs for biopsies; and 5 healthy pigs for nitroglycerin infusion.
I
Intervention
Intravenous infusion of BAY 41-8543 (1 and 3 μg·kg−1·min−1 for 30 min, respectively)
C
Comparator
Baseline (before infusion)
O
Outcome
Left ventricular end-diastolic pressure-volume relationships (EDPVRs)surrogate

Acute pharmacological stimulation of soluble guanylate cyclase does not increase left ventricular compliance in normal and hypertrophied porcine hearts, indicating that increased titin phosphorylation does not necessarily translate to increased in vivo LV capacitance.

Limitations

  • Effects of long-term soluble guanylate cyclase stimulation with oral compounds in disease conditions remain to be investigated.

Cite This Study

Alogna et al. (2018) studied Healthy and DOCA-induced hypertension with LV concentric hypertrophy (n=34). BAY 41-8543 vs. Baseline was evaluated on Left ventricular end-diastolic pressure-volume relationships (EDPVRs). Acute pharmacological stimulation of soluble guanylate cyclase with BAY 41-8543 did not increase left ventricular compliance in normal and hypertrophied porcine hearts.

synapsesocial.com/papers/6a1c12f9d54006be995f813ahttps://doi.org/10.1152/ajpheart.00510.2017
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