Distinct hemodynamic responses to (pyr)apelin-13 in large animal models

Johnathan D. Tune; Hana E. Baker; Zachary Berwick; Steven P. Moberly; Eli D. Casalini; Jillian N. Noblet; Eugene Zhen; Mark C. Kowala; Michael E. Christe; Adam G. Goodwill

doi:10.1152/ajpheart.00365.2019

Distinct hemodynamic responses to (pyr)apelin-13 in large animal models

Johnathan D. Tune, Hana E. Baker, Zachary Berwick, Steven P. Moberly, Eli D. Casalini, Jillian N. Noblet, Eugene Zhen, Mark C. Kowala, Michael E. Christe, Adam G. Goodwill

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dt_max (P = 0.26), or dP/dt_min (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P < 0.01), which was accompanied by a significant increase in coronary blood flow (P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P < 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow (P = 0.83) or vasorelaxation in isolated, endothelium-intact (P = 0.89) or denuded (P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs (P < 0.001; R² = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species (P < 0.001; R² = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs. NEW & NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.

Original language	English
Pages (from-to)	H747-H755
Journal	American Journal of Physiology - Heart and Circulatory Physiology
Volume	318
Issue number	4
DOIs	https://doi.org/10.1152/ajpheart.00365.2019
State	Published - Apr 2020

Keywords

Apelin
Coronary blood flow
Dog
Inotropy
Pig

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10.1152/ajpheart.00365.2019

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@article{b087d13b747d4f58842d715e81403e97,

title = "Distinct hemodynamic responses to (pyr)apelin-13 in large animal models",

abstract = "This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dtmax (P = 0.26), or dP/dtmin (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P < 0.01), which was accompanied by a significant increase in coronary blood flow (P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P < 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow (P = 0.83) or vasorelaxation in isolated, endothelium-intact (P = 0.89) or denuded (P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs (P < 0.001; R2 = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species (P < 0.001; R2 = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs. NEW & NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.",

keywords = "Apelin, Coronary blood flow, Dog, Inotropy, Pig",

author = "Tune, {Johnathan D.} and Baker, {Hana E.} and Zachary Berwick and Moberly, {Steven P.} and Casalini, {Eli D.} and Noblet, {Jillian N.} and Eugene Zhen and Kowala, {Mark C.} and Christe, {Michael E.} and Goodwill, {Adam G.}",

note = "Funding Information: This work was supported by Eli Lilly and Company and American Heart Association Grant 13POST16810018 (to A. G. Goodwill). Publisher Copyright: Copyright {\textcopyright} 2020 the American Physiological Society",

year = "2020",

month = apr,

doi = "10.1152/ajpheart.00365.2019",

language = "English",

volume = "318",

pages = "H747--H755",

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T1 - Distinct hemodynamic responses to (pyr)apelin-13 in large animal models

AU - Tune, Johnathan D.

AU - Baker, Hana E.

AU - Berwick, Zachary

AU - Moberly, Steven P.

AU - Casalini, Eli D.

AU - Noblet, Jillian N.

AU - Zhen, Eugene

AU - Kowala, Mark C.

AU - Christe, Michael E.

AU - Goodwill, Adam G.

N1 - Funding Information: This work was supported by Eli Lilly and Company and American Heart Association Grant 13POST16810018 (to A. G. Goodwill). Publisher Copyright: Copyright © 2020 the American Physiological Society

PY - 2020/4

Y1 - 2020/4

N2 - This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dtmax (P = 0.26), or dP/dtmin (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P < 0.01), which was accompanied by a significant increase in coronary blood flow (P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P < 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow (P = 0.83) or vasorelaxation in isolated, endothelium-intact (P = 0.89) or denuded (P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs (P < 0.001; R2 = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species (P < 0.001; R2 = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs. NEW & NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.

AB - This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dtmax (P = 0.26), or dP/dtmin (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P < 0.01), which was accompanied by a significant increase in coronary blood flow (P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P < 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow (P = 0.83) or vasorelaxation in isolated, endothelium-intact (P = 0.89) or denuded (P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs (P < 0.001; R2 = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species (P < 0.001; R2 = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs. NEW & NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.

KW - Apelin

KW - Coronary blood flow

KW - Dog

KW - Inotropy

KW - Pig

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U2 - 10.1152/ajpheart.00365.2019

DO - 10.1152/ajpheart.00365.2019

M3 - Article

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AN - SCOPUS:85081946482

SN - 0363-6135

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JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

IS - 4

ER -

Distinct hemodynamic responses to (pyr)apelin-13 in large animal models

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