Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion

Birgitte S. Kousholt, Jens K Rolighed Larsen, Line Bisgaard, John C Jr. Burnett, John Michael Hasenkam, Jens P. Goetze

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aim The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia-reperfusion damage. Materials and methods The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect was determined by assessment of intracellular caspase activity and troponin T release from cultured HL-1 cells subjected to short-term hypoxia-reperfusion. Cardiac effects were further examined in pigs (n =25) that had been subjected to 1 h of regional cardiac ischemia, followed by 3 h of reperfusion. Results HL-1 cardiomyocytes responded to exogenous BNP with increased cGMP activity (~3-fold, P = 0.0037) and hypoxia-reperfusion with increased vascular endothelial growth factor and BNPmRNA contents (2.3- and 2.5-fold, respectively, P <0.0001) and caspase activity (2.9-fold, P = 0.03), but without a decrease in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (~15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared with controls (P= 0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P = 0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P = 0.0015 and 0.0019), and were associated with improved RNA integrity in the ischemic left ventricular region (P <0.05). Conclusion We report that natriuretic peptide infusion in vivo reduces cardiomyocyte injury in acute ischemia-reperfusion, possibly through indirect mechanisms (e.g. increased diuresis and vasodilation). The results suggest a role for natriuretic peptide therapy in human cardiac ischemia. Cardiovasc Endocrinol 1:4-12

Original languageEnglish (US)
Pages (from-to)4-12
Number of pages9
JournalCardiovascular Endocrinology
Volume1
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Natriuretic Peptides
Brain Natriuretic Peptide
Reperfusion
Ischemia
Swine
Wounds and Injuries
Cardiac Myocytes
Troponin T
Diuresis
Caspases
Ventricular Pressure
Reperfusion Injury
Vasodilation
Vascular Endothelial Growth Factor A
RNA
Blood Pressure

Keywords

  • BNP
  • CD-NP
  • Ischemia-reperfusion injury
  • Myocardial infarction
  • Porcine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Endocrine and Autonomic Systems

Cite this

Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion. / Kousholt, Birgitte S.; Larsen, Jens K Rolighed; Bisgaard, Line; Burnett, John C Jr.; Hasenkam, John Michael; Goetze, Jens P.

In: Cardiovascular Endocrinology, Vol. 1, No. 1, 2012, p. 4-12.

Research output: Contribution to journalArticle

Kousholt, Birgitte S. ; Larsen, Jens K Rolighed ; Bisgaard, Line ; Burnett, John C Jr. ; Hasenkam, John Michael ; Goetze, Jens P. / Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion. In: Cardiovascular Endocrinology. 2012 ; Vol. 1, No. 1. pp. 4-12.
@article{8be12ebce70643168c501a3ba6662707,
title = "Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion",
abstract = "Aim The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia-reperfusion damage. Materials and methods The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect was determined by assessment of intracellular caspase activity and troponin T release from cultured HL-1 cells subjected to short-term hypoxia-reperfusion. Cardiac effects were further examined in pigs (n =25) that had been subjected to 1 h of regional cardiac ischemia, followed by 3 h of reperfusion. Results HL-1 cardiomyocytes responded to exogenous BNP with increased cGMP activity (~3-fold, P = 0.0037) and hypoxia-reperfusion with increased vascular endothelial growth factor and BNPmRNA contents (2.3- and 2.5-fold, respectively, P <0.0001) and caspase activity (2.9-fold, P = 0.03), but without a decrease in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (~15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared with controls (P= 0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P = 0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40{\%}, respectively (P = 0.0015 and 0.0019), and were associated with improved RNA integrity in the ischemic left ventricular region (P <0.05). Conclusion We report that natriuretic peptide infusion in vivo reduces cardiomyocyte injury in acute ischemia-reperfusion, possibly through indirect mechanisms (e.g. increased diuresis and vasodilation). The results suggest a role for natriuretic peptide therapy in human cardiac ischemia. Cardiovasc Endocrinol 1:4-12",
keywords = "BNP, CD-NP, Ischemia-reperfusion injury, Myocardial infarction, Porcine",
author = "Kousholt, {Birgitte S.} and Larsen, {Jens K Rolighed} and Line Bisgaard and Burnett, {John C Jr.} and Hasenkam, {John Michael} and Goetze, {Jens P.}",
year = "2012",
doi = "10.1097/XCE.0b013e328356c67b",
language = "English (US)",
volume = "1",
pages = "4--12",
journal = "Cardiovascular Endocrinology and Metabolism",
issn = "2574-0954",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "1",

}

TY - JOUR

T1 - Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion

AU - Kousholt, Birgitte S.

AU - Larsen, Jens K Rolighed

AU - Bisgaard, Line

AU - Burnett, John C Jr.

AU - Hasenkam, John Michael

AU - Goetze, Jens P.

PY - 2012

Y1 - 2012

N2 - Aim The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia-reperfusion damage. Materials and methods The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect was determined by assessment of intracellular caspase activity and troponin T release from cultured HL-1 cells subjected to short-term hypoxia-reperfusion. Cardiac effects were further examined in pigs (n =25) that had been subjected to 1 h of regional cardiac ischemia, followed by 3 h of reperfusion. Results HL-1 cardiomyocytes responded to exogenous BNP with increased cGMP activity (~3-fold, P = 0.0037) and hypoxia-reperfusion with increased vascular endothelial growth factor and BNPmRNA contents (2.3- and 2.5-fold, respectively, P <0.0001) and caspase activity (2.9-fold, P = 0.03), but without a decrease in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (~15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared with controls (P= 0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P = 0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P = 0.0015 and 0.0019), and were associated with improved RNA integrity in the ischemic left ventricular region (P <0.05). Conclusion We report that natriuretic peptide infusion in vivo reduces cardiomyocyte injury in acute ischemia-reperfusion, possibly through indirect mechanisms (e.g. increased diuresis and vasodilation). The results suggest a role for natriuretic peptide therapy in human cardiac ischemia. Cardiovasc Endocrinol 1:4-12

AB - Aim The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia-reperfusion damage. Materials and methods The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect was determined by assessment of intracellular caspase activity and troponin T release from cultured HL-1 cells subjected to short-term hypoxia-reperfusion. Cardiac effects were further examined in pigs (n =25) that had been subjected to 1 h of regional cardiac ischemia, followed by 3 h of reperfusion. Results HL-1 cardiomyocytes responded to exogenous BNP with increased cGMP activity (~3-fold, P = 0.0037) and hypoxia-reperfusion with increased vascular endothelial growth factor and BNPmRNA contents (2.3- and 2.5-fold, respectively, P <0.0001) and caspase activity (2.9-fold, P = 0.03), but without a decrease in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (~15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared with controls (P= 0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P = 0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P = 0.0015 and 0.0019), and were associated with improved RNA integrity in the ischemic left ventricular region (P <0.05). Conclusion We report that natriuretic peptide infusion in vivo reduces cardiomyocyte injury in acute ischemia-reperfusion, possibly through indirect mechanisms (e.g. increased diuresis and vasodilation). The results suggest a role for natriuretic peptide therapy in human cardiac ischemia. Cardiovasc Endocrinol 1:4-12

KW - BNP

KW - CD-NP

KW - Ischemia-reperfusion injury

KW - Myocardial infarction

KW - Porcine

UR - http://www.scopus.com/inward/record.url?scp=84889600415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84889600415&partnerID=8YFLogxK

U2 - 10.1097/XCE.0b013e328356c67b

DO - 10.1097/XCE.0b013e328356c67b

M3 - Article

AN - SCOPUS:84889600415

VL - 1

SP - 4

EP - 12

JO - Cardiovascular Endocrinology and Metabolism

JF - Cardiovascular Endocrinology and Metabolism

SN - 2574-0954

IS - 1

ER -