Vascular Endothelial Growth Factor Improves Myocardial Functional Recovery Following Ischemia/Reperfusion Injury

Michael J. Guzman, Paul R. Crisostomo, Meijing Wang, Troy A. Markel, Yue Wang, Daniel R. Meldrum

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery. Materials and methods: Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3× physiological (13 nm, n = 4), 5× physiological (20 nm, n = 4), or 10× physiological (40 nm, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, ±dP/dt were continuously recorded. Results: End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10× VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 ± 10.35 mmHg versus 80.73 ± 6.08 mmHg at end reperfusion). 10× VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 ± 9.69% versus 39.74 ± 7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3× nor 5× VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia. Conclusion: This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value.

Original languageEnglish
Pages (from-to)286-292
Number of pages7
JournalJournal of Surgical Research
Volume150
Issue number2
DOIs
StatePublished - Dec 2008

Fingerprint

Reperfusion Injury
Vascular Endothelial Growth Factor A
Ischemia
Reperfusion
Ventricular Pressure
Blood Pressure
Myocardium
Analysis of Variance
Stem Cells
Warm Ischemia
Endothelium
Sprague Dawley Rats
Intercellular Signaling Peptides and Proteins

Keywords

  • cardiac
  • I/R
  • stem cell paracrine
  • VEGF

ASJC Scopus subject areas

  • Surgery

Cite this

Vascular Endothelial Growth Factor Improves Myocardial Functional Recovery Following Ischemia/Reperfusion Injury. / Guzman, Michael J.; Crisostomo, Paul R.; Wang, Meijing; Markel, Troy A.; Wang, Yue; Meldrum, Daniel R.

In: Journal of Surgical Research, Vol. 150, No. 2, 12.2008, p. 286-292.

Research output: Contribution to journalArticle

Guzman, Michael J. ; Crisostomo, Paul R. ; Wang, Meijing ; Markel, Troy A. ; Wang, Yue ; Meldrum, Daniel R. / Vascular Endothelial Growth Factor Improves Myocardial Functional Recovery Following Ischemia/Reperfusion Injury. In: Journal of Surgical Research. 2008 ; Vol. 150, No. 2. pp. 286-292.
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abstract = "Background: Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery. Materials and methods: Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3× physiological (13 nm, n = 4), 5× physiological (20 nm, n = 4), or 10× physiological (40 nm, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, ±dP/dt were continuously recorded. Results: End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10× VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 ± 10.35 mmHg versus 80.73 ± 6.08 mmHg at end reperfusion). 10× VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 ± 9.69{\%} versus 39.74 ± 7.01{\%} of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3× nor 5× VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia. Conclusion: This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value.",
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T1 - Vascular Endothelial Growth Factor Improves Myocardial Functional Recovery Following Ischemia/Reperfusion Injury

AU - Guzman, Michael J.

AU - Crisostomo, Paul R.

AU - Wang, Meijing

AU - Markel, Troy A.

AU - Wang, Yue

AU - Meldrum, Daniel R.

PY - 2008/12

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N2 - Background: Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery. Materials and methods: Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3× physiological (13 nm, n = 4), 5× physiological (20 nm, n = 4), or 10× physiological (40 nm, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, ±dP/dt were continuously recorded. Results: End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10× VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 ± 10.35 mmHg versus 80.73 ± 6.08 mmHg at end reperfusion). 10× VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 ± 9.69% versus 39.74 ± 7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3× nor 5× VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia. Conclusion: This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value.

AB - Background: Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery. Materials and methods: Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3× physiological (13 nm, n = 4), 5× physiological (20 nm, n = 4), or 10× physiological (40 nm, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, ±dP/dt were continuously recorded. Results: End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10× VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 ± 10.35 mmHg versus 80.73 ± 6.08 mmHg at end reperfusion). 10× VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 ± 9.69% versus 39.74 ± 7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3× nor 5× VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia. Conclusion: This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value.

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