Functional outcome of new blood vessel growth into ischemic skeletal muscle

Steven L. Lee, William C Pevec, Richard C. Carlsen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: The administration of angiogenic growth factors and the transfer of well-vascularized tissues have been shown to induce development of new blood vessels in ischemic muscle. The functional significance of these new vessels is unknown. The hypothesis of this study is that the transfer of vascularized muscle and the local infusion of basic fibroblast growth factor (bFGF) synergistically improve contractile function of ischemic skeletal muscle. Methods: Twenty-six rabbits were divided into four groups. An ischemic hindlimb was created in each by ligating the right common iliac artery. The flap + bFGF group (n = 6) had transposition of a contralateral rectus muscle flap onto the thigh. Additionally, bFGF (3 ng/h) was continuously infused at the flap-thigh interface. In the flap group (n = 6), a similar muscle flap was created, but carrier solution was infused at the interface. In the bFGF group (n = 6), no muscle flap was created; instead, bFGF (3 ng/h) was infused into the external iliac artery of the ischemic limb. In the control group (n = 8), carrier solution was infused into the external iliac artery (no flap, no bFGF). After 1 week, the soleus muscle was isolated and stimulated. Maximum twitch tension, the fatigue index (force of contraction after 2 minutes of continuous stimulation/initial force of contraction), maximum recovery, and the number of limbs recovered (ie, limbs that achieve a force of contraction during the recovery period of > 75% of the force of the initial contraction at the start of continuous stimulation) were recorded. Blood vessel density (number of vessels per •••) was determined by immunostaining the soleus muscle with anti-α-actin antibody. Results: All values were indexed to the contralateral normal limb. The flap + bFGF group showed significant improvement versus the control group in maximum twitch tension (1.07 ± 0.13 vs 0.63 ± 0.12, P < .05), maximum recovery (0.94 ± 0.05 vs 0.58 ± 0.05, P < .05), and the number of limbs recovered (5/5 vs 0/6, P < .05). This improved function correlated with increased vessel density (flap + bFGF group, 1.44 ± 0.11 vs control group, 0.72 ± 0.01, P < .05). Conclusion: Reperfusion of an ischemic limb with a well-vascularized muscle flap and local bFGF infusion promoted increased blood vessel density in distal ischemic muscle. This increased vascularity was associated with restoration of otherwise impaired muscle function. Improved function occurred rapidly (1 week). A transposed muscle flap provided a functional blood supply to the site of maximum ischemia; this could be used to salvage otherwise nonreconstructible ischemic limbs.

Original languageEnglish (US)
Pages (from-to)1096-1102
Number of pages7
JournalJournal of Vascular Surgery
Volume34
Issue number6
DOIs
StatePublished - Dec 2001

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Fibroblast Growth Factor 2
Blood Vessels
Skeletal Muscle
Muscles
Extremities
Growth
Iliac Artery
Fibroblast Growth Factor 3
Thigh
Control Groups
Angiogenesis Inducing Agents
Hindlimb
Reperfusion
Fatigue
Actins
Anti-Idiotypic Antibodies
Intercellular Signaling Peptides and Proteins
Ischemia
Rabbits

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Functional outcome of new blood vessel growth into ischemic skeletal muscle. / Lee, Steven L.; Pevec, William C; Carlsen, Richard C.

In: Journal of Vascular Surgery, Vol. 34, No. 6, 12.2001, p. 1096-1102.

Research output: Contribution to journalArticle

Lee, Steven L. ; Pevec, William C ; Carlsen, Richard C. / Functional outcome of new blood vessel growth into ischemic skeletal muscle. In: Journal of Vascular Surgery. 2001 ; Vol. 34, No. 6. pp. 1096-1102.
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abstract = "Purpose: The administration of angiogenic growth factors and the transfer of well-vascularized tissues have been shown to induce development of new blood vessels in ischemic muscle. The functional significance of these new vessels is unknown. The hypothesis of this study is that the transfer of vascularized muscle and the local infusion of basic fibroblast growth factor (bFGF) synergistically improve contractile function of ischemic skeletal muscle. Methods: Twenty-six rabbits were divided into four groups. An ischemic hindlimb was created in each by ligating the right common iliac artery. The flap + bFGF group (n = 6) had transposition of a contralateral rectus muscle flap onto the thigh. Additionally, bFGF (3 ng/h) was continuously infused at the flap-thigh interface. In the flap group (n = 6), a similar muscle flap was created, but carrier solution was infused at the interface. In the bFGF group (n = 6), no muscle flap was created; instead, bFGF (3 ng/h) was infused into the external iliac artery of the ischemic limb. In the control group (n = 8), carrier solution was infused into the external iliac artery (no flap, no bFGF). After 1 week, the soleus muscle was isolated and stimulated. Maximum twitch tension, the fatigue index (force of contraction after 2 minutes of continuous stimulation/initial force of contraction), maximum recovery, and the number of limbs recovered (ie, limbs that achieve a force of contraction during the recovery period of > 75{\%} of the force of the initial contraction at the start of continuous stimulation) were recorded. Blood vessel density (number of vessels per •••) was determined by immunostaining the soleus muscle with anti-α-actin antibody. Results: All values were indexed to the contralateral normal limb. The flap + bFGF group showed significant improvement versus the control group in maximum twitch tension (1.07 ± 0.13 vs 0.63 ± 0.12, P < .05), maximum recovery (0.94 ± 0.05 vs 0.58 ± 0.05, P < .05), and the number of limbs recovered (5/5 vs 0/6, P < .05). This improved function correlated with increased vessel density (flap + bFGF group, 1.44 ± 0.11 vs control group, 0.72 ± 0.01, P < .05). Conclusion: Reperfusion of an ischemic limb with a well-vascularized muscle flap and local bFGF infusion promoted increased blood vessel density in distal ischemic muscle. This increased vascularity was associated with restoration of otherwise impaired muscle function. Improved function occurred rapidly (1 week). A transposed muscle flap provided a functional blood supply to the site of maximum ischemia; this could be used to salvage otherwise nonreconstructible ischemic limbs.",
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N2 - Purpose: The administration of angiogenic growth factors and the transfer of well-vascularized tissues have been shown to induce development of new blood vessels in ischemic muscle. The functional significance of these new vessels is unknown. The hypothesis of this study is that the transfer of vascularized muscle and the local infusion of basic fibroblast growth factor (bFGF) synergistically improve contractile function of ischemic skeletal muscle. Methods: Twenty-six rabbits were divided into four groups. An ischemic hindlimb was created in each by ligating the right common iliac artery. The flap + bFGF group (n = 6) had transposition of a contralateral rectus muscle flap onto the thigh. Additionally, bFGF (3 ng/h) was continuously infused at the flap-thigh interface. In the flap group (n = 6), a similar muscle flap was created, but carrier solution was infused at the interface. In the bFGF group (n = 6), no muscle flap was created; instead, bFGF (3 ng/h) was infused into the external iliac artery of the ischemic limb. In the control group (n = 8), carrier solution was infused into the external iliac artery (no flap, no bFGF). After 1 week, the soleus muscle was isolated and stimulated. Maximum twitch tension, the fatigue index (force of contraction after 2 minutes of continuous stimulation/initial force of contraction), maximum recovery, and the number of limbs recovered (ie, limbs that achieve a force of contraction during the recovery period of > 75% of the force of the initial contraction at the start of continuous stimulation) were recorded. Blood vessel density (number of vessels per •••) was determined by immunostaining the soleus muscle with anti-α-actin antibody. Results: All values were indexed to the contralateral normal limb. The flap + bFGF group showed significant improvement versus the control group in maximum twitch tension (1.07 ± 0.13 vs 0.63 ± 0.12, P < .05), maximum recovery (0.94 ± 0.05 vs 0.58 ± 0.05, P < .05), and the number of limbs recovered (5/5 vs 0/6, P < .05). This improved function correlated with increased vessel density (flap + bFGF group, 1.44 ± 0.11 vs control group, 0.72 ± 0.01, P < .05). Conclusion: Reperfusion of an ischemic limb with a well-vascularized muscle flap and local bFGF infusion promoted increased blood vessel density in distal ischemic muscle. This increased vascularity was associated with restoration of otherwise impaired muscle function. Improved function occurred rapidly (1 week). A transposed muscle flap provided a functional blood supply to the site of maximum ischemia; this could be used to salvage otherwise nonreconstructible ischemic limbs.

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