Functional outcome of new blood vessel growth into ischemic skeletal muscle.
OBJECTIVE
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-alpha-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).


CONCLUSIONS
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.
Lee
S L
SL
Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, USA.
Pevec
W C
WC
Carlsen
R C
RC
D043925:Angiogenesis Inducing Agents / Q000502:physiology; D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D007083:Iliac Artery / Q000601:surgery; D007261:Infusions, Intra-Arterial; D007263:Infusions, Parenteral; D007511:Ischemia / Q000503:physiopathology* / Q000628:therapy*; D008026:Ligation; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D020127:Recovery of Function; D015424:Reperfusion / Q000379:methods*; D016879:Salvage Therapy; D013524:Surgical Flaps / Q000098:blood supply; D013997:Time Factors
D043925:Angiogenesis Inducing Agents; D016222:Fibroblast Growth Factor 2