Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease: anesthetic management and results.
Gene transfer for therapeutic angiogenesis represents a novel treatment for medically intractable angina in patients judged not amenable to further conventional revascularization. We describe the anesthetic management of 30 patients with class 3 or 4 angina, enrolled in a Phase 1 clinical trial to assess the safety and bioactivity of direct myocardial gene transfer of naked DNA-encoding vascular endothelial growth factor (phVEGF(165)), as sole therapy for refractory angina. The phVEGF(165) was injected directly into the myocardium through a mini-thoracotomy. All patients had major clinical predictors for adverse perioperative cardiac complications. Fast-track anesthetic management with remifentanil and desflurane, multimodal analgesia, and aggressive hemodynamic control with nitroglycerin and esmolol were used. All patients tolerated anesthesia and surgery without problems. No perioperative myocardial infarction, hemodynamic instability, or ventricular failure occurred. VEGF injections caused no clinically significant changes in cardiovascular function. Mean hospital stay was 3.8 days. There was one late death (5 months postoperative). Twenty-nine of 30 patients experienced reduced angina (56.2 +/- 4.1 episodes/week preoperatively versus 3.8 +/- 1.6 postoperatively, P < 0.0001) and reduced sublingual nitroglycerin consumption (60.1 +/- 4.4 tablets/week preoperatively versus 2.9 +/- 1.1 postoperatively, P < 0.0001).


CONCLUSIONS
Previously revascularized patients now judged "inoperable," continue to present with chronic, recurrent angina. Our study describes the anesthetic considerations and management of such patients treated with a novel approach by using gene therapy to stimulate angiogenesis and improve perfusion to ischemic myocardium.
Lathi
K G
KG
Department of Anesthesiology, St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA. klathi@mediaone.net
Vale
P R
PR
Losordo
D W
DW
Cespedes
R M
RM
Symes
J F
JF
Esakof
D D
DD
Maysky
M
M
Isner
J M
JM
D000768:Anesthesia, General / Q000379:methods*; D000787:Angina Pectoris / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004333:Drug Administration Routes; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006439:Hemodynamics; D006801:Humans; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization / Q000379:methods*; D009206:Myocardium; D018919:Neovascularization, Physiologic / Q000235:genetics; D005996:Nitroglycerin / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents / Q000008:administration & dosage
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D004247:DNA; D005996:Nitroglycerin