Faculty Bibliography

OBJECTIVE: This experiment examined the feasibility of minimally invasive port-access mitral valve replacement via a 2.5 cm incision. METHODS: The study evaluated valvular performance and myocardial functional recovery in six mongrel dogs after port-access mitral valve replacement with a St. Jude Medical prosthesis (St. Jude Medical, Inc., St. Paul, Minn.). Femoro-femoral cardiopulmonary bypass and a balloon catheter system for myocardial protection with cardioplegic arrest (Heartport, Inc., Redwood City, Calif.) were used. The mitral valve was replaced through a 2.5 cm port in the left side of the chest, and the animals were weaned from bypass. Cardiac function was measured before and at 30 and 60 minutes after bypass. Left ventricular pressure and electrical conductance volume were used to calculate changes in load-independent indexes of ventricular function. RESULTS: Each procedure was successfully completed. Recovery of left ventricular function was excellent at 30 and 60 minutes after bypass compared with the prebypass values for elastance (30 minutes = 4.04 +/- 0.97 and 60 minutes = 4.27 +/- 0.57 vs prebypass = 4.45 +/- 0.96; p = 0.51) and for preload recruitable stroke work (30 minutes = 76.23 +/- 4.80 and 60 minutes = 71.21 +/- 2.99 vs prebypass = 71.23 +/- 3.75; p = 0.45). Preload recruitable work area remained at 96% and 85% of baseline at 30 and 60 minutes (p = not significant). In addition, transesophageal echocardiography demonstrated normal prosthetic valve function, as well as normal regional and global ventricular wall motion. Autopsy revealed secure annular-sewing apposition and normal leaflet motion. CONCLUSIONS: These results suggest that minimally invasive mitral valve replacement using percutaneous cardiopulmonary bypass with cardioplegic arrest is technically reproducible, achieves normal valve placement, and results in complete cardiac functional recovery. Minimally invasive mitral valve replacement is now feasible, and clinical trials are indicated

OBJECTIVES: Although minimally invasive coronary artery bypass grafting is now feasible, using this technique to perform anastomoses on the beating or fibrillating heart may yield poorer graft patency than the standard open techniques that use cardioplegic arrest. This study tested the feasibility and anastomotic reproducibility of minimally invasive coronary bypass using newly developed port-access coronary artery bypass technology (Heartport, Inc., Redwood City, Calif.), which allows endovascular cardiopulmonary bypass, cardiac venting, aortic occlusion, and cardioplegic arrest for internal thoracic artery-coronary artery anastomoses. METHODS: Nineteen dogs had thoracoscopic takedown of either single (n = 14) or bilateral (n = 5) internal thoracic arteries followed by minimally invasive coronary bypass with cardioplegic arrest, done by means of the port-access system. The anastomotic technique was modified after the fourth animal by switching from a microscope to a 2.5 cm oval port and performing a conventional anastomosis with operative loupes. The adequacy of delivery of cardioplegic solution, ventricular decompression, and anastomotic patency was assessed. RESULTS: The crossclamp and bypass times were 50 +/- 15 minutes and 87 +/- 28 minutes (mean +/- standard deviation), respectively. The mean myocardial temperature after cardioplegia was 17 degrees +/- 1 degree C and the aortic pressure (-3 +/- 9 mm Hg) and pulmonary artery pressure (4 +/- 1 mm Hg) were low throughout the procedure. All animals were weaned from bypass without inotropic agents. Angiograms and autopsies demonstrated successful thoracic artery takedown and anastomotic patency in 18 of 19 animals, with 100% anastomotic patency after the technique had been modified after the fourth animal. CONCLUSION: This study describes a reproducible technique for minimally invasive coronary bypass that allows myocardial protection, anastomotic precision, and predictable thoracic artery graft patency. Clinical trials are indicated

Human endothelium obtained from both the aorta and the pulmonary artery has been evaluated for the presence of the messenger RNA coding for the expression of sterol 27-hydroxylase. Unique oligomers were designed to detect the mRNA by reverse transcription followed by the polymerase chain reaction. The amplified product was sequenced and was found to be identical to the published sequence for nucleotides 491 to 802 of the human sterol 27-hydroxylase cDNA. Northern blot analysis confirmed the presence of 27-hydroxylase mRNA in pulmonary artery and aortic endothelium. As part of these studies, enzymatic activity was assayed in cultured arterial endothelium using cholesterol as a substrate and isotope ratio gas-liquid chromatography-mass spectrometry to identify the metabolites, 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, in the medium. Localization of sterol 27-hydroxylase to vascular endothelium indicates intracellular production of the biologically active metabolite 27-hydroxycholesterol

Platelet activating factor (PAF) enhances polymorphonuclear leukocyte (PMN) superoxide (.O2-) production, CD11b expression, and elastase release, all essential components in the pathophysiology of multiple-organ failure. This study was designed to determine the effects of Lexipafant, a PAF receptor antagonist, on PAF-mediated PMN functions. PMNs from 10 healthy volunteers were isolated and pretreated with various concentrations of Lexipafant (0-100 microM). PMNs were then incubated for 5 min with 200 nM PAF for .O2- detection or 2000 nM PAF for elastase measurement and activated with 1 microM N-formylmethionylleucylphenylalanine. The mean rate of .O2- production was determined by a cytochrome c reduction assay (nmole .O2-/min/1.33 x 10(5) PMN +/- SEM). Elastase release was measured by the cleavage of the synthetic elastase substrate Meo-Suc-Ala-Ala-Pro-Val-pNA (mean elastolytic activity +/- SEM). In parallel experiments, PMNs were incubated with 200 nM PAF for 30 min following pre-treatment with Lexipafant and CD11b expression was determined by flow cytometry (mean fluorescence intensity +/- SEM). Statistical analysis was performed using repeated-measures ANOVA (P < 0.05). Lexipafant inhibited PAF-enhanced PMN .O2- generation, CD11b expression and elastase release in a dose dependent fashion. The IC50 of Lexipafant for .O2- production, CD11b expression, and elastase release was 0.046, 0.285, and 0.05 microM, respectively. Lexipafant attenuated the PAF-mediated upregulation of PMN .O2- production, CD11b expression, and elastase release in a dose dependent fashion. These data support the hypothesis that Lexipafant may reduce the severity of the inflammatory response to injury produced by PAF-enhanced activation of PMNs

New techniques for minimally invasive cardiac surgery have recently emerged. This report describes the Port-Access technique for coronary artery bypass grafting, which involves a small left anterior thoracotomy, femoral cannulation for endovascular cardiopulmonary bypass, and cardioplegic arrest using an endoaortic occlusion catheter and cardioplegia delivery system. This technique allows for minimally invasive single or multivessel revascularization in an arrested, protected heart, while maintaining a high level of anastomotic precision. The Port-Access surgical techniques are described, along with the indications and contraindications for this procedure. The initial New York University clinical results with Port-Access coronary bypass grafting are presented

PURPOSE: To evaluate gadolinium-enhanced three-dimensional magnetic resonance (MR) angiography for thoracic aortic disease and to compare this technique with conventional thoracic MR imaging. MATERIALS AND METHODS: One hundred eight consecutive patients underwent 122 thoracic MR examinations, including conventional MR imaging followed by enhanced three-dimensional MR angiography. A gradient-echo sequence was used at 1.5 T (116 examinations) and 1.0 T (6 examinations) during infusion of 0.2 mmol/kg gadopentetate dimeglumine. Two independent readers (A and B), with varied experience in thoracic MR angiography, retrospectively evaluated the images for presence of aortic dissection, aneurysm, arch vessel disease, and protruding atheroma. Correlation with findings of surgery or other imaging modalities was available in 98 cases. RESULTS: Enhanced MR angiography was sensitive (92%-96%) and specific (100%) for acute and chronic aortic dissection (n = 26) and was as useful as conventional MR imaging in the diagnosis of aneurysm (n = 43) and arch vessel disease (n = 7). One of two intramural hematomas were overlooked at MR angiography by reader A, and both were overlooked by reader B. CONCLUSION: Enhanced three-dimensional MR angiography is a rapid and accurate imaging modality in diagnosis of thoracic aortic disease but is insensitive to intramural hematoma