Ignacio G. Duarte

Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis

BACKGROUND Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. METHODS Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. RESULTS In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%). CONCLUSIONS DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.

Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone: late results ☆

BACKGROUND In cases of moderate mitral regurgitation and coronary artery disease operative strategy continues to be debated between coronary artery bypass grafting alone and concomitant valve replacement or repair. We previously reported on 58 patients with moderate mitral regurgitation who had coronary artery bypass grafting between 1977 and 1983. We present the late results for this original cohort (test group), and a matched control group of coronary artery bypass grafting patients without mitral regurgitation (n = 58). METHODS AND RESULTS In the original cohort, the hospital mortality rate was 3.4% (2 of 58), and 80.4% (45 of 56) of hospital survivors were alive at the time of initial follow-up (mean, 4.3+/-2.3 years). Hospital mortality in the control group was 6.9% (4 of 58 patients). Follow-up was 98.2% (108 of 110 patients) complete, with a mean follow-up time of 10.3+/-5.5 years. Kaplan-Meier curves for hospital survivors showed similar 5- and 10-year survival rates between the two groups (p = 0.59). On multivariate analysis, age 65 years or more, congestive heart failure class III or IV, and pulmonary capillary wedge pressure more than 17 mm Hg were significant (p < 0.05) independent predictors of diminished survival in the test group. CONCLUSIONS Patients with moderate mitral regurgitation and coronary artery disease treated solely with coronary artery bypass grafting had acceptable early and late results. Moderate mitral regurgitation at the time of revascularization does not always warrant operative correction.

Angiogenesis As A Predictor Of Survival After Surgical Resection For Stage I Non-Small-Cell Lung Cancer

OBJECTIVES Some patients with surgically resected stage I non-small-cell lung cancer eventually have metastatic disease. A histologic marker of metastatic potential and diminished survival for stage I non-small-cell lung cancer may distinguish this patient population. This study evaluates the degree of angiogenesis as a predictor of cancer-related death after operation for stage I non-small-cell lung cancer. METHODS Demographic, surgical, and histopathologic data, including presence of vascular invasion, were reviewed for 106 patients with stage I non-small-cell lung cancer from 1985 through 1990. Visual quantitation of microvessels immunostained with factor VIII-related antigen and CD31 in 5 microm sections from the paraffin blocks of tissue defined rumor angiogenesis. RESULTS Follow-up was 95.1% complete, mean 5.2 +/- 3.0 years. Lung cancer-related mortality rate was 24.4% at 5 years. Mean microvessel counts were 20.7 +/- 11.2 for FVIII and 29.6 +/- 18.1 for CD31. Univariate analysis revealed an FVIII count of at least 20 (p = 0.025) and blood vessel invasion (p = 0.017) to be significant predictors of disease-related death. After adjustment for other patient and tumor characteristics, multivariate Cox regression analysis found an FVIII count of at least 20 (hazard ratio 2.9) and blood vessel invasion (hazard ratio 3.7) to be significant independent correlates of lung cancer death (p = 0.018 and p = 0.011, respectively). CD31 quantitation did not predict survival on univariate or multivariate analyses and did not correlate strongly with FVIII quantitation (Spearmans rank correlation r = 0.19). CONCLUSIONS This analysis reveals a significant association between tumor neovascularization and cancer-related mortality rate among patients with stage I non-small-cell lung cancer. Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and metastatic potential, may define a subset of patients with stage I non-small-cell lung cancer who could benefit from adjuvant therapy after surgical resection.

Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally invasive direct coronary artery bypass grafting

OBJECTIVE Unmodified reperfusion without cardioplegia in minimally invasive direct coronary artery bypass grafting procedures causes endothelial dysfunction that may predispose to polymorphonuclear neutrophil-mediated myocardial injury. This study tested the hypothesis that ischemic preconditioning in a minimally invasive direct coronary artery bypass grafting model attenuates postischemic endothelial dysfunction in coronary vessels. METHODS In anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes and reperfused for 3 hours without ischemic preconditioning (no-ischemic preconditioning; n = 7); in 7 dogs, the left anterior descending occlusion was preceded by 5 minutes occlusion followed by 5 minutes of reperfusion. Relaxation responses to stimulators of nitric oxide synthase were used to evaluate endothelial function in arteries from the ischemic-reperfused (left anterior descending) and nonischemic (left circumflex coronary artery) zones. RESULTS Stimulated endothelial-dependent relaxation of epicardial left anterior descending artery to incremental concentrations of acetylcholine in the no-ischemic preconditioning animals was shifted to the right, and maximal relaxation was attenuated compared with the nonischemic left circumflex coronary artery (117% +/- 4% vs 138% +/- 5%). In contrast, acetylcholine-induced maximal relaxation was comparable in the left anterior descending artery versus left circumflex coronary artery in the ischemic preconditioning group (130% +/- 6% vs 135% +/- 5%). In 150- to 200- microm left anterior descending microvessels, 50% relaxation occurred with a lower concentration (log[M]) of acetylcholine in ischemic preconditioning versus no-ischemic preconditioning (-8.0 +/- 0.4 vs -7.0 +/- 0.1) with no group differences in smooth muscle relaxation to sodium nitroprusside, suggesting endothelial-specific damage. Adherence of fluorescent labeled polymorphonuclear neutrophils to epicardial coronary artery endothelium, used as an index of basal (unstimulated) anti-polymorphonuclear neutrophil function, was significantly attenuated by ischemic preconditioning versus no-ischemic preconditioning (293 +/- 25 polymorphonuclear neutrophils/mm2 vs 528 +/- 29 polymorphonuclear neutrophils/mm2). CONCLUSION In this minimally invasive direct coronary artery bypass grafting model, both agonist-stimulated and basal postischemic endothelial dysfunction were attenuated by ischemic preconditioning.

Preoperative risk assessment for marginal patients requiring pulmonary resection

Surgical resection remains the mainstay of treatment for pulmonary malignancy. The ability of patients to undergo resection is dependent on the anatomic characteristics of the tumor, and the respiratory and cardiovascular status of the patient. There have been recent advances in our understanding of respiratory function in the patient with marginal lung function that have allowed surgical therapy of lung cancer in patients previously deemed inoperable. This review will define the marginal patients who can safely undergo pulmonary resection.

In vivo hemodynamic, histologic, and antimineralization characteristics of the Mosaic bioprosthesis

BACKGROUND Performance of bioprosthetic valves is limited by tissue degeneration due to calcification with reduced performance and longevity. The Mosaic bioprosthetic valve (Medtronic Heart Valves, Inc, Minneapolis, MN) combines zero pressure fixation, antimineralization properties of alpha-amino oleic acid (AOA), and a proven stent design. We tested the hypothesis that AOA treatment of Mosaic valves improves hemodynamics, antimineralization properties, and survival in a chronic ovine model. METHODS Mitral valves were implanted in juvenile sheep with Mosaic valves with AOA treatment (n = 8) or without AOA treatment (non-AOA, n = 8), or Hancock I (HAN, n = 4) tissue valves, and explanted at 20 postoperative weeks. RESULTS Survival was equivalent in AOA and non-AOA (140 +/- 0.4 and 129 +/- 30 days), but was significantly less in HAN (82 +/- 35). Leaflet calcium (microgCa/mg tissue) was less in AOA (9.6 +/- 13.9; p < 0.05 versus non-AOA and HAN) than non-AOA (96.3 +/- 63.8) and HAN (130.8 +/- 43.2). Explant valve orifice area (cm2) was significantly preserved in the AOA group compared with the non-AOA group (1.5 +/- 0.7 vs 0.8 +/- 0.3; p < 0.05 versus non-AOA and HAN). CONCLUSIONS We conclude that AOA treatment of Mosaic valves reduces leaflet calcification and valve gradient in juvenile sheep, and that the Mosaic design and fixation features may offer survival advantages that must be confirmed in extended trials.

Late Survival After Valve Operation in Patients With Left Ventricular Dysfunction

BACKGROUND Left ventricular dysfunction is a predictor of hospital mortality after cardiac valve operation. We evaluated late survival in a large cohort of these patients. METHODS From 1980 to 1993, 257 patients with a preoperative ejection fraction of 0.40 or less underwent aortic (n = 177), mitral (n = 72), or combined (n = 8) valve operation, with or without concomitant coronary artery bypass grafting. RESULTS Hospital mortality was 12.5%. Follow-up was 98% complete. Logistic regression analysis showed that an ejection fraction of less than 0.30, mitral regurgitation, concomitant coronary artery bypass grafting, emergency operation, and reoperation were independent correlates of hospital mortality (all at p < 0.05). Kaplan-Meier survival curves of the 220 hospital survivors showed a 65% 5-year survival. Multivariate analysis revealed preoperative use of diuretics, male sex, reoperation, age exceeding 60 years, and aortic regurgitation to be independent predictors of poor late outcome (all at p < 0.05). CONCLUSIONS The liability of left ventricular dysfunction with regard to diminished long-term survival is not completely reversed by valve operation. If operation is not performed before left ventricular dysfunction develops, postoperative medical treatment of these dilated, remodeled ventricles should be considered.

Embryology and surgical anatomy of the mediastinum with clinical implications.

This article discusses general mediastinal embryology, and provides anatomy and algorithms for the investigation of mediastinal masses. The superior, anterior, middle, and posterior mediastina also are detailed.

Preconditioning during simulated MIDCABG attenuates blood flow defects and neutrophil accumulation

BACKGROUND Ischemic preconditioning (IP) may be cardioprotective in minimally invasive direct coronary artery bypass where cardioplegia is not used. This study tested the hypothesis that IP of the area at risk (AAR) would attenuate postischemic injury from transient coronary artery occlusion. METHODS In 19 anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes (simulating coronary occlusion during anastomosis) followed by 3 hours of reperfusion. In 10 dogs, occlusion was preceded by 5 minutes of occlusion and 5 minutes of reperfusion (IP), whereas 9 other dogs had no IP (control, C). RESULTS Thirty minutes of left anterior descending occlusion caused comparable dyskinesis (systolic shortening, sonomicrometry) in the AAR in C (baseline, 29% +/- 3% to 3% +/- 2%) and in IP (baseline, 29% +/- 2% to -0.3% +/- 2%). After 3 hours of reperfusion, systolic shortening was significantly depressed in C (20% +/- 4%), and was not significantly improved by IP (24% +/- 3%, p = 0.8 versus C). Postischemic diastolic stiffness in the AAR was not altered by IP versus C (0.60 +/- 0.12 versus 0.41 +/- 0.13). Plasma creatine kinase activity was similar between C and IP at the end of reperfusion (20 +/- 11 versus 16 +/- 5 U/g). Postischemic AAR blood flow (in milliliters per minute per gram of tissue) at 180 minutes of reperfusion decreased by 56% versus baseline in C (from 1.04 +/- 0.4 to 0.46 +/- 0.12; p < 0.05) compared with no change in IP (from 0.74 +/- 0.23 to 0.60 +/- 0.10), but there was no significant group difference at this time. Myeloperoxidase activity as an index of neutrophil accumulation in AAR was decreased in IP versus C (0.4 +/- 0.09 versus 0.7 +/- 0.04 U/microg tissue). CONCLUSIONS Ischemic preconditioning does not decrease postischemic wall motion and only modestly increases postischemic blood flow abnormalities in the AAR, but does significantly inhibit neutrophil accumulation.

Papillary endothelial hyperplasia presenting as a chest wall neoplasm.

Soft tissue hematomas generally resolve but may persist and develop into slow-growing, organized masses. These chronic expanding hematomas are characterized by a pseudocapsule and a predominantly necrotic central cavity, with foci of newly formed capillaries. These have been called chronic expanding hematomas or Massons papillary endothelial hyperplasia. These lesions can mimic vascular neoplasms and must be considered in the evaluation of expanding soft tissue vascular malformations.