Management of the anomalous origin of the left coronary artery from the pulmonary artery.
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Biomedical subjects
Publications and source records attributed to A Ardehali.
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BACKGROUND: Cardiac allograft vasculopathy (CAV) is the major cause of late death among heart transplant recipients. The pathogenesis of CAV is poorly understood. METHODS AND RESULTS: To better characterize CAV, we performed immunohistochemical analysis of vascular lesions in a previously described murine model of CAV. The B10.A strain hearts were transplanted heterotopically into B10.BR strain recipients. The cardiac allografts were harvested from 1 to 2 months after implantation. The majority of epicardial and intramyocardial coronary arteries in explanted hearts had developed intimal thickening. The cellular infiltrate of the intimal thickening, major histocompatibility (MHC) antigens, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression were studied with the use of immunohistochemistry. In experimental CAV in mice, the cellular infiltrate of expanded intima consisted of macrophages, T lymphocytes, and smooth muscle cells. A substantial number of macrophages and T lymphocytes within the expanded intima expressed MHC class II antigen, a marker of cellular activation. The vessel wall cells also appeared to be activated due to their expression of endothelium-leukocyte adhesion molecules. The vascular endothelium of cardiac allografts displayed ICAM-1, VCAM-1, and unmatched MHC antigen (MHC class I in this model) upregulation. The medial smooth muscle cells also expressed VCAM-1 and unmatched MHC antigen. CONCLUSIONS: These findings suggest that (1) the cellular infiltrate of the expanded intima in experimental CAV is similar to that of human CAV, (2) experimental CAV is a local immune-mediated process requiring active participation of donor vessel wall cells and recipient mononuclear cells, and (3) coexpression of adhesion molecules and unmatched MHC antigen identifies endothelial cells as immune targets for activated host mononuclear cells. Furthermore, the presence of both VCAM-1 and unmatched MHC antigen supports a central role for medial smooth muscle cells as allogeneic immune stimulator.
BACKGROUND: A modification of the Fontan procedure with unidirectional cavopulmonary connection is described in which the superior vena cava (SVC) is connected to the left pulmonary artery (PA) and the inferior vena cava (IVC) is connected to the right PA via a lateral tunnel with a snare-controlled, adjustable atrial septal defect (ASD). This allows matching of the SVC and IVC flows with the lung of appropriate size. The obligatory left Glenn shunt provides an adequate arterial oxygen saturation, and the elevation in SVC pressure is well tolerated. The adjustable ASD allows selective decompression of the IVC that maintains cardiac output and reduces fluid accumulation in the serous cavities. METHODS AND RESULTS: Since March 1992, we have performed this procedure in 18 patients. There were 17 children and 1 adult. Median age was 3 years and 9 months (range, 13 months to 36 years). Six patients had been staged with a previous bidirectional Glenn shunt. Preoperative cardiac catheterization revealed a PA pressure of 13 +/- 2 mm Hg and a transpulmonary gradient of 5 +/- 3 mm Hg. Ventricular function was satisfactory in all patients. At the completion of bypass, the pressures in the SVC and IVC were 16 +/- 4 mm Hg and 10 +/- 3 mm Hg, respectively (P < .01). The left atrial pressure was 6.0 +/- 3.0 mm Hg and the arterial O2 saturation on 100% oxygen was 93 +/- 3%. There was one death as a result of intractable atrial arrhythmias. The remaining 17 patients had a mean hospital stay of 9.7 days (6 to 18 days). The length of pleural drainage was 7 +/- 3 days. The ASD was adjusted in 11 patients before discharge. Oxygen saturation at discharge was 85.4 +/- 4%. Nine patients had repeat catheterization. The ASD was completely closed in 6 patients, an average of 2.5 months after surgery (range, 3 weeks to 5 months). After ASD closure, the arterial oxygen saturation was 96 +/- 3%, and the SVC and IVC pressures were both 13 +/- 3 mm Hg. CONCLUSIONS: The Fontan procedure with unidirectional cavopulmonary connection and adjustable ASD has several advantages that may reduce mortality and morbidity for the high-risk Fontan candidate.
BACKGROUND: The complete and uniform distribution of cardioplegia to the microvasculature of the heart is considered critical for myocardial protection. This study explores the hypothesis that enhanced microvascular perfusion can be achieved by using both antegrade and retrograde cardioplegia. METHODS: Infant piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised, and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then perfused retrograde with an inert intracapillary marker (NTB-2). Six of these hearts served as controls (group 1) to anatomically demonstrate the degree of capillary perfusion achieved by the retrograde delivery route. Nine experimental hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde delivery techniques. Sections of the left ventricular free wall and anterior-mid interventricular septum were taken and examined by light microscopy at four separate sites (average, 126 capillaries per section). RESULTS: In control hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal capillaries were perfused by retrograde cardioplegia. After antegrade blood cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the septum. CONCLUSIONS: In this experimental model, antegrade blood cardioplegia did not coperfuse (and therefore washout) 12.5% to 14% (p < 0.05) of capillaries perfused by retrograde cardioplegia. This suggests that an additional 12.5% to 14% of capillaries within the myocardium may receive cardioplegia if retrograde cardioplegia is used in addition to antegrade cardioplegia. We conclude that by combining both antegrade and retrograde cardioplegia, there is a potential for enhanced overall microvascular perfusion.
OBJECTIVES: This study sought to determine the impact of acute aortic regurgitation on coronary blood flow reserve and phasic epicardial coronary blood flow in closed-chest dogs. BACKGROUND: Hemodynamic changes in acute aortic regurgitation are known to precipitate myocardial ischemia. Coronary blood flow reserve has not been studied in closed-chest experimental preparations with acute aortic regurgitation. METHODS: Graded temporary acute aortic regurgitation was produced in 11 mongrel dogs. Phasic coronary blood flow velocities were measured using a Doppler guide wire. Coronary flow reserve was defined as the ratio of the time average of spectral peak velocity after administration of papaverine to that of the baseline state. RESULTS: Under control conditions (mean [+/- SEM] diastolic blood pressure 82.2 +/- 4.5 mm Hg), coronary flow reserve was 3.51 +/- 0.27 with predominantly diastolic epicardial coronary blood flow. With mild acute aortic regurgitation (diastolic blood pressure 61.8 +/- 3.0 mm Hg), coronary flow reserve decreased to 2.38 +/- 0.27, with an increase in phasic systolic epicardial coronary blood flow. At the onset of moderate acute aortic regurgitation (diastolic blood pressure 42.1 +/- 0.9 mm Hg), coronary flow reserve declined further to 1.46 +/- 0.12, and the phasic systolic epicardial coronary blood flow became more prominent. With severe aortic regurgitation (diastolic blood pressure 29.2 +/- 2.2 mm Hg), coronary flow reserve reached 1.20 +/- 0.05, and the phasic epicardial coronary blood flow pattern was found to be predominantly systolic with retrograde diastolic flow. The ratio of diastolic to systolic pressure-time indexes with severe aortic regurgitation suggested subendocardial underperfusion. CONCLUSIONS: This study demonstrates a marked decline in coronary blood flow reserve and documents a progressive change in the phasic epicardial blood flow to a predominantly systolic pattern with increasing degrees of acute aortic regurgitation.
Anomalous origin of the left coronary artery from the pulmonary artery may present a technical challenge. Direct implantation of the anomalous left coronary artery into the aorta to provide a two coronary artery system is the preferred surgical approach. We describe a modification of this technique to allow anastomosis of the anomalous left coronary artery with the excised button of pulmonary artery from within the lumen of the aorta. We have used this procedure in six children and one adult with anomalous left coronary artery with favorable outcome. The potential benefits of this modified technique are (1) improved operative exposure, (2) ability to implant the anomalous left coronary artery in the appropriate sinus, (3) avoidance of aortic valve damage or distortion because of improved exposure, and (4) applicability to patients of all ages.
Warm retrograde blood cardioplegia is frequently used for myocardial protection, despite experimental studies questioning the adequacy of capillary flow to the right ventricle and septum. The capillary distribution of retrograde blood cardioplegia in the human heart is unknown. Hearts from eight transplant recipients with the diagnosis of idiopathic or dilated cardiomyopathy were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. Within 20 minutes of explanation, colored microspheres mixed in 37 degrees C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg for 2 minutes. Twelve transmural myocardial samples were taken horizontally at the level of midventricle and apex to determine regional capillary flow rates. When retrograde warm blood cardioplegia was administered at a rate of 0.42 +/- 0.06 ml/gm/min, the left ventricle, the septum, the posterior wall of the right ventricle, and the apex consistently received capillary flow rates in excess of their metabolic requirements. The capillary perfusion of anterior and lateral walls of the right ventricle was marginally adequate to sustain aerobic metabolism. In explanted human hearts, retrograde blood cardioplegia provides adequate capillary flow to the left ventricle, the septum, the posterior wall of the right ventricle, and the apex; however, capillary flow to the anterior and lateral walls of the right ventricle is marginal. This study delineates the tenuous balance between supply and demand for right ventricular protection with warm continuous retrograde blood cardioplegia.
UNLABELLED: This study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed. METHODS: Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow). RESULTS: Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 +/- 0.40 ml/gm versus 1.06 +/- 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% +/- 15.1% to 61.3% +/- 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex. CONCLUSION: Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered.
Access to the donor heart at the time of harvest provides a unique opportunity for genetic manipulation of this organ before transplantation. We sought to determine (1) if donor mouse hearts express a foreign gene administered at harvest and, (2) if so, what route of gene delivery is most effective. At harvest, 30 micrograms of promoter cytomegalovirus-luciferase deoxyribonucleic plasmid in cationic liposomes was injected directly into the myocardial apex (group I), into the right atrium (group II), or into the coronary arteries (group III). The donor hearts were then transplanted into the abdomen of recipient mice of the same strain. The transplanted hearts were removed in 4 days and luciferase expression was assayed by immunohistochemistry. In group I, luciferase activity was localized to the apex. In group II, where plasmid was delivered into the right atrium, luciferase expression was detected in the right ventricle and sparsely in the coronary perivascular area. In group III, where plasmid was injected into the coronary arteries, the transplanted hearts demonstrated luciferase expression in (1) perivascular areas surrounding coronary arteries and veins, (2) coronary capillaries, and (3) the endocardia of both ventricles. This study suggests that (1) donor mouse hearts can be genetically modified at the time of harvest and (2) intracoronary infusion of plasmid yields the most effective method of delivery. Administration of plasmid in the coronary arteries localizes the expression to the endocardium and the coronary vasculature, both sites of immunologic interactions after heart transplantation.
BACKGROUND: In human hearts, as much as two thirds of retrograde cardioplegia is shunted through thebesian and arteriosinusoidal channels into the ventricular cavities. This ventricular effluent is believed to have bypassed the myocardial capillary beds and is therefore considered nonnutritive. METHODS: To test this hypothesis, we studied the explanted hearts from 9 cardiac transplant recipients with the diagnosis of idiopathic cardiomyopathy. These hearts were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. The left and right coronary ostia and the coronary sinus then were cannulated. Colored microspheres (15 +/- 5 microns) mixed in 37 degrees C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg. Effluents from the coronary arteries and ventricular chambers were collected and analyzed for microsphere concentration. RESULTS: Approximately 80% of retrograde cardioplegia solution was recovered in the ventricular chambers. Nearly 40% of this ventricular chambers effluent had traversed capillary beds and, thus, we believe has nutritive properties. Almost all of the coronary artery effluent of retrograde cardioplegia solution had traversed capillary beds. The total nutritive fraction of retrograde warm blood cardioplegia in this explanted human heart model was approximately 55%. CONCLUSIONS: These findings suggest that the ventricular chamber effluent of retrograde blood cardioplegia contributes to the metabolic homeostasis of the arrested human heart.
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Mitral valve repair in children has the advantage of avoiding mitral valve replacement with its attendant need for anticoagulation and reoperation. Seventy-nine children between the ages of 2 months and 17 years (mean 4.9 years) underwent mitral valve repair between May 1982 and April 1993. There were five patients with mitral stenosis and 74 patients with mitral regurgitation, and 19 children were less than 2 years of age. Patients were divided into anatomic subgroups on the basis of the primary cardiac pathologic condition. Forty-three had severe mitral regurgitation, 21 had moderate mitral regurgitation, and 12 patients with primum atrial-septal defect and 2 patients with univentricular hearts had minimal to moderate mitral regurgitation. Associated cardiac anomalies were present in 68 patients and 85% of the patients required concomitant intracardiac procedures. The methods of mitral valve repair included annuloplasty in 68 (86%), repair of cleft leaflet in 41 (52%), chordal shortening in 9 (11%), triangular leaflet resection in 8 (10%), splitting of papillary muscles with resection of subvalvular apparatus in 7 (9%), and chordal substitution in 1 (1%). The technique of annuloplasty was modified to allow for annular growth. Follow-up was available from 1 to 10 years (mean 4 +/- 2.5 years). There were three early deaths (4%), all occurring as a result of low output cardiac failure in patients with minimal postoperative mitral regurgitation. Three late deaths (4%) occurred in patients with persistent moderate to severe mitral regurgitation and progressive cardiac failure and eight patients (10%) required either rerepair or replacement of the mitral valve. Actuarial survival was 94% at 1 year, 84% at 2 years, and 82% at 5 years, and actuarial freedom from reoperation was 89% at 8 years. All patients received postoperative echocardiography with 82% having minimal to no mitral regurgitation and 98% of long-term surviving patients being free of symptoms. We conclude that mitral valve repair can be done with low early and late mortality. The need for reoperation is relatively low and valve growth has occurred with the use of a modified annuloplasty.
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In the last decade, the number of patients undergoing heart transplantation has steadily increased as a result of expanding indications for cardiac transplantation. The limitation on the number of transplants performed has been the scarcity of donor organs. At UCLA, 320 heart transplant procedures were performed in adults through the end of 1992; 173 patients (54%) underwent transplantation for ischemic cardiomyopathy; 104 (33%) for dilated cardiomyopathy, and 13 (4%) for severe rejection or cardiac allograft vasculopathy. The mean number of rejection episodes and infections per patient per year in the first posttransplant year was 1.28 and 0.58, respectively. Early mortality (30 days) was 5.7%, while 1-, 3-, and 5-year survival rates were 84.3%, 74.3%, and 67.5%, respectively. Survival of patients transplanted for ischemic cardiomyopathy and idiopathic cardiomyopathy was nearly equal. Survival was also comparable in patients aged 60 years and over (n = 71) and those under age 60. We observed improved patient outcome including shorter posttransplant hospital stay, time to extubation, and lower incidences of infections, rejection episodes, and renal failure in patients transplanted in 1991 and 1992. This observation was interesting in view of the increased proportion of critically ill patients in this group (46% UNOS Status 1) compared with patients transplanted in the previous years (30% UNOS Status 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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The supply of oxygen to the myocardium is determined by coronary blood flow and oxygen carrying capacity. Coronary blood flow is a dynamic process modulated via multiple parameters. Cardiac metabolism is also affected by several factors. Under normal physiologic conditions, the demand is easily met by the supply of oxygen. In fact, there is a significant reserve on the supply side. Under certain pathologic states such as coronary artery disease, the supply of oxygen may be exhausted and an imbalance between supply and demand occurs which is translated into ischemia. The area of myocardium most susceptible to ischemia is the subendocardium due to mechanical and metabolic forces. In therapy of coronary artery disease, attention should be directed to directional changes in factors influencing supply and demand to improve blood flow to the most susceptible area.
Biosynthesis of cysteine from methionine via the hepatic transsulfuration pathway is impaired in some cirrhotic patients, who therefore might require cysteine in the diet. However, because further metabolism of cysteine also occurs primarily in the liver, the metabolic clearance of this amino acid could be impaired in cirrhosis. We administered oral loads of L-cysteine to cirrhotic patients and healthy volunteers. Plasma cyst(e)ine (free and protein-bound cysteine, and 1/2 cystine) and urinary sulfur-containing constituents were measured at various times postload. Cirrhotic subjects exhibited a greater maximal plasma cyst(e)ine concentration and plasma elimination half-life (t1/2) and a delayed excretion of metabolic end products after an oral L-cysteine load. The postload increase in total plasma cyst(e)ine was accounted for primarily by an increase in the disulfide form (cystine). These studies show that cirrhotics have an impaired ability to clear cyst(e)ine from the plasma.
A 34-year-old man presented with pulmonary aspergillosis on the 75th day after marrow transplant for chronic myelogenous leukemia. The patient had smoked marijuana heavily for several weeks prior to admission. Cultures of the marijuana revealed Aspergillus fumigatus with morphology and growth characteristics identical to the organism grown from open lung biopsy specimen. Despite aggressive antifungal therapy, the patient died with disseminated disease. Physicians should be aware of this potentially lethal complication of marijuana use in compromised hosts.