Bobby J. Heath

Tissue inhibitor of metalloproteinase-4 instigates apoptosis in transformed cardiac fibroblasts.

Tumor cells become malignant, in part, because of their activation of matrix metalloproteinases (MMPs) and inactivation of tissue inhibitor of metalloproteinases (TIMPs). Myocardial tumors are rarely malignant. This raises the possibility that the MMPs and TIMPs are differentially regulated in the heart compared to other tissues. Therefore, we hypothesized that a tissue specific tumor suppressor exists in the heart. To test this hypothesis we prepared cardiac tissue extracts from normal (n = 4), ischemic cardiomypathic (ICM) [n = 5], and dilated cardiomyopathic (DCM) [n = 8] human heart end‐stage explants. The level of cardiospecific TIMP‐4 was determined by SDS‐PAGE and Western‐blot analysis. The results suggested reduced levels of TIMP‐4 in ICM and DCM as compared to normal heart. TIMP‐4 was purified by reverse phase HPLC and gelatin‐sepharose affinity chromatography. Collagenase inhibitory activity of chromatographic peaks was determined using fluorescein‐conjugated collagen as substrate and fluorescence spectroscopy. The activity of TIMP‐4 (27 kDa) was characterized by reverse zymography. The role of TIMP‐4 in cardiac fibroblast cell migration was examined using Boyden chamber analysis. The results suggested that TIMP‐4 inhibited cardiac fibroblast cells migration and collagen gel invasion. To test whether TIMP‐4 induces apoptosis, we cultured cardiac normal and polyomavirus transformed fibroblast cells in the presence and absence of TIMP‐4. The number of cells were measured and DNA laddering was determined. The results suggested that TIMP‐4 controlled normal cardiac fibroblast transformation and induced apoptosis in transformed cells. Cardiospecific TIMP‐4 plays a significant role in regulating the normal cell phenotype. The reduced levels of TIMP‐4 elicit cellular transformation and may lead to adverse extracellular matrix degradation (remodeling), cardiac hypertrophy and failure. This study suggests a possible protective role of TIMP‐4 in other organs which are susceptible to malignancy. J. Cell. Biochem. 80:512–521, 2001.

Discrete Membranous Subaortic Stenosis: Improved Results After Resection and Myectomy

BACKGROUND Despite an adequate resection, a significant recurrence rate is encountered in patients undergoing operation for discrete membranous subaortic stenosis. The fibrous membrane and hypertrophied myocardium commonly are removed, but because of the involved risks, the resection may be inadequate and contribute to the recurrence rate. METHODS A review of the cases of 23 patients undergoing operation for discrete membranous subaortic stenosis from 1980 to 1994 was undertaken. Fourteen patients (61%) had coexisting cardiac lesions, all of which were concomitantly repaired. RESULTS The left ventricle-aorta gradient decreased from a preoperative mean of 63.39 +/- 7.63 mm Hg to 15.17 +/- 3.06 mm Hg postoperatively (p < .001) during a mean follow-up of 3.32 +/- 0.58 years. Aortic insufficiency decreased postoperatively in 8 patients (34.8%), remained unchanged in 6 patients (26.1%), and showed only insignificant progression in 4 patients (17.4%). There were no early deaths, and the single late death was not cardiac related. No patient had development of endocarditis or heart block or required a pacemaker. One patient (4.3%) had a recurrence, which required reoperation. CONCLUSIONS Our results suggest that aggressive myectomy in concert with membrane resection constitutes safe treatment for discrete membranous subaortic stenosis and is associated with low rates of endocarditis, recurrence, and progression of aortic insufficiency.

Origin of the left pulmonary artery from the aorta: embryologic considerations

We observed a case of anomalous origin of the left pulmonary artery from the aorta in which the media of the abnormal vessel and the main pulmonary artery were fused, but without communication. This is the fifth isolated case of repair without the use of cardiopulmonary bypass reported in the literature. This pathology should be included in the aortic arch anomalies as a partial or complete failure of development of the left sixth arch.

A staged expanding pulmonary artery band

Pulmonary artery banding is indicated in numerous congenital cardiac defects not amenable to a total repair. One complication of pulmonary artery banding, especially in neonates who require early banding, is progressive cyanosis during the rapid growth phase requiring earlier than anticipated total correction, which may produce a less than optimal result. A simple pulmonary artery band that enlarges as the patient grows would avoid this early complication. We report a technique of pulmonary artery banding in an animal model using different absorbable sutures. The band enlarges in a prescribed staged fashion without any further intervention, hopefully allowing growth of neonates and infants with complex congenital heart disease.

Mitral valve replacement: Techniques to eliminate myocardial rupture and prevent valvular disruption

Twenty fresh canine hearts were used to compare the peak left ventricular pressures required to disrupt prosthetic mitral valves sutured in place with horizontal mattress sutures using either subannular or supraannular placed pledgets. Separate groups were developed to determine the effect of leaving the whole mitral valve apparatus or only the posterior leaflet apparatus intact and what effect, if any, each had on the ventricular pressure required to disrupt the implanted prosthetic mitral valve. Group 1 consisted of 10 hearts with the entire mitral apparatus left in place (5 valves implanted with supraannular pledgets and 5 with subannular pledgets). Group 2 consisted of 10 hearts with only the posterior leaflet apparatus left in place (5 valves implanted with supraannular pledgets and 5 with subannular pledgets). A 29-mm Medtronic mitral valve was secured in the mitral position with a fixed number of ten pledgeted sutures in each annulus. The aorta was cannulated and normal saline solution infused into the left ventricle until end-point rupture occurred. The peak pressure and mechanism of any disruption were then noted. No specimen exhibited subannular myocardial rupture or left atrial wall dissection. Similar protection was provided by leaving the posterior leaflet only or the entire mitral valve. In each case peak left ventricular pressure resulted in only paravalvular leaking around the limited number of sutures as the end point. In each of these four groups the peak left ventricular pressures required for end-point rupture were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Postsurgical use of Amplatzer septal occluder in cyanotic patients with pulmonary atresia/intact ventricular septum: Significance of cor triatriatum dexter and dilated right atrium

Percutaneous closure of secundum atrial septal defects (ASDs) has been shown to be safe and effective. However, its role after surgery in patients with cyanotic congenital heart disease who may have associated cor triatriatum dexter and a dilated right atrium has not been established. This article reports on successful closure in such patients, including precautions and results. Cathet. Cardiovasc. Intervent. 51:186–191, 2000.

Selective use of chest tubes in thoracotomies for congenital cardiovascular procedures.

BACKGROUND Advantages and complications have been reported from the use of chest tubes (CT). To reduce the incidence of complications we have employed a selective use of CT in thoracotomy for congenital cardiovascular procedure; ie, in absence of air leaks and fluid to be drained, no CT was inserted. METHODS The lung was reexpanded and air evacuated during the chest closure. Early and 6 hours chest roentgenograms were performed on every patient. This study retrospectively reviews the results of this selective approach in 546 patients operated on between 1980 and 1998 mainly for patent ductus arteriosum ligation, pulmonary artery band, aortic coarctation, Blalock-Taussig shunt. Four hundred and eighteen patients did not receive a CT at the initial surgery (group I), and 128 patients received a CT either before or at surgery (group II). RESULTS 40 patients in group I developed an air or fluid collection large enough to require a CT. Only one patient had complication, from an undetected hemothorax. Nine patients in group II required another CT, and one patient developed a pneumothorax upon pulling out the CT. No death in either group was related to the use or lack of use of the CT. A total of 378 CTs and collecting chambers were saved. CONCLUSIONS A selective approach to the use of CT in thoracotomies for cardiovascular procedures can be employed with minimal complications, more comfort for the patient, and cost savings.

Comparison of supraannular and subannular pledgeted sutures in mitral valve replacement

Ten fresh canine hearts were used to compare the peak left ventricular pressure required to disrupt prosthetic mitral valves sutured in place with horizontal mattress sutures with either subannular or supraannular pledgets. Each group consisted of 5 animals. A 29-mm Medtronic mitral valve was secured in the mitral position with ten pledgeted sutures. The aorta was cannulated and normal saline solution was infused into the left ventricle until valvar disruption occurred. The peak pressure and the location and mechanism of disruption were then noted. At the peak left ventricular pressure required for valvar disruption, no individual sutures were broken. Instead, in all specimens a subannular myocardial rupture occurred in the posterior portion of the mitral annulus along the extent of the atrioventricular groove. In addition, the posterior wall of the left atrium dissected upward subsequently. Significantly greater pressures were required in the group with subannular suture placement as compared with the supraannular group (354 +/- 37 versus 236 +/- 33 mm Hg; p less than 0.0007). These data suggest that placement of horizontal mattress sutures with pledgets in the subannular position is superior to the currently recommended method of supraannular suture placement in mechanical valves.