Biomedical subjects

V M Reddy

Publications and source records attributed to V M Reddy.

At least 91 records · Page 5Linked to original sources

PubMed1997

Outcomes after bidirectional cavopulmonary shunt in infants less than 6 months old.

OBJECTIVES: We sought to assess the results after bidirectional cavopulmonary shunt (BCPS) in infants < 6 months old and to identify risk factors for poor outcome. BACKGROUND: Although BCPS is a well established procedure for the palliation of patients with a single-ventricle heart, there have been very few reports of outcomes after BCPS in young infants. METHODS: Since 1990, 42 infants between 0.8 and 6.0 months of age (mean [+/-SD] 3.7 +/- 1.4) have undergone BCPS for primary (n = 16) or secondary (n = 26) palliation of tricuspid atresia (n = 13), hypoplastic left heart syndrome (n = 10) or other forms of functional single-ventricle heart (n = 19). Accessory pulmonary blood flow was included in 18 patients. Preoperative and perioperative data were gathered on retrospective review of patient records, and follow-up was conducted by means of direct physician contact or record review. RESULTS: The overall hospital mortality rate, including that associated with reoperations, was 4.8% (2 of 42 patients). Seven patients (17%) required reoperation related to the BCPS or pulmonary blood flow in the early postoperative period: Procedures included take-down of the BCPS in four patients, with one early death, and procedures to decrease pulmonary blood flow in three patients. Age < 1 month correlated significantly with early death and with early failure of the BCPS (death or take-down). Follow-up of the 37 patients discharged with intact BCPS was obtained at a mean +/-SD of 14.3 +/- 11.3 months postoperatively, during which time three patients died (at 6.5 +/- 2.5 months). The 2-year actuarial survival rate for patients undergoing BCPS at < 6 months of age was 86%. Overall freedom from death or take-down (including early and late events) was significantly lower in patients < 2 months old than in those > 2 months old. Four patients have undergone successful Fontan completion (18.3 +/- 2.9 months postoperatively), and one patient whose BCPS was taken down subsequently underwent successful restoration of a BCPS. CONCLUSIONS: Outcomes after BCPS in young infants are comparable to those in older infants and children. However, our current preference is to defer this procedure until after 2 months of age.

Actuarial Analysis↗

PubMed1997

Systemic venous collateral channels causing desaturation after bidirectional cavopulmonary anastomosis: evaluation and management.

OBJECTIVES: We sought to characterize the frequency, anatomic details and factors associated with the development of collateral channels between the superior and inferior vena caval systems after bidirectional cavopulmonary anastomosis. BACKGROUND: It is well known that systemic venous collateral channels often develop in patients who have undergone a classic Glenn shunt or bidirectional cavopulmonary anastomosis and that such collateral channels can lead to profound systemic desaturation. However, there have been few reports focusing on this problem. METHODS: Fifty-four patients (median age 1.4 years) who underwent bidirectional cavopulmonary anastomosis and had preoperative and postoperative angiograms available for review were studied retrospectively. Postoperative connections between the superior and inferior vena caval systems were identified and measured. Sites of collateral origin and entry from the superior and inferior venous systems, as well as the course taken in between, were recorded. RESULTS: At follow-up angiography performed 17 days to 46 months postoperatively, a total of 31 venous collateral channels were observed in 18 patients with a wide variety of primary morphologic diagnoses. The majority of these collateral channels (80%) originated from the brachiocephalic vein or its junction with the superior vena cava, and over half of them drained below the diaphragm. In patients who developed venous collateral channels, the mean transpulmonary pressure gradient early after bidirectional cavopulmonary anastomosis was higher (p = 0.005), and mean arterial oxygen saturation at follow-up was lower (p = 0.009). There were trends toward higher superior vena caval pressure early after the operation and at follow-up in patients with collateral channels and a higher likelihood of absent upper lobe pulmonary blood flow in these patients. Successful coll embolization of 10 collateral channels was performed in six patients, with a median increase in arterial oxygen saturation of 16%. CONCLUSIONS: Angiographically detectable systemic venous collateral channels develop after bidirectional cavopulmonary anastomosis in a substantial number of patients (33% in the present series) with a variety of forms of a functional univentricular heart. Patients with venous collateral channels can be treated successfully with coil embolization, but the indications for embolization will depend on individual circumstances.

Adolescent↗

PubMed1997

The double switch procedure for anatomical repair of congenitally corrected transposition of the great arteries in infants and children.

AIMS: To assess outcomes of anatomical repair (double switch procedure) in infants and children with congenitally corrected transposition of the great arteries. METHODS AND RESULTS: Between September 1993 and August 1996, 17 patients with congenitally corrected transposition underwent surgery at UCSF. Anatomical repair was performed in 11 of these patients, at ages ranging from 4.8 months to 7.8 years (median 3.2 years). The remaining six patients did not undergo anatomical repair due to unfavourable anatomy (n = 2), prior conduit repair (n = 2), biventricular dysfunction (n = 1), and isolated complete atrioventricular block (n = 1). The 11 patients who underwent anatomical repair make up the study group for the present report. All 11 patients had a malalignment ventricular septal defect, while pulmonary outflow tract obstruction was present in nine patients and significant tricuspid valve pathology or dysfunction was present in five. Anatomical repair was achieved with a Senning (n = 7) or a Mustard (n = 4) procedure combined with an arterial switch operation plus ventricular septal defect closure (n = 4), or a Rastelli procedure with left ventricle to aortic baffle and right ventricle to pulmonary artery conduit (n = 7). There was one early death and no patients developed surgical complete atrioventricular block. At a median follow-up of 22 months, there were no late deaths. Two patients required a total of three late reoperations, and all patients were asymptomatic on no cardiac medication. Follow-up echocardiography revealed normal biventricular function in all patients. CONCLUSIONS: Anatomical repair of corrected transposition can be achieved with low rates of early mortality and surgical heart block, and favourable mid-term results. Long-term follow-up will be necessary to determine if the double switch approach improves the natural history of corrected transposition when compared to less aggressive surgical approaches that leave the right ventricle in the systemic circulation.

Adult↗

PubMed1997

Update on prospects for fetal cardiovascular surgery.

With progress in the field of fetal echocardiography, it has become clear that certain obstructive lesions of the heart and great vessels may progress in utero, leading to more severe disease. Prenatal intervention may mitigate this process, ultimately leading to improved outcomes for patients with certain severe congenital cardiac defects. In this review, we provide an update on the prospects for fetal cardiac intervention, with a focus on the field of fetal cardiac surgery.

Animals↗

PubMed1996

Optimal burr and adjunctive balloon sizing reduces the need for target artery revascularization after coronary mechanical rotational atherectomy.

We analyzed the effect of differing burr and balloon sizes during mechanical rotational atherectomy on the need for target vessel revascularization at 6 months. The ideal burr/artery ratio and adjunctive balloon/artery ratio for optimizing acute luminal results and minimizing restenosis is unknown. Six-month clinical follow-up was obtained in 311 patients (339 lesions) treated with rotational atherectomy from August 1993 to September 1994, to determine whether procedural results or technique were related to the need for target vessel revascularization. Target vessel revascularization, defined as repeat percutaneous intervention or bypass surgery within 6 months after rotational atherectomy, occurred in 19% of patients. Larger burr/artery ratios, defined as the final burr size divided by the reference artery size, were correlated with decreased postatherectomy diameter stenosis (p <0.009) and decreased final diameter stenosis (p <0.03). However, there was no statistical association between postatherectomy or final diameter stenosis with need for revascularization (p = not significant [NS]). The need for revascularization was lowest for burr/artery ratio between 0.6 to 0.85 (15%) versus burr/artery <0.6 or >0.85 (25%) (p <0.04). Postatherectomy, smaller balloon/artery ratios, defined as the final balloon size divided by the reference artery size, were correlated with lower repeat revascularization rates. Balloon/artery ratios <0.95 (target vessel revascularization = 11% vs 25% in balloon/artery >0.95) were associated with the best luminal results and the least risk for clinical restenosis (p <0.006). For rotational atherectomy, despite improvement in acute luminal results with increased burr/artery ratio, the use of a moderate burr/artery ratio correlated with the lowest revascularization rates. There was no correlation between postatherectomy or final diameter stenosis and need for repeat interventions. However, the use of large balloon/artery ratios after rotablator was associated with higher target vessel revascularization rates.

Aged↗

PubMed1996

Key role of the alternate complement pathway in hyperacute rejection of rat hearts transplanted into fetal sheep.

Hyperacute rejection (HAR) mediated by xenoreactive natural antibodies (XNA), which are thought to develop in early infancy, is a major impediment to transplantation between widely disparate species. The ability to diagnose certain forms of congenital heart defects early in prenatal life suggests the potential for these defects to be corrected by cardiac transplantation, prior to the development of XNA and host immunocompetence. This study investigated whether discordant cardiac xenotransplantation into fetal and neonatal recipients might obviate HAR due to the relative lack of XNA. Six neonatal lambs at 3 days (n=3) or 7 days (n=3) of life, and two fetal lambs at 125 and 142 days of gestation (term = 145 days) received cardiac grafts from adult Wistar-Furth (275-350 g) rats. All eight cardiac xenografts showed clinical evidence of HAR, with rapid swelling, loss of contractility, and ecchymosis and a mean survival time of 12.5 +/- 6.4 min. Sections of explanted grafts showed classical histologic features of HAR, including interstitial hemorrhages, platelet microthrombi, and edema, without leukocyte infiltration. Immunopathology of grafts harvested from fetal recipients showed a lack of significant intragraft deposition of sheep IgM, IgG, or C1q, but widespread endothelial labeling for C3, factor B, and properdin. In contrast, grafts in neonatal recipients showed IgM, IgG, and C1q deposition, as well as C3, factor B, properdin, and terminal complement (C) components. Fibrin deposition and platelet thrombi were seen in both groups of recipients. Injection of cobra venom factor resulted in prolongation of cardiac xenograft survival in neonatal lambs (n=3) to 12 hr. Analysis by immunohistology showed that normal sera from neonatal and adult, but not fetal, sheep contained IgM and IgG XNA reactive with rat cells. In conclusion, rodent grafts transplanted into fetal sheep undergo HAR, likely through direct activation of the alternate pathway of C, whereas neonatal lambs acquire XNA in the very early postnatal period and reject rat hearts through activation of both the classical and alternate pathways of C. Thus, at least in some species combinations, cardiac transplantation during the early postnatal period, or even in utero, may still be subject to development of HAR.

Acute Disease↗

PubMed1996

Pathobiological significance of colony morphology in Mycobacterium avium complex.

Mycobacterium avium complex (MAC) strains are known to exhibit variation in colony morphology. In addition to the smooth transparent (ST), smooth opaque (SO) and rough opaque (RO), which are the most common morphological forms, intermediate (IM) and pin point (PP) forms were also occasionally observed. In order to understand the pathobiological significance of these different colony forms, we investigated their virulence in beige mice, ability to bind to plastic and epithelial cells, differences in the lipids, and modulation of macrophage functions by the bacillary extracts. ST variants, the most common form seen in AIDS patients, were more virulent with increased multiplication in lungs, livers and spleens of beige mice and showed increased adherence to plastic and epithelial cells. SO, RO, PP colonial forms did not show increase in growth in any of the organs over a period of 4 weeks. IM colonial variants showed increased growth in lungs and spleens but not in livers. Thin layer chromatographic (TLC) analysis of lipid extracts showed one specific component in the high polar lipids of the SO variant, while ST variant did not show any specific component in any of the three families of lipids (high, intermediate and low polarity). The RO variant either expressed low levels or lost many of the components of lipids of high and intermediate polarity, however produced increased levels of lipids of low polarity. One of the components of low polar lipids was specific for RO variant and was produced in large quantity. The isogenic variants differed in the total lipid and sugar contents and also differed in their ability to modulate macrophage functions.

Animals↗

PubMed1996

Coarctation repair using end-to-side anastomosis of descending aorta to proximal aortic arch.

BACKGROUND: Recurrent aortic coarctation after primary operative repair in the neonate and small infant is seen most commonly within the first year of life. Inadequate removal of ductal tissue, failure to address hypoplasia of the aortic arch, and suture line tension have been cited as important factors in early recurrence. METHODS: To address these issues, we have used a technique of coarctation resection and extended anastomosis of the descending aorta to the undersurface of the aortic arch. THe salient features of this approach include extensive mobilization of the aortic arch and neck vessels, careful trimming of all ductal tissue, ligation of the isthmus just beyond the left subclavian artery, and end-to-side anastomosis of the descending aorta to a separate incision in the undersurface of the aortic arch proximal to all tubular hypoplasia. Between July 1992 and January 1995, 19 consecutive neonates (median age, 13 days) and 4 consecutive infants under 3 months of age (median age, 69 days) with a mean peak systolic upper to lower extremity resting gradient of 27.9 +/- 16.9 mm Hg underwent repair of aortic coarctation and tubular hypoplasia of the arch. Other procedures performed at the time of repair included ligation of a patent ductus arteriosus (n = 19), pulmonary artery banding (n = 3), and closure of ventricular septal or atrial septal defect (n = 3). RESULTS: There were no perioperative deaths. Early postoperative complication included a recurrent laryngeal nerve injury and a transient focal tonic clonic seizure. There was one late death, after a subsequent intracardiac surgical procedure, at a median follow-up of 16 months (range, 1 to 29 months). Twenty-one of 22 late survivors were free of recurrent aortic coarctation by echocardiography findings and clinical examination, with a median upper to lower extremity gradient of 0 mm Hg. Reintervention for recurrent aortic coarctation was not required in any survivor. CONCLUSIONS: The technique described herein completely removes all potentially abnormal tissue from the aorta, including ductal tissue and all tubular hypoplastic tissue proximal to the coarctation site.

Anastomosis, Surgical↗

PubMed1996

Intraatrial baffle repair of isolated ventricular inversion with left atrial isomerism.

Isolated ventricular inversion with left atrial isomerism, partial anomalous pulmonary venous connection, and interruption of the inferior vena cava with azygos continuation to a right superior vena cava was diagnosed by echocardiography in a neonate. At 48 days of age, the patient underwent successful anatomic correction with redirection of flow from the superior vena cava and hepatic veins to the left-sided tricuspid valve, and flow from the pulmonary veins to the right-sided mitral valve. In the present report, the surgical techniques of this case are described, along with a survey of the surgical literature covering anatomic repair of isolated ventricular inversion.

Echocardiography↗

PubMed1996

Revision of previous Fontan connections to extracardiac or intraatrial conduit cavopulmonary anastomosis.

BACKGROUND: In patients who have received an atriopulmonary Fontan connection, complications such as right pulmonary vein obstruction, atrial arrhythmias, and thromboembolism are often secondary to right atrial enlargement. When such complications develop despite good ventricular function, there are few management options available. Extracardiac or intraatrial conduit cavopulmonary anastomosis, which improves central systemic venous flow patterns, avoids atrial distention, and does not involve the extensive atrial suturing required by other forms of cavopulmonary anastomosis, may provide relief for this group of patients. METHODS: Between October 1992 and October 1995, 7 patients presented 8 to 20 years after atriopulmonary connection with severe right atrial dilatation (7), Fontan pathway obstruction (4), progressive congestive heart failure (4), atrial tachydysrhythmias (3), right atrial thrombus (1), obstruction of right pulmonary veins by an enlarged right atrium (1), and subaortic stenosis (1). After evaluation of the options, they underwent revision of the atriopulmonary connection to extracardiac (5) or intraatrial (2) conduit cavopulmonary anastomosis. RESULTS: One patient with severe cachexia, in whom transplantation was contraindicated for social reasons, died in the early postoperative period of massive effusions. Two patients eventually required permanent pacing for atrial dysrhythmias (1) or complete heart block secondary to subaortic fibromuscular resection (1), and 2 demonstrated marked improvement in unstable preoperative rhythm disturbances. At a median follow-up of 17 months, 4 of the 6 survivors were functioning at higher New York Heart Association levels than preoperatively, and 1 had recently undergone heart transplantation. CONCLUSIONS: In properly selected patients with atrial complications, revision of a prior Fontan connection to extracardiac or intraatrial conduit cavopulmonary anastomosis appears to be a viable option.

Adolescent↗

PubMed1996

Pulmonary artery growth after bidirectional cavopulmonary shunt: is there a cause for concern?

OBJECTIVE: Our objective was to analyze changes in pulmonary artery size after bidirectional cavopulmonary shunt. METHODS: All 47 patients who underwent bidirectional cavopulmonary shunt between March 1990 and May 1995 who had preoperative and postoperative angiograms available for review were selected for study. This included 24 patients who had also undergone a modified Fontan operation. Clinical records were reviewed retrospectively and cross-sectional follow-up was obtained by direct physician contact. Angiograms were reveiwed, and the right and left pulmonary artery diameters were each measured at two locations: immediately distal to their origin and at the narrowest point. In addition, the lower lobe pulmonary artery branch was measured just distal to its origin. Cross-sectional areas (left, right, and total) at each point of measurement were indexed to body surface area. Angiographic and hemodynamic data were analyzed. RESULTS: Changes in the various measures of pulmonary artery size after bidirectional cavopulmonary shunt varied considerably. On average the absolute diameters increased for all measures, but the increase in diameter was significant only for the lower lobe arteries. All pulmonary artery indices decreased on average, but these changes did not approach significance. Patients who underwent pulmonary artery augmentation at the time of bidirectional cavopulmonary shunt had significantly smaller pulmonary artery indices before pulmonary artery augmentation, relative to those who did not undergo pulmonary artery repair, and significantly greater changes (possibly to a large extent owing to pulmonary artery repair) in the right and left pulmonary artery index after bidirectional cavopulmonary shunt. Lower lobe indices did not differ preoperatively or exhibit different degrees of change in size between patients who did and did not undergo pulmonary artery repair. One patient died after Fontan completion (pulmonary artery index: 305 mm2/m2), and none of the factors analyzed correlated with Fontan outcomes. CONCLUSIONS: A more appropriate measure of pulmonary artery growth is the indexed cross-sectional area of the lower lobe branch of the right and left pulmonary arteries, which is less likely to be altered surgically with systemic-pulmonary shunts, pulmonary artery repair, and the bidirectional cavopulmonary anastomosis itself. Pulmonary artery indices, including the lower lobe index, do not change significantly after bidirectional cavopulmonary shunt during medium-term follow-up and do not influence the Fontan outcome.

Cardiac Catheterization↗

PubMed1996

Morphologic determinants favoring surgical aortic valvuloplasty versus pulmonary autograft aortic valve replacement in children.

UNLABELLED: The pulmonary autograft is being used with increasing frequency to replace the diseased aortic valve in the pediatric population. Attempted surgical aortic valvuloplasty with an unacceptable result and return to cardiopulmonary bypass for aortic valve replacement with a pulmonary autograft results in prolonged bypass time and increased potential for morbidity. Therefore, the ability to predict an unsuccessful outcome for valvuloplasty would be of significant clinical benefit. This issue is addressed in the present study. METHODS: Twenty-two patients (median age 5.7 years, range 3 weeks to 14 years) with bicuspid (n = 11), tricuspid (n = 9), or quadricuspid (n = 2) aortic valves underwent valvuloplasty for aortic stenosis (n = 9), aortic regurgitation (n = 7), or a combination (n = 6). Previous related procedures included balloon aortic valvuloplasty (n = 3) and open surgical valvotomy (n = 1). Median pressure gradient across the aortic valve was 80 mm Hg. Surgical valvuloplasty techniques included thinning of leaflets (n = 18), commissurotomy (n = 15), suspension of reconstructed leaflet to the aortic wall (n = 10), closure of leaflet fenestration (n = 5), shortening of free edge of prolapsed cusp (n = 4), repair of torn leaflets (n = 3), and augmentation of scarred leaflets with autologous pericardium (n = 3). Concomitant subvalvular and supravalvular stenosis were repaired in nine and four patients, respectively. In five patients, during the same hospital stay, a failed valvuloplasty was converted into a valve replacement with a pulmonary autograft because of residual or resultant stenosis (n = 3) or regurgitation (n = 2). RESULTS: No early or late deaths occurred. At a median follow-up of 16.3 months the median pressure gradient across the aortic valve in the 15 patients with preoperative stenosis or combined stenosis and regurgitation was 16 mm Hg (p < 0.01 versus preoperative gradient). Of the 22 patients, the aortic valve functioned normally (defined as < or = mild stenosis or regurgitation, or both) in 14 patients (including five patients with valve replacement); four patients had stenosis (gradients 40, 45, 60, and 60 mm Hg), two patients had regurgitation, and two patients had combined stenosis (gradients 40 and 50 mm Hg) and regurgitation. Three of the patients with recurrent stenosis underwent secondary surgical valvuloplasty without improvement. Outcome after valvuloplasty was examined according to valve structure: six of nine tricuspid valves functioned normally, whereas only three of 13 nontricuspid valves functioned normally (P = 0.07). Patients with a nontricuspid aortic valve and regurgitation had a high probability of requiring immediate valve replacement (P = 0.009). The actuarial freedom from significant native valve stenosis or regurgitation at 24 months was 82% for tricuspid valves and 36% for nontricuspid valves (P = 0.007). CONCLUSIONS: (1) Surgical aortic valvuloplasty should be the preferred approach when the aortic valve is tricuspid. (2) In contrast, aortic valve replacement with a pulmonary autograft should be the preferred strategy in the presence of a nontricuspid aortic valve (especially when the aortic valve is regurgitant) and after failed surgical valvuloplasty.

Adolescent↗

PubMed1996

Fetal model of single ventricle physiology: hemodynamic effects of oxygen, nitric oxide, carbon dioxide, and hypoxia in the early postnatal period.

BACKGROUND: In patients with single ventricle physiology, the distribution of flow to the systemic and pulmonary circulations, which are in parallel, largely depends on the relative resistances in the respective vascular beds. Although neonatal palliation in patients with single ventricle physiology has become more common, medical management during the perinatal and perioperative periods is often based primarily on personal and institutional experience and is complicated by the transition to postnatal life and the effects of cardiopulmonary bypass. The lack of an animal model that suitably mimics single ventricle physiology has impeded progress in this area. OBJECTIVE: The purpose of the current study was to investigate the effects of respiratory manipulations on pulmonary hemodynamics in the early neonatal period in a reproducible model of single ventricle physiology created in utero. METHODS: A 10 mm Damus-Kaye-Stansel aortopulmonary anastomosis was created in fetal sheep (n = 14) at 140 +/- 1.2 days' gestation, with pulmonary blood flow provided through a 5 mm aortopulmonary shunt after ligation of the main pulmonary artery distally. Two to 3 days after delivery at term, lambs (n = 11) underwent an open sternotomy and 30 minutes of deep hypothermic circulatory arrest. Both before and after bypass, respiratory manipulations, including administration of nitric oxide (80 ppm), 100% oxygen, 10% oxygen, and 5% carbon dioxide, were performed and hemodynamic variables were measured. RESULTS: Nitric oxide and oxygen caused a decrease in pulmonary vascular resistance and an increase in the pulmonary/systemic blood flow ratio, both before and after bypass. Hypoxia and carbon dioxide produced a significant rise in pulmonary vascular resistance and a significant drop in the ratio of pulmonary to systemic blood flow. CONCLUSIONS: Oxygen, nitric oxide, and carbon dioxide all appear to be useful means of manipulating pulmonary vascular resistance and pulmonary/systemic blood flow ratio in neonatal lambs with single ventricle physiology, but further investigation is necessary to understand their dose responsive effects and the effects of prolonged administration.

Animals↗

PubMed1996

Long-term outcome after fetal cardiac bypass: fetal survival to full term and organ abnormalities.

BACKGROUND: Earlier work suggests that fetal cardiac bypass is technically feasible but results in significant placental dysfunction. Many of the stimuli that initiate this placental dysfunction have been identified in the past several years and these involve fetal stress, extracorporeal surfaces, priming substances (maternal blood), and flow characteristics. Fetal survival with conventional methods of bypass has been far less than optimal. A novel fetal bypass circuit requiring no priming volume was designed incorporating an in-line axial flow pump (Hemopump, Johnson & Johnson Interventional Systems, Rancho Cordova, Calif.) and was demonstrated to have a marked beneficial effect on placental function. OBJECTIVE: The purpose of this study was to investigate the effect of this newly developed customized fetal bypass circuit on fetal survival and developing fetal organs. METHODS AND RESULTS: Nine fetuses at 122 to 126 days of gestation were subjected to fetal cardiac bypass via a transsternal approach, with a 16F single right atrial venous cannula and a 12F arterial cannula. Normothermic cardiac bypass was continued for 30 minutes at flow rates of 320 +/- 32 ml/kg. Of the nine fetuses, one fetus was stillborn 4 days after bypass and eight (89%) were delivered alive after progressing to term gestation. One lamb died of blunt trauma 1 day after birth. All other lambs (n = 7) thrived normally, and at 1 week of age they were subjected to autopsy. No gross hemorrhagic or thromboembolic lesions were detected in the organs examined including the brain. Microscopic examination of representative sections from all organs revealed mild pleural reaction in two lambs, and in two other lambs the hepatocytes showed evidence of mild increase in glycogen content, the significance of which is unknown in relation to fetal bypass. In one fetus that was aborted there was evidence of mild to moderate neuronal loss in the cerebral cortex. CONCLUSION: This study demonstrates that with improvements in fetal extracorporeal circuitry and techniques very favorable fetal outcome can be achieved. Further studies are necessary to evaluate the effects of bypass on fetal brain in an appropriate animal model. Advances in extracorporeal circuitry to suit the unique fetal physiology increase the possibility of future clinical application.

Animals↗

PubMed1996

Aortoventriculoplasty with the pulmonary autograft: the "Ross-Konno" procedure.

BACKGROUND: For patients with complex left ventricular outflow tract obstruction, including hypoplastic aortic anulus with or without severe diffuse subaortic stenosis, various aortoventriculoplasty procedures (e.g., Konno procedure and its modifications; extended aortic allograft root replacement) are important management options. In younger patients, however, reoperation for valve replacement is inevitably required, and anticoagulation issues pose additional problems. The pulmonary autograft provides a promising option for aortic valve replacement as part of the aortoventriculoplasty procedure in children. Long-term follow up shows that the pulmonary autograft functions well as the systemic arterial (neoaortic) valve and that valve growth occurs. METHODS: Between July 1993 and May 1995, 11 patients 4 days to 17 years old (median 12 months) underwent aortoventriculoplasty with pulmonary autograft (Ross-Konno procedure). The diagnoses were aortic stenosis with or without subaortic stenosis (n = 8), Shone complex (n = 2), and interrupted aortic arch with subaortic stenosis (n = 1). On average, 1.9 previous interventions had been performed per patient, including a previous Konno procedure in one patient. The aortic root was replaced with a pulmonary autograft valve. The left ventricular outflow tract was enlarged with a Dacron polyester fabric patch in two patients, with an allograft aortic patch in two patients and a right ventricular infundibular free wall muscular extension harvested in continuity with the autograft in seven patients. RESULTS: Intraoperative transesophageal echocardiographic assessment revealed mild aortic insufficiency in one patient. One patient had a residual left ventricular outflow tract gradient of 15 mm Hg. Significant complications were cardiac tamponade from bleeding (n = 1) and complete heart block necessitating a permanent pacemaker (n = 1). Follow-up ranged from 2 weeks to 16 months. To date, there have been no late deaths or reoperations. Follow-up echocardiography revealed mild autograft insufficiency in one patient and a 16 mm Hg residual left ventricular outflow tract gradient in one patient. CONCLUSIONS: Initial experience suggests that aortoventriculoplasty with the pulmonary autograft is an excellent alternative for young patients with complex left ventricular outflow tract obstruction. Because the pulmonary autograft has been shown to grow after implantation, reoperation on the left ventricular outflow tract is likely to be avoided.

Adolescent↗

PubMed1996

Regression of tricuspid regurgitation after two-stage arterial switch operation for failing systemic ventricle after atrial inversion operation.

The cases of five patients with previous Senning (n = 4) or Mustard (n = 1) operations and failing systemic ventricles in whom banding of the pulmonary artery was performed as an interim step toward an arterial switch procedure are reported. The rise in the ratio of left to right mean systolic ventricular pressure, from 0.35 before operation to 0.90 during operation and 0.80 on the first postoperative day, caused a shift of the ventricular septum from a leftward to a midline or nearly midline position. This shift was associated with a reduction of tricuspid regurgitation. At a median interval of 5.1 months after pulmonary artery banding, the mean left ventricular posterior wall thickness had increased to 8.2 mm, versus 5 mm before operation, and the mean left ventricular myocardial mass index had increased to 90 gm/m2, versus 55.6 gm/m2 before operation. After the arterial switch operation, which was performed in four patients, the tricuspid regurgitation decreased to a trivial amount (n = 1) or disappeared completely (n = 3).

Adult↗

PubMed1996

Hemodynamic effects of epinephrine, bicarbonate and calcium in the early postnatal period in a lamb model of single-ventricle physiology created in utero.

OBJECTIVES: A reproducible fetal animal model of single-ventricle physiology was created to examine the effects of pharmacologic agents commonly used in the perinatal and perioperative intensive care management of patients with a single ventricle. BACKGROUND: Single-ventricle physiology is characterized by parallel pulmonary and systemic circulations, with effective blood flow to each determined by the relative resistances in the pulmonary and systemic vascular beds. Perinatal and perioperative management of these patients is largely based on empiric observations and differs considerably between institutions and is further complicated by the transitional physiology of the newborn. The lack of animal models of single-ventricle physiology has hindered the understanding of this problem. METHODS: A 10-mm, Damus-Kaye-Stansel-type aortopulmonary anastomosis was created in 10 fetal sheep at 140 +/- 1.2 days of gestation. The main pulmonary artery was ligated distally, and pulmonary blood flow (Qp) was provided through a 5-mm aortopulmonary shunt. Eight lambs were delivered at term and placed on cardiopulmonary bypass (30 min) 48 to 72 h after birth. Pharmacologic interventions (0.1 microgram/kg body weight per min of epinephrine, 2 mEq/kg of sodium bicarbonate and 10 mg/kg of calcium chloride) were performed before and after bypass, and hemodynamic responses were observed. The response to the epinephrine bolus was determined only in the postbypass study. RESULTS: Both before and after bypass, epinephrine infusion and calcium and bicarbonate administration increased Qp and systemic blood flow (Qs) (total cardiac output) but produced only small changes in the Qp/Qs ratio (-0.5% to -7.3% change). With the epinephrine bolus, Qp increased enormously, and the Qp/Qs ratio increased by 584% (p < 0.001). CONCLUSIONS: In neonatal lambs with single-ventricle physiology created in utero, epinephrine infusion and calcium and bicarbonate administration increased total cardiac output without significantly compromising the Qp/Qs ratio. However, epinephrine bolus seems to be hemodynamically detrimental in circumstances of single-ventricle physiology and should be used with caution and probably in relatively lower doses in the resuscitation of patients with single-ventricle physiology. Further investigation of the dose-dependent effects and the effects of prolonged administration of common pharmacologic agents will enable better management of patients with single-ventricle physiology.

Animals↗

PubMed1996

Antituberculosis activities of clofazimine and its new analogs B4154 and B4157.

In our efforts to develop new drugs for the treatment of tuberculosis, especially that caused by multidrug-resistant strains, we investigated clofazimine (CFM) and two of its analogs, B4154 and B4157, for their antituberculosis activities. Twenty M. tuberculosis strains were tested, including 16 drug-resistant strains (strains resistant to one or more antituberculosis drugs), for their susceptibilities to these three agents. All of the strains were found to be susceptible to B4154 and B4157, and one strain showed moderate resistance to CFM. The MICs of B4154, B4157, and CFM at which 90% of strains were inhibited were 0.25, 0.12, and < or = 1.0 microgram/ml, respectively. The intracellular activities of CFM and B4157 were superior to that of B4154. The chemotherapeutic activities of the three compounds were evaluated in C57BL/6 mice. At a dose of 20 mg/kg of body weight, the activity of CFM was slightly superior to that of B4157; however, both compounds prevented mortality and caused a significant reduction in the numbers of CFU in the lungs and spleens. The animals treated with B4157 showed less pigmentation than animals treated with CFM. The chemotherapeutic activity of CFM was comparable to those of rifampin and isoniazid. Complete susceptibility of multidrug-resistant strains to CFM and B4157 and the therapeutic efficacies of these compounds against mouse tuberculosis make these drugs attractive agents for the treatment of drug-resistant tuberculosis.

Animals↗