Structural valve deterioration of the Labcor Dokimos aortic prosthesis: a single-centre experience.

OBJECTIVES: The goal of this study was to assess the performance and incidence of the deterioration of the Labcor Dokimos bioprosthetic aortic valve. METHODS: We performed a retrospective medical chart review of 116 patients who underwent surgical aortic valve replacement with the Labcor Dokimos aortic valve between 2010 and 2018. Abstracted data included patient demographic and echocardiographic data. Patients were divided into 2 groups: patients with structural valve deterioration (SVD) and patients without SVD. RESULTS: Among the patients with complete follow-up (n = 95), 10 patients were excluded because they died within a year; 85 patients were included in the final analysis. Of the 85 patients, 32 (38%) developed SVD; 22 (26%) had severe SVD, 15 (18%) of whom underwent reintervention. The most common aetiology of SVD was severe central aortic regurgitation, which was detected in 91% of the patients who had severe SVD. The average time from operation to severe SVD was 4.7 years with a minimum of 1.5 years and a maximum of 7.9 years. CONCLUSIONS: Bioprosthetic aortic valve deterioration due to severe aortic regurgitation is common and occurs early with the Labcor Dokimos valve. This occurrence needs to be furthered investigated in larger registries.

Large congenital left atrial wall aneurysm: An updated and comprehensive review of the literature.

BACKGROUND: Congenital left atrial wall aneurysms are rare abnormalities that arise from a developmental weakness in the muscular wall. It may be misdiagnosed or go undetected and the delay in diagnosis can lead to catastrophic consequences. CASE PRESENTATION: An updated and comprehensive review of the literature was performed for all patients with this abnormality under the age of 18. A total of 15 cases including ours are presented in this article. We present a 10-month-old boy who was referred to our center for cardiomegaly. Workup revealed a large atrial wall aneurysm that was successfully corrected with surgery. CONCLUSION: Historically, left atrial aneurysms were uncommon in the absence of valvular heart disease or other cardiac conditions. Congenital aneurysms are rare phenomenon because they arise without an acquired cardiac disease and surgical correction is crucial for survival.

Equipoise between radial artery and right internal thoracic artery as the second arterial conduit in left internal thoracic artery-based coronary artery bypass graft surgery: a multi-institutional study†.

OBJECTIVES: Multiple arterial coronary artery grafting (MABG) improves long-term survival compared with single arterial CABG (SABG), yet the best second arterial conduit to be used with the left internal thoracic artery (LITA) remains undefined. Outcomes in patients grafted with radial artery (RA-MABG) versus right internal thoracic artery (RITA-MABG) as the second arterial graft were compared with SABG. METHODS: Multi-institutional, retrospective analysis of non-emergent isolated LITA to left anterior descending coronary artery CABG patients was performed using institutional Society of Thoracic Surgeon National Adult Cardiac Surgery Databases. 4484 (54.5%) SABG [LITA ± saphenous vein grafts (SVG)], 3095 (37.6%) RA-MABG (RA ± SVG) and 641 (7.9%) RITA-MABG (RITA ± SVG) patients were included. The RITA was used as a free (68%) or in situ (32%) graft. RA grafts were principally anastomosed to the ascending aorta. Long-term survival was ascertained from US Social Security Death Index and institutional follow-up. Triplet propensity matching and covariate-adjusted multivariate logistic regression were used to adjust for baseline differences between study cohorts. RESULTS: Compared with the SABG cohort, the RITA-MABG cohort was younger (58.6 ± 10.2vs65.9 ± 10.4, P < 0.001), had a higher prevalence of males (87% vs 65%, P < 0.001) and was generally healthier (MI: 36.7% vs 56.7%, P < 0.001, smoking: 56.8% vs 61.1%, IDDM: 3.0% vs 14.4%, CVA: 2.6% vs 10.0%). The RA-MABG cohort was generally characterized by a risk profile intermediate to that of SABG and RlTA-MABG. Unadjusted 5-, 10- and 15-year survival rates were best in RITA-MABG (95.2%, 89% and 82%), intermediate in RA-MABG (89%, 74%, 57%) and worst in SABG (82%, 61% and 44%) cohorts (all P < 0.001). Propensity matching yielded 551 RA-MABG, RITA-MABG and SABG triplets, which showed similar 30-day mortality. Late survival (16 years) was equivalent in the RA-MABG and RITA-MABG cohorts [68.2% vs 66.7%, P = 0.127, hazard ratio (HR) = 1.28 (0.96-1.71)] and both significantly better than SABG (61.1%). The corresponding SABG versus RITA-MABG and SABG versus RA-MABG HRs (95% confidence interval) were 1.52 (1.18-1.96) and 1.31 (1.01-1.69) with P < 0.002 and P = 0.038, respectively. CONCLUSIONS: RA-MABG or RITA-MABG equally improve long-term survival compared with SABG and thus should be embraced by the Heart Team as the therapy of choice in LITA-based coronary artery bypass surgery.

The cleft sternum: a possible role for pliable prosthetic reconstruction.

BACKGROUND: Faced with our intraoperative inability to primarily close a very wide isolated cleft sternum of a pediatric patient without causing cardiovascular decompensation, we describe our use of a synthetic material for partial approximation allowing muscular coverage. METHOD: We report an infant who was born with an isolated large complete sternal cleft where a trial of primary surgical repair had to be abandoned because of cardiovascular compromise. A similar difficulty was encountered in approximating the origins of both pectoralis major muscle flaps at the midline. Thus, a pliable synthetic patch was helpful in partially obliterating the widened sternal defect allowing successful muscular coverage. RESULT: Closure of a wide congenital sternal cleft using a synthetic material that partially obliterated an otherwise widely separated cleft sternum which was neither amenable for primary repair, nor by bilateral pectoralis major advancement alone, was possible. CONCLUSION: Strong prosthetic pliable material may offer a simple and useful procedure allowing obliteration of the widely separated cleft sternum not amenable for primary repair.

Research in congenital heart disease: a comparative bibliometric analysis between developing and developed countries.

Congenital heart disease (CHD) is the most common congenital anomaly, affecting 1 % of live births. The field of pediatric cardiology has witnessed major advances over the past 25 years triggered by research initiatives focusing on CHD. However, large disparities exist in research capabilities between Arab developing nations and the developed nations. This study used bibliometric analysis to assess the contribution of the Arab countries to CHD research. To identify articles on CHD published in the Arab countries, the United States, and Europe, a systematic search was run on MEDLINE, PubMed, and Scopus. The Arab countries, with an estimated population of 362 million, published 530 research articles addressing CHD in the last 25 years (average, 1.5 articles/10(6) population). This compares with 12,936 research articles published in the United States (average, 41 articles/10(6) population) and 12,260 published in Europe (average, 24.3 articles/10(6) population). Basic research relating to genetics and animal models of CHD is emerging sparsely in the Arab world, with few articles published in high-impact-factor journals. The Arab world research output in the field of CHD per capita is substantially low, estimated to be 29 times less than in developed countries. Despite the minimal increase in published research articles in global periodicals, most of the research relating to CHD continues to be far from innovative. Regional collaborations with international linkage are starting to evolve. The research facilities in the Arab countries need to increase substantially in research and infrastructure funding to keep up with the pace of research in developing countries.

Rupture of sinus of Valsalva aneurysm with aorto-biventricular fistulas and right-ventricular outflow tract obstruction: a unique association.

Sinus of Valsalva aneurysms are a rare entity. Rupture of such aneurysms is a major cause of aortocardiac fistulas usually occurring between the right sinus of Valsalva and right cardiac chambers. We report an exceptional case of a ruptured congenital sinus of Valsalva aneurysm with fistulas involving both the right- and left-ventricular outflow tracts and causing RVOT obstruction. We also demonstrate the utility of computed tomography angiography and transesophageal echocardiography in diagnosing these fistulas.

The status of pediatric cardiology at a tertiary center in Lebanon.

PROBLEM: Cardiac disease, both congenital and acquired, contributes significantly to morbidity and mortality in children. METHODS: This article describes the status of pediatric cardiology at the Children's Heart Center in the American University of Beirut Medical Center. It addresses the available clinical services as well as the research and educational activities that are present at a tertiary center in Lebanon, a developing country with a population of 4 million. RESULTS: Lebanon has witnessed major developments in the field of pediatric cardiology over the past few years. About 650 babies are born with heart disease every year, with more than 425 needing treatment. Nearly all types of interventional catheterization procedures are currently being performed. About 300 open and closed pediatric cardiac surgeries are performed per year in Lebanon. In 2008, the in-hospital surgical mortality rate at our center was 2.6%, reflecting the good level of care in the treatment of children with congenital heart disease (CHD) in Lebanon. Basic research in the field of pediatric cardiology is emerging at our center. Our team has been studying the effect of chronic hypoxemia on the neonatal myocardium in an animal model of chronic hypoxia, as well as the study of molecular basis of CHD. CONCLUSION: Appropriate identification of cardiac disease, its epidemiology, and outcome is of utmost importance in guiding adequate care. Centralization of facilities is important to improve results and level of care.

Absence of GJA1 gene mutations in four patients with anomalous left coronary artery from the pulmonary artery (ALCAPA).

PROBLEM: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare form of congenital heart disease with no known genetic cause. It is usually diagnosed within the first year of life; it results in myocardial cell death, congestive heart failure and lethality if left untreated. Connexin 43alpha1 is a member of the gap junction family of proteins demonstrated by animal studies to have a role in coronary artery patterning during development. No previous studies have investigated the role of this gene in patients with ALCAPA. METHODS: We forth herein describe the clinical presentation of four patients who presented to the Children's Heart Center at AUBMC and had the final diagnosis of ALCAPA. Screening the GJA1 gene coding for connexin 43alpha1 was undertaken. RESULTS: No mutations were found in the patients or their parents, except for one polymorphism in one of the parents in the 3' untranslated region. All four patients underwent surgical repair with excellent outcome. CONCLUSION: This paper raises the awareness of this rare condition enabling physicians to reach the adequate diagnosis which will allow early surgical intervention and better prognosis. Our patient sample did not exhibit any evidence of association between connexin 43alpha1 and the clinical phenotype.

Femoral vein cannulation performed by residents: a comparison between ultrasound-guided and landmark technique in infants and children undergoing cardiac surgery.

BACKGROUND: Percutaneous cannulation of the femoral vein, in the pediatric age group, can be technically challenging, especially when performed by residents in training. We examined whether the use of real-time ultrasound guidance is superior to a landmark technique for femoral vein catheterization in children undergoing heart surgery. METHODS: Patients were prospectively randomized into 2 groups. In group LM, the femoral vein was cannulated using the traditional method of palpation of arterial pulse. In group US, cannulation was guided by real-time scanning with an ultrasound probe. The time to complete cannulation (primary outcome), success rate, number of needle passes, number of successful cannulations on first needle pass, and incidence of complications were compared between the 2 groups. RESULTS: Forty-eight pediatric patients were studied. The time to complete cannulation was significantly shorter (155 [46-690] vs 370 [45-1620] seconds; P = 0.02) in group US versus group LM. The success rate was similar in both groups (95.8%). The number of needle passes was smaller (1 [1-8] vs 3 [1-21]; P = 0.001) and the number of successful cannulations on first needle pass higher (18 vs 6; P = 0.001) in group US compared with group LM. The incidence of femoral artery puncture was comparable between the 2 groups. CONCLUSIONS: Ultrasound-guided cannulation of the femoral vein, in pediatric patients, when performed by senior anesthesia residents, is superior to the landmark technique in terms of speed and number of needle passes, with remarkable improvement in first attempt success.

Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts.

This study focused on the regulation and affinity modulation of the insulin receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ-induced type 1 diabetic rats. Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. The results showed that diabetes (D) decreased the tau value on the coronary endothelium and increased it on cardiomyocytes compared with the nondiabetic group (N). Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on the coronary endothelium only. On the coronary endothelium, tau values of DI and DIDp were normalized. Western blots of the insulin receptor showed upregulation in D, downregulation in DI, and normalization in DE and DDp. Immunohistochemistry and RT-PCR findings indicated atrial natriuretic factor (ANF) in all diabetic ventricles, thus ascertaining hypertrophy. Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4.

A young female with an unusual cause of dyspnea.

Within the context of coronary artery anomalies, coronary fistulas are classified by termination. A coronary artery fistula (CAF) involves a sizable communication between a coronary artery and a heart chamber (coronary-cameral fistula) or a segment of the systemic or pulmonary system (coronary artery arteriovenous fistula). These are often due to deviations from normal embryological development. CAF may be present in patients at any age, but is usually suspected in early childhood and accounts for 0.08-0.4% of congenital cardiac anomalies. They may also be acquired by trauma or from invasive cardiac procedures. The majority of CAF arises from the right coronary artery (55%) and the left anterior descending coronary artery, with the circumflex rarely involved. The outcome of these connections depends upon the termination site. The pathophysiology of these lesions is identical. Coronary artery anomalies are difficult to detect clinically. Most are benign but some may produce symptoms that can be life threatening. We present a female with an unusual cause of dyspnea found to have a continuous heart murmur, cardiac catheterization showed an evidence of a long tract arising from the origin of the right coronary artery with flow directed towards the right atrium and the right atrial appendage.

A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot.

In vertebrates, heart formation which integrates different structures and cell types is a complex process that involves a network of genes regulated by transcription factors. Proper spatiotemporal expression of these factors ensure the highly needed tight control of each step in organogenesis. A mistake at any step from cell-commitment to valve formation will have a major impact on heart morphogenesis and function leading to congenital heart disease (CHD). Cardiac abnormalities occur with an incidence of one per 100 live births and represent 25% of all congenital malformations. As an alternative approach to linkage-analysis of familial cases of CHD, we started screening familial and sporadic cases of CHDs in a highly consanguineous population for mutations in genes encoding cardiac-enriched transcription factors. The evolutionarily conserved role of these proteins in cardiac development suggested a role in CHD. In this study, we report a mutation in the gene encoding GATA4, one of the earliest markers of heart development. This mutation was found in two out of 26 patients with Tetralogy of Fallot (TOF), and in none of the 94 patients with different phenotypes included in the study, nor in 223 healthy individuals. The heterozygous mutation results in an amino acid substitution in the first zinc finger of GATA4 that reduced its transcriptional activation of downstream target genes, without affecting GATA4 ability to bind DNA, nor its interaction with ZFPM2.

Patterns of congenital heart disease in unoperated adults: a 20-year experience in a developing country.

BACKGROUND: The number of patients with congenital cardiac disease reaching adulthood is increasing steadily. Many adults with such disease face both medical and surgical difficulties. HYPOTHESIS: This retrospective study was undertaken to assess the frequency and outcome of congenital heart disease (CHD) in unoperated adults. METHODS: The charts of all patients with unoperated CHD, who were admitted to a tertiary care center in Beirut, Lebanon, between 1980 and 2000 were reviewed. Of these, 206 patients (52% men, age at admittance 18-71 years [32.8 +/- 13.3 years]) with a diagnosis of CHD were evaluated. Atrial septal defect (ASD) was the most common cardiac malformation with a relative frequency of 53%, followed by ventricular septal defects (11%), tetralogy of Fallot (11%), aortic anomalies (7%), pulmonary stenosis (6%), and Ebstein anomaly (4%). Most patients were symptomatic upon presentation, with dyspnea on exertion being the most common presenting symptom. Twenty-seven patients (13%) had cyanotic CHD. Of 179 acyanotic patients, 113 (63%), and 17 of 27 cyanotic patients (63%) underwent surgical intervention. In-hospital surgical complications for the acyanotic group included cerebrovascular accident (2%) and heart block (1%). Total surgical mortality was 4 of 130 (3%). One patient with tetralogy of Fallot presented with endocarditis and died. CONCLUSION: Atrial septal defect is the most common defect reported in our experience; however, it occurs more frequently than that reported in the literature. Although most patients were symptomatic on presentation, their functional status was stable. Accordingly, their hospital course, whether managed medically or surgically, held a relatively low complication rate. This could be attributed to the uncomplicated nature of pathologies in our series. The surgical mortality and in-hospital complications were slighter higher than those reported for similar lesions if repaired during childhood. This study reflects the relative frequency of various cardiac malformations in selected patients with "grown up" congenital heart disease (GUCH) and their natural survival pattern.

Tissue-specific ceramide response in the chronically hypoxic rat model mimicking cyanotic heart disease.

BACKGROUND AND OBJECTIVE: Acute hypoxia is associated with apoptosis and increase in ceramide levels in various organs. To assess the effect of chronic hypoxia on ceramide accumulation in the lungs and kidneys, we utilized an animal model mimicking cyanotic heart disease. METHODS: Rats were placed in a hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglas chamber. Controls remained in room air. Animals were sacrificed and the lung and kidneys were harvested and weighed at 1 and 4 weeks, respectively. Ceramide levels were measured using a modified diacylglycerol kinase assay. RESULTS: Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed lung and kidney masses were significantly increased in the hypoxic animals as compared to controls at 1 and 4 weeks, respectively. The ceramide levels in the hypoxic lungs and kidneys were not significantly different from control groups at 1 and 4 weeks. [Ceramide/phosphate ratio in the kidneys was 1.28 +/- 0.17 (C) versus 1.18 +/- 0.12 (H) at 1 week; P = 0.39, and 1.46 +/- 0.08 (C) versus 1.33 +/- 0.15 (H) at 4 weeks (P = 0.44)] and [ceramide/phosphate ratio (pmol/nmol) in the lungs was 2.29 +/- 0.14 (C) versus 1.98 +/- 0.12 (H) at 1 week (P = 0.17), and 2.42 +/- 0.16 (C) versus 2.30 +/- 0.05 (H) at 4 weeks, P = 0.34]. CONCLUSION: The response of lungs and kidneys to chronic hypoxia includes increase in indexed mass and lack of ceramide accumulation. This is similar to the response previously reported in the chronically hypoxic brain and heart. Thus, various organs appear to have similar ceramide response pattern to chronic hypoxia.

Coronary artery bypass surgery in octogenarians: outcomes in a tertiary referral university hospital in a developing country.

BACKGROUND: The number of people older than 80 years is increasing worldwide and many of these patients are being referred for coronary artery bypass surgery (CABG). Several recent reports from the USA and Europe have shown that CABG can be performed in octogenarians with an acceptable risk. However, data from developing countries regarding this subject is lacking. The objective of this study was to analyze the clinical characteristics and in-hospital events of octogenarian patients undergoing CABG at a tertiary referral university hospital in a developing country. METHODS: The study included 28 consecutive octogenarian patients who underwent CABG at the American University of Beirut, between January 1998 and December 2000. The medical records of these patients were reviewed for demographic information, clinical and catheterization findings, operative characteristics, and in-hospital events (death, myocardial infarction, and stroke). RESULTS: The mean age of the study group was 82 +/- 2 years and 75% were males. Seventy-eight percent of the patients had an acute myocardial infarction or unstable angina prior to CABG. All of the patients were in NYHA class I or II and none of the operations were done on an emergent basis. The mean ejection fraction was 48 +/- 7%. Eighty-six percent of patients had multivessel disease and four patients had aortic valve replacement (AVR) concomitantly with the CABG. The in-hospital mortality was 0%. Three patients (11%) had a post-operative myocardial infarction, and one patient (4%) had a stroke. The mean post-operative stay was 9 +/- 7 days with only three patients (11%) staying for more than 14 days. The multivariate predictors of in-hospital cardiovascular events were concomitant AVR (P=0.01), and an ejection fraction <40% (P=0.03). CONCLUSION: In carefully selected octogenarian patients who are clinically stable in NYHA class I or II, and where the operation is not done on an emergent basis, CABG can be performed with an acceptable risk and a low in-hospital mortality.

Acute respiratory distress associated with external jugular vein catheterization in the newborn.

We report on the acute onset of respiratory distress secondary to fluid accumulation in the chest within hours of placement of an external jugular venous line in a newborn. External jugular venous catheterization in the newborn is a procedure with potentially serious complications, and should be avoided unless the patient is monitored closely.

Endocrine changes in a rat model of chronic hypoxia mimicking cyanotic heart disease.

OBJECTIVE: The endocrine system plays an important role in the adaptation to hypoxia. The aim of this study is to assess the effect of chronic hypoxia on endocrine changes in a neonatal animal model mimicking cyanotic heart disease. METHODS: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% in an airtight Plexiglas chamber. Controls remained in room air. Animals were sacrificed at 4 and 8 weeks of life. Hematocrit, Free T4 (FT4), Thyrotropin (TSH), corticosterone, and Growth hormone (GH) were measured. RESULTS: Significant polycythemia developed in the hypoxic rats. Free T4 levels were significantly lower in the hypoxic (H) group compared to the control (C) group at 4 and 8 weeks with FT4 of 2.44 +/- 1.11 ng/dL (H) and 4.35 +/- 1.62 (C) at 4 weeks with a p value < 0.005 and FT4 of 2.01 +/- 0.36 (H) and 3.25 +/- 0.54 (C) ng/dL at 8 weeks with p < 0.01. At 8 weeks TSH levels were significantly lower in the hypoxic group (1.84 +/- 0.9 ng/mL (H) vs. 3.11 +/- 1.1 (C)) with p < 0.05. Corticosterone levels were higher in the hypoxic group with values of 126 +/- 14.8 ng/mL (H) and 114.1 +/- 12.6 (H) at 4 and 8 weeks respectively, when compared to the control group with values of 82.9 +/- 18.1 (C) and 92.7 +/- 10.3 (C) and 4 and 8 weeks with p < 0.0005 and < 0.05 respectively. Growth hormone levels were lower in the hypoxic group at 4 and 8 weeks with p < 0.05 and p < 0.001, respectively. CONCLUSION: Chronic hypoxia in our neonatal rat model was associated with decrease in growth hormone levels and an increase in corticosterone levels. Furthermore, hypoxia resulted in thyroid hormone axis suppression. This effect seems to centrally mediated.

Parental consanguinity and congenital heart malformations in a developing country.

The association between isolated congenital heart defects and consanguinity was examined in 759 Lebanese patients with different types of congenital heart malformations. The subjects were patients of the Children's Cardiac Registry Center (CCRC) at the American University of Beirut Medical Center. The proportion of first-cousin marriages among cardiac subjects was compared to that of the National Collaborative Perinatal Neonatal Network (NCPNN), after adjusting for the subjects' geographic distribution, and to the highest proportion reported by NCPNN. In general, the proportion of overall parental consanguinity and first-cousin matings among CCRC subjects (34.7 and 20.2%, respectively) were significantly higher than the highest proportion of first-cousin marriages reported by NCPNN (Bekaa subjects; 13.2%) (P < 0.0001). Comparison with the NCPNN-adjusted first-cousin mating proportion revealed a significantly increased rate of consanguinity in all categories of cardiac malformations except great vessel and coronary artery lesions (P < 0.05). The following lesions were significantly associated with increased parental consanguinity: aortic anomalies (aortic insufficiency, aortic stenosis, bicuspid aortic valve), atrial septal defect, double-outlet right ventricle, pulmonary atresia, patent ductus arteriosus, pulmonic stenosis, tetralogy of Fallot, and ventricular septal defect (P < 0.05). Higher maternal education was the only variable that was negatively correlated with parental consanguinity (P = 0.037). Our study emphasizes the role of homozygous recessive genes in the causation of different types of isolated congenital heart malformations, known to follow a multifactorial pattern of inheritance. There is an urgent need for educating the public on the deleterious effects of inbreeding, especially in developing countries with high overall consanguinity rates and limited financial resources.

Cardiac growth patterns in response to chronic hypoxia in a neonatal rat model mimicking cyanotic heart disease.

OBJECTIVE: Myocardial growth during fetal life is accomplished by the proliferation of myocytes. Shortly after birth, normal myocytes largely lose their capability to replicate. The present study aims to assess the effect of persistent postnatal hypoxia on myocardial growth patterns in an animal model mimicking cyanotic heart disease. METHODS: Sprague-Dawley rats were placed in a normobaric hypoxic environment at birth and oxygen levels were maintained at 10% (group H). Controls (group C) remained in room air. The animals were sacrificed and the hearts were harvested at one, four and eight weeks. RESULTS: Significant polycythemia developed in the hypoxic rats. There was a significant increase in indexed right ventricle (RV) and left ventricle (LV) masses compared with controls. Myocardial DNA concentrations were significantly increased in both ventricles of the hypoxic rats. For the RV, the increase in DNA content for group H was 135%, 132% and 112% that of group C values at one, four and eight weeks, respectively. RV and LV myocardial protein:DNA ratios were lower in the one-week- and four-week-old hypoxic rats, and significantly higher in the hypoxic eight-week-old rats. Polyploidy, hydroxyproline concentrations and dry:wet weight ratios were not significantly different in the LV and RV between both group H and group C animals. CONCLUSION: Cardiac mass increases in response to chronic hypoxia were greater in the RV than the LV. This increase was mainly due to myocardial proliferation in the first four weeks of life. Although the three groups of hypoxic rats had significant elevations in DNA concentration compared with controls, there was a shift from proliferation to hypertrophy after week 4 of life. The age of the myocyte appears to be the most important factor in triggering proliferation in this hypoxic animal model.