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Biomedical subjects

Peter J Gruber

Publications and source records attributed to Peter J Gruber.

15 recordsLinked to original sources
PubMed2006

Early results of single-stage biventricular repair of severe aortic hypoplasia or atresia with ventricular septal defect and normal left ventricle.

OBJECTIVE: Biventricular repair of aortic atresia (or severe aortic hypoplasia) is possible in the presence of a ventricular septal defect and normal left ventricle. We considered whether primary biventricular repair was a safe alternative in all cases, even in the presence of interrupted aortic arch. METHODS: This was a retrospective analysis of patients who underwent primary biventricular repair consisting of a combination Norwood-type reconstruction of the aortic arch, baffle of the left ventricle to both semilunar roots, and conduit placement from the right ventricle to pulmonary arteries. RESULTS: Between January 1995 and January 2005, a total of 21 patients underwent primary biventricular repair at a median age of 5 days and a median weight of 3.0 kg. Aortic atresia was present in 7 and aortic stenosis in 14; 6 had interrupted aortic arch. All patients with aortic stenosis had annular diameters 3 mm or smaller. Median circulatory arrest time was 55 minutes, aortic crossclamp time was 56 minutes, and total support time was 99 minutes. In-hospital survival was 100%. Postoperative echocardiography in 19 patients demonstrated no significant outflow tract obstruction. Total stay was a median of 17 days. At midterm follow-up, there has been 1 late death, and reoperation has been necessary in 10 cases. CONCLUSION: Primary biventricular repair is a safe alternative to staged repair in all cases of aortic hypoplasia with ventricular septal defect and normal left ventricle.

Aorta, Thoracic↗
PubMed2006

Factors influencing neurologic outcome after neonatal cardiopulmonary bypass: what we can and cannot control.

Advances in cardiopulmonary bypass and surgical techniques have led to progress in the early repair of congenital heart defects in children. However, as increasing numbers survive their initial cardiac operation, an awareness is emerging that significant early and late neurologic morbidities continue to complicate otherwise successful operative repairs. Adverse neurologic outcomes after neonatal cardiac surgery are multifactorial and relate to both fixed and modifiable mechanisms. The purpose of this review is to (1) review mechanisms of brain injury after neonatal cardiopulmonary bypass, (2) examine risk factors, and (3) speculate on how investigations may improve our understanding of neurologic injury.

Alkalosis↗
PubMed2006

Outcomes of the Fontan procedure using cardiopulmonary bypass with aortic cross-clamping.

BACKGROUND: Avoidance of cardiopulmonary bypass (CPB) and aortic cross-clamping during the Fontan procedure has been advocated to improve outcomes. We continue to use CPB with aortic cross-clamping for the Fontan procedure. METHODS: We performed a review of patients undergoing the Fontan procedure between January 1, 2000 and December 31, 2004. RESULTS: The Fontan procedure was performed in 160 patients. The median age was 2.2 years (range, 1.0 to 29.1 years). Hypoplastic left heart syndrome or a variant was present in 114 patients (71%), and heterotaxy was present in 19 (12%). CPB and modified ultrafiltration were used in all patients. Aortic cross-clamping was used in 154 (96%) of 160 patients and deep hypothermic circulatory arrest (DHCA) in 132 (83%). A lateral tunnel Fontan was performed in 69 patients (43%) and an extracardiac Fontan in 91 (57%). A fenestration was created in 144 patients (90%). Two patients died. Freedom from death or takedown was 98% (157/160). Median duration of pleural drainage was 2 days (range, 1 to 44 days) and was more than 14 days in 16 patients. Median duration of hospitalization was 6 days (range, 3 to 55 days). The small number of deaths precluded assessment of risk factors for mortality. By multivariable analysis, risk factors for pleural drainage longer than 3 days were extracardiac connection (p < 0.001) and increasing mean pulmonary artery pressure before the Fontan procedure (p = 0.033). By multivariable analysis, risk factors for hospitalization for more than 7 days were extracardiac connection (p = 0.003), increasing duration of total support (CPB and DHCA, p = 0.027), and decreasing systemic oxygen saturation before the Fontan procedure (p = 0.048). CONCLUSIONS: The Fontan procedure can be performed using CPB and aortic cross-clamping with low morbidity and mortality.

Adolescent↗
PubMed2006

Extracorporeal membrane oxygenation after stage I reconstruction for hypoplastic left heart syndrome.

OBJECTIVE: Although extracorporeal membrane oxygenation (ECMO) is an acceptable strategy for children with refractory cardiac dysfunction after cardiac surgery, its role after stage I reconstruction for hypoplastic left heart syndrome and its variants is controversial. Our objective is to describe the outcome of "nonelective" ECMO after stage I reconstruction. DESIGN: Retrospective case series. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Infants placed on ECMO after stage I reconstruction from January 1998 to May 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 382 infants who underwent stage I reconstruction during the study period, 36 (9.4%) required ECMO in the postoperative period. There were 22 infants with hypoplastic left heart syndrome. Indications for ECMO included inability to separate from cardiopulmonary bypass in 14 and cardiac arrest in 22. Fourteen infants (38.8%) survived to hospital discharge. Nonsurvivors had longer cardiopulmonary bypass time (150.1 +/- 70.0 mins vs. 103.9 +/- 30.0 mins, p =. 01). 9/14 infants (64%) supported with ECMO> than 24 hrs after stage I reconstruction survived while only 5/22 infants (22%) requiring ECMO< 24 hrs of stage I reconstruction survived (p =. 02). Of note, all five infants diagnosed with an acute shunt thrombosis were early survivors. Mean duration of ECMO was 50.1 +/- 12.5 hrs for survivors and 125.2 +/- 25.0 for nonsurvivors (p =. 01). 7/14 early survivors are alive at a median follow-up of 20 months (2-78 months). CONCLUSIONS: In our experience, ECMO after stage I reconstruction can be life saving in about a third of infants with otherwise fatal conditions. It is particularly useful in potentially reversible conditions such as acute shunt thrombosis and transient depression of ventricular function.

Extracorporeal Membrane Oxygenation↗
PubMed2005

Predominant fusion of bone marrow-derived cardiomyocytes.

OBJECTIVES: Here we address the capacity of bone marrow-derived cells (BMDCs) to trans-differentiate into mature myocytes under the physiological stimulus of exercise training. METHODS: For this purpose, we have transplanted bone marrow from mice ubiquitously expressing enhanced green fluorescence protein (eGFP) into host mice that have been subjected to a prolonged program of exercise. RESULTS: In all successful bone marrow reconstitutions (greater than 80%), we observed rare but consistent events of bone marrow-derived cardiomyocytes, the frequency of which was unchanged upon exercise training. We have further determined whether these recruited myocytes are a product of trans-differentiation or fusion by the use of a genetic system that distinguishes cell fusion from trans-differentiation in a single-cell assay. CONCLUSIONS: We concluded that both in the unchallenged mouse and in the trained specimens, fusion is the most prominent mechanism by which bone marrow-derived cells are observed in the myocyte compartment.

Animals↗
PubMed2005

Outcomes after the stage I reconstruction comparing the right ventricular to pulmonary artery conduit with the modified Blalock Taussig shunt.

BACKGROUND: Recent reports advocate that a right ventricular to pulmonary artery (RV-PA) conduit improves outcome after the stage I reconstruction. METHODS: We retrospectively compared the outcomes of all neonates who underwent a stage I reconstruction between January 1, 2002, and October 1, 2004, with use of the RV-PA conduit and modified Blalock-Taussig shunt (mBTS) interspersed over this time period. RESULTS: In all, 149 infants underwent a stage I reconstruction (95 mBTS, 54 RV-PA) for hypoplastic left heart syndrome (HLHS) or variants. There was a preference for the RV-PA conduit in patients with aortic atresia (mBTS 30% versus RV-PA 67%, p < 0.01). There was no difference in surgical mortality (mBTS 14% versus RV-PA 17%, p = 0.67), time to extubation (mBTS 4.5 +/- 4.8 days versus RV-PA 3.9 +/- 3.5 days, p = 0.47), or length of hospital stay (mBTS 25 +/- 29 days versus RV-PA 21 +/- 23 days, p = 0.52). There was an increased incidence of shunt reinterventions in the patients with the RV-PA conduit (mBTS 17% versus RV-PA 32%, p = 0.04). Patients with RV-PA conduit returned earlier for stage II reconstruction (mBTS 6.5 +/- 2.5 months versus RV-PA 5.6 +/- 1.7 months, p = 0.05). There was no difference in overall mortality (mBTS 32% versus RV-PA 30%, p = 0.45) with a median duration of follow-up of 18 +/- 8 months. CONCLUSIONS: Comparing shunt strategies (mBTS versus RV-PA) over the same time period, we found no difference in outcome. These data support the need for a larger prospective, randomized trial.

Arteriovenous Shunt, Surgical↗
PubMed2005

Cardiac development: new concepts.

Understanding normal development is a prerequisite to unraveling the mechanisms that underlie congenital heart disease, a critical step if one is to design rational new therapies. Over the past 20 years, human molecular genetics and developmental biology have provided a group of powerful tools to uncover a number of now well-defined pathways. There is now a confluence of new technologies and experimental systems that may allow for a more profound understanding in the near future.

GATA4 Transcription Factor↗
PubMed2004

Creation of a novel hemodialysis bridge graft to extend the life of an adolescent.

All conventional dialysis access options were exhausted in a 19-year-old girl with end-stage renal disease (ESRD). Her course was medically and psychosocially complicated. To save her life, a subclavian artery to right atrium hemodialysis bridge graft was created so that she could be dialyzed successfully. Adolescents and young adults confronted with the exhaustion of dialysis access and transplant options face extremely difficult management decisions. Attention to the multi-disciplinary needs of these patients and a combined effort by medical, surgical, psychological, and social work teams are necessary to address properly these dilemmas.

Adolescent↗
PubMed2004

Development gone awry: congenital heart disease.

Significant advances in the understanding of the molecular and genetic basis of congenital heart disease have emerged from gene inactivation studies in mice and from human genetic investigations. However, the ability to utilize information gleaned from animal models to inform clinical care of patients depends on an accurate anatomic analysis and presentation in terms that are meaningful to the clinical pediatric cardiologist. Likewise, the enormous depth and breadth of accumulated clinical experience can inform the developmental biologist and can highlight the importance and interrelationships of particular phenotypes. The explosion of potentially informative genetic tools demands that basic scientists and clinicians concerned with congenital cardiac disease enhance the ongoing bidirectional dialogue. In some cases, categories of congenital disease familiar to clinicians are not recognized by developmental biologists, and mechanisms accepted by the biologist seem inconsistent with clinical experience. In this review, we summarize some of the more clinically significant forms of congenital heart disease, and we highlight relevant genetic and developmental pathways.

Animals↗
PubMed2004

In vivo imaging of MLC2v-luciferase, a cardiac-specific reporter gene expression in mice.

RATIONALE AND OBJECTIVES: A reporter or marker gene that is detectable by in vivo imaging permits longitudinal monitoring of certain fundamental biological processes (eg, differentiation) within the context of physiologically authentic environments. Tissue-specific expression of a reporter gene can be achieved when it is under the transcriptional control of a tissue-specific promoter. The objective of this study was to construct a plasmid vector containing firefly luciferase (Fluc) marker gene downstream of the promoter sequence of rat ventricular myosin light chain 2 (MLC2v); to detect the in vivo expression of this cardiac-specific reporter (MLC2v-Fluc) in the mouse heart by bioluminescent imaging; and to correlate the bioluminescent signal with postmortem luminometer assay. MATERIALS AND METHODS: MLC2v-Fluc plasmid was generated by molecular cloning of 3 kb promoter sequence into a pGL3-Basic vector containing the Fluc reporter. Twenty microg of MLC2v-Fluc plasmid DNA in phosphate-buffered saline was directly injected into mouse myocardium through a midline sternotomy. RESULTS: At 1 week after injection, MLC2v-Fluc expression was detected by in vivo bioluminescent imaging in 60% of injected animals; the average in vivo signal intensity was (1.5 +/- 0.6) x 10(4) radiance (p/sec/cm2/sr); in vivo signal was well above the detection threshold over 3 weeks after injection. In vivo bioluminescent signal is correlated (r2 = 0.8) with the luminometer assay results from homogenized heart samples. CONCLUSION: The capability of noninvasive imaging of the MLC2v-Fluc in the heart will encourage applications that aim at monitoring and tracking the marker gene expression over time in cells undergoing cardiac differentiation.

Animals↗
PubMed2003

Molecular markers of cardiac endocardial cushion development.

Endocardial cushions are precursors of mature heart valves. They form within the looped heart tube as discrete swellings and develop into thin, pliable leaflets that prevent regurgitation of blood. The embryonic origins of cardiac valves include endothelial, myocardial, and neural crest cells. Recently, an increasing number of animal models derived from mutational screens, gene inactivation, and transgenic studies have identified specific molecules required for normal development of the cardiac valves, and critical molecular pathways are beginning to emerge. To further this process, we have sought to assemble a diverse set of molecular markers encompassing all stages of cardiac valve development. Here, we provide a detailed comparative gene expression analysis of thirteen endocardial cushion markers. We identify endocardial cushion expression of the transcription factor Fog1, and we demonstrate active Wnt/beta-catenin signaling in developing endocardial cushions suggesting pathways that have not been previously appreciated to participate in cardiac valve formation.

Animals↗
PubMed2002

Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects.

BACKGROUND: A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model. METHODS: MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-I-labeled MSCs (6 x 10(7)) were implanted into the infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation. RESULTS: Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% +/- 2.2% versus -3.37% +/- 2.7% in control). In addition, the extent of wall thinning after myocardial infarction was markedly reduced in treated animals. CONCLUSIONS: Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with myocardial infarction.

Animals↗
PubMedDate not supplied

MRL mice fail to heal the heart in response to ischemia-reperfusion injury.

The MRL/MpJ mouse strain has been reported to recover after right ventricular cryoinjury without scar formation or evidence of ventricular dysfunction, suggesting that this mouse strain harbors genetic traits that confer the capacity for adult myocardium to regenerate. We therefore sought to assess the capacity of adult MRL myocardium to regenerate in a left ventricular ischemia-reperfusion model of myocardial infarction, which more closely recapitulates injury that occurs in human disease. MRL (n = 13) and control C57/Bl6 (n = 12) mice underwent transient occlusion of the left anterior descending coronary artery. After 10 weeks, MRL and C57Bl/6 mice were euthanized and the extent of infarcted myocardium quantified with (2,3,5)-triphenyltetrazolium chloride and trichrome staining. There was no evidence of resistance to cardiac injury or of reduced scar formation in the MRL mice compared to C57/Bl6 controls. Myocardial infarct size (percentage of total heart weight +/- SEM) did not significantly differ between MRL and C57/Bl6 controls (18.9 +/- 1.8% for MRL vs. 15.7 + 1.3% for C57/Bl6, p = 0.20). Thickness of the infarcted anterior LV wall at the mid-papillary level normalized to body weight was not significantly different between the two groups (0.017 + 0.003 mm/mg for MRL and 0.017 + 0.002 mm/mg for C57/BL6, p = 0.91). Trichrome staining showed intense scar formation in both C57/BL6 and MRL hearts. We conclude that there appears to be no effect of the MRL genetic background on resistance to myocardial infarction in mice.

Animals↗