Biomedical subjects

Ingeborg Friehs

Publications and source records attributed to Ingeborg Friehs.

14 recordsLinked to original sources

PubMed2006

Vascular endothelial growth factor prevents apoptosis and preserves contractile function in hypertrophied infant heart.

BACKGROUND: Cardiac hypertrophy is an adaptive response to increased workload that, if unrelieved, leads to heart failure. It has been reported that cardiomyocyte apoptosis contributes to failure, and that vascular endothelial growth factor (VEGF) treatment of hypertrophied myocardium increases capillary density and improves myocardial perfusion. In this study we hypothesized that VEGF treatment reduces cardiomyocyte apoptosis and thereby preserves myocardial contractile function. METHODS AND RESULTS: Newborn rabbits underwent aortic banding. At 4 and 6 weeks of age, hypertrophied animals were treated with intrapericardial administration of recombinant VEGF protein. Three groups of animals were investigated: age-matched controls (C), untreated hypertrophied (H), and VEGF-treated hypertrophied hearts (T). Cardiomyocyte apoptosis was determined by TUNEL staining and PARP cleavage (immunoblotting of nuclear extracts) and cardiac function by transthoracic echocardiography. Death attributable to severe heart failure occurred in 14 of 43 untreated and 2 of 29 VEGF-treated animals (P<0.01). TUNEL-positive cardiomyocyte nuclei (n/1000 nuclei) were significantly increased in untreated hearts at 5 weeks (H: 10+/-1.8 versus T: 3+/-0.7) and at 7 weeks (H: 13+/-3.6 versus T: 5+/-1.5; P<0.05). Increased apoptosis in untreated hypertrophy was also confirmed by the presence of PARP cleavage (H: 74+/-7 versus T: 41+/-4 arbitrary densitometry units; P<0.05). VEGF treatment preserved left ventricular mass, prevented dilation (T: 1.01+/-0.06 versus H: 0.77+/-0.07; P<0.05), and preserved contractility indices compared with untreated hearts. CONCLUSIONS: Lack of adaptive capillary growth impairs myocardial perfusion and substrate delivery in hypertrophying myocardium. VEGF treatment reduces myocardial apoptosis and prolongs survival in a model of severe progressive left ventricular hypertrophy. Promoting capillary growth with VEGF reduces apoptosis, preserves myocardial contractile function, and delays the onset of failure in pressure-loaded infant myocardium.

Animals↗

PubMed2006

Dopamine induces postischemic cardiomyocyte apoptosis in vivo: an effect ameliorated by propofol.

BACKGROUND: Dopamine is commonly used to improve postischemic myocardial contractile function. However, there is evidence that dopamine augments apoptosis after ischemia through increased intracellular calcium and opening of the mitochondrial permeability transition pore. Propofol (2,6-diisopropylphenol) is an anesthetic that has been shown to prevent mitochondrial permeability transition pore opening. We evaluated the effects of propofol given during reperfusion on dopamine-mediated apoptosis. METHODS: Hearts from 8-week-old inbred New Zealand White rabbit siblings were subjected to 2 hours of cold cardioplegic ischemia and 6 hours of reperfusion in a heterotopic transplant model. Controls consisted of the recipient rabbit's nonischemic heart. The ischemia-reperfusion (IR) group consisted of postischemic hearts reperfused with no drugs; the IR plus dopamine (IR+D) group received dopamine (20 microg x kg(-1) x min(-1)) continuously; the IR+D plus propofol (IR+D+P) group received dopamine (20 microg x kg(-1) x min(-1)) plus propofol (500 to 600 microg x kg(-1) x min(-1)); and the IR plus propofol (IR+P) group received propofol only (500 to 600 microg x kg(-1) x min(-1)) throughout reperfusion (n = 7 to 9 in each group). Myocardial function was measured using a left ventricular balloon; terminal nick-end labeling (TUNEL) staining, DNA electrophoresis, and immunoblotting for caspase-3 cleavage were performed at the end of reperfusion. RESULTS: Dopamine increased the number of TUNEL-positive nuclei significantly (14.0 +/- 2.0/1,000 for IR+D versus 6.7 +/- 2.0/1,000 for IR, p = 0.01). Propofol (IR+D+P) reduced the total number of apoptotic cells in hearts receiving dopamine (7.1 +/- 1.8/1,000, p = 0.01 versus IR+D) to the extent seen in IR alone. DNA laddering and caspase-3 cleavage were observed at greater frequency in the IR+D group compared with the IR and IR+D+P groups. Propofol had no effect on dopamine-mediated increased systolic function, but improved diastolic function after ischemia. CONCLUSIONS: Dopamine infusion has a positive inotropic effect on the postischemic heart at the expense of increased cardiomyocyte apoptosis. The addition of propofol prevents dopamine-induced apoptosis after ischemia while maintaining positive inotropy.

Anesthetics, Intravenous↗

PubMed2006

Cardiac conduction through engineered tissue.

In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal's natural life. Perfusion of hearts with fluorescently labeled lec-tin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding re-cipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy.

Animals↗

PubMed2005

Impaired insulin-signaling in hypertrophied hearts contributes to ischemic injury.

Despite increased glucose utilization by hypertrophied myocardium, these hearts exhibit a slower rate of glucose uptake (GU). We hypothesized that, in hypertrophied myocardium, a defect of the insulin-responsive glucose transporter is responsible for impaired GU and metabolism during ischemia, contributing to post-ischemic myocardial dysfunction. In a rabbit model of pressure-overload hypertrophy, GU ((31)P NMR spectroscopy) and total/phosphorylated insulin-signaling intermediates were assayed: insulin-receptor, insulin-receptor-substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3-k), GLUT-4 translocation and contractile function in an isolated heart ischemia/reperfusion model. Total protein was not different between hypertrophied and control hearts. Phosphorylation of IRS-1 and PI3-k activity was significantly lower in hypertrophy during ischemia. GU was impaired pre-ischemia in hypertrophy, remained lower during early reperfusion, and was associated with impaired recovery of contractile function. In conclusion, a defect in IRS-1 phosphorylation and PI3-k activation in hypertrophied hearts restricts insulin-mediated GLUT-4 translocation and ischemia, a known stimulus of GLUT-4 translocation, does not compensate for this defect.

Animals↗

PubMed2005

Cyclosporin A but not FK-506 protects against dopamine-induced apoptosis in the stunned heart.

BACKGROUND: Dopamine given at moderate doses for inotropy to postischemic hearts has been shown to augment myocyte apoptosis in association with elevated cytosolic calcium. We hypothesize that dopamine-mediated apoptosis occurs through calcium-induced opening of the mitochondrial permeability transition (mPT) pore. We also hypothesize that cyclosporin A (CSA), a calcineurin inhibitor known to block mPT pore opening, would prevent dopamine-induced apoptosis primarily by inhibiting pore opening (cyclophilin D binding). METHODS: Isolated perfused rabbit hearts (n = 6/group) were subjected to 30 minutes of 37 degrees C cardioplegic arrest followed by 120 minutes reperfusion (ischemic injury that produces < 3% infarct by triphenyl-tetrazolium chloride [TTC] staining). Four groups were studied: (1) control; (2) dopamine (10 micromol/L) postischemia (dopa); (3) dopamine+CSA (0.2 micromol/L) (CSA+D) group; (4) dopamine+FK-506 (0.2 micromol/L) (FK+D) group. Left ventricular developed pressure and oxygen consumption were measured preischemia and postischemia. Bax, caspase-3 and caspase-9, and poly-ADP-ribose polymerase (PARP) activation were measured by Western blotting. Apoptotic nuclei were quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. RESULTS: Dopamine postischemia improved contractile function and heart rate and this was not affected by CSA or FK. However, TUNEL positive nuclei, Bax, caspase-3 and caspase-9 activation, and PARP cleavage were all increased in dopa and FK+D groups, but not in CSA+D. CONCLUSIONS: Cyclosporin is effective in preventing dopamine-induced apoptosis in the postischemic heart. The mechanism is likely due to inhibition of mPT pore opening since FK-506, a potent calcineurin inhibitor that does not bind to cyclophilin, did not prevent this. Low dose cyclosporin may prove useful to prevent dopamine-induced apoptosis resulting in long-term preservation of cardiac function.

Animals↗

PubMed2004

Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury.

BACKGROUND: Myocardial hypertrophy is associated with progressive contractile dysfunction, increased vulnerability to ischemia-reperfusion injury, and is, therefore, a risk factor in cardiac surgery. During the progression of hypertrophy, a mismatch develops between the number of capillaries and cardiomyocytes per unit area, suggesting an increase in diffusion distance and the potential for limited supply of oxygen and nutrients. We hypothesized that promoting angiogenesis in hypertrophied hearts increases microvascular density, thereby improves tissue perfusion and substrate availability, maintains myocardial function, and improves postischemic recovery. METHODS: Left ventricular hypertrophy was created in 10-day-old rabbits by aortic banding and progression was monitored by echocardiography. At 4 weeks (compensated hypertrophy), 2 microg of vascular endothelial growth factor (VEGF) or placebo was administered intrapericardially. After 2 weeks, microvascular density, coronary flow (CF), and glucose uptake (GU) were measured. Tolerance to ischemia was determined by cardiac function measurements before and after ischemia-reperfusion using an isolated heart preparation. RESULTS: Microvascular density increased significantly following VEGF treatment (1.43 +/- 0.08/nuclei/field vs 1.04 +/- 0.06/nuclei/field untreated hypertrophy). Concomitantly, there was an increase in CF (7 +/- 0.5 vs 5 +/- 0.4 mL/min/g) and GU (1.24 +/- 0.2 vs 0.69 +/- 0.2 micromoles/g/30 minutes; p <or= 0.05). In vivo contractile function (-0.08 +/- 0.48 vs -1.39 +/- 0.35 untreated hypertrophy; p <or= 0.05) and postischemic myocardial recovery (% recovery: 93 +/- 2.0 vs 73 +/- 6.8 untreated hypertrophy; p <or= 0.05) were significantly improved in VEGF-treated hearts compared to untreated hypertrophied hearts. CONCLUSIONS: Treatment of hypertrophied hearts with VEGF resulted in an increase of microvascular density, improved tissue perfusion, and glucose delivery. Promoting angiogenesis proved useful in preserving myocardial function in late hypertrophy and improving postischemic recovery of contractile function.

Angiogenesis Inducing Agents↗

PubMed2003

Cytosolic calcium in the ischemic rabbit heart: assessment by pH- and temperature-adjusted rhod-2 spectrofluorometry.

OBJECTIVES: Cytosolic calcium ([Ca(2+)](i)) mediates ischemia-reperfusion (I/R) injury, but magnitude and time course of I/R-induced [Ca(2+)](i) overload remain unclear. Fluorescent indicators are commonly used to measure [Ca(2+)](i), and have a dissociation constant (K(d)) that depends on pH and temperature. We hypothesized that changes of K(d) during I/R lead to misleading interpretations of [Ca(2+)](i) recordings. METHODS: (1) In isolated rabbit hearts (n=4 each), intracellular pH was measured during I/R at 37 degrees C, 20 degrees C, and 4 degrees C with and without cardioplegic arrest by (31)P-NMR-spectroscopy. (2) K(d) for rhod-2 and calcium was determined at varying pH and temperature in in vitro experiments. (3) Isolated rabbit hearts were subjected to I/R, and [Ca(2+)](i) was recorded by surface rhod-2 spectrofluorometry. Finally, [Ca(2+)](i) was computed using either the conventional K(d), or the pH- and temperature-adjusted K(d). RESULTS: K(d)(Ca(2+)Rhod-2) remained stable between pH 7.1 and 6.8, but increased exponentially with lower pH and/or temperature. Calculations using a static K(d) indicated that [Ca(2+)](i) rose only mildly during warm ischemia and did not rise during cardioplegic arrest, while a large Ca(2+) influx appeared to occur during early reperfusion. When the pH and temperature-adjusted K(d) was used for calculation, [Ca(2+)](i) rose significantly during ischemia (431+/-37% during 20 min 37 degrees C ischemia, and 78+/-19% during 20 min cardioplegic arrest at 20 degrees C). During early reperfusion, [Ca(2+)](i) decreased rapidly, without significant further [Ca(2+)](i) elevation. CONCLUSIONS: In contrast to previous reports, [Ca(2+)](i) accumulation occurs during unprotected ischemia as well as hypothermic ischemia with cardioplegic arrest, without further net Ca(2+) influx on reperfusion. This finding has important implications for timing of protective strategies during myocardial ischemia.

Animals↗

PubMed2003

Noninvasive serial evaluation of myocardial mechanics in pressure overload hypertrophy of rabbit myocardium.

BACKGROUND: The determination of progression from afterload mismatch to myocardial failure in small animals requires invasive monitoring to assess ventricular pressure. OBJECTIVE: We sought to (1) validate the noninvasive determination of blood pressure using optical plethysmography, and (2) determine the time course and progression from afterload mismatch to myocyte failure in neonatal rabbits with coarctation (aortic banding at 7-10 days of life) compared to normal rabbits. METHODS AND RESULTS: Comparison of continuous arterial pressure determined by optical plethysmography with high-fidelity intraarterial recording was performed in nine animals. An accuracy of 5.9 +/- 4.7 and 9.2 +/- 6.9 mm Hg for systolic and diastolic blood pressure was noted. Fourier analysis confirmed similar frequency components. Simultaneous transthoracic echocardiography and optical plethysmography were serially performed in 33 banded and 13 control animals. Load-dependent and -independent measures of myocardial function were obtained. Midwall contractility, initially normal, showed a gradual significant deterioration (0.22 +/- 1.68 [week 3] to -1.36 +/- 1.24 [week 6]; Z-scores). CONCLUSIONS: This novel noninvasive method for determination of myocardial mechanics allows for serial evaluation of cardiac function and the determination of the time course from compensated hypertrophy to myocyte failure.

Analysis of Variance↗

PubMed2003

Increased susceptibility of hypertrophied hearts to ischemic injury.

Cardiac hypertrophy is an adaptive response that compensates for increased workload by normalizing wall stress and preserving cardiac contractile function. In advanced stages, however, clinical and experimental studies have shown that when the high workload is maintained, hypertrophy progresses to ventricular dilatation, contractile dysfunction, and decreased tolerance to ischemia/reperfusion. Development of hypertrophy is accompanied by distinct qualitative and quantitative changes in contractile protein expression and isoform switching, cytosolic calcium regulation, and substrate delivery and use. We have focused our investigations on changes in substrate delivery and capillary density in pressure overload hypertrophy and on the effects that these changes have on tolerance to ischemia/reperfusion. This report summarizes our work in this area using a model of aortic banding in 10-day-old rabbits, which exhibits the same pattern of concentric hypertrophy early, followed by ventricular dilatation and contractile dysfunction that is clinically apparent.

Animals↗

PubMed2003

Postnatal increase in insulin-sensitive glucose transporter expression is associated with improved recovery of postischemic myocardial function.

OBJECTIVE: Glucose is an important substrate for energy production in the developing heart. Increased glucose uptake rate and metabolism during ischemia and reperfusion are closely linked to postischemic myocardial recovery. The initial rate-limiting step for glycolysis is the transport of glucose across the plasma membrane by glucose transporters (GLUT-1 and GLUT-4). We hypothesized that changes in GLUT-1 and GLUT-4 expression in developing hearts lead to age-dependent adaptive changes in glucose uptake capacity and influence tolerance to ischemia. METHODS: Western-immunoblotting was performed to determine GLUT-1 and GLUT-4 expression in myocardial tissue from 1, 2, and 3-week-old and adult rabbits. Glucose uptake rate was measured with (31)P-nuclear magnetic resonance spectroscopy using 2-deoxyglucose as substrate in isolated perfused hearts. Hearts from same age rabbits were perfused in the Langendorff mode with crystalloid buffer or buffer plus a GLUT-4 specific antibody in order to determine GLUT-4 mediated effects on myocardial protection. The hearts were subjected to 30 minutes of normothermic ischemia followed by reperfusion. Cardiac contractile function measurements were obtained pre- and postischemia. Tissue lactate accumulation was measured in all groups at end-ischemia CONCLUSIONS: Insulin-regulated glucose transporter (GLUT-4) expression in the heart increased gradually after birth reaching nearly adult levels by 3 weeks of age. Corresponding with the higher amount of GLUT-4 protein, improved recovery of postischemic contractile function was seen in older hearts in association with increased anaerobic glycolytic capacity. Interventions to accelerate postnatal GLUT-4 expression may improve ischemic tolerance in the neonatal heart.

Age Factors↗

PubMed2002

Dopamine treatment of postischemic contractile dysfunction rapidly induces calcium-dependent pro-apoptotic signaling.

BACKGROUND: Ischemia and adrenergic stimulation of cardiomyocyte cultures have been shown to induce apoptotic cell death. We hypothesized that in a model of contractile dysfunction following ischemia, a commonly used catecholamine such as dopamine augments cardiomyocyte apoptosis via activation of calcium-dependent signaling cascades. METHODS AND RESULTS: Isolated perfused rabbit hearts were subjected to 45 minutes of normothermic ischemia with cardioplegic arrest. Hearts were reperfused for 120 minutes with unmodified perfusate (control), perfusate containing 20 nM dopamine, dopamine+2,3-butanedione monoxime (BDM), a MgATPase-inhibitor, or the calcium-sensitizing inotrope ORG 30029. Ischemia-reperfusion alone caused contractile dysfunction without significant myocardial necrosis (left ventricular pressure-volume curves; 1% triphenyltetrazolium chloride staining; creatine kinase release) or apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling [TUNEL] analysis; immunoblotting for poly(ADP-ribose) polymerase [PARP] cleavage; activation of caspases-3, -8, and -9; expression of Bax/Bcl-2). Intracellular calcium [Ca2+]i measured by rhod-2 spectrofluorometry was increased in dopamine-reperfused hearts. Although postischemic dopamine treatment improved contractility, the number of apoptotic cardiomyocytes was significantly higher than in untreated postischemic hearts (32.5+/-9 versus 5.5+/-1.6/1000 nuclei, P<0.01). Further evidence of dopamine-stimulated apoptosis included PARP cleavage, activation of mitochondrial-derived caspase-9, and the terminal effector caspase-3. Dopamine also increased cellular content of pro-apoptotic Bax while decreasing anti-apoptotic Bcl-2. Simultaneous treatment with BDM suppressed contractility without affecting [Ca2+]i and did not reduce dopamine-stimulated apoptotic markers. When contractility was increased without elevating [Ca2+]i using ORG 30029, no activation of pro-apoptotic signaling cascades was found. Dopamine infusion in nonischemic hearts did not result in cardiomyocyte apoptosis. CONCLUSIONS: Postischemic dopamine treatment of contractile dysfunction activates pro-apoptotic signal cascades, most likely via a calcium-dependent process and mitochondrial damage.

Animals↗

PubMed2002

Protective effects of protein kinase C during myocardial ischemia require activation of phosphatidyl-inositol specific phospholipase C.

BACKGROUND: Protein kinase C (PKC) activation during myocardial ischemia is thought to be cardioprotective. However, the mechanism of ischemia-induced PKC activation remains unclear. We hypothesized that ischemic PKC activation occurs through activation of phosphatidyl-inositol specific phospholipase C (PI-PLC) and protects the heart from ischemic injury. METHODS: Isolated rabbit hearts were subjected to 20 minutes of normothermic ischemia and reperfusion. The PI-PLC inhibitor U73122 (0.5 micromol/L), its inactive analogue U73343 (0.5 micromol/L), or the PKC inhibitor chelerythrine (2 micromol/L) were given just before ischemia. Another group received U73122 plus the direct PKC activator phorbol 12-myristate-13-acetate (PMA, 10 pmol/L). Measurements included contractile function, intracellular calcium, PI-PLC activity, and translocation of PKC isoforms. RESULTS: PI-PLC activity increased during myocardial ischemia and was inhibited by U73122. PI-PLC inhibition prevented the ischemic translocation of PKC-alpha, PKC-epsilon, and PKC-eta, and impaired cardiac recovery and cytosolic calcium regulation without significant changes in energy metabolism. PMA restored both contractile function and PKC translocation pattern in U73122-treated hearts. Direct PKC inhibition with chelerythrine mimicked the effects of U73122. CONCLUSIONS: PI-PLC mediates PKC translocation during myocardial ischemia. Inhibition of PI-PLC or PKC activation, or both, during ischemia significantly impairs postischemic myocardial recovery.

Adenosine Triphosphate↗

PubMed2002

Improving results of the modified Fontan operation in patients with heterotaxy syndrome.

BACKGROUND: Historically the Fontan operation in patients with single ventricle heterotaxy syndrome and atrial isomerism has been associated with high mortality. We studied whether recent modifications of the surgical technique have improved outcome. METHODS: A retrospective review of 135 patients with heterotaxy syndrome who underwent a Fontan operation between 1981 and 2000 was performed. RESULTS: There were 93 patients with right isomerism and 42 with left isomerism. Anomalies of venous return included 25 patients with extracardiac pulmonary venous connection (19%) and 37 patients with an interrupted inferior vena cava (27%). Thirty-six patients (27%) had at least moderate atrioventricular valve regurgitation. The type of Fontan procedure included 17 patients with an atriopulmonary Fontan connection, 67 with a lateral tunnel modification, 19 with an intraatrial tube graft, 25 with an extracardiac tubegraft, and 7 with an intra-extra atrial tube graft. A fenestration was placed in 93 patients (78%). Early mortality was 19% before 1991, 3% since 1991, and no patient has died early since 1993. Ten-year survivals were 70% for Fontan operations before 1990 and 93% for Fontan operations after 1990. Thirty-two patients (23%) had prolonged pleural effusions. Risk factors for death included anomalous pulmonary venous connection (p = 0.02) and higher preoperative pulmonary vascular resistance (p = 0.002). Sixty-two patients (47%) had some form of early postoperative arrhythmia. At 10 years, freedom from late bradyarrhythmia and late tachyarrhythmia were 78% and 70%, respectively. Preoperative arrhythmias, older age at operation, and anatomic features were each independent predictors of late arrhythmia. CONCLUSIONS: The Fontan operation can now be performed in patients with heterotaxy syndrome with excellent survival. However, morbidity in terms of postoperative arrhythmias and prolonged pleural effusions remains significant. Fontan staging, appropriate choice of Fontan modification, aggressive treatment of concomitant malformations, and use of a baffle fenestration contribute to improved outcome.

Abnormalities, Multiple↗

PubMed2002

Outcome after reconstruction of discontinuous pulmonary arteries.

OBJECTIVE: This study was undertaken to determine outcomes of and optimal treatment strategies for reconstruction of congenital or acquired discontinuity of branch pulmonary arteries. METHODS: Between 1985 and 2000 pulmonary artery continuity was established in 102 patients with discontinuous central pulmonary arteries and normal peripheral arborization. Data were obtained retrospectively. RESULTS: Techniques to connect both pulmonary arteries included direct pulmonary artery-pulmonary artery anastomosis (n = 33), tube graft interposition (n = 47), or pulmonary arterial implantation in right ventricular-pulmonary arterial conduits (n = 22). Among patients with biventricular repair (n = 66), survival was 85% +/- 8% at 5 years, and freedom from surgical or interventional pulmonary arterioplasty was 31% +/- 11%. At most recent follow-up, mean branch pulmonary arterial z scores were -0.5 +/- 1.6 (right pulmonary artery) and -1.4 +/- 1.3 (left pulmonary artery). Mean right to left ventricular pressure ratio was 0.61 +/- 0.26, and this value was more than 0.75 in 13 of 58 cases. Fifteen of 51 had a lung perfusion mismatch of more than 75:25, and in 9 of 58 one branch pulmonary artery was occluded. Twenty-two patients who underwent primary establishment of antegrade pulmonary artery flow without previous shunt procedures had comparable survival and reintervention rates, with a tendency toward higher pulmonary arterial z scores and lower right to left ventricular pressure ratios. Among patients with single-ventricle repair (n = 33), 5-year survival was 93% +/- 8% and freedom from pulmonary arterioplasty was 39% +/- 9%. Ten of 19 patients had a lung perfusion mismatch, and one branch pulmonary artery was occluded in 4 of 31. Overall, a direct pulmonary artery anastomosis was associated with better survival (P =.006). The presence of aortopulmonary collaterals was a risk factor for pulmonary artery occlusion (P =.03). CONCLUSION: Good survival can be achieved for patients with pulmonary artery discontinuity, but this requires frequent reinterventions. Direct pulmonary artery- pulmonary artery anastomoses and control of all collateral vessels may further improve outcome.

Angioplasty↗