ABSTRACT
Understanding developmental changes in contractility is critical to improving therapies for young cardiac patients. Isometric developed force was measured in human ventricular muscle strips from two age groups: newborns (<2 wk) and infants (3-14 mo) undergoing repair for congenital heart defects. Muscle strips were paced at several cycle lengths (CLs) to determine the force frequency response (FFR). Changes in Na/Ca exchanger (NCX), sarcoplasmic reticulum Ca-ATPase (SERCA), and phospholamban (PLB) were characterized. At CL 2000 ms, developed force was similar in the two groups. Decreasing CL increased developed force in the infant group to 131 +/- 8% (CL 1000 ms) and 157 +/- 18% (CL 500 ms) demonstrating a positive FFR. The FFR in the newborn group was flat. NCX mRNA and protein levels were significantly larger in the newborn than infant group whereas SERCA levels were unchanged. PLB mRNA levels and PLB/SERCA ratio increased with age. Immunostaining for NCX in isolated newborn cells showed peripheral staining. In infant cells, NCX was also found in T-tubules. SERCA staining was regular and striated in both groups. This study shows for the first time that the newborn human ventricle has a flat FFR, which increases with age and may be caused by developmental changes in calcium handling.
Subject(s)
Heart Defects, Congenital/physiopathology , Heart Ventricles/physiopathology , Muscle Strength , Myocardial Contraction , Ventricular Function , Age Factors , Calcium Signaling , Calcium-Binding Proteins/metabolism , Cardiac Pacing, Artificial , Cardiac Surgical Procedures , Female , Heart Defects, Congenital/metabolism , Heart Defects, Congenital/surgery , Heart Ventricles/growth & development , Heart Ventricles/metabolism , Humans , In Vitro Techniques , Infant , Infant, Newborn , Male , RNA, Messenger/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sodium-Calcium Exchanger/metabolismABSTRACT
Dopamine is used to treat heart failure, particularly after cardiac surgery in infants, but the mechanisms of action are unclear. We investigated differences in the effect of dopamine on L-type calcium current (I(Ca)) between newborn (NB, 1-4 days) and adult (AD, 3-4 mo) rabbit ventricular myocytes. Myocytes were enzymatically dissociated from NB and AD rabbit hearts. I(Ca) was recorded by using the whole cell patch-clamp technique. mRNA levels of cardiac dopamine receptor type 1 (D1), type 2 (D2), and beta-adrenergic receptors (beta-ARs) were measured by real-time RT-PCR. Dopamine (100 microM) increased I(Ca) more in NB (E(max) 87 +/- 10%) than in AD ventricular cells (E(max) 21 +/- 3%). Further investigation of this difference showed that mRNA levels of the D1 receptor were significantly higher in NB, and, with beta-AR blockade, dopamine increased I(Ca) more in NB than AD cells. Additionally, SKF-38393 (selective D1 receptor agonist) significantly increased I(Ca) by 55 +/- 4% in NB (P < 0.05, n = 4) and by 11 +/- 1% in AD (P < 0.05, n = 6). Dopamine in the presence of SCH-23390 (D1 receptor antagonist) increased I(Ca) in NB cells by 67 +/- 5% and by 22 +/- 2% in AD cells, suggesting a role for beta-AR stimulation. Selective blockade of beta(1)- or beta(2)-receptors (with block of D1 receptors) showed that the beta-AR action of dopamine in the NB was largely mediated via beta(2)-AR activation. Dopamine produces a larger increase in I(Ca) in NB cardiomyocytes compared with ADs. The mechanism of action is not only through beta(2)-ARs but also due to higher expression of cardiac D1 receptor in NB.
Subject(s)
Adrenergic beta-2 Receptor Agonists , Calcium Channels, L-Type/drug effects , Calcium/metabolism , Cardiotonic Agents/pharmacology , Dopamine/pharmacology , Myocytes, Cardiac/drug effects , Receptors, Dopamine D1/agonists , Signal Transduction/drug effects , Adrenergic beta-1 Receptor Agonists , Adrenergic beta-Antagonists/pharmacology , Age Factors , Animals , Animals, Newborn , Calcium Channels, L-Type/metabolism , Dopamine Agonists/pharmacology , Dopamine Antagonists/pharmacology , Membrane Potentials/drug effects , Myocytes, Cardiac/metabolism , Patch-Clamp Techniques , RNA, Messenger/metabolism , Rabbits , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/metabolism , Receptors, Dopamine D1/genetics , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/agonists , Reverse Transcriptase Polymerase Chain Reaction , Up-RegulationABSTRACT
OBJECTIVE: To report our experience on patients less than 18 months of age in whom stents were placed either in the right ventricular outflow tract (RVOT) or pulmonary arteries. BACKGROUND: Although percutaneous placement of intravascular stents in congenital heart disease is common practice, there are few reports regarding placement in young children. METHODS: Retrospective review of our database identified 19 patients less than 18 months of age who underwent placement of 26 stents in either the RVOT or pulmonary arteries. Data evaluated were patient age, gender, weight, site of narrowing, type of stent, gradient across the area of narrowing pre- and post-stent placement, vessel size pre- and post-stent placement, gradient, and vessel size on followup, and ability to redilate the stent if necessary. RESULTS: Mean patient age was 9.7 months (range 0.5-17.5 months). There were 14 males and 5 females with a mean weight of 7.1 kg (range 2.3-10.2 kg). Five patients had stents placed in the RVOT and 14 patients had 21 stents placed in the branch pulmonary arteries. Two Johnson and Johnson P188 stents were used, 23 premounted Genesis biliary stents and 1 other. Gradient across the stenotic area decreased from a mean of 52.9 mm Hg (range 20-80 mm Hg) to 15 mm Hg (range 3-40 mm Hg) (P<.001). CONCLUSIONS: Percutaneous placement of intravascular stents in young children is a viable procedure, can provide excellent relief of stenoses, and increases vessel size in the short term. Although many of these stents cannot be dilated to adult size, their efficacy in small infants and children in whom further surgery will ultimately be required makes them desirable for this group of patients.
