1. Cardiovascular system begins forming at 3 weeks Pediatric Fundamentals – Heart and Circulation Embryology 1. Cardiovascular system begins forming at 3 weeks (diffusion no longer adequate) 2. Angiogenetic cell cluster and blood islands -> intraamniotic blood vessels 3. Heart tube 4. Heart begins to beat 22 – 23 days 5. Heart looping -> 4 chambers, 27 – 37 days 6. Valves 6 – 9 weeks

umbilical vein (UV)-> ductus venosus (50%) -> IVC -> RA -> Pediatric Fundamentals - Growth and Development Cardiovascular system In utero circulation placenta -> umbilical vein (UV)-> ductus venosus (50%) -> IVC -> RA -> foramen ovale (FO) -> LA -> Ascending Ao -> SVC -> tricuspid valve -> RV (2/3rds of CO) -> main pulmonary artery (MPA) -> ductus arteriosus (DA) (90%) -> descending Ao -> umbilical arteries (UAs)->

Transitional circulation Placenta Out and Lungs In Pediatric Fundamentals – Heart and Circulation Transitional circulation Placenta Out and Lungs In PVR drops dramatically (endothelial-derived NO and prostacyclin) FO closes DA closes 10-12 hours to 3 days to few weeks prematures: closes in 4-12 months PFO potential route for systemic emboli DA and PFO routes for R -> L shunt in PPHN

Persistent pulmonary hypertension of the newborn (PPHN) Pediatric Fundamentals – Heart and Circulation Persistent pulmonary hypertension of the newborn (PPHN) Old PFC misnomer Primary Secondary meconium aspiration sepsis birth asphyxia Treatment cardiopulmonary support inhaled NO ECMO

↓ ↓ ↓ ↓ ↓ Pediatric Fundamentals – Heart and Circulation Nitric oxide (NO) – cGMP transduction pathway l-arginine ↓ eNOS (endothelial NO synthetase) oxidation of quanidine N moiety NO activates ↓ GTP ↓ sGC (soluble guanylate cyclase) cGMP (cyclic-3’,5’-guanosine monophosphate) activates ↓ ↓ PDE (phosphodiesterase) protein kinase GMP

Increased sensitivity to calcium channel blockers (e.g. verapamil) Pediatric Fundamentals – Heart and Circulation Neonatal myocardial function Contractile elements comprise 30% (vs 60% adult) of newborn myocardium Alpha isoform of tropomyosin predominates more efficient binding for faster relaxation at faster heart rates Relatively disorganized myocytes and myofibrils Most of postnatal increase in myocardial mass due to hypertrophy of existing myocytes Diminished role of relatively disorganized sarcomplasmic reticulum (SR) and greater role of Na-Ca channels in Ca flux so greater dependence on extracellular Ca may explain: Increased sensitivity to calcium channel blockers (e.g. verapamil) hypocalcemia digitalis

lactate: primary metabolite Pediatric Fundamentals – Heart and Circulation Myocardial energy metabolism Young infant heart lactate: primary metabolite later: glucose oxidation and amino acids (aa’s) metabolize glucose and aa’s under hypoxic conditions (may lead to greater tolerance of ischemic insults) Gradual transition to adult: fatty acid primary metabolite by 1-2 years

Age (months) Sys/Dias mean 1 85/65 50 3 90/65 50 6 90/65 50 9 90/65 55 Pediatric Fundamentals – Heart and Circulation Normal aortic pressures Wt (Gm) Sys/Dias mean 1000 50/25 35 2000 55/30 40 3000 60/35 50 4000 70/40 50 Age (months) Sys/Dias mean 1 85/65 50 3 90/65 50 6 90/65 50 9 90/65 55 12 90/65 55

Babies are vagotonic Adrenergic receptors Sympathetic receptor system Pediatric Fundamentals – Heart and Circulation Adrenergic receptors Sympathetic receptor system Tachycardic response to isoproterenol and epinephrine by 6 weeks gestation Myocyte β-adrenergic receptor density peaks at birth then decreases postnatally but coupling mechanism is immature Parasympathetic, vagally-mediated responses are mature at birth (e.g. to hypoxia) Babies are vagotonic

Age (days) Rate 1-3 100-140 4-7 80-145 8-15 110-165 Age (months) Rate Pediatric Fundamentals – Heart and Circulation Normal heart rate Age (days) Rate 1-3 100-140 4-7 80-145 8-15 110-165 Age (months) Rate 0-1 100-180 1-3 110-180 3-12 100-180 Age (years) Rate 1-3 100-180 3-5 60-150 5-9 60-130 9-12 50-110 12-16 50-100

Avoid (excessive) vasoconstriction Maintain heart rate Pediatric Fundamentals – Heart and Circulation Newborn myocardial physiology Type I collagen (relatively rigid) predominates (vs type III in adult) Neonate Adult Cardiac output HR dependent SV & HR dependent Starling response limited normal Compliance less normal Afterload compensation limited effective Ventricular high relatively low interdependence So: Avoid (excessive) vasoconstriction Maintain heart rate Avoid rapid (excessive) fluid administration