Mechanical Function and Palmitate Oxidation with Oxygen Supply-Demand Mismatch in Neonatal Pig Hearts ♦ 145

Abstract

Understanding mechanical and metabolic performance in neonatal hearts with oxygen (O2) supply-demand mismatch is an important clinical problem. Hearts from pigs (<3d, N=16), were subjected to hypoxia (H, ↓ O2 supply) or tachycardia (T, ↑ O2 demand), but with a comparable O2 supply/demand ratio. Isolated, paced, isovolumically beating hearts underwent retrograde aortic perfusion at 60 mmHg with a buffer solution (95% O2 (or N2), 5% CO2) containing glucose (5.5 mM), palmitate (0.55 mM) and insulin (100 μU/ml). Since perfusion pressure was fixed, coronary flow (CF) was not compromised. Hearts were perfused during 3 consecutive 30 min periods: 1) Baseline(B), pO2 550 mmHg and HR 150 bpm; 2) H, pO2 55 mmHg and HR 150 bpm, or T, pO2 550 mmHg and HR 300 bpm and 3) Recovery (R). Developed pressure (ΔP), CF, palmitate oxidation (POx, 14C-palmitate to 14CO2) and lactate release (LR) were studied. POx was referenced to contractile activity(ΔP × HR) to assess oxidative efficiency. During B, H and R: ΔP was 118±5, 37±3* and 77±4* ** mmHg; CF was 36±2, 69±5* and 42±4 ml/min/g and POx was 358±19, 28±0.2* and 326±25* ** nmol/min/g, respectively. During B, T and R: ΔP was 124±7, 77±5* and 103±5* ** mmHg; CF was 37±2, 41±3 and 40±4 ml/min/g; and POx was 332±35, 502±54* and 419±31* ** nmol/min/g, respectively. LR increased ≅14-fold during H and≅2-fold with T; then returned to B duringR. Fig shows (POx)103/(ΔP × HR). In conclusion, neonatal hearts subjected to O2 mismatch exhibit: I) Improved recovery of contractile function after T vs. H and 2) Accelerated POx relative to contractile activity after T and H, suggesting a dissociation between these measures of mechanical and metabolic performance.