Isolated, paced, isovolumically beating, neonatal pig (n = 32) hearts underwent retrograde aortic perfusion with a solution containing insulin (100 µU/ml), glucose (5.5 mM), and palmitate (0.55 mM). Glycolysis, lactate release, glucose oxidation, palmitate oxidation, and oxygen consumption were assessed. The hearts were perfused during three periods: (1) baseline, pO2 ≈ 500 mm Hg, heart rate 150 bpm; (2) hypoxia, pO2 ≈ 60–80 mm Hg, heart rate 150 bpm, or tachycardia, pO2 ≈ 500 mm Hg, heart rate 300 bpm, and (3) recovery, return to baseline conditions. For hypoxia and tachycardia, the oxygen supply-demand ratio was comparable (≈1 nmol O2/mm Hg/gdry). During baseline, the left ventricular peak systolic pressure (PSP) averaged 126 ± 6 mm Hg, the end-diastolic pressure (EDP) 5 mm Hg, and the relaxation time constant (Tau) 34 ± 2 ms; the coronary flow was 36 ± 2 ml/min/gdry. During hypoxia, the PSP decreased to 70 ± 2 mm Hg, while EDP, Tau, and coronary flow increased to 26 ± 2 mm Hg, 104 ± 14 ms, and 70 ± 2 ml/min/gdry, respectively; palmitate oxidation and oxygen consumption decreased well below baseline. During tachycardia, the PSP decreased to 88 ± 1 mm Hg, and the EDP increased to 11 ± 1 mm Hg, while Tau and coronary flow did not change significantly; palmitate oxidation and oxygen consumption increased above baseline. For both stressors, the predicted lactate release underestimated the measured values by a factor of ≈2, but were comparable during baseline and recovery. Upon recovery, PSP returned to ≈80% of baseline, while EDP remained elevated, for both stressors. Glucose oxidation returned to baseline, but palmitate oxidation became accelerated. We conclude for neonatal pig hearts subjected to oxygen insufficiency: (1) that PSP decreases and (2) that EDP and Tau increase with hypoxia, whereas EDP increases, while Tau remains unchanged with tachycardia. Following both stressors, palmitate oxidation becomes enhanced and dissociated from mechanical activity.
The objective of this study was to test whether chronically hypoxic immature hearts exhibit greater tolerance to no-flow ischemia than normoxic hearts. Rabbits (N = 36) were raised from birth to 5 weeks of age in either hypoxic (10% O2/90% N2) or normoxic (room air) environment. Isolated, isovolumically beating hearts, with a fluid-filled balloon catheter in the left ventricular chamber, were perfused with a well-oxygenated buffer and studied during baseline [30 minutes; perfusion pressure, 60 mmHg; end diastolic pressure (EDP), 5 mmHg], no-flow ischemia (until onset of contracture or for 30 minutes), and Reperfusion (30 minutes; perfusion pressure, 60 mmHg). Time for onset of contracture (TOC) was defined by an increase in balloon pressure of 5 mmHg. The results were as follows: hypoxic vs normoxic: Hct, 56.4 +/- 2.5* vs 36.3 +/- 0.4%, (right ventricle/left ventricle) weight (dry) ratio, 0.50 +/- 0.04* vs 0.28 +/- 0.02. Baseline: developed pressure (DeltaP), 96 +/- 4 vs 93 +/- 5 mmHg; coronary flow, 90 +/- 10* vs 62 +/- 4 ml/min/gdry. No-flow ischemia: TOC, 12 +/- 1* vs 24 +/- 2 minutes. All hypoxic (no normoxic) hearts reached peak contracture. Reperfusion: Just after onset of contracture, DeltaP, 80 +/- 3* vs 67 +/- 4 mmHg; EDP, 5 +/- 1* vs 13 +/- 2 mmHg; after 30 minutes of no-flow ischemia, DeltaP, 58 +/- 5 vs 46 +/- 4 mmHg; EDP, 13 +/- 1* vs 24 +/- 3 mmHg; lactate release (LR), 0.15 +/- 0.01 vs 0.17 +/- 0.01 mmol/gdry, creatine kinase release (CKR), 46 +/- 8* vs 242 +/- 28 U/gdry. For hypoxic hearts reperfused after onset of contracture, LR was 0.11 +/- 0.03 mmol/gdry, comparable to that following 30 minutes of no-flow ischemia (*p < 0.05). Rabbit hearts subjected to hypoxia from birth developed ischemic contracture earlier and reached peak contracture, showed no significant increase in LR after onset of contracture, exhibited better recovery of EDP, and had markedly reduced CKR compared to normoxic controls.
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