Performance of the Neonatal Pig Heart Subjected to Oxygen Insufficiency

Abstract

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/g_dry). 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/g_dry. 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/g_dry, 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.

Dobutamine alters carnitine metabolism in the neonatal piglet heart

“…This was primarily due to increased HR, not augmented LVDP. The findings agree with previous experiments (Penn et al 1999;Ascuitto et al 1999, Uy et al 2004, which demonstrated an adverse effect of accelerated-paced HR on left ventricular pressure development and LVEDP in the isolated isovolumically beating heart. The mechanisms of these effects are not completely clear.…”

“…However, other investigators (Goodwin et al 1998;Ochiai et al 2001) have contested this view. Uy et al (2004) demonstrated that, although pacing the isolated neonatal pig heart at 300 bpm (a much higher rate than in our study) created an oxygen supply/demand ratio similar to that of hypoxia, oxygen extraction was measured at approximately 50%, indicating adequate oxygen availability. Therefore, it seems unlikely that the inability of the hearts to maintain LVDP in our model was a direct effect of the mismatch between oxygen supply and demand.…”