Restoration of cardiopulmonary function with 21% versus 100% oxygen after hypoxaemia in newborn pigs.

OBJECTIVE: To assess the consequences of hypoxaemia and resuscitation with room air versus 100% O(2) on cardiac troponin I (cTnI), cardiac output (CO), and pulmonary artery pressure (PAP) in newborn pigs. DESIGN: Twenty anaesthetised pigs (12-36 hours; 1.7-2.7 kg) were subjected to hypoxaemia by ventilation with 8% O(2). When mean arterial blood pressure fell to 15 mm Hg, or arterial base excess was < or = -20 mmol/l, resuscitation was performed with 21% (n = 10) or 100% (n = 10) O(2) for 30 minutes, then ventilation with 21% O(2) for 120 minutes. Blood was analysed for cTnI. Ultrasound examinations of CO and PAP (estimated from tricuspid regurgitation velocity (TR-Vmax)) were performed at baseline, during hypoxia, and at the start of and during reoxygenation. RESULTS: cTnI increased from baseline to the end point (p<0.001), confirming a serious myocardial injury, with no differences between the 21% and 100% O(2) group (p = 0.12). TR-Vmax increased during the insult and returned towards baseline values during reoxygenation, with no differences between the groups (p = 0.11) or between cTnI concentrations (p = 0.31). An inverse relation was found between increasing age and TR-Vmax during hypoxaemia (p = 0.034). CO per kg body weight increased during the early phase of hypoxaemia (p<0.001), then decreased. Changes in CO per kg were mainly due to changes in heart rate, with no differences between the groups during reoxygenation (p = 0.298). CONCLUSION: Hypoxaemia affects the myocardium and PAP. During this limited period of observation, reoxygenation with 100% O(2) showed no benefits compared with 21% O(2) in normalising myocardial function and PAP. The important issue may be resuscitation and reoxygenation without hyperoxygenation.

Resuscitation with 100% O(2) does not protect the myocardium in hypoxic newborn piglets.

BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction secondary to myocardial ischaemia. Cardiac troponin I (cTnI) is a marker of myocardial necrosis. Raised concentrations in the blood are related to perinatal asphyxia and increased morbidity. OBJECTIVE: To assess porcine myocardial damage from enzyme release during hypoxaemia induced global ischaemia, and subsequent resuscitation with ambient air or 100% O(2). To investigate whether CO(2) level during resuscitation influences myocardial damage. DESIGN: Newborn piglets (12-36 hours) were exposed to hypoxaemia by ventilation with 8% O(2) in nitrogen. When mean arterial blood pressure had fallen to 15 mm Hg, or base excess to < -20 mmol/l, the animals were randomly resuscitated by ventilation with either 21% O(2) (group A, n = 29) or 100% O(2) (group B, n = 29) for 30 minutes. Afterwards they were observed in ambient air for another 150 minutes. During resuscitation, the two groups were further divided into three subgroups with different CO(2) levels. ANALYSIS: Blood samples were analysed for cTnI, myoglobin, and creatine kinase-myocardial band (CK-MB) at baseline and at the end of the study. RESULTS: cTnI increased more than 10-fold (p < 0.001) in all the groups. Myoglobin and CK-MB doubled in concentration. CONCLUSION: The considerable increase in cTnI indicates seriously affected myocardium. Reoxygenation with 100% oxygen offered no biochemical benefit over ambient air. CK-MB and myoglobin were not reliable markers of myocardial damage. Normoventilation tended to produce better myocardial outcome than hyperventilation or hypoventilation.

Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide.

BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia-reoxygenation injury. OBJECTIVE: To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O(2) at different PaCO(2)-levels. METHODS: Newborn pigs (12-36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O(2) at different PaCO(2) levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay. RESULTS: Matrix metalloproteinase-2 more than doubled from baseline values (P < 0.001), and was higher in piglets resuscitated with 100% O(2) than with ambient air (P = 0.012). The ORAC value was considerably decreased (P < 0.001). In piglets with elevated PaCO(2), total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0.008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO(2) than in the piglets with elevated PaCO(2) (P = 0.013). CONCLUSION: In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O(2). Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO(2) during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.