Antonio Corno

OXIDATIVE INJURY IN REOXYGENATED AND REPERFUSED HEARTS

In this study, we separated the effects of low oxygen supply and low coronary flow in isolated perfused rat hearts to focus on the genesis of free radicals-induced reperfusion injury. Hearts were exposed to either hypoxemia/reoxygenation or ischemia/reperfusion in various sequences, with hypoxemia and ischemia matched for duration (20 min), temperature (37 degrees C), and oxygen supply (10% of baseline). Hypoxemia/reoxygenation (n = 7) resulted in lower (developed pressure) x (heart rate) (p < 0.001) and higher end-diastolic pressure (p < 0.001) than ischemia/reperfusion (n = 9). The presence of 40 IU/ml superoxide dismutase and 104 IU/ml catalase nearly blunted the rise of the end-diastolic pressure (p = 0.02 vs. baseline), but could only partially prevent the depression of myocardial contractility (p < 0.001 vs. baseline, n = 7). Similar patterns were observed when hearts were made ischemic after hypoxemia, eliminating the intermediate reoxygenation step. We conclude that the major determinant of the reperfusion injury is associated with low oxygen supply rather than low coronary flow. Part of the injury is mediated by oxygen-derived free radicals, but a substantial portion of it is associated with energetic processes.

Ischaemia/reperfusion in the posthypoxaemic re-oxygenated myocardium: haemodynamic study in the isolated perfused rat heart

In order to study the haemodynamics of reperfusion injury in the post hypoxaemic heart, we exposed buffer-perfused isolated rat hearts to either: (1) 20-minute low-flow ischaemia or (2) 20-minute hypoxaemia followed by re-oxygenation and further ischaemia/reperfusion. In group 2, the myocardial contractility recovered less (p <0.002) than in group 1. This model therefore represents with sufficient reliability the clinical situation where hypoxaemic hearts are re-oxgenated before ischaemia/reperfusion and receive more severe injury than hearts exposed to ischaemia/reperfusion only. To locate the major site of the injury, further data were obtained (1) with infusion of superoxide dismutase and catalase during hypoxaemia and in the first five minutes of re-oxygenation, and (2) by eliminating re-oxygenation. It appears that the major determinant of reperfusion injury in hypoxaemic hearts is to be looked for in the events underlying hypoxaemia or re-oxygenation, and is mediated by oxygen- derived free radicals.

Myocardial Damage Induced by Uncontrolled Reoxygenation

To evaluate myocardial impairment induced by uncontrolled reoxygenation, the effects of hypoxia-reoxygenation were compared with ischemia-reperfusion in isolated rat hearts. After stabilization, 2 groups (n = 8) of Langendorff-perfused rat hearts were exposed to 40 minutes of ischemia (10% of baseline flow) or hypoxia (10% of baseline oxygen content) followed by a sudden return to baseline conditions (reperfusion or reoxygenation). The O2 content was identical for the two groups during baseline conditions, O2 shortage, and O2 readmission. Metabolic (lactate production) and functional parameters (heart rate, peak systolic pressure, left ventricular developed pressure, maximal contraction and relaxation rates, end-diastolic pressure, coronary perfusion pressure) were recorded at the end of stabilization, after O2 deficiency, and after 2 minutes of reoxygenation. Systolic function was significantly depressed after ischemia (p < 0.0001) but completely recovered to baseline values after 2 minutes of reperfusion. In contrast, systolic function was less severely depressed after hypoxia but failed to return to baseline after 2 minutes of reoxygenation. Diastolic function, unchanged during ischemia-reperfusion, remained significantly impaired during hypoxia-reoxygenation.

Effects of Energy Demand in Ischemic and in Hypoxemic Isolated Rat Hearts

Aim of this study was to assess the role of O2, lactate and energy demand in the regulation of myocardial work during severe dysoxia. For this purpose, we measured function and metabolism in isolated Langendorff-perfused rat hearts exposed to either ischemia or hypoxemia (matched for the O2 supply, 10% of baseline) with/out electrical stimulation. When hearts could adjust their HR, hypoxemia demanded more energy than ischemia (p < 0.05) despite same O2 supply. Venous PO2 was 12 +/- 2 or 139 +/- 20 mmHg (p < 0.0001), respectively, but VO2 was the same. After 10 min at HR = 300 min-1, myocardial performance increased in ischemic but not in hypoxemic hearts. PvO2 and VO2 were not affected by pacing. In contrast, both venous [lactate] and lactate production rate increased, but in ischemic hearts only. We conclude that ischemic hearts were downregulated while hypoxemic hearts were not. Likely, depressed washout of lactate during ischemia could offset the effects of O2 in severely dysoxic hearts. Anaerobic glycolysis provided the energy necessary to meet increased energy demand in ischemic hearts, but could not exploit this action in hypoxemic hearts probably because in these hearts it was already working near maximum.

Bilateral Partial Anomalous Pulmonary Venous Connection with Intact Atrial Septum

Bilateral partial anomalous pulmonary venous connection is a very rare malformation; its association with intact atrial septum is even more unusual. This report concerns a 5-year-old girl with this condition who underwent successful surgical repair.

Intussusception of Left Atrial Appendage through the Mitral Valve

In Volume 7 issue Number 2 of the Asian Cardiovascular & Thoracic Annals, Dhaded and colleagues1 reported the case of a 4-month-old child who died shortly after repair of a ventricular septal defect. Autopsy showed intussusception of the left atrial appendage, projecting into the mitral valve orifice, as the cause of death. The authors did not provide us with enough details of the clinical picture between the end of repair and death, in particular, we are not aware if an intraoperative or postoperative echocardiographic investigation had been performed. Therefore, it is possible that the complication had not been ruled out in time.