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D A Mickle

Publications and source records attributed to D A Mickle.

129 records · Page 8Linked to original sources

The effect of lactate infusion on myocardial metabolism and ventricular function following ischemia and cardioplegia.

Impaired myocardial fatty acid and glucose metabolism following ischemia and cardioplegia may limit the recovery of myocardial oxidative metabolism and ventricular function. Lactate, a simple three carbon compound, can be readily metabolized to pyruvate and is possibly the preferred substrate for aerobic metabolism. Therefore, increasing arterial lactate concentrations may improve myocardial metabolic recovery after ischemia and cardioplegia. Myocardial lactate metabolism and ventricular function were assessed in a canine model of 45 mins of global normothermic ischemia followed by 60 mins of cold potassium cardioplegic arrest. Thirteen dogs received a perioperative infusion of sodium lactate to elevate arterial concentrations (from 6 to 12 mmol/L) and 12 dogs received an equivalent amount of saline. The high arterial lactate concentrations were associated with an increased myocardial lactate consumption and oxidation (as assessed by 14C-labelled lactate) during reperfusion. Myocardial ATP concentrations fell during reperfusion despite improved myocardial oxidation. The recovery of ventricular function (as assessed by a compliant intraventricular balloon) was incomplete and only marginally better with the high arterial lactate concentrations. An infusion of lactate improved myocardial oxidative metabolism following ischemia and cardioplegia. However, the recovery of ventricular function was incomplete perhaps because of inadequate preservation of myocardial ATP.

Adenosine Triphosphate↗

Future directions of vitamin E and its analogues in minimizing myocardial ischemia-reperfusion injury.

Oxidant injury contributes to myocardial stunning, and cardiac ischemic and reperfusion injury. Vitamin E is the major--and perhaps the only--lipid soluble, chain-breaking antioxidant in the heart. Vitamin E and its analogues potentially offer significant advantages for the prevention of ischemic and reperfusion injury. Recent investigations have suggested that modified vitamin E analogues may be more efficacious than vitamin E and may permit myocardial salvage from acute myocardial ischemic injury.

Animals↗

Cardiac storage with University of Wisconsin solution, calcium, and magnesium.

BACKGROUND: Previous investigations from this institution and others support the role of University of Wisconsin solution for prolonged hypothermic cardiac storage. Modification of the divalent cation concentrations has been beneficial for cardioplegic investigations and may enhance cardiac recovery after extended preservation. METHODS: To investigate this hypothesis, isolated rodent hearts were obtained from Sprague-Dawley rats and mounted on a Langendorff apparatus. Rat hearts were flushed (15 ml/kg) and stored (30 ml) for 8 hours at 0 degree C in unmodified University of Wisconsin solution (n = 16/group) or University of Wisconsin solution with calcium concentrations of 0.025 to 10 mmol/L or magnesium concentrations of 10 to 20 mmol/L (six to eight hearts/group). Finally, combinations of calcium and magnesium were examined. Rat hearts were studied before storage and after 45 minutes of reperfusion with an intraventricular balloon. RESULTS: Developed pressure (mean +/- standard deviation) was increased with calcium 0.1 mmol/L (University of Wisconsin solution: 69.2% +/- 7.0%; Ca++ 0.1 mmol/L: 78.9% +/- 6.1%, p < 0.05), whereas only the addition of the highest calcium concentration (10 mmol/L) was significantly harmful (developed pressure: 58.3% +/- 8.4%, p < 0.05; creatine kinase release: 408 +/- 200 versus 170 +/- 104 IU/gm, p < 0.05; lactate dehydrogenase release: 103 +/- 43 versus 37 +/- 26 IU/gm, p < 0.05). Coronary flow recovered to control values with magnesium 15 mmol/L, which was significantly greater than that achieved with unmodified University of Wisconsin solution (97.1% +/- 14.6% versus 72.1% +/- 8.4%, p < 0.05). Of the calcium-magnesium combinations tested, developed pressure was increased compared with unmodified University of Wisconsin solution with calcium 0.1 and magnesium 20 mmol/L (76.8% +/- 6.4%, p < 0.05). Diastolic function was reduced in all groups (p < 0.0001) and not significantly different between groups. CONCLUSIONS: The experiments indicated that recovery after storage with University of Wisconsin solution is enhanced with the addition of calcium and magnesium. The addition of high concentrations of calcium (> or = 2.5 mmol/L) appears harmful.

Adenosine↗