http://repub.eur.nl/res/aut/3041/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/8911/ 1996-01-01T00:00:00Z We assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of 40 min global ischemia and 45 min reperfusion; (2) preconditioning by 5 min global ischemia and 15 min reperfusion prior to sustained ischemia and reperfusion; (3) Preconditioning by three episodes of brief ischemia-reperfusion prior to sustained ischemia. Repetitive episodes of brief ischemia-reperfusion were associated with increased reactive hyperemia, decreased release of purines and prostaglandin 6-keto F1 alpha, lower tissue glycogen but no change in lactate washout. After 40 min ischemia, release of lactate was 173 +/- 17, 196 +/- 6 and 149 +/- 9 mumol/g in groups 1, 2 and 3, respectively (P < 0.01, group 2 v group 3). Preconditioning had no effect on ischemic arrest but had divergent effects on the development and the magnitude of ischemic contracture: delay and attenuation in group 2 but enhanced onset in group 3. Preconditioning provided a dose-dependent protection from the increase in left ventricular end-diastolic pressure, reduced the reperfusion release of purine metabolites and of creatine kinase, but neither improved systolic function nor prevented arrhythmia. 6-Keto F1 alpha production was 87 +/- 13, 132 +/- 19 and 241 +/- 35 pmol/g in groups 1, 2, 3, respectively (P < 0.01 group 1 v group 3). We conclude that when subjected to prolonged global ischemia, preconditioned isolated rat hearts develop less post-ischemic contracture, lose less purine nucleosides and creatine kinase activity. In addition, preconditioning leads to increased production of prostacyclin. Differences among preconditioning protocols in lactate production seem to be related to the ischemic contracture development, but may not play an ultimate role in attenuation of myocardial damage or improvement of postischemic recovery. http://repub.eur.nl/res/pub/4332/ 1989-01-01T00:00:00Z Xanthine oxidoreductase has been demonstrated in the heart of various species. However, its presence in human heart is still debated. In the literature, high to undetectable levels have been reported. We studied the arterial-venous urate difference across the heart of patients undergoing both routine cardiac catheterization and percutaneous transluminal coronary angioplasty. Urate is the end product of the reaction catalysed by xanthine oxidoreductase. In 10 patients, studied before angioplasty, the plasma urate level in the great cardiac vein exceeded the arterial one by 26 +/- 10 nmol/ml (P = 0.028). In a further 13 patients, urate production was maximal immediately after the last of four consecutive occlusions (23 +/- 8 nmol/ml, P = 0.018) and concomitant with increased coronary sinus hypoxanthine levels. We conclude that xanthine oxidoreductase is probably present in the heart of patients, suffering from ischemic heart disease, and responsible for the increase in urate production during transient myocardial ischemia. http://repub.eur.nl/res/pub/4235/ 1987-01-01T00:00:00Z Twelve patients with proximal stenosis of the left anterior descending artery, normal myocardial wall motion but without angiographically demonstrable collateral circulation, were studied during transluminal occlusion. Prior to the first transluminal occlusion before crossing the lesion with the balloon, patients were randomly given 0.2 mg nifedipine or its solvent in the left mainstem. The same dose was repeated via the balloon catheter, positioned across the lesion, immediately prior to the second transluminal occlusion. In all patients great cardiac venous flow and ST-elevation were monitored during and after each transluminal occlusion. The lactate extraction ratio A-GCV/A (A = arterial, GCV = great cardiac vein) was determined prior to the angioplasty procedure, 10-15 seconds after each transluminal occlusion and 10 minutes after the third transluminal occlusion. Great cardiac venous flow rose significantly to an average of 160% of basal flow when nifedipine was administered into the mainstem before the angioplasty procedure while its solvent had no effect. During each transluminal occlusion, great cardiac venous flow diminished on average by 30% in those who received nifedipine and by 28% in those who received only its solvent. This difference was statistically not significant. After angioplasty great cardiac venous flow was slightly, but not significantly, increased in both groups with respect to basal flow (104% resp. 120% of control). Patients who received nifedipine in the post-stenotic area just before the second transluminal occlusion, had significantly lower lactate production, measured immediately after the transluminal occlusion compared with the patients who received only its solvent (P less than 0.01). The ST-elevation during the second transluminal occlusion was significantly lower in the nifedipine group (0.1 mm in nifedipine group versus 1.4 mm in solvent group; P less than 0.05, unpaired t-test). Nifedipine given intracoronary in the post-stenotic area just before coronary angioplasty reduces lactate release and electrocardiographic signs of myocardial ischemic injury. This regional cardioprotective effect seems not due to an enhanced collateral flow, but to a regional cardioplegic effect, which precedes the ischemic event.