[Ischemic preconditioning of the myocardium: the role of changes in the permeability of the coronary microcirculation]. / Precondizionamento ischemico del miocardio: ruolo delle alterazioni della permeabilità del microcircolo coronarico.

In isolated working rat hearts we have evaluated the effects of preconditioning on postischemic coronary endothelial permeability. Isolated Wistar male rat hearts were used and subdivided into three groups: Group A, control hearts submitted to 20 min global normothermic ischemia; Group B, hearts subjected, before ischemia, to preconditioning (three phases of 3 min ischemia, each one followed to 2 min Langendorff reperfusion; Group C, hearts submitted to preconditioning and hypertonic reperfusion (by adding 80 mM sucrose to normal perfusion buffer), in order to increase the effects on postischemic interstitial fluid accumulation (osmotic forces balance). A 65 min working heart reperfusion was also performed to assess functional response. We have evaluate the hemodynamic changes (coronary and aortic flows, systolic aortic pressure, work minute), reperfusion arrhythmias, heart weight changes (ww/dw), myocardial enzyme release (creatine phosphokinase and lactic dehydrogenase) and microcirculation permeability changes (FITC.albumin diffusion), as an index of endothelial function. In Group B, a significant reduction of ischemia-reperfusion damage (functional recovery, enzyme release and arrhythmias) was detected with respect to Group A. In Group C this reduction was significantly more evident with respect to groups A and B. In Groups B and C, a significant reduction in myocardial reperfusion (ww/dw: A: 5.9 +/- 0.5, B: 4.9 +/- 1.1, p < 0.02 vs A, C: 4.4 +/- 0.6, p < 0.01 vs A) edema and FITC-albumin diffusion (A: 32.8 +/- 5.9% area; B: 16.3 +/- 6.1% area, p < 0.01 vs A; C: 13.3 +/- 4.5% area, p < 0.01 vs A), especially in perimyocytic space was also observed. Data show that preconditioning may exert a cardioprotective effect by reducing endothelial postischemic functional alterations (vascular permeability) and reperfusion edema. The importance of fluid diffusion within the interstitium in the development of reperfusion damage is supported by better postischemic recovery in Group C, in which an interference on osmotic load was performed.

[Endothelium-protective effects of epinine (N-methyldopamine) in myocardial ischemia-reperfusion in the isolated working rat heart]. / Effetto endotelio-protettivo dell'epinina (N-metildopamina) in corso di ischemia-riperfusione nel cuore isolato e lavorante di ratto.

The effect of cardiac dopaminergic receptors stimulation with epinine (N-methyldopamine) on reperfusion injury was investigated in isolated working rat heart submitted to 15 min of global ischemia. Isolated Wistar rat hearts (n = 75) were used and subdivided into five groups: Group A control hearts, Group B epinine 10 ng/ml, Group C epinine 20 ng/ml, Group D epinine 40 ng/ml, Group E epinine 80 ng/ml. The drug was added to the perfusion buffer at the beginning of experimental procedures. Hemodynamic parameters, heart rhythm (epicardial ECG), heart weight changes, coronary microvascular permeability (FITC-albumin diffusion) and myocytes damage (necrosis enzymes release, immunoperoxidase labeling anti-LDH antibody) were evaluated. After ischemia in groups B and C a significant reduction of functional alterations and myocytes damage was observed with respect to Group A associated with a significant reduction of reperfusion edema (heart weight: Group A +29 +/- 3.5%, Group B +15 +/- 3.8%, Group C 16 +/- 5%, Group D 27 +/- 5%, Group E 33 +/- 4%). At reperfusion time, a significant proarrhythmic effect occurred only in groups D and E. A significant reduction of postischemic endothelial FITC-albumin diffusion was also observed in groups B and C (FITC-albumin diffusion, Group A 32.8 +/- 6% area, Group B 16.33 +/- 5% area, Group C 21.7 +/- 4.5% area, Group D 30 +/- 5% area, Group E 35 +/- 7% area). Our data show that, in isolated working rat heart, the dopaminergic stimulation with low-doses epinine may exert a cardioprotective effect against ischemia-reperfusion damage by modulating endothelial permeability changes and improving coronary microcirculation. The importance of dopaminergic receptors is also suggested by the evidence that at higher doses, when alpha and beta-adrenoceptors stimulation occurs, this cardioprotective effect is significantly reduced or lost.