[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.

[The effects of verapamil on the postischemic changes in the coronary microcirculation: the role of nitric oxide]. / Effetti del verapamil sulle alterazioni postischemiche della microcircolazione coronarica: ruolo dell'ossido nitrico.

BACKGROUND: The aim of this study was to evaluate, in the model of isolated working rat heart, the effects of verapamil on postischemic changes in cardiac mechanical function and microvascular coronary permeability, and the possible role of nitric oxide. METHODS: We used 72 male Wistar rats, weighing 250-300 g, divided into six groups: Group A, hearts perfused with modified Krebs-Henseleit solution (KH); Group B, hearts perfused with KH + verapamil 0.25 microM; Group C, hearts perfused with KH + verapamil 0.5 microM; Group D, hearts perfused with KH + verapamil 1 microM; Group E, hearts perfused with KH + NG-nitro-L-arginine methyl ester (L-NAME) 30 microM; Group F, hearts perfused with KH + verapamil 0.25 microM + L-NAME 30 microM. Hemodynamic parameters, necrosis enzyme release and fluoroscein isothiocyanate-albumin extravasation were evaluated. RESULTS: We observed a clear preservation of cardiac mechanical function and microvascular function in Group B (low dose verapamil) compared to groups A (control), C and D (high dose verapamil); the inhibition of nitric oxide-synthase in the presence of verapamil, obtained in Group F, elicited a loss of myocardial protective effects of verapamil. CONCLUSIONS: Our data suggest that low dose verapamil is effective on postischemic damage reduction and most probably nitric oxide plays a determinant role in this effect.

[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.

[Effect of A1 adenosine receptor blockade on postischemic damage to the coronary microcirculation]. / Effetti del blocco dei recettori A1 dell'adenosina sul danno postischemico della microcircolazione coronarica.

Recent studies suggest that A1 adenosine receptor antagonists may prevent reperfusion injury in the lung and heart. The pathophysiology of this protective effect is unclear; a possible inhibition of superoxide anion release from neutrophils, or leukocyte activation and platelet aggregation are reported. We tested the hypothesis of a blood-independent cardioprotection following A1 adenosine receptor antagonism with 1,3 dipropyl,8-cyclopentylxanthine (DPCPX). Isolated working rat hearts were submitted to 10 and 20 min global ischemia in order to assess functional alterations, necrosis enzyme and purine release in coronary effluent, arrhythmias, heart weight, ultrastructural morphometry and microvascular permeability by FITC-albumin diffusion technique. DPCPX (100 nM) was administered to the perfusion buffer before ischemia. In untreated hearts we detected a significant impairment of function, associated with a significant enzyme and purine release, myocardial edema and ultrastructural damage. In DPCPX-treated hearts functional and histological damage was significantly reduced compared to controls. Moreover, a significant reduction in postischemic endothelial permeability (FITC-albumin diffusion, p < 0.02) and ultrastructural damage was observed. Our data suggest that A1 adenosine receptor antagonism with DPCPX significantly reduces ischemia-reperfusion damage in isolated, crystalloid perfused rat heart by a direct reduction of endothelium damage, fluid diffusion within the interstitium and improvement of coronary microcirculation.

Color duplex scanning for the identification of extracranial atherosclerosis in patients with suspected coronary artery disease.

BACKGROUND: The presence of extracranial artery disease has been used as a predictor of coronary artery disease (CAD). The present study was conducted to test the prevalence of extracranial artery disease among patients with suspected CAD. METHODS: Among candidates for coronary arteriography, 400 consecutive patients (mean age 63 +/- 11 years, 78% males, 22% females) underwent color duplex ultrasound of carotid arteries. RESULTS: Extracranial artery disease was documented in 60 patients (15%), CAD in 309 patients (77%). Patients with extracranial artery disease were significantly older (p < 0.001), smoked a higher amount of pack-years (p < 0.001), showed a higher incidence of diabetes (p < 0.01), hypertension (p < 0.05) and CAD (p < 0.05) when compared to extracranial artery disease-free subjects. Plotting age against extracranial artery disease and CAD distribution, extracranial artery disease occurred later in life than CAD (p < 0.001). The best cut-off point of age for predicting extracranial artery disease was 68 years. Carotid angiography was performed in 114 patients after cardiac catheterization (k = 0.8044 with color duplex scanning). CONCLUSIONS: Extracranial artery disease is frequent among patients undergoing coronary arteriography. Carotid ultrasound screening is useful in older patients.