Berent Discigil

Hypoxia increases vasodilator release from internal mammary artery and saphenous vein grafts

BACKGROUNDnGreater release of endothelium-derived nitric oxide is implicated in the superior patency of the internal mammary artery (IMA) used in coronary artery bypass grafting. This study compared the release of endothelium-derived nitric oxide into the lumen of the IMA and the saphenous vein under normoxic versus hypoxic conditions.nnnMETHODSnSegments of canine IMA and saphenous vein were perfused in vitro. Vasorelaxant activity was measured as vasodilatation of coronary artery smooth muscle induced by the effluent.nnnRESULTSnEffluents from the IMA and saphenous vein caused comparable vasodilation of coronary artery smooth muscle. The vasodilatation reversed when perfusion was switched to a prosthetic conduit. Vasodilator activity from the IMA and saphenous vein was attenuated by removing the intima of the grafts or by adding N(G)-monomethyl-L-arginine (10(-4) mol/L) or N(G)-nitro-L-arginine (10(-4) mol/L), two inhibitors of nitric oxide synthesis. Indomethacin attenuated vasorelaxant activity from saphenous vein grafts but not IMA grafts (n = 10). Vasodilator release from the IMA and saphenous vein was augmented by hypoxia. This augmentation was inhibited by indomethacin (n = 10, p < 0.05). Hypoxic augmentation reversed with return to normoxia.nnnCONCLUSIONSnThe release of endothelium-derived nitric oxide and prostacyclin from bypass grafts into the lumen, particularly during hypoxemia, could promote the vasodilation of distal coronary arterial beds, enhancing myocardial perfusion.

Novel technique to bioassay endocardium-derived nitric oxide from the beating heart

Nitric oxide is a potent vasodilator and antiplatelet substance released by the vascular endothelium. In the current study, isolated rabbit hearts were perfused retrograde in the aortic root with a balanced salt solution using a Langendorff technique. To perfuse the right cardiac chambers, an inflow cannula was placed in the superior vena cava and an outflow cannula in the right ventricular apex via the pulmonary artery. To detect endocardial vasodilator production, right heart perfusate was used to bathe a bioassay segment of canine coronary artery denuded of endothelium. Perfusate from unstimulated hearts did not alter smooth muscle tone in the bioassay tissue. Calcium inophore, a potent stimulus for endothelial nitric oxide production, produced relaxation of the bioassay smooth muscle when added to the cardiac perfusate but not when applied directly to the bioassay segment. Cardiac effluent vasodilator activity was abolished by removal of the endocardium or addition of nitric oxide synthesis inhibitors, but not by prostanoid inhibitors. These experiments describe a practical method to bioassay endocardial nitric oxide production in the beating heart.

Efeito protetor da criocardioplegia cristalóide na isquemia global e reperfusäo durante circulaçäo extracorpórea: um mecanismo dependente do endotélio?

Previous experiments showed evidence of impaired receptor-mediated production of EDRF/NO following reperfusion injury could be due to G-protein dysfunction which links endothelial cell receptors to the pathway of EDRF/NO synthesis. This experimental research suggested that criocrystalloid cardioplegia, associated to topic hypotermia, could prevent or reverse the endothelium disfunction under same experimental conditions. More experiments will be necessary to get definitive conclusions, because fine statystical analysis suggested increasing the number of experiments. Otherwise, the present study proved for the first time that hypothermia alone can cause the release of PGI2 and EDRF/NO from the endothelium. This suggests that the endothelium could be an important temperature sensor and has important implications for the understanding of cardiopulmonary bypass physiology and local vascular autoregulation.

Comparisons of the release of vasodilator substances from left and right cardiac chambers of the isolated perfused rabbit heart: Implications for intraventricular thrombus formation

Prostacyclin (PgI(2)) and endothelium-derived nitric oxide (EDNO) are produced by the arterial and venous endothelium. In addition to their vasodilator action on vascular smooth muscle, both act together to inhibit platelet aggregation and promote platelet disaggregation. EDNO also inhibits platelet adhesion to the endothelium. EDNO and PgI(2) have been shown to be released from the cultured endocardial cells. In this study, we examined the release of vasoactive substances from the intact endocardium by using isolated rabbit hearts perfused with physiological salt solution (95% O(2)/5% CO(2), T=37 degrees C). The right and left cardiac chambers were perfused through separate constant-flow perfusion loops (physiological salt solution, 8 ml min(-1)). Effluent from left and right cardiac, separately, was bioassayed on canine coronary artery smooth muscle, which had been contracted with prostaglandin F(2alpha_)(2 x 10(-6)M) and no change in tension was exhibit. However, addition of calcium ionophore A23187 (10(-6)M) to the cardiac chambers perfusion line induced vasodilation of the bioassay coronary ring, 61.4+/-7.4% versus 70.49+/-6.1% of initial prostaglandin F(2alpha) contraction for the left and right cardiac chambers perfusate, respectively (mean+/-SEM, n=10, p>0.05). Production of vasodilator was blocked totally in the left heart but, only partially blocked in the right heart by adding indomethacin (10(-5)M) to the perfusate, respectively, 95.2+/-2.2% versus 41.5+/-4.8% (mean+/-SEM, n=10, p<0.05). 6-Keto prostaglandin F(1alpha), measured in the endocardial superfusion effluent was also higher for the left cardiac chambers than for the right at the time of stimulation with the A23187, respectively, 25385.88+/-5495 pg/ml (n=8) versus 13,132.45+/-1839.82 pg/ml (n=8), (p<0.05). These results showed that cyclooxygenase pathway plays major role in generating vasoactive substances for the left cardiac chamber endocardium; while it is not the main pathway for the right ventricular endocardium at which EDNO and PgI(2) could act together and potentiate their antithrombogenic activities in isolated perfused rabbit heart. This may be an explanation for the intraventricular thrombus mostly seen in left ventricle rather than in right ventricle as a complication of myocardial infarction.

Reatividade vascular da artéria mamária interna: estudos farmacológicos comparativos entre artérias caninas direita e esquerda

To study factors which modulate the tone of internal mammary artery (IMA) bypass grafts, right and left canine IMAs were studied in vitro in organ chambers: 1) increasing concentrations of the platelet-derived products adenosine diphosphate (ADP) or serotonin (5-HT) induced vasodilation of contracted right and left IMAs. The vasodilation caused by ADP was endothelium-dependent while serotonin acted directly on the vascular smooth muscle; 2) the autacoids histamine and bradykinin also induced IMA vasodilation, histamine via a direct action on the smooth muscle, and bradykinin through the release of nitric oxide; 3) in canine IMAs, the calcium ionophore A23187, which acts independently of receptors produced endothelium-dependent vasodilation of contracted blood vessels; 4) dopamine, dobutamine, and papaverine induced vasodilation of the IMA, regardless of the presence or absence of an intact intima; 5) norepinephrine induced profound IMA vasoconstriction which was comparable to contraction to potassium ions or the constrictor peptide endothelin; 6) in 83% of 20 biological assays the basal release of nitric oxide was bigger in left IMAs than right IMAs; 7) biological assays of IMAs confirmed the importance of prostacyclin (PGI2) in response to hypoxia; 8) no differences between right and left IMAs were observed studying the different drugs.

Cardioplegia cristalóide, barotrauma e função endotelial: considerações experimentais

Experiments were performed in organ chambers to investigate if high pressures infusions of crystalloid cardioplegia effect the endothelium function of epicardic canine coronary arteries. These experiments did not show any alterations at level of receptors (dose-response curves to ACH and ADP); signal transduction/G-proteins (dose-response curve to sodium fluoride); intracellular mechanisms of the EDRF/NO release (dose-response curves to phospholipase C and calcium ionophores A23187). The smooth muscular relaxant function (dose-response curves to sodium nitroprusside and isoproterenol) and contarctions (doseresponse curves to KCI and PGF2alpha) were also preserved. These experimental observations allow the following speculative considerations: a) Should barotrauma be a phenomenon present only in damaged coronary circulation? b) All infusion were performed in no more than two or three minutes. Is cardioplegia barotrauma a phenomenon time-dependente? c) High levels of potassium could be associated with barotrauma, d) Cardioplegia barotrauma is a fancy, at least in our experimental conditions? e) Experiments in organ chambers study only epicardic arteries. Could barotrauma damage the microcirculation? f) The canine coronary circulation is less affeccted by high pressure than human coronaries? These data are suggestive that crystalloid moderately hyperkalemic infusions at high pressures for two or three minutes, do not impair the endothelium release of EDRF/NO of canine epicardic coronary arteries.