Search PubMed⌕ Search

Biomedical subjects

D Tousoulis

Publications and source records attributed to D Tousoulis.

At least 37 records · Page 2Linked to original sources
PubMed2000

L-Arginine in coronary atherosclerosis.

Nitric oxide is formed from the N-guanido terminal of the amino acid L-arginine and from molecular oxygen by nitric oxide synthase enzymes. L-arginine administration improves the coronary blood flow response to acetylcholine in patients with normal coronary arteries and hypercholesterolemia, reverses the defective endothelium-dependent vasodilation associated with an elevated plasma low-density lipoprotein level or hypercholesterolemia, dilates coronary epicardial arteries and stenoses, enhances nitric oxide generation, and inhibits lesion formation after balloon angioplasty. Stimulation of endogenous nitric oxide production could inhibit atherogenesis, and therefore may be of benefit in patients with risk factors for atherosclerosis.

Arginine↗
PubMed2000

Serum cholesterol level, cigarette smoking, and vasomotor responses to L-arginine in narrowed epicardial coronary arteries.

We examined the impact of serum cholesterol and cigarette smoking on the coronary vasomotor effects of L-arginine in patients with atherosclerotic coronary artery disease. The dilation of proximal and distal segments in response to low-dose L-arginine was greater in patients with a serum cholesterol level < or =200 mg/dl than in patients with a level >200 mg/dl, whereas the response was the same in smokers and nonsmokers.

Arginine↗
PubMed2000

Aortic pressure-diameter relation in patients with non-insulin dependent diabetes mellitus: new insights.

AIMS/HYPOTHESIS: Type II (non-insulin-dependent) diabetes mellitus is associated with macrovascular disease. Therefore, we investigated the aortic elastic properties by a new method in patients with diabetes and control patients matched with them. METHODS: Patients with Type II diabetes (n = 20) and control patients without diabetes (n = 21) were enrolled in the study. All patients had coronary artery disease. Instantaneous aortic diameter was measured by an intravascular catheter developed in our institution. Instantaneous aortic pressure was measured simultaneously at the same aortic level with a catheter-tip micromanometer. Thus, aortic pressure-diameter loops were obtained and slope and intercept were calculated. Aortic distensibility, stiffness constant and energy loss were also calculated. RESULTS: The mean age and the heart rate were similar in the two groups. The pulsatile changes in aortic diameter were greater in the control group (0.94 +/- 0.4 vs 1.28 +/- 0.4 mm, p < 0.01). The stiffness of the aortic wall was greater in diabetic patients as indicated from the following variables: the distensibility was less in patients with diabetes (1.16 +/- 0.6 vs 1.95 +/- 0.9 cm2 x dyne(-1) x 10(-6), p <0.01); the slope was greater (113.4 +/- 120.1 vs 51.61 +/- 3.3 mmHg/mm, p < 0.01) and the intercept was less in diabetic patients (-2301.9 +/- 2692.9 vs -1114.45 +/- 295.6 mmHg, p < 0.01); the stiffness constant was greater in patients with diabetes (1.66 +/- 1.8 vs 0.77 +/- 0.8 mm(-1), p < 0.03). Aortic energy loss was, however, similar between the groups. CONCLUSION/INTERPRETATION: In patients with non-insulin dependent diabetes aortic elastic properties, evaluated by pressure-diameter relation, are impaired. This could play an important part in the development of vascular complications related to diabetes.

Aorta, Thoracic↗
PubMed2000

Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing coronary arteriography.

OBJECTIVE: To examine the contribution of endothelin type A (ET(A)) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans. DESIGN: Controlled clinical study. SETTING: Tertiary cardiovascular referral centre. PATIENTS: 14 subjects were studied, seven with normal coronary arteries and seven with coronary artery disease, mean (SEM) age, 53 (2) years. INTERVENTIONS: After diagnostic coronary arteriography, BQ-123 (a selective ET(A) receptor antagonist; 100 nmol/min) in 0.9% saline, was infused into the left coronary artery at a rate of 1 ml/min for 60 minutes. Eight control subjects received saline alone. MAIN OUTCOME MEASURES: Blood flow velocity in the left anterior descending coronary artery, measured using a Doppler flow guidewire; coronary arteriography performed at baseline and immediately at the end of the BQ-123 or saline infusion to measure the diameter of proximal and distal left anterior descending coronary artery segments. RESULTS: The diameter of the proximal segment increased by 6 (2)%, while that of the distal segment increased by 12 (3)% after BQ-123 (both p < 0.05 v baseline). Coronary blood flow increased from 75 (10) to 92 (10) ml/min and coronary vascular resistance decreased from 1.99 (0.36) to 1.44 (0. 22) mm Hg/ml/min after BQ-123 (both p < 0.05 v baseline). The response to BQ-123 of patients with and without coronary artery disease was similar. There was no effect of saline in the controls. CONCLUSIONS: Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans by ET(A) receptor stimulation. The role of ET(B) receptors remains to be defined.

Blood Flow Velocity↗
PubMed2000

Complex stenosis morphology and vasomotor responses to inhibition of nitric oxide synthesis.

OBJECTIVE: To assess the relation between coronary vasomotor effects of N(G)-monomethyl-L-arginine (LNMMA) administration and coronary stenosis morphology, length, and severity in patients with stable angina. DESIGN: In 28 patients (24 male, four female) with coronary artery disease and chronic stable angina, intracoronary normal saline and 4 micromol/min LNMMA were infused for four minutes each, followed by an intracoronary bolus of 250 microg glyceryl trinitrate. Coronary stenoses were classified as concentric (smooth), eccentric (smooth), or complicated (irregular). The diameters of these stenoses and their adjacent reference proximal segments were measured by quantitative angiography. RESULTS: During LNMMA infusion a significantly larger proportion of complicated stenoses than concentric and eccentric stenoses constricted by >/= 5% (p < 0.01) and the magnitude of vasoconstriction was greater in complicated than in concentric and eccentric stenoses (p < 0.05). For complicated stenoses the magnitude of constriction (in mm) with reference to normal saline was greater than that of the concentric and eccentric stenoses (p < 0.05), whereas concentric and eccentric stenoses constricted similarly. Irrespective of the type of morphology, there was a correlation (p < 0.05) between both the severity and the length of stenoses and the magnitude of vasoconstriction to LNMMA. A similar proportion of concentric, eccentric, and complicated stenoses showed >/= 5% increase in diameter with glyceryl trinitrate, and the magnitude of the response was similar in the three groups. CONCLUSIONS: In patients with coronary artery disease, the response to LNMMA is greater when stenosis morphology is complex, indicating greater nitric oxide activity. This provides further evidence that plaques with complex morphology are in an active state.

Aged↗
PubMed2000

The impact of risk factors for atherosclerosis on the vasomotor effects of inhibition of nitric oxide synthesis in patients with normal angiograms.

We assessed the impact of systematic risk factors on the vasomotor effects of inhibition of nitric oxide synthesis. N(G)-monomethyl-L-arginine (LNMMA) was infused intracoronarily at 4, 8 and 16 micromol/min followed by intracoronary bolus administration of 250 microg nitroglycerin. Computerized angiography was used to assess the changes in the diameter of coronary segments. During the LNMMA infusions there was no significant difference in LNMMA response between smokers and non-smokers (-5.5+/-0.8 and -6.6+/-0.6%, respectively) or between hypertensives and normotensives (-6.4+/-1.1 and -6.1+/-0.6%, respectively), but the response was less in hypercholesterolaemic patients (-4.5+/-0.7 vs. -8.0+/-0.6%, p<0.05). Thus, the reduced nitric oxide activity is related to hypercholesterolaemia but not to smoking and hypertension.

Aged↗
PubMed1999

Vasomotor responses of coronary stenoses to acetylcholine and their relation to serum lipid levels in stable angina pectoris.

The effects of acetylcholine administration on coronary stenoses in relation to serum lipids level were evaluated in 18 patients (15 men, 3 women) with coronary artery disease and stable angina. Intracoronary acetylcholine was infused in concentrations 10(-7), 10(-6), 10(-5) M, followed by intracoronary bolus administration of isosorbide dinitrate. Computerized angiography was used to assess the changes in the diameter of stenoses and of proximal and distal segments. During acetylcholine infusion, at concentrations between 10(-7) to 10(-5) M, there was a significant (p <0.01) dose-dependent constriction of proximal and distal segments and of stenoses reversed by isosorbide dinitrate. There was no correlation between the serum total cholesterol level and the responses of proximal and distal segments to acetylcholine or nitrate. A correlation (p <0.05) was found between the serum total cholesterol level and the response of stenoses to acetylcholine, but there was no correlation with the response to isosorbide dinitrate. In conclusion, in patients with stable angina current serum total cholesterol level correlates with the vasomotor response of coronary stenoses to intracoronary acetylcholine. These findings are consistent with a direct effect of cholesterol, increasing basal coronary vasomotor tone and increasing the stimulated vasoconstrictor response of stenoses.

Acetylcholine↗
PubMed1999

Relation between exercise and dobutamine stress-induced wall motion abnormalities and severity and location of stenosis in single-vessel coronary artery disease.

BACKGROUND: Quantitative coronary angiography has been shown to allow accurate assessment of coronary stenosis. Exercise and dobutamine stress echocardiography both are established methods for assessing the functional importance of coronary stenosis. The relation, however, between exercise and dobutamine stress-induced wall motion abnormalities and the severity and location of stenosis remains controversial. METHODS AND RESULTS: Thirty patients with single-vessel coronary artery disease with >/=50% minimal luminal reduction and stable angina participated in the study. Severity of coronary artery stenosis was assessed by means of computed angiography. During peak exercise echocardiography 23 patients had wall motion abnormalities and 7 did not. A positive test result was associated with severity of stenosis >/=80% for 65% of stenoses (P <.05 versus severity of stenosis <80%) and with a proximal location of 94% of stenoses (P <.01 versus middle and distal stenoses). A significant correlation was found between area of stenosis and difference in wall motion score between rest and peak exercise (r = 0.53, P <.01). The proportion of positive exercise stress was greater among stenoses with severity <80% (62% versus 46% dobutamine stress, P <.05). During dobutamine stress echocardiography 18 patients had wall motion abnormalities and 12 patients did not. A positive test result was associated with severity of stenosis >/=80% in 72% of stenoses (P <.05 versus severity of stenosis <80%) and with a proximal location in 81% of stenoses (P <.01 versus middle and distal stenoses). A weak correlation was found between area of stenosis and difference in wall motion score between rest and peak dobutamine stress (r = 0.37, P <.05). CONCLUSIONS: Among patients with single-vessel coronary artery disease, positive stress echocardiographic test results usually are associated with proximal >/=80% stenosis. Patients with <80% stenoses are more likely to have a positive exercise stress test result than a positive dobutamine stress test result.

Cardiotonic Agents↗
PubMed1999

Inhibition of nitric oxide synthesis in human epicardial coronary arteries and stenoses in relation to serum lipid level.

Administration of N(G)-monomethyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthase, causes a reduction in epicardial coronary artery and stenosis diameter in patients with coronary artery disease, indicating that these diseased vessels produce nitric oxide. Elevations of low density lipoprotein cholesterol impair human endothelium-dependent relaxation. The relationship between serum lipid level and nitric oxide production by normal and atheromatous human epicardial coronary arteries in vivo is unknown. The effects of an intracoronary infusion of LNMMA (8 and 16 micromol/min) followed by intracoronary administration of 250 mcg nitroglycerin on non-stenotic proximal and distal coronary segments and coronary stenoses were studied in 11 patients with coronary artery disease and in 19 patients with 'normal arteriograms'. Coronary luminal diameter was measured by computerized quantitative angiography. In patients with cholesterol level> or = 220 mg/dl, no significant response to LNMMA was observed in the proximal segments in either those with 'normal angiograms' or those with coronary disease. In patients with cholesterol <220 mg/dl significant constriction (P<0.01) was observed in the proximal segments of patients with 'normal coronary angiograms' at both 8 and 16 micromol doses, but occurred only at the 16 micromol/min dose (P<0.01) in those with coronary disease. In conclusion the difference in vasomotor response to LNMMA in relation to cholesterol level is localised to the proximal coronary segments, and the response does not correlate with cholesterol or triglyceride level. This is therefore more likely to be an indirect effect of elevated cholesterol, e.g. undetected atheroma, than a direct effect on nitric oxide synthesis.

Adult↗
PubMed1999

Vasomotion of coronary arteries: from nitrates to nitric oxide.

The vascular endothelium is a source of substances particularly nitric oxide that act in a paracrine fashion either to contract or relax smooth muscle cells and this function is disturbed in atherosclerotic arteries. The endothelium derived nitric oxide contribute in the basal vasomotor tone of epicardial normal and atheromatous coronary coronary arteries, and of atheromatous coronary stenoses in patients with stable angina. Nitrates, by acting indirectly to increase cGMP in smooth muscle cells, dilate most coronary stenoses and normal coronary segments, decrease left ventricular afterload and diastolic filling pressure and improve the distribution of coronary flow to subendocardial zone. Large and small epicardial coronary vessels responded differently to endothelium-dependent and independent vasodilators.

Arteriosclerosis↗
PubMed1999

Effects of L- and D-arginine on the basal tone of human diseased coronary arteries and their responses to substance P.

OBJECTIVE: To assess the effects of substance P administration alone and in combination with L- and D-arginine in patients with normal angiograms and in patients with coronary artery disease. DESIGN: Intracoronary infusions of (a) normal saline, (b) the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min) before and after L- or D-arginine (50 and 150 micromol/min), and (c) glyceryl trinitrate (250 microg bolus) were given to 17 patients with coronary artery disease and stable angina, and to six patients with normal angiograms. The diameter of angiographically normal proximal and distal segments and coronary stenoses were measured by computerised quantitative angiography. RESULTS: L-arginine administration was associated with significant dilatation of stenoses (p < 0.01) of proximal segments of both "normal" (p < 0.05) and diseased (p < 0.01) arteries, and of distal segments of diseased arteries (p < 0.01). No significant changes were associated with D-arginine administration. Dose dependent dilatation of all segments including stenoses, was observed with substance P both before and after L-arginine infusion (p < 0.01). The magnitude of dilatation of stenoses and all segments of both "normal" and diseased coronaries was greater after L-arginine (p < 0.05) but not D-arginine and substance P infusion, than it was after saline and substance P infusion. Administration of D- or L-arginine did not change the magnitude of substance P induced dilatation. CONCLUSIONS: Diseased and "normal" coronary arteries dilated in response to substance P and L-arginine but were unaffected by D-arginine infusion. The magnitude of the response to substance P was not increased by L-arginine administration, indicating that it is not critically dependent on the availability of substrate for nitric oxide synthase.

Analysis of Variance↗
PubMed1999

Evidence of partially preserved endothelial dilator function in diseased coronary arteries.

OBJECTIVE: To examine the effects of substance P (endothelium dependent vasodilator) and glyceryl trinitrate (endothelium independent vasodilator) on epicardial coronary arteries in patients with normal coronary angiograms and patients with coronary artery disease. DESIGN: Intracoronary infusions of normal saline, the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min each for five minutes), and glyceryl trinitrate (250 microg bolus) were given in 24 patients with coronary artery disease and stable angina, and in nine patients with normal angiograms. The diameter of proximal and distal coronary segments was measured by computerised quantitative angiography RESULTS: Proximal segments of patients with coronary artery disease dilated less than those of patients with normal angiograms in response to 27.8 pmol/min substance P (mean (SEM): 7.9 (1.3)% v 15 (2.3)% respectively, p < 0. 01). The proximal segments of diseased arteries also dilated less than those of "normal" arteries in response to glyceryl trinitrate (10.2 (1.6)% v 18.4 (2.9)%, respectively, p < 0.01). The responses of distal segments to substance P and glyceryl trinitrate were similar in the two patient groups. There were correlations (all p < 0.001) between the coronary diameter after substance P and after glyceryl trinitrate in normal proximal segments (r = 0.94) and normal distal segments (r = 0.64), in diseased proximal segments (r = 0.95) and diseased distal segments (r = 0.89), and for coronary stenoses (r = 0.93). CONCLUSIONS: Proximal segments of patients with coronary disease dilated less than the proximal segments of "normal" patients in response to substance P and glyceryl trinitrate. The response to substance P is substantial and closely correlated with the response to glyceryl trinitrate in both "normal" patients and those with coronary disease. This suggests that although the proximal segments of diseased coronary arteries have a reduced capacity to dilate in response to direct stimulation of smooth muscle cell relaxation, they retain much of their endothelium dependent vasodilator function.

Case-Control Studies↗
PubMed1998

Effects of changing the availability of the substrate for nitric oxide synthase by L-arginine administration on coronary vasomotor tone in angina patients with angiographically narrowed and in patients with normal coronary arteries.

We assessed the effects of intracoronary administration of substance P, LNMMA, L-arginine, and nitroglycerin in patients with normal coronary angiograms and in patients with coronary artery disease. LNMMA constricted (p <0.01) and both substance P and nitroglycerin dilated normal and diseased proximal and distal segments and stenoses (p <0.01). L-Arginine reversed the effect of LNMMA in all segments and caused greater dilation of the diseased arteries, including stenoses (p <0.05), indicating that there is a relative deficiency of L-arginine in diseased coronary arteries.

Aged↗