[Efficacy of radiofrequency catheter ablation in a patient with sinus node reentrant tachycardia].

We performed electrophysiological study and catheter ablation on a 62-year-old patient with supraventricular tachycardia(SVT). This SVT was reproducibly initiated and terminated by atrial stimulation during the electrophysiological testing. The P-wave morphology and atrial activation sequence of intracardiac electrograms were identical to those in normal sinus rhythm. SVT was terminated with carotid sinus massage that increased vagal tone, and for this reason, the reentry circuit of SVT could be localized in sinus node. On the basis of these findings, the SVT was diagnosed as sinus node re-entrant tachycardia and was successfully eliminated by radiofrequency catheter ablation. Radiofrequency catheter ablation would be effective in patients with sinus node reentrant tachycardia refractory to anti-arrhythmic drugs. It should, however, be performed with careful consideration to the influence of the sinus node.

The role of nitric oxide in bradykinin-induced dilation of coronary resistance vessels in patients with hypercholesterolemia.

OBJECT: In hypercholesterolemic patients, acetylcholine- and substance P-mediated endothelium-dependent dilation of the coronary resistance vessels is impaired due to decreased nitric oxide production. However, it is not clear if bradykinin-induced coronary vasodilation is impaired in these patients. We investigated whether the endothelium-dependent dilation of coronary resistance vessels mediated by bradykinin is impaired in patients with hypercholesterolemia and, if so, whether this impairment is caused by a decreased production of nitric oxide. METHODS: We examined the coronary vascular responses to acetylcholine and bradykinin. The vascular responses to bradykinin were also assessed after N(G)-monomethyl-L-arginine was infused to inhibit nitric oxide production. Drugs were infused into the left coronary ostium and coronary blood flow (CBF) and coronary vascular resistance were evaluated by quantitative angiography and Doppler flow velocity measurements. PATIENTS: Twelve hypercholesterolemic patients and 11 control patients with angiographically normal coronary arteries were studied. RESULTS: The vasodilator responses to acetylcholine and bradykinin were reduced in hypercholesterolemic patients compared with control patients (p<0.005 and p<0.04, respectively, by two-way analysis of variance (ANOVA)). The CBF responses to acetylcholine and bradykinin were significantly correlated (r=0.56; p<0.01). Bradykinin-induced dilation was similar in hypercholesterolemic patients and control patients after inhibition of nitric oxide. CONCLUSION: These results suggest that the bradykinin-mediated endothelium-dependent dilation of coronary resistance vessels may be impaired due to depressed nitric oxide production in patients with hypercholesterolemia.

Adenosine 5'-triphosphate induced dilation of human coronary microvessels in vivo.

OBJECT: This study was performed to compare the coronary microvascular response to adenosine 5'-triphosphate (ATP) with the response to adenosine in humans. METHODS: Coronary blood flow velocity was determined using a Doppler flow wire. After intracoronary nitroglycerin infusion, intracoronary bolus injections of adenosine (20 microg) and ATP (20 microg) were performed to induce reactive hyperemia. PATIENTS: Twenty-nine patients (23 men and 6 women, mean age: 63+/-9 years) with coronary artery disease and risk factors for coronary atherosclerosis were studied. RESULTS: Coronary flow reserve in response to ATP was similar to that for adenosine (2.7+/-0.7 vs. 2.7+/-0.7). However, the duration of ATP-induced vasodilation was longer than that of adenosine-induced dilation (39+/-25 seconds vs. 26+/-12 seconds, p<0.0001). The coronary flow reserve obtained with either ATP or adenosine was significantly reduced in the interventioned arteries compared with non-stenosed arteries. The coronary flow reserve obtained with ATP was similar to that obtained with adenosine in both artery groups. The duration of the vasodilator effect of ATP was significantly greater than that of adenosine in both artery groups. CONCLUSION: These results suggest that ATP induces maximal dilation of coronary microvessels, most likely through an endothelium-independent mechanism. The degradation of ATP to adenosine 5'-monophosphate (AMP) and adenosine, as well as the direct action of ATP on A2-adenosine receptors may be responsible for the dilation. We conclude that coronary flow reserve can be determined safely with intracoronary ATP administration.

Effect of adenosine triphosphate on human coronary circulation.

We investigated in humans the effects of adenosine triphosphate (ATP), administered by intracoronary bolus (4-16 microg) or intravenous infusion (25-200 microg/kg/min), on coronary and systemic hemodynamics and electrocardiogram (ECG) variables. All patients had normal epicardial coronary arteries. The maximal coronary blood flow velocity (CBFV) was determined with intracoronary bolus of papaverine. A 12 microg bolus of ATP (n=12) caused maximal coronary hyperemia similar to that caused by papaverine. Intracoronary boluses caused a small brief decrease in arterial pressure but no significant changes in HR or ECG variables. Intravenous infusion of ATP at 150 microg/kg/min (n=15) caused a decrease in the coronary resistance index similar to that caused by papaverine, but the rate of increase in CBFV by ATP was smaller than that caused by papaverine. No patients had a significant change in ECG variables, but some patients (40%) had a serious decrease in arterial pressure. These studies suggest that maximal coronary vasodilation can be achieved safely with intracoronary ATP administration and that intravenous infusions at 150 microg/kg/min cause near-maximal coronary hyperemia in most patients.

Increased cytosolic free Mg2+ and Ca2+ in platelets of patients with vasospastic angina.

This study was designed to test the hypothesis that the cellular metabolism of Ca2+ and Mg2+, which is important in platelet function, is abnormal in the platelets of patients with vasospastic angina. Cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ handling were determined in the platelets of 24 patients with vasospastic angina and 24 control subjects by use of mag-fura 2 and fura 2. Platelet aggregation was also examined. Basal [Mg2+]i and cytosolic free Ca2+ concentration ([Ca2+]i) in platelets were significantly higher in patients with vasospastic angina than in control subjects. The amplitude of the [Ca2+]i transient induced by thrombin (0.03-1.0 U/ml) was significantly increased in the presence, but not in the absence, of extracellular Ca2+ in patients with vasospastic angina, as compared with controls. Therefore, the influx of Ca2+ across the plasma membrane may be accelerated in vasospastic angina. Thrombin (0.1-1.0 U/ml)-induced maximum aggregation response was significantly greater in patients with vasospastic angina than in controls. Results suggest that increased [Mg2+]i and altered Ca2+ handling by platelets may be associated with coronary vasospasm.

Vasomotility and nitric oxide bioactivity of the bridging segments of the left anterior descending coronary artery.

We compared bridging and nonbridging coronary artery segments with respect to the vasoconstrictor effect of acetylcholine. Bridging segments were hypersensitive to the constrictor effect of acetylcholine, and results suggest that the effect of nitric oxide on the acetylcholine-stimulated condition is decreased, or that the smooth muscle sensitivity to acetylcholine is increased.

Coronary segmental responses to acetylcholine and bradykinin in patients with atherosclerotic risk factors.

This study was designed to elucidate the nature of coronary endothelial dysfunction in patients with hypertension and/or hypercholesterolemia and normal smooth coronary arteries by evaluating the coronary vascular responses to acetylcholine and bradykinin. The study included 19 patients (10 men; age [mean +/- SD] 61 +/- 9 years) with angiographically normal smooth coronary arteries and either hypertension (n = 7) and/or hypercholesterolemia (n = 13). Patients received acetylcholine (3 or 30 microg/min) infusions followed by bradykinin (0.5, 1.5, 2.5 microg/min) and nitroglycerin (200 microg/min) infusions into the left coronary ostium. Epicardial coronary artery diameters were measured by quantitative angiography. Angiography detected both vasoconstricted and dilated segments following acetylcholine infusion. Bradykinin significantly dilated both types of segments (p <0.001, respectively). However, bradykinin-induced dilation was significantly greater in segments exhibiting acetylcholine-induced vasodilation than in those exhibiting vasoconstriction (p <0.01 in the proximal portion and p <0.02 in the distal portion). Nitroglycerin-induced dilation was similar in all segments. These results suggest that coronary endothelial dysfunction may be a heterogeneous process in patients with coronary risk factors. Moreover, the mechanism underlying diminished endothelium-dependent dilation involves not only the muscarinic receptor, but also B2-kinin receptor.

Bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo: effect of inhibition of nitric oxide synthesis.

OBJECTIVE: To clarify whether endothelium derived nitric oxide contributes to exogenous bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo. DESIGN: Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), on bradykinin induced dilatation of the epicardial and resistance coronary arteries. SETTING: Hiroshima University Hospital. PATIENTS: 20 patients (16 men and four women, mean (SD) age 56 (9) years) with angiographically normal smooth epicardial coronary arteries. INTERVENTIONS: Serial infusions of bradykinin (0.5, 1.5, and 2.5 micrograms/min) were given into the left coronary ostium before and after L-NMMA infusion (60 mumol/min). MAIN OUTCOME MEASURES: Epicardial coronary diameter, coronary blood flow, and coronary vascular resistance. RESULTS: Bradykinin-induced epicardial coronary vasodilatation after L-NMMA (dilatation by 2.5 micrograms/min, 3.8(1.4)% in the proximal and 5.9(1.8)% in the distal segments, mean (SEM)) was less (p < 0.001, respectively) than before L-NMMA (11.7(2.5)% and 15.1(2.0)%, respectively). In contrast, L-NMMA did not affect the bradykinin induced increase in coronary blood flow and decrease in coronary vascular resistance. CONCLUSIONS: Endothelium derived nitric oxide contributes to bradykinin induced dilatation of epicardial coronary arteries, but may be less important in coronary resistance vasodilatation.

Nitric oxide production by coronary conductance and resistance vessels in hypercholesterolemia patients.

NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide (NO) synthesis, was used to investigate the effects of inhibition of NO synthesis on the coronary conductance and resistance vessels in hypercholesterolemic patients. Acetylcholine (3 and 30 micrograms/min) was administered to 10 hypercholesterolemic and 10 control patients before and after L-NMMA (25 micromol/min) infusion. Epicardial coronary diameter was measured by quantitative angiography, and coronary blood flow (CBF) was derived from Doppler flow-velocity and coronary diameter measurements. In hypercholesterolemic patients, acetylcholine-induced dilation of epicardial arteries was attenuated, and the percentage increase in CBF caused by acetylcholine was smaller than that in control patients. L-NMMA attenuated acetylcholine-induced dilation of epicardial arteries in control patients. L-NMMA had no effect on CBF responses to acetylcholine in both patient groups. L-NMMA significantly decreased the baseline coronary diameter and CBF in both groups. These results indicated that hypercholesterolemia impaired the acetylcholine-induced dilation of the conductance and resistance coronary vessels. This impairment in the conductance vessels was dependent on NO production; that of resistance vessels was not. The basal release of NO in conductance and resistance vessels was preserved in hypercholesterolemic patients.

Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis.

OBJECTIVES: This study sought to investigate the role of nitric oxide, an endothelium-derived relaxing factor, in flow-mediated vasodilation in human epicardial coronary arteries. BACKGROUND: Endothelium-derived relaxing factors may be released from the coronary artery endothelium in response to increases in blood flow. METHODS: We studied the effect of the nitric oxide synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA) on the flow-mediated vasodilation of epicardial coronary arteries in 12 patients, using quantitative angiographic and Doppler flow velocity measurements. Adenosine at 100 micrograms/min was infused into the left anterior descending coronary artery to test the dilator response of the proximal artery to increases in blood flow. Acetylcholine at 3 and 30 micrograms/min was infused into the left coronary ostium to determine endothelium-dependent vasodilation of the proximal left anterior descending artery. Adenosine and acetylcholine were infused before and after the intracoronary infusion of L-NMMA (25 mumol/min for 5 min). RESULTS: Infusion of L-NMMA caused a significant decrease in the baseline diameter of the proximal left anterior descending artery (from 2.90 +/- 0.14 to 2.74 +/- 0.13 mm [mean +/- SEM], p < 0.01). Adenosine increased coronary blood flow before and after L-NMMA (+399.5 +/- 27.5% and +511.9 +/- 33.3%, respectively). Flow-mediated vasodilation was observed in the proximal left anterior descending artery before and after L-NMMA (+9.2 +/- 1.5%, p < 0.01 and +8.6 +/- 2.1%, p < 0.01, respectively). A dose of 3 micrograms/min of acetylcholine significantly dilated the proximal left anterior descending artery before L-NMMA (+7.6 +/- 1.0%, p < 0.01), but acetylcholine-induced vasodilation was attenuated after L-NMMA (-1.8 +/- 1.0%). CONCLUSIONS: Our data suggest that nitric oxide modulates basal coronary artery tone but that mediators other than nitric oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries.

Impaired endothelium-dependent vasodilation of coronary resistance vessels in hypercholesterolemic patients.

To determine the relationship between hypercholesterolemia and the endothelial function of coronary resistance vessels, we studied the changes in coronary blood flow (CBF) in response to acetylcholine, an endothelium-dependent vasodilator, and adenosine, an endothelium-independent vasodilator, in patients with hypercholesterolemia (n = 17) and in control patients (n = 17). All patients had normal epicardial coronary arteries. Serial 2-min infusions of acetylcholine, at 3 micrograms/min and 30 micrograms/min, caused a dose-dependent increase in CBF in each group. The acetylcholine-induced maximal increases in CBF were inversely correlated with the serum cholesterol level (r = -0.55, p < 0.01), and were significantly smaller in the hypercholesterolemic patients than in control patients. However, the adenosine-induced increases in CBF were similar in the two groups. These results suggest that the endothelium-dependent vasodilation of resistance vessels is lessened in patients with hypercholesterolemia even before the formation of atherosclerotic stenotic lesions in epicardial coronary arteries, and that hypercholesterolemia impairs endothelium-dependent vasodilation of coronary resistance vessels.

Coronary segmental responses to acetylcholine in patients with hypercholesterolemia.

We investigated coronary segmental response to intracoronary acetylcholine (ACh) in 19 patients with hypercholesterolemia and 18 patients with normal cholesterol levels. All patients had atypical and chest pain and angiographically normal coronary arteries. After baseline angiography, ACh (3 and 30 micrograms/min) was infused into the left coronary artery, followed by infusion of nitroglycerin. Percent changes in diameter of the proximal, middle, and distal segments of the left coronary arteries were measured by quantitative angiography. In the normocholesterolemic group, 3 micrograms/min of ACh produced significant coronary vasodilation in the distal segments (+8.2 +/- 2.6%, p < 0.005), while 30 micrograms/min did not cause any changes. In the hypercholesterolemic group, 30 micrograms/min of ACh caused significant coronary vasoconstriction in the middle and distal segments (-7.2 +/- 1.9% and -6.2 +/- 1.9%, p < 0.001 and p < 0.01, respectively), while 3 micrograms/min caused no changes. In each group, vasodilator responses to nitroglycerin in the middle and distal segments were significantly greater than those in the proximal segments (p < 0.001). Our results suggest that impaired endothelial function may be evaluated more effectively in the distal coronary segments in patients in the early stage of epicardial coronary atherosclerosis attributable to hypercholesterolemia.