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PubMed1993

Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells.

The effect of nitric oxide (NO) donors on the release of mucus from a suspension of isolated gastric cells was investigated by using an enzyme-linked immunosorbent assay for rat gastric mucin. Isosorbide dinitrate (ISDN, 0.1-2 mM) produced a dose-related stimulation of mucus secretion, without affecting the viability of the isolated cells as determined by trypan blue exclusion or acid phosphatase release. In a comparable concentration range to that stimulating mucus release, ISDN elevated the guanosine 3',5'-cyclic monophosphate (cGMP) content of cell suspensions enriched with mucous cells. The nitrosothiol S-nitroso-N-acetylpenicillamine (0.3 mM), which spontaneously liberates NO, likewise stimulated mucus release, and this action was blocked by 10 microM oxyhemoglobin, which scavenges NO. Nitroprusside (1 mM), dibutyryl cGMP (0.01-1 mM), and the cGMP phosphodiesterase inhibitor M & B 22948 (0.1 mM) also increased mucus release. Thus generators of NO stimulate mucus secretion by rat gastric mucosal cells, which may reflect the elevation of intracellular cGMP. These findings, along with the presence of NO synthase in the gastric epithelial cells, suggest an effector role for NO in mediation of gastric mucus release.

Animals↗
PubMed1988

Hemodynamics, circulating catecholamines and response to intravenous nitrate therapy in a specific subset of acute myocardial infarction: the hypertensive-hyperkinetic-coronary-active group.

A specific subset of acute myocardial infarction was defined and named 'the hypertensive-hyperkinetic-coronary-active' subgroup. This subgroup included patients with acute myocardial infarction without pump failure or hypovolemia who continued to have hypertension and tachycardia, after relief of pain and who also had at least two recurrent ischemic episodes in the first days after a transmural event. Fifteen patients belonging to this group (group A) were studied in comparison with 15 other patients with acute myocardial infarction complicated by pump failure (group B). The alterations in hemodynamics, in circulating catecholamine levels and the clinical course during an intravenous infusion of isosorbide dinitrate were evaluated and the data obtained in the two groups were compared. The patients in group A had tachycardia, hypertension and upper normal filling pressures (pulmonary capillary wedge pressures: 15.8 +/- 1.8 mm Hg). They had high levels of circulating catecholamines (1,343 +/- 407 ng/l), a cardiac output of 5.9 +/- 0.6 liters/min and stroke work index of 78 +/- 11 (mean +/- SD). The effect of intravenous nitrates on the left ventricular function curves of the two groups was the following: a marked shift downward and slight shift to the left in group A, as opposed to a moderate but significant shift upward and marked shift to the left in group B. The episodes of recurrent ischemia subsided in 13 out of 15 patients from group A. It appears therefore that the hyperkinetic patients with acute infarction are characterized by a hypersympathetic response, a typical hemodynamic profile and a particular response to nitrate therapy directionally opposite to the changes obtained in patients with acute infarction complicated with failure.

Aged↗
PubMed1992

[Response of coronary arteries to intracoronary acetylcholine infusion in patients with familial hypercholesterolemia].

Loss of the vasodilator response to acetylcholine (Ach), an endothelium-dependent vasodilator, has been demonstrated in animal models of atherosclerosis and in atherosclerotic coronary arteries of humans studied in vitro. The response of normal coronary arteries on angiograms to the intracoronary injection of Ach in patients with familial hypercholesterolemia (FH) was studied. Ten patients with FH (mean age, 53.6 +/- 6.5 years) with a mean serum total cholesterol of 334.8 mg/dl and 12 controls (mean age, 55.8 +/- 14.5 years) with a total cholesterol level of 183.6 mg/dl, and with normal coronary arteries on angiograms were studied. Patients with clinical histories suggestive of coronary spastic angina were excluded from this study. A bolus of 20, 50 micrograms Ach and 2 mg isosorbide dinitrate (ISDN) were infused into the left coronary artery in each subject. Changes in coronary diameters were measured after each injection with a videodensitometric analysis system. In the control group, the diameter at the middle segments of the left anterior descending artery (LAD) and at the proximal and middle segments of the left circumflex artery (LCX) increased significantly in response to Ach; whereas, in the FH group the diameter at the proximal segments of the LAD decreased significantly. There were significant differences in the coronary diameter changes in response to 50 micrograms Ach at the proximal and middle segments of the LAD and the LCX between the 2 groups. In contrast, between these 2 groups, there were no significant differences in the vasodilator responses to ISDN, a direct vascular smooth muscle dilator. The vasodilator response of coronary artery to Ach was diminished in patients with FH.

Acetylcholine↗
PubMed1991

[Comparative effect of anti-anginal drugs on myocardial ischemia in patient with effort angina: evaluation by ambulatory electrocardiographic monitoring].

The purpose of this study was to compare the efficacy of three standard antianginal agents, nitrate, Ca antagonist, and beta blocker on myocardial ischemia in patients with effort angina (EA) using ambulatory electrocardiographic monitoring (AEM). Forty-three patients, mean age 57 +/- 11 years, with positive exercise tests were studied. AEM was performed for 24-hours, initially with the patients off all antianginal medication and then after 1-2 weeks treatment with each agent. Antianginal drugs used were long-acting isosorbide dinitrate 40-80 mg/day for nitrate (17 patients), diltiazem 90-180 mg/day for Ca antagonist (13 patients), and propranolol 30-60 mg/day or metoprolol 60-120 mg/day for beta blocker (13 patients). The following results were obtained: 1) The severity of ischemia (total magnitude and duration of ST depression) was improved with each three agent. 2) Although the number of total ischemic episodes was reduced significantly with each three agent, the number of asymptomatic episodes was reduced significantly only with beta blocker. 3) Circadian variation of ischemic episodes displayed a pattern with a peak frequency in daytime. In addition, nitrate and Ca antagonist did not reduce ischemic episodes in daytime (especially asymptomatic episodes), while beta blocker reduced both symptomatic and asymptomatic episodes in daytime resulting in change in the pattern of circadian variation of ischemia. Thus, it was concluded that beta blocker was the most effective means of reducing myocardial ischemia, including silent ischemia, in patients with EA.

Adrenergic beta-Antagonists↗
PubMed1995

Nitrate versus rest myocardial scintigraphy with technetium 99m-sestamibi: relationship of tracer uptake to regional left ventricular function and its significance in the detection of viable hibernating myocardium.

Rest technetium 99m-sestamibi uptake may underestimate myocardial viability in asynergic territories. Because nitrate administration was reported to improve thallium 201 uptake in perfusion defects, this study aimed to test the influence of nitrates on 99mTc-sestamibi uptake and on the tracer capability to recognize viable tissue in asynergic segments. In 23 patients with prior infarction and left ventricular dysfunction, regional wall motion was assessed by echocardiography before and after revascularization (13 segments/patient). Group 1 included 97 normokinetic; group 2, 97 hypokinetic; and group 3, 105 akynetic or dyskinetic segments; group 3 was divided into group 3A (72 segments unchanged after revascularization) and group 3B (33 segments with functional recovery). 99mTc-sestamibi uptake was graded using a scoring scheme in the same 13 segments both at rest and, on a separate day, injecting the tracer during isosorbide dinitrate infusion (ISDN). At rest, the mean 99mTc-sestamibi uptake decreased significantly from group 1 through group 3. With ISDN, the mean 99mTc-sestamibi uptake increased in all groups compared with rest, but the increase was significant only in groups 2 and 3, and within the latter, only in group 3B. Thus, with ISDN group 3B was no longer different from group 2. Only 6% of group 3A segments showed an improved uptake with ISDN, versus 33% of group 3B (P < .00005). At rest only 14 of 33 segments of group 3B showed a normal or slightly reduced uptake, whereas these were 25 of 33 with ISDN (P < .02). In conclusion, the acute administration of ISDN increases the uptake of 99mTc-sestamibi mainly in those asynergic territories that show postrevascularization functional recovery. Therefore, ISDN 99mTc-sestamibi imaging might improve the tracer capability to detect viable hibernating myocardium.

Angioplasty, Balloon, Coronary↗
PubMed1982

Combined exercise radionuclide and hemodynamic evaluation of left ventricular aneurysmectomy.

Twelve patients were studied by rest and exercise radionuclide ventriculography following left ventricular aneurysmectomy (LVA). Left ventricular filling pressure (LVFP) was also measured. Nine patients had been studied pre-LVA at rest and exercise before and after isosorbide dinitrate (ISDN). Resting ejection fraction (LVEF) improved after LVA (p less than 0.25), but exercise LVEF did not. End-diastolic volume (EDV) and resting LVFP also fell after LVA (p less than 0.25 for EDV, p less than 0.05 for LVFP) and although exercise LVFP fell (p less than 0.02), the values were abnormal in all patients. Ejection fraction of contractile segment (EFCS) from the resting radionuclide study pre-LVA was related to resting LVEF post-LVA (r = 0.71 p less than 0.02), although postoperative LVEF could not be predicted from preoperative EFCS in individual patients. Deterioration in LVEF and LVFP from rest to exercise post-LVA occurred both in patients with single-vessel occlusion and in those with multivessel coronary disease, irrespective of whether or not revascularization had been performed. Thus LVA is effective in improving resting ventricular function; exercise performance may remain abnormal even in patients without residual coronary disease.

Adult↗
PubMed1984

[Acute treatment of severe cardiogenic pulmonary edema. Effect and tolerability of ISDN as bolus and continuous infusion].

Isosorbide dinitrate (ISDN) was administered intravenously to 21 patients with severe cardiogenic pulmonary edema. In 15 cases the condition was due to coronary heart disease (3 of them had arterial hypertension additionally), and 3 patients due to cardiomyopathy. In the remaining 3 valvular disorders were prevailing. The ISDN solution was administered as an i.v. bolus followed by continuous i.v. injection from an automatic perfusion device. Oxygen, furosemide, and in some cases digitalis were given in addition. Monitoring consisted of clinical surveillance, blood gas analyses, and repeated X-ray control. The results obtained confirm the efficacy and safety of this mode of ISDN administration. This applies particularly for patients in whose therapy is aimed at fast control of life-threatening hypoxia. Despite extreme asphyxia, only three patients needed artificial respiration, one died in cardiogenic shock, while all others were rapidly improved. It could thus be demonstrated that this type of therapy may be safely and efficiently handled by careful clinical supervision, without invasive hemodynamic monitoring.

Acute Disease↗
PubMed1991

[Does captopril produce an antianginal effect in patients with stable exercise-induced angina pectoris?].

Captopril (C), isosorbide dinitrate (ID), and nifedipine (N) were evaluated for antianginal effects (AAE) in 12 patients with ischemic heart disease. The effects were assessed by treadmill exercise tests performed before and repeatedly 1, 2, 3, and 6 hours after the single dose of a drug or placebo. C, ID, and N were given in doses of 50, 10, and 20 mg, respectively. The drugs were equally effective in lowering systolic blood pressure at rest. Unlike ID and N, C failed to affect the duration of exercise testing until an anginal episode occurred and the magnitude of ST-segment depression at the same exercise intensity. ID and N caused a significant increase in the duration of exercise and a decrease in ST-segment depression during exercise 1-3 h later. An individual analysis has shown that C, ID, and N produced an antianginal effect only in 2, 9, and 10 patients, respectively. Thus, C is unable to show a substantial antianginal effect.

Adult↗
PubMed1992

Placebo effect of nitrate monotherapy for myocardial ischemia.

Nitrate monotherapy was assessed by treadmill exercise stress testing in 18 patients with significant but relatively asymptomatic myocardial ischemia who were receiving no other antianginal therapy. In addition, prolonged ambulatory electrocardiographic monitoring was performed in 7 patients with demonstrable ischemia during baseline monitoring. After baseline assessment, 5 treatment periods were used in a random order (each of 1 week duration), incorporating 2 dose levels of transdermal nitrate (10 and 20 mg/24 hours) and isosorbide dinitrate (ISDN) (30 and 60 mg/day in divided doses) with a 10-hour nitrate-free interval every 24 hours, as well as a placebo period using a double-blind technique. All treatment periods (including placebo) showed a significant (p < 0.01) 45 to 69% prolongation in the time to 1 mm ST depression during exercise. Paired baseline times of 231 +/- 28 and 233 +/- 30 seconds increased to 367 +/- 37 seconds with 30 mg/day of ISDN, 393 +/- 37 seconds with 60 mg/day of ISDN, 381 +/- 31 seconds with 10 mg/day of transdermal nitrate, and 372 +/- 33 seconds with 20 mg/day of transdermal nitrate. The value for placebo was 342 +/- 29 seconds, which was not significantly different from active treatment (p > 0.1). Some patients appeared to individually respond to > or = 1 nitrate preparation significantly more than to placebo, but this appeared to be unpredictable and largely independent of dosage level and route of administration. There was a qualitatively similar but statistically insignificant reduction in total ischemic time during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1991

Reactivity of proximal and distal angiographically normal and stenotic coronary segments in chronic stable angina pectoris.

To assess whether vasoreactivity of significant coronary stenosis (greater than 50% intraluminal diameter reduction) and that of angiographically normal coronary segments differs in proximal and distal locations, 53 patients (40 men, 13 women, mean +/- standard deviation age 55 +/- 11 years) with chronic stable angina and angiographically documented coronary artery disease were studied. While abstaining from antianginal therapy, all 53 patients underwent coronary arteriography before and after 1 mg of intracoronary isosorbide dinitrate and 21 of the 53 also before and after 20 to 30 micrograms intracoronary ergonovine. Computerized quantitative angiography was used to assess changes in the intraluminal diameter of 126 normal coronary segments (63 proximal, 63 distal) and 43 significant coronary stenoses. Nitrates dilated proximal normal coronary segments by 7.4 +/- 1.2% and distal normal coronary segments by 15 +/- 1.7% (p less than 0.01). Significant proximal coronary stenoses dilated by 11 +/- 2.5% and distal stenoses by 23 +/- 2.8% (p less than 0.01) after nitrates. Ergonovine reduced the diameter of proximal normal coronary segments by 9.3 +/- 1.7% and that of normal distal segments by 15.5 +/- 1.4% (p less than 0.01). Proximal stenoses constricted by 11 +/- 2.2% and distal stenoses by 18.4 +/- 2.8% (p = 0.06). Analysis of segments showed that nitrates dilated 19 of 63 (30%) proximal normal segments by (greater than or equal to 10%), 31 of 63 (49%) distal (p less than 0.05) and 21 of 43 (49%) stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1987

A possible role for the endothelium in porcine coronary smooth muscle responses to dihydropyridine calcium channel modulators.

The role of the endothelium in contraction and relaxation produced by the dihydropyridine calcium channel modulators was examined in porcine coronary smooth muscle. The optically pure dihydropyridine calcium agonists (+)-S202-791 and (-)-Bay k 8644 both produced greater contractions in tissues without endothelium compared with tissues with intact endothelium. In contrast, histamine produced the same degree of contraction in tissues with and without endothelium. In the presence of KCl-induced active muscle tone, the optically pure calcium antagonists (-)-R202-791 and (+)-Bay k 8644 and the nitrovasodilator isosorbide dinitrate all produced the same degree of relaxation in tissues with and without endothelium. These results suggest that the endothelium plays an inhibitory role in dihydropyridine-induced contraction. When coronary rings with intact endothelium were pretreated for 60 min with 10 or 100 nM (-)-R202-791, the contraction to subsequent addition of (+)-S202-791 was significantly greater than in control tissues pretreated with only solvent. However, in rings with denuded endothelium, pretreatment with (-)-R202-791 resulted in a rightward shift of the dose-response curve to (+)-S202-791, and a depression of the maximal contraction compared with controls. Thus, the interaction between the calcium agonist [(+)-S202-791] and antagonist [(-)-R202-791] is more complex than competitive inhibition. We suggest that the calcium agonists produce two effects, a release of endothelium-derived relaxant factor and a direct contraction of smooth muscle; the calcium antagonists can inhibit both processes.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Nitric oxide regulates clonal expansion and activation-induced cell death triggered by staphylococcal enterotoxin B.

Increased interest has recently been focused on nitric oxide (NO) due to its several biological roles. Apart from being a potential antimicrobial defense and a mediator of autoimmune diseases, NO also appears to be a strong mediator of T-cell responses. In this report, we have characterized the effect of NO on T-cell function. For this purpose, we analyzed in vivo T-cell responses to the bacterial superantigen produced by Staphylococcus aureus, staphylococcal enterotoxin B (SEB), in mice treated with an NO donor (isosorbide dinitrate [ISO]). We show that ISO partially prevents SEB-triggered activation-induced cell death of spleen and lymph node CD4Vbeta8+ T cells but not of CD8Vbeta8+ T cells. SEB-promoted thymic deletion is not abolished by ISO; however, a rapid recovery of thymocyte numbers due to increased double-positive (DP) CD4+ CD8+ thymocyte proliferation was clearly observed in ISO-treated, SEB-injected mice but not in controls (untreated SEB-injected mice). It was also found that ISO inhibits the early SEB-induced cell proliferation (i.e., that found 12 h after SEB injection), accelerating the clonal anergy usually observed 3 days after SEB injection. Inhibition of T-cell proliferation by the NO donor does not appear to be due to inhibition of cytokine production. These results show that NO interferes with apoptosis and facilitates thymic proliferation of DP thymocytes, although it inhibits peripheral T-cell proliferation.

Animals↗
PubMed1997

Nitric oxide and the neurotoxic effects of methamphetamine and 3,4-methylenedioxymethamphetamine.

The role of nitric oxide (NO) in the long-term, amine-depleting effects of methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) was investigated in the rodent central nervous system. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) antagonized the dopamine- and serotonin-depleting effects of both METH and MDMA. The protective actions of L-NAME in METH-treated mice were reversed by prior administration of the NO generator isosorbide dinitrate. However, pretreatment with N(G)-monomethyl-L-arginine or N(G)-nitro-L-arginine, two other NO synthase inhibitors, failed to block the neurotoxic effects of METH or MDMA. L-NAME was also the only NO synthase inhibitor that antagonized the hyperthermic effects of METH, reducing colonic temperatures in mice by a mean of 3 degrees C, in comparison with control. Moreover, if the hypothermic effects of L-NAME in METH-treated mice were prevented by raising the ambient room temperature, the dopamine-depleting actions of the stimulant were fully restored. The latter findings suggest that it is the hypothermic actions of L-NAME, rather than its NO inhibitory properties, that are responsible for the prevention of neurotoxicity. Together with the results of the N(G)-monomethyl-L-arginine and N(G)-nitro-L-arginine experiments, the data suggest that NO plays little or no role in the toxic mechanism of action of METH or MDMA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine.

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients were studied both before, during an asymptomatic phase (t0), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide donor able to induce an experimental migraine attack (t1). The nitric oxide levels were analyzed as nitrite accumulation in serum samples, in peripheral blood mononuclear cell extracts, and culture supernatants. Basal nitrite levels in serum samples and peripheral blood mononuclear cell culture supernatants or migraine patients and healthy subjects indicated that migraine patients possess an activated nitric oxide synthesis pathway (t0 vs. CF = 8.16, P < 0.01 and F = 16.2, P < 0.01, respectively). As expected, in the migraine patients treated with the nitric oxide donor, a marked increase of nitrite levels was observed in sera (t1 vs. t0 P < 0.05, t = 3.05). In contrast, during the nitric oxide donor-induced migraine attacks a statistically significant decrease of nitrite levels in peripheral blood mononuclear cell culture supernatants was observed (t1 vs. t0 P < 0.01, t = -4.03), whereas a significant increase of nitrite in total cell extracts was detected (t1 vs. t0 P < 0.001, t = -6.89). These preliminary data suggest that nitric oxide could be involved in the neurovascular modifications leading to a migraine attack.

Adult↗
PubMed1990

Nitric oxide-generating vasodilators inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism.

The purpose of this study was to investigate the effects of nitric oxide-generating vasodilators and 8-bromo-cGMP on serum-induced mitogenesis in BALB/c 3T3 fibroblasts that lack soluble guanylate cyclase activity. Two such vasodilators, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, decreased the incorporation of (3H)thymidine in these cells dose-dependently whereas 8-bromo-cGMP was ineffective at concentrations of up to 10 mM. Moreover, S-nitroso-N-acetylpenicillamine also inhibited cell proliferation, consistent with the data on (3H)thymidine incorporation. S-nitroso-N-acetylpenicillamine had no effect on cGMP accumulation, confirming previous studies that these cells lack soluble guanylate cyclase activity. Hemoglobin and FeSO4/ascorbate, agents that inhibit the actions of nitric oxide, both decreased S-nitroso-N-acetylpenicillamine-induced antimitogenesis, supporting the view that this effect was related to the generation of nitric oxide. The antimitogenic activity of S-nitroso-N-acetylpenicillamine was unlikely to be the expression of nitric oxide-induced degradation of serum mitogens, as indicated by the decrease of the antimitogenic activity on prolonged preincubation of SNAP in serum-containing medium. We conclude that nitric oxide-generating vasodilators inhibit serum-induced mitogenesis and cell proliferation in BALB/c 3T3 fibroblasts by a cGMP-independent mechanism.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Abnormal diffuse coronary vasomotion.

Although coronary artery spasm and abnormal vasoconstriction have undergone considerable investigation, it remains difficult to assess coronary vasomotor tone. To address this problem, the combination of two pharmacological tests (IV injection of 0.4 mg ergometrine followed 5 min later by IV injection of 3 mg isosorbide dinitrate) was performed after the routine procedure of coronary arteriography. Two indexes were defined: total coronary vasomotion (TCV) and maximal total coronary vasomotion (max TCV). These indexes were measured in 20 normal subjects and the normal values were 28.2 +/- 14% and 50.8 +/- 19.2% respectively. Among the 2758 patients who underwent the two tests, a group of 40 patients with normal coronary arteries, no focal spasm and diffuse abnormal coronary vasomotion (DAV) was identified. Eleven patients had vasoconstriction and vasodilatation within the normal range and were identified only by the combination of the 2 tests. All the 40 patients complained of angina at rest and three had had a previous myocardial infarction in the area supplied by the vessel with DAV. During a spontaneous episode of pain at rest 7 patients had ST segment elevation, and 7 a T wave inversion. Thus, these indexes of total coronary vasomotion could be useful to identify patients with abnormal vasomotor tone which could not be detected by the conventional provocative tests.

Adult↗
PubMed2006

Comparison of flow characteristics and vascular reactivity of radial artery and long saphenous vein grafts [NCT00139399].

BACKGROUND: The morphological and functional differences between arteries and veins may have implications on coronary artery bypass graft (CABG) survival. Although subjective differences have been observed between radial artery (RA) and long saphenous venous (LSV) grafts, these have not been quantified. This study assessed and compared the flow characteristics and in-vivo graft flow responses of RA and LSV aorto-coronary grafts. METHODS: Angiograms from 52 males taken 3.7 +/- 1.0 months after CABG surgery were analyzed using adjusted Thrombolysis in Myocardial Infarction (TIMI) frame count. Graft and target coronary artery dimensions were measured using quantitative coronary angiography. Estimated TIMI velocity (V(E)) and volume flow (F(E)) were then calculated. A further 7 patients underwent in-vivo graft flow responses assessments to adenosine, acetylcholine and isosorbide dinitrate (ISDN) using intravascular Doppler. RESULTS: The V(E) for RA grafts was significantly greater than LSV grafts (P = 0.002), however there was no difference in volume F(E) (P = 0.20). RA grafts showed positive endothelium-dependent and -independent vasodilatation, and LSV grafts showed no statistically significant response to adenosine and acetylcholine. There was no difference in flow velocity or volume responses. Seven RA grafts (11%) had compromised patency (4 (6%) > or = 50% stenosis in the proximal/distal anastomoses, and 3 (5%) diffuse narrowing). Thirty-seven (95%) LSV grafts achieved perfect patency and 2 (5%) were occluded. CONCLUSION: The flow characteristics and flow responses of the RA graft suggest that it is a more physiological conduit than the LSV graft. The clinical relevance of the balance between imperfect patency versus the more physiological vascular function in the RA graft may be revealed by the 5-year angiographic follow-up of this trial.

Acetylcholine↗
PubMed1996

Nitrate-induced headache in patients with stable angina pectoris: beneficial effect of starting on a low dosage. 5-ISMN headache study group.

BACKGROUND: Nitrates, although important for the management of angina pectoris, cause significant headache in many patients. METHODS: In a randomized, double-blind, crossover study, 89 patients with stable angina pectoris were studied to compare two different dosage strategies of isosorbide-5-mononitrate (5-ISMN). Patients were randomized to either 60 mg 5-ISMN once daily (od) for two weeks or to 30 mg 5-ISMN od for one week followed by 60 mg 5-ISMN od for one week. Then, there was a two-week placebo washout, after which the alternative treatment was given. The authors assessed the occurrence of angina pectoris and headache by diary cards while taking into account the number of isosorbide dinitrate sublingual puffs and paracetamole tablets required. Data were assessed for carryover and time effects. RESULTS: The two dosage regimens were equally efficient for the relief of angina pectoris without development of tolerance. Thirty percent of the patients never experienced headache from the given dosages. In the remainder of them there was a highly significant time effect: the overall numbers of headache attacks in the first period of active treatment versus the second were 2,380 vs 1,400 (P < 0.003). Yet significantly fewer patients had headache on low dosage than on high dosage (45 vs 57, P < 0.02). CONCLUSIONS: (1) Starting on a low dosage was associated with a reduced frequency and severity of headache and did not notably influence the beneficial effect on angina pectoris. (2) One in 3 patients never experienced headache from the given dosages. (3) The overall number of headache attacks in the first period of active treatment was significantly higher than in the second period irrespective of the dosages given.

Adult↗