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At least 1,621 records · Page 90Linked to original sources
PubMed1999

Is it possible to develop drugs that act more selectively on large arteries?

BACKGROUND: Patients with high pulse pressures have an increased risk for cardiovascular events. Drugs that selectively decrease high pulse pressure may be of interest for these patients. Such drugs have a more pronounced effect on large arteries than on resistance vessels. OBJECTIVE: To compare the selectivity to large arteries of the new nitric oxide donor sinitrodil with the classic nitrate isosorbide dinitrate in healthy young men in order to investigate whether it is possible to develop drugs that act more selectively on large arteries. DESIGN: The study had a double-blind, 5-way cross-over design. In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sinitrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements were performed before and 45 min after administration of the drugs. Between each drug administration, at least 3 days of wash-out was allowed. METHODS: The effects of the drugs on large arteries and resistance vessels were assessed by their effects on brachial artery compliance and total peripheral resistance, respectively. RESULTS: Brachial artery compliance increased gradually with increasing doses of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respectively). Total peripheral resistance index decreased with isosorbide dinitrate (by 11%) and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil. CONCLUSIONS: The results of this study show that it may be possible to develop drugs with a higher selectivity for large arteries. Such drugs may be good candidates to decrease high pulse pressure without substantially decreasing mean and diastolic blood pressures.

Adult↗
PubMedDate not supplied

A randomised study of the haemodynamic changes induced by venodilatation and arteriolar dilatation singly and together in left ventricular failure complicating acute myocardial infarction.

A randomised between-group study of the immediate haemodynamic effects of venodilatation by intravenous isosorbide dinitrate infusion (50-200 micrograms/kg/h) and arteriolar dilatation by intravenous hydralazine bolus (0.15 mg/kg) given either in random sequence (Groups 1 and 2; n = 12) or simultaneously (Group 3; n = 6) was undertaken in 18 men with radiographic and haemodynamic evidence (left ventricular [LV] filling pressure greater than 20 mm Hg) of LV failure 6-19 h following acute myocardial infarction. Control measurements (1 h) preceded either two consecutive 90-min treatment periods (Groups 1 and 2) or a single 90-min period (Group 3). Given independently, both drugs reduced systemic arterial pressure and vascular resistance, whereas only isosorbide dinitrate reduced LV filling pressure and only hydralazine increased cardiac output and stroke volume. Isosorbide dinitrate/hydralazine in combination significantly reduced LV filling pressure, systolic and diastolic arterial pressure, and total systemic vascular resistance. Cardiac output, stroke volume, and heart rate were increased. In conclusion, combined arteriolar dilatation and venodilatation appears to be of greater haemodynamic benefit than either alone, if the fall in mean systemic pressure does not compromise peripheral perfusion.

Adult↗
PubMed1992

Nicorandil and cardiovascular performance in patients with coronary artery disease.

To establish the cardiovascular profile of nicorandil in patients with coronary artery disease, we recently conducted three studies at our institution. In two groups of patients undergoing cardiac catheterization, the effects of 20 mg nicorandil sublingually (s.l.) on, first, left ventricular hemodynamics (n = 10) and, second, coronary vasodilatation (n = 11) were investigated. In the first group, despite a significant decrease of 12% in left ventricular systolic pressure, heart rate did not increase significantly after nicorandil. Both left ventricular end-diastolic pressure (-43%) and the time constant of early isovolumic relaxation (-11%) decreased, whereas peak Vce and Vmax increased (+19%) (all significantly). In the second group, as mean aortic pressure decreased (-13%, p < 0.05), coronary sinus blood flow did not change significantly, and calculated coronary vascular resistance tended to decrease (-10%). Myocardial oxygen consumption decreased significantly by 14%. Quantitative coronary angiography confirmed a significant increase in the mean diameter of nonstenotic coronary artery segments (+ 14%, n = 43) and, importantly, in mean obstruction diameter of stenotic segments (+ 14%, n = 7) after s.l. nicorandil. In a third continuing study, the effects of intracoronary (i.c.) nicorandil (6 micrograms/kg) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in 10 patients undergoing coronary angioplasty. In nonstenotic coronary artery segments, mean coronary diameter increased significantly after either nicorandil (+ 12%) or isosorbide dinitrate (+ 17%). In stenotic segments, however, where the increase in obstruction diameter (+ 20%) after i.c. nicorandil was significant, the 8% increase of isosorbide dinitrate was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMed1992

Desensitization of nitrate-induced venodilation: reversal with oral N-acetylcysteine in humans.

The objective of this study was to determine whether the dorsal hand vein could be used as a model to study tolerance to oral nitrates, and whether oral N-acetylcysteine (NAC) could reverse tolerance if present. Dose-response curves to nitroglycerin were constructed for 11 normotensive volunteers before and during treatment with a sustained-release formulation of isosorbide dinitrate, 80 mg, three times daily for 7 days and followed by concurrent treatment with NAC at a mean dose of 150 mg/kg/day, in divided doses, for 2 days. In separate studies, dose-response curves were constructed for seven normotensive volunteers before and after treatment with oral NAC at the same dose for 2 days. Nitroglycerin's Emax was significantly attenuated from 115 +/- 36 to 77 +/- 22% after treatment with isosorbide dinitrate alone (p < 0.009). Concurrent treatment with NAC reversed this decrease, as nitroglycerin's Emax of 108 +/- 26% during coadministration of isosorbide dinitrate and NAC was not different from its Emax in the control period. There was also no difference in the dose of phenylephrine required to cause 80% of maximal venoconstriction throughout the study. These studies demonstrate that smooth muscle tolerance to nitrates can be demonstrated in medium-sized veins in humans. In addition, high-dose oral NAC can reverse existing tolerance to oral nitrates in human veins. These results indicate that the dorsal hand vein compliance technique is a good model for the clinical investigation of tolerance to nitrates in humans.

Acetylcysteine↗
PubMed1997

Comparison of proarrhythmogenic effects of two potassium channel openers, levcromakalim (BRL 38227) and nicorandil (RP 46417): a high-resolution mapping study on rabbit heart.

This study was designed (a) to test and (b) to compare proarrhythmic effects of levcromakalim and nicorandil; and (c) determine the mechanism of arrhythmia initiation by using high-resolution ventricular epicardial mapping on 44 Langendorff-perfused rabbit hearts. Eighteen hearts were kept intact and received incremental doses (1-500 microM) of levcromakalim, nicorandil, and isosorbide dinitrate. In 26 hearts, a thin layer of epicardium was obtained after endocardial cryotechnique (frozen hearts). In intact hearts, isosorbide dinitrate did not produce any arrhythmia. In contrast, levcromakalim induced spontaneous ventricular fibrillation (VF) in all hearts at 50 microM, whereas only one VF occurred at 500 microM nicorandil. These three drugs produced a dose-dependent bradycardia in intact hearts. In frozen hearts, arrhythmias were induced by 5 microM levcromakalim and 50 microM nicorandil. Isosorbide dinitrate had no proarrhythmogenic effect. Epicardial mapping showed that most of induced ventricular tachycardias were based on reentry around an arc of functional conduction block. Ventricular conduction velocities did not change, but levcromakalim and nicorandil shortened ventricular effective refractory period. We conclude that (a) levcromakalim and nicorandil, used in toxic concentrations, have direct proarrhythmic effects; (b) nicorandil proarrhythmogenic effects are 10 times less marked than those of levcromakalim (arrhythmia is solely the result of the potassium channel opener property of nicorandil); and (c) most of ventricular tachycardias induced are based on reentry.

Animals↗
PubMed1985

The influence of captopril, the nitrates and propranolol on apparent liver blood flow.

Indocyanine green estimated apparent liver blood flow was measured in normal volunteers following glyceryl trinitrate, propranolol, isosorbide mononitrate and captopril. Glyceryl trinitrate and propranolol significantly reduced apparent liver blood flow. Isosorbide mononitrate did not alter apparent liver blood flow or produce an additional reduction in apparent liver blood flow when combined with propranolol. Captopril did not alter apparent liver blood flow despite a significant fall in mean arterial pressure and rise in plasma renin activity. Captopril and isosorbide mononitrate if shown to reduce portal pressure, do so without a fall in apparent liver blood flow.

Adult↗
PubMed1995

Effects of chronic treatment with a nitric oxide donor on nerve conduction abnormalities and endoneurial blood flow in streptozotocin-diabetic rats.

This study examined the ability of nitrovasodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin-induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity (P < 0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively (P < 0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% (P < 0.001). Isosorbide dinitrate treatment for 1 month in non-diabetic and diabetic rats significantly increased blood flow (P < 0.01). When between-group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non-diabetic and diabetic rats, respectively (P < 0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium-derived nitric oxide release or action.

Animals↗
PubMed1995

Effects of organic nitrate vasodilators on platelet function before and after cardiopulmonary bypass.

Various in vitro, ex vivo and in vivo tests have shown that organic nitrates attenuate platelet function. Because organic nitrates are commonly administered to patients undergoing cardiac surgery, the postoperative bleeding tendency observed in these patients might be strengthened by nitrates. Therefore, we compared the acute effects of nitroglycerin (0.5 micrograms kg-1 min-1) and isosorbide dinitrate (0.5 or 2.5 micrograms kg-1 min-1) with those of placebo on platelet function both before and after cardiopulmonary bypass in 40 patients undergoing coronary artery bypass grafting (CABG). Bleeding time, platelet retention on glass beads, i.e. platelet adhesiveness, and thromboelastograph tracings were used as indicators of platelet function. Although nitroglycerin and isosorbide dinitrate induced significant haemodynamic changes, e.g. decreases in arterial and pulmonary arterial pressure, they had no significant effects on the indices of platelet function. We conclude that, when given in haemodynamically effective doses, neither nitroglycerin nor isosorbide dinitrate have any measurable acute effect on platelet function as evaluated with on-site tests in patients undergoing CABG surgery.

Adult↗
PubMed1997

Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial.

OBJECTIVE: To determine whether nitric oxide donors can induce cervical ripening before surgical termination of pregnancy in the first trimester. DESIGN: Prospective, randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. PARTICIPANTS: Forty-eight primigravid women undergoing surgical termination of pregnancy before 12 weeks of gestation. METHODS: The women were randomised to receive per vaginam before surgery either the nitric oxide donor isosorbide mononitrate, the nitric oxide donor glyceryl trinitrate, the prostaglandin analogue gemeprost, or no treatment. MAIN OUTCOME MEASURES: The cumulative force required to dilate the cervix to 8 mm was measured objectively and the cervical diameter before surgical dilatation was recorded. RESULTS: Following isosorbide mononitrate or gemeprost, a lower cumulative force was required to dilate the cervix to 8 mm and a higher cervical diameter before dilatation was recorded. Pretreatment with glyceryl trinitrate reduced the cumulative force required to dilate the cervix but had no effect on cervical diameter. CONCLUSIONS: Like the prostaglandin analogue gemeprost, the nitric oxide donors isosorbide mononitrate and glyceryl trinitrate can effect cervical ripening. Nitric oxide donors may provide an alternative to prostaglandins for cervical ripening before surgical procedures in the first trimester.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

Renal artery vasomotion: in vivo assessment in the pig with intravascular Doppler.

Intravascular Doppler is widely used for experimental studies in the coronary circulation. We designed this study to assess baseline bloodflow and arteriolar resistance in the porcine renal circulation and to study the vasomotor responses of vasoactive drugs. In anesthesized piglets (n = 15), renal arterial diameter was measured with quantitative angiography and blood flow velocity with a Doppler wire (Cardiometrics). Bloodflow and resistances were calculated at baseline and after injection of vasoactive drugs (isosorbide dinitrate, papaverine). This allowed us to determine the renal bloodflow reserve (the capacity of the kidney to augment basal bloodflow). Injection of isosorbide dinitrate was associated with an increase in average peak velocity of 64% (P < 0.01) and a small (from 4.5 to 4.74, P < 0.01) but significant increase in renal artery diameter, resulting in an increase in bloodflow of 82% (P < 0.01) and a decrease in arteriolar resistance of 46% (P < 0.01). Bloodflow returned to baseline (4.76 +/- 1.48 mL/s) approximately 5 min after isosorbide injection. Average Peak Velocity increased almost twofold after papaverine injection (60 +/- 10 to 108 +/- 24 cm/sec, P < 0.01). There was a significant (P < 0.01) increase in arterial bloodflow of 96% in the right and 79% in the left renal artery after injection of papaverine with a corresponding significant (P < 0.01) decrease in arteriolar resistance of 49% in the right and 44% in the left renal artery. Using a combination of quantitative angiography and intravascular Doppler allows easy measurement of baseline renal blood flow and of the effects of vasodilator drugs on bloodflow and resistance. The results show that a vasodilatator reserve exists in the renal circulation but is less marked than that reported in the coronary circulation.

Animals↗
PubMed1987

Preoperative myocardial ischaemia: its relation to perioperative infarction.

One hundred consecutive patients undergoing coronary artery bypass surgery were randomly allocated to a preoperative (24 h) intravenous infusion of isosorbide dinitrate (1.5-15 mg/hr) (50 patients) or to placebo (50 patients). The characteristics of the two groups were similar. Evidence of acute myocardial ischaemia was sought by continuous electrocardiographic Holter recordings and acute myocardial infarction by the appearance of new Q waves and increased activity of the creatine kinase MB isoenzyme. Episodes of acute myocardial ischaemia were found in 18% of patients in the control group and in none of those who received isosorbide dinitrate. None the less, the frequency of perioperative myocardial infarction was similar (22% and 18% respectively) in the two groups. Perioperative infarction was significantly more common in women, in patients with unstable angina or poor left ventricular function, in those who had coronary endarterectomy, and in those in whom the aortic clamping time was greater than 50 minutes. These factors may have obscured any effect that prevention of preoperative ischaemia had on perioperative infarction. Preoperative infusion of isosorbide dinitrate eliminated preoperative ischaemia but did not influence the occurrence of perioperative infarction. The probable benefits of prevention of preoperative ischaemia on postoperative left ventricular function, which is a determinant of long term survival, remain to be established.

Acute Disease↗
PubMed1996

Effects of gradual volume loading on left ventricular diastolic function in dogs: implications for the optimisation of cardiac output.

BACKGROUND: Volume loading is commonly used to adjust preload and optimise cardiac output. It is difficult to monitor preload at the bedside because filling affects ventricular diastolic function and consequently end diastolic pressure, which is the variable used to monitor preload. OBJECTIVE: To assess the effects of gradual volume loading on the different components of left ventricular diastolic function---filling velocities, relaxation, and chamber compliance---to identify how excessive loading produces diastolic dysfunction. METHODS AND RESULTS: Eight mongrel dogs, anaesthetised and mechanically ventilated with both the chest and the pericardium closed, were studied during basal conditions (B), during gradual volume loading with physiological saline---5 ml/kg (VL5), 10 ml/kg (VL10), and 15 ml/kg (VL15)---and during infusion of isosorbide dinitrate (10 g/kg/min) started after the VL15 load was achieved. Dogs were monitored haemodynamically and by transthoracic Doppler echocardiography to assess peak modal velocities of the E and A waves, E/A ratios, and the deceleration time of the E wave. M mode recordings of aligned mitral and aortic valve motion were also obtained to calculate the isovolumic relaxation time. Effects of volume loading on ventricular diastolic function seemed to occur in two phases. Small and moderate volume loads (VL5 and VL10) promoted early ventricular filling, increasing E wave velocities, improving the mean (SD) E/A ratio from 1.95 (0.3) (B) to 2.0 (0.27) (VL5) and 2.6 (0.3) (VL10) (P < 0.00005), prolonging the E wave deceleration time, and only slightly increasing ventricular diastolic pressures. These changes suggest an improvement in ventricular compliance. Extreme volume loads (VL15) produced an abrupt reduction in early ventricular filling, which was transfered to late in diastole, by decreasing E wave velocity, by increasing A wave velocity, and by decreasing E/A ratio from 2.6 (0.3) (VL10) to 0.8 (0.05) (VL15) (P < 0.00005). The E wave deceleration time was shortened and left ventricular diastolic pressures were much increased, all suggesting a deterioration in chamber compliance. All these restrictive changes were promptly reversed by the perfusion of isosorbide dinitrate. The isovolumic relaxation time steadily increased with volume loading. CONCLUSIONS: Small and moderate volume loads improved ventricular diastolic function by promoting early ventricular filling and increasing ventricular compliance. Extreme volume loads promptly induced a diastolic restrictive pattern, transferring filling to the second part of diastole (increasing dependence on atrial contraction) and reducing ventricular compliance. These changes in ventricular diastolic function were independent of simultaneously measured haemodynamic systolic performance and were promptly reversed by isosorbide dinitrate, which after extreme loading promoted early filling, myocardial relaxation, and improved chamber compliance.

Animals↗
PubMed1994

The effect of different nitrate preparations on plasma heparin concentrations and the activated partial thromboplastin time.

There is evidence that intravenous nitrates which are frequently used in acute coronary syndromes may interfere with the anticoagulant effect of heparin. We compared the effect of two different nitrate preparations on the activated partial thromboplastin time (APTT), anti-thrombin III activity (AT III) and plasma heparin levels in patients (n = 50) undergoing routine percutaneous transluminal coronary angioplasty (PTCA) for stable angina. Patients were randomized to either: (1) intravenous heparin and nitroglycerin (GTN); or (2) intravenous heparin and isosorbide dinitrate. The APTT, plasma heparin concentration and AT III activity were measured before PTCA and at 2 and 4 hours after commencement of infusions. Both groups received identical doses of heparin. Group 1 patients received a constant dose of 16.6 micrograms/minute of GTN, and group 2 patients received 33.3 micrograms/minute of isosorbide dinitrate. At 4 hours the median APTT ratio was significantly lower in group 1 compared with group 2 (2.6 versus 4.5) (P < 0.05) as was the plasma heparin concentration (0.18 U/ml versus 0.32 U/ml (P < 0.05). However, no significant difference in APTT ratios or plasma heparin concentrations were noted at any of the other sample times. AT III activity was not significantly different between the groups at any sample time. Within-group analysis showed significantly lower APTT ratio and heparin concentrations at 4 hours compared with the respective 2 hour values. These results would suggest that there is a potential impairment of anticoagulation with low-dose intravenous nitroglycerin and to a lesser extent with low-dose isosorbide dinitrate. Early and frequent monitoring may therefore be appropriate when intravenous nitrates and heparin are used in combination.

Angina Pectoris↗
PubMed2001

A double-blind, parallel-group study of amlodipine versus long-acting nitrate in the management of elderly patients with stable angina.

Ninety-seven elderly patients with stable angina were included in a 28-week, randomized, double-blind, parallel-group comparison of amlodipine 5-10 mg and isosorbide mononitrate 25-50 mg once daily. The total exercise time, as limited by angina, was recorded together with the median incidence per week of angina attacks and glyceryl trinitrate consumption. Safety was assessed by adverse event frequency, measurement of vital signs and laboratory parameters, and quality of life. At the final visit, the total exercise time was significantly greater relative to baseline with amlodipine than isosorbide mononitrate (final/baseline difference: 112.2 vs. 32.2, p = 0.016). There were no statistically significant differences between the groups in relation to the incidence of adverse events. Once daily amlodipine provides significantly better control of stable angina than isosorbide mononitrate in this elderly population.

Aged↗
PubMed2006

Systemic augmentation of nitric oxide: is there an immediate effect on the urinary flow rate in healthy men?

INTRODUCTION: Nitric oxide (NO) is an important neurotransmitter in the lower urinary tract. Data from experimental studies in animals and humans suggest that NO donors like isosorbide dinitrate could be used to lower the infravesical resistance. Despite the potentially significant clinical benefit of such an effect, it has hardly been studied in vivo in men. We investigated the immediate effect of isosorbide dinitrate on the urinary flow rate and the functional bladder capacity in healthy young men. PATIENTS AND METHODS: A free urinary flow was measured in 20 healthy male volunteers on two consecutive micturitions. 15-25 min prior to the second micturition, 10 mg of the NO donor isosorbide dinitrate was administered sublingually. RESULTS: We found no significant difference between baseline measurement and the micturition after NO administration with regard to the totally voided volume, the maximal or the average flow rate as well as the flow rate corrected for the voided volume. CONCLUSION: Systemic augmentation of NO does not produce a relevant immediate effect on the urinary flow rate or the functional bladder capacity in healthy men.

Adult↗
PubMed1987

A comparison of intravenous elantan and frusemide in patients with chronic cardiac failure.

Opiates and loop diuretics are the mainstay of treatment of acute pulmonary oedema, but it is now recognized that immediate response to intravenous loop diuretics is acute vasoconstriction with impaired cardiac performance. It therefore seemed appropriate to compare the effects of intravenous isosorbide 5-mononitrate and frusemide on systemic and coronary haemodynamics in a group of patients with chronic cardiac failure at cardiac catheterization. Intra-arterial blood pressure was recorded from the ascending aorta, pulmonary capillary wedge pressure and cardiac output were measured using a Swan-Ganz thermodilution catheter. Coronary venous blood flow was measured using a thermodilution technique and A-V oxygen difference across the myocardium was obtained from simultaneous blood sampling in the aorta and coronary sinus. Absolute myocardial nutrient blood flow was measured using a 133Xe clearance technique. Frusemide in a dosage of 0.5 mg/kg given intravenously provoked acute vasoconstriction with falls in cardiac output and stroke volume. Pulmonary capillary wedge pressure was unchanged in the first 60 min after administration of frusemide. Isosorbide 5-mononitrate in a dosage of 15 mg intravenously, significantly reduced the pulmonary capillary wedge pressure within 5 min, and with the subsequent fall in systolic arterial blood pressure, cardiac output was maintained. These results suggest that intravenous isosorbide 5-mononitrate could well be of value in the immediate management of the patient with acute pulmonary oedema.

Blood Pressure↗
PubMed1992

The response to drug therapy in unstable angina on the basis of coronary angiography findings.

Among 366 unstable angina pectoris patients at our hospital, myocardial infarction was common (15.7%) in those with attacks of chest pain lasting for at least 20 min. There was also a high incidence (30.3%) when chest pain continued after the start of inpatient treatment. To investigate the etiology of unstable angina, coronary arteriography was performed in both the unstable and stable stages in these patients and the results were compared. The role of coronary spasm and coronary thrombosis in unstable angina was investigated, and the efficacy of continuous infusion of either diltiazem or isosorbide dinitrate as treatment for these patients was compared. Coronary arteriography in the unstable stage showed, no clear differences in the morphology of the stenotic site and the degree of stenosis between the patients with and without infarcts when urokinase or isosorbide dinitrate were injected into the coronary arteries. When drug treatment was effective, the angina was stabilized without any improvement in the degree of stenosis or the morphology of the involved coronary vessel. Thus, it was difficult to predict the response to treatment from coronary arteriography performed in the unstable stage. Diltiazem was more effective than isosorbide dinitrate, and it appears that some action other than coronary dilatation was involved in achieving the remission of unstable angina.

Angina, Unstable↗
PubMed2000

Relationship between plasma oxidized low-density lipoprotein and the coronary vasomotor response to acetylcholine in patients with coronary artery disease.

The present study examined the relation of plasma oxidized low-density lipoprotein (LDL) levels to plasma LDL cholesterol levels and the impairment of endothelium-dependent coronary vasorelaxation in patients with coronary artery disease (CAD). In the first study, the relationship between plasma levels of oxidized LDL and LDL cholesterol were investigated in 88 patients with CAD. In the second study, the changes in the diameter of the left anterior descending (LAD) and the left circumflex (LCX) coronary arteries were measured after intracoronary administration of acetylcholine (15 microg) and isosorbide dinitrate (2.5 mg) in 15 patients with CAD. Plasma oxidized LDL levels were determined with a sandwich enzyme-linked immunosorbent assay. Plasma oxidized LDL levels did not correlate with plasma LDL cholesterol levels (r=-0.03, p=NS). The % diameter changes (mean+/-SEM) in the LAD and LCX after intracoronary acetylcholine were -8.3+/-3.5% and -10+/-4.2%, respectively. The % diameter changes in the LAD and LCX after intracoronary isosorbide dinitrate were 23+/-4.8% and 23+/-5.1%, respectively. The % diameter changes in the LAD and LCX inversely correlated with plasma oxidized LDL levels after intracoronary acetylcholine (LAD: r=-0.55, p=0.03; LCX: r=-0.59, p=0.02), but were not after intracoronary isosorbide dinitrate. Plasma LDL cholesterol, triglyceride, and high-density lipoprotein cholesterol levels did not correlate with the coronary vasoreaction to acetylcholine. In conclusion, plasma oxidized LDL levels do not correlate with plasma LDL-cholesterol levels and are related to impairment of endothelium-dependent coronary vasodilation in patients with CAD.

Acetylcholine↗