Increase In Coronary Artery Diameter Research Articles

Triglyceride-Glucose Index Could be Used to Predict Severity of Coronary Artery Ectasia

Introduction: Coronary artery ectasia (CAE) refers to a 1.5 fold increase in coronary artery diameter compared to the normal segment. Although the underlying pathophysiological mechanism is not fully elucidated, coronary atherosclerosis is thought to play a role in more than half of the cases. Triglyceride glucose (TyG) index is an indicator of insulin resistance. In the present study, aimed to evaluated TyG index values in CAE cases and find if a predictive value of TyG index existed. Patients and Methods: Sixty-one patients with CAE (study group) and 64 patients with normal coronary arteries (control group) were included in the study. TyG index was calculated as ln (fasting triglyceride × fasting glucose/2). Results: There were no differences between the two groups with respect to age, sex, diabetes mellitus prevalence, and biochemical parameters including, white blood cell, platelet, lymphocyte, monocyte counts, hemoglobin, hematocrit, urea, glucose, total cholesterol, high density lipoprotein-cholesterol, triglyceride levels and TyG index value. Twenty-five patients (41.0%) had one-vessel involvement, 24 (39.3%) patients had twovessel involvement and 12 (19.7%) patients had three-vessel involvement. Right coronary artery was the most commonly affected vessel (11, 44%), followed by left anterior descending artery (8, 35%), left main coronary artery (4, 16%) and circumflex artery (1, 4%). TyG index was statistically significantly higher in patients who had two/three vessel involvement (8.80 ± 0.48 vs 9.14 ± 0.62, p= 0.027). TyG index had statistically significant correlation with the number of ectatic vessels (r= 0.275, p= 0.032). ROC curve analysis showed that TyG index was useful for the prediction of ectasia severity (AUC= 0.653, 95% CI= 0.515-0.792, p= 0.043). TyG index value of 9.16 had 41.7% sensitivity and 84% specificity for prediction of CAE severity. Conclusion: TyG index, which is easily calculated from biochemical parameters, might be used for the assessment of CAE severity.

Abstract 14553: Clonal Hematopoiesis of Indeterminate Potential is Associated With Atrial Fibrillation in Patients With Early Coronary Artery Disease

Introduction: The mechanistic link between early coronary artery disease (CAD) and atrial fibrillation (AF) continues to be explored. Clonal hematopoiesis of indeterminate potential (CHIP) is increasingly recognized as a risk factor for cardiovascular disease. We hypothesize CHIP further increases the risk for AF in early CAD. Methods: 184 participants underwent invasive coronary angiogram with endothelial function testing. Buffy coat was used for whole exosome sequencing to identify CHIP (variant allele frequency > 2% and minor allele frequency ≤ 0.1%). Early CAD was defined by the presence of coronary endothelial dysfunction (CED) in the absence of obstructive CAD. Invasive coronary angiography with endothelial function testing characterized CED as ≥ 20% increase in coronary artery diameter or ≤ 50% increase in coronary blood flow in response to acetylcholine. AF was identified by ICD-10 code or patient survey and confirmed by an independent investigator by chart review. Cox proportional hazard regression was adjusted for age, sex, and conventional cardiovascular comorbidities (hypertension, diabetes, and total cholesterol). Results: Of the 184 participants, we identified 23 cases with both early CAD and CHIP and 62 normal controls without CHIP or CAD. Case patients were significantly older (mean 60 ±9 vs 52 ±10 years, p = 0.004 years) and predominantly female (74% vs 81%, p = 0.506). AF was more likely among case participants when compared to normal controls (29% vs 10%, p = 0.036). Mean time to AF or last follow-up was 11 ±7 years. Case patients with both early CAD and CHIP were nearly 10 times more likely to develop AF when compared to normal controls in a Cox regression model adjusted for age, sex, and conventional cardiovascular comorbidities (HR 9.52, 95% CI 1.93 - 47.02, p = 0.006). The risk for AF was not significant if we defined cases by only the presence of CHIP (n = 30) or early CAD (n = 122). Conclusions: Patients with both CHIP and early CAD may have greater risk for developing AF beyond the presence of CHIP or CAD alone. Our findings suggest an added mechanistic role of CHIP that further increases the risk for AF in early CAD.

Differential role of endothelial versus neuronal nitric oxide synthase in the regulation of coronary blood flow during pacing-induced increases in cardiac workload

Endothelial nitric oxide synthase (eNOS) was assumed to be the only source of nitric oxide (NO) involved in the regulation of human coronary blood flow (CBF). However, our recent first-in-human study using the neuronal NOS (nNOS)-selective inhibitor S-methyl-L-thiocitrulline (SMTC) showed that nNOS-derived NO also plays a role. In this study, we investigated the relative contribution of nNOS and eNOS to the CBF response to a pacing-induced increase in cardiac workload. Incremental right atrial pacing was undertaken in patients with angiographically normal coronary arteries during intracoronary infusion of saline vehicle and then either SMTC or N(G)-monomethyl-l-arginine (l-NMMA; which inhibits both eNOS and nNOS). Intracoronary SMTC (0.625 μmol/min) and l-NMMA (25 μmol/min) reduced basal CBF to a similar extent (-19.2 ± 3.2% and 25.0 ± 2.7%, respectively; n = 10 per group). Pacing-induced increases in CBF were significantly blunted by l-NMMA (maximum CBF: 83.5 ± 14.2 ml/min during saline vs. 61.6 ± 9.5 ml/min during l-NMMA; P < 0.01). By contrast, intracoronary SMTC had no effect on the maximum CBF during pacing (98.5 ± 12.9 ml/min during saline vs. 102.1 ± 16.6 ml/min during SMTC; P = not significant). l-NMMA also blunted the pacing-induced increase in coronary artery diameter (P < 0.001 vs. saline), whereas SMTC had no effect. Our results confirm a role of nNOS in the regulation of basal CBF in humans but show that coronary vasodilation in response to a pacing-induced increase in cardiac workload is exclusively mediated by eNOS-derived NO.

106 Role of neuronal vs endothelial nitric oxide synthase in the coronary blood flow response to pacing

BackgroundEndothelial nitric oxide synthase (eNOS) has been assumed to be the major source of nitric oxide (NO) regulating human coronary blood flow (CBF). In recent first-in-human studies with a neuronal...

Prospective Open-Label Trial of Etanercept as Adjunctive Therapy for Kawasaki Disease

To determine the safety and pharmacokinetics of etanercept (Amgen, Thousand Oaks, California) a tumor necrosis factor-α receptor blocker, in children with acute Kawasaki disease (KD). Standard therapy of acute KD includes intravenous immunoglobulin (IVIG) and high-dose aspirin, but a substantial number of patients are refractory and require additional treatment. Tumor necrosis factor-α levels are elevated in children with KD, suggesting a role for etanercept in treatment. We performed a prospective open-label trial of etanercept in patients with KD (age range, 6 months-5 years; n = 17) meeting clinical criteria and with fever ≤ 10 days. All received IVIG and high-dose aspirin. They received etanercept immediately after IVIG infusion and then weekly two times. For the initial safety evaluation, the first 5 patients received 0.4 mg/kg/dose. Subsequent subjects received 0.8 mg/kg/dose. Fifteen patients completed the study. The pharmacokinetics were similar to that in older children in published series. No serious adverse events related to etanercept occurred. No patient demonstrated prolonged or recrudescent fever requiring re-treatment with IVIG. No patient showed an increase in coronary artery diameter or new coronary artery dilation/cardiac dysfunction. Etanercept appears to be safe and well tolerated in children with KD. The data support performance of a placebo-controlled trial.

Sirolimus as primary immunosuppression is associated with improved coronary vasomotor function compared with calcineurin inhibitors in stable cardiac transplant recipients

The aim of this study was to evaluate coronary vasomotor function in cardiac transplant recipients maintained on sirolimus (SRL)- or cyclosporin (CyA)-based immunosuppression. Endothelium-independent response to intracoronary nitroglycerin and adenosine and endothelium-dependent response to intracoronary acetylcholine (Ach) were assessed in 15 SRL- and 21 CyA- treated subjects with angiographically normal coronary arteries. Baseline mean blood pressure was lower in the SRL group (85.6 +/- 10.3 vs. 105.2 +/- 8.7 mmHg, P = 0.002). There was no difference between the groups in coronary flow reserve after adenosine administration in multivariable analysis (P = 0.34). Nitroglycerin administration resulted in increase in coronary artery diameter in the SRL compared with the CyA groups (2.79 +/- 0.54 vs. 2.57 +/- 0.61, P = 0.0036). In 13 SRL-treated subjects without evidence of cardiac allograft vasculopathy (CAV), Ach administration resulted in less epicardial vasoconstriction compared with CyA-treated subjects (2.7 +/- 17.7 vs. -15.6 +/- 17.2%, P = 0.005). Two SRL-treated subjects with three-dimensional intravascular ultrasound evidence of CAV developed coronary spasm in response to Ach 10(-4). Microvascular endothelial function did not differ between the groups. Sirolimus immunosuppression is associated with less pronounced coronary epicardial endothelial dysfunction compared with CyA immunosuppression. Improvement of coronary vasomotor function with SRL may be an important mechanism for the prevention of CAV.

The Effect of Acute Hypoxemia on Coronary Arterial Dimensions in Patients with Coronary Artery Disease

Objectives: To assess the influence of acute hypoxemia on the dimensions of diseased and nondiseased coronary arterial segments in humans. Methods: In 18 subjects (age 53 ± 8 years) with known or suspected coronary artery disease, quantitative coronary angiography was performed before and after being randomly assigned to breathing (1) an inspired oxygen concentration (fraction of inspired oxygen, FIO₂) of 21% (room air, RA) for 20 min (n = 4, controls) or (2) an FIO₂ of 15 and 10% for 10 min each (corresponding to altitudes of 2,500 and 5,500 m, respectively; n = 14). Results: In the control subjects, no hemodynamic, oximetric or angiographic variable changed. In the 14 study subjects, the arterial partial pressure of oxygen averaged 85 ± 13 mm Hg on RA, 65 ± 15 mm Hg on 15% FIO₂ and 44 ± 13 mm Hg on 10% FIO₂. Average arterial segment diameter was 2.52 ± 0.63 mm on RA, 2.55 ± 0.62 mm on 15% FIO₂ (not significant vs. RA) and 2.66 ± 0.66 mm on 10% FIO₂ (p < 0.001 vs. RA). The increase in coronary arterial diameter with 10% FIO₂ occurred only in normal segments (2.74 ± 0.64 vs. 2.97 ± 0.64 mm; p < 0.001), but not in diseased segments (2.34 ± 0.57 vs. 2.38 ± 0.55 mm; not significant). Conclusions: In humans, severe hypoxemia induces vasodilation of angiographically normal coronary arterial segments, whereas it causes no change in diseased segments.

Detection of a fusiform coronary artery aneurysm using CT angiography

Coronary artery aneurysm is a rare form of ectasia characterized by a 50% or greater increase in coronary arterial diameter as compared to adjacent normal arterial segments [1]. One study observed aneurysms in as many as 4.9% of patients undergoing coronary angiography, most frequently with involvement of the right coronary artery, followed by the left anterior descending and circumflex coronary arteries [1]. Some investigators have noted an association with coronary artery stenosis and speculate that aneurysms may be pathologic manifestations of coronary atherosclerosis [1]. We report the rare case of a relatively healthy 43-year-old woman with aneurysm of the left main coronary artery and present the computed tomographic (CT) findings using 64-slice CT.

Statins decrease perioperative cardiac complications in patients undergoing noncardiac vascular surgery: The Statins for Risk Reduction in Surgery (StaRRS) study

We sought to assess whether statins may decrease cardiac complications in patients undergoing noncardiac vascular surgery. Cardiovascular complications account for considerable morbidity in patients undergoing noncardiac surgery. Statins decrease cardiac morbidity and mortality in patients with coronary disease, and the beneficial treatment effect is seen early, before any measurable increase in coronary artery diameter. A retrospective study recorded patient characteristics, past medical history, and admission medications on all patients undergoing carotid endarterectomy, aortic surgery, or lower extremity revascularization over a two-year period (January 1999 to December 2000) at a tertiary referral center. Recorded perioperative complication outcomes included death, myocardial infarction, ischemia, congestive heart failure, and ventricular tachyarrhythmias occurring during the index hospitalization. Univariate and multivariate logistic regressions identified predictors of perioperative cardiac complications and medications that might confer a protective effect. Complications occurred in 157 of 1,163 eligible hospitalizations and were significantly fewer in patients receiving statins (9.9%) than in those not receiving statins (16.5%, p = 0.001). The difference was mostly accounted by myocardial ischemia and congestive heart failure. After adjusting for other significant predictors of perioperative complications (age, gender, type of surgery, emergent surgery, left ventricular dysfunction, and diabetes mellitus), statins still conferred a highly significant protective effect (odds ratio 0.52, p = 0.001). The protective effect was similar across diverse patient subgroups and persisted after accounting for the likelihood of patients to have hypercholesterolemia by considering their propensity to use statins. Use of statins was highly protective against perioperative cardiac complications in patients undergoing vascular surgery in this retrospective study.

Measurement of interstitial lactate during hypoxia-induced dilatation in isolated pressurised porcine coronary arteries.

Lactate is formed in the coronary arterial wall and in the myocardium as a consequence of ischaemia and infarction. We combined direct measurement of coronary artery diameter and interstitial arterial wall lactate concentration ex vivo in order to ascertain the possible role of lactate in hypoxia-induced vasodilatation. The wall of porcine coronary arteries, precontracted during an intraluminal pressure of 40 mmHg by addition of prostaglandin F2alpha, was cannulated using a microdialysis catheter, and exposed to hypoxia for 60 min, followed by 45 min of reoxygenation. The exchange fraction of [14C]lactate over the microdialysis membrane increased from 0.38 +/- 0.04 to 0.52 +/- 0.05 (P < 0.001) during the study period. Coronary artery diameter increased by 15.5 +/- 2.0 % (n = 20) during hypoxia (P < 0.001, compared to normoxic controls) and interstitial lactate concentration rose from 1.07 +/- 0.21 to 2.50 +/- 0.40 mmol x l(-1) during hypoxia (P < 0.01) and was unchanged in controls. The increase in coronary artery diameter correlated with the increase in interstitial lactate concentration in the period between 30 and 60 min of hypoxia (r = 0.62; P = 0.02). Dichloroacetate (10(-5) M), an agent that reduces lactate generation by activating pyruvate dehydrogenase, abolished hypoxia-induced lactate production, but caused a further increase in coronary arterial diameter (30.2 +/- 4.4 %, n = 9; P < 0.001 vs. hypoxia and no dichloroacetate). Under control conditions, the addition of L-lactate (10(-3)-10(-2) M) increased dose-dependently coronary arterial diameter by 22.0 +/- 4.2 % (n = 5) and interstitial lactate concentration from 0.52 +/- 0.04 to 5.70 +/- 0.66 mmol x l(-1) (P < 0.001). There was a correlation between the increase in coronary artery diameter and interstitial lactate concentration (r = 0.60; P = 0.02). The present observations represent the first direct measurements of metabolites by microdialysis in a blood vessel wall. The lactate concentration may affect, but is not essential for, hypoxia-induced vasodilatation in porcine coronary arteries.

Bradykinin-Induced Vasodilation of Human Coronary Arteries In Vivo: Role of Nitric Oxide and Angiotensin-Converting Enzyme

Objectives. The present study aimed to determine the role of nitric oxide (NO) and angiotensin-converting enzyme (ACE) in bradykinin (BK)-induced dilation of human coronary arteries in vivo.Background. BK, produced by way of the kinin-kallikrein system, causes endothelium-dependent vasodilation. However, little is known about the mechanism of BK-induced dilation of coronary arteries in humans in vivo.Methods. The effects of an inhibitor of NO synthesis and of an ACE inhibitor on BK-induced coronary vasodilation were examined in 20 patients who had no significant atherosclerotic stenosis in the artery under study. Lumen diameters of the large epicardial coronary arteries and coronary blood flow (CBF) were measured by quantitative coronary arteriography and intracoronary Doppler technique.Results. Intracoronary infusion of BK (0.6 and 2.0 μg/min) increased coronary artery diameter and CBF with no change in arterial pressure or heart rate. The BK-induced increases in coronary artery diameter and CBF were significantly reduced (p < 0.01) after pretreatment with NG-monomethyl-l-arginine (200 μmol) and were significantly increased (p < 0.01) after pretreatment with enalaprilat (50 μg).Conclusions. BK-induced dilation of human large epicardial and resistance coronary arteries is mediated by NO and increased by prior ACE inhibition.(J Am Coll Cardiol 1997;30:108–12)

Basal Coronary Artery Tone and Insulin Resistance in Vasospastic Angina

Background：Insulin resistance syndrome has been proposed as a major promotor of atherosclerotic disease and earlier studies have implied the hyperinsulinemia itself may enhance coronary vasomotor tone. In patients with vasospastic angina, previous studies have been inconclusive whether to basal coronary artery tone is elevated at the spasm related and non-spasm related artery. This study was performed to investigate whether basal coronary artery tone is elevated and insulin resistance syndrome correlates to vasospastic angina. If insulin resistance syndrome correlates to vasospastic angina, we also investigated whether insulin resistance syndrome correlates to basal coronary artery tone. Methods：The study comprised 27 patients with vasospastic angina(M/F；19/8, mean age；52 ＋/-2 year and 21 control subjects with atypical chest pain(M/F；9/8, mean age；47＋/-3 year. We assessed basal coronary artery tone by obtaining the percent increase in coronary artery diameter induced by nitroglycerin and also examined glucose and insulin response to an oral glucose load of 75g. Results： 1 There were no significant differences in body surface area, abdominal hip ratio, body mass index, incidence of hypertension, lipid profile, von-Willebrand factor, fibrinogen, and microalbumin except smoking incidence [vasospastic angina；16(59% vs control；5(24%, p<0.05] between vasospastic angina group and control. 2 Basal coronary artery tone was greater at the nonspastic site of the spasm-related artery(28.1± 2.2% vs 13.1±0.9%, p<0.0001 and non-spasm related artery(23.7±1.6% vs 13.1±0.9, p<0.0001 in the patients with vasospastic angina than in control subjects. In the patients with vasospastic angina, high activity group had a greater basal coronary artery tone than low activity group at the nonspastic site of the spasm-related artery(31.7±2.6 vs 20.4±2.7%, p<0.001 and non-spasm related

Role of EDRF in the Regulation of Shear Rate in Large Coronary Arteries in Conscious Dogs

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 ± 1% in external diameter and by 11 ± 4% in internal diameter) and for 30 s occlusions before NLA (by 5 ± 1% in external diameter and by 14 ± 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 μmol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.

Coronary haemodynamics and vasodilatory profile of a potassium channel opener in patients with coronary artery disease

Previous studies have indicated that nicorandil reduces both preload and afterload, clearly distinguishing nicorandil from conventional nitrates, whose predominant action is that of preload reduction. In association with the decrease in afterload following nicorandil, the contractile responses during isovolumic contraction and relaxation improved significantly, indicating that nicorandil does not demonstrate negative inotropic actions. Furthermore, despite a marked decrease in mean aortic pressure after nicorandil, coronary sinus blood flow remains unchanged. Therefore, coronary vasodilatation must have taken place, while myocardial oxygen consumption decreased significantly. The vasodilatory action of nicorandil on the epicardial coronary artery has also been demonstrated in our previous study. Nicorandil, at a dose of either 20 or 40 mg, induces a significant increase in coronary artery diameter favourably by acting not only on the non-stenotic but also on the stenotic coronary segments. In our recent study, the effects of intracoronary nicorandil (6 mu.kg-1) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in patients undergoing coronary angioplasty. In non-stenotic coronary artery segments, the mean coronary diameter increased significantly after either nicorandil (+12%) or isosorbide dinitrate (+17%). In stenotic segments, however, increase in the diameter of the obstructed segment by 20% after intracoronary nicorandil was much more pronounced when compared to that of 8% after isosorbide dinitrate. There was a significant additional increase of 13% in the diameter of the obstructed segment when nicorandil was administered following isosorbide dinitrate, while no such additional effect was observed when isosorbide dinitrate was given after nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of basal coronary artery tone with constrictive response to ergonovine in patients with variant angina

Objectives. This study was conducted to examine whether basal coronary artery tone is elevated at the spastic site in patients with variant angina and to determine the significance of basal artery tone in predicting provocation of coronary artery spasm.Background. Previous data have been conflicting on whether basal coronary artery tone is elevated in patients with variant angina.Methods. We assessed basal coronary artery tone by obtaining the percent increase in coronary artery diameter induced by nitroglycerin in 20 patients with variant angina and 24 control subjects. We also examined the correlation between basal coronary artery tone and the constrictive response to ergonovine.Results. In the patients with variant angina in whom spasm was provoked by the lower doses (1 or 5 μg) of ergonovine, basal coronary artery tone was greater (p < 0.05) at the spastic site (54 ± 15% or 36 ± 16%, respectively) than at the nonspastic site (40 ± 25% or 25 ± 15%, respectively). Basal coronary tone at the nonspastic site in these patients was greater (p < 0.01) than that in control subjects (15 ± 6%). In the patients with variant angina in whom spasm was provoked only by the higher doses (15 or 50 μg) of ergonovine, basal coronary artery tone was comparable at the spastic and nonspastic sites and was not different from that in control subjects. The diagnostic sensitivity and specificity of elevated basal coronary artery tone (≥40%) in predicting provocation of spasm were 26% and 98%, respectively.Conclusions. These results indicate that elevated basal coronary artery tone may be useful in predicting provocation of coronary spasm, but the normal level of basal coronary artery tone does not exclude such provocation.

Effects of an Orally Active NO-Releasing Agent, CAS 936, and Its Active Metabolite, 3754, on Cardiac and Coronary Dynamics in Normal Conscious Dogs and After Pacing-Induced Heart Failure

The mechanism of action of nitrates, compounds that have been used classically in the treatment of heart failure, appears to be the stimulation of guanylate cyclase in vascular smooth muscle, perhaps the same physiologic action as endothelium-derived relaxing factor, now thought to be synonymous with nitric oxide (NO). Drugs that release NO either inside cells or in plasma have been developed recently. One such compound, CAS 936, when taken orally, is converted to an active metabolite, 3754. The goal of our studies was to determine the effects of CAS 936 and 3754 on cardiovascular function in conscious dogs before and after the development of pacing-induced heart failure. CAS 936 (10 mg/kg, p.o.) increased large coronary artery diameter 9.1 +/- 1.2% and reduced left ventricular end diastolic pressure (LVEDP) 2.5 +/- 0.5 mm Hg, but had no significant effects on coronary blood flow or vascular resistance. The metabolite 3754 caused dose-related increases in coronary artery diameter, and large reductions in LVEDP. The effect of these compounds on large coronary artery diameter was significantly greater (p < 0.05) than that of nitroglycerin (25 micrograms/kg). After heart failure, both CAS 936 and 3754 caused significant increases in large coronary artery diameter (10%) and a reduction in preload, up to 10 mm Hg, which was even larger than in normal dogs. Thus, these NO-releasing agents are potent selective large-vessel dilators that also reduce preload and maintain this unique vasodilator profile even in the failing heart.

Immune hemolysis, disseminated intravascular coagulation, and serum sickness after large doses of immune globulin given intravenously for Kawasaki disease

One week after treatment with intravenously administered immune globulin and aspirin, a child with Kawasaki disease had persistent fever and an increase in coronary artery diameter to greater than 3 mm. Two additional doses of immune globulin were given intravenously. Rapid hemolysis occurred, followed by disseminated intravascular coagulation and serum sickness. Clinicians should be aware that immune globulin preparations contain antibodies to blood-type antigens that may cause significant hemolysis and disseminated intravascular coagulation.

Opposed responses of large and small coronary arteries to propranolol during exercise in dogs

This study was carried out to determine the relative role of alpha- and beta-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise. The responses of left circumflex coronary diameter and blood flow were examined at rest and during treadmill exercise in seven chronically instrumented dogs during control conditions (saline) and after propranolol administration (1 mg/kg) either alone or in combination with phentolamine (1.5 mg/kg). In control conditions, graded treadmill exercise (5, 10, and 12 km/h) resulted in a progressive increase in coronary artery diameter and decrease in coronary vascular resistance. After propranolol, coronary vascular resistance slightly increased at rest and then progressively decreased during exercise. Surprisingly, coronary artery diameter significantly decreased at rest as well as throughout the exercise period. Phentolamine significantly reduced the propranolol-induced effects on coronary arterial diameter but did not restore the exercise-induced dilation of the large coronary arteries observed during control conditions. In addition, phentolamine prevented the propranolol-induced increase in coronary vascular resistance at rest and reinforced the exercise-induced decrease in coronary vascular resistance observed under propranolol. Thus beta-adrenoceptors are essential in the mediation of exercise-induced dilation of large coronary arteries. In contrast, activation of beta-adrenoceptors is only partially responsible for the decrease in coronary vascular resistance during exercise. Finally, constriction of large coronary arteries after propranolol is mainly explained by the unmasking of alpha-adrenergic tone at rest, but other mechanisms are involved during exercise.

Changes in epicardial coronary arterial diameter following intracoronary papaverine in man.

The effect of intracoronary papaverine administration on epicardial coronary arterial diameter was examined in 18 male patients. Coronary-artery cineangiograms were acquired with a power injector before intervention, 20 sec after intracoronary saline (control), and 20 sec after administration of papaverine into either the left (12 mg) or right (8 mg) coronary artery. Absolute coronary arterial diameter of a normal-appearing segment was quantified using a previously validated, fully automated digital edge detection program with an ADAC digital radiographic unit. Baseline coronary arterial diameter of 3.1 +/- 0.8 mm did not significantly change after saline administration (3.1 +/- 0.9 mm) but did significantly increase (p less than .001) to 3.4 +/- 0.9 mm after papaverine administration. No significant percent change in diameter occurred in either the left anterior descending (-.5 +/- 1.7%), left circumflex (-.2 +/- 1.1%), or right (-3.0 +/- 3.8%) coronary arteries with saline, but significant (p less than .001) increases occurred with papaverine (7.2 +/- 4.1%, 7.0 +/- 4.5%, 6.8 +/- 2.7%, respectively). The response of 7 coronary arteries examined immediately proximal to a significant lesion was not significantly different from the response of the remaining 11 coronary arteries. In conclusion, intracoronary papaverine causes a significant increase in coronary arterial diameter. This has clinical implications for assessing coronary flow reserve with devices that defect flow velocity.

Regulation of large coronary arteries by increases in myocardial metabolic demands in conscious dogs.

In order to assess the effects of increasing myocardial metabolic demand on the large epicardial coronary arteries, we measured left circumflex coronary artery diameter (ultrasonic transit time technique) and blood flow in conscious dogs with chronically implanted transducers. Myocardial oxygen consumption was increased by pacing-induced tachycardia and aortic constriction, and monitored by multiplying left circumflex coronary arterial blood flow by coronary arterio-venous oxygen content difference. Increase of heart rate by 90 beats/min caused myocardial oxygen consumption to increase by 34 +/- 4.3% (1 SEM); coronary blood flow at constant arterial pressure to increase by 32 +/- 6.8%; and coronary diameter to increase by 0.07 +/- 0.01 mm, P less than 0.01. Aortic constriction, producing a 53 +/- 5.1% increase of left ventricular systolic pressure, caused myocardial oxygen consumption to increase by 49 +/- 7.2%, coronary blood flow to increase by 50 +/- 6.0%, and coronary diameter to increase 0.03 mm, P less than 0.01. The increases in coronary artery diameter were gradual, not immediate, in onset and not altered by beta-adrenergic blockade. Thus, increased myocardial metabolic demand dilates large epicardial coronary arteries, but with a slower response time than the rapid dilation of the smaller resistance vessels.