Best treatment for single-vessel coronary artery disease.
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It has been reported that there are striking differences between large and small coronary arteries in their responsiveness to adenosine, nitroglycerin and catecholamines. The differential pharmacological responsiveness indicates differences in their excitation-contraction coupling mechanisms. Therefore, agents such as lyotropic anions (SCN-, NO3-, CH3SO4-) known to modulate these processes, and which by themselves do not have an inotropic effect, would be expected to differentially modulate the action of these substances on large and small coronary vessels. To test this hypothesis we studied the modulation by lyotropic anions of the effects of adenosine, nitroglycerin and verapamil on large and small intramural (0.5-0.6 mm diameter) dog coronary arteries. We have confirmed that small vessels are more sensitive to adenosine and verapamil and less sensitive to nitroglycerin than are large vessels. Replacement of Cl- by the lyotropic anions diminished the relaxing effects of adenosine in small vessels with the following order of potency, SCN- greater than NO3- greater than CH3SO4- greater than Cl-. NO3-. Replacement of Cl- resulted in almost total blockade of the adenosine response in small coronary arteries, whereas in large coronary vessels, the effects of nitroglycerin were reduced only 30%. The effects of verapamil in small vessels were slightly depressed whereas in large vessels its effects were unchanged. Our results further confirm that there are marked differences between the pharmacological responsiveness of large and small coronary vessels, indicating that these differences reside in the nature of their mechanisms controlling Ca++ translocation.
AIM: 1) to assess effect of coronary lesion morphology on changes of grafts during first year after surgery; 2) to study the state of native coronary vascular bed during first year after surgery; 3) to elucidate special features of atherosclerosis in grafts and coronary arteries in remote period after surgery. MATERIAL AND METHODS: One hundred eighty seven patients with 3-vessel coronary artery disease subjected to aorto-coronary or mammary-coronary grafting. RESULTS AND CONCLUSION: Proportions of closed venous grafts were 24,2% among grafts to arteries with 50-75% stenoses, 13.1% among grafts to occluded arteries (p=0.023), and 20.1% among grafts to arteries with 75-99% stenoses. Among venous grafts to arteries with lumen diameter <1.5 mm 30.4% were occluded what was significantly more than among grafts to vessels with 1.5-2.5 mm (15.5%, p=0.003) and >2.5 mm (14.5%, p=0.004) diameter. Morphological risk factors of venous graft closure in immediate postoperative period were 50-75% stenosis and lumen diameter <1.5 mm. All mammary-coronary anastomoses were patent in 1 year, 99% of them remained patent 5 years after surgery. No relationship was found between patency of venous grafts after 5 years of follow-up and morphological characteristics (lumen diameter and percent stenosis) of bypassed arteries. During first year there was no significant differences between patients with patent and occluded grafts both in incidences of novel atherosclerotic lesions (10.4 and 10.3%, respectively, p=0.943) and proportion of closures of initially stenotic arteries (9.6 and 10.3%, respectively, p=0.085). After 5 years novel atherosclerotic lesions were found in 31.9 and 33.6% of patients with patent and occluded grafts, respectively (p=0.910). Complete occlusions of stenosed vessels proximal to anastomosis occurred more often among patients with patent than with occluded grafts (28.6 and 15.9%, respectively, p=0.047). Thus in remote postoperative period development of atherosclerosis in proximal segments of arteries with patent grafts was more 'aggressive' than in arteries with occluded grafts.
The effects of nitroglycerin (NTG) and nitroprusside (NPR) were examined in conscious dogs on measurements of left circumflex coronary blood flow and coronary diameter and on calculations of late diastolic coronary resistance (LDCR) and left circumflex coronary internal cross-sectional area (CSA). The effects of infusions of NTG, 8 microgram/kg/Min for 7 minutes, and NPR, 2.5 microgram/kg/min for 7 minutes, were compared. These doses of NTG and NPR induced similar effects on mean arterial and left ventricular (LV) systolic and end-diastolic pressure, heart rate and LV dP/dt. However, NTG induced significantly greater (p less than 0.05) increases in CSA than NPR, while NPR induced significantly greater (p less than 0.05) reductions in LDCR than NTG. Just before cessation of infusion, CSA rose by 29.2 +/- 4.7% with NTG and by 22.7 +/- 3.9% with NPR, while LDCR fell by 8.8 +/- 3.3% with NTG and by 21.6 +/- 2.7% with NPR. Moreover, the effects of NTG on CSA were significantly more sustained than those for NPR. Thus, NTG and NPR in conscious dogs, in doses that exert similar general hemodynamic effects, elicit qualitatively similar but quantitatively different effects on small vs large coronary vessels. Whereas NTG induced significantly less dilation of small coronary vessels, it exerted significantly larger and longer lasting effects on large coronary arteries.
BACKGROUND: The development of transplant coronary artery disease is associated with neovascularization in the thickened neointima. We previously reported that captopril inhibits neointimal proliferation in a rat allograft model. We postulated that angiogenic inducers are upregulated post-transplantation and captopril ameliorates transplant coronary artery disease by suppressing the angiogenic activity of coronaries. METHODS: Animals received no treatment or captopril (50 mg/kg/day). Allograft hearts were analyzed at post-transplantation Days 0, 14, and 21 and angiogenic inducer, plasma platelet-activating factor, determined. The conditioned media from coronaries and myocardium were tested for vascular endothelial growth factor, thrombospondin-1 and angiogenic activity using an endothelial migration assay and rat corneal neovascularization assay. RESULTS: The captopril-treated group had reduced plasma platelet-activating factor and coronary media revealed earlier upregulation of thrombospondin-1 secretion, diminished vascular endothelial growth factor and no angiogenic activity. At Day 0, the coronary and myocardial conditioned medium had inhibitory activity due to thrombospondin-1, and circulating levels of platelet-activating factor were negligible. By 21 days post-transplantation, plasma platelet-activating factor was elevated and the conditioned medium from untreated coronaries had significantly higher angiogenic activity due to increased vascular endothelial growth factor whereas the myocardium remained non-angiogenic. CONCLUSIONS: After transplantation, coronary vessels switch to an angiogenic phenotype and vascular endothelial growth factor contributes to the high angiogenic activity, possibly exacerbated by high circulating levels of platelet-activating factor. The ability of captopril to modulate angiogenic mediators and maintain the allograft coronary to its normal anti-angiogenic phenotype may be one mechanism by which it suppresses transplant coronary artery disease.
The contribution of the L-arginine/nitric oxide pathway to beta-adrenergic dilation of resistance coronary vessels was examined in conscious dogs instrumented for measuring coronary blood flow (CBF), left ventricular (LV) wall thickening, and LV and aortic pressures and for intracoronary injections of acetylcholine (0.003 micrograms/kg), nitroglycerin (0.175 micrograms/kg), and graded doses of isoproterenol (0.0005 to 0.004 micrograms/kg). Peak increases in CBF with intracoronary isoproterenol (0.001 micrograms/kg) averaged 105 +/- 10% from baseline. With acetylcholine, CBF increased by 158 +/- 11%, and with nitroglycerin, CBF increased by 139 +/- 10%. After the administration of intracoronary N omega-nitro-L-arginine methyl ester (L-NAME, 10 micrograms/kg per minute for 12 minutes) to block nitric oxide synthesis from L-arginine, baseline CBF was not altered, and CBF increased by 49 +/- 7% with isoproterenol and by 94 +/- 6% with acetylcholine; both values were smaller (P < .01) than those before the arginine analogue. With nitroglycerin, CBF was increased by 145 +/- 11%, not significantly different from the value before L-NAME. Intracoronary L-arginine (1.0 mg/kg per minute for 12 minutes), the precursor of nitric oxide synthesis, partially reversed the inhibition of L-NAME on CBF responses to acetylcholine and isoproterenol. After beta 1-adrenergic blockade, CBF responses to isoproterenol and acetylcholine were also reduced (P < .05) by the arginine analogue. When increases in CBF were prevented, peak changes in coronary vascular conductance with intracoronary bolus doses of acetylcholine and isoproterenol were attenuated (P < .01) by L-NAME. Thus, nitric oxide formation is an important intermediate in beta-adrenergic dilation of resistance coronary vessels in conscious dogs.
In the experiments on dogs was investigated participation of coronary vessels in the reflexive regulation of the circulatory system. Electrical, hemodynamic and metabolic heart functions, pressures, and flow in peripheral vessels were measured. Hemodynamic reactions obtained by changes of the perfusion pressure and gas composition of blood in the left coronary artery and in coronary sinus were compared with the activity of cervical baro and chemoreceptors. Results of this investigation indicate that responses initiated by the changes in coronary perfusion pressure were manyfold smaller. Occlusion or decrease of the pressure in the left coronary artery caused pressor effect, which was diminish by myocardial ischemia. Declamping or increase of the perfusion pressure in the left coronary artery was leading to decrease of systemic arterial pressure. This response was next replaced by the pressor effect caused by the rapid myocardial blood flow. In the systemic hypertension blood flow changes in the left coronary artery caused smaller effects than in the normotension. In the hypertension increase of the coronary perfusion pressure initiated significant pressor reaction. Opposite effect was observed with the decrease of coronary perfusion pressure. Decrease of coronary oxygen content moderate pressor reaction in the systemic normotension also in hypertension. In systemic hypotension the depressor reactions was observed. Elevation of the coronary sinus perfusion pressure was correlated with the decrease in the systemic arterial pressure with significant bradycardia. Additional coronary sinus blood arterialisation caused pressor effect in systemic pressure. It possible that the coronary vessels in dogs are the source of the circulatory reflexes which seems possess essential physiological role.
The effects of melatonin on porcine pulmonary and coronary vessels have been studied. Vessels were isolated from normal pigs, placed in a tissue bath, and precontracted with 30 mM KCl. The biophysical responses to cumulative doses of melatonin were then assessed. In the pulmonary artery, melatonin caused a dose-dependent relaxation which was blocked by vasoactive intestinal peptide antagonists or prior 6-hydroxydopamine treatment of the vessels. In the coronary artery, melatonin caused the reverse, a dose-dependent contraction which was blocked by the alpha antagonist prazosin or prior 6-hydroxydopamine treatment. These experiments indicate that melatonin has different mechanisms of action in the coronary and pulmonary circulation, although both seem to depend on the integrity of perivascular 6-hydroxydopamine sensitive nerves. Such differing mechanisms may provide insight into pathophysiological events in the lungs (such as nocturnal asthma) and heart (early morning coronary infarction).
PURPOSE: To compare radial and spiral k-space sampling in navigator-gated ECG-triggered three-dimensional (3D) coronary vessel wall imaging. MATERIALS AND METHODS: The right coronary artery (RCA) vessel walls of eight healthy subjects were imaged using a modified double-inversion prepulse in concert with radial and spiral data acquisition. For data analysis, two investigators blinded to the sequence parameters subjectively assessed image quality in terms of artifacts and vessel wall visualization. Objective measures of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and vessel wall definition were also determined. RESULTS: Radial k-space sampling demonstrated fewer artifacts and led to improved visualization of the coronary vessel wall compared to spiral imaging (P < 0.05). This finding was also reflected in a better vessel wall definition using radial data acquisition (P < 0.05). SNR and CNR were found to be higher when spiral k-space sampling was used (n.s.). CONCLUSION: Radial k-space sampling in concert with free-breathing navigator-gated cardiac-triggered MRI of the coronary vessel wall resulted in fewer motion artifacts and improved vessel wall definition compared to spiral k-space sampling. The proposed approach therefore appears to be preferable.
Advanced coronary artery disease, defined as left main or three-vessel coronary disease, was identifiable noninvasively by means of adenosine Tl-201 single photon emission tomography. Among 75 consecutive patients with angiographically documented coronary artery disease, there were 11 patients with the presence (group 1) and 64 patients with the absence (group 2) of advanced coronary artery disease. The lung-to-heart ratio (L/H ratio) of Tl-201 uptake was calculated as the fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. The left ventricular dilation ratio (LVDR) was determined as a ratio of left ventricular cavity size in the early image to that in the delayed image. The patients in group 1 had more defects (2.3 +/- 0.6 seg. vs. 0.9 +/- 0.7 seg., p < 0.001), a higher L/H ratio (35 +/- 4% vs. 28 +/- 5%, p < 0.001) and a higher LVDR (1.13 +/- 0.04 vs. 1.06 +/- 0.04, p < 0.001) than those in group 2. The diagnostic accuracy of the identification of advanced coronary artery disease was 89% by perfusion defects, 68% by L/H ratio and 81% by LVDR. Stepwise discriminant analysis revealed that LVDR (F = 36.2, p < 0.0001) and perfusion defects (F = 8.9, p < 0.004) were the significant and independent discriminators of advanced coronary disease. Identification of patients with left main or three-vessel coronary disease was enhanced by additional analysis of cavity dilation of the left ventricle and increased Tl-201 activity in the lung.
Coronary angioplasty is a widely applied revascularization procedure for patients with multivessel coronary artery disease. However, follow-up in this patient subgroup is relatively limited. From 1983 to 1986, coronary angioplasty was performed in 349 and 121 patients with, respectively, two- and three-vessel coronary disease with a primary success rate of 83 and 88%. The in-hospital mortality rate was 2.8% (13 of 470 patients). Complete revascularization was achieved in 128 patients. Among the 397 patients with a successful outcome, 373 (94%) were followed up greater than or equal to 1 year; 79% were free of death, nonfatal myocardial infarction or the need for coronary bypass grafting, and 82% of patients had symptomatic improvement by at least one angina functional class. A second coronary angioplasty procedure was required in 13% of patients. After a mean follow-up period of 27 months, an increased incidence of coronary bypass grafting was noted in patients with incomplete versus complete revascularization (16 versus 7%, p less than 0.05). Among the 222 patients who had repeat cardiac catheterization performed an average of 7 months after angioplasty, 103 were symptomatic; 50% of the 222 patients had at least one vessel with greater than or equal to 50% restenosis and 14% of patients had multiple restenoses. In conclusion, coronary angioplasty can be performed with a high initial success rate and marked symptomatic improvement in patients with multivessel coronary disease. However, in this group's experience, the majority of patients selected for coronary angioplasty with multivessel coronary disease will have incomplete revascularization that can be predicted in the majority of patients before the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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The association of acute myocardial infarction (AMI) with normal coronary arteries was analyzed prospectively. A series of 128 consecutive patients underwent coronary angiography within 1 week from AMI. Seven patients, all females, had no coronary artery lesions and were considered eligible for the study. All 7 patients underwent atrial pacing (10 g/min increments every 2 min), ergonovine testing (E; total dose 0.650 mg i.v.). Great cardiac vein flow (GCVF; thermodilution technique), mean aortic pressure (MAP), anterior coronary resistance (ACR) and myocardial lactate extraction [(Lac art-Lac gcv)/Lac art] were measured at baseline and during testing. Pacing-induced typical chest pain occurred in 5 patients: 4 of them showed concurrent significant (> or = 0.15 mV) ST downsloping. At peak pacing, GCVF increased only by < 50%, or even decreased, in all patients. Baseline lactate extraction (0.13 +/- 0.11) changed to lactate production (-0.15 +/- 0.10) in 7/7 patients. None of the patients showed focal epicardial coronary artery spasm following E. During testing, however, all 7 patients showed decrease in GCVF (110 +/- 47 versus 74 +/- 21; p < 0.005), increase in ACR (0.92 +/- 0.29 versus 1.43 +/- 0.20; p < 0.001), and significant coronary lactate production (-0.18 +/- 0.12). Six patients referred slight to moderate chest pain, which was accompanied by ST downsloping in 4.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the relation between the ischemic threshold at the onset of wall motion abnormality on exercise echocardiography (EE) and the severity of coronary stenosis in patients with 1-vessel coronary artery disease (CAD). We screened 216 consecutive patients who underwent coronary angiography and EE for suspected CAD. Ninety-five (74 men; age, 56 +/- 12 years) satisfied the study criteria, that is, the presence of 1-vessel disease or no evidence of CAD on angiography and a normal baseline echocardiogram. Eighty-seven patients had 1-vessel CAD on angiography, and exercise-induced wall motion abnormality occurred in 73 (77%). Optimal cutoff values of percent diameter stenosis and minimal lumen diameter for predicting a positive EE were 61% (sensitivity and specificity of 76%) and 1.12 mm (sensitivity and specificity of 74%). Among patients with positive EE, heart rate-blood pressure product at ischemic threshold was correlated with quantitative coronary stenosis (r = -0.72, P <.001). The ischemic threshold from continuous monitoring of left ventricular function during semisupine EE is correlated with the severity of coronary stenosis among patients with 1-vessel disease and a normal resting echocardiogram.