Increase In Coronary Diameter Research Articles

Percutaneous Coronary Intervention (PCI) Enhances the Amplitude of the Early Diastolic Suction Wave in the Treated Artery

Background: Coronary flow is critically dependent on suction developed by the myocardium in diastole and left ventricular ejection during systole, both of which accelerate flow. Wave intensity analysis enables quantification and separation of these forces. The impact of (PCI) on the coronary wave intensity (CWI) profile is unclear. Methods: We performed simultaneous intracoronary pressure and velocity measurements in 17 patients undergoing elective PCI. Measurements were made distal to the target lesion prior to and following PCI during adenosine induced hyperaemia. Coronary wave speed (SPc) was calculated utilising the “single point sum-of-squares” method. Wave intensity profiles of ensemble averaged cardiac cycles were constructed applying previously described equations. The peak intensities of the dominant forward travelling “pushing” wave (Wave 2) and the dominant backward travelling “suction” wave (Wave 5) were calculated prior to and following PCI. Results: CWI profiles demonstrated the previously described six major waves. PCI resulted in substantial increases in peak intensity of Wave 2 and Wave 5 (mean increases in peak intensity of 227% p = 0.0007 and 170% p = 0.0005, respectively). Significant decreases were seen in SPc distal to the lesion following PCI (p = 0.003) and with intracoronary adenosine (p = 0.0003). Conclusion: PCI appears to augment both the forward travelling “pushing” wave and backward travelling “suction” waves. These findings are consistent with the enhancement of coronary flow seen with PCI. The decrease in wave speed following PCI and intracoronary adenosine may be explained by an increase in coronary diameter induced by increased flow.

Hemodynamic and Coronary Effects of the Endothelin Antagonist Bosentan in Patients With Coronary Artery Disease

Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease. In a double-blind, placebo-controlled randomized study, we investigated the effects of the ETA/ETB endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (P<0. 05), whereas heart rate increased slightly (P<0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (P<0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (P<0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated. Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ETA/ETB endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease.

Effect of alpha-adrenergic blockade with prazosin on large coronary diameter during exercise.

Exercise-induced dilation of coronary resistance vessels is limited by alpha-adrenergic mechanisms. However, the effect of alpha-adrenergic mechanisms on large coronary arteries during exercise is not known. In the present study, sonomicrometry was used to measure circumflex coronary arterial diameter during treadmill exercise before and after alpha 1-adrenergic blockade with prazosin in eight instrumented dogs. Before infusion of prazosin, exercise caused a fall in coronary vascular resistance (2.1 +/- 0.4 to 1.6 +/- 0.2 units, p less than 0.05) and dilation of the circumflex coronary artery (4.66 +/- 0.37 to 4.79 +/- 0.34 mm, p less than 0.05). Intracoronary infusion of prazosin during exercise caused a further decrease in coronary vascular resistance (1.6 +/- 0.2 to 1.4 +/- 0.2 units, p less than 0.05) and a further increase in circumflex coronary arterial diameter (4.79 +/- 0.34 to 4.83 +/- 0.34 mm, p less than 0.05). Intracoronary infusion of vehicle without prazosin during exercise did not cause a further decrease in coronary vascular resistance or increase in coronary diameter. Prazosin caused no significant increase in heart rate, aortic pressure, or coronary blood flow. Therefore, both small coronary resistance vessels and large epicardial coronary arteries dilated during exercise and dilated further after alpha-adrenergic blockade. This finding indicates that alpha 1-adrenergic activity during exercise limits dilation of both large and small coronary arteries.

Coronary hemodynamics and coronary flow reserve after intracoronary diltiazem in humans

To analyze the effect of the calcium antagonist diltiazem on coronary hemodynamics, epicardial coronary artery diameter, coronary blood flow and coronary blood flow velocity were assessed at baseline and after a 0.5 mg intracoronary bolus of diltiazem in nonstenotic coronary arteries of awake humans. Patients (n = 20) were first randomized to pretreatment with either placebo (n = 10) or isosorbide dinitrate (0.5 μg/kg/min infusion; n = 10), and coronary flow reserve was measured before and after administration of diltiazem. There were significant increases in epicardial coronary artery diameter (10%; p = 0.0001) and coronary blood flow (30%; p = 0.0001) in all patients after administration of diltiazem. Whereas basal coronary blood flow velocity increased only slightly (7%; p = not significant), there was a significant decrease in coronary flow reserve (10%; p = 0.004). Increases in coronary diameter and blood flow after diltiazem were comparable in patients pretreated with placebo or nitrates. However, the decrease in coronary flow reserve was significant only in patients pretreated with placebo (19%; p = 0.0008). This reduction in coronary flow reserve could be due to “raising the floor” (increased baseline coronary blood flow) or “lowering the ceiling” (reduction of maximal coronary blood flow).

Changes in Human Coronary Flow Reserve After Administration of Intracoronary Diltiazem

Epicardial coronary artery diameter (ECAD), coronary blood flow velocity (CBFV), and coronary flow velocity reserve (CFVR) were analyzed at baseline and after a 500 micrograms i.c. bolus of diltiazem in nonstenotic coronary arteries of awake humans. Furthermore, patients (n = 25) were first randomized to pretreatment either with placebo (n = 12) or isosorbide dinitrate (0.5 micrograms/kg/min infusion) (n = 13). Diltiazem resulted in a significant increase in epicardial diameter (+10%; p = 0.001) and in coronary blood flow (CBF) (+30%; p = 0.0001). Whereas basal CBFV only slightly increased (+7%; NS), there was a significant fall in CFVR (-11%; p = 0.001). The increase in coronary diameter and CBF after administration of i.c. diltiazem was comparable in placebo- and nitrate-pretreated patients. The decrease in CFVR, however, was restricted to the placebo-pretreated patients (-21%; p = 0.0004). Apparently, diltiazem attenuated the CFVR but only in the absence of nitrates. Thus, diltiazem i.c. appears to enhance myocardial oxygen supply without deleterious effects on the distal coronary perfusion pressure.

Changes in Human Coronary Flow Reserve After Administration of Intracoronary Diltiazem

Epicardial coronary artery diameter (ECAD), coronary blood flow velocity (CBFV), and coronary flow velocity reserve (CFVR) were analyzed at baseline and after a 500 μg i.e. bolus of diltiazem in nonstenotic coronary arteries of awake humans. Furthermore, patients (n = 25) were first randomized to pretreatment either with placebo (n = 12) or isosorbide dinitrate (0.5 μg/kg/min infusion) (n = 13). Diltiazem resulted in a significant increase in epicardial diameter (+ 10%; p = 0.001) and in coronary blood How (CBF) (+ 30%; p = 0.0001). Whereas basal CBFV only slightly increased (+7% NS), there was a significant fall in CFVR (− 11%; p = 0.001). The increase in coronary diameter and CBF after administration of i.e. diltiazem was comparable in placebo- and nitrate-pretreated patients. The decrease in CFVR, however, was restricted to the placebo-pretreated patients (−21%; p = 0.0004). Apparently, diltiazem attenuated the CFVR but only in the absence of nitrates. Thus, diltiazem i.e. appears to enhance myocardial oxygen supply without deleterious effects on the distal coronary perfusion pressure.

Effects of ionic and nonionic contrast media on coronary diameter and blood flow in chronically instrumented dogs

The effects of intracoronary administration of ionic and nonionic contrast media on coronary circulation were studied in 14 chronically instrumented dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery, under sterile conditions, to measure the epicardial coronary diameter and coronary blood flow, respectively. A polyethylene tube for drug infusion was inserted into the circumflex coronary artery proximal to the sonomicrometers. In the conscious dogs ( n = 8), iopamidol, 2 ml and 5 ml, increased the coronary diameter by 64 ± 19 μm and 66 ± 19 μm and coronary blood flow by 35 ± 10% and 61 ± 18%, respectively ( p < 0.01 vs control level). Meglumine diatrizoate, 2 ml and 5 ml, increased coronary diameter by 102 ± 20 μm and 114 ± 18 μm and coronary blood flow by 87 ± 32% and 107 ± 26%, respectively ( p < 0.01 vs control level). In the anesthetized dogs ( n = 6), a bolus intracoronary injection of 5 ml iopamidol and meglumine diatrizoate within a few seconds increased the coronary diameter by 103 ± 23 μm and 164 ± 39 μm ( p < 0.05) and increased the coronary blood flow by 126 ± 33% and 180 ± 40% ( p < 0.05), respectively. Balloon denudation of the endothelium was performed in six anesthetized dogs. The increases in coronary diameter and coronary blood flow after a bolus injection of contrast medium remained the same after the denudation. Thus application of iopamidol seems to be more suitable than meglumine diatrizoate for quantitative coronary angiography because of the milder and more transient effects on coronary circulation.

Effect of cutaneous nitroglycerin patches on coronary artery diameter: Issues concerning development of tolerance

The coronary dilative and systemic responses to graded doses of intracoronary nitroglycerin were studied in 53 patients undergoing diagnostic coronary arteriography, 43 of whom had received a cutaneous nitroglycerin patch. During coronary arteriography, graded doses of 50, 100 and 200 μg of intracoronary nitroglycerin were given 5 min apart. An arteriogram and hemodynamic measurements were obtained after each dose. In the control group (n = 10) cumulative intracoronary nitroglycerin doses of 50,150 and 350 μg caused an increase in coronary diameter in the left anterior descending artery of 20 ± 4%, 21 ± 3% and 22 ± 7%, respectively, and in the circumflex artery of 18 ± 6%, 23 ± 8% and 18 ± 5% (p < 0.01 versus values in untreated group).In Group 1 (15 patients given a 5 mg/24 h nitroglycerin patch 2 to 12 h before coronary arteriography), the same intracoronary nitroglycerin doses increased the left anterior descending artery diameter by 6 ± 2%, 7 ± 2% and 7 ± 2%, respectively, and the circumflex artery diameter by 3 ± 2%, 3 ± 2% and 1 ± 3%. All values were statistically different from control (p < 0.05). An even more pronounced blunting (p < 0.01) of the coronary dilative response was observed in Group 2 (14 patients given a 15 mg/24 h nitroglycerin patch 2 to 12 h before arteriography). The diameter responses to intracoronary nitroglycerin observed in Group 3 (seven patients given a 5 mg/24 h nitroglycerin patch 24 h before arteriography) and Group 4 (seven patients given a 15 mg/24 h nitroglycerin patch 24 h before arteriography) were not significantly different from those of the control group.The results demonstrate that a nitroglycerin patch administered a few hours before coronary arteriography caused significant coronary artery dilation and that the incremental dilation due to the intracoronary nitroglycerin was small. On the other hand, 24 h after arteriography, the coronary dilative effect of the patch was attenuated (suggesting development of tolerance) and the increment in diameter induced by intracoronary nitroglycerin was much larger.

Effects of atrial natriuretic peptide on proximal epicardial coronary arteries and coronary blood flow in conscious dogs.

The effects of atrial natriuretic peptide (ANP) on proximal epicardial coronary artery dimensions and coronary blood flow were examined in 7 awake dogs chronically instrumented with miniature coronary dimension crystals and Doppler flow probes on the circumflex coronary artery. ANP (10, 50, and 150 micrograms) was infused as a bolus via the left atrial catheter. Aortic pressure, left ventricular end-diastolic pressure, heart rate, and dP/dt did not change significantly with any dose of ANP. ANP caused transient (1-5 minutes) dose-related increases in coronary blood flow; maximum increases were 28.1 +/- 6.9%, 40.2 +/- 6.2%, and 73.9 +/- 12.5% with the 10-, 50-, and 150-micrograms doses, respectively. ANP also induced prolonged (average 70.2 +/- 28.6 minutes with 150-micrograms dose) dose-related increases in coronary diameter; maximum increases were 3.1 +/- 1.0%, 3.9 +/- 1.5%, and 5.7 +/- 1.3% with the 10-, 50-, and 150-micrograms doses, respectively. The increase in diameter was not attenuated when the transient increase in blood flow was prevented by partial occlusion with a pneumatic snare. Combined autonomic blockade with propranolol (1 mg/kg), phentolamine (1 mg/kg), and atropine (0.06 mg/kg) attenuated the relative increase in coronary flow but did not alter the increases in epicardial coronary diameter produced by ANP. These data demonstrate that bolus injection of ANP effects preferential, sustained, dose-dependent, flow-independent increases in epicardial coronary dimensions and relatively brief dose-dependent increases in coronary blood flow. The vasodilator effects of ANP on epicardial vessels are direct and are not mediated via the autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasodilation by nitrates is not mediated by the prostaglandin system: A quantitative cineangiographic study

The possible role of prostaglandins in mediating large coronary artery vasodilation by nitrates was investigated by quantitative magnification coronary angiography. The effects of aspirin (1 g systemically and 100 mg intracoronary) in preventing large coronary artery vasodilation induced by intracoronary isosorbide dinitrate was investigated in 16 patients. Of these, 5 received 0.3 mg (Group 1A) and 11 received 3 mg (Group 1B) intracoronary isosorbide dinitrate, before and 15 minutes after aspirin. Relative to control, 0.3 mg isosorbide dinitrate induced a 19 +/- 9% (mean +/- SD) (p less than 0.01) and 19.5 +/- 11% (p less than 0.01) increase in coronary diameter before and after aspirin, respectively (p = NS). Changes after 3 mg isosorbide were 23 +/- 12% (p less than 0.01) and 26.5 +/- 14% (p less than 0.01), respectively, before and after aspirin (p = NS). In 10 additional patients (Group 2), the effect of the same dose of aspirin on rest coronary artery tone was assessed: changes relative to control were 0.9 +/- 5.5% (p = NS) minutes after aspirin. The intracoronary administration of 3 mg isosorbide dinitrate produced a 24.7 +/- 11% increase in coronary diameter (p = NS versus pre- and postaspirin isosorbide in Group 1B). Urinary 6-ketoprostaglandin-F1 alpha values in urine samples collected in the 8 hours before and the 8 hours after the study in five patients in Group 1B and five patients of Group 2, revealed a 36 +/- 14% (mean +/- SD) reduction in excretion of prostacyclin (p less than 0.01). These data rule out a role for prostaglandins both in mediating dilation of large coronary arteries by nitrates and in affecting their vascular tone at rest.

Subtypes of beta-adrenergic receptors in bovine coronary arteries.

Whether large coronary artery dilation induced by beta-adrenergic stimulation is mediated by beta 1- or beta 2-adrenergic receptors remains controversial. This problem is particularly difficult to address in vivo due to the concomitant increase in coronary blood flow with beta-adrenergic stimulation, which by itself can dilate large coronary arteries. To reconcile this problem, 5 calves were instrumented with intraaortic and intracoronary (i.c.) catheters, ultrasonic diameter transducers, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. Two to six weeks following surgery, beta-adrenergic agonists were administered i.c. to avoid complicating systemic effects. Isoproterenol (0.0025 micrograms/kg, a beta 1 + beta 2-adrenergic agonist) increased coronary diameter (7.1 +/- 0.8% from 5.80 +/- 0.58 mm) (p less than 0.01). Similar increases (p less than 0.01) in coronary diameter occurred with prenalterol (0.4 micrograms/kg, beta 1-adrenergic agonist) (9.5 +/- 1.4%) and pirbuterol (0.25 micrograms/kg, beta 2-adrenergic agonist) (8.1 +/- 1.2%). When coronary blood flow was prevented from rising with the hydraulic constrictor, increases in coronary diameter to all three beta-adrenergic agonists were not attenuated. Large coronary artery dilation with prenalterol and pirbuterol was abolished with beta 1- and beta 2-adrenergic receptor blockade, respectively, while neither beta 1- nor beta 2-adrenergic blockade alone abolished the large coronary artery dilation with isoproterenol. To identify the predominant subtype of beta-adrenergic receptor, competitive inhibition curves utilizing 125I-cyanopindolol (125I-CYP) as the radiolabel versus isoproterenol, epinephrine, and norepinephrine were generated in membrane preparations from calf heart (predominant beta 1), calf lung (predominant beta 2) and calf coronary artery. The coronary artery membrane preparations demonstrated an intermediate pattern. Competition curves with selective beta 1- and beta 2-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both beta-adrenergic receptor subtypes in large coronary arteries, with a ratio of beta 1: beta 2 of 1.5-2.0:1.0. Thus, large coronary arteries of the calf contain both beta 1- and beta 2-adrenergic receptors identified utilizing ligand binding techniques, and stimulation of both receptor subtypes in the intact conscious animal results in large coronary artery dilation, independent of blood-flow-mediated vasodilation.

Effects of dilazep on coronary and systemic hemodynamics in humans

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O 2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg · min · ml −1, p < 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p < 0.01), and a 23% increase in coronary diameter (four patients) ( p < 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.