Decrease In Coronary Flow Reserve Research Articles

Attenuation of coronary flow reserve and myocardial function after temporary subtotal coronary artery occlusion and increased myocardial oxygen demand in dogs

Objectives. We examined whether subtotal coronary artery occlusion and reperfusion alter coronary flow reserve and regional myocardial function.Background. Total coronary artery occlusion followed by reperfusion results in decreased coronary flow reserve and regional myocardial dysfunction.Methods. Thirteen anesthetized dogs were subjected to subtotal occlusion of the left anterior descending coronary artery for 1 h, followed by reperfusion for 1 h. During subtotal left anterior descending occlusion, heart rate was increased by atrial pacing. After reperfusion, coronary flow reserve, indicated by reactive hyperemia, as well as coronary flow responses to acetylcholine and nitroglycerin, regional myocardial function and myocardial leukocyte accumulation were measured.Results. After reperfusion, coronary flow reserve was decreased in the ischemic left anterior descending but not the nonischemic circumflex coronary artery region. Myocardial function was also depressed in the left anterior descending coronary region and did not improve on reperfusion. Histologic study showed no leukocyte infiltration in the ischemic left anterior descending coronary region. Myeloperoxidase, an index of inyocardiai leukocyte accumulation, was similar in the left anterior descending and circumflex coronary regions. Sensitivity of epicardial left anterior descending coronary artery rings to the thromboxane A2analog U46,619 was enhanced, and relaxation of these rings in response to endothelium-dependent relaxants was decreased.Conclusions. Coronary flow reserve is reduced and regional myocardial function depressed after subtotal coronary artery occlusion and increased heart rate. A decreased synthesis or increased breakdown of endothelium-derived relaxing factor may be related to a decrease in coronary flow reserve. However, the reduction in coronary flow reserve appears to be unrelated to leukocyte accumulation in the reperfused region.

Digital angiographic impulse response analysis of regional myocardial perfusion. Detection of autoregulatory changes in nonstenotic coronary arteries induced by collateral flow to adjacent stenotic arteries.

Our study compares the effect of acute proximal stenosis of a coronary artery supplying a myocardial perfusion bed with that of stenosis of an adjacent artery resulting in collateral flow diversion supplied by the same perfusion bed. These alterations in coronary physiology were quantified by digital angiographic impulse response analysis of contrast material mean transit time for the coronary microcirculation, Tmicro, and by flowmeter and microsphere assessment of flow and regional flow distribution. In 25 open-chest, anesthetized dogs, progressive circumflex artery stenosis led to a concordant decrease of circumflex artery resting and hyperemic flow, coronary flow reserve, and inverse angiographic mean transit time Tmicro-1 (P < .01). Progressive left anterior descending artery stenosis led to no or only minor changes of circumflex artery resting or hyperemic flow or flow reserve; only occlusion induced a significant decrease of coronary flow reserve (from 4.0 +/- 0.7 to 3.2 +/- 0.5, P < .05), whereas resting flow was increased by +8.6 +/- 5.9%. In contrast, circumflex artery Tmicro-1 diminished significantly with critical left anterior descending artery stenosis and occlusion (from 16.7 +/- 4.2 to 12.6 +/- 2.2 [P < .05] and 12.0 +/- 3.0 min-1 [P < .01], respectively). In 8 dogs, collateral flow induced by left anterior descending artery occlusion was quantified by microsphere injections. The decrease of circumflex artery Tmicro-1 correlated with the magnitude of collateral flow (r = .76) and was associated with the angiographic extent of collateral filling. Digital angiographic impulse response analysis is a sensitive method to detect the influence of proximal artery stenosis on an artery's myocardial perfusion bed as well as the changes induced by an adjacent artery stenosis inducing collateral flow diversion from the supplying myocardial perfusion zone.

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).

Relationship of left ventricular mass to impairment of coronary vasodilator reserve in hypertensive heart disease

An impaired coronary vasodilator reserve has been demonstrated in all stages of hypertensive heart disease but is most likely in the setting of hypertrophy. The decrease in coronary flow reserve has, however, not been predictable previously. We postulated that flow reserve depression might be related to a left ventricular mass threshold. Seventy-two patients (82% with hypertension) with suspected ischemic heart disease who were found to be free of significant coronary artery disease at cardiac catheterization were evaluated utilizing the intracoronary Doppler catheter and two-dimensional directed M-mode echocardiography for determination of coronary flow reserve and left ventricular mass. For left ventricular mass indexed (LVMI) by body surface area (BSA) ≥ 50% above normal using established gender-specific norms, American Society of Echocardiography (ASE) and PENN methods (correction of LV mass by regression equation agreeing with necropsy estimates of mass) predicted impairment of flow reserve ( p = 0.005 and 0.009, respectively). Unindexed left ventricular mass and LVMI by height were not helpful in this regard. Using the ASE method for LV mass determination, coronary flow reserve was moderately depressed (2.4 ± 1.0) for those with LVMI ≥ 50% above normal; in comparison, flow reserve was normal (3.5 ± 1.3) for those with LVMI < 50% above normal. A rare patient was able to maintain a normal flow reserve when ASE- and Penn-indexed mass estimates were ≥ 50% above normal, but only in the setting of a markedly elevated mean arterial pressure.

Evidence for decreased coronary flow reserve in viable postischemic myocardium.

To try to unravel the complexity and heterogeneity of the "no-reflow" phenomenon and its underlying mechanisms, we studied tissue perfusion in reperfused heart muscle by using tracer microspheres in an anesthetized dog model of 90-minute coronary occlusion followed by reperfusion for 2 1/2 hours, 24 hours, or 1 week. Regional myocardial blood flow was determined both in basal flow conditions and during reactive hyperemia. The effect of intracoronary adenosine administration was examined, and the ultrastructure of postischemic myocardium was analyzed. In viable reperfused tissue (as delineated by triphenyltetrazolium chloride staining), reflow in basal conditions is unimpaired. Coronary flow reserve (as approximated by peak reactive hyperemic flow) is intact at the start of reperfusion, decreases by more than half after 2 1/2 hours, and recovers completely within 1 week. This impairment of coronary reserve can be relieved by intracoronary adenosine administration. On ultrastructural examination, the capillaries are patent. On the other hand, in irreversibly damaged myocardium, both the basal reflow impairment and the decrease in coronary flow reserve are severe and permanent. Coronary flow reserve is already decreased at the start of reperfusion, and the pharmacological intervention has no beneficial effect. Ultrastructurally, extracellular and intracellular edema invariably are present, whereas the vascular endothelium is damaged and the capillaries are packed with red blood cells. We conclude that the no-reflow phenomenon (i.e., mechanical obstruction to blood flow) is limited to infarcted tissue. In viable myocardium, however, coronary flow reserve is transiently diminished, probably because of washout and subsequent insufficient availability of the chemical mediator adenosine after breakdown and slow recovery of the precursor ATP pool.

The effect of diltiazem on coronary flow reserve in humans.

Calcium channel antagonists have been shown to blunt maximal coronary flow after brief coronary occlusion and during pharmacologic coronary dilation in animals. This property, if present in humans, would result in a reduction in coronary flow reserve in the absence of intrinsic abnormalities of the coronary circulation. A reduction of maximal vasodilator capacity by calcium channel antagonists could also constitute an important anti-ischemic mechanism of action of these agents. To evaluate the effect of calcium channel antagonists on coronary flow reserve in awake humans, we measured coronary flow reserve using the coronary Doppler catheter and intracoronary papaverine at baseline and after diltiazem administered by intravenous (125 or 250 micrograms/kg bolus, 5 micrograms/kg/min infusion, n = 8) or intracoronary (150-600 micrograms bolus, n = 10) routes. Intravenous diltiazem reduced heart rate from 77 +/- 18 to 72 +/- 17 beats/min (mean +/- SD, p less than 0.005) and reduced mean arterial pressure from 96 +/- 11 to 86 +/- 15 mm Hg (p less than 0.005). Intravenous diltiazem resulted in a small decrease in coronary flow reserve (peak-to-resting flow velocity ratio) from 3.9 +/- 1.2 to 3.6 +/- 1.1 (p less than 0.01). After intracoronary diltiazem, mean arterial pressure was unchanged (control 99 +/- 12 mm Hg, diltiazem 97 +/- 13 mm Hg), and heart rate was maintained constant by atrial pacing. Coronary flow reserve was unchanged at 3.8 +/- 0.9 at baseline and after intracoronary diltiazem. Thus, treatment with diltiazem does not invalidate the measurement of coronary flow reserve for diagnostic purposes. Furthermore, these results suggest that attenuation of maximal coronary dilation by diltiazem is not a mechanism responsible for its antianginal effects.

Influence of acute aortic insufficiency on the hemodynamic importance of a coronary artery narrowing. II. Various magnitudes of aortic insufficiency

Coronary hemodynamic effects of controlled acute aortic insufficiency were studied in 40 open chest dogs with and without graded coronary diameter narrowing. An adjustable basket device was used to regulate aortic insufficiency, creating three groups: group 1, mild to moderate aortic insufficiency (regurgitant fraction less than 50%); group 2, moderately severe aortic insufficiency (regurgitant fraction greater than 50%); and group 3, aortic insufficiency with mean aortic pressure restored to control levels. Mean coronary blood flow was similar to control values in group 1, but was higher in groups 2 and 3. The endocardial/epicardial flow ratio was similar with and without aortic insufficiency. With graded coronary narrowing greater than 80%, coronary flow and endocardial/epicardial flow ratio decreased with or without aortic insufficiency. However, endocardial/epicardial flow ratio usually decreased more during aortic insufficiency. Peak reactive hyperemic flow after release of a 10 second coronary occlusion also decreased during aortic insufficiency. The amount of decrease compared with control values was related to the magnitude of aortic insufficiency. This value with no coronary narrowing in group 1 was similar to peak reactive hyperemic flow with a 60% coronary narrowing during the control period. In group 2, peak reactive hyperemic flow was similar to that with an 80% coronary narrowing during the control period. Restoring mean aortic pressure to control values in group 3 did not restore peak reactive hyperemic flow to control values. These data suggest that coronary flow reserve assessed with coronary narrowings or during reactive hyperemia is decreased during aortic insufficiency. The decrease in coronary flow reserve was more pronounced as the magnitude of aortic insufficiency increased.