Comparison of intima-media thickness and ophthalmic artery resistance index for assessing subclinical atherosclerosis in HIV-1-infected patients

Background

The determination of coronary flow reserve (CFR) is an essential concept at the moment of decision-making in ischemic heart disease. There are several direct and indirect tests to evaluate this parameter. In this sense, dobutamine stress echocardiography is one of the pharmacological method most commonly used worldwide. It has been previously demonstrated that CFR can be determined by this technique. Despite our wide experience with dobutamine stress echocardiography, we ignored the necessary heart rate to consider sufficient the test for the analysis of CFR. For this reason, our main goal was to determine the velocity of coronary flow in each stage of dobutamine stress echocardiography and the heart rate value necessary to double the baseline values of coronary flow velocity in the territory of the left anterior descending (LAD) coronary artery.

Methods

A total of 33 consecutive patients were analyzed. The patients included had low risk for coronary artery disease. All the participants underwent dobutamine stress echocardiography and coronary artery flow velocity was evaluated in the distal segment of LAD coronary artery using transthoracic color-Doppler echocardiography.

Results

The feasibility of determining CFR in the territory of the LAD during dobutamine stress echocardiography was high: 31/33 patients (94%). Mean CFR was 2.67 at de end of dobutamine test. There was an excellent concordance between delta HR (difference between baseline HR and maximum HR) and the increase in the CFR (correlation coefficient 0.84). In this sense, we found that when HR increased by 50 beats, CFR was ≥ 2 (CI 93-99.2%). In addition, 96.4% of patients reached a CFR ≥ 2 (IC 91.1 - 99%) at 75% of their predicted maximum heart rate.

Conclusions

We found that the feasibility of dobutamine stress echocardiography to determine CFR in the territory of the LAD coronary artery was high. In this study, it was necessary to achieve a difference of 50 bpm from baseline HR or at least 75% of the maximum predicted heart rate to consider sufficient the test for the analysis of CFR.     

Increased nonoxidative glycolysis despite continued fatty acid uptake during demand-induced myocardial ischemia

During stress, patients with coronary artery disease frequently fail to increase coronary flow and myocardial oxygen consumption (MVO(2)) in response to a greater demand for oxygen, resulting in "demand-induced" ischemia. We tested the hypothesis that dobutamine infusion with flow restriction stimulates nonoxidative glycolysis without a change in MVO(2) or fatty acid uptake. Measurements were made in the anterior wall of anesthetized open-chest swine hearts (n = 7). The left anterior descending (LAD) coronary artery flow was controlled via an extracorporeal perfusion circuit, and substrate uptake and oxidation were measured with radiotracers. Demand-induced ischemia was produced with intravenous dobutamine (15 microg x kg(-1) x min(-1)) and 20% reduction in LAD flow for 20 min. Despite no change in MVO(2), there was a switch from lactate uptake (5.9 +/- 3.1) to production (74.5 +/- 16.3 micromol/min), glycogen depletion (66%), and increased glucose uptake (105%), but no change in anterior wall power or the index of anterior wall energy efficiency. There was no change in the rate of tracer-measured fatty acid uptake; however, exogenous fatty acid oxidation decreased by 71%. Thus demand-induced ischemia stimulated nonoxidative glycolysis and lactate production, but did not effect fatty acid uptake despite a fall in exogenous fatty acid oxidation.     

Use and limitations of magnetic resonance phase-contrast assessment of coronary flow reserve in a model of collateral dependence

Phase-contrast magnetic resonance imaging (PC-MRI) is useful for assessing coronary artery flow reserves (CFR) in man and acute animal models with intermediate coronary lesions. The present study examines the use of PC-MRI for assessing CFR in a model with critical stenosis and collateral dependence. PC-MRI quantitative flow measurements from the proximal left anterior descending (LAD) and left circumflex (LCX) coronary arteries were compared with myocardial tissue perfusion reserve measurements (microsphere techniques) after placement of a 2.25-mm ameroid constrictor on the proximal LCX in a porcine model; measurements were obtained at implantation (n = 4) and at 3 to 4 weeks (n = 4) and 6 weeks (n = 5) postimplantation. CFR is defined as the ratio of maximal hyperemic flow to baseline flow. Hyperemia was induced using intravenous adenosine (140 mg/kg/min). Collateral dependence in the LCX distri bution was evidenced by angiographic findings of critical stenosis with minimal myocardial histological changes and normal baseline myocardial perfusion (microsphere techniques). In this setting, PC-MRI CFR was correlated with microsphere measures of perfusion reserve. Collateral dependence was confirmed by Evan's blue dye injection. This study provides angiographic, myocardial perfusion, and histological correlates associated with PC-MRI epicardial CFR changes during chronic, progressive coronary artery constriction. It also demonstrates the disparity between epicardial and myocardial measures of coronary flow reserve with collateral dependence and the caveats for PC-MRI use in models of progressive coronary constriction.     

Early time course of myocardial electrical impedance during acute coronary artery occlusion in pigs, dogs, and humans.

Changes in myocardial electrical impedance (MEI) and physiological end points have been correlated during acute ischemia. However, the importance of MEI's early time course is not clear. This study evaluates such significance, by comparing the temporal behavior of MEI during acute total occlusion of the left anterior descending coronary artery in anesthetized humans, dogs, and pigs. Here, interspecies differences in three MEI parameters (baseline, time to plateau onset, and plateau value normalized by baseline) were evaluated using Kruskal-Wallis ANOVA and post hoc tests (P < 0.05). Noteworthy differences in the MEI time to plateau onset were observed: In dogs, MEI ischemic plateau was reached after 46.3 min (SD 12.9) min of occlusion, a significantly longer period compared with that of pigs and humans [4.7 (SD 1.2) and 4.1 min (SD 1.9), respectively]. However, no differences could be observed between both animal species regarding the normalized MEI ischemic plateau value (15.3% (SD 4.7) in pigs, vs. 19.6% (SD 2.6) in dogs). For all studied MEI parameters, only swine values resembled those of humans. The severity of myocardial supply ischemia, resulting from coronary artery occlusion, is known to be dependent on collateral flow. Thus, because dogs possess a well-developed collateral system (unlike humans or pigs), they have shown superior resistance to occlusion of a coronary artery. Here, the early MEI time course after left anterior descending coronary artery occlusion, represented by the time required to reach ischemic plateau, was proven to reflect such interspecies differences.     

Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates

ST-segment depression is commonly seen in patients with acute coronary syndromes. Most authors have attributed it to transient reductions in coronary blood flow due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and dynamic focal vasospasm at the site of coronary artery stenosis. However, ST-segment depression was never reproduced in classic animal models of coronary stenosis without the presence of tachycardia. We hypothesized that ST-segment depression occurring during acute coronary syndromes is not entirely explained by changes in epicardial coronary artery resistance and thus evaluated the effect of a slow, progressive epicardial coronary artery occlusion on the ECG and regional myocardial blood flow in anesthetized pigs. Slow, progressive occlusion over 72 min (SD 27) of the left anterior descending coronary artery in 20 anesthetized pigs led to a 90% decrease in coronary blood flow and the development of ST-segment elevation associated with homogeneous and transmural myocardial blood flow reductions, confirmed by microspheres and myocardial contrast echocardiography. ST-segment depression was not observed in any ECG lead before the development of ST-segment elevation. At normal heart rates, progressive epicardial stenosis of a coronary artery results in myocardial ischemia associated with homogeneous, transmural reduction in regional myocardial blood flow and ST-segment elevation, without preceding ST-segment depression. Thus, in coronary syndromes with ST-segment depression and predominant subendocardial ischemia, factors other than mere increases in epicardial coronary resistance must be invoked to explain the heterogeneous parietal distribution of flow and associated ECG changes.     

Locations of ectopic beats coincide with spatial gradients of NADH in a regional model of low-flow reperfusion

We studied the origins of ectopic beats during low-flow reperfusion after acute regional ischemia in excised rat hearts. The left anterior descending coronary artery was cannulated. Perfusate was delivered to the cannula using an high-performance liquid chromatography pump. This provided not only precise control of flow rate but also avoided mechanical artifacts associated with vessel occlusion and deocclusion. Optical mapping of epicardial transmembrane potential served to identify activation wavefronts. Imaging of NADH fluorescence was used to quantify local ischemia. Our experiments suggest that low-flow reperfusion of ischemic myocardium leads to a highly heterogeneous ischemic substrate and that the degree of ischemia between adjacent patches of tissue changes in time. In contrast to transient ectopic activity observed during full-flow reperfusion, persistent ectopic arrhythmias were observed during low-flow reperfusion. The origins of ectopic beats were traceable to areas of high spatial gradients of changes in NADH fluorescence caused by low-flow reperfusion.     

A very rare image in cardiology: posterolateral artery myocardial bridge

Muscle overlying of an epicardial coronary artery is termed a myocardial bridge. The frequency of myocardial bridging reported in angiographic studies varies from 0.5 to 16%.1 Myocardial bridging is usually confined to the left anterior descending coronary artery. A myocardial bridge of the branches of the right coronary artery is very rare.     

Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans

Nine patients with coronary artery disease and normal left ventricular (LV) function underwent two episodes of dobutamine-induced ischemia to determine whether repeated episodes of ischemia lead to cumulative stunning. Positron emission tomography (PET) and oxygen 15-labeled H(2)O was used to assess myocardial blood flow (MBF) at baseline, peak stress, and after stress for each ischemic episode. Quantitative echocardiographic assessment of global ejection fraction (EF) and regional systolic function (SF) was performed at rest and regular intervals after dobutamine. SF was assessed for regions subtended by a coronary artery with a >70% diameter stenosis. Both EF and SF were more severely impaired 45 min after the second episode of stress compared with 45 min after the first (both P < 0.01), despite no difference in duration of the two dobutamine infusions or MBF at peak stress (1.72 vs. 1.69). After both episodes of ischemia, when LV function was impaired but subsequently recovered, MBF (1.15 +/- 0.39 and 1.20 +/- 0.43, respectively) was no different to baseline MBF (1.02 +/- 0.35), confirming that repeated episodes of dobutamine-induced ischemia lead to cumulative myocardial stunning.     

Effects of thromboxane analog U46619 on endothelial damaged canine coronary arteries in vivo

We studied the effects of the thromboxane analog, U46619, infused into the left anterior descending (LAD) artery of intact dogs before and after producing endothelial denudation of the mid portion of the LAD. Proximal artery cross-sectional area (CSA) decreased by 47% with 0.1 microgram/min infusion of U46619 with intact and denuded endothelium, while resting CSA reduced spontaneously following denudation. Coronary resistance vessels demonstrated a marked constrictor response to U46619 with a rise in resistance and a fall in flow and myocardial O2 consumption. U46619 produces significant narrowing of proximal epicardial coronary arteries as well as resistance coronary vessels. This effect could cause ischemia in patients with moderate coronary atherosclerosis.     

Dynamic capacitance of epicardial coronary arteries in vivo

The dynamic capacitance of epicardial coronary arteries (i.d. greater than or equal to 0.4 mm) in vivo was assessed from the volume stiffness and volume of these arteries. The volume stiffness was derived from the pressure wave front velocity as determined in dogs by measuring the delay time between the pressure pulses recorded proximal and distal to a segment of the anterior descending branch of the left coronary artery. The pressure pulse was generated elsewhere in the arterial system during diastole. The volume of the epicardial coronary arteries was calculated from the lengths and diameters as measured in araldite casts, making corrections for in-vitro/in-vivo differences in dimensions. The dynamic capacitance of the right coronary artery, and the anterior descending and circumflex branches of the left coronary artery at an arterial pressure of 13.3 kPa and a frequency between 7 and 30 Hz was found to be 0.0024 +/- 0.0013, 0.0062 +/- 0.0028 and 0.0079 +/- 0.0035 mL/kPa (mean +/- SD), respectively. The total capacitance of the epicardial coronary arteries was calculated to be (0.007 mL/kPa)/100 g, which is small as compared to the total capacitance of the coronary vasculature, including the intramyocardial compartment, which is in the order of (0.5 mL/kPa)/100 g [1].     

The transient nature of myocardial ischemia during partial occlusion of the coronary artery in waking immobilized rabbits

The radioactive microsphere technique was used to study mechanisms of disappearance of myocardial ischemia during partial occlusion of the left descending anterior coronary artery with implanted device in conscious immobilized rabbits. Microspheres (15 microns, NEN, USA) were injected before occlusion, immediately after ST-segment elevation and after disappearance of ST-segment shift. In ischemic region blood flow dropped by 45% (p less than 0.05) and mean blood pressure decreased by 12% (P less than 0.05) on the 1st minute of coronary occlusion. 8-15 min later ST-segment elevation disappeared and the blood flow in ischemic region became higher than control level (on the average by 35%). It is suggested that ischemia is abolished mainly by dilatation of distal coronary vessels, than by activation of collateral blood flow.     

Cerebral blood flow assessment with indocyanine green bolus transit detection by near-infrared spectroscopy in the rat

In this study we evaluated the feasibility of measuring cerebral blood flow in rats by monitoring the transit of an indocyanine green bolus through the brain with multiwavelength near-infrared spectroscopy. Different volumes of a 1 mg/ml indocyanine green solution (5, 15, 25, 50 microl) were injected intravenously in the search for an optimal dose. Clear transit curves were obtained with all doses and a blood flow index could easily be determined. The indocyanine green signal obtained with the bolus of 5 microl rapidly returned to baseline and interfered minimally with the haemoglobin and cytochrome oxidase signals. This dose was used in a second study to evaluate the reproducibility of the signal and the effect of hypercapnia. Two groups of rats received 7 repetitive boli of indocyanine green. In one group, 7% CO(2) was added to the gas mixture before the second, fourth and sixth indocyanine green injection. Hypercapnia consistently caused a significant increase in blood flow index, cerebral haemoglobin concentration and O(2)-saturation. In the control group these variables remained stable in time. We conclude that monitoring of the transit of an indocyanine green bolus with multiwavelength near-infrared spectroscopy can be used to assess cerebral blood flow qualitatively in rats in combination with continuous monitoring of brain oxygenation.     

Transcardiac adiponectin gradient is independently related to endothelial vasomotor function in large and resistance coronary arteries in humans

Adiponectin, an adipocyte-derived protein, has been shown to have vasculoprotective effects. This study examined the possible relationship between coronary vasomotor function and the transcardiac gradient of adiponectin, reflecting adiponectin utilization and/or accumulation in the coronary vascular bed. The epicardial diameter and blood flow response of the left anterior descending coronary artery to intracoronary infusions of ACh was analyzed in 108 consecutive subjects who had a normal coronary angiogram and left ventriculogram. Adiponectin levels were measured by ELISA in plasma obtained from the aortic root (Ao) and the anterior interventricular vein (AIV). Adiponectin levels in the AIV were lower than levels in the Ao. In multivariate linear regression analysis, the transcardiac gradient of adiponectin (Ao - AIV levels) showed a positive correlation with increases in epicardial coronary diameter and coronary blood flow in response to ACh that was independent of traditional coronary risk factors. The transcardiac gradient of adiponectin was not significantly associated with the coronary dilator response to isosorbide dinitrate and the coronary flow response to sodium nitroprusside. In other groups of patients with coronary spastic angina (n = 41) or microvascular angina (n = 32) who had impaired coronary vasomotor responses, there was no significant gradient of adiponectin between the Ao and AIV. The transcardiac gradient of adiponectin may modulate endothelial vasomotor function in large and resistance coronary arteries and may play a role in the pathogenesis of diseases presenting with coronary vasomotor dysfunction.     

Regional transcranial oximetry with near infrared spectroscopy (NIRS) in comparison with measuring oxygen saturation in the jugular bulb in infants and children for monitoring cerebral oxygenation]

Using a dual channel near infrared (NIR) in vivo optical spectroscopy (INVOS) system (INVOS 3100A, Somanetics Corp. Troy, MI, USA) we investigated the relationship between jugular venous oxygen saturation (SjvO2) and regional cerebral oxygen saturation (rSO2) in 30 infants and children (mean age 4.5 years) with congenital heart disease undergoing cardiac catheterisation. The NIRS-SomaSensor (emitter and dual receiver probe) was applied at a standardised right fronto-temporal location (over the right frontal cortex) on the infant's head and covered with an adhesive flexible bandage. Using NIR light (730 and 810 nm) and two source-detector spacings (3 and 4 cm from the transmitter), percentage values of rSO2 were calculated from detected haemoglobin saturations. Simultaneously, jugular venous oxygen saturation (SjvO2) monitoring was performed via a catheter placed in the right internal jugular vein with its tip positioned in the jugular bulb, as verified by fluoroscopy. To compare the reliability of NIRS measurement characteristics, jugular venous blood was analysed for SjvO2 as a reference measure of global cerebral oxygenation, by co-oximetry (OSM3-Hemoximeter, Radiometer Copenhagen, Denmark). Other measured variables included pulse oximetry, arterial blood pressure, and venous and arterial oxygen saturations. Over a jugular venous oxygen saturation range of 31-83%, a significant positive linear correlation was found between rSO2 (NIRS measurement) and SjvO2 (jugular bulb oximetry) (r = 0.93, p < 0.001). No significant correlation was observed between rSO2 values and arterial blood saturation or pulse oximetry. The quantitative correlation between rSO2 (haemoglobin oxygenation in a small hemi-elliptical area of the brain) and reference SjvO2 measurement (method for monitoring global cerebral oxygenation) suggests that NIRS measurement with subtraction algorithm should identify predominantly intracranial saturation in the pediatric age group, and will tend to reflect global oxygenation under physiological conditions. Transcranial oximetry using dual receiving channel NIRS offers a noninvasive, real-time, reliable and practicable means of monitoring cerebral haemoglobin oxygenation changes infants and children with cyanotic and noncyanotic congenital heart disease.     

Hyperbaric oxygen solution infused into the anterior interventricular vein at reperfusion reduces infarct size in swine

This study was designed to test the hypothesis that raising myocardial O2 via diffusion of a hyperbaric oxygen solution (AO) administered through the anterior interventricular vein (AIV) will reduce infarct size by reducing reperfusion injury associated with reduced neutrophil activation. In three pilot open-chest swine experiments, myocardial tissue Po2 was monitored using an oxygen probe during coronary occlusion (Occl) and reperfusion (Rep). One control experiment had no AIV infusion; a second control received arterial blood drawn from the femoral artery infused into the AIV during Rep. In a third open-chest experiment, AO mixed with arterial blood was infused through the AIV at Rep. In controls, tissue Po2 in the risk region (RR) rose early in Rep and then fell to Occl levels, whereas in AO-treated animals, myocardial Po2 remained above baseline. The following three groups of five swine then underwent 60 min of left anterior descending coronary artery Occl and Rep: 1) arterial blood infused at Rep as controls (Con), 2) AO infused beginning 30 min after Rep (AO 30 min), and 3) AO infused immediately at Rep (AO 0 min). There were no differences among the three groups in hemodynamics or myocardial blood flow during baseline (BL) or Occl or in RR size. However, endocardial blood flow was significantly higher in RR during Rep in AO 0 min vs. control and AO 30 min (P=0.01). Both infarct size (IS) as %heart and IS as %RR were lower in AO 0 min compared with Con and AO 30 min (P <0.01 for both), and myeloperoxidase values were lower for epicardial (P <0.001), midmyocardial (P=0.03), and endocardial (P <0.001) layers in AO 0 min. AO infused into the AIV immediately at Rep diffuses into the RR and reduces IS by reducing Rep injury associated with neutrophil activation.     

Long-term preservation of myocardial energetic in chronic hibernating myocardium

We previously reported that the myocardial energetic state, as defined by the ratio of phosphocreatine to ATP (PCr/ATP), was preserved at baseline (BL) in a swine model of chronic myocardial ischemia with mild reduction of myocardial blood flow (MBF) 10 wk after the placement of an external constrictor on the left anterior descending coronary artery. It remains to be seen whether this stable energetic state is maintained at a longer-term follow-up. Hibernating myocardium (HB) was created in minipigs (n = 7) by the placement of an external constrictor (1.25 mm internal diameter) on the left anterior descending coronary artery. Function was assessed with MRI at regular intervals until 6 mo. At 6 mo, myocardial energetic in the HB was assessed by (31)P-magnetic resonance spectrometry and myocardial oxygenation was examined from the deoxymyoglobin signal using (1)H-magnetic resonance spectrometry during BL, coronary vasodilation with adenosine, and high cardiac workload with dopamine and dobutamine (DpDb). MBF was measured with radiolabeled microspheres. At BL, systolic thickening fraction was significantly lower in the HB compared with remote region (34.4 ± 9.4 vs. 50.1 ± 10.7, P = 0.006). This was associated with a decreased MBF in the HB compared with the remote region (0.73 ± 0.08 vs. 0.97 ± 0.07 ml · min(-1) · g, P = 0.03). The HB PCr/ATP at BL was normal. DpDb resulted in a significant increase in rate pressure product, which caused a twofold increase in MBF in the HB and a threefold increase in the remote region. The systolic thickening fraction increased with DpDb, which was significantly higher in the remote region than HB (P < 0.05). The high cardiac workload was associated with a significant reduction in the HB PCr/ATP (P < 0.02), but this response was similar to normal myocardium. Thus HB has stable BL myocardial energetic despite the reduction MBF and regional left ventricular function. More importantly, HB has a reduced contractile reserve but has a similar energetic response to high cardiac workload like normal myocardium.     

Effect of endurance training on coronary artery size and function in healthy men: an invasive followup study

In eight healthy male volunteers (cardiologists; age 36 +/- 5 yr), bicycle spiroergometry, Doppler echocardiography, and quantitative coronary angiography with intracoronary Doppler measurements before and after completion of a physical endurance exercise program of >5 mo duration were performed. Maximum oxygen uptake increased from 46 +/- 6 to 54 +/- 5 ml x kg(-1) x min(-1) (P = 0.04), maximum ergometric workload changed from 3.8 +/- 0.3 to 4.4 +/- 0.3 W/kg (P = 0.001), and left ventricular mass index increased from 82 +/- 18 to 108 +/- 29 g/m(2) (P = 0.001). The right, left main, and left anterior descending coronary artery cross-sectional area increased significantly in response to exercise. Before versus at the end of the exercise program, flow-induced left anterior descending coronary artery cross-sectional area was 10.1 +/- 3.5 and 11.0 +/- 3.9 mm(2), respectively (P = 0.03), nitroglycerin-induced left coronary calibers increased significantly, and coronary flow velocity reserve changed from 3.8 +/- 0.8 to 4.5 +/- 0.7 (P = 0.001). Left coronary artery correlated significantly with ventricular mass and maximum oxygen uptake, and coronary flow velocity reserve was significantly associated with maximum workload.     

The anti-ischemic action of a perfluorocarbon emulsion (PFCE) on the canine myocardium

On the 60th minute after inducing the acute ischemia in the canine myocardium by the occlusion of the left anterior descending coronary artery, the animals were intravenously infused with perfluorochemical emulsion (PFCE), its salt composition (SC) or 4% surface-active substance (SAS), proxanol, at a dose of 10 ml/kg. Two hours after infusion, the occlusion was removed (reperfusion). The arterial pO2 was maintained at 120 mm Hg. Analysis of the blood flow, oxygen supply, acid-alkali balance, ECG, as well as creatine phosphokinase activity, measured in the ischemic area, has shown that PFC emulsion is capable of reducing ischemic damage and preventing reperfusion-induced myocardium injury. Thus, the presence of perfluorochemicals in the PFC emulsion is an essential factor in its ischemia-protective effect.     

Wall shear stress in normal left coronary artery tree

Despite the fact that the role of wall shear stress (WSS) as a local mechanical factor in atherogenesis is well established, its distribution over the entire normal human left coronary artery (LCA) tree has not yet been studied. A three-dimensional computer generated model of the epicardial LCA tree, based on averaged human data set extracted from angiographies, was adopted for finite-element analysis of the Navier-Stokes flow equations treating blood as non-Newtonian fluid. The LCA tree includes the left main coronary artery (LMCA), the left anterior descending (LAD), the left circumflex artery (LCxA) and their major branches. In proximal LCA tree regions where atherosclerosis frequently occurs, low WSS appears. Low WSS regions occur at bifurcations in regions opposite the flow dividers, which are anatomic sites predisposed for atherosclerotic development. On the LMCA bifurcation, at regions opposite to the flow divider, dominant low WSS values occur ranging from 0.75 to 2.25 N/m2. High WSS values are encountered at all flow dividers. This work determines, probably for the first time, the topography of the WSS in the entire normal human LCA epicardial tree. It is also the first work determining the spatial WSS differentiation between proximal and distal normal human LCA parts. The haemodynamic analysis of the entire epicardial LCA tree further verifies the implications of the WSS in atherosclerosis mechanisms.     

Coronary smooth muscle reactivity to muscarinic stimulation after ischemia-reperfusion in porcine myocardial infarction.

This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine (n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion (n = 12), LAD deendothelization (n = 11), or a sham operation (n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin (n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 +/- 4.6 to 1.9 +/- 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 +/- 7.0 to 3.4 +/- 3.9 ml/min), with a significant delay in recovery (P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.