Epicardial Coronary Blood Flow Research Articles

Coronary flow reserve and microcirculatory resistance in patients with coronary tortuosity and without atherosclerosis.

ObjectiveCoronary tortuosity may affect epicardial coronary arterial blood flow. This study aimed to investigate the effect of coronary tortuosity on coronary flow reserve and the coronary microcirculation in patients without apparent coronary atherosclerosis.MethodsProspective patients (n = 8, 3 men, mean age: 58 ± 6.0 years) with coronary tortuosity and without apparent coronary atherosclerosis were enrolled. Coronary tortuosity was defined by the finding of ≥three bends (defined as a ≥45° change in vessel direction) along the main trunk of the left anterior descending artery or left circumflex artery. Coronary flow reserve and the index of microcirculatory resistance were measured by the thermodilution technique.ResultsA total of eight coronary arteries with coronary tortuosity were analyzed. The mean fractional flow reserve was 0.98 ± 0.007. The mean coronary flow reserve was 1.5 ± 0.3, which is much lower than that in the normal coronary artery as reported in the literature. The mean index of microcirculatory resistance was 26.7 ± 2.3, which is much higher than that in the normal coronary artery.ConclusionsCoronary tortuosity is associated with decreased coronary flow reserve and an increased index of microcirculatory resistance.Trial registration: This study is registered at the Chinese Clinical Trial Registry, NCT No: ChiCTR2000033671

The role of RIPK3-regulated cell death pathways and necroptosis in the pathogenesis of cardiac ischaemia-reperfusion injury.

Despite advancements in management of acute myocardial infarction, this disease remains one of the leading causes of death. Timely reestablishment of epicardial coronary blood flow is the cornerstone of therapy; however, substantial amount of damage can occur as a consequence of cardiac ischaemia/reperfusion (I/R) injury. It has been previously proposed that the pathway leading to major cell death, apoptosis, is responsible for cardiac I/R injury. Nevertheless, there is compelling evidence to suggest that necroptosis, a programmed necrosis, contributes remarkably to both myocardial injury and microcirculatory dysfunction following cardiac I/R injury. Receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL) are shown as the major mediators of necroptosis. In addition to the traditional perception that RIPK1/RIPK3/MLKL-dependent plasma membrane rupture is fundamental to this process, several RIPK3-related pathways such as endoplasmic reticulum stress and mitochondrial fragmentation have also been implicated in cardiac I/R injury. In this review, reports from both in vitro and in vivo studies regarding the roles of necroptosis and RIPK3-regulated necrosis in cardiac I/R injury have been collectively summarized and discussed. Furthermore, reports on potential interventions targeting these processes to attenuate cardiac I/R insults to the heart have been presented in this review. Future investigations adding to the knowledge obtained from these previous studies are needed in the pursuit of discovering the most effective pharmacological agent to improve cardiac I/R outcomes.

Circulating miR-320a as a Predictive Biomarker for Left Ventricular Remodelling in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention.

Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR.

Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction.

Early mechanical reperfusion of the epicardial coronary artery by primary percutaneous coronary intervention (PCI) is the guideline-recommended treatment for ST-elevation myocardial infarction (STEMI). Successful restoration of epicardial coronary blood flow can be achieved in over 95% of PCI procedures. However, despite angiographically complete epicardial coronary artery patency, in about half of the patients perfusion to the distal coronary microvasculature is not fully restored, which is associated with increased morbidity and mortality. The exact pathophysiological mechanism of post-ischaemic coronary microvascular dysfunction (CMD) is still debated. Therefore, the current review discusses invasive and non-invasive techniques for the diagnosis and quantification of CMD in STEMI in the clinical setting as well as results from experimental in vitro and in vivo models focusing on ischaemic-, reperfusion-, and inflammatory damage to the coronary microvascular endothelial cells. Finally, we discuss future opportunities to prevent or treat CMD in STEMI patients.

P2706Persistent impairment of coronary endothelial vasomotor responses is related to atheroma plaque progression in the infarct-related coronary artery of AMI survivors

Abstract Background Although coronary endothelial vasomotor dysfunction predicts future coronary events, there are few human studies showing the relationship between endothelial vasomotor dysfunction and atheroma plaque progression in the same coronary artery. Purpose This study examined whether endothelial vasomotor dysfunction is related with atheroma plaque progression in the infarct-related coronary artery of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessment of coronary plaque size with intravascular ultrasound (IVUS) and coronary vasomotor responses to acetylcholine (ACh). Methods This study included 50 patients with a first acute STEMI due to occlusion of left anterior descending coronary artery (LAD) and successful reperfusion therapy with percutaneous coronary intervention (PCI). IVUS and vasomotor response to ACh in the LAD were measured within 2 weeks after AMI (1st test) and repeated 6 months (2nd test) after AMI under optimal anti-atherosclerotic therapies. The impairment of vasomotor response to ACh was defined as <10% of the responses to ACh in 25 control subjects. Results Percent atheroma volume (PAV) and total atheroma volume (TAV) in the LAD progressed over 6 months of follow-up in 18 and 14 patients, respectively. Epicardial coronary artery dilation and coronary blood flow increase in response to ACh were persistently impaired at both the 1st and 2nd tests in 18 and 19 patients. In logistic regression analysis, the progression of PAV and TAV was significantly associated with patients with the persistent impairment of epicardial coronary diameter and blood flow response to ACh (PAV, OR, 6.2 [95% CI, 1.4–28], P=0.02 and 4.3 [1.2–16], P=0.03, respectively. TAV, 6.0 [1.4–26], P=0.02 and 5.5 [1.4–21], P=0.01, respectively). The progression of PAV and TAV had no significant association with the coronary vasomotor responses to ACh at the 1st test, traditional risk factors, PCI-related variables, medications, and the coronary vasomotor responses to sodium nitroprusside, an endothelium-independent vasodilator. Conclusions Persistent impairment of endothelial vasomotor function in the conduit arterial segment and the resistance arteriole was related to atheromatous plaque progression in the infarct-related coronary arteries of STEMI survivors despite optimized anti-atherosclerotic therapies. Acknowledgement/Funding None

Persistent Dysfunction of Coronary Endothelial Vasomotor Responses is Related to Atheroma Plaque Progression in the Infarct-Related Coronary Artery of AMI Survivors.

Aim: Although coronary endothelial vasomotor dysfunction predicts future coronary events, there are few human studies showing the relationship between endothelial vasomotor dysfunction and atheroma plaque progression in the same coronary artery. This study examined whether endothelial vasomotor dysfunction is related to atheroma plaque progression in the infarct-related coronary artery of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessment of coronary plaque size with intravascular ultrasound (IVUS) and coronary vasomotor responses to acetylcholine (ACh).Methods: This study included 50 patients with a first acute STEMI due to occlusion of the left anterior descending coronary artery (LAD) and successful reperfusion therapy with percutaneous coronary intervention (PCI). IVUS and vasomotor response to ACh in the LAD were measured within two weeks of acute myocardial infarction (AMI) (1st test) and repeated six months (2nd test) after AMI under optimal anti-atherosclerotic therapies.Results: Percent atheroma volume (PAV) and total atheroma volume (TAV) in the LAD progressed over six months of follow-up in 18 and 14 patients, respectively. PAV and TAV progression was significantly associated with persistent impairment of epicardial coronary artery dilation and coronary blood flow increase in response to ACh at both the 1st and 2nd tests. PAV and TAV progression had no significant association with traditional risk factors, PCI-related variables, medications, and the coronary vasomotor responses to sodium nitroprusside, an endothelium-independent vasodilator.Conclusions: Persistent impairment of endothelial vasomotor function in the conduit arterial segment and the resistance arteriole was related to atheromatous plaque progression in the infarct-related coronary arteries of STEMI survivors.

Microvascular obstruction in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: another frontier to conquer?

Over the past decades, a significant reduction in mortality due to ST elevation myocardial infarction (STEMI) has been observed worldwide (1,2). Prompt restoration of the epicardial coronary blood flow with timely primary percutaneous coronary intervention (PCI), as well as adjunctive pharmacological therapies have largely reduced the myocardial infarct size and improved short- and longterm outcomes (3,4). Nevertheless, residual cardiovascular risk persists after STEMI.

TCT-723 Clinical and Angiographic Predictors of No-Reflow Phenomenon in ST Segment Elevation Myocardial Infarction Treated with Successful Primary Percutaneous Intervention

In ST segment elevation myocardial infarction (STEMI) primary percutaneous coronary intervention remains the optimal treatment modality to restore normal epicardial coronary artery blood flow. However, despite successful PCI a small, but still significant proportion of patients continue to present

Cardiovascular magnetic resonance profiling of coronary atherosclerosis: vessel wall remodelling and related myocardial blood flow alterations.

To determine the association between coronary vessel wall morphology and haemodynamic consequences to the myocardium using a combined cardiovascular magnetic resonance (CMR) imaging protocol. Non-invasive CMR profiling of coronary atherosclerotic wall changes and related myocardial blood flow impairment has not been established yet. Sixty-three patients (45 men, 61.5 ± 10.7 years) with suspected or known coronary artery disease underwent 3.0 Tesla CMR imaging. The combined CMR protocol consisted of the following imaging modules at rest: 3D vessel wall imaging and flow measurement of the proximal right coronary artery (RCA), myocardial T2*, and first-pass perfusion imaging. During adenosine stress coronary flow, T2* and first-pass perfusion imaging were repeated. Coronary X-ray angiography classified patient groups: (i) all-smooth (n = 19); (ii) luminal irregular (diameter reduction < 30%; n = 35); and (iii) stenosed RCA (diameter reduction ≥ 50%; n = 9). The ratio of CMR-derived vessel wall area-to-lumen area significantly increased stepwise for the comparison of all-smooth vs. luminal irregular vs. stenosed RCA (1.9 ± 0.6 vs. 2.6 ± 0.6 vs. 3.6 ± 0.9, P < 0.01). Epicardial coronary flow reserve exhibited a stepwise significant decrease (3.4 ± 0.5 vs. 2.9 ± 0.7 vs. 1.7 ± 0.3, P < 0.01). On the myocardial level, stress-induced percentage gain of T2* values (ΔT2*) was significantly decreased between groups (29.2 ± 10.6 vs. 9.0 ± 9.8 vs. 2.2 ± 11.8%, P < 0.01) while perfusion reserve index decreased in the presence of stenosed RCA only (2.2 ± 0.6 vs. 2.0 ± 0.4 vs. 1.3 ± 0.3, P = ns and P < 0.01, respectively). The proposed comprehensive CMR imaging protocol provided a non-invasive approach for direct assessment of coronary vessel wall remodelling and resultant pathophysiological consequences on the level of epicardial coronary and myocardial blood flow in patients.

Effect of Statin Pretreatment on Myocardial Perfusion in Patients Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta‐analysis

To achieve sufficient myocardial perfusion in ST-segment elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PPCI), many adjunctive therapies have been proposed. Previous trials have reported variances in myocardial perfusion improvement for statin pretreatment, which made it inconvincible to confirm the beneficial effects of statins. Therefore, we performed a systematic review and meta-analysis to determine whether statin pretreatment was effective in improving myocardial perfusion. Statin pretreatment could improve myocardial perfusion in STEMI patients undergoing PPCI. We searched the PubMed, Web of Knowledge, and the Cochrane Library databases for studies evaluating the impact of statin pretreatment on myocardial perfusion in STEMI patients receiving PPCI. Twelve trials were finally included in our meta-analysis. There were no significant differences in patients' baseline characteristics between the statin pretreatment and control groups. Overall pooled analysis showed that patients in the statin pretreatment groups had significantly better epicardial coronary blood flow (measured by Thrombosis in Myocardial Infarction [TIMI] grade, odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.28 to 0.84; measured by corrected TIMI frame count, mean difference: -5.63; 95% CI: -9.66 to -1.6). A trend toward myocardial tissue level perfusion improvement was seen in the statin pretreatment arm rather than the control arm (measured by myocardial blush grade, OR: 0.74; 95% CI: 0.50 to 1.09). This present meta-analysis suggests that statin pretreatment might be effective in improving myocardial perfusion in STEMI patients.

Clinical, angiographic, and intravascular ultrasound predictors of early stent thrombosis in patients with acute myocardial infarction

Risk factors reported for early stent thrombosis (EST) included acute coronary syndrome, suboptimal antiplatelet therapy, procedural factors such as residual dissection and underexpansion of stents, and smaller final lumen area and inflow/outflow disease (residual stenosis or dissection) by intravascular ultrasound (IVUS) [1–4]. However, the predictors of EST including all variables such as baseline characteristics, laboratory data, angiographic and IVUS findings in patients with acute myocardial infarction (AMI) are still not well known. From January 2007 to December 2009, we identified 418 consecutive patients with a first AMI who underwent pre-percutaneous coronary intervention (PCI) IVUS within 24 h from symptom onset, were stented successfully, and had post-PCI IVUS imaging. EST included acute (b24 h) and subacute ST (1 to 30 days) after stent implantation. Cardiac-specific troponin I (cTnI) levels were measured by a paramagnetic particle, chemiluminescent immunoenzymatic assay (Beckman, Coulter Inc., Fullerton, California). No-reflow was defined as postPCI TIMI grade 0, 1, or 2 flow. Tissue prolapse was defined as tissue extrusion through the stent strut at post-PCI. The baseline characteristics, angiographic and IVUS findings are summarized in Table 1. EST occurred in 16 patients (3.8%). Glycoprotein IIb/IIIa inhibitor was used more frequently in patients with EST compared with those without EST. Pre-PCI peak creatine kinase-MB and cTnI were significantly higher in patients with EST compared with those without EST. Pre-PCI TIMI flow grade was significantly lower in patients with EST compared with those without EST. More stents were deployed in patients with EST compared with those without EST. Noreflow during or after PCI was developed more frequently in EST group than in non-EST group (87.5% vs. 12.2%, p b 0.001). Plaque burden at the minimum lumen site was significantly greater in patients with EST compared with those without EST. Pre-PCI plaque rupture and IVUSdetected thrombuswere observedmore frequently in patients with EST compared with those without EST. Post-stenting tissue prolapse was observed more frequently in patients with EST compared with those without EST (68.8% vs. 32.6%, p= 0.003). Independent predictors of EST are summarized in Table 2. Multivariate analysis showed that noreflow, pre-PCI peak cTnI, and tissue prolapse were the independent predictors of EST. No-reflow can occur easily in lesions with various kinds of vulnerable plaque including plaque rupture and thrombus and this no-reflow is associated with microvascular damage which is likely to slow the epicardial coronary blood flow and to stagnate blood flow which may accelerate local thrombus formation [5]. The mechanism underlying the association between pre-PCI peak cTnI level and EST is not clear, although cTnI is associated with high thrombus grade with promoted thrombus formation in patients with AMI, who already have heightened systemic and intracoronary platelet reactivity, thrombin generation, and inflammation. Tissue prolapse may represent a source for thrombus accumulation in an environment that already has a high potential for thrombogenesis. Impaired arterial healing and ST have been associated with the prolapse of the necrotic core between stent struts. This is especially relevant in the setting of AMI, because such patients already have an increased risk for this devastating event [6]. In conclusion, the incidence of EST after stenting of infarct-related arteries was 3.8%. No-reflow, pre-PCI peak cTnI and tissue prolapse were associated with the development of EST after stent implantation in patients with AMI.

The effect of distal coronary embolization on infarct size in a porcine acute myocardial infarction model

Background Reperfusion no-reflow (R-NR), characterized by TIMI 0/1 flow grade, is a phenomenon that occurs in up to 20% of percutaneous coronary intervention cases for acute myocardial infarction (AMI). R-NR involves reduced myocardial tissue perfusion in the presence of a reperfused and patent epicardial coronary artery. This phenomenon is associated with worse patient outcome and increased mortality. Potential contributing factors of R-NR include the initial ischemic insult, injury as a result of reperfusion, and possibly distal coronary embolization (DCE) of thrombotic material. The objective of this study was to develop a novel large animal model to investigate the effects of DCE in the setting of ischemia-reperfusion using microthrombi derived from autologous porcine blood. Methods 3.0 T CMR was performed on 25-30kg female Yorkshire pigs to determine baseline values of cardiac function, as well as the myocardial perfusion territory at risk using direct intracoronary injection of dilute GadoliniumDTPA. Pigs were then subjected to balloon occlusion mediated myocardial ischemia distal to the second diagonal branch of the left anterior descending coronary artery (LAD) for 60 minutes. Following reperfusion, intracoronary injection of sterile saline (n=4) or microthrombi particles to simulate DCE (n=7) was performed. Epicardial coronary blood flow was assessed at each stage using x-ray angiography. At 72 hours following ischemia-reperfusion, CMR was used to assess changes in cardiac function, extent of edema/hemorrhage using T2/T2* relaxation times, evaluate infarct size, and to determine the presence/absence of microvascular obstruction (MVO). Myocardial tissue samples were subsequently collected for biochemical and histological analysis.

Unique Morphological Variations of Transient Midventricular Syndrome: A Case Series‐Review

Older individuals (especially women) enduring an inciting emotional or physical event are prone to developing left ventricular ballooning syndrome. Ballooning of apical distribution is the most common type. However, a midventricular variant is increasingly reported. As this variant becomes further delineated, we describe a case series in which various morphological patterns of midleft ventricular segments are seen. Each case involves a female patient with a presumptive diagnosis of acute coronary syndrome, who upon further cardiac workup demonstrated normal epicardial coronary blood flow. Subsequent cardiac imaging, including transthoracic echocardiography, revealed unique midventricular dilation and akinesis, with preserved or hypercontractility of the basal and apical segments. However, more unique to this, was the fact that the left ventricular regional wall motion abnormalities were of either "symmetric" ballooning morphology, involving all mid segments of the left ventricle; or more dramatically, "asymmetric" ballooning morphology, which involves abnormal regional motion of only a focal left ventricular wall. Furthermore, we review current literature on midventricular ballooning and propose likely mechanisms and optimal treatment strategies in the face of potential complications of midventricular ballooning syndrome.

Adenosine transport, erythrocyte deformability and microvascular dysfunction: An unrecognized potential role for dipyridamole therapy

Reperfusion injury and no-reflow phenomenon are known entities that contribute to persistent impairment in myocardial perfusion and regional myocardial dysfunction following restoration of epicardial coronary blood flow after a myocardial infarction. Following prolonged ischemia, oxidative stress and inflammation-mediated alterations in erythrocyte mechanics and microvascular architecture play a major role in ischemia/reperfusion injury and no-reflow phenomenon. An increase in red cell rigidity is an important rheological aspect of RBCs, which facilitates platelet aggregation with the subendothelium. Dipyridamole inhibits the reuptake of adenosine which causes platelet inhibition and vasodilatation. Dipyridamole improves microvascular function by increasing RBC deformability and reducing blood viscosity. In addition, it has anti-oxidant and anti-inflammatory properties that provide protection to the microvasculature. This review discusses the potential role for dipyridamole therapy in the treatment of microvascular dysfunction.

Treatment of Acute Myocardial Infarction With Sirolimus-Eluting Stents Results in Chronic Endothelial Dysfunction in the Infarct-Related Coronary Artery

Sirolimus-eluting stent (SES) implantation aggravated endothelial vasomotor dysfunction in infarct-related coronary arteries. This study examined the effect of SES implantation on the duration of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and on postinfarct left ventricular dysfunction in acute myocardial infarction (AMI). Patients with a first AMI due to occlusion of the left anterior descending coronary artery and successful reperfusion using SES (n=15) or bare metal stents (BMS; n=18) were examined. The vasomotor response of the left anterior descending coronary artery to acetylcholine and left ventriculography were examined 2 weeks and 6 months after AMI. At 6 months after AMI, the impairment of epicardial coronary artery dilation and coronary blood flow increase in response to acetylcholine was recovered from 2 weeks after AMI in BMS-treated patients, whereas the responses of SES-treated patients improved but remained impaired compared with BMS-treated patients (% increase in blood flow, 77+/-12% in SES versus 116+/-15% in BMS at 10 microg/min of acetylcholine, P<0.01). Left ventricular regional wall dysfunction in the left anterior descending coronary artery territory improved from 2 weeks to 6 months after AMI in BMS-treated patients but not in SES-treated patients (% improvement of average SD/chord, 6% in SES versus 19% in BMS, P<0.05), although left ventricular global ejection fraction was similar between the groups at any time points. SES implantation may delay recovery of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and left ventricular regional dysfunction for at least 6 months after AMI.

1032 Prognostic impact of contrast-enhanced CMR early after acute ST-segment elevation myocardial infarction (STEMI) in a regional STEMI network

Introduction In acute ST-segment elevation myocardial infarction (STEMI), rapid restoration of epicardial coronary blood flow and myocardial perfusion limits infarct size and improves survival. Primary percutaneous coronary intervention (PCI) is superior to systemic fibrinolysis when instantly performed by experienced operators. The Herzinfarktverbund Essen (HIVE) is an urban STEMI network supporting direct patient transfer for primary PCI to 4 PCI centers covering a city area of 600.000 inhabitants. Integrated health care is an optional part of the HIVE allowing for reimbursement of medical innovations such as the evaluation of infarct size and the presence and extent of microvascular obstruction by contrast-enhanced CMR.

Myocardial contrast echocardiography in ST elevation myocardial infarction: ready for prime time?

Acute myocardial infarction (AMI) continues to be a significant public health problem in industrialized countries and an increasingly significant problem in developing countries. ST elevation myocardial infarctions (STEMI) constitute approximately 40% of all AMIs with approximately 670,000 cases yearly in the United States alone. The risk of further cardiac complications such as re-infarction, sudden death, and heart failure for those who survive AMI is substantial. Thus, early assessment and risk stratification during the acute phase of STEMI is important. Furthermore, it is essential to assess the efficacy early after any initial therapeutic intervention, not only to facilitate further management, but also to enable development of new treatment algorithms/approaches to further improve the outcome. The aim of reperfusion therapy in AMI is not only to rapidly restore epicardial coronary blood flow but also to restore perfusion at the microcirculatory level. Myocardial contrast echocardiography (MCE) which utilizes microbubbles can assess myocardial perfusion in real time. Its ability to assess myocardial perfusion and function in one examination allows it to ascertain the extent of myocardial reperfusion achieved in the risk area. Furthermore, in stable patients after AMI, MCE allows assessment of LV function, residual myocardial viability, and ischaemia which are all powerful prognostic markers of outcome. Its portability, rapid acquisition and interpretation of data, and the absence of radiation exposure make it an ideal bedside technique.

Effect of Percutaneous Coronary Intervention on Coronary Blood Flow at Rest in Myocardial Sites Remote from the Intervention Site in Patients With Stable Angina Pectoris

Little is known about changes in myocardial perfusion of myocardial regions supplied by angiographically normal or near-normal coronary arteries after percutaneous coronary intervention (PCI) of the target lesion. The purpose of this study was to assess the effect of PCI on coronary blood flow at rest in sites remote from the PCI. We studied 85 patients who underwent successful elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction frame count to provide a simple continuous index of coronary flow and myocardial perfusion in the target and nontarget arteries. Coronary artery diameters of nontarget vessels did not significantly differ before and after PCI and at 6 months' follow-up. At baseline, the greater the percent diameter stenosis in the target artery, the slower the flow in the target (r = 0.22, p <0.01) and nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not account for simultaneous changes in epicardial coronary blood flow of the nontarget artery. After 6 months, coronary blood flow improved in both the target (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided evidence of a functional link between coronary blood flow in diseased and nondiseased arteries. Relief of a significant stenosis using PCI globally improved regional and global myocardial blood flow at rest in patients with stable angina. Flow improvement was not apparent at the time of revascularization, but at 6 months' follow-up. Late upturn of the microcirculation may account for delayed recovery of myocardial perfusion.

Plasma asymmetric dimethylarginine and L-arginine levels in patients with cardiac syndrome X

Endothelial dysfunction and subsequently impaired microvascular circulation are the leading mechanisms in the development of cardiac syndrome X (CSX). The study evaluated the plasma asymmetric dimethylarginine (ADMA) and L-arginine levels of the patients with CSX and the control group and aimed to determine any relationship between these parameters and epicardial coronary blood flow and myocardial tissue perfusion. The study group consisted of 32 patients (mean age: 52.6+/-9.4 years, 14 men) with typical exertional angina, positive exercise test, and normal coronary arteries diagnosed as CSX. Plasma ADMA, L-arginine levels, and L-arginine/ADMA ratio were compared with the values of the control group, which consisted of 17 age-matched and sex-matched individuals. Concentrations of L-arginine and ADMA were measured by high-performance liquid chromatography. In all the coronary territories, epicardial coronary flow was assessed by thrombolysis in myocardial infarction (TIMI) frame count (TFC) method, and tissue level perfusion, by myocardial blush grade (MBG) method. A MBG score less than 3 was considered an impaired myocardial perfusion, and a MBG score of '3' in all the coronary territories, a normal myocardial perfusion. The plasma ADMA levels of the study group were higher than those of the control group (0.83+/-0.38 vs. 0.55+/-0.44 micromol/l, P=0.03), whereas plasma L-arginine levels were similar in both groups (70.25+/-21.89 vs. 76.09+/-18.22 micromol/l, P=0.36), resulting in a diminished L-arginine/ADMA ratio in the patients with CSX [82.3 (60.2-128.8) vs. 242.2 (76.7-386.4), P=0.003]. In CSX group, the patients with abnormal myocardial tissue perfusion had increased plasma ADMA levels compared with those with normal tissue perfusion (0.99+/-0.37 vs. 0.69+/-0.34 micromol/l, P=0.02), whereas plasma L-arginine levels were similar in both groups. No correlations were observed between TFC values and plasma ADMA, L-arginine levels, and L-arginine/ADMA ratio. Plasma ADMA levels, however, were negatively correlated with MBG scores (r=-0.349, P=0.014). We have shown for the first time that in the patients with CSX, increased plasma ADMA levels might be associated with impaired myocardial tissue perfusion when assessed by MBG.

ICAM-1 in Acute Myocardial Infarction: A Potential Therapeutic Target

Current treatments for AMI centre on prompt restoration of epicardial coronary blood flow. Despite improvements, AMI is still associated with significant morbidity and mortality. Novel approaches are therefore keenly sought. Intercellular adhesion molecule-1 (ICAM-1, CD54) is a member of the immunoglobulin superfamily. It is implicated in neutrophil and monocyte-endothelial cell adhesion, processes contributing to myocardial neutrophil infiltration and microvascular coronary slow flow, both viewed as important to the pathophysiologic responses in AMI. ICAM-1 would therefore appear an important potential therapeutic target in this context, and is the subject of this review.