Coronary Blood Flow Response Research Articles

Coronary microvascular dysfunction after elective percutaneous coronary intervention: Correlation with exercise stress test results

ObjectivesWe assessed whether exercise stress test (EST) results are related to the presence of coronary microvascular dysfunction (CMVD) in patients undergoing elective percutaneous coronary intervention (PCI). BackgroundPrevious studies showed that EST is poorly reliable in predicting restenosis after PCI; some studies also showed CMVD in the territory of the treated vessel. MethodsWe studied 29 patients (age 64±6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the left anterior descending (LAD) coronary artery, undergoing successful PCI with stent implantation. EST and assessment of coronary microvascular function were performed 24h, 3months and 6months after PCI. Coronary blood flow (CBF) response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography. ResultsPatients with ST-segment depression ≥1mm at EST performed 24h after PCI (n=11, 38%) showed a lower CBF response to adenosine compared to those with negative EST (1.65±0.4 vs. 2.11±0.4, respectively, p=0.003), whereas the difference in CBF response to CPT was not significant (1.44±0.4 vs. 1.64±0.3, respectively; p=0.11). At 3-month and 6-month follow-up a positive EST was found in 12 (41%) and 13 (44%) patients, respectively; patients with positive EST also had lower CBF response to adenosine compared to those with negative EST (3months: 1.69±0.3 vs. 2.20±0.3, respectively; 6months: 1.66±0.2 vs. 2.32±0.3, respectively; p<0.001 for both). ConclusionsPositive EST after elective successful PCI consistently reflects impairment of hyperemic CBF due to CMVD, which persists over a follow-up period of 6months.

The Long-Term Effect of Coronary Stenting on Epicardial and Microvascular Endothelial Function

Coronary stents, drug-eluting stents in particular, have been linked to coronary epicardial endothelial dysfunction after implantation. However, less is known about their impact on coronary microvascular function and their long-term effects on the vasculature. We evaluated 71 patients (mean age, 53.0±10.1 years) with chest pain and angiographically nonsignificant coronary artery disease 17.1±17.1 months after left anterior descending coronary artery stenting. Seventy-one age- and sex-matched patients (mean age, 53.0±10.3 years) with chest pain but no prior coronary intervention served as controls. Coronary blood flow in response to the endothelium-dependent vasodilator acetylcholine as well as the microvascular (endothelium-independent) coronary flow reserve in response to intracoronary adenosine were evaluated. Quantitative coronary angiography was used to study epicardial diameter changes to acetylcholine. Microcirculatory function was not significantly different between the stenting and control groups (median [interquartile range] coronary flow reserve, 2.9 [2.5-3.4] versus 3.0 [2.4-3.4] mL/min, P=0.24; change of coronary blood flow, 34.9% [-34.4% to 90.0%] versus 54.7% [-5.6% to 104.6%], P=0.18). Both groups exhibited epicardial endothelial dysfunction (-23.0% [-47.4% to -7.6%] versus -20.0% [-40.0% to 0.0%], P=0.4). Results did not differ between patients with drug-eluting stents (n=46) and patients with bare-metal stents (n=24). This study demonstrates that in patients with coronary arteries in which a stent has been placed, coronary microcirculatory and epicardial vascular function are not significantly different from that of an age- and sex-matched population with similar symptoms but nonsignificant coronary artery disease.

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels

We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1) channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple coronary blood flow to metabolism are not fully understood. We employed mice lacking TRPV1 [TRPV1((-/-))], db/db diabetic, and control C57BKS/J mice to determine the extent to which TRPV1 channels modulate coronary function and contribute to vascular dysfunction in diabetic cardiomyopathy. Animals were subjected to in vivo infusion of the TRPV1 agonist capsaicin to examine the hemodynamic actions of TRPV1 activation. Capsaicin (1-100 μg·kg(-1)·min(-1)) dose dependently increased coronary blood flow in control mice, which was inhibited by the TRPV1 antagonist capsazepine or the nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (L-NAME). In addition, the capsaicin-mediated increase in blood flow was attenuated in db/db mice. TRPV1((-/-)) mice exhibited no changes in coronary blood flow in response to capsaicin. Vasoreactivity studies in isolated pressurized mouse coronary microvessels revealed a capsaicin-dependent relaxation that was inhibited by the TRPV1 inhibitor SB366791 l-NAME and to the large conductance calcium-sensitive potassium channel (BK) inhibitors iberiotoxin and Penetrim A. Similar to in vivo responses, capsaicin-mediated relaxation was impaired in db/db mice compared with controls. Changes in pH (pH 7.4-6.0) relaxed coronary vessels contracted to the thromboxane mimetic U46619 in all three groups of mice; however, pH-mediated relaxation was blunted in vessels obtained from TRPV1((-/-)) and db/db mice compared with controls. Western blot analysis revealed decreased myocardial TRPV1 protein expression in db/db mice compared with controls. Our data reveal TRPV1 channels mediate coupling of myocardial blood flow to cardiac metabolism via a nitric oxide-dependent, BK channel-dependent pathway that is corrupted in diabetes.

106 Role of neuronal vs endothelial nitric oxide synthase in the coronary blood flow response to pacing

BackgroundEndothelial nitric oxide synthase (eNOS) has been assumed to be the major source of nitric oxide (NO) regulating human coronary blood flow (CBF). In recent first-in-human studies with a neuronal...

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

Coronary Microvascular Function and Cortical Pain Processing in Patients With Silent Positive Exercise Testing and Normal Coronary Arteries

ST-segment depression during exercise stress testing in asymptomatic subjects showing normal coronary arteries is considered a "false-positive" result. Coronary microvascular dysfunction, however, might be a possible cause of ST-segment depression in these cases. We assessed the coronary blood flow response to adenosine and to cold pressor test in the left anterior descending artery, using transthoracic Doppler echocardiography in 14 asymptomatic subjects with exercise-induced ST-segment depression and normal coronary arteries (group 1), 14 patients with microvascular angina (group 2), and 14 healthy subjects (group 3). Flow-mediated dilation was assessed in the brachial artery. Central pain processing was assessed using cortical laser evoked potentials during chest and right hand stimulation with 3 sequences of painful stimuli. The coronary blood flow response to adenosine was 1.8 ± 0.4, 1.9 ± 0.5, and 3.1 ± 0.9 in groups 1, 2, and 3, respectively (p <0.001). The corresponding coronary blood flow responses to the cold pressor test were 1.74 ± 0.4, 1.53 ± 0.3, and 2.3 ± 0.6 (p <0.001). The flow-mediated dilation was 5.5 ± 2.3%, 4.6 ± 2.4%, and 9.8 ± 1.2% in the 3 groups, respectively (p <0.001). The laser evoked potential N2/P2 wave amplitude decreased throughout the 3 sequences of stimulation in groups 1 and 3 but not in group 2 (chest, -19 ± 22%, +11 ± 42% and -36 ± 12%, p <0.001; right hand, -22 ± 25%, +12 ± 43% and -30 ± 20%, p = 0.009; in groups 1, 2, and 3). In conclusion, exercise stress test-induced ST-segment depression in asymptomatic subjects with normal coronary arteries cannot be considered as a simple false-positive result, because it can be related to coronary microvascular dysfunction. The different symptomatic state compared to patients with microvascular angina can, at least in part, be explained by differences in cortical processing of neural pain stimuli.

Aging attenuates the coronary blood flow response to cold air breathing and isometric handgrip in healthy humans

The purpose of this echocardiography study was to measure peak coronary blood flow velocity (CBV(peak)) and left ventricular function (via tissue Doppler imaging) during separate and combined bouts of cold air inhalation (-14 ± 3°C) and isometric handgrip (30% maximum voluntary contraction). Thirteen young adults and thirteen older adults volunteered to participate in this study and underwent echocardiographic examination in the left lateral position. Cold air inhalation was 5 min in duration, and isometric handgrip (grip protocol) was 2 min in duration; a combined stimulus (cold + grip protocol) and a cold pressor test (hand in 1°C water) were also performed. Heart rate, blood pressure, O(2) saturation, and inspired air temperature were monitored on a beat-by-beat basis. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, and CBV(peak) was used as an index of myocardial O(2) supply. The RPP response to the grip protocol was significantly blunted in older subjects (Δ1,964 ± 396 beats·min(-1)·mmHg) compared with young subjects (Δ3,898 ± 452 beats·min(-1)·mmHg), and the change in CBV(peak) was also blunted (Δ6.3 ± 1.2 vs. 11.2 ± 2.0 cm/s). Paired t-tests showed that older subjects had a greater change in the RPP during the cold + grip protocol [Δ2,697 ± 391 beats·min(-1)·mmHg compared with the grip protocol alone (Δ2,115 ± 375 beats·min(-1)·mmHg)]. An accentuated RPP response to the cold + grip protocol (compared with the grip protocol alone) without a concomitant increase in CBV(peak) may suggest a dissociation between the O(2) supply and demand in the coronary circulation. In conclusion, older adults have blunted coronary blood flow responses to isometric exercise.

Functional contribution of P2Y1receptors to the control of coronary blood flow

Activation of ADP-sensitive P2Y(1) receptors has been proposed as an integral step in the putative "nucleotide axis" regulating coronary blood flow. However, the specific mechanism(s) and overall contribution of P2Y(1) receptors to the control of coronary blood flow have not been clearly defined. Using vertically integrative studies in isolated coronary arterioles and open-chest anesthetized dogs, we examined the hypothesis that P2Y(1) receptors induce coronary vasodilation via an endothelium-dependent mechanism and contribute to coronary pressure-flow autoregulation and/or ischemic coronary vasodilation. Immunohistochemistry revealed P2Y(1) receptor expression in coronary arteriolar endothelial and vascular smooth muscle cells. The ADP analog 2-methylthio-ADP induced arteriolar dilation in vitro and in vivo that was abolished by the selective P2Y(1) antagonist MRS-2179 and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. MRS-2179 did not alter baseline coronary flow in vivo but significantly attenuated coronary vasodilation to ATP in vitro and in vivo and the nonhydrolyzable ATP analog ATPγS in vitro. Coronary blood flow responses to alterations in coronary perfusion pressure (40-100 mmHg) or to a brief 15-s coronary artery occlusion were unaffected by MRS-2179. Our data reveal that P2Y(1) receptors are functionally expressed in the coronary circulation and that activation produces coronary vasodilation via an endothelium/nitric oxide-dependent mechanism. Although these receptors represent a critical component of purinergic coronary vasodilation, our findings indicate that P2Y(1) receptor activation is not required for coronary pressure-flow autoregulation or reactive hyperemia.

Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X

The causes of coronary microvascular dysfunction (CMVD) in patients with cardiac syndrome X (CSX) are largely unknown. Common cardiovascular risk factors (CVRFs) and increased markers of inflammation have been associated with CMVD in some studies, but their role in determining CMVD in CSX patients remains poorly known. We studied 71 CSX patients (56 ± 9 years, 23 men) and 20 healthy volunteers (52 ± 7 years, nine men). Using transthoracic Doppler echocardiography, coronary microvascular vasodilator function was assessed in the left anterior descending coronary artery as the ratio of diastolic coronary blood flow (CBF) velocity at peak intravenous adenosine administration and during cold pressor test (CPT) to the respective basal CBF velocity values. Common CVRFs tended to be more frequent and C-reactive protein (CRP) levels were higher (P < 0.001) in CSX patients than in controls. Both CBF responses to adenosine (2.05 ± 0.6 vs. 2.92 ± 0.9, P < 0.001) and to CPT (1.71 ± 0.6 vs. 2.42 ± 0.7, P < 0.001) were lower in CSX patients than in controls. The differences between the two groups in CBF response to adenosine and in CBF response to CPT remained highly significant (P < 0.01 for both) after adjustment for all CVRFs, including serum CRP levels. In CSX patients, both endothelium-dependent and endothelium-independent CMVD cannot be reliably predicted by CVRFs (including serum CRP levels), alone or in combination.

Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function

Background and aimsTo assess the effects of bariatric surgery (BS) on peripheral endothelial function and on coronary microvascular dilator function. Methods and resultsWe studied 50 morbidly obese patients (age 38 ± 9, 13 M) who underwent BS and 20 comparable obese controls (age 41 ± 11, 6 M) without any evidence of cardiovascular disease. Peripheral vascular dilator function was assessed by brachial artery diameter changes in response to post-ischemic forearm hyperaemia (flow-mediated dilation, FMD). Coronary microvascular function was assessed by measuring coronary blood flow (CBF) velocity response to i.v. adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery by transthoracic Doppler echocardiography. The tests were performed at baseline and at 3-month follow-up. At baseline, FMD and CBF response to adenosine and CPT were similar in the 2 groups. Compared to baseline, FMD at follow-up improved significantly in BS patients (5.9 ± 2.7% to 8.8 ± 2.4%, p < 0.01), but not in controls (6.3 ± 3.2% vs. 6.4 ± 3.1%, p = 0.41). Similarly, a significant improvement of CBF response to adenosine (1.63 ± 0.47 to 2.45 ± 0.57, p < 0.01) and to CPT (1.43 ± 0.26 to 2.13 ± 0.55, p < 0.01) was observed in BS patients but not in controls (1.55 ± 0.38 vs. 1.53 ± 0.37, p = 0.85; and 1.37 ± 0.26 vs. 1.34 ± 0.21, p = 0.48, respectively). The favourable vascular effects of BS were similar independently of the presence and changes of other known cardiovascular risk factors and of basal values and changes of serum C-reactive protein levels. ConclusionsOur data show that, in morbidly obese patients, together with peripheral endothelial function, BS also improves coronary microvascular function. These effects suggest global improvement of vascular function which can contribute significantly to the reduction of cardiovascular risk by BS reported in previous studies.

Acetylcholine acutely modifies nitric oxide synthase function in the human coronary circulation

Intracoronary infusions of acetylcholine (ACh) and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) are routinely used to assess endothelial function in the human coronary circulation. Currently, there are no studies that examine whether the response to one of these agents predicts the response to the other in a given individual. We sought to determine whether human coronary vasomotor responses to intracoronary ACh are predictive of the response to intracoronary l-NMMA. Following diagnostic coronary angiography, a coronary sinus catheter was placed. Sequential intracoronary infusions of ACh and l-NMMA were performed in 14 patients without severe coronary artery disease (CAD). In nine patients with severe CAD, only l-NMMA was infused. Quantitative coronary angiography was performed immediately following infusions to determine changes in coronary diameter. Coronary sinus oxygen saturation and the transcardiac oxygen saturation gradients were determined during infusions as an index of coronary blood flow (CBF). There were no significant differences in the prevalence of hypertension, diabetes, smoking or plasma creatinine or cholesterol levels between patients with and without severe CAD. In the 14 patients without severe CAD, ACh reduced coronary diameter on average by 8% (from 2.7 ± 0.8 to 2.5 ± 0.8 mm, P = 0.003) and reduced the transcardiac oxygen saturation gradient from 63 ± 8 to 42 ± 16% (P = 0.0001). N(G)-Monomethyl-l-arginine had no significant effect on coronary diameter (from 2.7 ± 0.8 to 2.7 ± 0.8 mm, n.s.) and did not alter the transcardiac oxygen saturation gradient (from 63 ± 8 to 63 ± 7%, n.s.). A positive rather than negative correlation was observed between the ACh- and l-NMMA-induced changes in coronary diameter (r = 0.752, P = 0.0002). In nine patients with severe CAD who did not receive ACh, l-NMMA had no effect on coronary diameter but produced an increased transcardiac oxygen saturation gradient consistent with reduced CBF (from 58 ± 5 to 62 ± 4%, P = 0.003). The CBF response to l-NMMA was significantly different between the two groups (P = 0.002). The failure of l-NMMA to reduce CBF following ACh infusion, in contrast to the results seen in the l-NMMA-only group, suggests that NOS had been rendered dysfunctional by the ACh infusion itself. The positive correlation in changes to coronary diameter between ACh and l-NMMA suggests that the degree of NOS dysfunction was directly correlated to the degree of preceding activation by ACh. Combined, these unexpected results suggest that ACh administration may acutely modify the function of NOS in the human coronary circulation.

Long-Term Administration of Endothelin Receptor Antagonist Improves Coronary Endothelial Function in Patients With Early Atherosclerosis

Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET(A)) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET(A) receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10(-6) to 10(-4) mol/L) in the left anterior descending coronary artery. N(G)-monomethyl-l-arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus -2.22%, 95% confidence interval -27.37% to 15.28%; P<0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N(G)-monomethyl-l-arginine were similar between the groups at baseline and at 6 months. This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271492.

Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo

The effect of a novel free radical scavenger, edaravone, on coronary endothelial dysfunction was examined in patients who had no significant stenosis of coronary arteries, to elucidate the role of free radicals on coronary endothelial dysfunction. The coronary blood flow (CBF) responses to acetylcholine (ACh) were measured by quantitative coronary arteriography and the intracoronary Doppler technique before and after the administration of edaravone. Twenty-four patients were divided into two groups on the basis of CBF responses to ACh; those with "attenuated" (%Delta CBF < 300%, n = 12) and "normal" (%Delta CBF > 300%, n = 12) flow responses. An intracoronary infusion of edaravone significantly improved ACh-induced increases in CBF in patients with attenuated flow responses; however, edaravone had no effect in those with normal flow responses (36.8% +/- 7.3% vs 0.0% +/- 5.1%, P < 0.01). The plasma levels of nitric oxide compounds (NOx) in the attenuated response group were lower than those in the normal group (35.7 +/- 2.3 vs 49.4 +/- 6.2 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.566, P < 0.01). The plasma level of malondialdehyde and 4-hydroxynonenal, which indicates the level of oxidative stress, in the attenuated group was higher than that in the normal group (6.9 +/- 0.9 vs 3.3 +/- 0.5 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.854, P < 0.01). A free radical scavenger improved the ACh-induced CBF response in patients with coronary atherosclerosis in vivo. Therefore, the current results suggest that scavenging free radicals has a beneficial effect for patients with coronary endothelial dysfunction.

The muscle metaboreflex: reining in the heart?

the muscle metaboreflex, also known as the muscle chemoreflex, is one of the principal mediators of the cardiovascular exercise response. This reflex is thought to be triggered by metabolic by-products of ischemia that stimulate afferent nerve endings in skeletal muscle and leads to an increase in

Enhanced coronary ET‐1 responsiveness and altered K+ channel Ca2+ sensitivity in aortic‐banded miniature swine is attenuated by aerobic interval training

Altered responsiveness to mediators of vascular tone is observed in several models of congestive heart failure (HF). Recent evidence indicates exercise training is beneficial for patients with HF but the precise intensity and underlying mechanisms are unknown. The purpose of this study was to examine coronary vascular function (CVF) in aortic‐banded (AB) sedentary (HFSED, n=6), AB exercise trained (HFTR, n=5) and control sedentary (SED, n=5) male Yucatan miniature swine. In vivo coronary blood flow (CBF) responses to intracoronary infusion of ET‐1 (1–20 ng/kg/min) and adenosine (ADO; 0.5–5 ug/kg) were measured in the left anterior descending coronary artery (LAD) under anesthesia. Resting CBF was reduced and coronary vascular resistance (CVR) increased (p&lt;0.05) in HFSED animals. The diminished CBF response to ADO in HFSED was attenuated with exercise training and occurred despite unaltered capillarization. ET‐1 induced reductions in conductance (p≤0.05) and increases in resistance (p=0.056) were greater in HFSED vs. SED and HFTR groups. A shift from 200 to 500 nM internal Ca2+ increased total K+ current (whole‐cell voltage clamp) in HFTR and SED but not HFSED LAD smooth muscle cells. In conclusion, interval exercise training attenuates increased basal CVR in AB miniature swine. Increased in vivo ET‐1 and altered K+ channel Ca2+ sensitivity potentially underlie altered CVF. NIH HL093982 &amp; HL52490

Impaired coronary artery vasodilation during skin surface cooling in healthy older adults

Cardiovascular‐related mortality increases in the cold winter months, particularly in older adults. To determine whether coronary artery blood flow responses to skin surface cooling differ with age, we studied 9 young (25±1 yrs) and 10 older healthy adults (65±2 yrs). We hypothesized that left anterior descending coronary artery blood velocity (CBV) responses, measured using Doppler transthoracic echocardiography, to skin surface cooling (15–18° C water perfused suit for 20 min) would be impaired with age. We found that cooling increased left ventricular wall stress, a determinant of myocardial oxygen consumption, in young (185.6±6.5 to 202.9 ±10.4 mmHg, P &lt; 0.05) and older adults (189.1±8.8 vs. 222.7±14.7 mmHg, P &lt; 0.01) although the magnitude of this response was twofold greater in older adults (Δ9.13±3.48% vs. Δ17.62±3.24%, young and older, respectively; P=0.09). Despite increased left ventricular wall stress during cooling in young and older adults CBV increased only in the young (20.86±1.32 to 25.56±1.24 cm/s, p&lt;0.01) and not older group (17.60±1.09 to 19.93 ±0.97 cm/s, p=0.11). These data suggest that an impaired coronary vasodilator response to cold stress may contribute to age‐dependent increases in cardiovascular‐related mortality during the winter months in healthy adults.Support: NIH HL92309, AG24420 and M01 RR10732

Delivery of Glycoprotein IIb/IIIa Inhibitor Therapy for Percutaneous Coronary Intervention

A major goal of any antithrombotic regimen administered during percutaneous coronary intervention (PCI) is the preservation of coronary microvascular perfusion, which is critical for myocardial survival. In addition to macrovascular thrombosis, microembolization into the downstream coronary artery bed that occurs during spontaneous plaque rupture and PCI plays a prominent role in the development of microvascular dysfunction that leads to myocardial infarction. In addition to physical obstruction of the lumen by the embolus, vasoconstriction and edema due to inflammation also impair microvascular flow.1 These events likely occur more frequently during PCI performed in the setting of unstable coronary syndromes.2 With Doppler guidewire technology, it was estimated that an average of 25 embolic events occurred during primary PCI for ST-segment elevation myocardial infarction.3 Article see p 784 Platelet aggregates are important components of coronary microemboli, along with leukocytes, erythrocytes, platelet-leukocyte aggregates, cholesterol crystals, and hyalin. Platelets and leukocytes within microemboli play a particularly important role in the pathophysiological changes of blood flow by promoting in situ microvascular thrombosis, vasoconstriction, and inflammation. Interestingly, the composition of the embolized material is similar in the settings of spontaneous and catheter-induced plaque rupture.1 In animal models, distal microembolization of inert microspheres is associated with an immediate reduction in flow due to vessel occlusion, followed by enhanced blood flow due to the effects of adenosine released from the embolized myocardium into the adjacent noninvolved myocardium.4 Microembolization results in overall reduced flow reserve and the progressive loss of contractile function, which often reverses within weeks. The degree of myocardial contractile dysfunction is disproportionate to the degree of infarction and is the result of inflammation.5 However, in the clinical condition, a more complex pathophysiology exists due to the influence of multiple components of the emboli. Platelets aggregate when fibrinogen binds to the active …

Impaired coronary microvascular endothelial function in men with metabolic syndrome

To assess coronary endothelial function of conduit and resistance vessels in patients with metabolic syndrome (MS). Seventy-eight men (mean age, 57 years) with chest pain and angiographically normal coronary arteries were included in the study. Patients with coronary spastic angina were excluded. Changes in coronary artery diameter and coronary blood flow (CBF) in response to acetylcholine (ACh) were determined using quantitative coronary angiography and Doppler velocity measurements. Coronary flow reserve was calculated as the ratio of coronary blood velocity after adenosine triphosphate infusion relative to baseline values. Patients were divided into two groups based on the presence or absence of MS. There were 24 patients in the MS group (31%). The increase in CBF in response to ACh infusion was impaired in the MS group (P < 0.0001) compared to the non-MS group, whereas changes in coronary artery diameter in response to ACh infusion did not differ between the two groups. Multivariate regression analysis revealed that MS was a significant factor associated with the lesser change in CBF induced by ACh infusion at 30 μg/min (P < 0.0001, r(2) = 0.46). Coronary endothelial dysfunction was present at the level of resistance vessels but not conduit vessels in the MS patients included in our study.

Relationship between coronary endothelial function and coronary calcification in early atherosclerosis

BackgroundThe relationship between coronary endothelial function and coronary calcification is not well established. MethodsForty-six patients 17 men [37%]; age, 47.4±11.4 years prospectively underwent testing for coronary endothelial function and measurement of coronary artery calcification (CAC). ResultsLog CAC scores were not significantly different between patients with normal (n=31) and abnormal (n=15) response of epicardial coronary artery diameter to acetylcholine (%CADAch) (median (25, 75 percentile) 1.1 (0.0, 3.7) vs. 0.3 (0.0, 2.4), P=.32) and with normal (n=28) and abnormal (n=18) response of coronary blood flow to acetylcholine (%CBFAch) (0.5 (0.0, 3.6) vs. 0.5 (0.0, 3.2), P=.76). Log CAC scores did not correlate with %CADAch (r=0.08, P=.59), %CBFAch (r=0.14, P=.35). ConclusionsIn patients without significant coronary artery disease, coronary endothelial dysfunction showed no apparent association with coronary calcification. Our findings suggest that these 2 markers may represent separate, independent processes in the progression of coronary atherosclerosis.

Endothelial and Non-Endothelial Coronary Blood Flow Reserve and Left Ventricular Dysfunction in Systemic Hypertension

OBJECTIVES:We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease.INTRODUCTION:Coronary blood flow reserve reduction has been proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction.METHODS:Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS). Group 1 (FS ≥0.25): n=8, FS=0.29 ± 0.03; Group 2 (FS <0.25): n=10, FS= 0.17 ± 0.03.RESULTS:Baseline coronary blood flow was similar in both groups (Group 1: 80.15 ± 26.41 mL/min, Group 2: 100.09 ± 21.51 mL/min, p=NS). In response to adenosine, coronary blood flow increased to 265.1 ± 100.2 mL/min in Group 1 and to 300.8 ± 113.6 mL/min (p <0.05) in Group 2. Endothelium-independent coronary blood flow reserve was similar in both groups (Group 1: 3.31 ± 0.68 and Group 2: 2.97 ± 0.80, p=NS). In response to acetylcholine, coronary blood flow increased to 156.08 ± 36.79 mL/min in Group 1 and to 177.8 ± 83.6 mL/min in Group 2 (p <0.05). Endothelium-dependent coronary blood flow reserve was similar in the two groups (Group 1: 2.08 ± 0.74 and group Group 2: 1.76 ± 0.61, p=NS). Peak acetylcholine/peak adenosine coronary blood flow response (Group 1: 0.65 ± 0.27 and Group 2: 0.60 ± 0.17) and minimal coronary vascular resistance (Group 1: 0.48 ± 0.21 mmHg/mL/min and Group 2: 0.34 ± 0.12 mmHg/mL/min) were similar in both groups (p= NS). Casual diastolic blood pressure and end-systolic left ventricular stress were independently associated with FS.CONCLUSIONS:In our hypertensive patients, endothelium-dependent and endothelium-independent coronary blood flow reserve vasodilator administrations had similar effects in patients with either normal or decreased left ventricular systolic function.