Reduction In Luminal Diameter Research Articles

Abstract 3308: New Doppler Ultrasound Criteria for Renal Artery In-Stent Restenosis

Background: Renal artery Doppler ultrasound (DUS) has been well established as an effective non-invasive screening tool for renal artery stenosis in native renal arteries. Stent placement alters the elastic properties of arteries and would be expected to decrease arterial compliance resulting in higher DUS velocities than non-stented arteries. To date, no criteria have been established for detecting in-stent restenosis (ISR) with DUS. Purpose: To establish the optimal DUS parameters to detect hemodynamically significant renal artery in-stent restenosis. Methods: We included consecutive patients (N=68) with clinically suspected renal artery ISR. Each patient underwent DUS and quantitative renal angiography that were blindly interpreted. Pearson’s correlation coefficients of 0.80 to 0.87 (P<0.0001) suggested strong agreement among observers. Significant ISR was defined as ≤ 70% reduction of in-stent luminal diameter when compared to the nearest normal reference segment. Angiographic criteria were compared to the renal artery peak systolic velocity (PSV) and the renal-aortic ratio (RAR) from corresponding DUS measurements. Receiver Operating Characteristic curves were constructed using PSV and RAR as continuous variables to determine the DUS parameters with the highest sensitivity and specificity for detecting ISR. Results: There was a statistically significant correlation for both PSV and RAR in detecting ISR as defined by quantitative angiography (P<0.0001). PSV>325 cm/sec and RAR>4.9 were most predictive of angiographically significant ISR, while a combination of the two criteria resulted in a greater sensitivity and specificity than either one alone. Conclusion: Renal artery Doppler ultrasound is an effective screening tool for renal artery in-stent restenosis. A PSV of 325 cm/sec and a RAR of 4.9 are most predictive of angiographic in-stent restenosis, with a combination of the two criteria offering the greatest sensitivity and specificity. DUS DETECTION OF ≥70% RENAL ARTERY IN-STENT RESTENOSIS (ISR)

Clinical Utility of Cardiac Troponin I in the Diagnosis of Acute Coronary Syndrome in Patients With Renal Failure

To analyze sensitivity and specificity of cardiac troponin I (cTnI) in detecting obstructive coronary artery disease in African American population with renal insufficiency presenting with acute coronary syndrome. Retrospective analysis of 108 patients who underwent coronary angiography over a 3-year period in a single institution. A troponin I level of 0.1 ng/mL or higher was considered abnormal troponin I. Renal insufficiency was defined as creatinine of 1.2 mg/dL or higher. Obstructive coronary artery disease (CAD) was defined as luminal diameter reduction of 70% or more (or total occlusion) in at least 1 coronary artery. Patients were divided into group 1 (renal insufficiency without need for hemodialysis, n = 76, mean age = 65) and group 2 (patients requiring hemodialysis, n = 32, mean age = 60). Access Accu TnI method was used to quantitate cTnI where murine monoclonal antibodies specifically bind to the C-terminal end of cTnI. In group 1, 41 (54%) patients had abnormal troponin of whom 37 (90%) had CAD and 4 (10%) had normal angiogram; 35 (46%) patients had normal troponin, of whom 25 (71%) had CAD and 10 (29%) had normal angiogram yielding a sensitivity of 60% and specificity of 71% (P = 0.003; 95% confidence interval). In group 2, 20 (63%) had abnormal troponin of whom 19 (95%) had CAD and 1(5%) had normal angiogram; 12 (38%) had normal troponin of whom 7 (59%) had CAD and 5 (41%) had normal angiogram yielding a sensitivity of 73% and specificity of 83% (P = 0.06; 95% confidence interval). cTnI has a sensitivity of 60% and specificity of 71% in acute coronary syndrome patients with renal insufficiency. In patients on hemodialysis, troponin I has a sensitivity of 73% and specificity of 83% for detection of obstructive CAD.

Simultaneous echocardiographic evaluation of coronary flow velocity reserve and aortic distensibility indices in hypertension

The coronary flow velocity reserve (CFVR), a measure of endothelial function in coronary circulation, can be measured semi-invasively in the left anterior descending coronary artery by using stress transesophageal echocardiography (TEE). During the same stress TEE, aortic distensibility indices (elastic modulus [E(p)] and Young's circumferential static elastic modulus [E(s)]) can be assessed. The purpose of the present study was to examine whether stress TEE is valuable method for parallel evaluation of CFVR, E(p), and E(s) in patients with hypertension. A total of 38 patients with chest pain but with a negative coronary angiogram were enrolled into the present study, which included examination of the presence or absence of hypertension. Significant coronary stenosis was considered present in the event of a luminal diameter reduction of >50% on use of the "worst view method." Patients with significant coronary or valvular heart disease, atrial fibrillation, heart failure, unstable angina pectoris, acute myocardial infarction, or diabetes mellitus were excluded from the study. Stress TEE was performed in each case to evaluate CFVR, E(p), and E(s). Coronary flow velocity reserve and diastolic coronary flow velocities measured at peak stress were decreased in hypertensive patients as compared with normotensive subjects. E(p) and E(s) were significantly increased in hypertensive patients. In conclusion, it can be stated that Stress TEE is a useful tool for the simultaneous evaluation of the CFVR, E(p), and E(s) in hypertension. The CFVR and aortic distensibility are decreased in hypertension.

Is cardiac computed tomography a reliable alternative to percutaneous coronary angiography for patients awaiting valve surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether a CT angiogram could replace routine percutaneous coronary angiography for excluding coronary arterial disease for patients undergoing a non coronary cardiac procedure. Using the reported search 595 papers were identified. Eleven papers represented the best evidence on the subject and the author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated. We conclude that angiography with 64-slice multi-detector CT scanner provides reliable non-invasive imaging to exclude significant coronary artery stenoses prior to valve surgery. The negative predictive value of a normal CT scan is around 97%, thus providing a good alternative to conventional angiography in lower atherosclerotic risk patients. The ability of CT angiography to assess the reduction in luminal diameter is reduced in the presence of calcium deposits, and is also reduced in vessels under 1.5 mm. Further disadvantages include an inability to perform scans in patients with arrhythmias or atrial fibrillation, and a five times increased radiation dose compared to conventional angiography.

Clinical Utility of Multislice Computed Tomographic Angiography for Detection of Cerebral Vasospasm in Acute Subarachnoid Hemorrhage

Digital subtraction angiography (DSA) has been used as the standard method for detecting cerebral vasospasm after subarachnoid hemorrhage (SAH). Multislice computed tomographic angiography (CTA) is a relatively recent method used for evaluating the vasculature of the intracranial arteries. The purpose of this study was to compare multislice CTA and DSA for the detection and quantification of cerebral vasospasm after SAH, and to analyze the usefulness of multislice CTA. Eight patients with SAH underwent initial CTA with DSA within 72 hours after the onset of symptoms and follow-up multislice CTA and DSA 8 to 48 days after SAH. Five arterial locations were established in the A1 and A2 segments of the anterior cerebral artery, the M1 and M2 segments of the middle cerebral artery and the posterior cerebral artery (PCA) on both multislice CTA and DSA images. Vasospasm was classified as none, mild (up to 30% reduction in luminal diameter), moderate (31-60% reduction), and marked (at least 60% reduction) using the scale of Schneck and Kricheff. The multislice CT system used the following parameters: 1.25 mm collimation and 3.75 pitch with a 4-channel system. The degree of vasospasm revealed by the multislice CTA was significantly correlated with the degree of vasospasm revealed by DSA. In general, most discrepancies between CTA and DSA were in the detection of mild and moderate vasospasm. We found that the consistency between multislice CTA and DSA was greater for mild (100%, n=3) or moderate (100%, n=3) vasospasm than none (n=1) or marked vasospasm (n=1). However, it was unclear whether multislice CTA was more specific for a proximal location (A1, M1, PCA) or distal location (A2, M2) for evaluation of cerebral arteries. Multislice CTA can detect angiographic vasospasm after SAH with an accuracy similar to that of DSA. Multislice CTA is highly sensitive, specific and accurate in detecting mild and moderate cerebral vasospasm. It is less accurate for detecting no vasospasm and marked vasospasm. Therefore, the authors propose that multislice CTA be considered as a useful tool for the detection and management of intracranial vasospasm after SAH.

Determination of interobserver variability for identifying inducible left ventricular wall motion abnormalities during dobutamine stress magnetic resonance imaging

To determine the interobserver variability for identifying inducible left ventricular (LV) wall motion abnormalities during high-dose dobutamine/atropine stress cardiovascular magnetic resonance (DSMR). Four readers from various institutions were supplied with the image data from 150 consecutive DSMR examinations and asked to grade wall motion and image quality throughout graded doses of dobutamine infusion administered to achieve 85% of the maximum age-predicted heart rate. Inducible ischaemia was identified if more than one segment demonstrated a new or worsening LV wall motion abnormality, and significant stenosis was defined as > or =50% luminal diameter reduction by quantitative contrast coronary angiography. Seventy-seven patients (51%) had luminal narrowings > or =50%. Diagnostic performance (sensitivity, specificity, diagnostic accuracy) of all readers was 78.2, 87.0 and 82.5%. Disagreement between two readers occurred in every seventh examination. Agreement on the presence or absence of inducible wall motion abnormalities was moderate (mean kappa value 0.59, range 0.52-0.76). Diagnostic performance and disagreement were independent of the presence of luminal narrowings > or =50% or the number of diseased coronary vessels. Image quality was regarded excellent in 89.3% of standard views. In the setting of multiple observers from different institutions performing a diagnostic reading of DSMR examinations carried out at a single centre, the interobserver variability was low for identifying inducible LV wall motion abnormalities indicative of coronary arterial luminal narrowings > or =50%.

Prevalence and Risk Factors of Intracranial Atherosclerosis in an Asymptomatic Korean Population

Background and PurposeIntracranial atherosclerosis (ICAS) is one of the major risk factors for ischemic stroke, particularly in Asian populations. We investigated the prevalence and risk factors of ICAS in asymptomatic subjects.MethodsWe prospectively evaluated 835 asymptomatic Korean adults who voluntarily visited a tertiary referral hospital for a health screening examination that included brain magnetic resonance angiography. The subjects had no history of stroke or transient ischemic attacks; those who had potential cardiac sources of emboli were excluded. ICAS and extracranial atherosclerosis were defined as a reduction in luminal diameter of at least 50%. Vascular risk factors were screened through questionnaires, interviews, and examinations.ResultsICAS was found in 25 subjects (3.0%) and extracranial atherosclerosis was found in 4 patients (0.5%). No patient had combined lesions. ICAS was distributed in 31 arteries in 25 subjects: anterior cerebral arteries (5 subjects, 16%), middle cerebral arteries (16 subjects, 52%), posterior cerebral arteries (8 subjects, 26%), and distal internal carotid arteries (2 subjects, 7%). The ratio of ICAS of the anterior circulation (23 of 31 arteries with ICAS, 74%) to that of the posterior circulation (8 of 31 arteries with ICAS, 26%) was 3:1. The ratio of ICAS (23 of 27 arteries with atherosclerosis in the anterior circulation, 85%) to extracranial atherosclerosis (4 of 27 arteries with therosclerosis in the anterior circulation, 15%) was 6:1. An older age [odds ratio (OR)=1.05, 95% confidence interval (CI)=1.00-1.10] and hypertension (OR=2.41, 95% CI=1.01-5.72) were independent risk factors for ICAS.ConclusionsICAS is more prevalent than extracranial atherosclerosis among neurologically asymptomatic Korean adults. Subjects with ICAS are significantly older and have an increased frequency of hypertension compared to those subjects without atherosclerotic stenosis.

Perfusion Impairment in Patients with Normal-appearing Coronary Arteries: Identification with Contrast-enhanced MR Imaging

To prospectively determine the feasibility of using first-pass magnetic resonance (MR) imaging to distinguish between myocardial segments in patients with coronary artery disease (CAD) of different degrees of obstruction and those in patients with normal-appearing coronary arteries. The study was approved by the institutional ethics committee, and all patients provided informed consent. First-pass contrast material-enhanced MR imaging was performed at rest and after the infusion of dipyridamole in 37 patients (29 men, eight women; mean age, 57.2 years +/- 10.5 [standard deviation]) who had positive exercise test results or a clinical history of CAD. Myocardial segments were divided into five groups according to the degree of obstruction in the supplying artery. Signal intensity upslope, peak signal intensity, and time to peak signal intensity, as well as hyperemia-to-rest (HR) ratios for each of these three variables, were analyzed for each segment by using a generalized linear model. Signal intensity upslope in patients with normal coronary arteries at angiography was significantly higher than that in patients with CAD (P < .001). Signal intensity upslope for segments in patients without CAD was significantly different from that for normal-appearing segments in patients with CAD (P < .001). Signal intensity upslope (P < .05) and peak signal intensity (P < .01) enabled the differentiation of segments with more than 70% reduction in luminal diameter from those in all other groups. HR ratios demonstrated findings that were similar to those obtained by using each signal intensity variable alone. First-pass MR imaging can be used to distinguish segments with different degrees of obstructive CAD. Importantly, MR imaging can help identify segments with impaired perfusion and normal-appearing coronary arteries in patients with CAD and can demonstrate obstructive lesions in other territories.

Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients with stable angina pectoris

Multislice computed tomography (CT) is an emerging technique for the non-invasive detection of coronary stenoses. While the diagnostic accuracy of 4-slice scanners was limited, 16-slice CT imagers showed promising results due to increased temporal and spatial resolution. These technical advances prompted us to evaluate the diagnostic performance of 64-slice CT coronary angiography in the detection of significant stenoses (defined as > or = 50% luminal diameter reduction) versus invasive quantitative coronary angiography (QCA). Thirty-five patients with stable angina pectoris underwent CT coronary angiography performed with a 64-slice scanner (gantry rotation time 330 ms, individual detector width 0.6 mm) prior to conventional coronary angiography. Patients with heart rates >70 beats/min received 100 mg metoprolol orally. One hundred millilitres of contrast agent with an iodine concentration of 400 mgl/ml were injected at a rate of 5 ml/s into the antecubital vein. The CT scan was triggered with the bolus tracking technique. The sensitivity, specificity and the positive and negative predictive values of 64-slice CT were 99%, 96%, 78% and 99%, respectively, on a per-segment basis. The values obtained on a per-patient basis were 100%, 90%, 96% and 100%, respectively. When referral to catheterisation is questionable, CT coronary angiography may identify subjects with normal angiograms and consistently decrease the number of unnecessary invasive procedures.

Dobutamine stress echocardiography and cardiac troponin T for the detection of significant coronary artery disease and predicting outcome in renal transplant candidates

Ischaemic heart disease is the leading cause of mortality and morbidity in patients with end-stage renal disease (ESRD) and after renal transplantation. However, the optimal non-invasive test for coronary artery disease (CAD) diagnosis in this population has yet to be established. The aim of this study was to assess the diagnostic accuracy of dobutamine stress echocardiography (DSE) and baseline plasma cardiac troponin T (cTnT) for detecting significant CAD and predicting adverse cardiac events in patients referred for renal transplantation. Coronary angiography, DSE, and baseline cTnT measurements were performed in 118 consecutive patients (mean age 52+/-12 years, 75 male) with ESRD (mean creatinine 608+/-272 micromol/L) referred for renal transplantation. The mean follow-up period was 1.32+/-0.48 years. Significant CAD was defined as a reduction in luminal diameter >70% by visual estimation in at least one major epicardial vessel. An abnormal DSE result defined as the development of a new regional wall motion abnormality in one or more normal resting segments or a deterioration of wall motion in one or more resting hypokinetic segments. A baseline cTnT>0.1 microg/L was taken as positive. Significant CAD in at least one vessel was present in 35 patients (30%). The number of patients with significant 3 vessel and 2 vessel disease was 6 and 7, respectively. An abnormal DSE result was present in 36 (31%) patients. Thirty-one (26%) had cTnT>0.1 microg/L. Sixty-four (54%) patients were on dialysis and 46 (39%) were diabetic. The sensitivity, specificity, positive and negative predictive values for DSE in detecting significant coronary artery disease were 88%, 94%, 86% and 95%, respectively. The same values for a raised cTnT were 54%, 62%, 40% and 74%, respectively. The combination of an abnormal DSE result and raised cTnT gave values of 61%, 91%, 76%, and 80%, respectively. Over the follow-up period, mortality was significantly higher in those with a raised baseline cTnT but not those with an abnormal DSE result or significant CAD. DSE is an accurate technique for the detection of significant CAD in renal transplant candidates. An elevated cTnT does not predict significant CAD in this population and when used in conjunction with DSE, reduces the sensitivity of the combined tests. cTnT is an important marker of prognosis in renal transplant candidates.

Toll-like receptor (TLR)-9 promotor polymorphisms and atherosclerosis

Background Currently, the primary cause of atherosclerosis remains controversial: while oxidized or enzymatically altered LDL is widely accepted as one cause of the inflamed lesion, microorganisms such as C. pneumoniae or cytomegalovirus (CMV) also have recently been postulated to be involved in the pathogenesis of atherosclerosis. Microbial products activate innate immune cells of the host via Toll-like receptors (TLRs). Common polymorphisms of the TLR-2 and TLR-4 genes have been shown to be associated with an increased risk for restenosis after PTCA, and a lower risk of carotid atherosclerosis, respectively. Microbial DNA has been shown to activate immune cells via the cytosolic TLR-9. Specially, C. pneumonia and CMV as intracellular pathogens may be potent trigger of TLR-9 signaling. Therefore, we investigated whether the two common promotor polymorphisms of the TLR-9 gene are correlated with atherogenesis. Methods The T-1237C and the T-1486C polymorphisms were analyzed by Real Time PCR in 202 (derivation study, age 58.1, SD 10.0) and 182 (validation study, age 59.7, SD 9.6) patients that underwent angioplasty and 188 healthy controls (age 52.5, SD 6.1). Restenosis was defined as > 50% luminal diameter reduction at follow-up angiography. Results We found the two polymorphism being able to create new potential binding sites for transcription factors, however, no association of the TLR-9 polymorphisms with atherogenesis or restenosis was detectable. Conclusion Our data indicate that the two TLR-9 promotor polymorphisms are not involved in atherogenesis.

Inflow stenosis in arteriovenous fistulas and grafts: A multicenter, prospective study

Traditionally, arteriovenous hemodialysis access inflow stenosis has been reported to occur infrequently (0% to 4%). In contrast, recent reports have suggested a significantly higher incidence (14% to 42%). Interpretation of these studies has been complicated by the presence of one or more confounding factors such as retrospective study design, small sample size, arteriovenous fistulas grouped with grafts to determine the incidence of inflow stenosis, inclusion of fistulas that had failed primarily, failure to provide adequate definition of inflow stenosis, and the technique of retrograde angiography. This is a report of a prospective, multicenter study to examine the incidence of inflow stenosis separately in arteriovenous fistulas and grafts. Patients were referred to interventional nephrology either for percutaneous balloon angioplasty or thrombectomy procedures. Angiography to evaluate access inflow (arterial anastomosis and adjacent vascular structures) was performed in all cases. This was accomplished by retrograde angiography using either manual occlusion of the venous side and/or advancing a diagnostic catheter across the arterial anastomosis. Multiple images using digital subtraction angiography were recorded in multiple planes. An inflow stenosis was defined as stenosis within the arterial system, artery-graft anastomosis (graft cases), artery-vein anastomosis (fistula cases) and juxta-anastomotic region (the first 2 cm downstream from the arterial anastomosis). Vascular stenosis was defined as >/=50% reduction in luminal diameter judged by comparison with either the adjacent vessel or graft. A standardized definition for anastomotic stenosis was applied. Two hundred and twenty three consecutive procedures (grafts, 122; fistulas, 101) were performed in 158 patients. Inflow stenosis occurred in 36/122 (29%) in graft cases. All had a coexisting stenosis on the venous side. In fistula cases, 41/101 (40%) had inflow stenosis. Of these, 22 (54%) had a coexisting lesion on the venous side. Overall, inflow stenosis occurred in 77/223 procedures (35%). This prospective, multicenter study demonstrates that access inflow stenosis occurs in one third of the cases referred to interventional facilities with clinical evidence of venous stenosis or thrombosis. This is much higher than has been traditionally reported.

Prinzmetal’s Angina

Prinzmetal's angina, often referred to as "variant" angina, is a temporary increase in coronary vascular tone (vasospasm) causing a marked, but transient reduction in luminal diameter. This coronary vasospastic state is usually focal at a single site and can occur in either a normal or diseased vessel. Patients are predominantly younger women who may not have the classical cardiovascular risk factors (except for cigarette use). PVA has been associated with vasospastic disorders such as Raynaud's phenomenon and migraine headaches. Arrhythmias are common and may be life threatening especially when the effects of vasospasm are seen in those ECG leads that reflect the potential variations of the epicardial surface of the left ventricle. Endothelial dysfunction has been considered as primarily responsible for PVA. The diagnosis is made by observing transient ST-segment elevation during the attack of angina. Since PVA is not a "demand"- induced symptom, but rather a supply (vasospastic) abnormality, exercise treadmill stress testing is of no value in the diagnosis of PVA. The most sensitive and specific test for PVA is the administration of ergonovine intravenously. Fifty micrograms at 5-minute intervals is given until a positive result or a maximum dose of 400 microg has been administered. When positive, the symptoms and associated ST-segment elevation should be present. Nitroglycerin rapidly reverses the effects of ergonovine if refractory spasm occurs. Medical therapy classically employs vasodilator drugs, which include nitrates and calcium channel blockers. The prognosis is good when there is no significant coronary artery stenosis. Treatment of associated coronary atherosclerosis in elderly patients with PVA is advised. When PVA is associated with coronary atherosclerosis, the prognosis is determined by the severity of the underlying disease. beta-Blockers and large doses of aspirin are contraindicated in PVA.

Elevated Remnant-Like Particle Cholesterol Concentration

Patients at increased risk of coronary artery disease (CAD) frequently exhibit an atherogenic lipoprotein phenotype characterized by elevated plasma levels of both triglyceride-rich lipoproteins (TRL) and small, dense LDL and low concentrations of HDL cholesterol. Recently, in a large observational study, the calculated non-HDL plasma cholesterol concentration (the sum of the cholesterol contents of LDL, intermediate-density lipoprotein [IDL], and very-low-density lipoprotein [VLDL]) was a stronger predictor of cardiovascular events than plasma cholesterol alone.1–3 Improvement in the predictability of CAD on inclusion of VLDL and IDL cholesterol emphasizes the proatherogenic nature of TRL and their remnant particles. The atherogenic lipoprotein phenotype has been defined by Austin et al4 as the presence of a predominance of small, dense LDL particles, elevated plasma triglyceride (TG) levels, and low plasma HDL cholesterol levels in the lipoprotein profile, which is associated with an approximately 3-fold increased risk of atherosclerotic disease.5–8 It is now commonly accepted that small, dense LDL particles are the products of the intravascular remodeling of TG-rich VLDL particles after interaction primarily with lipoprotein lipase, hepatic lipase, and cholesterol ester transfer protein9,10 (Figure). The atherogenic lipoprotein phenotype is strongly linked to obesity, insulin resistance, familial combined hyperlipidemia (FCHL), hypertension, and abnormalities in postprandial lipid metabolism.7,11,12 Epidemiological data from the Framingham study have already revealed that plasma TG concentration is an important independent risk indicator of CAD in women13; additional evidence supporting this observation was obtained by Yarnell et al14 in a 10-year follow-up study and confirmed by others.15,16 In the PROCAM (Prospective Cardiovascular Munster) study,17 this relationship was dependent on plasma HDL cholesterol concentration. Criqui et al,18 however, could not demonstrate an independent relationship between plasma TG and cardiovascular mortality in a North American population participating in the Lipid Research Clinics Follow-up. …

Effects of smoking on nitric oxide synthesis in epicardial normal and atheromatous coronary arteries

The effects of an intracoronary infusion of N G-monomethyl- l-arginine (LNMMA) followed by intracoronary administration of nitroglycerin in non-stenotic proximal and distal coronary segments were studied in 11 patients with coronary artery disease and in 19 subjects with “normal arteriograms”. In normal subjects, LNMMA induced significant constriction ( p<0.01) of proximal and distal vessels in non-smokers and smokers. In normal non-smokers, the reduction in coronary luminal diameter of proximal segments was significantly greater compared to normal smokers ( p<0.05). In patients with coronary artery disease, LNMMA induced significant constriction of proximal and distal vessels in smokers, and only distal constriction in non-smokers ( p<0.01). The reduction in coronary luminal diameter of the distal segments in normal smokers, and in both groups in patients with coronary artery disease was significantly greater compared with proximal segments ( p<0.05). Therefore, the difference in vasomotor response to LNMMA in relation to smoking is localised to the proximal coronary segments.

Extracellular matrix biology: a new frontier in linking the pathology and therapy of hypertension?

The extracellular matrix (ECM) is a vital component of connective tissue, and collagen is a major constituent. There is growing evidence that changes in the composition of the cardiac and vascular matrix occurs during hypertension. Clinically, these effects are manifested as left ventricular hypertrophy and a reduction in arterial compliance and luminal diameter, which results in end organ ischaemia. The matrix metalloproteinases and their inhibitors have a central role in the regulation of the composition of the ECM. In this review, we discuss the mediators that affect the structure of the ECM in hypertension using results from animal and human studies.

Relationship between dobutamine response of dyssynergic myocardium and angiographically documented blood supply

Objective Because hibernation is considered a down-regulation of contractile function in response to reduced regional myocardial perfusion, hibernating myocardium is expected to be supplied by a critically stenosed or even occluded coronary artery. Thus, high-dose dobutamine has been postulated to cause ischemia and reworsening of myocardial function (biphasic response), whereas myocardium that demonstrates sustained improvement with high-dose dobutamine should not be supplied by a significantly stenosed vessel. This study evaluates the type of dobutamine response–biphasic versus sustained improvement–of dyssynergic myocardium in relation to its angiographically documented blood supply. Methods In 38 patients (5 women; mean age 60 ± 9 years) with chronic coronary artery disease and impaired left ventricular ejection fraction (≤35%), dobutamine echocardiography and quantitative coronary angiography were performed within 4 weeks. Wall-motion response of dyssynergic myocardium to dobutamine, classified as no improvement, biphasic response, or sustained improvement, was comparedwith the angiographically documented blood supply (presence of coronary stenosis in the corresponding artery, collaterals, and stenoses of the collateral supplying artery) in a segment-by-segment analysis. Results Of the 465 segments with abnormal wall motion at rest, 201 (47%) showed improvement during dobutamine infusion at low dose. Of these, 145 (72%) were supplied by significantly stenosed epicardial vessels. Only 27 (19%) of these 145 segments showed a biphasic response whereas in the remaining 118 segments wall-motion improvement persisted during high-dose dobutamine infusion. Although mean stenosis severity in the supplying vessel was significantly greater for segments presenting with biphasic response as compared with sustained improvement (95 ± 7% and 86 ± 12% luminal diameter reduction, respectively; P < .0001), 69% of segments with sustained improvement were supplied by a critically stenosed artery. Only 7 of 27 segments with biphasic response and 22 of 118 segments with sustained improvement had visible collaterals supplied by a vessel without significant stenosis. The percentage of segments viable by thallium-single photon emission computed tomography imaging was similar for those with sustained and biphasic response (96% and 83%, respectively). Conclusions In this group of patients with coronary artery disease and impaired left ventricular function, the great majority of dyssynergic segments that exhibited a sustained, rather than biphasic, dobutamine response were supplied by a critically stenosed artery. Furthermore, the percentage of segments viable by thallium-single photon emission computed tomography did not appear to be different for segments with sustained improvement and those with biphasic response. These findings challenge the hypothesis that biphasic response is the best criterion to identify viable myocardium.

Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats.

The subchronic treatment of mature female Wistar-strain albino rats in diestrous phase with sodium arsenite at a dose of 0.4 ppm/100 g body weight/rat/day via drinking water for period of 28 days (seven estrous cycles) caused a significant reduction in the plasma levels of leutinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol along with a significant decrease in ovarian activities of delta five, 3 beta-hydroxysteroid dehydrogenase (Delta5,3beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD) followed by a reduction in ovarian and uterine peroxidase activities. A significant weight loss of the ovary and uterus was also observed after this treatment, along with a prolonged diestrous phase and a high accumulation of arsenic in the plasma and these organs. Moreover, sodium arsenite was also responsible for ovarian follicular and uterine cell degeneration characterized by a high number of regressing follicles and a reduction in the uterine luminal diameter, respectively, in comparison with the controls. A dietary supplementation of sodium selenite at the dose of 0.6 mg/100 g body weight/rat/day for a period of 28 days along with arsenic treatment minimized the gonadal weight loss significantly and increased the activities of the ovarian steroidogenic enzymes as well as the ovarian and uterine peroxidase at the control level. Selenium was also able to increase the plasma levels of LH, FSH, and estradiol toward the control level. Vaginal smears showed normal estrous cyclicity in sodium selenite-supplemented arsenic-treated rats along with lower arsenic levels in the plasma and gonadal tissue in comparison with arsenic-only-treated rats. Histological sections of ovary and uterine tissues in the control and experimental groups confirmed that sodium selenite supplementation was able to prevent arsenic-induced histopathological changes in the ovary and uterus. Plasma levels of norepinephrine and dopamine in the midbrain and diencephalon decreased significantly, whereas the serotonin level was increased significantly after 28 days of sodium arsenite treatment. All of these parameters were, in most cases, unchanged from the control level when sodium selenite was co-administered with sodium arsenite. Arsenic intoxication was also associated with increased liver weight and elevation in the activities of hepatic and renal acid phosphatase, alkaline phosphatase, and transaminases, but selenium co-administration was not able to change these toxic effects of arsenic. The results of our experiments indicate the significant protective action of sodium selenite on arsenic-induced toxicity in the female reproductive system, while there was no significant protective effect of selenium on arsenic-induced toxicity in other organs.

Balloon angioplasty versus medical therapy for hypertensive patients with renal artery obstruction.

Atherosclerotic renal artery stenosis is the most common cause of secondary hypertension. Balloon angioplasty is widely used for the treatment of hypertensive patients with renal artery stenosis. The objective of this systematic review was to compare the effectiveness of balloon angioplasty (with and without stenting) with medical therapy on blood pressure control, renal function, frequency of renovascular complications, and side effects in hypertensive patients with atherosclerotic renal artery stenosis. The reviewers performed a search of MEDLINE from 1966 to December 2002, EMBASE from 1980 to 2002, Science Citation Index from 1990 to 2002, the Cochrane Central Register of Controlled Trials and personal files to identify randomised controlled trials comparing balloon angioplasty with medical therapy in hypertensive patients with renal artery stenosis. In addition, reference lists of papers resulting from this search were hand-searched, and authors of published trials were contacted to enquire if they were aware of any eligible unpublished trials. Randomised and quasi-randomised controlled trials comparing balloon angioplasty with medical therapy in hypertensive patients with haemodynamically significant renal artery stenosis (greater than 50 per cent reduction in luminal diameter and minimal follow-up of six months). Two investigators independently extracted data on trial design, characteristics of trial participants, types of interventions, and outcome measures. The quality of the available data precluded a formal meta-analysis to assess the effect on blood pressure, renal function, and number and defined daily doses of antihypertensive drugs. Peto's odds ratios and corresponding 95% confidence intervals (CI) were calculated for dichotomous outcomes such as the presence or absence of patent vessels and renovascular complications. Three randomised controlled trials involving 210 patients met the inclusion criteria. In unselected patients there was a consistent, but statistically non significant trend towards lower blood pressure in the balloon angioplasty group. Patients treated with balloon angioplasty required less antihypertensive drugs in two of three trials, and were more likely to have patent renal arteries after 12 months (OR 4.2, 95% CI 1.8 to 9.8). There were no differences in renal function. There were significantly fewer cardiovascular and renovascular complications in patients treated with angioplasty (OR 0.32, 95% CI 0.15 to 0.70, test for heterogeneity p > 0.1). Available data are insufficient to conclude that balloon angioplasty is superior to medical therapy in lowering blood pressure of patients with renal artery stenosis in whom blood pressure can be controlled with medical therapy. In patients with hypertension refractory to medical therapy, there is some weak evidence that balloon angioplasty lowers blood pressure more effectively than medical therapy. Balloon angioplasty appears to be safe and leads to fewer cardiovascular and renovascular complications. There is a need for randomised controlled trials comparing the effect of balloon angioplasty and medical therapy on the preservation of renal function in the long term.

Occurrence of Transient U-Wave Inversion During Vasospastic Anginal Attack Is Not Related to the Direction of Concurrent ST-Segment Shift

We sought to assess the incidence of transient U-wave inversion during vasospasm of the left anterior descending coronary artery (LAD) with ST-segment depression as opposed to that with ST-segment elevation. Retrospective study. Cardiology division of acute-care hospitals. We studied 49 patients with vasospastic angina whose vasospasm was induced in the LAD, not in the left circumflex coronary artery, by intracoronary injection of acetylcholine. The ECG traces obtained during acetylcholine-induced vasospasm of the LAD were examined. Based on the direction of ST-segment shift, the patients were categorized into two groups: the ST-segment elevation group (n = 27) and the depression group (n = 22). There were no differences in age, gender, or cardiovascular risk factors between the two groups. The distribution of the spastic site in the LAD was also similar. A total reduction in luminal diameter during a provoked attack was more often observed in the ST-segment elevation group than in the ST-segment depression group (37% vs 9%, p = 0.02). Collateral circulation to the LAD was found in only one patient in each group. There were no differences between the two groups in heart rate, systolic BP, and double product of heart rate and systolic BP during the attack. The incidence of acetylcholine-induced anginal attack with U-wave inversion in the ST-segment depression group was nearly as high as that in the ST-segment elevation group (77% vs 78%, p > 0.99). The development of transient U-wave inversion during vasospasm of the LAD induced by intracoronary injection of acetylcholine does not depend on the magnitude of myocardial ischemia as judged by the direction of ST-segment shift.