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PubMed2004

Incidence and characterization of patient motion in myocardial perfusion SPECT: Part 1.

UNLABELLED: Despite advances in (99m)Tc-based radiopharmaceuticals and multiple-detector gantries, patient motion in myocardial perfusion SPECT acquisitions is still problematic and may produce artifacts that mimic coronary artery disease. METHODS: A prospective cross-sectional study of 800 myocardial perfusion SPECT studies performed with (99m)Tc-based radiopharmaceuticals at 3 private nuclear medicine sites was used to determine the incidence, type, and location of visually detectable motion. The rotating cinematic display and sinograms of the ungated datasets were visually assessed by 2 experienced technologists unaware of the other observer's responses and the clinical outcome. RESULTS: Among the 800 studies analyzed, 36% contained visually detectable motion. Motion was seen on 31.5% of rest studies, compared with 40.5% of stress studies (P = 0.004). The most common type of motion detected was multiple bounce, which represented 47.6% of motion. Left anterior oblique and anterior were the most common specific locations in which patient motion was detected in the raw data. CONCLUSION: This investigation established the significant incidence of patient motion during (99m)Tc-based myocardial perfusion SPECT studies that, fully realized, has the potential to introduce artifacts leading to false-positive findings. Further investigation of the impact of various types and degrees of patient motion is recommended.

Adolescent↗
PubMed1992

Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF.

Hemodilution has had limited success as a treatment of cerebral ischemia. When using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced increases in CBF are offset by concomitant decreases in oxygen content. The effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct, (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for areas with a CBF of 0-10 and 11-20 ml 100 g-1 min-1. In addition, oxygen delivery was calculated. In the center of the ischemic zone, both areas of low CBF were less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct groups; and both areas were less in the 9/Hct group compared with the other five groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a direct correlation between hematocrit and oxygen delivery. However, for the hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit decreased (44/Hct, 8.6 +/- 0.3 vs. 9/Hct, 13.6 +/- 0.4 [mean +/- SD, ml 100 g-1 min-1]). The results of this study support a hypothesis that hemodilution with DCLHb decreases the extent of focal cerebral ischemia.

Animals↗
PubMed1995

Systemic and cerebral hemodynamic responses to the noncompetitive N-methyl-D-aspartate (NMDA) antagonist CNS 1102.

The excitatory amino acid antagonists are being developed as neuroprotective drugs aimed at limiting ischemic neuronal damage. Their hemodynamic and neurologic side effects are important in assessing safety and tolerability. We studied CNS 1102, a high-affinity noncompetitive N-methyl-D-aspartate (NMDA) receptor-channel antagonist, in normal volunteers. The effects of 2 mg CNS 1102 were assessed in a single-blind, placebo-controlled, fixed-dose, cross-over trial comparing administration by intravenous infusion for 15 min or bolus for 2 min in 8 healthy male subjects. Cerebral hemodynamics were studied with carotid and vertebral duplex ultrasound imaging, common carotid artery walltracking, and middle cerebral artery velocity readings. CNS 1102 administration was associated with light-headedness, mild disorientation, perioral and peripheral paresthesias, and flushing. Mean arterial blood pressure (MAP) increased significantly from baseline 1 h after CNS 1102 administration, with a maximal increase of 17 mm Hg over placebo. Pulse rate was unchanged. Common carotid artery pulsatility decreased by 38.4% [8.3-64.5, 95% confidence interval (CI)] and vertebral pulsatility by 43.8% [11.5-74.1], both p < 0.02. No significant differences were detected for other velocity and flow parameters. Middle cerebral artery mean velocity increased by 4.6 cm/s (1.6-7.8 cm/s) and diastolic velocity by 4.6 cm/s (2.4-7.3 cm/s) (both p < 0.01), but systolic velocity was unchanged. The middle cerebral pulsatility index decreased by 11% (3.8-16.1), p < 0.001. CNS 1102 is well tolerated at a fixed dose of 2 mg in normal volunteers. Cerebral arteriolar constriction is inferred from the ultrasound results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Water drinking improves orthostatic tolerance in patients with posturally related syncope.

Water drinking improves OT (orthostatic tolerance) in healthy volunteers; however, responses to water in patients with PRS (posturally related syncope) are unknown. Therefore the aim of the present study was to examine whether water would improve OT in patients with PRS. In a randomized controlled cross-over fashion, nine patients with PRS ingested 500 ml and 50 ml (control) of water 15 min before tilting on two separate days. OT was determined using a combined test of head-up tilting and lower body suction and expressed as the time required to induce presyncope. We measured blood pressure and heart rate (using Portapres) and middle cerebral artery velocity (using transcranial Doppler). SV (stroke volume) and TPR (total peripheral resistance) were calculated using the Modelflow method. OT was significantly (P<0.02) greater after drinking 500 ml of water than after 50 ml (25.4+/-1.5 compared with 19.8+/-2.3 min respectively). After ingestion of 500 ml of water, blood pressure during tilting was higher, the tiltinduced reduction in SV was smaller and the increase in TPR was greater (all P<0.05). The correlation coefficient of the relationship between cerebral blood flow velocity and pressure was lower after 500 ml of water (0.43+/-0.1 compared with 0.73+/-0.1; P<0.05), indicating better autoregulation. In conclusion, drinking 500 ml of water increased OT and improved cardiovascular and cerebrovascular control during orthostasis. Patients with PRS should be encouraged to drink water before situations likely to precipitate a syncopal attack.

Adult↗
PubMedDate not supplied

Effect of gallopamil on myocardial microperfusion in patients with stable effort angina: a randomized, cross-over, double-blind, placebo-controlled trial.

We evaluated the efficacy and safety of daily administration of gallopamil 150 mg/day and its effects on myocardial perfusion in a medium-term, randomized, double-blind, cross-over, placebo-controlled trial. We studied 19 patients (17 males and 2 females; mean age 57 +/- 6.8 years) with stable effort angina, angiographically documented coronary artery disease and reversible perfusion defects during exercise thallium-201 myocardial scintigraphy of at least one segment of the left ventricle. After 2 weeks of a single-blind placebo run-in period, during which each patient underwent at least 2 exercise tests and a 48-hour Holter ECG recording, all patients were treated with either placebo or gallopamil 50 mg t.i.d. for 28 days. At the end of this period, patients crossed over to the alternate regimen. This phase was double blind. After treatment with placebo or gallopamil, patients underwent exercise tests, 24-hour Holter ECG recording and thallium-201 myocardial scintigraphy. Weekly angina frequency and trinitroglycerin (TNT) consumption and safety were also evaluated. No patients dropped out of the study because of major side effects. The number of total ischemic and symptomatic events recorded at 24-hour ECG monitoring, weekly angina frequency and TNT consumption were significantly reduced during gallopamil treatment. After gallopamil administration, exercise duration significantly increased (run-in: 419 +/- 116 s, placebo: 420 +/- 118 s, gallopamil: 511 +/- 144 s; p < 0.05), and ST segment depression was significantly reduced (run-in: -1.3 +/- 0.3 mm, placebo: -1.3 +/- 0.3 mm, gallopamil: -0.94 +/- 0.68 mm; p < 0.01), while heart rate, systolic blood pressure and rate-pressure product were unchanged at rest, at submaximal and at peak exercise. Qualitative and quantitative evaluation of myocardial perfusion and the myocardial uptake percentage of thallium-201 in ischemic zones were significantly improved by gallopamil treatment. These findings demonstrate that gallopamil can improve myocardial perfusion and reduce myocardial oxygen consumption.

Aged↗
PubMed1996

Thoracic epidural anesthesia improves functional recovery from myocardial stunning in conscious dogs.

The effects of thoracic epidural anesthesia (TEA) on the contractile performance of ischemic and postischemic myocardium have not been well investigated. The purpose of this investigation was to examine the effects of TEA on severity and duration of myocardial stunning in an experimental model for sublethal acute myocardial ischemia. Seven dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic and left ventricular pressure (LVP), LV dP/dtmax' and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischemia. TEA was performed with lidocaine 4 mg/kg through a chronically implanted epidural catheter at the second thoracic level. Regional myocardial blood flow was determined with colored microspheres. Two experiments were performed in a cross-over design on separate days: Experiment 1, induction of 10 min of LAD ischemia without TEA; and Experiment 2, induction of 10 min of LAD ischemia with TEA. WTF was measured at baseline (BL) and predetermined time points until complete recovery from ischemic dysfunction occurred. LAD ischemia caused a significant decrease of LAD-WTF with (-28% +/- 5.1% versus BL) and without TEA (-15.5% +/- 5.3% versus BL). After 3 h of reperfusion, WTF as percent of BL values was significantly higher with TEA (P < 0.001). BL values of WTF were reached after 24 h with TEA and after more than 48 h without TEA (P < 0.05). There were no significant differences for mean arterial pressure (MAP), heart rate (HR), LVP, LAP, and LVdP/dtmax between the groups during ischemia and reperfusion. In nonischemic myocardium TEA caused an increase of subendocardial blood flow. During ischemia neither the subendocardial/subepicardial nor the occluded/ normal zone blood flow was affected by TEA. TEA attenuates myocardial stunning in conscious dogs. This finding is consistent with data regarding a reduction of infarct size due to TEA.

Anesthesia, Epidural↗
PubMed2005

Myocardial tissue Doppler and long axis function in the fetal heart.

UNLABELLED: Current echocardiographic assessment of fetal ventricular function uses relatively crude measures and this has led to inconsistencies in assessment of diastolic function. Long axis parameters may be more insightful. OBJECTIVE: To describe fetal long axis cardiac function and construct reference ranges. DESIGN: 159 normal fetuses were studied cross-sectionally using long axis M-mode to measure displacement of the atrioventricular ring and pulsed wave Doppler ultrasound to record myocardial tissue Doppler velocities at the base of the heart. RESULTS: There was a strong, almost linear gestational relationship for all but late left basal myocardial velocities. Systolic amplitude of the atrioventricular ring increased significantly. Wall thickness increased with gestation and heart rate reduced. Late diastolic mitral and tricuspid flow velocities showed no age-dependence. Right ventricular filling (p<0.0001) and myocardial lengthening (p<0.0001) and shortening velocities (p<0.0001) were higher than left. Aortic velocities were higher than pulmonary (p<0.0001). Right ventricular long axis amplitude was greater than left (p<0.0001). There were no significant differences in right (RV) and left (LV) ventricular and septal thicknesses (RV 2.5 mm [1.2-4.1]; LV (2.4 mm [1.0-4.0] and septum 2.6 mm [1.0-4.3]). Left and right myocardial tissue Doppler velocities showed similar maturation in systole (LV 0.14 vs. RV 0.10 cm/s/week) and early diastole (LV 0.16 vs. RV 0.14 cm/s/week). CONCLUSIONS: This study demonstrates maturational changes occur in both fetal systolic and diastolic ventricular function and moreover the maturational rate of myocardial tissue velocities is similar in both ventricles, despite differential loading conditions.

Blood Flow Velocity↗
PubMed2005

Identification of Alzheimer disease risk by functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials. OBJECTIVE: To determine whether functional magnetic resonance imaging can reliably distinguish risk groups for AD among cognitively normal middle-aged adults. DESIGN: Cross-sectional case-control study. SETTING: University of California, San Diego, Alzheimer Disease Research Center participants and San Diego community volunteers. PARTICIPANTS: Twenty cognitively normal individuals (10 high risk and 10 low risk), aged 58 to 65 years, were divided into 2 groups based on the presence or absence of the apolipoprotein E epsilon4 allele and a positive family history of AD. MAIN OUTCOME MEASURES: Word pairs were presented in a blocked design alternating between conditions of novel pairs, repeated pairs, and fixation. Whole-brain differences in blood oxygenation level-dependent brain responses between conditions were compared across risk groups. RESULTS: Compared with the low-risk group, the high-risk group showed many areas of differential blood oxygenation level-dependent response in regions commonly associated with AD pathology (eg, the left medial temporal lobe). Furthermore, different patterns of association between left medial temporal lobe activity and memory performance were demonstrated. CONCLUSIONS: Results support a theory of up-regulation in neuronal memory systems in people at risk for AD many years before the typical age at disease onset. They further demonstrate that functional magnetic resonance imaging is a viable technique to identify persons at risk for AD.

Aged↗
PubMed2001

Comparison of the effect of perindopril and acebutolol on cerebral hemodynamics in hypertensive patients.

PURPOSE: The aim of the study was to compare effect of perindopril (4 mg once a day) versus acebutolol (400 mg once a day) on cerebral hemodynamics in hypertensive patients. METHODS: Thirty untreated patients with mild-to-moderate hypertension were studied. Drug influences on Doppler-derived parameters from the cerebral blood flow (CBF) velocity wave form were evaluated in a randomized, double blind, cross-over, placebo controlled study. The mean CBF velocity, pulsatility index (PI), cerebrovascular resistance and index of CBF were calculated from concomitant transcranial Doppler measurements and systemic blood pressure. RESULTS: Acebutolol and perindopril significantly decreased systolic, diastolic and mean blood pressure in relation to placebo. The mean value of CBF velocity increased to a comparable level after both drugs (54.9 +/- 9.1 cm/s on placebo vs 62.8 +/- 14.5 cm/s on perindopril p<0.01 and 61.4 +/- 9.2 cm/s on acebutolol, p<0.01). Also, the cerebrovascular resistance index decreased similarly after both drugs (2.26 +/- 0.35 on placebo vs 1.68 +/- 0.42 on perindopril p<0.01 and 1.7 +/- 0.36 on acebutolol p<0.01). The calculated CBF index increased significantly after each drug (25.23 +/- 7.99 on placebo vs 33.98 +/- 11.23 p<0.01 on perindopril and 30.90 +/- 8.04 on acebutolol p<0.01). However, perindopril augmented the CBF index more effectively than acebutolol (p<0.05). CONCLUSIONS: Among patients with mild-to-moderate hypertension both acebutolol and perindopril beneficially decreased cerebrovascular resistance and increased the CBF index in comparison with placebo. The increase of CBF index was greater after perindopril than acebutolol, which suggests a more significant improvement in cerebral perfusion by perindopril. The non-invasive transcranial Doppler ultrasonography method of CBF velocity measurement may contribute to choosing optimal antihypertensive therapies and to monitor their effect.

Acebutolol↗
PubMed1998

Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine enantiomers in sheep.

UNLABELLED: Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (levobupivacaine) is the subject of current clinical evaluation. We conducted partial cross-over systemic and regional pharmacokinetic studies of i.v. bupivacaine (12.5-200 mg) and levobupivacaine (6.25-200 mg) in ewes. Enantiospecific analysis of blood drug concentration-time data and of regional myocardial and brain drug mass balance data indicated that (a) there was a higher mean total body clearance of R(+)-bupivacaine than of S(-)-bupivacaine (as previously reported); (b) there were no differences in the systemic pharmacokinetics of S(-)-bupivacaine whether administered alone or as a component of bupivacaine; (c) there was no evidence of dose-dependent pharmacokinetics with either enantiomer; (d) for both enantiomers, mean calculated myocardial tissue concentrations of 1%-4% dose occurred between 3 and 5 min. Mean brain concentrations of 0.2%-1% dose occurred between 2 and 4 min after the administration of bupivacaine but between 4 and 5 min after the administration of levobupivacaine. There was no evidence that systemic toxicity induced by these local anesthetics significantly modified their pharmacokinetics, and there was no evidence of an enantiomer-enantiomer pharmacokinetic interaction for bupivacaine. IMPLICATIONS: Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. As a part of its preclinical evaluation, this study considered whether levobupivacaine behaved kinetically in the body in the same way as when administered as a component of bupivacaine.

Anesthetics, Local↗
PubMedDate not supplied

Risk factors for poor collateral development in claudication.

The objective of this retrospective, cross-sectional study was to determine risk factors for poor collateral development in patients with claudication. The authors listed all patients with calf claudication who had undergone angiography in this hospital between 1999 and 2001 and extracted those with superficial femoral artery (SFA) occlusion, a popliteal artery without major lesions, and at least 1 patent calf artery. Forty-five patients met the criteria, and concomitant disease and claudication characteristics, ankle/brachial index (ABI) and number of outflow vessels were recorded. Three blinded observers calculated the number of collaterals on the angiograms, and the collateral count was related to the other factors by use of regression analysis. The mean patient age was 69 years (SD 11), and 62% were women. Their walking distance was 90 m (77) and ABI 0.47 (0.15). Thirty-three percent had diabetes and 50% had duration of symptoms longer than 5 years. The mean number of collaterals bypassing the occlusion was 15.1 (SD 4.8). Univariate regression analysis indicated an association (p <0.08) between few collateral vessels and diabetes, short duration of symptoms, current smoking habits, and old age. In the multivariate analysis only diabetes and short duration of symptoms were related to having few collaterals. In patients with claudication and SFA occlusion, few collaterals from the deep femoral artery appear to be associated with having diabetes and a short duration of symptoms.

Age Factors↗
PubMed2004

Cardiovascular risk factor profiles and endothelial function in coronary artery disease patients treated with statins.

Although endothelial dysfunction is associated with cardiovascular risk factors and is improved by cholesterol-lowering therapy, the relationship between endothelial function and cardiovascular risk factor profiles has not been fully investigated in coronary artery disease patients who have been treated with statins. We investigated endothelial function in male hypercholesterolemic patients (n=53) who underwent statin therapy over 6 months in a cross-sectional study. Patients were classified into three groups based on the results of coronary angiography: a normal coronary artery group (n=15), an angina pectoris group (n=20) and a myocardial infarction group (n=18). Endothelial function was assessed by measuring flow-mediated dilatation after reactive hyperemia in the brachial artery, and serum lipid, lipoprotein (a), glucose and insulin levels were measured. Significant associations were observed between the status of coronary disease and systolic blood pressure, lipoprotein (a), glucose and insulin levels (p <0.05, respectively), and the levels of these risk factors in the myocardial infarction group were higher than those in the other groups. Flow-mediated dilatation was also associated with the status of coronary disease (p <0.05), and the myocardial infarction group showed the lowest levels of flow-mediated dilatation (p <0.05). Flow-mediated dilatation was negatively correlated with systolic and diastolic blood pressures, serum levels of lipoprotein (a), glucose and insulin, and the status of coronary disease. Stepwise multiple regression analysis also revealed that lipoprotein (a), diastolic blood pressure and the status of myocardial infarction were significantly correlated with impaired vasodilatation. Serum lipids, age and smoking habit were independent of flow-mediated dilatation. In conclusion, even after cholesterol-lowering treatment, male patients with myocardial infarction still had endothelial dysfunction, and higher levels of lipoprotein (a) may be associated with endothelial dysfunction in such patients.

Aged↗
PubMed1996

Effects of various degrees of compression and active decompression on haemodynamics, end-tidal CO2, and ventilation during cardiopulmonary resuscitation of pigs.

UNLABELLED: The effects of various degrees of compression and active decompression during cardiopulmonary resuscitation were tested in a randomized cross-over-design during ventricular fibrillation in eight pigs using an automatic hydraulic chest compression device. Compared with 4/0 (compression/decompression in cm), mean carotid arterial blood flow rose by 60% with 5/0, by 90% with 4/2 and 4/3, and 105% with 5/2. Two cm active decompression increased mean brain and myocardial blood flow by 53% and 37%, respectively, as compared with 4/0. Increasing standard compression from 4 to 5 cm caused no further increase in brain or heart tissue blood flow whether or not combined with active decompression. Tissue blood flow remained unchanged or decreased when active decompression (4/3) caused that 50% of the pigs were lifted from the table due to the force required. Myocardial blood flow was reduced with 5/0 vs. 4/0 despite no reduction in end decompression coronary perfusion pressure ((aortic-right atrial pressure) (CPP), (7 +/- 8 mmHg with 4/0, 14 +/- 11 mmHg with 5/0)(NS)). End decompression CPP increased by 186% with 4/2 vs. 4/0, by 200% with 4/3, and by 300% with 5/2. Endo-tracheal partial pressure of CO2 was significantly increased during the compression phase of active decompression CPR compared with standard CPR. Active decompression CPR generated an significantly increased ventilation compared with standard CPR. CONCLUSION: Carotid and tissue blood flow, ventilation, and CPP increase with 2 cm of active decompression. An attempt to further increase the level of active decompression or increasing the compression depth from 4 to 5 cm did not improve organ blood flow.

Animals↗
PubMed1998

Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep.

UNLABELLED: Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (i.e., levobupivacaine) is currently undergoing preclinical evaluation. Cross-over studies with i.v. levobupivacaine and bupivacaine were conducted in two groups of seven conscious sheep. Doses were chosen to avoid convulsions (smaller dose 6.25-37.5 mg/min) or to be potentially toxic (larger dose 75-200 mg/3 min). In subconvulsive doses, both drugs produced similar time- and dose-dependent depression of left ventricular systolic contractility (dP/dt(max)). Convulsions occurred consistently with > or = 75 mg of bupivacaine and > or = 100 mg of levobupivacaine, producing an abrupt reversal of dP/dt(max) depression. Subconvulsive doses produced minor cardiovascular effects on heart rate and blood pressure, whereas both were increased by convulsions. Cardiac output and myocardial blood flow were decreased with larger doses of both drugs. Doses > 75 mg of bupivacaine or > 100 mg of levobupivacaine induced QRS widening and ventricular arrhythmias, but significantly fewer and less deleterious arrhythmias were induced by levobupivacaine. Three animals died after 150, 150, and 200 mg of bupivacaine from the sudden onset of ventricular fibrillation. These doses of levobupivacaine produced nonfatal arrhythmias that automatically returned to sinus rhythm. We conclude that levobupivacaine could offer a greater margin of clinical safety than bupivacaine. IMPLICATIONS: Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. Local anesthetics can cause toxicity to the cardiovascular and central nervous systems. As a part of a preclinical evaluation of levobupivacaine, this study compared the toxic effects of levobupivacaine and bupivacaine in sheep.

Anesthetics, Local↗
PubMed2005

Effects of a pharmacologically-induced shift of hemoglobin-oxygen dissociation on myocardial energetics during ischemia in patients with coronary artery disease.

BACKGROUND: Conventional strategies to treat myocardial ischemia include interventions that reduce oxygen demand and/or increase myocardial blood flow. Animal experiments suggest that right-shifting the hemoglobin-oxygen dissociation curve may also attenuate the metabolic consequences of myocardial ischemia. We evaluated whether exercise-induced myocardial ischemia can be alleviated in subjects with coronary artery disease (CAD) by enhancing oxygen release with an allosteric modifier of hemoglobin's affinity for oxygen (RSR13). METHODS AND RESULTS: Seven subjects with CAD underwent a randomized, double-blind, cross-over study of the metabolic consequences of RSR13 administration on myocardial ischemia. Myocardial high-energy phosphates were quantified with 31P nuclear magnetic resonance (NMR) spectroscopy before, during, and after isometric handgrip-exercise. Subjects underwent NMR studies at baseline and on two separate occasions following the infusion of RSR13 (100 mg/kg) or placebo. RSR13 infusion significantly increased mean p50 by 8.1 +/- 2.7 mmHg at the end of the infusion, and it was still elevated by 4.9 +/- 3.3 mmHg after the completion of the treadmill tests while placebo had no effect. The myocardial creatine-phosphate (PCr) to adenosine-triphosphate (ATP) ratio decreased during handgrip-exercise in the baseline studies (from 1.39 +/- 0.23 before exercise to 0.95 +/- 0.21 during handgrip-exercise, p = 0.0001) and in the placebo studies (from 1.29 +/- 0.16 to 0.98 +/- 0.37, p = 0.06) but not during administration of RSR13 (from 1.28 +/- 0.18 to 1.02 +/- 0.24, p = 0.12). However, the mean values of cardiac PCr/ATP during handgrip-exercise did not differ significantly among the three measurements (baseline, placebo, RSR13). CONCLUSIONS: A single infusion of RSR13 to subjects with CAD increased mean p50 by 4.9-8.1 mmHg but did not significantly alter myocardial PCr/ATP during exercise. This is the largest right-shift in hemoglobin-oxygen binding affinity achieved in CAD subjects, and it did not provide clear evidence of protection from cardiac ischemia.

Adenosine Triphosphate↗
PubMed2002

Concurrent arterial aneurysms in brain arteriovenous malformations with haemorrhagic presentation.

OBJECTIVE: To assess the effect of concurrent arterial aneurysms on the risk of incident haemorrhage from brain arteriovenous malformations (AVMs). METHODS: In a cross sectional study, 463 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analysed. Concurrent arterial aneurysms on brain angiography were classified as feeding artery aneurysms, intranidal aneurysms, and aneurysms unrelated to blood flow to the AVM. Clinical presentation (diagnostic event) was categorised as intracranial haemorrhage proved by imaging or non-haemorrhagic presentation. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size, venous drainage pattern, and the three types of aneurysms on the risk of AVM haemorrhage at initial presentation. RESULTS: Arterial aneurysms were found in 117 (25%) patients with AVM (54 had feeding artery aneurysms, 21 had intranidal aneurysms, 18 had unrelated aneurysms, and 24 had more than one aneurysm type). Intracranial haemorrhage was the presenting symptom in 204 (44%) patients with AVM. In the univariate model, the relative risk for haemorrhagic AVM presentation was 2.28 (95% confidence interval (CI) 1.12 to 4.64) for patients with intranidal aneurysms and 1.88 (95% CI 1.14 to 3.08) for those with feeding artery aneurysms. In the multivariate model an independent effect of feeding artery aneurysms (odds ratio 2.11, 95% CI 1.18 to 3.78) on haemorrhagic AVM presentation was found. No significant effect was seen for intranidal and unrelated aneurysms. The attributable risk of feeding artery aneurysms for incident haemorrhage in patients with AVM was 6% (95% CI 1% to 11%). CONCLUSIONS: The findings suggest that feeding artery aneurysms are an independent determinant for increased risk of incident AVM haemorrhage.

Adult↗
PubMed1997

[Perfusion changes in hemodilution. The effect of extensive isovolemic hemodilution with gelatin and hydroxyethylstarch solutions on cerebral blood flow velocity and cutaneous microcirculation in humans].

OBJECTIVE: Quantifying the influence of extreme isovolemic hemodilution (NH) with different colloids on cerebral blood flow velocities (transcranial Doppler sonography) and cutaneous microcirculatory blood flow (laser Doppler flowmetry) in healthy, non-premedicated volunteers was the aim of this study. METHODS: In seven volunteers (randomized cross-over design) 20 ml/kg blood was withdrawn within 30 min and simultaneously replaced with 6% hydroxyethyl starch (200,000/0.5, HES) or 3% gelatin (GEL). Thirty minutes later, the autologous blood was retransfused (RT) within 30 min. Due to a severe allergic reaction to gelatin in one volunteer, only 6 GEL-NH were evaluated. Recorded parameters were: mean blood flow velocities (Vm-MCA) as well as the pulsatility index (PI) and the resistance index (RI) over the middle cerebral artery. In addition laser Doppler flux (FLUX), cell velocity (SPEED), mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb) and hematocrit (Hc) were monitored. RESULTS: NH resulted in a withdrawal volume of 1498 +/- 85 ml (HES) and 1493 +/- 95 ml (GEL), (mean +/- SD) and induced a decrease in hemoglobin from 40.9 to 29.0% (HES) and from 39.8 to 30.0% (GEL). RT increased Hc to 34.2% (HES) and 34.5% (GEL). MAP and HR showed no significant alterations in both groups. Following NH, Vm-MCA rose almost the same way in either case (26% HES), 21% (GEL), but decreased continuously again during RT. After completing RT, only in the HES group Vm-MCA still remained higher than baseline values (14% HES, only 3% GEL). Similar inverse regression lines were found for the two groups between Hc and Vm-MCA: [Vm-MCAHES (cm/s) = -1.27 x Hc + 110.9; r = 0.98, P < 0.001 and Vm-MCAGEL (cm/s) = -1.32 x Hc + 110.9; r = 0.91, P < 0.001]. Furthermore, as a result of NH, FLUX and SPEED increased about 61% and 38% in the HES group and remained on higher values in comparison with starting positions (21% FLUX, 13% SPEED). However, the results in the GEL group were of a different kind: FLUX and SPEED increased stupendously to 291% and 114% combined with NH, but both were reduced by RT on a large scale (39 and 27% below baseline values). Whereas RI showed no group differences, there was a remarkable drop in PI during RT (17% HES, 12% GEL). CONCLUSION: The two plasma expanders studied show a close inverse correlation between the alterations of blood flow velocities in the middle cerebral artery and systemic hemoglobin and hematocrit values. In both groups the change in blood flow velocities is comparable. For the first time the results of relative changes in blood flow velocities following hemodilution and retransfusion in healthy volunteers are described that correspond closely by relative cerebral blood flow alterations found in animal studies as well. Moreover, a non-linear correlation of cutaneous microcirculation was shown by means of HES, but also by GEL. Obviously, there was the GEL group to be responsible for pronounced differences in cutaneous circulation.

Adult↗
PubMed2004

Coronary vasomotor abnormalities in insulin-resistant individuals.

BACKGROUND: Insulin resistance is a metabolic spectrum that progresses from hyperinsulinemia to the metabolic syndrome, impaired glucose tolerance, and finally type 2 diabetes mellitus. It is unclear when vascular abnormalities begin in this spectrum of metabolic effects. OBJECTIVE: To evaluate the association of insulin resistance with the presence and reversibility of coronary vasomotor abnormalities in young adults at low cardiovascular risk. DESIGN: Cross-sectional study followed by prospective, open-label treatment study. SETTING: University hospital. PATIENTS: 50 insulin-resistant and 22 insulin-sensitive, age-matched Mexican-American participants without glucose intolerance or traditional risk factors for or evidence of coronary artery disease. INTERVENTION: 3 months of thiazolidinedione therapy for 25 insulin-resistant patients. MEASUREMENTS: Glucose infusion rate in response to insulin infusion was used to define insulin resistance (glucose infusion rate < or = 4.00 mg/kg of body weight per minute [range, 0.90 to 3.96 mg/kg per minute]) and insulin sensitivity (glucose infusion rate > or = 7.50 mg/kg per minute [range, 7.52 to 13.92 mg/kg per minute]). Myocardial blood flow was measured by using positron emission tomography at rest, during cold pressor test (largely endothelium-dependent), and after dipyridamole administration (largely vascular smooth muscle-dependent). RESULTS: Myocardial blood flow responses to dipyridamole were similar in the insulin-sensitive and insulin-resistant groups. However, myocardial blood flow response to cold pressor test increased by 47.6% from resting values in insulin-sensitive patients and by 14.4% in insulin-resistant patients. During thiazolidinedione therapy in a subgroup of insulin-resistant patients, insulin sensitivity improved, fasting plasma insulin levels decreased, and myocardial blood flow responses to cold pressor test normalized. LIMITATIONS: The study was not randomized, and it included only 1 ethnic group. CONCLUSIONS: Insulin-resistant patients who do not have hypercholesterolemia or hypertension and do not smoke manifest coronary vasomotor abnormalities. Insulin-sensitizing thiazolidinedione therapy normalized these abnormalities. These results suggest an association between insulin resistance and abnormal coronary vasomotor function, a relationship that requires confirmation in larger studies.

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