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PubMed1993

Cell-free hemoglobin potentiates acetylcholine-induced coronary vasoconstriction in rabbit hearts.

Cell-free hemoglobin (Hb) preparations have been shown to alter vascular tone in vitro and in vivo. The high affinity of Hb for nitric oxide, the putative endothelium-derived relaxing factor (EDRF), may be primarily responsible for this activity, but the contribution of tissue-damaging oxygen-derived free radicals has not been established. We investigated the effects of human Hb interdimerically cross-linked with bis-(3,5-dibromosalicyl)fumarate (alpha alpha Hb) on the coronary vasomotor response to acetylcholine (ACh) in isolated perfused rabbit hearts. Infusion of 0.1 g/dl alpha alpha Hb altered the dose-dependent response to ACh, decreasing the calculated IC50 (ACh concn at which coronary pressure is 50% of its maximal value) from 3.96 +/- 0.34 to 0.85 +/- 0.06 microM (P < 0.01). This augmented sensitivity to ACh was only partially reversed upon washout of alpha alpha Hb (IC50 1.93 +/- 0.13 microM). Simultaneous infusion of 60 microM deferoxamine mesylate with alpha alpha Hb attenuated this response (IC50 decreased from 3.86 +/- 0.27 to 1.73 +/- 0.38 microM), which was completely reversed after removal of alpha alpha Hb (IC50 3.41 +/- 0.17 microM). NG-nitro-L-arginine methyl ester (50 microM) and cross-linked cyanomethemoglobin (CNmet alpha alpha Hb, 0.1 g/dl) induced a significant (P < 0.05) increase in ACh-induced vasoconstriction accompanied by a reduction in myocardial functions in the same range as that caused by alpha alpha Hb. Infusion of deferoxamine mesylate (60 microM) with CNmet alpha alpha Hb completely prevented the reduction in IC50 elicited by the infusion of CNmet alpha alpha Hb alone. These data demonstrate that alpha alpha Hb can alter coronary vasomotor responsiveness and suggest the involvement of at least two mechanisms, one that is related to an accessible ferrous heme and is reversible and another that does not require an open heme site and is irreversible.

Acetylcholine↗
PubMedDate not supplied

Abstention from cigarette smoking improves cerebral perfusion among elderly chronic smokers.

A cross-sectional study of cerebral blood flow (CBF) levels in 268 neurologically normal volunteers contrasting nonsmokers, smokers who quit, and current cigarette smokers indicated that subjects who quit smoking had significantly higher cerebral perfusion levels than subjects who had continued to smoke but remained lower than subjects without a history of cigarette smoking. All subjects were matched for age and sex, and smoking groups were matched for duration and amount of smoking. A prospective study of 11 subjects who were able to stop smoking in which CBF levels were available both antecedent to and following cessation of the habit indicated that significant gains occurred in cerebral perfusion levels within one year following cessation of smoking. A control group of 22 subjects who continued to smoke (matched for age, sex, duration of smoking, and duration of time between baseline and follow-up) showed no change in CBF values. A correlation between magnitude of CBF change and duration of cessation of cigarette smoking demonstrated a significant linear increase in CBF during the one-year period. These results suggest that elderly individuals who have smoked for three to four decades can benefit substantially by abstaining from cigarette smoking and that significant improvement in cerebral circulation occurs within a relatively short period.

Aged↗
PubMed1996

Vascular effects of oxytocin on human middle cerebral artery determined by transcranial Doppler sonography.

Neurohypophysial hormones may exert regulatory influences on cerebral blood flow. This double-blind cross-over study in healthy humans (n = 6) examined effects of oxytocin (OX) on blood flow in the middle cerebral artery (MCA) by transcranial Doppler sonography. Compared to placebo, intravenous infusion of OX (0.5 IU, within 2.5 min via a forearm catheter) reduced blood flow velocity (V) within 10 min after the start of the infusion (P < 0.05). The pulsatility index (PI) was at the same time increased following OX (P < 0.05). The effects of OX were not accompanied by changes in expiratory endtidal pCO2 or blood pressure. But, heart rate was slightly enhanced immediately after infusion of OX (P < 0.05). The changes in MCA blood flow velocity following OX could reflect a vasoconstrictory effect on small cerebral resistance vessels or a vasodilating effect on the large cerebral arteries.

Adult↗
PubMed1975

Histochemical and structural changes in human myocardial cells after cardiopulmonary bypass.

The histochemical and ultrastructural effects of extracorporeal circulation and aortic cross-clamping during coronary heart surgery have been examined in drill biopsy samples of the left ventricle in 22 patients. The biopsies were obtained before and after bypass with a DeSoutter drill. Histochemical studies indicated definite differences between control and experimental biopsies, with increased succinic dehydrogenase, cytochrome oxidase, and LDH activity, while phosphorylase A and myosin ATPase activities declined. Furthermore, free phospholipid levels increased, as determined by the acid hematein reaction. Ultrastructural examination demonstrated loss of glycogen, intracellular swelling, and mitochondrial damage, which included loss of matrix density, loss of cristae, and eventual disruption in the postbypass biopsy. These results, which closely resemble the effects of ischemia and reperfusion observed in animal experiments, suggest that the initial insult is a change in membrane permeability regulation.

Adenosine Triphosphatases↗
PubMed2004

Caffeine reduces cerebral blood flow in patients recovering from an ischaemic stroke.

BACKGROUND: Caffeine is present in a variety of beverages and food and is widely consumed. In a previous study of patients recovering from an acute ischaemic stroke using transcranial Doppler ultrasound we demonstrated a fall in middle cerebral artery blood velocity of 12% following ingestion of 250 mg caffeine. The aim of this study was to investigate if this velocity change reflected a change in cerebral blood flow. METHODS: The study used a randomised, double blind, cross-over design. Nineteen patients recovering from an acute ischaemic stroke in the middle cerebral artery territory and 10 controls attended two sessions, having abstained from caffeine for 48 hours previously. At each session cerebral blood flow was measured four times using xenon clearance, twice before the oral administration of 250 mg caffeine or matched placebo, and twice after. Similarly, three middle cerebral artery blood velocity readings using transcranial Doppler were made prior to administration and four after. RESULTS: The caffeine resulted in a significant fall in cerebral blood flow and middle cerebral artery blood velocity compared to placebo. CONCLUSIONS: Since caffeine is present in the diet of most patients recovering from an acute ischaemic stroke this effect may have adverse clinical consequences.

Aged↗
PubMed2000

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression.

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.

Brain Mapping↗
PubMed2004

Acupuncture using laser needles modulates brain function: first evidence from functional transcranial Doppler sonography and functional magnetic resonance imaging.

Acupuncture using laser needles is a new totally painless stimulation method which has been described for the first time. This paper presents an experimental double-blind study in acupuncture research in healthy volunteers using a new optical stimulation method. We investigated 18 healthy volunteers (mean age +/- SD: 25.4 +/- 4.3 years; range: 21-30 years; 11 female, 7 male) in a randomized controlled cross-over trial using functional multidirectional transcranial ultrasound Doppler sonography (fTCD; n = 17) and performed functional magnetic resonance imaging (fMRI) in one volunteer. Stimulation of vision-related acupoints resulted in an increase of mean blood flow velocity in the posterior cerebral artery measured by fTCD [before stimulation (mean +/- SE): 42.2 +/- 2.5; during stimulation: 44.2 +/- 2.6; after stimulation: 42.3 +/- 2.4 cm/s, n.s.]. Mean blood flow velocity in the middle cerebral artery decreased insignificantly. Significant changes (p < 0.05) of brain activity were demonstrated in the occipital and frontal gyrus by fMRI. Optical stimulation using properly adjusted laser needles has the advantage that the stimulation cannot be felt by the patient (painless and no tactile stimulation) and the operator may also be unaware of whether the stimulation system is active. Therefore true double-blind studies in acupuncture research can be performed.

Acupuncture↗
PubMed2002

Cerebral vascular effects of non-invasive laserneedles measured by transorbital and transtemporal Doppler sonography.

Laserneedles represent a new non-invasive optical stimulation method which is described for the first time in this paper. We investigated 27 healthy volunteers (mean age+/-SD: 25.15+/-4.12 years; range: 21-38 years; 14 female, 13 male) in a randomised cross-over trial to study differences between laserneedle acupuncture and manual needle acupuncture in specific cerebral parameters. Mean blood flow velocity ( v(m)) showed specific and significant increases in the ophthalmic artery during laserneedle stimulation ( p=0.01) and during manual needle stimulation ( p<0.001) at vision-related acupoints. At the same time insignificant alterations in v(m) were found in the middle cerebral artery for both acupuncture methods. The eight laserneedles used in this study were arranged at the end of the optical fibres. Each fibre was connected to a semiconductor laser diode emitting at 685 nm with a primary output power of about 55 mW. Optical stimulation using properly adjusted laserneedles has the advantage that the stimulation can hardly be felt by the patient and the operator may also be unaware of whether the laserneedle system is active, and therefore true double blind studies in acupuncture research can be performed.

Acupuncture Points↗
PubMed1998

Syndrome X and endothelial dysfunction.

OBJECTIVE: Syndrome X (angina, normal coronary arteriogram and positive exercise test) remains an enigma with unexplained features and apparent conflicts of evidence. The present study addressed whether (i) the Syndrome is characterised by generalised flow-related endothelial dysfunction, (ii) myocardial thallium201 defects reflect myocardial or microvascular dysfunction, (iii) endothelial dysfunction and its consequences can be improved by oral L-arginine. METHODS: Flow-mediated brachial artery dilatation was measured by ultrasonic 'wall-tracking' in 7 Syndrome X patients, further characterised as having thallium201 defects and no known cause of endothelial dysfunction, and a normal control group. Syndrome X patients entered a 4-week randomised double-blind placebo-controlled cross-over trial of oral L-arginine (7 g twice daily), with brachial artery studies, exercise tests and technetium99 tetrafosmin scans. RESULTS: Flow-mediated dilatation was absent in Syndrome X vs. normal. Stress technetium99 tetrafosmin and thallium201 scans showed similar defects. Flow-mediated dilatation, symptom-limited exercise duration and peak oxygen consumption (VO2max) were increased but rate-pressure-product (RPP) and radionuclide defects were unchanged after L-arginine vs. placebo. CONCLUSIONS: The study supports coronary microvascular rather than myocardial dysfunction and shows loss of flow-mediated dilatation in systemic arteries. Oral L-arginine improved flow-mediated dilatation, exercise capacity and VO2max (by ca. 17%) despite unchanged RPP. The findings support generalised endothelial dysfunction. The arginine effects imply NO-mediated improvement of skeletal muscle perfusion suggesting improved homogeneity of microvascular distribution.

Administration, Oral↗
PubMed2003

No influence of melatonin on cerebral blood flow in humans.

Melatonin has been attributed a role in a number of physiological processes. Changes in distal skin temperature and blood pressure after intake of melatonin suggest that melatonin induces peripheral vasodilation. The effect on the cerebral blood flow is still unknown. We examined the effect of a single pulse of melatonin on cerebral and peripheral blood flow, using the latter as a positive control. Ten male healthy volunteers (mean age, 22 +/- 3.2 yr) participated in a double-blind, randomized, placebo-controlled, cross-over study. On one occasion 10 microg melatonin were infused i.v., and on the other occasion saline was infused as the matching placebo. Cerebral blood flow was measured using phase contrast magnetic resonance imaging. Peripheral blood flow was determined from changes in the distal to proximal skin temperature gradient and finger pulse volume. Serum melatonin concentration increased from 12 +/- 5 pg/ml at baseline to 487 +/- 377 pg/ml at 5 min and 156 +/- 68 pg/ml at 10 min after melatonin administration. There was no significantly different time course for cerebral blood flow and cerebrovascular resistance. Compared with placebo, melatonin significantly increased peripheral blood flow, as measured by distal to proximal skin temperature gradient and finger pulse volume. These data demonstrate that melatonin does not have an acute regulatory effect on cerebral blood flow in humans.

Adult↗
PubMed1994

Cyclic variation pattern of cerebral blood flow velocity and postconceptional age.

In preterm neonates, the risk for intracerebral haemorrhage is linked to immaturity of cerebral autoregulation. The preterm's 2-5/min cyclic variation pattern of cerebral blood flow velocity is thought to reflect the degree of immaturity of autoregulation--a speculation to be tested. In a cross-sectional study 15 infants (gestational age 26-40 weeks, postconceptional age (PCA) 26-42 weeks, age 1-99 days were investigated. We performed a 10 min pulsed Doppler tracing on an internal carotid artery by means of a computer controlled 5 MHz Duplex device. Systolic velocity (Vs) was recorded pulse by pulse. After appropriate data transformation, in all infants the Fast Fourier Transform of the time course of Vs revealed the presence of a 2-5/min cyclic variation pattern (one sample z-test, P < 0.0001). There was no significant correlation between proportionate spectral power of the 2-5/min frequency band and either PCA (r = 0.23, P = 0.42) or age (r = 0.41, P = 0.13). Between 26 and 42 weeks PCA, the cycling phenomenon is constant thus not reflecting cerebral maturation, and its presence does not mean immaturity of cerebral autoregulation.

Age Factors↗
PubMed1985

Effects of long-term exposure to solvents in the paint industry. A cross-sectional epidemiologic study with clinical and laboratory methods.

The effects of organic solvents on 50 male workers exposed 5-46 (mean 18) years were studied with a cross-sectional design. Referents were matched pairwise according to age and education. An analysis of confounders confirmed good comparability between the two groups. As indicators of organic brain dysfunction regional cerebral blood flow was measured and the power spectrum of the subjects' electroencephalograms was analyzed, the former being reduced 4% and the latter showing increased power in the delta and beta bands in the exposed group. Symptoms of brain dysfunction were significantly more frequent among the exposed subjects and showed an exposure-effect relationship. Neuropsychological tests revealed definite indication of brain dysfunction in 14% of the exposed subjects in comparison to none in the reference group. The exposed subjects performed significantly worse than the referents in tests measuring focused attention abilities. A neurophysiological examination of the peripheral nervous system showed no difference between the groups. Clinical chemistry demonstrated no differences that could be explained by solvent exposure.

Adult↗
PubMed1996

Measurement of DNA-protein cross-links in human leukocytes following acute ingestion of chromium in drinking water.

Increased DNA-protein cross-linking (DPX) in circulating leukocytes has been proposed as a potential biomarker for exposure and genotoxic damage caused by inhalation of certain reactive chemicals, such as hexavalent chromium [Cr(VI)]. This study was designed to determine whether ingestion of a single dose of potassium dichromate alone [Cr(VI)] or potassium dichromate fully reduced to Cr(III) with orange juice (prior to ingestion) causes an increase in DPX of circulating leukocytes in humans. Four adult male volunteers ingested a bolus dose of 5000 micro chromium in a 0.51 volume of water (10 p.p.m.), and blood samples were collected at 0, 60, 120, 180 and 240 min afterwards for analysis of DPX formation in circulating leukocytes. Results were compared to each person's own background concentration of DPX in leukocytes. Blood and urine samples were also collected for up to 2 weeks following the dose to examine the pattern of uptake and excretion of chromium. The results showed that there was no significant change in DPX observed following either Cr(VI) or Cr(III) ingestion, even though blood and urine chromium measurements indicated systemic uptake of a substantial fraction of the ingested chromium. Since Cr(III) does not possess DPX-inducing properties while Cr(VI) does, these results suggest that the Cr(VI) was reduced to Cr(III) intragastrically prior to absorption or that the amount of Cr(VI) absorbed into the blood was insufficient to produce DPX. These results are consistent with prior research that indicated that DPX would not occur following exposure to Cr(VI) except at very high doses.

Administration, Oral↗
PubMed2001

Is contrast-related vasodilatation after intra-coronary iodixanol and iopromide in vivo endothelium-dependent?

AIMS: Goals of the study were the assessment of the correlation between flow-dependent and contrast-related vasodilatation, comparison of iodixanol to iopromide and evaluation of the impact of plaque on vasodilatation in coronary arteries. METHODS AND RESULTS: A controlled randomized paired cross-over comparison between iodixanol (320mgI.ml(-1)) and iopromide (300mgI.ml(-1)) was performed in 10 consecutive patients. Vessel area (Visions Five-64 F/X intra-vascular ultrasound-catheter, Endosonics and blood flow velocity measurements (0.014inches Doppler guide wire, Cardiometrics were recorded simultaneously at an identical position, at baseline, after i.c. bolus injection of 10ml physiologic saline (flow-dependent vasodilatation), and after application of contrast agent 1 and contrast agent 2 as randomized. The action of iodixanol and iopromide on the vascular wall did not differ and was equal to local flow-dependent vasodilatation induced by a saline bolus (correlation 0.95-- 0.98). The increase in local luminal area after injection of saline, iodixanol and iopromide in morphologically normal vessels (approximately 2.5mm(2)) was absent in atherosclerotic segments. Both contrast agents and saline demonstrated a nearly identical flow increase. CONCLUSION: If iodixanol or iopromide are used as contrast agents, contrast-related vessel area increase in vivo seems to be endothelium-dependent.

Adult↗
PubMed1995

Age-response effectiveness of gallopamil for the treatment of myocardial exertional ischemia. A medium-term randomized cross-over double-blind placebo-controlled trial.

We evaluated the efficacy and safety of gallopamil 150 mg daily in middle-aged and elderly patients with stable exertional ischemia, using a medium-term randomized double-blind cross-over placebo-controlled trial. Twenty middle-aged patients (52.8 +/- 6 years; range 38-61 years) and 14 elderly patients (67.4 +/- 2.8 years; range 65-73 years) with stable exertional ischemia underwent a bicycle exercise test. After a run-in period, both groups received treatment with either placebo or gallopamil 50 mg tid for 28 days. At the end of this time, each patient crossed over to the alternate regimen. Gallopamil significantly reduced heart rate, blood pressure and rate pressure product (from 15.37 +/- 2.7 to 13.65 +/- 4.16 U x 10(-3); p < 0.01) in elderly patients at submaximal exercise, but had no effect in middle-aged patients (from 14.52 +/- 4.45 to 13.49 +/- 3.77 U x 10(-3); p = NS). At peak exercise, none of the hemodynamic parameters was modified with gallopamil in either group. At peak exercise, both middle-aged and elderly patients achieved rate-pressure products similar to those reached during placebo at higher work loads. Exercise duration and maximal work load significantly increased in both groups. Electrocardiographic signs of ischemia were favorably influenced by gallopamil in both groups (from 1.39 +/- 0.5 mm to 0.76 +/- 0.73 mm; p < 0.001 in the middle-aged patients and from 1.5 +/- 0.34 mm to 1 +/- 0.76 mm; p < 0.01 in the elderly patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Three-dimensional power Doppler ultrasound for the assessment of the fetal brain blood flow in normal gestation.

Early identification of the abnormal fetal brain vascularization and blood flow is very important, because the deficient perfusion of the fetal brain may be related to a poor prognosis of the central nervous system (CNS) development. To assess the fetal brain vascularization and the blood flow in normal gestation, we measured the fetal brain vascularization and the brain blood flow in normal fetuses using three-dimensional (3-D) power Doppler ultrasound (US) and the quantitative 3-D power Doppler histogram analysis. This study was undertaken by a prospective and cross-sectional design. In total, 155 normal singletons with gestational age (GA) between 21 and 40 weeks were included. The 3-D power Doppler US and the quantitative 3-D histogram analyses were used to assess the fetal brain vascular indexes, i.e., vascularization index (VI), flow index (FI) and vascularization-flow index (VFI), in each case. Our results revealed that all the fetal brain VI, FI and VFI increased significantly with GA (all p<0.001). In addition, the fetal brain VI, FI and VFI were all significantly correlated with the common fetal growth indices, such as biparietal diameter, occipitofrontal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight. Our study indicates that fetal brain vascularization and blood flow increase significantly with the advancement of GA as well as the fetal common growth indices during normal gestation. We believe our data may serve as a reference for further studies of the fetal brain blood flow in abnormal conditions.

Adult↗
PubMed2007

Maternal cardiac function in early pregnancies with high uterine artery resistance.

OBJECTIVE: To compare the maternal cardiac function and serum concentration of cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in first-trimester patients, according to uterine artery Doppler velocimetry (UADV). METHODS: This cross-sectional study included singleton pregnancies with normal UADV (n=17) and abnormal UADV (n=19). Maternal echocardiography was performed and blood samples were taken at 11-14 weeks. Echocardiographic parameters included: (a) left ventricular (LV) long axis velocities; (b) atrial size; (c) LV filling pressure; (d) the ratio of peak mitral flow velocity in early diastole and early mitral annular diastolic velocity (E/Ea ratio); and (e) the E/flow propagation velocity ratio. The maternal serum concentrations of cTnT and NT-proBNP were determined by sensitive and specific immunoassays. RESULTS: Patients with abnormal UADV had higher estimated left ventricular filling pressure (P=0.004), higher E/Ea ratio (P=0.03), higher E/flow propagation ratio (P=0.02), and lower LV long axis velocity (P=0.02) than those with normal UADV. There were no significant differences in the maternal serum concentration of cTnT or NT-proBNP. CONCLUSIONS: Patients with abnormal UADV in the first trimester have higher left ventricular filling pressure and may have left ventricular systolic dysfunction.

Adult↗
PubMed1997

Our distal aortic perfusion system in descending thoracic and thoracoabdominal aortic aneurysm repairs.

We have used heparin-bonded partial cardiopulmonary bypass to support distal aortic circulation during aortic cross-clamping. However, there were no cardiotomy reservoirs with fully reliable thromboresistance. To resolve this problem, a short-acting anticoagulant (nafamostat mesilate) was added into a cardiotomy reservoir. The present study was designed to evaluate the efficacy of our distal perfusion system. From May 1995 through the end of May 1996, 27 patients underwent descending thoracic and thoracoabdominal aortic aneurysm repairs with this adjunct, 4 being excluded from the experiment. Twenty patients who had undergone conventional partial cardiopulmonary bypass were defined as the control group. There were no significant differences between the 2 groups in the morbidity, mortality, gas transfer, or transfusion requirements despite the fact that more complicated surgical procedures (shown by a two-fold increase in the prevalence of reoperation) were required in the group that had received the current distal perfusion adjunct the heparin-bonded group. In conclusion, our perfusion system is very effective for descending thoracic and thoracoabdominal aortic aneurysm repairs.

Analysis of Variance↗