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Biomedical subjects

H K Iversen

Publications and source records attributed to H K Iversen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Experimental headache in humans.

The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose-dependent headache and dilatation of the temporal, radial and middle cerebral artery. NTG-induced headache, although less intense, resembles migraine in pain characteristics, but the accompanying symptoms are rarely present. Cephalic large arteries are dilated during migraine headache as well as during NTG headache. N-acetylcysteine enhances the formation of NO and potentiates NTG-induced headache, whereas mepyramine, a H1-antagonist capable of blocking histamine-induced headache, has no effect. Thus, the headache is dependent on NO or other steps in the NO cascade. The model is useful for pharmacological interventions and sumatriptan reduced the NTG-induced headache. The NTG model may be a valuable tool in the development of future migraine drugs.

Cerebrovascular Circulation↗
PubMed1995

Transcranial Doppler and cardiovascular responses during cardiovascular autonomic tests in migraineurs during and outside attacks.

The transcranial Doppler (TCD) and cardiovascular responses to established tests of autonomic function were studied in 50 migraineurs (23 of whom experienced aura and 27 who did not) and 30 healthy control subjects. In addition to the measurements outside attacks, 10 migraineurs were also tested during unilateral attacks of migraine without aura. Transcranial Doppler examinations of middle cerebral artery (MCA) blood velocity showed no differences between migraineurs and healthy subjects and no difference between migraineurs experiencing an attack and outside an attack when examined in response to a head-up tilt test, a cold-pressor test and a Valsalva manoeuvre. The cardiovascular reflexes in response to the Valsalva manoeuvre suggested a mild parasympathetic hypofunction in migraineurs, both those with and those without aura. On the basis of the present results and previous findings by others, we conclude that mild parasympathetic hypofunctioning with preserved sympathetic functioning is an established finding in migraine both with and without aura.

Adult↗
PubMed1995

Reduced arterial diameter during static exercise in humans.

In eight subjects luminal diameter of the resting limb radial and dorsalis pedis arteries was determined by high-resolution ultrasound (20 MHz). This measurement was followed during rest and during 2 min of static handgrip or of one-leg knee extension at 30% of maximal voluntary contraction of another limb. Static exercise increased heart rate and mean arterial pressure, which were largest during one-leg knee extension. After exercise heart rate and mean arterial pressure returned to the resting level. No changes were recorded in arterial carbon dioxide tension, and the rate of perceived exertion was approximately 15 units after both types of exercise. The dorsalis pedis arterial diameter was 1.50 +/- 0.20 mm (mean and SE) and the radial AD 2.45 +/- 0.12 mm. During both types of contractions the luminal diameters decreased approximately 3.5% within the first 30 s (P < 0.05), and during one-leg knee extension they continued to decrease to a final exercise value 7.6 +/- 1.1% lower than at rest (P < 0.05). Thus, they became smaller than during the handgrip. After exercise resting values were reestablished. When the arterial diameter was expressed in relation to mean arterial pressure for the radial and dorsalis pedis artery was 22 +/- 3 and 28 +/- 3% lower during handgrip than the relation during rest, respectively. After one-leg knee extension both arteries reached 30 +/- 4% lower values. This study demonstrated arterial constriction in the resting limbs within the first 30 s of static exercise, and continued constriction during one-leg knee extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Altered peripheral vasodilator profile of nitroglycerin during long-term infusion of N-acetylcysteine.

OBJECTIVES: The aim of this study was to compare the short- and long-term effects of intravenous nitroglycerin plus placebo and nitroglycerin plus N-acetylcysteine on peripheral arteries, veins and microcirculation in humans. BACKGROUND: The thiol donor N-acetylcysteine may potentiate the hemodynamic response to nitrates in nitrate-tolerant and nontolerant patients. The vascular changes responsible for this effect are not clear. METHODS: Eight male volunteers were treated with nitroglycerin (0.1 microgram/kg per min) combined with N-acetylcysteine (2 g intravenously, followed by 5 mg/kg per h) or placebo for 23 h in a double-blind, randomized, crossover study. Venous volume, the diameter of the radial and temporal arteries, calf blood flow and subcutaneous blood flow were measured at baseline and repeated after 1 and 23 h of infusion. RESULTS: Prolonged coadministration of N-acetylcysteine and nitroglycerin potentiated the acute venodilator effect of nitroglycerin as estimated by changes in venous volume (nitroglycerin plus N-acetylcysteine, 4.45 +/- 0.36 ml/100 g; nitroglycerin plus placebo, 3.65 +/- 0.46 ml/100 g, mean +/- SEM, p < 0.05) and prevented development of tolerance as seen after 23 h of treatment with nitroglycerin plus placebo (4.35 +/- 0.25 vs. 3.47 +/- 0.41 ml/100 g, p < 0.05). N-acetylcysteine had no effect on nitroglycerin-induced changes in arterial diameters (p > 0.05) but significantly increased microcirculatory subcutaneous blood flow after 1 h (nitroglycerin plus N-acetylcysteine: 6.3 +/- 1.3 ml/100 g per min vs. nitroglycerin plus placebo: 3.5 +/- 0.3 ml/100 g per min, p < 0.05) and after 23 h (4.4 +/- 0.6 vs. 3.1 +/- 0.5 ml/100 g per min, p < 0.05). CONCLUSIONS: The results suggest that coadministration of nitroglycerin and N-acetylcysteine in humans 1) potentiates and preserves nitroglycerin-induced venodilation and 2) augments the effect of nitroglycerin on small resistance vessels (regulating subcutaneous blood flow) without affecting the response to nitroglycerin in middle-sized arteries. Both the development of nitrate tolerance and the administration of N-acetylcysteine significantly change the normal vasodilator profile of nitroglycerin in humans.

Acetylcysteine↗
PubMed1994

CO2 measurements during transcranial Doppler examinations in headache patients: methodological considerations.

Transcranial Doppler (TCD) examinations are increasingly being used in studies of headache pathophysiology. Because blood velocity is highly dependent on PCO2, these parameters should be measured simultaneously. The most common way of performing measurements during TCD examinations is as end-tidal pCO2 with a capnograph. When patients are nauseated and vomit, as in migraine, the mask or mouthpiece connected to the capnograph represents a problem. We therefore evaluated whether a transcutaneous pCO2 electrode was as useful as the capnograph for pCO2 measurements in TCD examinations. We conclude that this is not the case, and recommend capnographic end-tidal pCO2 measurements during TCD examinations. However, transcutaneous pCO2 measurements may represent a supplement to spot measurements of end-tidal pCO2 in stable conditions when long-term monitoring is needed, and the mask or mouthpiece of the capnograph has to be taken on and off between recordings.

Adult↗
PubMed1994

Improved description of the migraine aura by a diagnostic aura diary.

We present a diagnostic aura diary for prospective recordings of migraine with aura. Three questionnaires are supplemented with sheets for drawings and plottings of visual and sensory auras. Twenty patients recorded 54 attacks of migraine with aura and 2 attacks of migraine aura without headache. The visual and sensory aura were usually gradually progressive, reaching maximum development in 15 and 25 min (median) respectively and had a total duration of 20 and 55 min (median) respectively. Approximately 13% of the attacks had acute onset of visual aura associated with other features more typical of migraine. The visual and sensory auras always preceded typical migraine headache, and headache occurring before aura symptoms was always of the tension type. The migraine headache was milder than in attacks of migraine without aura and often did not have migraine characteristics. In attacks with unilateral head pain, headache and aura symptoms were contralateral in 90% and ipsilateral in 10%.

Adolescent↗
PubMed1994

Nitroglycerin-induced headache is not dependent on histamine release: support for a direct nociceptive action of nitric oxide.

The molecular mechanisms of migraine pain have not yet been clarified. Monoamine and the peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Our previous studies of glyceryl trinitrate (GTN) and histamine-induced headaches have suggested that nitric oxide (NO) is the causative molecule in migraine pain. We furthermore suggest that substances capable of inducing experimental vascular headache do so via a common mediator which is NO. Finally, it is suggested that drugs exert their antimigraine activity by inhibiting NO or subsequent steps in the cascade of intracellular reactions triggered by NO. These novel observations change current views on vascular headache mechanisms and the importance of NO as an initiator of the migraine attacks dictates new approaches to the pharmacological treatment of migraine and other vascular headaches.

Analysis of Variance↗
PubMed1993

Lack of tolerance of headache and radial artery diameter during a 7 hour intravenous infusion of nitroglycerin.

Nitroglycerin-(NTG)-induced headache and dilatation of the radial artery were followed in a double blind, randomized, placebo-controlled, cross-over study in 6 healthy volunteers. NTG 0.5 microgram.kg-1 x min-1 or saline were infused i.v. for 7 h, and subsequently the infusion rate was doubled for 10 min. The radial artery diameter was measured repeatedly with high frequency ultrasound and pain was scored using a 10 point verbal scale. After 5 min of NTG infusion both headache and the arterial diameter differed significantly from baseline, and no further significant change occurred. The intensity of the headache was mild to medium (median headache score 3, range 1-7). The mean dilatation of the radial artery was 36%. The dilatation in each individual, was stable over time, both during NTG and placebo, and it did not change with the double infusion rate. The headache score in each individual was more fluctuant. No tolerance either to the NTG-induced headache or arterial dilatation was observed.

Adult↗
PubMed1993

Small arteries can be accurately studied in vivo, using high frequency ultrasound.

We have validated measurements of diameters of the superficial temporal artery and other small arteries in man with a newly developed 20 MHz ultrasound scanner with A, B and M-mode imaging. The diameter of a reference object was 1.202 mm vs. 1.205 mm as measured by stereomicroscopy (nonsignificant). In vitro measurements of porcine carotid arteries could be reproduced with a mean interobserver difference of 0.008 mm, and the repeatability coefficient was 0.04 mm (1.4%). The frontal branch of the human superficial temporal artery (mean 1.24 mm) was measured with intraobserver repeatability coefficients of 0.18 mm (13.8%) to 0.31 mm (23.4%). The interobserver mean difference was 0.01 mm (0.69%) and the interobserver repeatability coefficient was 0.16 mm (11.1%). Pulsatile changes of the cross sectional area of the radial plus the ulnar artery averaged 0.93 mm2 compared to 0.63 mm2 by strain-gauge plethysmography (nonsignificant). Pulsations were 4.6% in the radial artery. We conclude that high frequency ultrasound provides an accurate and reproducible measure of the diameter of small and medium sized human arteries in vivo.

Arteries↗
PubMed1993

Arterial supersensitivity to nitric oxide (nitroglycerin) in migraine sufferers.

The sensitivity to nitroglycerin-induced dilatation of large intracranial arteries was studied in 17 patients with migraine without aura, 17 age and sex-matched healthy subjects and 9 patients with episodic tension-type headache. Nitroglycerin in the doses of 0.015, 0.03, 0.25 microgram/kg/min was successively infused for 15 min per dose. Blood velocity (Vmean) in the middle cerebral artery (MCA) was recorded with transcranial Doppler before and at the end of every infusion period, and 30 and 60 min after end of the last infusion. In all three groups Vmean decreased with increasing doses (p < 0.001). The response was more pronounced in migraine patients at the two higher doses (p < 0.05). Since nitroglycerin acts as an exogenous source of nitric oxide (NO), these data support that NO supersensitivity may be an important molecular mechanism of migraine pain.

Adult↗
PubMed1993

Nitric oxide supersensitivity: a possible molecular mechanism of migraine pain.

Nitroglycerin, which may be regarded as a prodrug for nitric oxide, induces a mild to moderate headache in healthy subjects. In order to study whether migraine patients are more sensitive to nitric oxide than non-migrainous subjects, four different doses of intravenous nitroglycerin were given in a double blind design to 17 migraine patients, 17 age and sex matched healthy controls and 9 subjects with tension-type headache. The nitroglycerin-induced headache was significantly more severe in migraine sufferers, lasted longer and fulfilled diagnostic criteria for migraine more often. We have previously shown a similar supersensitivity to histamine which in human cerebral arteries activates endothelial H1 receptors and causes endothelial production of nitric oxide. Migraine patients are thus supersensitive to exogenous nitric oxide from nitroglycerin as well as to endothelially produced nitric oxide. It is suggested that nitric oxide may be partially or completely responsible for migraine pain.

Adult↗
PubMed1993

Experimental and biological variation of three-dimensional transcranial Doppler measurements.

A new transcranial Doppler system (3-D Transscan, Eden Medizinische Elektronik) was evaluated in relation to sex, age, intersubject, interobserver, side-to-side, and day-to-day variation. Fifty-eight healthy volunteers participated (aged 18-80 yr). Mean velocity was higher in females than in males and decreased with age. The coefficient of variation in the middle cerebral artery was 26% between subjects, 20% between sides, 16% between days, 13% between observers, and 7% during 5 min. The coefficient of variation was higher in the anterior and posterior cerebral arteries. Bruits were heard in 35 subjects, 24 females and 11 males (P = 0.002). When middle cerebral artery velocity was monitored, high- and low-frequency oscillations were found, with a mean frequency of 5 and 1.6/min, respectively. These variations underline the necessity of standardized conditions and very carefully matched control groups in studies using transcranial Doppler. This is especially important when expected changes are small and easy to overlook, as in studies of normal physiological responses and migraine.

Adolescent↗
PubMed1992

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate.

The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale. A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery. It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.

Adult↗
PubMed1992

N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses.

The effects of N-acetylcysteine, a sulfhydryl group donor, on nitroglycerin-induced headache and dilation of temporal and radial arteries were investigated in 11 healthy volunteers. Nitroglycerin, 0.06 microgram/kg/min, was infused for 20 minutes immediately after and 120 minutes after pretreatment with N-acetylcysteine (100 mg/kg) or placebo. Arterial diameters were measured with high frequency ultrasound, and pain was scored by use of a previously evaluated 10-point scale. Plasma levels of free (n = 2) and total (n = 11) N-acetylcysteine were determined. N-Acetylcysteine potentiated the headache response (median headache score, 3 versus 1), and the headache retained its vascular characteristics. Temporal artery dilation was also potentiated by N-acetylcysteine, 139% +/- 3% versus 127% +/- 3% of baseline, whereas the radial artery was unaffected. The potentiation was most pronounced after the first nitroglycerin infusion (12% versus 4.5% compared with placebo). A prolonged dilation of the temporal artery was observed only after the first nitroglycerin infusion, when high levels of N-acetylcysteine were present.

Acetylcysteine↗
PubMed1992

Presentation of a new instrument: the diagnostic headache diary.

A new instrument, the Diagnostic Headache Diary, based on the operational diagnostic criteria of the International Headache Society (IHS), was tested in 61 migraine patients from a headache research clinic using the clinical diagnosis (IHS criteria) for comparison. All patients kept the diary for one to eight months. The clinical and diary diagnosis of migraine with and without aura was the same in, respectively, 72 and 87% of the patients. Nausea, photophobia and phonophobia tended to be more pronounced at the clinical interview. The diary identified 20 more cases of episodic tension-type headache and 15 fewer cases of chronic tension-type headache than the clinical interview. Two blinded observers always made the same IHS diagnoses when interpreting the diagnostic headache diary. A combination of a clinical interview and the diagnostic headache diary gives a qualitatively and quantitatively more precise diagnosis than a clinical interview alone.

Adult↗
PubMed1991

Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan.

The combination of measurements of regional cerebral blood flow (rCBF) and blood velocity in the middle cerebral arteries (MCA) by transcranial doppler sonography was used to investigate cerebrovascular involvement in migraine. Ten migraine patients with unilateral headache were studied during an attack and when they had been free of attacks for 5 days (non-attack). On both occasions they were given as intravenous infusion of sumatriptan (2 mg), a 5-HT1-like receptor agonist, which relieved the symptoms within 30 min without affecting rCBF. The MCA velocity was normal on both sides on the non-attack day and on the unaffected side during the attack. However, during the attack the MCA velocity on the headache side was significantly lower than that on the non-headache side (45 vs 61 cm/s:mean difference 16.3 [95% confidence interval 10.3-22.3]; p = 0.02). The MCA velocity on the headache side returned to normal after treatment with sumatriptan and recovery. Since rCBF in the MCA supply territory was unaffected, the lower velocity can be explained only by dilatation of the MCA. The mean MCA diameter increase was estimated to be 20%. Thus, headache was associated with intracranial large arterial dilatation on the headache side. Sumatriptan predominantly had effects on the distended artery, which suggests that the 5-HT receptor system has a role in the pathogenesis of migraine.

Adult↗
PubMed1990

Arterial responses during migraine headache.

The superficial temporal artery has been thought to be the main focus of pain during migraine attacks, but its diameter has never been measured directly. The use of a new, high-resolution ultrasound machine to measure arterial size in 25 migraine patients with unilateral head pain showed that the lumen was wider on the painful than on the non-painful side during a migraine attack. The diameters of both radial arteries and the temporal artery on the non-painful side were smaller during than between attacks. The generalised vasoconstriction was not shared by the temporal artery on the affected side, which suggests a local vasodilatory response. The findings suggest that cephalic arteries may play a role in migraine pathogenesis.

Adult↗