Biomedical subjects

A F Van Leeuwen

Publications and source records attributed to A F Van Leeuwen.

7 recordsLinked to original sources

PubMed2000

Dexmedetomidine and haemodynamic responses to acute central hypovolaemia in conscious rabbits.

1. Effects of the alpha2-adrenoceptor agonist dexmedetomidine on vasoconstrictor and heart rate (HR) responses to acute central hypovolaemia were studied in eight chronically instrumented rabbits. We compared intravenous (i.v.) and fourth ventricular (V4) dexmedetomidine (0.1-10 microg/kg) and the reversal of effects by the alpha2-adrenoceptor antagonist idazoxan and the opioid agonist alfentanil. 2. Gradual inflation of an inferior vena cava (IVC) cuff reduced cardiac index (CI) by 8%/min, with progressive vasoconstriction and increased HR. In control rabbits, at approximately 40% baseline CI, there was sudden decompensation with failure of vasoconstriction and a fall in mean arterial pressure (MAP). 3. Dexmedetomidine (i.v. and V4) reduced resting MAP and HR and caused an earlier decompensation during central hypovolaemia. Intravenous dexmedetomidine (3 and 10 microg/kg) also reduced the slope of the initial vasoconstrictor response and the maximum HR. 4. The effects of dexmedetomidine were reversed by the antagonist idazoxan, which prevented the decompensation phase. Intravenous alfentanil was also effective in restoring the vasoconstrictor response and delaying decompensation with hypovolaemia after dexmedetomidine. Combining dexmedetomidine with an opioid, such as alfentanil, may provide the benefit of reduced sympathetic tone without increased risk of cardiovascular collapse.

Acute Disease↗

PubMed1998

Correction of hypovolemic hypotension by centrally administered naloxone in conscious rabbits.

Our goal was to test directly whether the vasoconstrictor action of naloxone during hypovolemic hypotension is centrally mediated. In eight chronically instrumented rabbits, progressive central hypovolemia and fall in cardiac output (CO) were produced by gradually inflating a cuff on the thoracic vena cava. Central hypovolemia was then sustained for 8 min by holding CO constant. In the main experiment (n = 4), each rabbit was studied eight times over 4 experimental days. Saline or naloxone treatment commenced 10 min before progressive hypovolemia (early treatment) or 2 min after the onset of sustained hypovolemia (late treatment), given by intravenous infusion or into the fourth ventricle (V4). With saline treatment, there was spontaneous recovery of systemic vasoconstriction and arterial pressure during sustained hypovolemia. Late treatment with naloxone (4 mg/kg i.v.; 4-37 micrograms/kg V4) accelerated and exaggerated these changes. Thus, under conditions of constant CO and central blood volume, the vasodilatation of the decompensatory phase of acute hypovolemia is not sustained, and intravenous nalox one's vasoconstrictor action is via a brain stem mechanism.

Animals↗

PubMed1997

Binocular saccadic eye movements in multiple sclerosis.

We attempted to increase the sensitivity for detection of abnormal binocular saccadic eye movements, particularly of the internuclear ophthalmoplegia (INO) type associated with multiple sclerosis (MS). Saccades of 10 and 20 degrees were binocularly recorded with scleral sensor coils in 10 normal control subjects and 26 patients with definite or probable MS, seven of whom had a clinically manifest INO in one or both directions. In the cases in which this was accompanied by a dissociated nystagmus of the abducting eye, our recordings showed that such secondary saccades were also expressed, in a strongly reduced form, by the adducting eye. The patients with manifest INO showed lower average peak velocities and peak accelerations, especially for adduction of the eye on the affected side, but the distribution of these parameters overlapped with the normal distribution. A much sharper distinction between normals and patients with INOs was found by considering the ratios between peak accelerations and velocities of saccade pairs (abducting eye/adducting eye). These ratios, which eliminate much intra- and inter-individual variability, had a narrow range in normals, and all values for INOs were outside this range. On this basis, the 19 patients without clinically manifest INO were easily separated into subgroups of 14 patients with completely normal interocular ratios and five patients with elevated peak velocity and acceleration ratios, identified as sub-clinical (uni- or bilateral) INOs. Measurements of vertical saccades and of interocular timing differences provided no useful criteria for disturbances of binocular coordination in MS. We conclude that in particular, the acceleration of the adducting eye is strongly reduced in patients with an INO, and that this reduction is best identified by interocular comparison between binocular pairs of saccades.

Adult↗

PubMed1995

Haemodynamic response to simulated haemorrhage in the rabbit: interaction of i.v. anaesthesia and hypoxia.

We have studied in eight rabbits the cardiovascular effects of midazolam, propofol and alfentanil with graded hypoxia. Central blood volume was reduced progressively by gradual inflation of a thoracic vena cava cuff so that cardiac index (CI) decreased at a constant rate. Under control conditions the haemodynamic response was biphasic. During phase I, mean arterial pressure (MAP) was maintained by a progressive decrease in systemic vascular conductance (SVCI). When CI had declined to a critical level, phase II occurred with an abrupt increase in SVCI and decrease in MAP. Phase I was prolonged by hypoxia, alfentanil and midazolam, but the effects were not additive. Phase I was shortened by propofol and this effect increased with hypoxia. The gradient of the SVCI response in phase I was also reduced by propofol > midazolam, but not by alfentanil. The occurrence of phase II was less frequent during alfentanil infusion than midazolam and propofol with all of the inspired gas mixtures. Thus the opioid was protective against circulatory collapse with hypoxia and simulated hypovalaemia.

Alfentanil↗

PubMed1990

Effects of halothane, ketamine, propofol and alfentanil anaesthesia on circulatory control in rabbits.

1. We have made a within-rabbit comparison of the effects of four general anaesthetic regimens on the haemodynamic response to acute reduction in central blood volume and on baroreflex control of heart rate. 2. Acute haemorrhage was simulated by gradually inflating a cuff on the inferior vena cava in order to cause cardiac output to fall at a constant rate of 8.5%/min while the responses of systemic vascular resistance, arterial pressure and heart rate were measured. The full range of the baroreceptor-heart rate reflex was elicited by inflating aortic and vena caval cuffs. These indices of circulatory control were repeatedly measured within five protocols, to which each rabbit was exposed in randomized order. 3. In each protocol the rabbit was first studied unanaesthetized. Then a small dose of thiopentone sodium was given (16 mg/kg). In the four main protocols the rabbit was then intubated and ventilated, first with 100% oxygen and then with 50% nitrous oxide, during administration of one of four anaesthetic agents. These were halothane (2.0 and 2.5%), ketamine (2.5 mg/kg per min), propofol (0.83 and 1.25 mg/kg per min) and alfentanil (2.5 and 3.33 micrograms/kg per min). In a sham protocol the effects of 100% oxygen, then those of 50 and 75% nitrous oxide, were studied while the rabbit remained conscious. 4. In unanaesthetized rabbits, in the presence or absence of nitrous oxide, the normal biphasic haemodynamic response to simulated haemorrhage occurred. The first, vasoconstrictor, phase was attenuated by halothane, ketamine and propofol, so that arterial pressure fell more steeply than normal. Not only was the vasoconstrictor phase unaffected by alfentanil but it was extended, so that arterial pressure remained at a normal level even when cardiac output had fallen by 59%. This effect of alfentanil appeared to be mediated centrally, since it could be reproduced by injecting small doses (1.5-7.5 micrograms) into the fourth ventricle. All four anaesthetic agents and nitrous oxide attenuated the baroreceptor control of heart rate. The effect was least with nitrous oxide and alfentanil, greatest with halothane.

Alfentanil↗

PubMed1989

Role of central opiate receptor subtypes in the circulatory responses of awake rabbits to graded caval occlusions.

1. In unanaesthetized rabbits, haemorrhage was simulated by inflating a cuff placed round the inferior vena cava so that cardiac output fell at a constant rate of approximately 8% of its resting value per minute. The circulatory responses were measured after injections into the fourth ventricle of saline vehicle, selective opioid antagonists, selective opioid agonists, and agonist-antagonist mixtures. Three sets of experiments were done to determine if a specific subtype of opiate receptor within the central nervous system is responsible for the circulatory decompensation that occurs during simulated haemorrhage. 2. In six rabbits the effects of ascending doses of the antagonists naloxone (mu-selective), Mr 2266 (kappa- and mu-selective), ICI 174864 (delta-selective) and nor-binaltorphimine (kappa-selective) were tested. In three rabbits the effects of the antagonist naloxone, the agonists HTyr-D-Ala-Gly-MePhe-NH(CH2)2OH (DAGO, mu-selective), U 50488H (kappa-selective), and [D-Pen2,D-Pen5]-enkephalin (DPDPE, delta-selective), and combinations of these agonists with naloxone were tested. In four rabbits the dose-related effects of DAGO on respiratory, as well as circulatory, functions were examined. 3. After injecting saline vehicle, the circulatory response to simulated haemorrhage had two phases. During the first phase, systemic vascular conductance fell, heart rate rose, and mean arterial pressure fell by only approximately 10 mmHg. A second, decompensatory, phase began when cardiac output had fallen to approximately 50% of its resting level. At this point, there was an abrupt rise in systemic vascular conductance and a fall in mean arterial pressure to less than or equal to 40 mmHg. 4. The lower range of doses of naloxone (3-30 nmol), Mr 2266 (10-100 nmol), ICI 174864 (10-30 nmol), and all doses of nor-binaltorphimine (1-100 nmol), were without effect on the circulatory response to stimulated haemorrhage. Higher doses of naloxone (30-100 nmol), Mr 2266 (100-300 nmol) and ICI 174864 (30-100 nmol) abolished the decompensatory phase. The relative order of antagonist potency was ICI 174864 greater than or equal to naloxone greater than Mr 2266 greater than or equal to nor-binaltorphimine. 5. In the second set of experiments, the critical dose of naloxone necessary to prevent circulatory decompensation during simulated haemorrhage was 30-150 nmol. The delta-agonist DPDPE (50 nmol) did not affect the haemodynamic response to simulated haemorrhage, but it did block the effect of naloxone on the response.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Haemodynamic responses to acute blood loss: new roles for the heart, brain and endogenous opioids.

Information has come forward recently from several sources which provides new insights into the mechanisms that underlie the haemodynamic responses to acute blood loss. In unanaesthetised animals and human volunteers there are two distinct phases to these responses. At first, the engagement of baroreflexes results in a progressive rise in sympathetic vasoconstrictor drive and peripheral resistance, and the maintenance of arterial blood pressure at a near-normal level. When about one-third of blood volume has been lost, reflex sympathetic drive is switched off, and peripheral resistance and blood pressure fall abruptly to low levels despite a burst of vasopressin release. Research in conscious animals has now shown that the onset of this decompensatory phase is triggered by a signal from the heart, which activates an endogenous opioid mechanism in the brain. Activation of this mechanism can be prevented by administering a selective delta-receptor antagonist, or selective mu-receptor agonists (including alfentanil). It has not yet been established that this endogenous opioid mechanism is responsible for the decompensatory phase of acute blood loss in man, nor that it can be prevented or reversed by selective opioid agonists or antagonists.

Acute Disease↗