Biomedical subjects

N Mayer

Publications and source records attributed to N Mayer.

At least 55 records · Page 3Linked to original sources

PubMed1990

Sufentanil does not increase cerebral blood flow in healthy human volunteers.

The effect of sufentanil on human cerebral blood flow (CBF) was studied in seven unpremedicated, healthy volunteers 31 +/- 3.5 yr of age (mean +/- SD) and either sex. CBF (ml.100 g-1.min-1) was measured noninvasively with the 133Xe clearance technique and a scintillation camera before and after sufentanil 0.5 micrograms/kg administered intravenously. This technique provides values for global blood flow and for gray and white matter blood flow, and from 13 preselected regions in one hemisphere. After the administration of sufentanil, the volunteers were stimulated verbally in order to prevent their loss of consciousness and hypercarbia. Heart rate (HR), arterial pressure, oxyhemoglobin saturation, and end-tidal CO2 (ETCO2 were recorded during the measurements. Neither global CBF (46.1 +/- 1.6 control and 43 +/- 1.9 after sufentanil, mean +/- SEM) nor gray (76.5 +/- 3.2 and 70.9 +/- 6.1) or white (22.7 +/- 1.5 and 24.2 +/- 1.6) matter blood flow changed significantly after sufentanil administration. As well, no significant differences in HR (72 +/- 4 control and 79 +/- 4 beats per min after sufentanil) and ETCO2 (39.8 +/- 1.4 and 41.1 +/- 1.1 mmHg) were observed. It is concluded that sufentanil has no significant effect on CBF in healthy human volunteers.

Adult↗

PubMed1990

Enflurane alters compensatory hemodynamic and humoral responses to hemorrhage.

This study examined the impact of enflurane (3%) on the hemodynamic and humoral defense mechanisms in a canine model of hemorrhagic shock. In order to obtain reasonable reference values with confounding influences of anesthesia and recent surgical preparation, the dogs were chronically instrumented 8-10 days prior to the experiments enabling measurements in the conscious state. While arterial pressure, cardiac output, and the corresponding derivatives were recorded continuously, plasma catecholamines and plasma renin activity were determined intermittently. As anticipated, the conscious dogs were able to tolerate considerable more severe levels of hemorrhage than the dogs anesthetized with enflurane. This finding is associated with reciprocal responses of both the renin-angiotensin system and the sympathoadrenal system in the conscious and anesthetized states. While the sympathoadrenal system prevailed in the conscious dogs, the renin-angiotensin system predominated during enflurane anesthesia. Despite the augmented response of the renin-angiotensin system, the activation of this defense mechanism was not sufficiently powerful enough to prevent overall hemodynamic deterioration with hemorrhage in the animals anesthetized with enflurane.

Anesthesia, Inhalation↗

PubMed1990

[The effects of propofol bolus administration on the intracranial pressure in craniocerebral trauma].

Previous investigations have revealed that propofol has a beneficial effect on intracranial dynamics in patients undergoing elective neurosurgery. In the present study we evaluated the impact of propofol in patients with normal or compromised intracranial compliance. METHODS. Epidural ICP probes were implanted in 14 patients with head injury. The heart rate, mean arterial pressure (MAP), intracranial pressure (ICP) and end-tidal CO2 were recorded continuously, and propofol was given in doses of 0.5, 1.0 and 2.0 mg/kg; there were 15 min between each application. The data were evaluated 1, 2, 5 and 10 min after each application. The patients were allocated to group I (ICP less than 20 mmHg) or group II (ICP greater than 20 mmHg) according to their ICP baseline level. A statistical analysis was performed by one-way ANOVA. A P value of less than 0.05 was regarded as significant. RESULTS. In group I decreases in MAP at all measuring points were detected with 1.0 and 2.0 mg/kg propofol; ICP with 1.0 and 2.0 mg/kg and CPP with 2.0 mg/kg fell significantly. In group II MAP decreased with all doses studied, as did ICP with 1.0 and 2.0 mg/kg; however, CPP was not particularly influenced. CONCLUSION. Propofol decreased ICP in patients with normal and compromised intracranial compliance, particularly with 2.0 mg/kg. As the responses to the hypotensive effects of propofol were mild and almost similar in both groups, no inadvertent CPP drops were observed with any of the doses studied. Thus, propofol as a bolus can be used safely for the sedation of ICU patients with head injury and normal or compromised intracranial compliance.

Adult↗

PubMed1989

UH-AH 37, an ileal-selective muscarinic antagonist that does not discriminate between M2 and M3 binding sites.

The novel antimuscarinic compound UH-AH 37 (6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidyl)acetyl]-11H- dibenzo-[b, e][1,4]diazepine-11-one hydrochloride) showed a 14-fold higher affinity for ileal than for atrial muscarinic receptors. In receptor binding studies UH-AH 37 showed no marked selectivity for either atrial, glandular or ileal muscarinic binding sites. Moreover, it did not reveal binding heterogeneity in membranes from ileal smooth muscle. These result indicate that UH-AH 37 possesses a unique and novel selectivity profile.

Animals↗

PubMed1989

Fentanyl inhibits the canine carotid chemoreceptor reflex.

To investigate the impact of fentanyl on the carotid chemoreceptor reflex, nine mongrel dogs were permanently monitored with electromagnetic flow transducers around the right common iliac artery and with heparin-filled catheters in the descending aorta and in one of the main carotid arteries with the tip just proximal to the carotid sinus. Carotid chemoreceptor activation (CCRA) produced by consecutive injections of nicotine (0.2-0.4 micrograms/kg) through the carotid catheter elicited bradycardia, expressed as an increase in cardiac cycle length by 140% +/- 18%, and a 252% +/- 16% increase in mean iliac arterial vascular resistance. These responses were markedly attenuated by fentanyl in a dose-dependent fashion: cardiac cycle length increased only by 50% +/- 7% (P less than 0.01) with 4 micrograms/kg and by 19% +/- 6% (P less than 0.01) with 8 micrograms/kg of intravenous fentanyl. These changes were paralleled by significantly (P less than 0.01) lesser increases in mean iliac arterial resistance (122% +/- 9% and 50% +/- 5%). It is concluded that fentanyl impairs the integrity of the carotid chemoreceptor reflex.

Animals↗

PubMed1989

Structure-activity relationships and pharmacological profile of selective tricyclic antimuscarinics.

The discovery of the M1-selective receptor antagonist pirenzepine was the impetus for a research project directed towards the development of selective muscarinic antagonists. In the pursuit of this objective, compounds with different selectivity profiles have been found. AF-DX 116 was the first cardioselective antagonist synthesized. Subsequently novel M2 receptor antagonists have been discovered with higher potency and selectivity. Moreover, a pirenzepine-type compound UH-AH 37 has been identified that, in contrast to pirenzepine, shows a higher affinity for ileal than for atrial muscarinic receptors. Among tricyclic muscarinic receptor antagonists three different selectivity profiles have been identified, namely: M1 greater than M3 greater than M2, Msm for pirenzepine; M2 greater than M1 greater than M3, Msm for AF-DX 116, AF-DX 384, AQ-RA 741; and Msm congruent to M1 greater than M2, M3 for UH-AH 37 and its (+) enantiomer.

Antidepressive Agents, Tricyclic↗

PubMed1988

The effects of nitroglycerin on regional myocardial contractile dysfunction produced by treadmill exercise or isoprenaline stimulation in dogs.

1. To compare different methods of cardiac stress testing that are clinically applied in the management of coronary heart disease, 2 groups of dogs each were chronically instrumented and subjected to treadmill exercise or isoprenaline infusion in the presence of coronary stenosis. 2. It was of interest to determine differences in haemodynamic and regional myocardial contractile parameters, the response to antianginal therapy (nitroglycerin 15 micrograms kg-1 15 min-1, i.v.), and, in particular, whether this response differed according to the mode of cardiac stimulation, i.e. treadmill exercise or isoprenaline infusion. 3. After stenosis of the circumflex branch of the left coronary artery which affected resting myocardial function only minimally, treadmill exercise or isoprenaline infusion induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular end-diastolic pressure and left ventricular dp/dtmax were registered and myocardial oxygen demand was calculated. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4. Treadmill exercise led to an increase in systolic arterial and left ventricular end-diastolic pressure. In contrast, isoprenaline-induced stimulation led to a decrease in diastolic arterial and left ventricular end-diastolic pressure. Regional contractile function in the critically underperfused area showed a deterioration during both modes of stress. Nitroglycerin completely abolished stress-induced contractile dysfunction only in the group where treadmill exercise was employed for stimulation. 5. The inability of nitroglycerin to prevent myocardial dysfunction in the isoprenaline group may be due to exhaustion of the arterial and/or venous vasodilator potency of nitroglycerin in the presence of adrenoceptor vasodilatation induced by isoprenaline. 6. These findings indicate that clinical antianginal drug testing and the evaluation of the course of disease in patients with coronary heart disease may be highly dependent on the test method chosen.

Animals↗

PubMed1988

Verapamil abolishes exercise-induced regional contractile dysfunction in dogs.

The effects of the Ca++-antagonist verapamil on hemodynamic and regional myocardial functional parameters were studied in a canine model of exercise-induced myocardial dysfunction which mimics exercise-induced angina pectoris. Six dogs, trained to submit to five treadmill exercise cycles, each consisting of 4 min of running and 11 min of recovery, were chronically instrumented with a microtip manometer in the left ventricle, two pairs of crystals for sonomicrometry, a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Control experiments with coronary stenosis clarified the reproducibility of exercise-induced regional contractile dysfunction and recovery of function in the intervening resting periods. In each individual dog, the same degree of stenosis was used in the subsequent experiments with verapamil. After two control runs which exhibited regional contractile dysfunction of comparable magnitude, verapamil was administered intravenously at a dosage of 0.3 mg/kg over a period of 5 min. Verapamil induced an increase in heart rate at rest due to sympathetic counterregulation secondary to a reduction of systolic and diastolic blood pressure. The exercise-induced increases in heart rate and rate-pressure product were reduced after verapamil, but the exercise-induced increase in left ventricular dp/dtmax was not significantly diminished. The hemodynamic changes led to a marked improvement of regional function during exercise in the area perfused by the stenosed coronary artery. In a study using identical experimental conditions, the Ca++-antagonist bepridil at a dosage of 2 mg/kg/5 min abolished the exercise-induced regional contractile dysfunction to a similar extent as verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Tricyclic compounds as selective antimuscarinics. 1. Structural requirements for selectivity toward the muscarinic acetylcholine receptor in a series of pirenzepine and imipramine analogues.

The M1-selective antiulcer drug pirenzepine (1) is a tricyclic compound with close resemblance to tricyclic psychotropic agents such as imipramine (2). Despite this fact, pirenzepine is devoid of any psychotropic effects, exhibiting measurable antagonistic effects in biochemical assays and receptor binding studies only toward the muscarinic receptor system. To understand how different groups in these tricyclic molecules affect binding affinities, a set of nine compounds structurally related to pirenzepine (1) and imipramine (2) has been selected for analysis, comprising three different tricycles and three different side chains. The compounds were tested for their affinity to the imipramine and muscarinic receptors in homogenized rat cortex tissue. The result of these studies suggests that it is the nature and placement of accessory groups that determine the differences in receptor recognition and the binding process. In the case of pirenzepine (1), preferential binding toward the muscarinic receptor is brought about by the endocyclic amide group, by the positioning of the protonated N atom of the side chain, and to a minor extent by the exocyclic amide group. From these findings a putative model for the explanation of selective binding of pirenzepine (1) to the muscarinic receptor has been derived.

Animals↗

PubMed1987

Effects of specific bradycardic agents on exercise-induced regional myocardial dysfunction in dogs.

Alinidine and ULFS 49, two specific bradycardic agents were comparatively investigated with propranolol in a model of exercise-induced regional myocardial contractile dysfunction in dogs. Standardized treadmill exercise resulted in a marked decrease in regional function in the myocardium supplied by the critically stenosed circumflex branch of the left coronary artery. All three drugs prevented exercise-induced myocardial dysfunction. The effect on the exercise-induced increase in heart rate and left ventricular dp/dt, however, suggests different modes of action. Propranolol prevents dysfunction by a marked negative inotropy and negative chronotropy, alinidine by a marked negative chronotropy and moderate negative inotropy, but ULFS 49 prevents dysfunction solely by a marked negative chronotropic effect.

Animals↗

PubMed1987

Antihypertensive effects of niguldipine-HCl (B 844-39), a new calcium antagonist in dogs.

B 844-39 is a new dihydropyridine calcium antagonist with a long-lasting antihypertensive action. Preliminary tests in chronically instrumented normotensive dogs revealed that B 844-39 (0.3 mg/kg p.o.) caused a marked decrease in blood pressure which was accompanied by a counterregulatory increase in heart rate. Both effects outlasted the 6-h observation period. There was no sign of cardiac depression in left ventricular positive dP/dtmax or sonomicrometrically evaluated subendocardial systolic shortening. B 844-39 was also tested in renal hypertensive dogs over a period of 12 days to investigate its potential in the long-term treatment of hypertension. A dosage of 0.3 mg/kg given orally twice a day led to a marked and persistent decrease in blood pressure, which was accompanied by a positive chronotropic effect and increases in plasma renin activity and angiotensin II. This initial counterregulatory response was blunted within several days of chronic treatment. After completion of the 12-day treatment period, the blood pressure reduction persisted for greater than 14 days. B 844-39 induced a marked and persistent reduction in blood pressure in hypertensive dogs, even with prolongation of the dosing interval to 24 h. The hypotensive effect of this drug was more pronounced in hypertensive than in normotensive animals.

Animals↗

PubMed1987

The effects of nitroglycerin on exercise-induced regional myocardial contractile dysfunction are not diminished by pretreatment with dihydroergotamine.

1 Because controversy exists regarding the effects of dihydroergotamine (DHE) on the performance of underperfused myocardium, the effects of DHE were investigated in a model of exercise-induced regional myocardial dysfunction in conscious dogs. 2 We also investigated a possible functional antagonism between DHE and nitroglycerin that might reduce the latter drug's antianginal efficacy. 3 Investigations were carried out in conscious dogs. After stenosis of the circumflex branch of the left coronary artery that minimally affected resting myocardial function, treadmill exercise induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular dp/dtmax and left ventricular end-diastolic pressure were registered. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4 DHE (5 micrograms kg-1, i.v.) induced a decrease in left ventricular dp/dtmax at rest and during exercise. DHE did not cause a deterioration in contractile function in the ischaemic myocardium, but led to a slight although not significant improvement in regional myocardial function. 5 After pretreatment with DHE, infusion of nitroglycerin (15 micrograms kg-1, i.v.) induced an improvement in the underperfused myocardial area during treadmill exercise, accompanied by a decrease in diastolic arterial pressure and left ventricular end-diastolic pressure and an increase in left ventricular dp/dtmax. 6 These results suggest that DHE will not worsen exercise-induced angina pectoris, and that the antianginal efficacy of nitroglycerin will not be neutralized by pretreatment with DHE.

Animals↗

PubMed1986

Effects of alinidine on exercise-induced regional contractile dysfunction in dogs.

The effects of the bradycardiac agent alinidine on hemodynamic parameters and regional contractile function were investigated in 6 chronically instrumented dogs trained to submit to 5 consecutive treadmill exercise runs. The experiments were performed during stenosis of the circumflex branch of the left coronary artery (LCX). After 2 control runs which had induced regional contractile dysfunction of comparable intensity, alinidine was infused intravenously at a dosage of 1 mg/kg per 5 min. The drug significantly reduced the resting function of both the LCX area (-16%) and the area perfused by the unstenosed anterior descending branch of the left coronary artery (LAD, -3%). However, the exercise-induced dysfunction of the LCX area was markedly improved in the 1st post-drug run and completely abolished during the 2nd and 3rd post-drug runs. As indicated by the reduction of heart rate (-18%) and positive dp/dtmax (-24%) during peak exercise, this improvement may be attributed to a bradycardiac and a negative inotropic effect of this drug. Further benefit may be ascribed to a decreased in arterial blood pressure after alinidine.

Animals↗

PubMed1986

A model of transient myocardial dysfunction in conscious dogs. Regional shortening in the presence of impaired coronary flow reserve and treadmill exercise.

An experimental model of treadmill exercise-induced regional myocardial dysfunction was developed in conscious dogs to mimic exertional angina pectoris in man. Twenty mongrel dogs, trained to run on a treadmill, were chronically instrumented with a miniature pressure transducer in the left ventricle and a hydraulic occluder placed around the circumflex branch of the left coronary artery. Two pairs of piezoelectric crystals for sonomicrometry were implanted subendocardially to measure regional myocardial function. Experiments were started 1 week after surgery. In the first group of ten dogs exercise with constant work load of 10 km/hr and 10% elevation during partial left coronary artery stenosis, induced by external filling of the occluder, produced comparable episodes of regional dysfunction in the left coronary artery area during five subsequent treadmill runs and recovery of function after each run. The second group of ten dogs, exercised with left coronary artery stenosis and increasing working load, exhibited minimal regional dysfunction in the left coronary artery area while running at 6 km/hr and 6% elevation, but maximal regional dysfunction during peak exercise (10 km/hr and 10% elevation). This load dependency and recovery of function after the runs was demonstrated during five identical consecutive exercise cycles. This model, in contrast to those using ameroid constrictors, enables various drugs to be tested in a single instrumented dog over a period of several weeks.

Angina Pectoris↗

PubMed1986

Bepridil abolishes exercise-induced regional contractile dysfunction in dogs.

The effects of bepridil, a calcium antagonist, on hemodynamic parameters and regional contractile function were investigated in six dogs trained to submit to five treadmill exercise cycles consisting of 4 min of running and 11 min of recovery. The animals were chronically instrumented with a microtip manometer in the left ventricle, two pairs of piezoelectric crystals for sonomicrometry and a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Experiments were started 1 week after surgery. After a warming-up exercise the vessel was partly stenosed by external filling of the hydraulic occluder. Stenosis was considered adequate and maintained when hemodynamic and functional parameters were virtually unchanged at rest, but episodes of comparable regional contractile dysfunction of the area perfused by the stenosed artery occurred in response to exercise in five subsequent runs; the same degree of stenosis was used for the experiments with bepridil. After two runs with comparable regional contractile dysfunction bepridil was infused intravenously at a dosage of 2 mg/kg per 5 min. The exercise-induced dysfunction was minimally improved in the 1st post-drug run but completely abolished during the 2nd and 3rd post-drug runs. This marked improvement may be partly attributable to the hemodynamic effects of this drug, namely a diminished increase in heart rate and left ventricular end-diastolic pressure and even a reduction in end-diastolic segment length during exercise. These results support the findings of initial clinical trials and suggest a beneficial effect of bepridil in the treatment of exercise-induced angina pectoris in man.

Animals↗

PubMed1986

Effects of long-term administration of propyldazine on blood pressure and counter-regulatory systems in conscious hypertensive dogs.

The counter-regulatory effects in response to blood pressure reduction by propyldazine were studied in conscious dogs with bilateral cellophane perinephritis hypertension. During a 22-day period of chronic treatment, the initial increase in heart rate, plasma renin activity, angiotensin II, aldosterone, and vasopressin, which indicate counter-regulation to the drug induced decrease in blood pressure, vanished. On the fifth day of treatment another, presumably cellular mechanism, had taken over the restitution of blood pressure and thereby led to tolerance towards the action of further propyldazine administration. Seven days after the end of chronic treatment a renewed propyldazine administration did not produce the same effects as obtained with the first administration; after 28 days the hypotensive effect of propyldazine was identical to the one observed before treatment.

Animals↗

PubMed1985

[Effect of enflurane on the function of the chronically ischemic myocardium].

The effects of enflurane on the function of the chronically ischemic myocardium were studied in nine dogs, 2-8 weeks after implantation of Doppler-ultrasound flow transducers around the circumflex branch of the left coronary artery, of pairs of ultrasonic crystals in normal and ischemic regions of the left ventricle, aortic catheters, and of solid-state left ventricular pressure gauges. Enflurane (2% and 4% inspired) caused an increase in heart rate and dose-dependent decreases in left ventricular pressure, dP/dt, mean arterial pressure and mean circumflex coronary resistance. However, in comparison to the normal myocardium neither exaggerated nor permanent dysfunction of the chronically ischemic but still contracting myocardium was noted. Thus, reduction of coronary perfusion pressure and coronary vasodilatation does not seem to be of major functional significance in determining ischemic left ventricular performance during anesthesia with enflurane.

Animals↗

PubMed1984

Distribution of spinal cord nerve endings containing various neurotransmitters on a continuous density gradient.

Homogenates of rat dorsal or ventral spinal cord were subjected to centrifugation on a continuous density gradient. The gradient was generated according to a new method with the aid of a microprocessor-controlled HPLC pump. The distribution of substance P-like immunoreactivity (SPI) and somatostatin-like immunoreactivity (SRIFI) across the gradient showed two peaks. The SPI peak seen at lower density was found only in dorsal spinal cord tissue. No peak of SPI was seen at this position in homogenates prepared from the spinal cords of capsaicin-pretreated rats. The second peak of SPI, found at a higher density, was accompanied by peaks in the levels of endogenous 5-hydroxytryptamine (5-HT), [14C]glycine, and [3H]norepinephrine uptake. This peak was seen at the same density in the dorsal and the ventral spinal cord. Tissue derived from capsaicin-pretreated rats exhibited one peak of SPI, accompanied by a maximum of [14C]glycine uptake. The uptake of [3H]gamma-aminobutyric acid ( [3H]GABA) was found to have a maximum at a somewhat lower density than that of [14C]glycine. It is concluded that the peak of SPI found at lower density in the dorsal spinal cord is associated with nerve endings belonging to capsaicin-sensitive primary afferents, while other endings, including those also containing 5-HT, are probably associated with the peak of SPI found at higher density.

Animals↗