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Biomedical subjects

N Mayer

Publications and source records attributed to N Mayer.

At least 37 records · Page 2Linked to original sources
PubMed1996

A new scoring system, using Doppler transmitral diastolic measurement, identifies transient myocardial ischaemia.

In patients with acute transient myocardial ischaemia, changes in left ventricular filling produce alterations in transmitral diastolic flow velocity and isovolumic relaxation time. In this study a scoring system derived from isovolumic relaxation time and indices from transmitral flow velocity was used to evaluate perioperative transient myocardial ischaemia. Fifty three patients with known coronary artery disease or at risk were studied. Ischaemic events were assessed using Doppler transoesophageal echocardiography midoesophageal left ventricular four-chamber view planes. Diastolic Doppler ratios of peak early to atrial peak (E/A), deceleration time, deceleration rate and isovolumic relaxation time were scored using standard methods. An evaluation of peri-operative ischaemic events could be important for patients with a non-ischaemic cause for abnormal segmental wall motion, as the use of a two-dimensional scoring system has limitations. Acute changes in the Doppler ratio of peak early to atrial peak must be interpreted cautiously during surgery. Diastolic dysfunction commonly occurs during ischaemia and recognition of this may alter the approach to monitoring as well as to treatment.

Adult↗
PubMed1996

Anaesthesia and systemic oxygenation.

BACKGROUND: Anaesthesia induction and deep anaesthesia may be accompanied by a considerable haemodynamic depression, especially in patients suffering from cardiovascular diseases. A decrease in cardiac index (CI) leads to a concomitant decrease in oxygen transport (DO2I). We examined whether these changes in haemodynamic performance and oxygenation can cause an oxygen debt and anaerobic metabolism. METHODS: DO2I, oxygen uptake (VO2I), oxygen extraction ratio (O2ER) and plasma lactate were analysed at 9 pre-defined study stages during anesthesia induction, deep anaesthesia prior to surgery and during surgery in 65 patients (ASA 3) undergoing elective vascular surgery. Polynomials of increasing order were fitted to the data for the determination of the critical value of oxygen transport from the inflection point of the regression curve. RESULTS: CI, heart rate, mean arterial pressure and DO2I decreased significantly after anaesthesia induction and during deep anaesthesia. VO2I showed an almost parallel change during the study period so that O2ER remained nearly constant. Plasma lactate did not exceed the physiological range in any patient and a critical value of DO2I could not be detected because a linear regression always provided the best fit for the data. CONCLUSIONS: We conclude that in patients suffering from a substantial cardiovascular disease systemic oxygenation is not impaired by considerable haemodynamic changes induced by general anaesthesia. This fact can be explained by the parallel decrease in oxygen demand, expressed by the decrease in VO2I.

Aged↗
PubMed1995

Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks.

Clonidine in spinal and epidural blocks prolongs anesthesia, but can cause hypotension and bradycardia. The aim of our study was to compare hemodynamic and analgesic effects of spinal versus epidural clonidine alone and after repetitive dosing. In a prospective, randomized, double-blind study, we evaluated 40 patients scheduled for lower extremity orthopedic surgery under continuous spinal or epidural anesthesia with bupivacaine 0.5% (initial dose 5 mg and 50 mg, respectively). In either spinal or epidural technique one-half of patients received clonidine (150 micrograms) in addition to bupivacaine. Repeat doses of the same anesthetic mixture were allowed in cases of subsequent pain. Mean arterial pressure (MAP) and heart rate were recorded for 6 h after each injection. Duration of clinically useful anesthesia was defined as the time from drug administration to first sensation of pain. Intrathecal, but not epidural, clonidine decreased MAP significantly compared with bupivacaine alone. MAP after intrathecal clonidine with bupivacaine was lower than epidural clonidine with bupivacaine 5 and 6 h after injection. Repetitive administration caused no further decrease in MAP. Onset time required to surgical anesthesia (sensory block of T11) did not differ among the four groups. Duration of spinal and epidural anesthesia was increased more than two fold by clonidine. In summary, the addition of clonidine prolongs analgesia by either route. These results may be explained by clonidine's sites of action in hemodynamic control and the density of bupivacaine-induced block.

Aged↗
PubMed1995

In vivo modulation of human neutrophil function by pentoxifylline in patients with septic syndrome.

The influence of pentoxifylline on human polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA) was studied in 23 patients fulfilling the established criteria of sepsis and in 10 healthy donors. Pentoxifylline (PTX) was administered (5 mg/kg) by intravenous infusion in 13 septic patients over a period of 180 min. The control group consisted of 10 patients with septic syndrome who received an infusion of physiological saline. For determination of RBA, 10 mL of blood was drawn at respective time intervals before, during, and after treatment with PTX or a placebo. RBA measurements were performed using a chemiluminescence assay after stimulation of PMN with formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-myristate-acetate, and opsonized zymosan, respectively. RBA measurements of each patient were performed in replicate samples. CL was measured for 1 h at respective time intervals (1, 3, 5, 8, 10, 15 min etc). RBA of PMN of septic patients was compared with RBA of PMN of healthy donors and patients receiving PTX were compared with controls. Our results demonstrate that PMN of patients with sepsis had an increased oxidative response compared with healthy donors. We found that PTX administered intravenously was able to reduce this reactivity. RBA was significantly decreased during PTX infusion when PMN were stimulated with FMLP and phorbol-myristate-acetate, compared with the control group. No significant decrease was observed when PMN were stimulated with opsonized zymosan. These data suggest that PTX may be a valuable drug in septic state.

Adult↗
PubMed1994

Pharmacological profile of selective muscarinic receptor antagonists on guinea-pig ileal smooth muscle.

The present study examined the effects of a series of tricyclic muscarinic receptor antagonists on muscarinic receptors present in the guinea-pig ileum, both in vitro and in vivo. The selectivity profiles of these antagonists and that of atropine were determined by their affinity for cortical muscarinic M1, cardiac M2 and submandibular M3 receptors and for m4 receptors expressed in CHO cells. The compounds pirenzepine, UH-AH 37, AQ-RA 391 and AQ-RA 618 possessed high affinity (pKi 7.94-8.22) for muscarinic M1 receptors. Pirenzepine exhibited the most pronounced muscarinic M1 selectivity. AF-DX 384 and AQ-RA 741 possessed an approximately 10-fold higher affinity for the cardiac muscarinic M2 receptor than AF-DX 116. However, both compounds also exhibited high affinity for muscarinic m4 receptors. High affinity for muscarinic M3 and m4 receptors was observed for UH-AH 37, AQ-RA 391 and AQ-RA 681. The antagonists were then tested for their interaction with the muscarinic receptors which are responsible for the methacholine-induced contraction of longitudinal muscle in vitro, circular muscle in vivo and muscarinic receptors which mediate the distension-evoked ascending reflex contraction of circular muscle in vitro. Compounds showing high affinity for muscarinic M3 receptors (e.g. AQ-RA 618) were the most potent antagonists in the functional experiments. Comparison of the binding displacement data with the functional results indicates that the effects of methacholine on the longitudinal and circular muscle of the guinea-pig ileum were predominantly mediated by muscarinic M3-type receptors. In contrast, the correlation between muscarinic M2 receptor affinity and antagonism of muscarinic receptors in the ileum was very weak.

Animals↗
PubMed1994

The relationship between oxygen delivery and uptake in the critically ill: is there a critical or optimal therapeutic value? A meta-analysis.

In order to identify a critical or an optimal therapeutic value for oxygen delivery and oxygen uptake, we analysed data from 40 publications concerning the relationship between oxygen delivery and consumption in patients with adult respiratory distress syndrome, trauma or during sepsis, and in nonseptic controls. According to the outcome, the patients were allocated to either group 1 (survivors) or group 2 (nonsurvivors). While oxygen delivery and uptake (mean, SEM) were significantly higher in patients with adult respiratory distress syndrome (636, SEM 31 ml.min-1.m-2 and 155, SEM 5 ml.min-1.m-2), trauma (782, SEM 77 ml.min-1.m-2 and 167, SEM 10 ml.min-1.m-2) and sepsis (654, SEM 28 ml.min-1.m-2 and 163, SEM 5 ml.min-1.m-2) than in nonseptic controls (452, SEM 18 ml.min-1.m-2 and 126, SEM 3 ml.min-1.m-2, p < 0.05), there were no significant differences in these parameters between survivors and nonsurvivors. Although therapeutic manoeuvres were effective in increasing both oxygen delivery and consumption, these improvements were not paralleled by an increase in survival rate. The correlation between oxygen delivery and uptake is generally a result of the use of pooled data and therefore prone to mathematical coupling. This is true particularly for patients with adult respiratory distress syndrome and sepsis. Thus, our study failed to identify either an optimal or a critical value of oxygen delivery or oxygen consumption in critically ill patients.

Bacterial Infections↗
PubMed1993

Effects of propofol on the function of normal, collateral-dependent, and ischemic myocardium.

To examine the effects of propofol on the function of normal, collateral-dependent, and acutely ischemic myocardium, nine mongrel dogs were chronically instrumented with hydraulic occluders and ameroid constrictors were inserted around the left coronary artery, pressure transducers in the left ventricle, and heparin-filled catheters in the descending aorta and the left atrium. Regional function of normal, collateral-dependent, and acutely ischemic myocardium was assessed by sonomicrometry. Propofol (5 mg/kg intravenously) reduced function in normal myocardium (-15% +/- 5%, 1 min and -14% +/- 5%, 3 min after injection) and in collateral-dependent myocardium (-14% +/- 5% and -13% +/- 5%) to similar degrees, whereas ischemic myocardial function deteriorated significantly more (-25% +/- 10% and -23% +/- 10%, P < 0.01). Although left ventricular end-diastolic pressure remained unchanged and left ventricular contractility was reduced (-16% +/- 4%, 1 min and -15% +/- 3%, 3 min after propofol, P < 0.01), significant increases in heart rate (35% +/- 7% and 26% +/- 7%, P < 0.01) and decreases in coronary perfusion pressure (-14% +/- 5%, P < 0.05 and -19% +/- 6%, P < 0.01) occurred, likely affecting the function of ischemic myocardium. Thus, whereas collateral-dependent myocardium tolerated these adverse hemodynamic effects, ischemic myocardium responded with impairment of regional function that was significantly more pronounced than the impairment which occurred in normal or collateral-dependent areas after a 5 mg/kg intravenous bolus of propofol.

Animals↗
PubMed1993

Continuous spinal anesthesia with a microcatheter and low-dose bupivacaine decreases the hemodynamic effects of centroneuraxis blocks in elderly patients.

This prospective randomized study was designed to investigate the hemodynamic effects and quality of continuous spinal anesthesia (CSA) after rapid injection of a low dose of 0.5% bupivacaine through a 32-gauge microcatheter. The method was compared with continuous epidural (CEA) and single-dose spinal anesthesia (SSA). Seventy-seven elderly patients (ASA II-III) ranging from 57 to 94 yr old and undergoing lower limb surgery were assigned to CSA (n = 26), CEA (n = 26), and SSA groups (n = 25). In all three groups, mean arterial pressure (MAP) and heart rate (HR) were assessed continuously for 30 min after initial injection, as well as after every reinjection of local anesthetic in the CSA and CEA groups. Bupivacaine (0.5%) was used as a local anesthetic. The initial doses were 1 mL of CSA, 10 mL of CEA, and 3 mL of SSA. The reinjection doses were 1 mL of CSA and 5 mL of CEA. In the CSA group, MAP did not decrease, whereas in the CEA group, the maximum decrease was 15% +/- 3% (mean +/- SEM) for the initial injection, 12% +/- 2% for the first repetition, and 13% +/- 2% for the second repetition. In the SSA group, the largest decrease of MAP was 19% +/- 2%. All changes of MAP in the CEA and SSA groups were significantly larger compared with CSA group (P < 0.05). A total of seven patients in these two groups needed vasopressors due to a decrease of MAP of more than 30% from baseline values. Heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Airway hyperreactivity test by measurement of specific airway conductance during quiet breathing].

In asthmatic patients, the threshold for specific airway conductance during quiet breathing (sGawqt) in the airway hypersensitivity test was determined using our newly developed pressure corrected flow type body plethysmograph and compared with that measured by means of respiratory resistance (Grs) Astograph in relation to the following parameters: 1) Dmin, an index of airway sensitivity (accumulated methacholine concentration at the time of onset of linear decrease in the dose-response curve), 2) SsGawqt and SGrs, indicators of airway sensitivity (slope when the value begins to decrease) and 3) PD35 (accumulated methacholine concentration when the valve has decreased to 35% of the initial value). Although no significantly difference was observed in SsGawqt and SGrs, significantly lower values of Dmin and PD35, indexes of airway sensitivity, were obtained with sGawqt method as compared to Astograph. These findings may indicate that the airway hypersensitivity test using our body plethysmography technique can be performed using a smaller amount of inhaled methacholine with less patient burden as compared to Astograph.

Adult↗
PubMed1992

Sufentanil decreases cerebral blood flow velocity in patients with elevated intracranial pressure.

Recent investigations revealed that sufentanil increases cerebral blood flow (CBF) and intracranial pressure (ICP) in dogs and man. The aim of our study was to evaluate the impact of sufentanil on cerebral blood flow velocity and ICP in neurosurgical patients. Eight neurosurgical ICU patients with elevated ICP (> 20 mmHg) were examined. Sufentanil was given in incremental doses of 0.5, 1.0 and 2.0 micrograms kg-1. Cerebral blood flow velocity decreased significantly from 54 +/- 4 cm s-1 to 48 +/- 3 cm s-1 with the dose of 1.0 microgram kg-1 sufentanil and 47 +/- 3 cm s-1 with 2.0 micrograms kg-1, respectively (mean +/- SEM). ICP values did not increase with any of the doses studied. Thus, changes of mean arterial pressure which fell with 1.0 microgram kg-1 and 2.0 micrograms kg-1 reflect cerebral perfusion pressure alterations. Although changes of cerebral blood flow velocity revealed changes in vascular tone, ICP remained unaltered.

Anesthesia, Intravenous↗
PubMed1991

Cardioselectivity of AQ-RA 741, a novel tricyclic antimuscarinic drug.

The interaction of the AF-DX 116 analogue, AQ-RA 741 (11-[[4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl]-5,11- dihydro-6H-pyrido[2,3-b] [1,4]benzodiazepin-6-one), with muscarinic receptors, in vitro and in vivo, was examined. In radioligand binding studies, AQ-RA 741 showed high affinity for cardiac M2 sites (pKi = 8.30), intermediate affinity for cortical M1 sites (pKi = 7.70) and low affinity for glandular M3 sites (pKi = 6.82). Functional studies showed AQ-RA 741 to be a competitive antagonist and to have a 60 to 87-fold higher affinity for cardiac muscarinic receptors than for muscarinic receptors in intestinal, tracheal or bladder smooth muscle. In vivo experiments confirmed the M2 selectivity of AQ-RA 741. In rats, cats and guinea-pigs AQ-RA 741 preferentially inhibited the vagally or agonist-induced bradycardia (-log ID50 = 7.24-7.53 i.v.). The ratio of potencies observed between effects mediated by cardiac and other muscarinic receptor ranged between 9- and more than 100-fold. The results show that AQ-RA 741 is a potent and selective M2 antagonist with remarkable in vivo selectivity.

Animals↗
PubMed1991

Effect of sufentanil on intracranial pressure in neurosurgical patients.

The effects of sufentanil on intracranial pressure, mean arterial pressure, cerebral perfusion pressure and heart rate were studied in 20 neurosurgical intensive care unit patients. Epidural intracranial pressure probes were implanted in patients who suffered head injury, intracerebral haemorrhage or underwent tumour resection. Sufentanil was given intravenously in sequential doses of 0.5, 1.0 and 2.0 micrograms/kg. Fifteen minutes elapsed after each dose. The patients were allocated to either group 1 (baseline intracranial pressure less than 20 mmHg) or group 2 (baseline intracranial pressure greater than 20 mmHg). Intracranial pressure did not change significantly in either group. Therefore the falls in mean arterial pressure with the highest dose in both groups and with 1.0 micrograms/kg in group 2, closely reflect corresponding reductions in cerebral perfusion pressure. As sufentanil in itself exerts no effects on intracranial pressure, concomitant haemodynamic changes are the critical factor for an adequate cerebral perfusion pressure.

Adult↗
PubMed1991

Isoflurane impairs the function of ischemic myocardium in acutely but not in chronically instrumented dogs.

To compare the effects of isoflurane on ischemic myocardium in acutely and chronically instrumented animals, 12 mongrel dogs were monitored with electromagnetic or Doppler ultrasonic flow transducers and hydraulic occluders around the left circumflex coronary artery, pressure transducers in the left ventricle, and heparin-filled catheters in the descending aorta. Regional function of normal and ischemic myocardium was assessed by sonomicrometry. The hemodynamic effects of isoflurane (2% inspired concentration) were more pronounced in the acutely than in the chronically instrumented dogs. Decreases in mean arterial pressure (-47% +/- 5% in the acute and -22% +/- 4% in the chronic preparation, P less than 0.01), left ventricular contractility (-51% +/- 6% and -33% +/- 4%, P less than 0.01), and coronary perfusion pressure (-59% +/- 6% and -12% +/- 9%, P less than 0.01) were more distinct in the acutely instrumented animals. Although the reduction of regional function during isoflurane anesthesia was similar in normal myocardium in both preparations (-33% +/- 4% acute and -34% +/- 6% chronic preparation, not a significant difference), an exaggerated dysfunction was observed in the ischemic myocardium of the acutely instrumented dogs (-66% +/- 2% and -30% +/- 4%, P less than 0.01). It is concluded that acutely instrumented dogs respond to the hemodynamic effects of isoflurane, resulting in ischemic myocardial dysfunction, significantly more than do chronically instrumented dogs.

Animals↗
PubMed1991

The binding of [3H]AF-DX 384 to rat ileal smooth muscle muscarinic receptors.

The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-[2-(-[8-dipropylamino)methyl]-1-piperidinyl]-ethyl] amino]-carbonyl]-6H-pyrido [2,3-b] [1,4]benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of [3H]AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that [3H]AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations.

Animals↗
PubMed1990

Efficacy of nitroglycerin in stress-induced regional myocardial dysfunction is dependent on the chosen model: investigations in anesthetized and conscious dogs.

The antianginal efficacy of nitroglycerin (1 microgram/kg per min) was investigated in two different experimental models, one using chloralose-anesthetized open-chest dogs, the other using conscious, chronically instrumented dogs. Heart rate, arterial pressure, left ventricular dp/dtmax, and left ventricular end-diastolic pressure were registered. Left ventricular regional contractile function in the area supplied by the left circumflex coronary artery (LCX) and the left anterior descending artery (LAD) were assessed using sonomicrometry. In both models, the coronary flow reserve was limited by a hydraulic occluder around the LCX. Cardiac stimulation was achieved by a bolus injection of isoproterenol (ISO 0.5 microgram/kg) in the anesthetized animals and by graded treadmill exercise in the conscious animals. In both cases, transient contractile dysfunction occurred in the area supplied by the stenosed vessel. This contractile dysfunction was completely abolished by nitroglycerin in the conscious animals, while nitroglycerin failed to show any antianginal effect in the anesthetized dogs. Although hemodynamic differences in open and closed chest should be considered, remarkable differences in mechanisms of blood-pressure regulation according to the mode of stimulation were observed: in contrast to the situation during treadmill exercise, the ISO-induced decrease in arterial blood pressure does not correspond to the clinical picture of an anginal attack. These results show that it is most important to mimic the complex pathophysiological reactions of angina pectoris in man as closely as possible in the experimental model.

Anesthesia, General↗
PubMed1990

Characterization of porcine coronary muscarinic receptors.

To determine the muscarinic receptor subtype involved in the contractile response of coronary smooth muscle, we investigated the profiles of various muscarinic receptor antagonists competing for [3H]N-methyl-scopolamine ([3H]NMS) binding to membrane preparations from porcine coronary arteries. [3H]NMS binds to a single population of muscarinic binding sites with a KD of 135 pM and a Bmax of 57 fmol/mg. The affinity profiles of AF-DX 116 [11-2((-((diethylamino)methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6H- pyrido (2,3-b)(1,4)-benzo-diazepin-6-one], atropine, 4-DAMP [4-diphenylacetoxy-N-methylpiperidine methiodide], methoctramine [N,N'-bis(6-((2-methoxybenzyl)amino)hexyl)-1,8-octane-diamine tetrahydrochloride], HHSiD [hexahydrosiladifenidol] and pirenzepine are consistent with binding to a mixed population of muscarinic binding sites, namely of the M2 and M3 subtype. Binding curves for AF-DX 116 and methoctramine are shallow with Hill-coefficients significantly less than unity. Comparison of data from binding studies with results obtained in functional experiments, i.e. antagonism of methacholine induced contraction of porcine coronary artery rings, it was found that only the low-affinity pKi values of AF-DX 116 (6.26) and methoctramine (6.51) correlated well with functional pA2 values. It is concluded that a mixed population of the M2 and M3 muscarinic receptor subtypes is present in porcine coronary arteries. Functional experiments do not support the contribution of the M2 subtype to the contractile response. Cholinergic induced contractions of porcine coronary arteries appear to be evoked via stimulation of the muscarinic M3 receptor subtype. However, since the compounds investigated here do not markedly discriminate between cloned m3, m4 and m5 receptors the involvement of muscarinic receptors different from M1, M2 and M3 cannot be excluded.

Animals↗