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Biomedical subjects

K Rehder

Publications and source records attributed to K Rehder.

At least 37 records · Page 2Linked to original sources

Cemented versus noncemented total hip arthroplasty--embolism, hemodynamics, and intrapulmonary shunting.

Bone cement implantation syndrome is characterized by hypotension, hypoxemia, cardiac arrhythmias, cardiac arrest, or any combination of these complications. It may result from venous embolization that occurs in conjunction with intramedullary hypertension in the femur during insertion of the prosthesis in patients undergoing cemented total hip arthroplasty (THA). Intramedullary hypertension does not occur in patients undergoing noncemented THA. In this study, we sought to compare embolization between patients undergoing cemented and noncemented THA and to determine whether this state resulted in cardiorespiratory deterioration. In this prospective investigation of 35 patients undergoing elective THA, we used transesophageal echocardiography and invasive hemodynamic monitoring, and in 12 of them, we monitored distribution of pulmonary ventilation and perfusion intraoperatively. Embolization was significantly greater after insertion of the prosthesis in patients undergoing cemented than in those undergoing noncemented THA. Cemented THA was also associated with decreased cardiac output and increased pulmonary artery pressure and pulmonary vascular resistance. Increases in ventilation-perfusion mismatching, however, could not be demonstrated 30 minutes after insertion of the femoral prosthesis. Intraoperative monitoring for embolism may help physicians assess patients in whom cardiorespiratory function deteriorates during THA.

Aged↗

Multicenter study of general anesthesia. III. Predictors of severe perioperative adverse outcomes.

Little information is available about the incidence of severe adverse outcomes, and even less information is available about the identification and quantification of independent predictors of severe perioperative adverse outcomes. The purpose of this study was to identify and quantitate independent predictors of severe perioperative adverse outcomes in a prospective randomized clinical trial of general anesthesia in 17,201 patients. Twenty-nine prognostic variables for 15 severe outcomes in 847 patients were tested by multiple stepwise logistic regressions from which 20 significant (P less than 0.05) predictors were identified. A history of cardiac failure or myocardial infarction less than or equal to 1 yr; ASA physical status 3 or 4; age greater than 50 yr; cardiovascular, thoracic, abdominal or neurologic surgery; and the study anesthetics were significant predictors of "any severe outcome, including death." There were 17 significant predictors for 10 severe cardiovascular outcomes in 608 patients, including a history of ventricular arrhythmia, hypertension, cardiac failure, myocardial ischemia, myocardial infarction less than or equal to 1 yr or myocardial infarction greater than 1 yr, and smoking; ASA physical status; age; cardiovascular, thoracic, abdominal, eyes-ears-nose-throat/endocrine, neurologic, musculoskeletal, or gynecologic surgery; and the study anesthetics. There were 9 significant predictors for 4 severe respiratory outcomes in 163 patients, including a history of cardiac failure, myocardial ischemia, or chronic obstructive pulmonary disease; obesity; smoking; male gender; ASA physical status; abdominal surgery; and the study anesthetics. Colinearity between related prognostic variables (such as disease and ASA physical status) was assessed using progressively segregated groups of variables in eight stepwise logistic regressions. We conclude that the comprehensive stepwise logistic regression of 29 prognostic variables reported here provides a valid estimate of the risks of severe perioperative outcomes associated with general anesthesia.

Anesthesia, General↗

Halothane changes the relationships between lung resistances and lung volume.

The authors hypothesized that relaxation of airway smooth muscle by halothane lessens the dependence of airway resistance on lung volume, and that halothane alters the relationship between pulmonary resistance and lung volume by changing both the airway and tissue components of pulmonary resistance. The relationship among airway resistance, tissue resistance, and lung volume was examined in mongrel dogs before and during the administration of halothane, both in airways with reduced smooth muscle tone (after vagotomy) and during moderate increases in smooth muscle tone caused by vagus nerve stimulation (VNS). Resistance were measured at several levels of positive end-expiratory pressure (PEEP, 4-15 cmH2O) using an alveolar capsule technique. Before halothane administration, airway resistance increased at low PEEP; VNS accentuated this increase. Tissue resistance increased at low PEEP only during VNS. Halothane had no significant effect on any resistance before VNS. During VNS, halothane markedly blunted increases in airway resistance and tissue resistance as PEEP decreased. The authors conclude that during stimulation of airway smooth muscle in dogs, halothane attenuates increases in airway resistance and tissue resistance with reductions in lung volume in dogs. Thus, moderate changes in lung volume have little effect on these resistances during halothane anesthesia under these conditions.

Airway Resistance↗

Electrical activation of expiratory muscles increases with time in pentobarbital-anesthetized dogs.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

Anesthesia↗

Gas exchange in dogs in the prone and supine positions.

To determine the cause of the difference in gas exchange between the prone and supine postures in dogs, gas exchange was assessed by the multiple inert gas elimination technique (MIGET) and distribution of pulmonary blood flow was determined using radioactively labeled microspheres in seven anesthetized paralyzed dogs. Each animal was studied in the prone and supine positions in random order while tidal volume and respiratory frequency were kept constant with mechanical ventilation. Mean arterial PO2 was significantly lower (P less than 0.01) in the supine [96 +/- 10 (SD) Torr] than in the prone (107 +/- 6 Torr) position, whereas arterial PCO2 was constant (38 Torr). The distribution of blood flow (Q) vs. ventilation-to-perfusion ratio obtained from MIGET was significantly wider (P less than 0.01) in the supine [ln SD(Q) = 0.75 +/- 0.26] than in the prone position [ln SD (Q) = 0.34 +/- 0.05]. Right-to-left pulmonary shunting was not significantly altered. The distribution of microspheres was more heterogeneous in the supine than in the prone position. The larger heterogeneity was due in part to dorsal-to-ventral gradients in Q in the supine position that were not present in the prone position (P less than 0.01). The decreased efficiency of oxygenation in the supine posture is caused by an increased ventilation-to-perfusion mismatch that accompanies an increase in the heterogeneity of Q distribution.

Animals↗

Halothane, enflurane, and isoflurane depress the peripheral vagal motor pathway in isolated canine tracheal smooth muscle.

Volatile anesthetics are potent bronchodilators, but the site of action for the dilation is unclear. To determine the site of action of halothane, enflurane, and isoflurane on the peripheral vagal motor pathway, isolated strips of canine trachealis muscle were stimulated before and during exposure to halothane at 0.3, 1.0, 1.7, or 2.4 MAC, enflurane at 1 MAC, or isoflurane at 1 MAC. The sites and methods of stimulation were: 1) postsynaptic nicotinic cholinergic receptors in the intramural parasympathetic ganglia, with 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP); 2) postganglionic cholinergic nerve fibers, with electrical field stimulation (EFS); and 3) muscarinic cholinergic receptors of the smooth muscle, with acetylcholine (ACh). The concentration-response curve to DMPP was significantly shifted to the right by 0.3 MAC halothane, whereas 0.3 MAC halothane had no significant effect on the concentration-response curves to ACh and EFS. At concentrations greater than 1 MAC of halothane, enflurane, or isoflurane, concentration-response curves to all three stimuli were shifted significantly to the right; i.e., the contractile responses to ACh, EFS, and DMPP were reduced. At all concentrations of halothane the force of contraction was significantly more reduced during stimulation with DMPP than during stimulation with ACh, and at halothane concentrations greater than or equal to 1.7 MAC the response to EFS was significantly more reduced than that to ACh. We conclude that halothane, enflurane, and isoflurane attenuated airway constriction by several mechanisms, including 1) reduced excitability of the postsynaptic nicotinic receptors of the intramural parasympathetic ganglia and 2) an effect on the smooth muscle and/or on the muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bronchodilation by halothane is not modulated by airway epithelium.

Halothane relaxes airway smooth muscles. To test the hypothesis that this relaxation is modulated by airway epithelium, we studied the effects of halothane on isolated second- and third-order canine bronchial rings and second-order canine bronchial segments. Paired rings or segments were examined, with the epithelium removed from one ring or segment of each pair. The bronchial rings were suspended in organ chambers and contracted with 10(-8)-10(-3) M acetylcholine (ACh), 10(-8)-10(-5) M 5-hydroxytryptamine (5HT), or 0.5-16 Hz electrical field stimulation (EFS, 15 V, 0.5-ms pulse duration). The tissue was contracted in the absence of halothane and during exposure to 1 and 2 MAC halothane. The bronchial segments were perfused intraluminally with physiologic salt solution (PSS) and contracted with 10(-6) M carbachol added to the tissue-bath PSS. One or 2 MAC halothane was then added to the perfusate. In the absence of halothane, epithelium removal increased the sensitivity of the bronchial rings to ACh and 5HT but not to EFS. Addition of 1 or 2 MAC halothane to the bathing fluid of the rings with or without epithelium decreased the sensitivity of the rings to ACh and 5HT. One MAC halothane decreased the sensitivity of the rings with and without epithelium to EFS. The decrease in sensitivity caused by halothane was not significantly different in rings with or without epithelium for any method of stimulation. In the bronchial segments, relaxations evoked by 1 or 2 MAC were not different in segments with or without epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Chest wall motion during epidural anesthesia in dogs.

To determine the relative contribution of rib cage and abdominal muscles to expiratory muscle activity during quiet breathing, we used lumbar epidural anesthesia in six pentobarbital sodium-anesthetized dogs lying supine to paralyze the abdominal muscles while leaving rib cage muscle motor function substantially intact. A high-speed X-ray scanner (Dynamic Spatial Reconstructor) provided three-dimensional images of the thorax. The contribution of expiratory muscle activity to tidal breathing was assessed by a comparison of chest wall configuration during relaxed apnea with that at end expiration. We found that expiratory muscle activity was responsible for approximately half of the changes in thoracic volume during inspiration. Paralysis of the abdominal muscles had little effect on the pattern of breathing, including the contribution of expiratory muscle activity to tidal breathing, in most dogs. We conclude that, although there is consistent phasic expiratory electrical activity in both the rib cage and the abdominal muscles of pentobarbital-anesthetized dogs lying supine, the muscles of the rib cage are mechanically the most important expiratory muscles during quiet breathing.

Anesthesia, Epidural↗

The snRNP E protein multigene family contains five pseudogenes with common mutations.

Sequence data from three previously-uncharacterized members of the snRNP E protein multigene family suggest that each is a non-transcribed processed pseudogene, even though one clone has the potential to code for a full-length protein with greater than 90% similarity to previously-characterized E protein cDNAs. Each of the newly-analyzed family members is without introns, contains a tract of polyadenylic acid residues, and is flanked by short direct repeats. In addition, the three sequences all contain point mutations that distinguish them from the E protein coding sequence. Seven point mutations are common to the three sequences described here and to two previously-described E protein pseudogenes. Although all of these mutations are transitions, only 5 of 7 could have been generated by deamination of methylated cytosines in inactive genes. Thus, the common mutations in the pseudogenes suggest an origin other than the expressed gene that we have described. Allelic variants for two of the pseudogenes were detected and repetitive elements are located near four of the five E protein pseudogenes that have been characterized.

Amino Acid Sequence↗

Multicenter study of general anesthesia. I. Design and patient demography.

A prospective randomized clinical trial of enflurane, fentanyl, halothane, and isoflurane is described. The 17,201 patients were stratified into two groups (preanesthetic medication and no preanesthetic medication) and were randomized to one of four study agents: enflurane, fentanyl, halothane, and isoflurane. Fifteen university-affiliated hospitals in the United States and Canada participated. All patients were first assessed preoperatively. Data were collected during anesthesia, in the immediate recovery period, and for up to 7 days after anesthesia/surgery. The mean age of the patients was 43 yr, the mean height 167 cm, and the mean weight 68 kg. Sixty-five percent of patients were female. In this study 90.7% of patients were classified as ASA Physical Status 1 or 2, and 34.7% of patients smoked. It is concluded that pooling of data across institutions was valid and does allow determination of the efficacy and relative safety of the four study agents.

Adult↗

Multicenter study of general anesthesia. II. Results.

A prospective, stratified, randomized clinical trial of the safety and efficacy of four general anesthetic agents (enflurane, fentanyl, halothane, and isoflurane) was conducted in 17,201 patients (study population). Patients were studied before, during, and after anesthesia for up to 7 days. Nineteen patients died (0.11%), and in seven of these (0.04%) the anesthetic may have been a contributing factor. The rates of death, myocardial infarction, and stroke in the study population were so low (less than 0.15%) that no conclusions regarding the relative rates of these outcomes among the four anesthetic agents could be reached. The rates of 16 of 66 types of adverse outcomes in the study population were significantly different among the four study agents. Most of these outcomes were minor. However, severe ventricular arrhythmia (P less than 10(-6)) was more common with halothane, severe hypertension (P less than 10(-6)) and severe bronchospasm (P = 0.028) were more common with fentanyl, and severe tachycardia (P = 0.001) was more common with isoflurane. Recovery from anesthesia during the first 30 min was slowest in those patients who received halothane (P less than or equal to 0.001). In addition, patients who received fentanyl experienced less pain during the first hour in the recovery room (P less than 10(-6)). In conclusion, clinically important differences do exist for some outcomes among the four study agents.

Adult↗

Direct and neurally mediated effects of halothane on pulmonary resistance in vivo.

It has been suggested that halothane inhibits contraction of airway smooth muscle in vivo mainly by reducing reflex activity in nerves innervating the muscle with only minimal direct effects on the muscle itself. To examine possible mechanisms of action of halothane at clinically relevant concentrations the authors studied the effect of halothane on increases in pulmonary resistance (RL) produced by either vagus nerve stimulation (VNS, which caused neurally mediated constriction) or the inhalation of nebulized acetylcholine (ACh, which directly stimulated the smooth muscle cell) in nine mongrel dogs. The frequency of bilateral VNS and the dose of nebulized ACh were adjusted to produce approximately equal increases in RL. Halothane reduced the response to both types of stimulation in a dose-dependent fashion. At halothane concentrations greater than or equal to 0.4 MAC, the VNS response was significantly less than the ACh response. When tetrodotoxin was given to block neural activity, the ACh response was unchanged, confirming that neural activation did not contribute significantly to smooth muscle contraction in response to ACh. The authors conclude that in addition to neurally mediated effects, halothane at clinically used concentrations has significant direct effects on airway smooth muscle stimulated by ACh. The relative importance of each factor in vivo should depend on the stimulus that causes contraction of airway smooth muscle.

Acetylcholine↗

Isoflurane and whole body leucine, glucose, and fatty acid metabolism in dogs.

Following 4 h of general anesthesia with halothane [1.5 minimum alveolar concentration (MAC)]-nitrous oxide (50% in oxygen), whole body protein synthesis is decreased and the rate of leucine oxidation is increased in dogs. To evaluate the effects of general anesthesia with isoflurane on whole body fuel metabolism and the effects of duration of anesthesia on these processes, eight dogs were studied, once in the conscious state (over 9 h) and again prior to and during isoflurane anesthesia (1.5 MAC) for 3.5 h (n = 8). Three additional dogs were studied in the conscious state and over 5 h of anesthesia. Changes in protein, fatty acid, and glucose metabolism were estimated using isotope dilution techniques, employing simultaneous infusions of L-[1-14C]leucine, [6-3H]glucose and [9,10-3H]palmitate. Ten minutes after the beginning of the administration of isoflurane, total leucine carbon flux, leucine oxidation, and leucine incorporation into proteins decreased (P less than 0.05), resulting in a slight decrease in the ratio of leucine oxidation to nonoxidative leucine disappearance (LOX/NOLD, P less than 0.05), an indicator of leucine catabolism. Throughout the 5 h of anesthesia, whole body protein synthesis remained decreased (P less than 0.01), whereas leucine flux and oxidation increased progressively throughout the remainder of the study, resulting in a more than 80% increase in the ratio of LOX/NOLD. After 10 min of isoflurane anesthesia, both plasma free fatty acid concentrations and palmitate turnover had decreased by more than 70% (P less than 0.001) and remained suppressed (P less than 0.001) throughout the remainder of the anesthesia, consistent with decreased lipolysis. Glucose production was increased 10 min (P less than 0.05) following induction of anesthesia and peripheral glucose utilization was decreased following 3.5 h of isoflurane anesthesia (P less than 0.05). These data strongly suggest a widespread and immediate metabolic effect of isoflurane anesthesia, which includes peripheral insulin resistance to glucose disposal, decreased lipolysis, and a progressive increase in protein wasting with increasing duration of anesthesia.

Anesthesia, General↗

Physiologic approach to mechanical ventilation.

An understanding of ventilator management must be predicated on physiologic principles. There is a considerable array of equipment, permitting an almost limitless number of permutations in ventilator therapy, to support patients with respiratory failure. The physician who understands patient-ventilator interactions and their effects on cardiopulmonary function will be best equipped to individualize therapy. We believe that further refinements in supportive equipment probably will not improve outcome significantly. Thus, more emphasis should be placed on elucidating the underlying disease process and its effects on respiratory structure and function.

Airway Obstruction↗

Ventilation-perfusion distribution after aortic valve replacement.

In eight patients, the ventilation-perfusion (Va/Q) relationships after uncomplicated aortic valve replacement were studied by the multiple inert gas technique. Postoperatively, all patients had a right-to-left intrapulmonary shunt (Qsp/Qt) (range 2.4% to 14.4%) and abnormal distribution of Va/Q patterns to varying degrees. No single mechanism was identified that defined gas exchange in all patients. In three patients, moving from the supine to the right lateral decubitus position resulted in improved oxygenation which occurred because of better matching of Va/Q, not because of a decrease in Qsp/Qt.

Adult↗

Muscarinic receptor subtypes in canine trachea.

Prejunctional and postjunctional muscarinic receptor subtypes were characterized in canine trachealis muscle strips. In vitro contractile responses of muscle strips to acetylcholine or electric field stimulation were determined in the absence and the presence of gallamine, pirenzepine, and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP). Gallamine had no effect on the contractile response to acetylcholine but enhanced the contractile response to electric field stimulation. Pirenzepine and 4-DAMP reduced the contractile response to acetylcholine and electric field stimulation. The pA2 value for pirenzepine vs. acetylcholine [7.18 +/- 0.59 (SD)] was consistent with the affinity of pirenzepine for M2 or M3-receptors; whereas the pA2 value for 4-DAMP vs. acetylcholine (8.92 +/- 0.42) and the extremely low affinity of gallamine indicated postjunctional muscarinic receptors of the M3 subtype. The enhancement of the contractile response to electric field stimulation by gallamine suggested the presence of M2-prejunctional receptors.

Acetylcholine↗

Effect of positional change on ventilation-perfusion distribution in unilateral pleural effusion.

The effect of pleural effusion on lung function and gas exchange has not been adequately defined. We used the multiple "inert" gas technique to study gas exchange and ventilation-perfusion relationships in both the left and the right lateral decubitus positions in a patient with a moderate unilateral (left) pleural effusion. With position change, only a small change in oxygenation (3 mm Hg) and no change in carbon dioxide tension occurred. The ventilation-perfusion relationships were also nearly identical for both body positions. We conclude that a pleural effusion of moderate size has little effect on overall gas exchange and ventilation-perfusion relationships and that complex mechanisms of the respiratory system compensate for the effusion.

Aged↗