Unanesthetized Subjects Research Articles

Effects of hemorrhagic shock on the microvasculature of skeletal muscle

The relationship between arteriolar and venular dimensions and the progressive failure of the homeostatic mechanisms leading to irreversibility in hemorrhagic shock was evaluated in mammalian skeletal muscle (rat cremaster). The small distribution arterioles (diameter = 17 μm) were observed to lose their tone and vasomotion at irreversibility although at 15 min after hemorrhage they exhibited enhanced vascular activity. Slowing of flow was seen to occur in the large venules (100 μm) and late in shock in smaller venules (25 μm). Venular dilatation was adjudged to be the vascular defect associated with the onset of irreversibility. Muscle surface pH and PO 2 followed a course similar to that seen in unanesthetized subjects. The red cell aggregation seen in the venules during the low flow state was generally reversed after reinfusion of the shed blood and restoration of arterial pressure.

Systemic circulatory responses to hypocapnia in man.

Systemic circulatory responses to hypocapnia in man.

Effect of intraventricular injections of brain isoantibodies on learning

The present method of assessing the effects of anti-brain isoantibody on learning involves multiple slow intraventricular injections of serum γ-globulin (IgG) into the lateral ventricles of chronically prepared unanesthetized subjects. Injections of 80 μl of normal rat IgG on the 8 days preceding training had no adverse effect on the abilities of the subjects to learn a visual discrimination problem. Such trained subjects also performed at criterion after they received an additional intraventricular injection of normal IgG on the day they reached criterion. In contrast, subjects that had received anti-brain IgG before training performed below criterion after they received an intraventricular injection of normal IgG on the day they reached criterion. Subjects that received intraventricular injections of immune IgG prepared from the sera of rats that had been immunized with the microsomal fraction of rat brain (RB F-III) or rat liver (RL F-III) required a statistically significant larger number of trials to learn a visual discrimination problem than control subjects that received normal rat IgG. The anti-RB F-III IgG had a more widespread effect than the anti-RL-F-III in that it produced subjects with statistically significantly higher latencies, poorer memories, and an unusual behavioral trait tentatively called “spinning”. The effect of the anti-RL F-III is believed to be due to its reaction with species-specific antigens in the brain whereas the more deleterious effect of the anti-RB F-III IgG is thought to be due to its reactivity with both species-specific and organ-specific antigens in the brain. The present experiments have confirmed and extended the results obtained earlier with actively immunized subjects.

Acid-base changes of arterial plasma during exogenous and endogenous hypercapnia in man

Acute hypercapnic conditions have been produced in man by exogenously given and endogenously accumulated CO 2 in order to compare the nature of the CO 2 titration curves of blood in vivo between these conditions. Effects of general anesthesia on these curves have also been investigated. In the anesthetized subjects there was no significant difference between the slopes of the titration curves for these two modes of hypercapnia. Neither were the slopes of the curves for the unanesthetized subjects determined during exogenous hypercapnia greatly different from those of the anesthetized subjects. A clinical implication of these findings is that a CO 2 titration curve of blood defined in any of the above conditions can be applied to other circumstances without serious error. Non-respiratory acidosis did not occur during the hypercapnic period while apparent non-respiratory acidosis developed during the reversal of hypercapnia. Discrepancy in the length of time spent for the establishment and reversal of hypercapnia is thought responsible for the development of this apparent non-respiratory acidosis.

Hemodynamic responses to controlled 100% oxygen breathing in emphysema

Cardiopulmonary hemodynamic responses to breathing 100% oxygen for 20 min were studied in 13 patients with moderate to severe chronic obstructive emphysema under conditions of controlled ventilation. A technique for regulating the level of ventilation in the unanesthetized subject is described. Cardiac output was measured by the indicator-dilution method. Arterial blood gas analysis and pH were performed in each phase of the study. A slight but statistically significant decrease in cardiac index occurred. There was a highly significant reduction in pulmonary arterial pressure and pulmonary vascular resistance. No change in heart rate, pulmonary wedge pressure, or aortic pressure occurred. It is concluded that oxygen breathing caused a release, in part at least, of a pulmonary vasoconstrictive element in these patients. pulmonary circulation; oxygen in pulmonary hypertension; hypoxia and pulmonary vasoconstriction; controlled ventilation during oxygen inhalation Submitted on May 27, 1964

Colon blood flow.

1. The intramural blood vessels of the human colon have been described. 2. Five methods that have been used to study colonic mucosal blood flow in patients with colostomies or with normal colons were briefly outlined along with some of the limitations of each technic. 3. It has been shown that the colonic mucosal blood flow in the human responds to heating or cooling an extremity, eating a meal, pharmacologic agents, and emotionally stressful situations. 4. Adequate evaluation of colonic mucosal blood flow requires the development of quantitative technics of measurement. It may be that methods of monitoring radioactive indicators with critically shielded detectors may meet some of these needs16 and offer a way of studying the intact colon of an unanesthetized human subject.

Studies with muscle relaxants in unanesthetized subjects.

Presented at the Annual Meeting of The American Society of Anesthesiologists, Inc., New York, New York, October 7, 1960, and accepted for publication November 28, 1960. The authors are in the Department of Anesthesiology, Mercy Hospital and the Section on Anesthesiology, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Extrathoracic airway resistance in man.

Simultaneous extrathoracic and intrathoracic flow resistance was measured in 19 unanesthetized subjects during mouth breathing. Lateral intratracheal pressure was recorded from a needle introduced 2 cm below the larynx. The intratracheal-oral pressure gradient was recorded during various respiratory maneuvers. The pressure drop from esophagus to trachea was also recorded. The extrathoracic pressure-flow relationships were alinear. Large inter- and intrasubject variability in upper airway resistance was encountered. Some factors contributing to this variability were defined. The upper airway accounted for approximately 45% of the total airway resistance in nine normal and 20% in 10 emphysematous human subjects. Upper airway resistance decreased with increasing lung inflation in four normal subjects. The magnitude and potential variability of the upper airway resistance must be considered in evaluating maneuvers designed to alter intrathoracic flow resistance, especially in normal human beings. It appears that during mouth breathing the major component of the upper airway resistance is located in the larynx. Submitted on September 14, 1960

Compliance of the respiratory system and its components in health and obesity.

The compliance of the total respiratory system and its components was studied in 24 normal and 12 obese spontaneously breathing unanesthetized subjects. The mean compliance of the total respiratory system was .119 l/cm H2O in normal individuals, but was .052 l/cm H2O in obese subjects. The difference indicated an increased elastic resistance to distention. The compliance of the lung in obese individuals was not different from that of the normals. The compliance of the chest wall was .224 l/cm H2O in normal subjects and was .077 l/cm H2O in obese individuals. In contrast to normal subjects, total respiratory compliance was markedly reduced by recumbency in obese individuals. This was entirely due to a further increase in the resistance of the chest wall. A significant correlation was demonstrated between vital capacity and total respiratory compliance in normal and obese subjects. It has been estimated that of the increase in the mechanical work of breathing in obesity is due to elastic work done on the chest wall. Submitted on November 2, 1959

Potential dangers associated with antibiotic administration during anesthesia and surgery

Antibiotic administration during surgery may be associated with hazards not normally encountered in unanesthetized subjects. We submit this contention on the bases of recent evidences in the literature and our laboratory investigations stimulated by clinical experiences. The potential dangers are not those usually associated with prolonged or repeated administration of these drugs, such as allergic responses, blood dyscrasias, nephro- and ototoxic phenomena, but rather acute states of respiratory or circulatory depression. A drug may be therapeutic under usual circumstances of administration and toxic when altered conditions prevail. The patient during surgery is indeed different from an unanesthetized subject. A number of factors could conceivably affect his response to a drug. Anesthesia poses the possibility of drug interaction with a variety of agents used for that purpose. Changes in concentrations of circulating hormones in response to surgical stress and anesthesia may modify the effect of exogenous agents. Hemodynamic changes such as

Potential dangers associated with antibiotic administration during anesthesia and surgery.

Antibiotic administration during surgery may be associated with hazards not normally encountered in unanesthetized subjects. We submit this contention on the bases of recent evidences in the literature and our laboratory investigations stimulated by clinical experiences. The potential dangers are not those usually associated with prolonged or repeated administration of these drugs, such as allergic responses, blood dyscrasias, nephro- and ototoxic phenomena, but rather acute states of respiratory or circulatory depression. A drug may be therapeutic under usual circumstances of administration and toxic when altered conditions prevail. The patient during surgery is indeed different from an unanesthetized subject. A number of factors could conceivably affect his response to a drug. Anesthesia poses the possibility of drug interaction with a variety of agents used for that purpose. Changes in concentrations of circulating hormones in response to surgical stress and anesthesia may modify the effect of exogenous agents. Hemodynamic changes such as

Electrical activity of the small intestine with special reference to the origin of rhythmicity.

Unipolar recordings of small intestinal potentials were obtained from chronic dog preparations with exteriorized segments of bowel, from anesthetized dogs, cats and rabbits at laparotomy and from unanesthetized human subjects. Two dominant types of electrical activity were observed and correlated with function. The first type consisted of brief, nonpropagated, spike-like negative potentials which occurred only immediately preceding and during contraction and varied in frequency of occurrence proportionate to intensity of contraction. It is concluded that they represent the action potentials of contracting muscle fibers. The second type of electrical activity consisted of a recurring complex of slow potential changes, the configuration of which varied with the region of intestine and type of preparation. The complex was most stable and most clearly defined in transplanted segments of dog jejunum. The form of the complex was not altered by anesthetics or by sympathomimetic or parasympathomimetic drugs, and was the same during inactivity as during contractions. Initiation of contractions occurred only during the relatively positive phase of the slow complex. It is concluded that the slow complex is a cyclic alteration of the resting potential of the smooth muscle cells of the intestine which originates more or less synchronously in adjacent cells and is associated with a mechanism which renders the muscle alternately relatively excitable and absolutely refractory.

Electrocardiographic changes associated with experimental alterations in blood potassium in cats

The increasing interest in electrocardiographic abnormalities which are not due to structural changes in the myocardium has prompted our study of the effect of potassium on the electrocardiogram. An intimate relationship of potassium to automatism and to bioelectric phenomena seems fairly certain, in the light of current knowledge, and numerous investigators have studied the effects of potassium on heart muscle strips, the intact heart, and heart-lung preparations. Electrocardiograms with concomitant potassium determinations on the intact, unanesthetized subject following potassium administration are rare. Wiggers 1 produced electrocardiographic changes similar to those due to coronary occlusion by applying with a brush a 20 per cent solution of potassium chloride directly to the ventricle of the dog. Wiggers and his associates 2, 3 described electrocardiographic changes in dogs following intravenous and intracardiac injections of potassium chloride. These changes varied with the amount of potassium chloride injected and with the site and speed of injection. Concentrations of serum potassium were not determined. Harris and Levin 4 noted slowing of the human heart and slight diminution in the height of the P waves following the administration of 5 c.c. of 5 per cent potassium chloride solution. They conclude that there is no relation between electrocardiographic changes and concentration of potassium in the serum, but from the data presented this conclusion does not seem justified. In five experiments on four dogs, Winkler, Hoff, and Smith 5 found marked changes in the electrocardiogram, with eventual cardiac arrest, following the intravenous administration of 1.12 per cent potassium chloride solution at the rate of 10 c.c. per minute. In the present study the potassium chloride was given intraperitoneally because Zwemer and Truszkowski 6 had found that this procedure gave more predictable results and smoother blood potassium curves.

The cerebral blood flow in man as influenced by adrenalin, caffein, amyl nitrite and histamine

Records of changes in cerebral blood flow were obtained by means of a thermoelectric blood flow recorder introduced into the internal jugular vein of unanesthetized subjects. Simultaneous records were also made of respiration and blood pressure. Intravenous injection of amounts of adrenalin chloride, sufficient to cause a marked rise in blood pressure, caused a great increase in cerebral blood flow, this increase undoubtedly being secondary to increase in blood pressure. Minute amounts of adrenalin caused a slight rise in flow without change (or with a fall) in blood pressure, suggesting a vasodilator action. Intravenous injection of caffein sodium benzoate usually caused a decrease in flow, with eventual restoration to a normal or slightly more than normal level. Since this occurred in the face of an invariable rise in blood pressure, a temporary constricting action, perhaps secondary to respiratory stimulation, is indicated. Inhalation of amyl nitrite produced usually an increase in flow in spite of a decrease in blood pressure, indicating a pronounced dilatation of cerebral vessels. Intravenous injection of histamine in one case caused a gradual but progressive increase in blood flow, independent of blood pressure changes.