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A detailed description is made of an acute closed cranial window method. The method is used for the study of cerebral pial microcirculation by intravital microscopy in the rat. Using these methods and techniques, the effects of systemic hypotension by SNP, i.v., on pial microvessel hemodynamics and on ICP were simultaneously measured and characterized under normophysiological conditions. The pH, PO2, PCO2 and temperature of the artificial cerebrospinal fluid (CSF) in the closed cranial window, intermittently measured, remained relatively constant, 30 to 60 min following the period of stabilization of the preparation. The infusion of SNP (6.2-35.0 micrograms/kg/min, 0.02% sol., i.v.) significantly decreased BP (52.1 +/- 13.4 mm Hg, mean +/- SD). From measurement of microvessels internal diameter (I. D.) and microhemodynamics, significant increases in pial arteriolar I.D. (from 35.4 +/- 10.1, microns, to 47.1 +/- 5.7, microns, mean and S.D., 33.0%) and estimated bulk flow (51.2%), occurred during the hypotension. The changes in hemodynamic parameter were predominantly in the arteriolar system. Only minimal changes in the venular diameter occurred during the SNP hypotension. The observed moderate (22.0%) increase in ICP during SNP hypotension in pentobarbital anesthetized rat correlates well with the microhemodynamic changes of the cerebral microcirculatory system.

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The hormonal responses to anaesthesia and cardiac surgery were studied in patients undergoing valve or coronary bypass surgery. Marked increases in antidiuretic hormone levels as a result of surgical stress were seen, and were of approximately equal magnitude in both groups. Although both groups also showed marked increases in plasma cortisol levels in response to operations, this response appeared to be relatively blunted in valve surgery patients, especially at the end of operation and in the intensive care unit. This blunted cortisol response may be a manifestation of exhaustion of adrenocortical reserves in valvular surgical patients whose sympathoadrenal system has already been chronically stimulated by a low output state. The important role of the neuroendocrine system in maintaining homeostasis postoperatively has long been recognized; this relative cortisol deficiency may be aetiologically related to poor postoperative recovery in critically ill valvular surgery patients.

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Observations and measurements of the responses of the rat's microcirculation and lymphatics during the Shwartzman reaction showed that (1) greater increases in arteriolar activity and more rapid derangement of capillary and postcapillary venular walls were induced by the Shwartzman phenomenon than by a single dose of endotoxin; (2) the hyperdynamic state persisted with the first dose of endotoxin but hypotensive low flow syndrome followed a delayed second administration of endotoxin; (3) the lymphatic contractile activity which was depressed with an initial dose also became hyper-reactive with the subsequent dose; (4) both the blood vessels and the lymphatics became hypersensitive to sympathomimetic amines. The pattern of events simulate the pattern seen during clinical endotoxin shock.

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Previous clinical reports indicate that nasal packing is frequently associated with arterial hypoxemia. Anesthesia and surgery in hypoxemic patients can be hazardous, especially when it is associated with acute blood loss. Nine patients with severe epistaxis, who failed to respond to anterior and posterior nasal packing, were anesthetized for emergency internal maxillary artery ligation. Arterial blood-gas and pH changes during the procedure were evaluated. The results indicate some degree of arterial hypoxemia and high alveolar/arterial PO2 difference without significant change in PaCO2 and pH in most of the patients observed. Arterial PO2 was within normal range 24 hours after operation. The anesthetic management is described and the various causes of such arterial hypoxemia are reviewed. It is important to recognize the presence of arterial hypoxemia and treat accordingly during surgery for such patients.

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Inverse correlations were established between the percentage of iron-laden macrophages (heart-failure cells), found in the sputum of patients with various types of heart ailment, and cardiac index. Less than 2% iron-laden macrophages were seen when cardiac index was in the region of 3 liter/min/sq mm of body surface area (BSA). This fraction increased to approximately 75% when the cardiac index attained 1 liter/min/sq mm of BSA. Since there was noticeable heterogeneity of data when the cardiac index was below 3 liters/min/sq mm of BSA and above 1 liter/min/sq mm of BSA, it was concluded that a second factor was probably at play: this was the degree of activity of the reticuloendothelial system of the subjects concerned.

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This experiment was designed to determine the microvascular responses to the two known naturally occurring vasoconstrictors, norepinephrine (NE) and vasopressin, at known levels of central vasomotor activity before, during and after halothane anesthesia. The responses to topical application of NE and vasopressin were studied in the microvasculature of the mesentery and cremaster muscle, using microscopic methods. Neural (CNS) stimulation was accomplished through electrodes chronically implanted in vasoactive sites of the forebrain and midbrain. The increase in blood pressure in response to CNS stimulation was decreased during halothane anesthesia (32.4 +/- 5.4 per cent before and 24.7 +/- 6.1 per cent during; P less than 0.001). There was no significant change in the steady-state diameter of the microvasculature under study during or after halothane anesthesia. Marked abatement of arteriolar vasoconstriction in response to CNS stimulation was seen prior to halothane. However, the same target vessel showed increased constriction in response to topically applied NE (from 32.3 +/- 4.7 to 53.2 +/- 7.8 per cent; P less than 0.01) during halothane anesthesia. By contrast, the response to vasopressin decreased (from 42.4 +/- 5.7 to 1.0 +/- 6 per cent; P less than 0.001) with halothane. The precise mechanism(s) underlying the described hypersensitivity to NE and hyposensitivity to vasopressin in the same vascular structure during halothane anesthesia remains undetermined.

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Allegedly toxic heme pigments have been described in the serum of animals bled to hemorrhagic shock (5,7). In addition, Sears et al. (9), and Braun et al. (1) have shown that the products derived from the degradation of hemoglobin following intravascular hemolysis were toxic (heme carried by hemopexin and albumin). The accumulation of metabolites, caused by the impeded circulation, degrades free hemoglobin into heme pigments and their concentration then reaches a level which exceeds the normal heme-carrying capacity of serum proteins. We have already demonstrated the presence of abnormal heme pigments in clinical cases of shock using scanning spectrophotometry (3). We have endeavored to identify these pigments by serum electrophoresis, and to relate the appearance of some of these compounds to mortality rates. There were no deaths associated with the presence of haptoglobin-hemoglobin alone in serum. As shock deepened and mortality rose, hemopexin-heme and methemalbumin appeared. The highest mortality rate (4 out of 5 cases) was found when both hemopexin-heme and methemalbumin were present. It appears, therefore, that the administration of serum proteins in shock may reduce the toxicity of the products of degradation formed in low-flow states.

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Frequency and time dependent changes in neuromuscular transmission were examined in 30 patients undergoing elective minor surgical procedures not requiring the use of muscle relaxants. Anesthesia was induced with sodium thiopenthal and maintained with N2O-O2 and fractional does of meperidine or fentanyl. Neuromuscular function was measured by recording the force of thumb adduction evoked by supramaximal stimulation of the ulnar nerve at the wrist. Single stimuli were applied every 2.5 seconds as square pulses of 0.1-millisecond duration. Tetanic trains of 10-second duration ranging from 10 Hz to 400 Hz were used. From analysis of present data, criteria for normal responses to 10-second tetanic trains of varying frequencies were established. At a frequency of 30 Hz, the tetanic response is fully maintained and followed by post-tetanic potentiation; at a frequency of 50 Hz, both tetanic and post-tetanic responses are maintained; at a frequency of 100 Hz, there is tetanic fade, followed by a post-tetanic depression of the single indirect twitch responses. It is concluded that frequency and duration of indirect stimulation are the most important factors in using tetanic maintenance and post-tetanic events in assessment of recovery from neuromuscular block.

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Significantly elevated numbers of iron laden histiocytes have been shown to appear in the tracheobronchial secretions of subjects in hemorrhagic shock and in patients undergoing open heart-surgery during cardiopulmonary bypass (3,4). Abnormal heme pigments have also been demonstrated in the serum of dogs bled to hemorrhagic shock (6) and have been felt to be toxic. Because the ingestion of abnormal heme pigments by histiocytes may be part of a defense mechanism, we have attempted to correlate the percentage of iron laden histiocytes found in the tracheobronchial secretions of patients in hemorrhagic shock (Prussian blue method) with the presence of degradation of products of hemoglobin found in their serum by scanning spectrophotometry. There were, generally speaking, few iron laden histiocytes when hemoglobin degradation was advanced, and always numerous iron laden histiocytes when abnormal heme pigments were absent or spectrophotometric findings revealed minor degrees of degradation. Our findings probably reflect the process in the reticuloendothelial systems which eliminates toxic products accumulating in the circulation in low-flow states.

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The two major groups of drug abusers are hard drug addicts and alcoholics. Pulmonary disease and hepatic dysfunction are common in both groups. Choice of anesthetic agents for drug abusers centers around associated illnesses and their severity. The alcoholic often needs vitamin therapy and sedation, but attempting to change drug habits in the face of an acute illness is dangerous. An organized plan of approach is more important than choice of therapeutic agent.

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We previously reported (1) that tracheobronchial secretions of patients in hemorrhagic shock contained significantly more iron laden histiocytes than secretions of matched controls and demonstrated by histiologic studies in rats bled to hemorrhagic shock that these animals' lungs contained significantly more iron laden histiocytes than those of a control group. Two explanations appeared plausible: 1) abnormal hemoglobin breakdown products of systemic hypoperfusion during shock (2, 3, 5) may have accumulated in the pulmonary circulation where they were phagocytozed by pulmonary histiocytes, or 2) circulating iron laden histiocytes may have been arrested in the lung, which is well known to act as a filter during low-flow states (4). The present study reports on assay of bronchial secretions of 12 open-heart surgery patients under cardiopulmonary bypass from specimens obtained 1) immediately after onset of anesthesia; 2) during; and 3) after termination of cardiopulmonary bypass. The percentage of iron laden histiocytes rose from 15.6+/-6.0 after intubation, to 49.6+/-6.8 after 1 hour on bypass with occluded pulmonary arteries (p less than 0.0025), remaining close to the latter value after pulmonary circulation was restored. Hypoperfusion, accumulation of metabolites, or falling pH at the tissue level are probable explanations for these findings.

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Smears were made from tracheobronchial washings of patients undergoing general endotracheal anesthesia for surgery. Morphologically abnormal histiocytes were noticed in specimens obtained from subjects during hemorrhagic shock. These cells were overloaded with Papanicolaou stain (a greenish orange compound) which compressed the nucleus against the cell membrane. Cytochemical staining methods were undertaken to discover the composition of this substance. In secretions suctioned from ten patients in shock, large numbers of histiocytes were found to have ingested inorganic iron detectable by the Prussian blue method. Only two patients from a matched control group had smears in which this phenomenon was discovered. The maximum proportion of histiocytes containing Prussian blue granules was 40% for patients in shock and only 2% in normal controls. Histologic studies conducted on rats submitted to hemorrhagic shock were carried out to investigate this phenomenon. Iron-laden histiocytes were found in the kidneys, spleen, and lungs of both shocked and control animals. However, substantially more histiocytes containing Prussian blue positive granules were discovered in the lungs of rats in shock than in controls. It may, therefore, be that iron is deposited in the lungs in low flow states.

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Multinucleated tracheobronchial ciliated epithelial cells seen in smears from 112 patients suffering from a wide variety of malignant tumors were found to be 2.08 times more numerous than in a control group comparable in sex, age (decades), and smoking habit but without prediagnosed malignancies. The recognition of this phenomenon may lead to the development of a new test for the diagnosis of occult cancer and may open new pathways for investigation of cancer-host relationships.

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