by Robert M. Epstein, lvI.D. Harold Carron Professor of Anesthesiology My first memories of Ray Fink follow his arrival at the Columbia-Presbyterian Medical Center in the summer of 1952, right after the start of my residency and the conclusion of his own at the Beth Israel Hospital in New York. The residents wondered, was this new at­ tending, barely two years ahead of us but fifteen years older? We learned quicldy that he was no usual retread! Only la ter did I discover the com­ plexities of Ray's background: from South Af­ rica, years in the United Kingdom, general prac­ tice of medicine. What unfolded for us was the pleasure of experiencing a man of questioning and creative imagination who had much to of­ fer his students and colleagues. Ray watched his patients closely. During his initial year he noted that blood oxygen desaturation during emergence from nitrous oxide-oxygen anesthesia was more common than most of us realized. It was easy to attribute this to partial obstruction or drug effects, but Ray-never satisfied with glib explanations­ thought physiologically. His velY earliest career days (presentation at the Federation meetings by the spring of 1954) thus saw the identifica­ tion of what he called diffusion anoxia. This important theory, of the effects of large volume gas exchanges during unsteady states, was the earliest identified of a group of similar effects, including the concentration and second gas ef­ fects found by others. My personal experience of Ray was inter­ rupted by militmy service in the Far East and by a return for two years of residency comple­ tion and research fellowship. After 1957 we were faculty members together for about seven years. For Ray they were years marked by an explo-

SHIH-HSU N Ngai, a distinguished anesthesiologist and pharmacologist and former Editor of ANESTHESIOLOGY, died of lung cancer on July 8, 1999, shortly before his 79th birthday. He was born in Wuchang, China, on September 15, 1920, the youngest and eighth child of a high school teacher. A graduate of China’s Central University Medical School, he spent almost his entire professional career at Columbia University’s Department of Anesthesiology after winning a competitive government fellowship to study anesthesiology abroad. At Columbia, he rose to be Professor of Anesthesiology in 1965 and of Pharmacology in 1974. He spent 2 yr in the US Army (1955–1957) and chaired the Department of Anesthesiology from 1969–1973. He was a distinguished clinician, scientist, teacher, and mentor. FIGUREAs a clinician, Dr. Ngai was knowledgeable, compassionate, and highly skilled. He was greatly regarded as a preceptor to residents because, while teaching them to provide anesthesia, he also made them think about their every action.Dr. Ngai began his research even as a resident, doing pioneering studies on central nervous system control of respiration with Dr. S. C. Wang, the renowned physiologist, that are classics. Later, at Columbia and with collaborators elsewhere, he studied the interactions of biogenic amines with general anesthetics. He also studied narcotics, narcotic antagonists, and the participation of opioid receptors in anesthetic-induced analgesia. His work always seemed a step ahead of his time. An article in Science in 1976 about the analgesic effect of nitrous oxide stimulated controversy, which persists to now. Seven of his nine research fellows remain in the academic practice of anesthesiology, a remarkable record. Upon his retirement in 1988 the Shih-hsun Ngai Research Fellowship was established to honor his accomplishments.For many years, Dr. Ngai was affiliated with the biomedical and anesthesiology communities of Taiwan. He was Visiting Professor at National Taiwan University in 1990, the Tri-service Hospital in 1992, and the Veteran’s General Hospital in 1994. During these visits, he upgraded the practice, teaching, and research of anesthesiology in Taiwan. He also was a founding member of the National Health Research Institute, which is similar to the National Institutes of Health in the United States.Perhaps only his closest associates knew that he had an uncanny mastery of scientific writing and English. He helped many at Columbia University and in Taiwan with grant applications and manuscripts, and edited all accepted papers for the Chinese anesthesiology journal Acta Anaesthesiologica Sinica . Dr. Ngai was a man with great integrity in both his personal and professional lives. He had a passionate curiosity informed by keen observation. His high standards, unwavering sense of fairness, and commitment to do the right thing, along with a quiet humor, touched everyone around him. Prestigious honors included the Commonwealth Fellowship (1964), election to the Academia Sinica (Taiwan, 1972), the National Research Council Anesthesia Committee (1961–1970), and several National Institutes of Health Study Sections (1962–1982). Elected to the editorial board of ANESTHESIOLOGY, he served for 10 years (1967–1977), having been asked to continue beyond the normal term because of his special contributions.Dr. Ngai is survived by his wife, Dr. Hsueh Hwa Wang, Professor Emeritus of Pharmacology of Columbia University; two daughters, Mae, Assistant Professor of History at the University of Chicago; Janet, a physical therapist in Massies Mill, Virginia; a son, John, Associate Professor of Neurobiology and Head of the Neurobiology Graduate Program at the University of California at Berkeley; five grandchildren; and memories of a joyous 50th wedding anniversary family reunion on Christmas, 1998.He is profoundly missed, but his memory lives in the hearts of his friends.

Last year, the Journal of Clinical Anesthesia (‘JCA) took note of the fiftieth “jubilee” of the journal Anesthesiology in an editorial by Dr. Leroy D. Vandam.’ It is the season for remembrances, for at almost the same time a half century ago, there was in creation the American Board of Anesthesiology (ABA). Its origin as an independent corporation took place in March 1938 after a brief spell as a subsidiary of the American Board of Surgery. This event marked an important milestone in the development of our specialty, leading ultimately to the acceptance of anesthesiology as a medical discipline among its peers. Recognition as a specialty board required the usual period of discussion, negotiation, and acceptance of formal status by the then Advisory Board for Medical Specialties (now the American Board of Medical Specialties) and its parent organizations. This event, in February 1941, followed the incorporation of the ABA by some three years. No one who has lived within the specialty through the intervening years (for this writer, all but a decade) would agree that acceptance of the ABA by organized medicine was other than a small beginning to the recognition of the specialty by the rank and file of medicine, the public, and the institutions of society generally. It was not the existence of the ABA itself that accomplished this acceptance. Ultimate legitimacy depended on continual dedication to the enhancement of the standards of knowledge and practice among anesthesiologists, along with the efforts of the American Society of Anesthesiologists (ASA) and its member practitioners working in the clinical, scientific, educational, and political arenas. The vision, energy, enthusiasm, and political skills of the founding directors of the ABA were thus all the more remarkable for the fact that success-whether in the sense of formal recognition or true acceptancewas by no means assured. “Let us now praise famous men”:* These directors, Drs. T. Drysdale Buchanan, John Lundy, Emory Rovenstine, Henry Ruth, H. Boyd Stewart, Ralph Tovell, Ralph Waters, Paul Wood, and Philip Woodbridge, were motivated by many desires, not the least of

To the Editor.— In their excellent retrospective study of 10,590 men for diseases or conditions related to vasectomy by an immunopathological mechanism, Massey and colleagues 1 discuss potential cardiovascular complications of the procedure in detail. These authors indicate an absence of adverse cardiovascular effects of vasectomy. However, they do not mention the possibility of adverse reactions in these patients during subsequent diagnostic or therapeutic interventions in which anticoagulation and its antagonism with protamine are used. Watson and coworkers 2 recently described an anaphylactoid reaction immediately following the administration of protamine to a vasectomized patient undergoing cardiac catheterization and coronary angiography. Pretreatment with steroids and antihistamines prevented another episode when protamine was administered during aortocoronary bypass surgery. 2 With increased use of vasectomy for birth control, and of coronary angiography, percutaneous transluminal angioplasty, and aortocoronary bypass grafting for coronary artery disease, the likelihood of hemodynamically significant responses to protamine merits heightened awareness

Naloxone increases arterial pressure in hemorrhaged animals, but its effects on organ blood flows are not well established. We measured central and regional hemodynamics immediately before and 25 min or 55 min after hemorrhage in 33 anesthetized rats. Fifteen minutes after the beginning of hemorrhage, animals received either vehicle (n = 17) or naloxone (n = 16), 10 mg/kg, intravenously. At 25 min, animals treated with naloxone had a greater blood flow to the left cerebral hemisphere than those receiving vehicle, but all other measurements were similar. At 55 min, the mean arterial pressure and heart rate were greater in animals treated with naloxone, but blood flow was increased to the spleen only. Vascular resistance values were greater in the gastrointestinal tract and less in the spleen in animals receiving naloxone. The data confirmed that, in anesthetized rats, naloxone increased mean arterial pressure and splenic blood flow and transiently increased cerebral blood flow, but other regional flows and cardiac output were similar to those in rats receiving vehicle only.

Because the belief that cyanide is released from nitroprusside in vivo recently was challenged, the authors performed a series of experiments that examined the conditions under which nitroprusside is degraded. These experiments include an examination of the release of cyanide and nitric oxide from nitroprusside in vitro, the release of cyanide in vivo, and a comparison of the biologic activity of intact and degraded nitroprusside. Nitroprusside in aqueous solution degraded when exposed to white or blue light but not to red light. While light at 20 microW X cm-2 produced 40% apparent photodegradation after 6 h exposure, while white light at 220 microW X cm-2 produced 100% apparent photodegradation after 2 h exposure. At 10% apparent photodegradation, 10% of the nitrosyl ligand was recovered as free nitric oxide, and 0.4% of the cyanide ligand was recovered as free cyanide. Following a 2-h infusion of light-protected nitroprusside in seven patients, cyanide concentrations ranged from 1.4 to 45.5 microM and 0.09 to 3.2 microM in blood and plasma, respectively. These values were not changed by exposing the samples to white light (220 microW X cm-2) for 4 h. Intact and photodegraded nitroprusside produced identical hypotensive responses in rats as would be expected, since the nitrosyl ligand was detected in solution following degradation, and it mediates this action. Cyanide was released from nitroprusside, both on its exposure to light in vitro and also in vivo. The latter was not an artifact of the assay for cyanide. Nitroprusside releases cyanide in vivo, and cyanide toxicity is a true complication of its use.

The authors studied 12 patients who required deliberate hypotension for spinal fusion operations in order to investigate the efficacy of captopril for reducing dose requirement for sodium nitroprusside (SNP). Six patients, selected at random, were pretreated with captopril, 3 mg/kg po, and the remaining six patients served as controls. All patients received a similar anesthetic technique, consisting of thiopental 3 mg/kg, pancuronium 0.1 mg/kg, morphine 0.5 mg/kg, plus nitrous oxide 70% in oxygen. SNP was used to maintain mean arterial pressure (MAP) at 50-55 mmHg during deliberate hypotension lasting 140 +/- 13 minutes (mean +/- SE). Patients who received captopril required less SNP than untreated patients both early during hypotension (1.4 +/- 0.5 micrograms X kg-1 X min-1 vs. 4.8 +/- 0.8 micrograms X kg-1 X min-1, P less than 0.05), as well as late during hypotension (2.2 +/- 0.2 micrograms X kg-1 X min-1 vs. 5.6 +/- 0.6 micrograms X kg-1 X min-1, P less than 0.05). Whole blood cyanide was significantly lower in the patients pretreated with captopril than the untreated controls both early in the hypotensive period (2.7 +/- 0.6 mumol/l vs. 13 +/- 4 mumol/l, P less than 0.05) and also late in the hypotensive period (3.7 +/- 0.8 mumol/l vs. 30 +/- 10 mumol/l, P less than 0.05). MAP was reduced by captopril pretreatment both following induction of anesthesia (64 +/- 4 mmHg captopril vs. 80 +/- 4 mmHg control, P less than 0.05) and during surgery before deliberate hypotension (86 +/- 5 mmHg captopril vs. 100 +/- 4 control, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Resonance Raman spectra of a number of protocatechuate 3,4-dioxygenase-inhibitor complexes were studied by use of the available lines of an argon and a krypton laser. Three types of inhibitors were investigated-hydroxybenzoates, dicarboxylates, and 4-nitrocatechol. The hydroxybenzoate study shows that the hydroxy group in 3-hydroxybenzoate does not coordinate to the active site iron, in agreement with earlier suggestions, and confirms the coordination of the hydroxy group in the isomeric 4-hydroxybenzoate. The dicarboxylate study demonstrates that both glutarate and terephthalate perturb the active-site environment, shifting the charge-transfer interaction to lower energy. The pH dependence of terephthalate binding as well as the spectral similarities of the dicarboxylate complexes to the ESO2 intermediate provides further evidence for the suggestion that this intermediate is a tightly bound enzyme-product complex. The 4-nitrocatechol study indicates that, unlike the substrate catechols, 4-nitrocatechol does not bind to the iron; a binding configuration wherein the acidic phenolate group interacts with the carboxylate binding site has been suggested by others. Finally the spectra of the 4-hydroxybenzoate and terephthalate complexes demonstrate the presence of two tyrosines coordinated to the active-site iron as suggested by others; these tyrosines have different vCO's and excitation profiles.

Cardiac output and distribution of blood flow using 15-micron radioactively labelled microspheres were determined in 25 Wistar rats. In seven awake control animals, first and second injections of microspheres did not change cardiac output (137 +/- 8 ml/min) or result in alteration in apparent blood flow to the various organs studied. Halothane anesthesia (n = 6) (1.3 per cent inspired) resulted in a decrease in cardiac output, with increases in the percentages of cardiac output going to the brain, kidney, liver and large intestine. Enflurane anesthesia (n = 6) (2.2 per cent inspired) did not decrease cardiac output. The percentages of cardiac output going to the liver, lung, spleen, and large intestine increased. Both halothane and enflurane caused decreases in the percentages of cardiac output going to the heart and skeletal muscle. Ketamine anesthesia (n = 6) (125 mg/kg, im) differed from the other two agents in that few changes occurred from the awake state except in brain, lung and muscle, Microspheres that were trapped after the first injection were released from muscle and skin with ketamine anesthesia, resulting in an apparent decrease in the distribution of cardiac output to muscle in the controls and an apparent increase in "flow" to the lung. The microsphere method gives reliable information about cardiac output and distribution of flow in rats anesthetized with halothane or enflurane. Further studies are necessary to determine whether microsphere studies are valid indicators of organ flow during ketamine anesthesia in the rat.

The effects of halothane and enflurane on the polarographic measurement of oxygen with five platinum and three gold microelectrodes were examined. Oxygen microelectrodes were calibrated in saline solution equilibrated with either nitrogen (N2) or air, then either halothane, 1.0 per cent, or enflurane, 2.0 per cent, was added to the gas mixture. For each electrode, polarographic curves were determined during exposure to five equilibrating gas mixtures: N2, air, N2 plus halothane, air plus halothane, and N2 plus enflurane. Halothane variably increased the current produced (and therefore the estimated oxygen tension) at all polarizing voltages in saline solution equilibrated with either N2 or air. The effect was present in both conical platinum electrodes and recessed-tip gold electrodes and was not prevented by membrane coatings of polystyrol, Rhoplex or collodion. Enflurane did not alter the polarographic measurement of oxygen. It is concluded that tissue oxygen tension measurements, made with these microelectrodes and membranes, may be unreliable in the presence of halothane.

Anesthetic exposure is usually necessary but rarely sufficient to the conduct of therapy. Consequently, there is a natural abhorrence of any worsening of a patient's condition secondary to the administration of anesthesia, which offers the patient no direct benefit. Highly safe anesthesia is a necessary precondition for the application of most surgical treatment, and the diversity of modern surgery provides support for the relative safety of contemporary anesthetic practice. The question arises as to whether this general sense of confidence is illusory. If current estimates are accurate, mortality rates associated with anesthesia may be 2000 patients each year in the United States alone. One assumes the correctness of the premise that errors of performance or malfunction of the anesthetic human-machine "system," rather than ignorance of the relevant biology, account for the great majority of untoward outcomes. If this is the case, examination of the critical incidents involved in anesthesia should provide some helpful guidance. The data of Cooper et al. show that the maintenance period of anesthesia is the time of the largest single number of critical incidents.

Anesthetic exposure is usually necessary but rarely sufficient to the conduct of therapy. Consequently, there is a natural abhorrence of any worsening of a patient's condition secondary to the administration of anesthesia, which offers the patient no direct benefit. Highly safe anesthesia is a necessary precondition for the application of most surgical treatment, and the diversity of modern surgery provides support for the relative safety of contemporary anesthetic practice. The question arises as to whether this general sense of confidence is illusory. If current estimates are accurate, mortality rates associated with anesthesia may be 2000 patients each year in the United States alone. One assumes the correctness of the premise that errors of performance or malfunction of the anesthetic human-machine "system," rather than ignorance of the relevant biology, account for the great majority of untoward outcomes. If this is the case, examination of the critical incidents involved in anesthesia should provide some helpful guidance. The data of Cooper et al. show that the maintenance period of anesthesia is the time of the largest single number of critical incidents.