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Quadrupole coupling constants at deuterium nitrogen in compounds that contain the imidazole group are discussed in the light of ab initio SCF calculations of field gradients in imidazole. In particular, estimates of the effect of hydrogen bonding to imino nitrogen on the field gradients at /sup 14/N and /sup 2/H are made by use of a point charge polarizing field. The calculations are intended to be relevant to experimental data on nucleosides and other biological species in which a significant feature of the structure is hydrogen bonding to imino nitrogen (-N:). The polarization density of imidazole in the point charge field is also discussed. The SCF calculations are at the level of Dunning-Hay + d,p polarization bases.

The role of endogenous opioids in systemic and renal circulatory changes during combined acute hypoxemia and hypercapnic acidosis was evaluated in seven conscious female mongrel dogs in rigid sodium balance. Animals were studied 2 wk apart in separate protocols of combined acute hypoxemia (arterial O2 tension = 33 +/- 1 mmHg) and hypercapnic acidosis (arterial CO2 tension = 56 +/- 1 mmHg, pH = 7.19 +/- 0.01) of 40 min duration during 1) naloxone, 5 mg/kg iv bolus followed by an intravenous infusion of 5 mg.kg-1.h-1, and 2) vehicle (5% dextrose in water) alone. Systemic circulatory changes during the combined acute blood-gas derangement including increased mean arterial pressure, heart rate, and cardiac output and decreased total peripheral resistance were comparable between naloxone and vehicle treatments. However, in striking contrast to the brief fall in renal hemodynamic function during combined acute hypoxemia and hypercapnic acidosis with vehicle, naloxone administration during the combined acute blood-gas derangement resulted in a sustained decrease in effective renal plasma flow, glomerular filtration rate, and filtered sodium load and enhanced rise in circulating norepinephrine and epinephrine. Changes in plasma renin activity were comparable between vehicle and naloxone protocols except that plasma renin activity increased from the first to the second 20-min periods of combined hypoxemia and hypercapnic acidosis with naloxone. These observations suggest that endogenous opioids may contribute to preservation of renal hemodynamic function during acute blood-gas derangements, possibly through attenuation of sympathetic nervous system and renin-angiotension activation.

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The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.

Serotonin (5-HT) in the central nervous system has been implicated in blood pressure control in both normotensive and hypertensive states. Parachlorophenylalanine (PCPA) depletes 5-HT in the central nervous system. Normotensive Wistar rats, Wistar rats made hypertensive by renal artery clipping (RHR), and spontaneously hypertensive rats (SHR) were depleted of central serotonin by the administration of PCPA. Mean arterial blood pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) levels were measured in rats both before and after they were administered anesthesia with enflurane. Blood pressure was further decreased by the administration of saralasin, a competitive inhibitor of angiotensin II. Principal results are as follows. Central 5-HT was depleted by 70% or more with PCPA. In general, brain catecholamines were not altered by this treatment. No consistent pattern of change in MAP, HR, or plasma NE was observed for Wistar rats, RHR, or SHR during an awake control period in rats treated with PCPA compared with rats treated with vehicle. However, during enflurane anesthesia or enflurane anesthesia with saralasin, MAP, HR, and plasma NE were significantly greater in Wistar rats and RHR treated with PCPA compared to similar groups treated with vehicle. This was not observed in SHR: MAP, HR, and plasma NE were similar to vehicle-treated SHR. Nonsignificant changes in plasma epinephrine, plasma renin activity, or arterial blood gas tensions could not explain the differences seen in Wistar rats, RHR, or SHR. Central serotonin plays an important role in cardiovascular control during anesthesia with enflurane in Wistar rats but does not appear to play a dominant role in SHR.

The role of the renin--angiotensin system in the regulation of blood pressure in dogs and in human subjects was assessed by the use of the nonapeptide converting enzyme inhibitor (CEI), permitting the following conclusions: 1) In the normal, sodium replete dog, the renin--angiotensin system plays little role in the regulation of blood pressure. 2) As sodium depletion progresses, the renin--angiotensin system becomes increasingly important in the maintenance of blood pressure. In the markedly hypovolemic animal, blocking the conversion of angiotensin I to angiotensin II leads to prolonged hypotension of shock-like levels. 3) The renin--angiotensin system is responsible for the initiation of renovascular hypertension. Blood pressure does not rise during chronic renal artery constriction when the generation of angiotensin II is prevented by the CEI. Although angiotensin II is essential for the initiation of the elevated blood pressure, the renin--angiotensin system plays a decreasing role in the maintenance of the chronic hypertension as sodium and water are retained, and plasma volume increases. 4) In congestive failure induced in the conscious dog by circulatory impairment, the renin--angiotensin--aldosterone system plays an essential role in the compensatory response. During chronic administration of the CEI, the animal cannot compensate even for a relatively mild degree of constriction, and remains hypotensive. In the dog with congestive failure, as in the dog with renovascular hypertension, plasma renin activity (PRA) and plasma aldosterone are elevated early in the syndrome; during this phase, injection of the nonapeptide produces a marked drop in blood pressure. With the retention of sodium and water, and expansion of plasma and extravascular fluid volumes, PRA and plasma aldosterone return to control levels in the new steady state. The inhibitor no longer produces a drop in blood pressure. Thus, the sequential changes in the renin--angiotensin--aldosterone system are remarkably similar in renovascular hypertension and congestive failure. 5) In the normal, salt replete human subject the renin--angiotensin system plays little role in the regulation of blood pressure either in the recumbent or upright posture. However, with relatively mild sodium depletion, the CEI transiently lowers blood pressure even in the recumbent subject. In the absence of angiotensin II such sodium-depleted subjects are unable to compensate when tilted upright, and faint within minutes.

Forty-two spontaneously hypertensive rats (SHR) and 42 normotensive Wistar-Kyoto rats (WKY) were anesthetized with either halothane or enflurane. Blood pressure, heart rate, cardiac output, distribution of blood flow, plasma renin activity, and plasma catecholamines were measured to determine in what manner the hypertensive animal responded to these two anesthetics. Major findings of the study were that plasma renin activity did not increase in the SHR despite a 25% reduction in MAP. The infusion of saralasin, an angiotensin II antagonist, resulted in a further decrease in blood pressure in SHR anesthetized with halothane but not with enflurane. Plasma catecholamine concentrations were elevated in the awake SHR and were decreased in SHR anesthetized with enflurane. Both halothane and enflurane anesthesia resulted in similar alterations in blood flow in the SHR. The normotensive WKY responded to halothane and enflurane in a different manner than the SHR. Plasma renin activity increased with the decrease in blood pressure with both agents. A further decrease in blood pressure occurred with saralasin infusion in WKY anesthetized with halothane or enflurane. Significant blood flow alterations occurred in the WKY anesthetized with both agents, but enflurane caused the greatest changes. The SHR may prove useful in examining the effects of anesthetic agents and other drugs so that we may have a better understanding of the perioperative management of the patients with essential hypertension.

Dichloroacetate (DCA) is known to prevent the phosphorylation of the pyruvate dehydrogenase complex (PDHC) by blocking the action of PDH kinase. This action allows the active PDHC to exert its effect on the metabolism of glucose, lactate and alanine to acetyl CoA. DCA has been shown to reduce serum lactate levels in humans and animals in such conditions as diabetes, phenformin-induced hepatic failure, exercise, and endotoxin-induced shock. Lactic acidosis in the brain has often been postulated as a cause of neuronal damage following ischemia and hypoxia. Therefore, we examined the effect of intravenously administered DCA (100 mg/kg) in rats that were rendered hyperglycemic by intravenous glucose (2 g/kg), and then made to undergo 15 minutes of incomplete cerebral ischemia by bilateral carotid ligation and systemic hypotension (mean arterial pressure of 50 mm Hg). DCA significantly reduced serum lactate levels pre-ischemia, but had no effect on serum lactate levels after ischemia induction. Brain levels of lactate, ATP and PCr after 15 minutes of incomplete ischemia were unaffected by DCA. We conclude that in this in-vivo model the control of PDHC activity in the brain may be different than that in the periphery, and that DCA was not effective in reducing brain tissue lactate levels.

Catecholamine and serotonin concentrations in the cord, medulla, and hypothalamus were measured in rats after saline, after sufentanil sufficient to reduce the minimum alveolar concentration (MAC) of halothane by 30% or less, or after sufentanil sufficient to reduce the MAC of halothane by 80% or more. In the cord, high doses of sufentanil resulted in a 13.4% reduction (P less than 0.05) in serotonin concentration compared to saline control and a 17.4% reduction (P less than 0.05) in serotonin concentration compared to low dosages of sufentanil. A 12.8% reduction (P less than 0.05) in medullary serotonin also was observed with high sufentanil compared to low sufentanil. Epinephrine decreased significantly in the hypothalamus at the high sufentanil dose. No other significant differences were found in catecholamine content. The experimental results support the hypothesis that sufentanil may contribute to an analgetic component of general anesthesia by modulating nociception via the release of 5-HT.

The importance of the brain noradrenergic sympathetic nervous system in blood pressure control during anesthesia with halothane and enflurane was investigated in normotensive and hypertensive rats. Central noradrenergic neurons were destroyed by instillation of 6-hydroxydopamine (6-OHDA) into the cerebral ventricle of both normotensive Wistar rats and spontaneously hypertensive rats (SHR). One week later, arterial and venous lines were placed in the rats under anesthesia; the rats were allowed to recover; and blood pressure and plasma renin activity were measured while the rats were awake. Anesthesia then was induced with 1.3 vol% halothane (Wistar n = 8, Wistar 6-OHDA n = 10, SHR n = 8, SHR 6-OHDA n = 6) or 2.2 vol% enflurane (Wistar n = 6, Wistar 6-OHDA n = 10, SHR n = 8, SHR 6-OHDA n = 6). A control group (Wistar n = 10, Wistar 6-OHDA n = 6, SHR n = 8, SHR 6-OHDA n = 6) was treated identically, but remained unanesthetized throughout the experiment. The untreated normotensive and hypertensive rats received no intraventricular injections. After 1 hr of stable anesthesia, plasma renin activity was measured again, and saralasin, a competitive inhibitor of angiotensin II, was infused to determine the importance of the renin--angiotensin system in blood pressure control. Treatment with 6-OHDA resulted in a 60-90% depletion of norepinephrine in the medulla and hypothalamus. Normotensive Wistar rats treated with 6-OHDA responded to halothane and enflurane anesthesia in a manner similar to untreated normotensive rats. In contrast, hypertensive animals treated with 6-OHDA and then anesthetized with halothane had a significantly greater decrease in blood pressure than untreated hypertensive rats (100 +/- 4 mm Hg vs 125 +/- 4 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Using subclavian vein catheterization after unsuccessful internal jugular venous puncture, the authors have been successful in 23 of 32 children younger than 2 years of age. There was no mortality, and minimal morbidity, with this procedure. Cannulation should be performed in most cases on the first insertion of the needle, and the Seldinger technique using a J-wire aids in catheter placement. Though we did not cause pneumothorax, the inability to obtain a chest x ray prior to the operative procedure in most patients causes us to suggest that this technique be used only on those patients requiring an open chest operative procedure.

Anesthetic agents have been shown to alter survival in animals subjected to hemorrhage. Since survival after hemorrhage is increased by inhibitors of the renin-angiotensin system, we asked whether anesthetic agents altered renin release during hemorrhage. We studied 33 rats which were subjected to one hour of hemorrhagic hypotension at a mean arterial pressure of 40 mm Hg. Animals were either awake or anesthetized with halothane or ketamine. Anesthesia alone did not alter plasma renin activity (PRA), whereas hemorrhage resulted in approximately a ten-fold increase in PRA in both awake and anesthetized animals. After the shed blood was returned to the animal, intravenous saralasin, an angiotensin II competitive inhibitor, produced a 21-24 mm Hg decrease in blood pressure in all animals, regardless of the severe hemorrhage is unaltered by halothane or ketamine anesthesia, that the renin-angiotensin system provides a similar amount of blood pressure support in both awake and anesthetized animals, and that the anesthetic influence on survival following severe hemorrhage does not result from anesthetic-induced alterations of the renin-angiotensin system.

Mitral valve replacement is frequently complicated by a low cardiac output syndrome and elevated pulmonary arterial pressures. In the present study, we used dobutamine to increase cardiac index and measured the pulmonary hemodynamic effects in 10 patients with increased pulmonary vascular tone following mitral valve replacement. Using increasing doses of dobutamine up to 10 micrograms.kg-1.min-1, we observed a statistically significant increase in mean cardiac index (from 2.39 +/- .14 liters.min-1.m-2 to 3.52 +/- .33, P less than 0.01) and mean heart rate (from 71.6 +/- 5.2 beats.min-1 to 84.3 +/- 8.1, P less than 0.01). This was associated with stable mean systemic arterial pressures and mean pulmonary arterial pressures. Both mean systemic and pulmonary vascular resistances decreased significantly (from 1210 +/- 99 dynes.sec.cm-5 to 809 +/- 90 [P less than 0.01], and from 195.9 +/- 30.6 dynes.sec.cm-5 to 129.4 +/- 41.2 [P less than 0.01] respectively) with dobutamine. Intrapulmonary shunt flow increased significantly in the five patients studied. Though increases in heart rate and pulmonary shunt flow may limit it use, dobutamine increases cardiac output and decreases pulmonary vascular resistance in patients with increased pulmonary arterial pressure following mitral valve replacement.

To systemically evaluate the effects of acute hypoxemia and hypercapnic acidosis on the sympathetic nervous system, five unanesthetized mongrel dogs were studied during acute hypoxemia [arterial O2 tension (PaO2) 33 +/- 2 Torr], acute hypercapnic acidosis [arterial CO2 tension (PaCO2) 53 +/- 1 Torr; pH, 7.19 +/- 0.02], and combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 Torr; PaCO2, 52 +/- 1 Torr; pH, 7.18 +/- 0.02). Combined acute hypoxemia and hypercapnic acidosis resulted in increased mean arterial pressure, cardiac output, and heart rate. Moreover, combining acute hypoxemia and hypercapnic acidosis acted synergistically to increase circulating norepinephrine and epinephrine. Acute hypoxemia alone and acute hypercapnic acidosis alone resulted in reversible increases in mean arterial pressure, cardiac output, heart rate, and circulating norepinephrine. Although plasma epinephrine concentrations increased during acute hypoxemia, circulating epinephrine was unchanged during acute hypercapnic acidosis. These data indicate that acute hypoxemia and hypercapnic acidosis result in synergistic increase in circulating catecholamines.

From human plasma of healthy subject, an inhibitor of Na+, K+-ATPase was prepared, using a gel filtration followed by anion exchange chromatography and by HPLC on reverse phase. This low molecular weight (less than 1,500 dalton) inhibitor is a substance which possesses anionic charges, and is absorbed on reverse phase. It inhibits Na+, K+-ATPase activity and the 3H-ouabain binding on human red blood cells.

The renin-angiotensin system has received considerable attention in the last several years and is one of a variety of vasoactive substances that are known to be important in controlling blood pressure. The presentation will focus on how the various aspects of the renin-angiotensin system may have important implications for the anesthesiologist. It should be remembered, though, that this is only one of many vasoactive substances and may be a model with which to look at other agents that are known to affect blood pressure. Certainly with the newer information that is now available and the recently synthesized drugs that affect the renin-angiotensin system, we, as anesthesiologists, are now seeing patients who are being treated with these agents both prior to operation and immediately after operation.

Male Wistar rats were anesthetized at 6 weeks of age and a silver clip placed around the renal artery to produce renovascular hypertension. The rats were allowed to grow on a normal sodium diet for the next 6-9 weeks. Using diethyl ether anesthesia, arterial and venous cannulae were placed and the animals allowed to awaken in restraining cages. The group of rats was divided into three groups: awake (n = 7), halothane 1.3 vol% (n = 9), and enflurane 2.2 vol% (n = 8). The protocol consisted of a 1-h control awake period, 1 h of stable anesthesia (one group received no anesthesia), and 30-min iv infusion of saralasin, a competitive inhibitor of angiotensin II. Plasma renin activity (PRA) and plasma catecholamines were measured after 1 h of stable anesthesia and after the saralasin infusion. In additional rats treated identically, radiolabelled microspheres were used to measure cardiac output and regional blood flows during halothane (n = 7) or enflurane (n = 6) anesthesia. Principal responses were as follows: mean arterial pressure (MAP) was 193 +/- 4 mmHg awake and decreased to 114 +/- 3 mmHg and 135 +/- 3 mmHg with halothane and enflurane, respectively. Saralasin decreased MAP in the awake group to 176 +/- 3 mmHg and to 69 +/- 3 mmHg and 96 +/- 5 mmHg with halothane and enflurane, respectively. PRA in the awake rats was 7.24 +/- 1.3 ng X ml-1 X h-1. PRA increased with halothane but decreased with enflurane. Plasma catecholamines were decreased markedly by saralasin and by both anesthetic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary New entrants to four medical schools in Britain were questioned with regard to those factors which made them choose one medical school rather than another. Approximately 400 replies were obtained which indicated that acceptance of the student's personal qualifications for entry and the buildings and facilities of the medical school were attractive features and an emphasis on community medicine and the availability of living accommodation also exerted a positive effect on would-be medical students. The fact that relatives went to the school, that the school had a traditional approach or that they were advised to choose that particular institution by their school teacher appeared to be found unattractive by possible applicants.

We present studies of the rheological properties and dispersion stability of MR fluids as a function of particle shape by comparing fluids made with uniform nickel spheres to those employing nickel microwires suspended in silicone oil. The wires were fabricated using template-based electrodeposition having diameters in the range 300 ± 30 nm and lengths in the range of 5 – 25 μm . The properties of these wires were compared to commercial nickel carbonyl spheres (1–10 μm dia.). Qualitatively, the off-state (field off) viscosity of fluids containing only wires was found to be substantially greater than those fluids that contain only spherical particles. Rheological measurements of the on-state viscosities were conducted using a custom rheometer equipped with an electromagnet capable of magnetic fields up to 0.6 T. Placed in this field, we observed yield stresses of 1.88 ± 0.23 and 1.86 ± 0.26 kPa for 7.6 volume percent of pure nickel spheres and microwires, respectively. The fluids containing spherical nickel particles tended to settle rather quickly (< 20 minutes), while those containing only wires remained suspended even after several months.