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Biomedical subjects

D Clough

Publications and source records attributed to D Clough.

At least 19 recordsLinked to original sources
PubMed2004

The deployment of an intensive care facility with a military field hospital to the 2003 conflict in Iraq.

The deployment of an intensive care unit with a forward British military field hospital to the conflict in Iraq in March 2003 is described. The 10 bedded unit treated 47 patients in the first month of activity. Thirty seven were adults and 10 were children. Forty two (89%) were trauma patients, mostly related to the conflict. Sixty eight percent of patients were ventilated and mortality to discharge was 6%. Mean bed occupancy was five beds and the mean duration of patient stay was 3.3 days. The difficulties of the working environment are described including the problems of a desert climate and close proximity to a conflict. Several critical incidents occurred including total power failure, extreme ambient temperatures and gas attack alarms. Despite these challenges, the facility attempted to provide a standard of intensive care similar to that seen in UK practice.

Adult↗
PubMed1997

Thermoregulatory vasoconstriction does not impede core warming during cutaneous heating.

Recent studies evaluating perioperative cutaneous-to-core heat transfer indicate that: Thermoregulatory vasoconstriction prevents further core cooling in anesthetized subjects during mild cooling. Thermoregulatory vasoconstriction only slightly decreases core cooling rates in anesthetized subjects during vigorous cooling. Thermoregulatory vasoconstriction does not impair vigorous core rewarming during anesthesia. Vigorous postanesthetic cutaneous warming increases core temperature much faster than passive insulation. Under conditions of mild thermal stress, thermoregulatory vasoconstriction is thus able to protect core temperature by reducing cutaneous heat transfer and functionally isolating the peripheral and core thermal compartment. Consequently, anesthetic-induced alterations in vasomotor tone is one of the major factors influencing core temperature in patients who are not actively cooled or warmed. In contrast, thermoregulatory tone is insufficient to prevent core temperature perturbations in patients undergoing vigorous cutaneous cooling or warming.

Body Temperature Regulation↗
PubMed1997

Efficacy of intraoperative cooling methods.

BACKGROUND: Patients may require perioperative cooling for a variety of reasons including treatment of a malignant hyperthermia crisis and induction of therapeutic hypothermia for neurosurgery. The authors compared heat transfer and core cooling rates with five cooling methods. METHODS: Six healthy volunteers were anesthetized with desflurane and nitrous oxide. The cooling methods were 1) circulating water (5 degrees C, full-length mattress and cover), 2) forced air (10 degrees C, full-length cover), 3) gastric lavage (500 ml iced water every 10 min), 4) bladder lavage (300 ml iced Ringer's solution every 10 min), and 5) ice-water immersion. Each method was applied for 40 min or until the volunteers' core temperatures approached 34 degrees C. The volunteers were rewarmed to normothermia between treatments. Core cooling rates were evaluated using linear regression. RESULTS: The first volunteer developed abdominal cramping and diarrhea after gastric lavage. Consequently, the technique was not again attempted. Bladder lavage increased heat loss approximately 10 W and decreased core temperature 0.8 +/- 0.3 degrees C/h (r2 = 0.99 +/- 0.002; means +/- SD). Forced-air and circulating-water cooling comparably increased heat flux, approximately 170 W. Consequently, core cooling rates were similar during the two treatments at 1.7 +/- 0.5 degrees C/h (r2 = 0.99 +/- 0.001) and 1.6 +/- 1.1 degrees C/h (r2 = 0.98 +/- 0.02), respectively. Immersion in an ice water slurry increased heat loss approximately 600-800 W and decreased core temperature 9.7 +/- 4.4 degrees C/h (r2 = 0.98 +/- 0.01). Immersion cooling was associated with an afterdrop of approximately 2 degrees C. CONCLUSIONS: Bladder lavage provided only trivial cooling and gastric lavage provoked complications. Forced-air and circulating-water cooling transferred relatively little heat but are noninvasive and easy to implement. Forced-air or circulating-water cooling, perhaps combined with intravenous administration of refrigerated fluids, may be sufficient in some patients. When noninvasive methods prove insufficient for rapid cooling, ice-water immersion or peritoneal lavage probably should be the next lines of defense.

Adult↗
PubMed1996

Rapid core-to-peripheral tissue heat transfer during cutaneous cooling.

Perioperative thermal manipulations are usually directed at the skin surface because methods of directly warming the core are invasive or ineffective. However, inadequate heat flow between peripheral and core compartments will decrease the rate at which core temperature changes. We therefore determined whether core hypothermia is delayed after initiation of surface cooling. Six volunteers were anesthetized with propofol and midazolam, and maintained under three layers of passive insulation for 2.5-4 h. Subsequently, the skin surface was cooled using forced air, 1000 L/min, at 10 degrees C. Isoflurane was added as necessary to maintain arteriovenous shunt vasodilation. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. Overall body heat content decreased approximately 234 kcal during 2.5 h of active cooling. Core temperature, which was nearly constant before active cooling, decreased approximately 1.3 degrees C/h. There was no delay between initiation of active cooling and the decrease in core temperature. Furthermore, peripheral (arm and leg) and core (trunk and head) tissue heat contents decreased at virtually the same rates: approximately 50 kcal/h and approximately 47 kcal/h, respectively. These data indicate that there is little restriction of heat flow between peripheral and core tissues in vasodilated, anesthetized subjects.

Adult↗
PubMed1996

Thermoregulatory vasoconstriction does not impede core warming during cutaneous heating.

BACKGROUND: Although forced-air warming rapidly increases intraoperative core temperatures, it is reportedly ineffective postoperatively. A major difference between these two periods is that arteriovenous shunts are usually dilated during surgery, whereas vasoconstriction is uniform in hypothermic postoperative patients. Vasoconstriction may decrease efficacy of warming because its major physiologic purposes are to reduce cutaneous heat transfer and restrict heat transfer between the two thermal compartments. Accordingly, we tested the hypothesis that thermoregulatory vasoconstriction decreases cutaneous transfer of applied heat and restricts peripheral-to-core flow of heat, thereby delaying and reducing the increase in core temperature. METHODS: Eight healthy male volunteers anesthetized with propofol and isoflurane were studied. Volunteers were allowed to cool passively until core temperature reached 33 degrees C. On one randomly assigned day, the isoflurane concentration was reduced, to provoke thermoregulatory arteriovenous shunt vasoconstriction; on the other study day, a sufficient amount of isoflurane was administered to prevent vasoconstriction. On each day, forced-air warming was then applied for 2 h. Peripheral (arm and leg) tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. Core (trunk and head) heat content was determined from core temperature, assuming a uniform compartmental distribution. Time-dependent changes in peripheral and core tissue heat contents were evaluated using linear regression. Differences between the vasoconstriction and vasodilation study days, and between the peripheral and core compartments, were evaluated using two-tailed, paired t tests. Data are presented as means +/-SD; P < 0.01 was considered statistically significant. RESULTS: Cutaneous heat transfer was similar during vasoconstriction and vasodilation. Forced-air warming increased peripheral tissue heat content comparably when the volunteers were vasodilated and vasoconstricted: 48 +/- 7 versus 53 +/- 10 kcal/h. Core compartment tissue heat content increased similarly when the volunteers were vasodilated and vasoconstricted: 51 +/- 8 versus 44 +/- 11 kcal/h. Combining the two study days, the increase in peripheral and core heat contents did not differ significantly: 51 +/- 8 versus 48 +/- 10 kcal/h, respectively. Core temperature increased at essentially the same rate when the volunteers remained vasodilated (1.3 degrees C/h) as when they were vasoconstricted (1.2 degrees C/h). CONCLUSIONS: The authors failed to confirm their hypothesis that thermoregulatory vasoconstriction decreases cutaneous transfer of applied heat and restricts peripheral-to-core flow of heat in anesthetized subjects. The reported difference between intraoperative and postoperative rewarming efficacy may result from nonthermoregulatory anesthetic-induced vasodilation.

Adult↗
PubMed1996

Thermoregulatory vasoconstriction and perianesthetic heat transfer.

Heat transfer between the core and its environment in normothermic and slightly hypothermic situations is determined largely by the influence of vasomotion on convection. Tonic vasoconstriction, the normal barrier to heat loss from the core, is impaired upon induction of anesthesia. The resulting dilation of the arteriovenous shunts leads to redistribution of heat from the core to the periphery, diminishing the temperature gradient between the two compartments. With reemergence of thermoregulatory vasoconstriction at core temperatures near 34 degrees C, the core and the periphery are again separated, with metabolic heat being largely constrained to the core. Under normal conditions of mild thermal stress, thermoregulatory vasoconstriction is thus able to protect core temperature by reducing cutaneous heat transfer and functionally isolating the peripheral and core thermal compartments. Consequently, anesthetic-induced alterations in vasomotor tone is one of the major factors influencing core temperature in patients who are not actively cooled or warmed. In contrast, thermoregulatory tone is insufficient to prevent core temperature perturbations in patients undergoing vigorous cutaneous cooling or warming.

Anesthesia, General↗
PubMed1995

Protection by pyruvate against inhibition of Na+, K(+)-ATPase by a free radical generating system containing t-butylhydroperoxide.

Global tissue damage due to oxygen-derived free radicals has been implicated in several pathological processes including exposure to ionizing radiation, and postischemic reperfusion of the heart or kidney. Recently pyruvate, a hydroperoxide scavenger, has been shown to protect against functional damage during postischemic reperfusion of the heart and in acute renal failure. In the present study, pyruvate was found to protect against inactivation of partially purified guinea pig renal and rat cardiac Na+,K(+)-ATPase which occurred when microsomal membranes were assayed for 1 hr at 37 degrees C (pH 7.5) in the presence of a free radical generating system (FRGS) containing 0.3 mM t-butylhydroperoxide and horseradish peroxidase. The presence of the FRG system inhibited the guinea pig renal Na+,K(+)-ATPase activity by 48.2 +/- 4.8% (N = 10, P < .05) and the presence of 0.2 to 20 mM pyruvate partially protected the Na+,K(+)-ATPase. At 5 mM pyruvate Na+,K(+)-ATPase was inhibited by only 18.8 +/- 2.5% (N = 10, P < .05) but increasing the pyruvate concentration gave no further protection. Equimolar concentrations of glucose, mannitol or lactate were without effect. The protection appeared to require an alpha-keto acid since alpha- but not beta-ketoglutarate was also effective and the mechanism is most probably the scavenging of t-BHO2. The results of the present study therefore support the hypothesis that, if free radical damage to native Na+,K(+)-ATPase does contribute to global tissue injury in certain pathological processes, pyruvate, in addition to being a powerful metabolic effector of recovery, may also protect against oxidative damage.

Animals↗
PubMed1993

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats.

We have previously reported that chronic hypertension develops consistently in Wistar rats with a 25% reduction in renal mass (RRM) following the induction of insulin dependent diabetes mellitus (IDDM) with streptozotocin (STZ, 65 mg/kg body weight, intravenously). In this study, we examined the role of the endogenous digitalis-like substance in the development of hypertension. Four groups of rats were studied: 1) 25% RRM rats with STZ-induced IDDM (25-DM), 2) normal rats with STZ-induced IDDM (2K-DM), 3) 25% RRM rats with vehicle treatment (25-V), and 4) normal rats with vehicle treatment (2K-V). In 25-DM rats, blood pressure progressively increased during the 3 weeks after STZ treatment and was associated with microalbuminuria, low plasma renin activity, and extracellular volume expansion. In contrast, the 2K-DM, 25-V, and 2K-V rats remained normotensive. Furthermore, the plasma and urine levels of digoxin-like immunoreactive factor (DIF), determined by digoxin radioimmunoassay (Baxter), were significantly higher in hypertensive 25-DM rats than in their controls. The same was the case for plasma digitalis-like substance (DLS), determined by exposing canine Na+,K(+)-ATPase to plasma fractions and observing the percent inhibition. Increased DIF and DLS in hypertensive 25-DM rats was associated with a significant decrease in Na+,K(+)-ATPase activity of microsomes prepared from the left and right ventricles, when compared with microsomes from normotensive 2K-DM animals. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The DIF and DLS correlated significantly with each other and with myocardial Na+,K(+)-ATPase activity and mean blood pressure. These results suggest that increased endogenous digitalis-like substance, which inhibits cardiovascular muscle cell Na(+)-K(+)-pump activity, may be involved in the mechanism of hypertension associated with IDDM in 25% RRM rats.

Animals↗
PubMed1993

Role of digitalis-like substance in experimental insulin-dependent diabetes mellitus hypertension.

Hypertension is frequently associated with insulin-dependent diabetes mellitus, but the mechanism of the hypertension is unknown. An animal model of insulin-dependent diabetes mellitus hypertension could be helpful in determining the mechanism, but experimental insulin-dependent diabetes mellitus has been infrequently and irregularly associated with hypertension. In an attempt to develop a dependable model of insulin-dependent diabetes mellitus hypertension, we studied seven series of rats receiving either streptozotocin, surgical reduction of renal mass, or both. We found that superimposing streptozotocin 65 mg/kg body weight on 25% reduced renal mass regularly produced insulin-dependent diabetes mellitus and low-renin volume-expanded hypertension and that the animals remained healthy and hypertensive for as long as followed (13 weeks). Microalbuminuria correlated temporally with blood pressure. We used this dependable model to examine the role of endogenous digitalis-like substance in the development of hypertension in insulin-dependent diabetes mellitus. Plasma levels of digoxin-like immunoreactive factor (DIF), determined with a digoxin radioimmunoassay, were significantly higher in these hypertensive rats than in normotensive control rats (two-kidney diabetic rats, 25% reduced renal mass rats receiving vehicle for streptozotocin). This increase in plasma DIF was associated with a decrease in Na+, K(+)-ATPase activity in microsomes prepared from left or right ventricle. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The plasma DIF level correlated inversely with myocardial Na+, K(+)-ATPase activity and positively with systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The impact of maternal serum on development of enolase activity in fetal rat brain cell culture.

The effect of gestational age on serum-mediated changes in enolase activity was tested in a fetal rat brain cell culture. After 6 days exposure to graded concentrations (10 and 20%) of nonpregnant female rat sera, enolase activity in brain cell cultures increased from 2.83 +/- 0.03 to 3.74 +/- 0.19 mumol/min/mg protein, P less than 0.01. By contrast, similar concentrations of 20-day maternal serum progressively decreased enzyme activity from 1.52 +/- 0.14 to 1.19 +/- 0.08 mumol/min/mg protein. The inhibitory effect was apparent at 14 days gestation and became progressively greater during late gestation to reach a maximum at 20 days. Combining equal concentrations of 20-day pregnant with either nonpregnant or adult male serum neutralized the inhibitory activity. When serum from 20-day pregnant rats was partitioned by a dialysis membrane with a 50,000 MW pore size, inhibitory activity could be similarly neutralized by male or nonpregnant female serum. When 20-day maternal serum was passed successively through filters with a greater than 300,000, 100,000, and 50,000 MW exclusion, the inhibitory activity was apparent in all fractions excluded by a molecular weight of 50,000. No inhibition was apparent in fractions that were not excluded by 50,000 MW pore size. Inhibition of enolase activity was greatest in the fraction with MW greater than 300,000. Binding of IGF II could also be demonstrated in this fraction. Binding of IGF II was evident in the fraction greater than 100,000 MW but could not be demonstrated in fractions with a lower molecular weight. The presence of mRNA for IGF II in 20-day fetal rat brain cell cultures was evident when total cellular RNA was analyzed by an RNAase protection assay. It is proposed that a high-molecular-weight component of maternal serum in late gestation can bind endogenously generated IGF II. Such binding, by depleting the necessary growth factors, could inhibit in vitro growth and development of enolase activity.

Animals↗
PubMedDate not supplied

Role of a humoral sodium-potassium pump inhibitor in experimental low renin hypertension.

Recent evidence suggests that the vascular sodium-potassium pump suppression previously observed in animals with various models of low renin hypertension results from a circulating heat stable ouabain-like agent. It appears to come from or be influenced by the anteroventral third ventricle area of the brain and its action on blood vessels results in depolarization of the smooth muscle cell. Suppression of the vascular sodium-potassium pump, with ouabain for example, increases contractile activity and the contractile responses to vasoactive agents. Thus the humoral pump inhibitor may be involved in the genesis and maintenance of experimental low renin hypertension.

Animals↗
PubMedDate not supplied

Angiotensin-converting enzyme inhibitor resets baroreceptor reflexes in conscious dogs.

The present experiments investigate whether the absence of tachycardia during lowering of blood pressure (BP) with an angiotensin-converting enzyme inhibitor (CEI) in salt-depleted dogs is due to an alteration in the activity of the baroreflex. Baroreflex activity was measured after pharmacological manipulation of BP using intravenous nitroglycerin or phenylephrine, and the heart period (R-R interval) relative to the arterial pressure pulse was recorded. The slope of the relationship between BP and R-R interval is a measure of the sensitivity of the baroreceptor reflex and displacement of the line indicates a change in the setpoint of BP. On normal sodium diet, the sensitivity and setpoint of the baroreflex were unaltered by the nonapeptide CEI given both intravenously and into a lateral cerebral ventricle. During salt depletion. however, intravenously but not centrally administered CEI altered the setpoint of the baroreflex without modifying the sensitivity. The alteration in the setpoint that occurred following intravenous CEI in the salt-depleted dog could well account for the fact that the fall in BP induced by CEI does not cause reflex tachycardia. These results indicate that circulating but not brain angiotensin II is essential for the maintenance of baroreflex function during sodium depletion and provide further evidence for the important interactions between angiotensin and the autonomic nervous system.

Angiotensin-Converting Enzyme Inhibitors↗