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Biomedical subjects

J H Milde

Publications and source records attributed to J H Milde.

At least 73 records · Page 4Linked to original sources
PubMed1983

The cerebral metabolic effects of isoflurane at and above concentrations that suppress cortical electrical activity.

The effects of 1.4-6.0% end-expired isoflurane on cerebral metabolism and hemodynamics were examined in dogs. A dose-related decrease in cerebral oxygen consumption (CMRO2) occurred until there was suppression of cortical electrical activity as reflected by the onset of an isoelectric electroencephalogram. This occurred at an end-expired concentration of 3% isoflurane when the mean CMRO2 was 2.02 ml X 100 g-1 X min-1. Thereafter, increasing concentrations of isoflurane to 6% had no further effect on the CMRO2. Brain biopsies taken at the end of the study revealed normal concentrations of ATP and phosphocreatine and a normal energy charge. Despite a normal cerebral energy state, there was a mild, dose-related, cerebral lactic acidosis (up to 2.84 mumol/g) that accompanied a mild systemic acidosis. It is concluded that the cerebral metabolic changes produced by isoflurane are secondary to an effect on cortical electrical activity, that abolition of this activity can be produced in dogs by a clinically relevant concentration of isoflurane (3%) without marked systemic hemodynamic effects, and that concentrations of isoflurane necessary to abolish cortical activity have no direct toxic effect on cerebral metabolic pathways.

Animals↗
PubMed1983

Inhibition of mitochondrial function is not the diuretic mechanism of ethacrynic acid in the dog.

Kidney metabolites were studied in five anesthetized dogs before and after 5 mg/kg i.v. of ethacrynic acid, followed by 3 mg X kg-1 X hr-1. This dose, which inhibits most of the reabsorption of sodium and chloride in the diluting segment, improved the energy state in biopsies from the outer medulla and caused an increase in ATP and a decrease in ADP and AMP levels and the lactate/pyruvate ratio. This was probably related to ongoing rapid metabolism in the control biopsies (with improved results after ethacrynic acid due to a primary reduction in an ATP requiring process) before they were completely frozen in liquid nitrogen. No changes occurred in ATP, ADP or phosphocreatine levels or the lactate/pyruvate ratio in cortical biopsies, which was in agreement with the previously shown lack of effect on proximal tubular reabsorption at this dosage of ethacrynic acid. These results indicate that the saluretic effect and parallel reduction in outer medullary metabolic rate with ethacrynic acid cannot be due to a direct inhibition of mitochondrial ATP production as suggested by others from in vitro experiments. The reduced rate of ATP production in vivo must be secondary to a reduced ATP demand.

Adenosine Triphosphate↗
PubMed1983

Hypothermia and barbiturates: individual and combined effects on canine cerebral oxygen consumption.

Following establishment of total spinal anesthesia, the cerebral metabolic effects of progressive hypothermia (37, 28, 18, and 14 degrees C) were studied initially in six awake dogs. The EEG became isoelectric at temperatures below 18 degrees C. At 14 degrees C, CMRO2 was reduced to 7% of control. Thereafter, 40 mg/kg thiopental, iv, was given and the dogs were rewarmed while an isoelectric EEG was maintained by a continuous thiopental infusion. The CMRO2 was then compared at the different temperatures with and without thiopental. The CMRO2 was unaffected by the barbiturate at 14 and 18 degrees C. At 28 and 37 degrees C the CMRO2 was significantly reduced by the barbiturate (at 37 degrees C to 55% of the 37 degrees C value without thiopental). The change in CMRO2 with temperature in the absence of EEG activity (due to barbiturates) closely approximated an Arrhenius curve (relating log CMRO2 to the reciprocal of absolute temperature). In the presence of EEG activity (no barbiturates) such a simple relationship was less apparent. The results support the following conclusions: barbiturates only affect CMRO2 in the presence of neuronal electrical activity; the combined effect of hypothermia and barbiturates on CMRO2 cannot be expressed as a simple additive relationship; and in the presence of electrical activity, the relationship between temperature and CMRO2 cannot be defined by any simple mathematical function.

Animals↗
PubMed1982

Pentoxifylline in regional cerebral ischemia in cats.

The effect of pentoxifylline on regional cerebral ischemia was evaluated in 22 cats. In one group of 10 cats the middle cerebral artery (MCA) was occluded by a transorbital approach, and the cats were maintained on an intensive care protocol for 48 h. Pentoxifylline 10 mg.kg-1 initiated intravenously 30 min post-occlusion and followed by 6.3 mg.kg-1.h-1 for 48 h failed improve the neurologic outcome or infarct size when compared to controls. In another group of 12 cats with the same ischemic lesion, regional cerebral blood flow in the anterior (ischemic) area and an ipsilateral parieto-occipital region was measured by 133Xe wash-out after intra-arterial injection. MCA occlusion reduced the anterior flow by 50% from a mean control value of 62.7 ml.100 g-1.min-1 to 31.9 ml.100 g-1.min-1. The parieto-occipital flow was reduced by 20-30%, probably due to diaschisis. Pentoxifylline produced only a brief, although approximately 50%, increase in flow detected over both brain regions and failed to improve the cerebral energy stores as measured 150 min following MCA occlusion. From the neurologic, blood flow and metabolic data, it is concluded that pentoxifylline failed to affect cerebral ischemia favorably in cats.

Animals↗
PubMed1981

Canine cerebral metabolic tolerance during 24 hours deep pentobarbital anesthesia.

The impact of tolerance on cerebral metabolism during prolonged pentobarbital-induced anesthesia was evaluated in 16 dogs. Cerebral metabolic rate for oxygen was calculated from direct measurements of venous blood flow rate and the difference in blood oxygen content between arterial and venous blood during four periods of continuous and unvarying deep pentobarbital anesthesia-0-3 hours, 3-6 hours, 12-15 hours, and 21-24 hours. During 0-3 h, the metabolic rate was 1.8-2.0 ml 02.100 g brain-1.min-1. This increased to 2.3-2.6 ml.100 g-1.min-1 during 3-6, 12-15, and 21-24 h. In all studies, the electroencephalogram indicated a constant deep burst-suppression level at 2-6 bursts/min, and blood pentobarbital levels were unchanged at 4.9-5.9 mg/dl throughout the entire period of anesthesia. The sustained increase in cerebral metabolism that occurred after 3 h and continued through 24 h of pentobarbital anesthesia is presumably due to tolerance. This was a phenomenon in which metabolism increased during steady deep anesthesia with unchanged blood levels of pentobarbital, rather than one in which greater blood levels were necessary to maintain the same level of anesthesia.

Animals↗
PubMed1981

Pentoxifylline does not change cerebral blood flow or metabolism in the dog.

Pentoxifylline 0.3--30 mg/kg was given intravenously to six dogs under nitrous oxide anesthesia. Cerebral blood flow was measured with a sagittal sinus outflow technique, cerebral oxygen consumption was calculated from the a-v difference, and metabolite levels were determined in biopsies of cerebral cortex. Pentoxifylline failed to influence cerebral blood flow or oxygen consumption. There was no increase in cerebral levels of phosphocreatine, ATP or total adenine nucleotides; the only significant effect was higher glucose levels in dogs given pentoxifylline (4.49 +/- 0.39 mumol/g vs 2.21 +/- 0.18 mumol/g). The latter has previously been reported to be deleterious during cerebral ischemia. Pentoxifylline thus failed to have any significant influence upon cerebral blood flow or metabolism in the dog likely to be of benefit during cerebral hypoxia or ischemia.

Animals↗
PubMed1981

Variations in onset of porcine malignant hyperthermia.

Variations in the onset of malignant hyperthermia were observed in five Poland China swine. These pigs were equivalently susceptible to malignant hyperthermia, based on the rapid onset in response to mask inhalation induction with halothane (five pigs) or sevoflurane (two pigs). A moderate dose of thiopental delayed the response to sevoflurane 10 minutes (one pig) and larger doses delayed it more than 60 minutes (two pigs). Total paralysis with pancuronium in the absence of other drugs delayed the response to halothane 30 and 60 minutes (two pigs). The results suggest that drugs that decrease either neuromuscular transmission or reflex responsiveness can delay the onset of episodes of malignant hyperthermia. These data suggest pancuronium as a relaxant of choice in anesthesia for susceptible subjects. Correlation with other data suggests that malignant hyperthermia may be difficult to initiate in subjects paralyzed by non-depolarizing relaxants in the absence of exposure to potent volatile agents. Thus the use of relaxant-induced paralysis might aid in the care of patients who develop recurrent malignant hyperthermia.

Anesthetics↗
PubMed1980

The detrimental effects of prolonged hypothermia and rewarming in the dog.

The authors had previously observed a deleterious cerebrovascular effect of prolonged hypothermia in primates and cats. In this study they examined the systemic as well as cerebral hemodynamic and metabolic effects of 24 hours of hypothermia in the dog. With decreases in temperature to 29 C, cardiac output (Q) and whole-body oxygen consumption (VO2) initially decreased 52 and 42 per cent, respectively. Thereafter, despite a stable temperature, both Q and VO2 continued to decrease, and at 24 hours values were 7 and 28 per cent of control, respectively, Cerebral blood flow (CBF) and cerebral oxygen consumption responded similarly. At 24 hours inhomogeneous perfusion of both brain and skeletal muscle was observed. With rewarming, cardiovascular collapse with severe tissue hypoxia and acidosis developed; CBF became grossly inadequate, resulting in depletion of brain energy stores.

Animals↗
PubMed1980

Porcine muscle responses to carbachol, alpha- and beta-adrenoceptor agonists, halothane or hyperthermia.

1. Whole body trans-section at the level of the first or second lumbar vertebra of stress-susceptible or normal Poland China swine provided a preparation of isolated perfused caudal muscle that was without nervous or hormonal influences. Metabolic responses to halothane anaesthesia were exaggerated in the susceptible preparation. 2. Carbachol (10(-4) M) increased O2 consumption threefold and elevated blood lactate levels from 3 to 8 mumole/ml. in susceptible but not in normal muscle preparations. 3. Isoprenaline in a continuous infusion (2.5 micrograms/kg caudal wt. per min for 12 min, subsequently diminished to 1.2 microgram/kg per min) did not increase O2 consumption of susceptible or normal muscle but did increase blood lactate by 2 mumole/ml. in both. 4. Simultaneous administration of carbachol and isoprenaline resulted in additive increases in blood lactate. 5. Incremental increases in temperature above 41 degrees C initiated exaggerated increases in O2 consumption and blood lactate in susceptible but not normal muscle; these were similar to whole body responses. 6. Phenylephrine (0.2-25 micrograms/kg per min continuous) produced (i) hypertension, (ii) no observed effects upon aerobic or anaerobic metabolism and (iii) progressive tissue oedema; these effects were similar in susceptible and normal muscle. 7. Skeletal muscle from stress-susceptible swine is evidently inherently capable of metabolic responses to cholinergic agonists and increased temperature; these responses are greater than those in normal muscle. This suggests that initiation of stress responses in intact swine is related to somatic motor and sympathetic stimulation of abnormal skeletal muscle, and not to a disorder of the somatic or sympathetic nervous system.

Animals↗
PubMed1979

No barbiturate protection in a dog model of complete cerebral ischemia.

Complete global ischemia was produced in 39 dogs by temporary ligation of the aorta. Prior to the ischemic episode, pentobarbital (30 to 45 mg per kilogram of body weight) was administered to 19 of these dogs. The neurological effects of cerebral ischemia episodes lasting 8, 9, or 10 minutes were compared in dogs treated with pentobarbital and those not treated. At 48 hours following the ischemic episode most of the dogs made ischemic for 8 minutes were normal, whereas most animals made ischemic for 10 minutes were dead or comatose. The 9-minute ischemic period resulted in a relatively even distribution of normal and damaged dogs. There were no differences between treated and untreated dogs. Cerebral blood flow, cerebral metabolic rate for oxygen, and various cerebral metabolites were measured in dogs surviving 48 hours. Again, there were no differences between treated and undertreated dogs. We conclude that barbiturates provide no protection in this model of complete global ischemia. This conclusion supports the hypothesis that the likely mechanism of barbiturate protection in models of incomplete ischemia or hypoxia is based on cerebral metabolic depression; such a mechanism would not be expected to be effective in complete global ischemia.

Animals↗
PubMed1979

Incomplete versus complete cerebral ischemia: improved outcome with a minimal blood flow.

It has been reported that incomplete cerebral ischemia with cerebral blood flow less than 10% of control may be more damaging than an equal period of complete ischemia. In this study, the effects of severe, incomplete cerebral ischemia on neurological outcome and cerebral metabolism were studied in dogs anesthetized with nitrous oxide. The results were compared with those of a previous study concerned with the effects of complete ischemia. Dogs could sustain only 8 to 9 minutes of complete ischemia with return of normal neurological function, whereas maintenance of a cerebral blood flow rate less than 10% of control extended this limit to 10 6o 12 minutes. Following a 10-minute exposure, only dogs undergoing incomplete ischemia regained a normal cerebral oxygen consumption within 90 minutes; similarly, animals subjected to incomplete ischemia enjoyed a faster return of EEG activity than dogs exposed to complete ischemia of the same duration. Cerebral metabolite levels did not prove to be a good index of return of neurological function. Within periods of cerebral ischemia in which meaningful neurological recovery might be expected, we conclude that some blood flow is better than no flow.

Animals↗
PubMed1977

Porcine malignant hyperthermia: role of skeletal muscle in increased oxygen consumption.

During malignant hyperthermia (MH) induced by halothane and succinylcholine, oxygen consumption (VO2) of whole body, muscle and the splanchnic area was calculated from measurements of blood flow and arteriovenous oxygen content difference. Caudal body blood flow was isolated and measured (six animals) for determination of average muscle VO2 in the hind limbs, buttocks, and flanks. The increase in muscle VO2 was extrapolated to total skeletal muscle and compared with the increase in whole body VO2 (same six animals). The average increase in VO2 for both total muscle and whole body during the period of maximum increase was about 6 ml O2/min/kg body weight. Splanchnic VO2 (four animals) tended to decrease during MH. The data support the hypothesis that the metabolic changes in MH are due to a disorder of skeletal muscle and that the increase in whole body VO2 is due to the increase in muscle VO2.

Animals↗
PubMed1977

The nonlinear responses of cerebral metabolism to low concentrations of halothane, enflurane, isoflurane, and thiopental.

The relationship between cerebral oxygen consumption (CMRO2) and anesthetic concentration has been assumed (based upon isolated measurements) to be approximately linear at concentrations less than 1 MAC. The shapes of the anesthetic dose-response curves for both CMRO2 and cerebral blood flow (CBF) were examined by multiple measurements made at small, progressive concentration increments from 0 to 2 MAC halothane (six dogs), enflurane (six dogs), and isoflurane (six dogs), and during a constant 23 mg/kg/hr infusion of thiopental (six dogs). The EEG was continuously recorded and changes in EEG patterns from "awake" to "anesthetic" were correlated with changes in anesthetic concentration, CBF, and CMRO2. The significance of changes in the slopes of regression lines for CMRO2 before, during and after changes in EEG patterns from "awake" to "anesthetic" were then determined. Contrary to previous inferences, CMRO2 dose-response curves were found to be nonlinear at anesthetic concentrations less than 1 MAC for all anesthetics studied. CMRO2 decreased precipitously until a stable "anesthetic" pattern was observed on the EEG; thereafter, CMRO2 decreased at a markedly reduced rate. The onset of this change occurred at concentrations well below MAC for the inhalational anesthetics. With the thiopental infusion, CMRO2 decreased most rapidly during the first 25 minutes. With halothane and enflurane, CBF was maximal during the period of transition in the EEG from an "awake" to an "anesthetic" pattern. CBF was elevated at all concentrations of isoflurane studied. CBF decreased rapidly during thiopental infusion until the EEG pattern changed from "awake" to "anesthetic" and then more slowly. The results demonstrate that the change in the EEG to an "anesthetic" pattern, which occurs at concentrations well below MAC, is accompanied by an abrupt metabolic depression. It is speculated that these events coincide with the onset of functional depression.

Animals↗
PubMed1976

Cerebral protection by barbiturate anesthesia. Use after middle cerebral artery occlusion in Java monkeys.

Regional cerebral ischemia was produced in 18 Java monkeys by permanent middle cerebral artery (MCA) occlusion. All monkeys were thereafter paralyzed (pancuronium bromide, 0.05 mg/kg/hr) and sedated (diazepam, 0.1 mg/kg/hr) for a 48-hour period. Thirty minutes after MCA occlusion, pentobarbital sodium anesthesia was induced in nine of the monkeys (14 mg/kg) and maintained for 48 hours (7 mg/kg every two hours), with continuous supportive care. After 48 hours, all drugs were discontinued; the monkeys were observed for five days, and then killed. Seven of the control monkeys developed a cerebral infarction, three did not survive past the 48 hours of intensive care, and the other four had a notable neurologic deficit. All pentobarbital monkeys survived the seven days, but four had a cerebral infarction and two of these had a notable neurologic deficit. These differences were statistically significant.

Anesthesia, Inhalation↗