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The effect of pregnancy on the pharmacokinetics of caffeine.

Caffeine is eliminated mainly by metabolism to demethylated and oxidised derivatives. High individual variability is therefore expected from variations and changes in the capability of the organism to metabolize xenobiotics. An increase of the half-life of elimination of caffeine has been reported during the final weeks of pregnancy. In this study, the half-lifes of caffeine were determined by HPLC-analysis of samples of saliva in male and non-pregnant females and in women during pregnancy and after parturition. The half-life of caffeine increases from an average of 3 h for non-pregnant women to 10.5 h during the last 4 weeks of pregnancy. This increase is already occurring during the first part of pregnancy. The individual values could not be correlated with age, weight, consumption of coffee or smoking habits. An increase of the apparent volume of distribution can also be ruled out as an explanation for the marked increase of the half-life. The main effect of a prolonged half-life is the accumulation of caffeine in the body, unless the consumption is reduced appropriately. Thus, the greatly increased half-life of caffeine during pregnancy could produce adverse effects at a consumption which although considered as high is not excessive under normal conditions. This possibly explains the observation that heavy coffee drinking during pregnancy is linked to a low birthweight in the neonate. Due to the non-specificity of some of the symptoms of caffeine toxicity, pregnant women with such symptoms might be unable to trace the reason for their discomfort if they are not instructed by their physician about the higher susceptibility to caffeine during pregnancy.

Caffeine↗

Risk factors for caesarean section in Italy: results of a multicentre study.

A recent large increase in Caesarean section (CS) in Italy was the initial stimulus for a study to identify risk factors for CS and, if possible, to suggest strategies to counteract the rise. The study was conducted in three hospitals where a wide range of individual variables was collected from the clinical records and from personal interviews. Crude CS rates and odds ratios were evaluated for each single variable while logistic regression has been used to investigate possible confounding factors. The study involved 1316 consecutive deliveries. Crude CS rates were 29.4%, 15.7% and 16.1%. Variables identified as high risk factors were pre-eclampsia, previous CS, breech and other non-vertex presentations. Antenatal care under an obstetrician working in the same hospital, a low number of antenatal consultations, previous miscarriages, offer (by obstetrician) and request (by women) for CS showed significantly high odds ratios (ORs). Previous live births was strongly negatively associated with CS. No relationship between type of delivery and social status was observed while a physician factor was detected in all three hospitals where rates for different physicians ranged from 0% to 52.8%. Apart from the main medical indications for Caesarean section (previous CS, breech presentation), the results seem to indicate that individual practice style may be an important determinant of the wide variation in the rates of Caesarean delivery. While this may have been suspected before this study, these results are the first hard data to indicate that, in Italy, CS is widely performed for non-medical reasons.

Adult↗

Is volume of distribution at steady state a meaningful kinetic variable?

Pharmacokinetic volumes of distribution (Vd) are commonly calculated either by the steady-state method (Vdss) or the area method (Vdarea). Vdss is traditionally perceived as the least biased and most reliable indicator of the extent of distribution, but Vdss in fact has far greater practical and theoretical limitation than does Vdarea. After single doses or multiple discrete doses of a drug, Vdarea correctly relates plasma concentration to amount of drug in the body at all times after distribution equilibrium is attained. Vdss, on the other hand, is a correct proportionality constant only during continuous intravenous infusion or at a single instant in time after discrete dosing. Furthermore, calculated values of Vdss are strongly dependent on the precise configuration of the initial distributional phase of the plasma concentration curve, which may be difficult or impossible to delineate because of variance arising from methodologic artefacts or unexplained causes. Such variance can lead to large nonphysiologic within- and between-individual variability in Vdss. Vdarea, on the other hand, is relatively independent or artefactual changes in the initial distribution profile. Finally, experimental observations indicate that elimination depends physiologically on distribution in the absence of changes in clearance, not the reverse. The relation of distribution and elimination holds whether the steady-state method or the area method is used to calculate Vd. Thus, Vdarea is a more reliable and generally valid descriptor of the extent of drug distribution than is Vdss.

Antipyrine↗

Population distribution of aldehyde dehydrogenase-2 genetic polymorphism: implications for risk assessment.

The role of genetic polymorphisms in modulating xenobiotic metabolism and susceptibility to cancer and other health effects has been suggested in numerous studies. However, risk assessments have generally not used this information to characterize population variability or adjust risks for susceptible subgroups. This paper focuses upon the aldehyde dehydrogenase-2 (ALDH2) system because it exemplifies the pivotal role genetic polymorphisms can play in determining enzyme function and susceptibility. Allelic variants in ALDH2 cause decreased ability to clear acetaldehyde and other aldehyde substrates, with homozygous variants (ALDH2*2/2) having no activity and heterozygotes (ALDH2*1/2) having intermediate activity relative to the predominant wild type (ALDH2*1/1). These polymorphisms are associated with increased buildup of acetaldehyde following ethanol ingestion and increased immediate symptoms (flushing syndrome) and long-term cancer risks. We have used Monte Carlo simulation to characterize the population distribution of ALDH2 allelic variants and inter-individual variability in aldehyde internal dose. The nonfunctional allele is rare in most populations, but is common in Asians such that 40% are heterozygotes and 5% are homozygote variants. The ratio of the 95th or 99th percentiles of the Asian population compared to the median of the U.S. population is 14- to 26-fold, a variability factor that is larger than the default pharmacokinetic uncertainty factor (3.2-fold) commonly used in risk assessment. Approaches are described for using ALDH2 population distributions in physiologically based pharmacokinetic-Monte Carlo refinements of risk assessments for xenobiotics which are metabolized to aldehyde intermediates (e.g., ethanol, toluene, ethylene glycol monomethyl ether).

Aldehyde Dehydrogenase↗

Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation.

Fifteen adult chronic asthmatic patients were studied on 6 consecutive days of the second week of treatment with a new sustained release theophylline formulation, and 8 were again studied after three months on the same dosing regimen (375 mg b.i.d.). Serum theophylline concentrations were maintained in the therapeutic range (peak - 19.7 +/- 5.0 micrograms/ml; trough - 13.0 +/- 3.2 micrograms/ml) throughout the 12 hour dosing interval, and were greater than 75% of the peak concentration over 8.6 +/- 2.9 h. A degree of drug accumulation was evident in that the 1-h and 5-h levels rose from 12.2 +/- 4.1 and 4.5 +/- 4.8 micrograms/ml during the second week to 16.9 +/- 4.6 and 18.4 +/- 4.5 micrograms/ml, respectively, at three months. Between-patient differences accounted for 61%-71% of the total variation in steady state theophylline concentrations. After accounting for differences due to sampling time and assay error, unexplained random, within-individual variability amounted to 11%-18% of the total. Quantitative estimation of these components of variability may be incorporated into dosage forecasting methods based on single determinations of serum concentration.

Administration, Oral↗

Cancer pharmacogenomics: international trends.

It is well known that inter-individual variability exists in the responses to many drugs. Many nongenetic factors, such as age, sex, diet, and organ function, are known to affect the therapeutic effects of drugs. However, recent advances in pharmacogenomics have revealed that genetic polymorphisms also significantly influence both the efficacy and the toxicity of drugs. Mutations in the genes encoding drug-metabolizing enzymes, transporters, and target molecules may alter their expression, activity, or affinity to drugs, thereby influencing the drugs' pharmacokinetics and pharmacodynamics. Numerous studies have reported on the correlations between therapeutic outcomes and polymorphisms in drug-metabolizing enzymes, transporters, target molecules, and DNA repair enzymes. These pharmacogenomic discoveries are expected to be useful for the individualization and optimization of cancer chemotherapy.

Antineoplastic Agents↗

Regulation of plasma growth hormone-binding proteins in health and disease.

Binding proteins (BP) for growth hormone (GH) have recently been discovered in human plasma. The main BP is related to the GH receptor and probably corresponds to the extracellular portion of the receptor. The BP influence several aspects of GH homeostasis and action. Their level and activity in blood, therefore, become important variables in overall GH physiology. However, to date little is known about the regulation of GH-BP in health and disease. To gain initial information about this point, GH-BP activity was examined in the plasma of 124 subjects with various physiologic and pathologic conditions. The conditions were selected to provide basic physiologic data (men, women, children, age, pregnancy and to investigate key disease states attended by abnormal GH physiology (liver cirrhosis, uremia, infection, acromegaly). A standardized GH binding assay was used to measure BP activity as an index of BP levels. Both the principal, high affinity BP (peak II) and the minor, low affinity BP (peak I) showed considerable individual variation in all groups. Neonates had the lowest levels of both BPs, but by the age of 1 year the levels had increased and remained fairly stable through the seventh decade. In males but not females between the ages of 1 and 20 years, the main (peak II) BP showed a slight upward trend, whereas the minor (peak I) BP declined moderately. Patients with cirrhosis showed the most variation in both BP, and uremic patients demonstrated decreased peak II, but not peak I, binding. Neither BP was affected in acromegaly. We conclude that BP activity in plasma is well conserved in most conditions, but substantial individual variability exists. BP activity increases dramatically during the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Correlation between individual differences in intraocular pressure reduction and outflow facility due to latanoprost in normal-tension glaucoma patients.

PURPOSE: The amount of intraocular pressure (IOP) reduction achieved by the use of latanoprost eyedrops varies among patients, and there are even nonresponders. This report examines whether there is any correlation between the amount of individual variability in IOP reduction and the uveoscleral outflow facility after latanoprost eyedrop instillation in normal-tension glaucoma patients. METHODS: Sixteen normal-tension glaucoma patients (mean age, 56.4 years) were enrolled in the study to investigate the relationship between the amount of IOP reduction and outflow facility. Before treatment, subjects underwent circadian IOP measurement and then tonography, and the outflow facility was calculated. Subsequently, patients began treatment once daily with latanoprost instillation in one eye. After 4 weeks of daily latanoprost treatment, circadian IOP was measured again. RESULTS: Mean pretreatment outflow facility was 0.23 +/- 0.05 microl/min per mmHg. On average, latanoprost instillation decreased IOP by 2.8 mmHg, but the reduction varied among individuals from -0.3 mmHg to 5.8 mmHg. No significant correlation was noted between the outflow facility and the IOP decline associated with latanoprost. CONCLUSION: Because there was no significant correlation between individual IOP reduction by latanoprost and outflow facility, the differences in substantial change in uveoscleral outflow after latanoprost administration may be one explanation for the individual variation in IOP reduction after treatment with this drug.

Adult↗

High repeatability of the amplitude and duration of the nycthemeral rhythm of the plasma melatonin concentration in the Ile-de-France ewe.

In order to determine individual variability in the amplitude and duration of the nycthemeral rhythm of the plasma melatonin concentration, 12 ovariectomized estradiol-treated Ile-de-France ewes were submitted to a sequence of 34 long days (LD1, 16L:8D), 21 short days (SD, 8L:16D), and 21 LD (LD2). Intensive blood sampling (hourly from 1 hr before dusk to 1 hr after dawn) was performed for 4 consecutive nights in each of the photoperiodic situations (LD1, SD, LD2), i.e., a total of 12 nights per ewe. Plasma melatonin was assayed by radioimmunoassay. Instantaneous amplitude (difference between each hourly measurement of the plasma melatonin concentration during the nocturnal elevation and the mean diurnal melatonin concentration), mean individual amplitude (same definition but using the mean melatonin concentration during the nocturnal elevation) and duration of elevation of plasma melatonin concentrations were calculated for each ewe and each night and analyzed by variance analysis. Instantaneous amplitude varied significantly with photoperiod, with night intra-photoperiod, with ewes, and time intra-night. Mean individual amplitude varied significantly with photoperiod and with ewe but not with night intra-photoperiod. Dramatic differences between individuals appeared in the amplitude and duration of melatonin rhythms. The lowest mean individual amplitude (all nights of measurement) found was 95 pg/ml and the highest was 544 pg/ml. Overall repeatability coefficient of the mean amplitude of melatonin elevation was 0.71 (P < 0.001). Duration of melatonin elevation varied significantly with photoperiod, with nights intra-photoperiod and with ewes. During LD periods, mean duration of melatonin elevation was equivalent to duration of the night (from 7 to 8 hr), while during SD it varied with ewes from 9 to 16 hr. Repeatability coefficient of the duration of melatonin elevation in SD was 0.57 (P < 0.05). It is concluded that amplitude and duration (in SD) of the nycthemeral rhythm of the plasma melatonin concentration are highly repeatable individual characteristics in the ewe.

Animals↗

Individual characterization of the peritoneal restriction barrier to macromolecules.

The transport of macromolecules such as proteins and dextrans during CAPD is restricted by the permeability of the peritoneum. When its degree is determined by diffusion characteristics of macromolecules, the intrinsic permeability of the peritoneal membrane can be expressed as the relation between clearance of macromolecules and parameters of diffusion velocity. In order to characterize the peritoneal restriction barrier in individual patients, such a relationship has to meet the following conditions: (a) a good fit to linearity, (b) a low inter- and intra individual variability and (c) similarity for proteins and equal sized dextran fractions. In the present study a comparison is made between the reciprocal plot (RP): C-1 = s (esr) + A and the diffusion plot (DP): C = A'. Ds20,w. In these equations C is clearance, esr is Einstein Stokes radius, D20,w is the free diffusion coefficient in water, A and A' are constants, while s is the slope of the regression line and therefore represents intrinsic peritoneal permeability to macromolecules. The 95% confidence interval of the correlation coefficient r was above 0.95 in all studies for the RP and the DP. In general it was somewhat higher for the DP. The inter-individual coefficient of variation was lower in the DP than in the RP. This was also the case for the intra-individual coefficient of variation of the slope for proteins (DP 4% vs RP 27%, p less than 0.01) and for dextrans (DP 18% vs RP 47%, p less than 0.05). The correlation coefficient between dextran slopes and protein slopes was higher for DP (r = 0.68) than for RP (r = 0.50).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗

Patient-controlled analgesia: An efficient therapeutic tool in the postoperative setting.

Patient-controlled analgesia (PCA) is one of the newer techniques for pain management. It was developed in reaction to the large number of unsatisfied postoperative patients suffering from moderate to severe pain despite the availability of potent analgesic drugs. With PCA, patients are allowed to self-administer small analgesic doses into a running intravenous infusion, intramuscularly, subcutaneously or even into the spinal space. Clinical experience soon demonstrated that individual variability in pain intensity and analgesic needs was extremely large. Psychological factors seem to be as important as the surgical trauma. Opioid consumption is usually higher than with conventional regimens, but without serious side effects. Although patients generally prefer self-control, pain relief is not necessarily better than with well-conducted conventional techniques. In addition to routine clinical pain management, PCA has proven its importance in research, e.g. for pain measurement, to determine predictors of postoperative pain, to evaluate drug interactions and the concept of pre-emptive analgesia, or for pharmacokinetic designs. PCA has been extremely important in order to change the mind of physicians and nursing staff with respect to individual pain management strategies.

Analgesia, Patient-Controlled↗

[Social-occupational risk factors for fetal growth retardation and preterm birth. I. Role of occupational and non-occupational work].

Clinical and control examinations were performed in order to assess the effect of certain demographic, social and occupational factors on a relative risk for fetus hypotrophia and preterm birth. Two groups of cases were distinguished: mothers of hypotrophic children (72 women) and mothers of eutrophic premature babies (41 women). The control group was composed of women who had given birth to eutrophic babies (438 persons). An analysis of individual variables indicated the following risk factors for preterm birth: mother's age over 35 years, unmarried status of mothers, a low level of education; while unmarried status increased the risk for fetus hypotrophia. Only a half of women under study worked when pregnant, and no relationship between working during pregnancy and increased risk for the pathologies discussed, were found. An aggravated risk for preterm birth in women overloaded with housekeeping duties was noted. This observation applied, in particular, to women who had not been working occupationally during pregnancy. Bearing in mind a multifactorial etiology of fetus hypotrophia and preterm birth, in the authors' opinion it would be useful to analyse an unrelated effect of individual risk factors with concomitant control of confounding factors.

Confounding Factors, Epidemiologic↗

Role of alcohol dehydrogenase 3 and cytochrome P-4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract.

Alcohol is a recognized risk factor for upper aerodigestive tract (UAT) cancers, but the mechanism by which alcohol causes cancer remains obscure. Ethanol is oxidized to acetaldehyde (the suspected carcinogenic agent in alcohol) by alcohol dehydrogenases (ADHs) and cytochrome P-4502E1 (CYP2E1), both of which exhibit great inter-individual variability in activity. The hypothesis that these polymorphisms influence susceptibility to alcohol-related cancers remains poorly documented. We investigated whether ADH(3) and CYP2E1 DraI and RsaI genotypes modified the risk of UAT cancers among 121 oral cavity/pharyngeal cancer patients, 129 laryngeal cancer patients, and 172 controls, all French Caucasians. Cancer risks and gene-alcohol interactions were analyzed by unconditional logistic regression, accounting for potential confounders. ADH(3) genotype was not associated with UAT cancer. In contrast, a 2-fold risk of oral cavity/pharyngeal (OR = 2.0, 95% CI 1.0-3.9) and laryngeal (OR = 1.8, 95% CI 1.0-3.5) cancers was observed for carriers of the CYP2E1 DraI C variant allele compared with other individuals. The risk associated with the CYP2E1 RsaI c2 variant allele also increased for oral cavity/pharyngeal cancer (OR = 2.6, 95% CI 1.0-6. 6). The effects of ADH(3) or CYP2E1 genotype and alcohol or tobacco were independent. The highest risk of oral cavity/pharyngeal cancer was observed among the heaviest drinkers (>80 g/day) with the CYP2E1 DraI C allele (OR = 5.8, 95% CI 1.9-18.2) or the CYP2E1 RsaI c2 allele (OR = 7.2, 95% CI 1.4-38.2) compared with lighter drinkers with other genotypes. Our study suggests that CYP2E1 genotype modifies the risk of UAT cancers, but due to the low frequency of CYP2E1 variant alleles, large-scale studies are needed to confirm our findings.

Alcohol Drinking↗

Behaviour evaluation for risk-taking adolescents (BERTA): an easy to use and assess instrument to detect adolescent risky behaviours in a clinical setting.

UNLABELLED: To create an instrument to be used in an outpatient clinic to detect adolescents prone to risk-taking behaviours. Based on previous research, five identified variables (relationship with parents and teachers, liking going to school, average grades, and level of religiosity) were used to create a screening tool to detect at least one of ten risky behaviours (tobacco, alcohol, cannabis and other illegal drugs use; sexual intercourse and sexual risky behaviour; driving while intoxicated, riding with an intoxicated driver, not always using a seat belt, and not always using a helmet). The instrument was tested using the Barcelona Adolescent Health Survey 1993. A Receiver Operating Characteristics curve was used to find the best cut-off point between high and low risk score. Odds ratios and 95% confidence intervals were calculated to detect at least one risky behaviour and for each individual behaviour. In order to assess its predictive value, the analysis was repeated using the Barcelona Adolescent Health Survey 1999. In both cases, analyses were conducted for the whole sample and for younger and older adolescents. Adolescents with a high-risk score were more likely to take at least one risky behaviour both when the whole sample was analysed and by age groups. With very few exceptions, the Behaviour Evaluation for Risk-Taking Adolescents showed significant odds ratios for each individual variable. CONCLUSION: The Behaviour Evaluation for Risk-Taking Adolescents has shown its potential as an easy to use instrument to screen for risk-taking behaviours. Future research must aim towards assessing this instrument's predictive value in the clinical setting and it's application to other populations.

Accidents, Traffic↗

The continuity equation tested in a bileaflet aortic prosthesis.

The continuity equation is valid for a population of aortic valves, but its accuracy in individual valves is uncertain. In bileaflet prostheses, obstruction to forward flow is small and individual variability in opening behaviour is minimal. In these valves, the area of the effective orifice should be close to that measured by the manufacturer. A total of 57 patients aged 58 +/- 11 years were studied at a mean of 3.6 months after implantation with a CarboMedics aortic prosthesis. Nine had additional implants in the mitral position and all prostheses were clinically normal. Peak subaortic and transaortic velocities were averaged over 5 beats. The area of the effective orifice was significantly different between the four diameters (P less than 0.00001), and the correlation between the effective and measured area of the orifice was moderate (rs = 0.73, P less than 0.00003). The 95% range for the differences between individual pairs of values, however, was 0.16 +/- 0.61 cm2. Discrepancies probably arose in the estimation of subaortic cross-sectional area and subaortic velocity. Thus, the continuity equation may be inaccurate in an individual prosthetic valve when functioning normally.

Aged↗

Identical twins are discordant for markers of eccentric exercise-induced muscle damage.

This study investigated whether the variability observed in the markers of exercise-induced muscle damage (EIMD) has a genetic etiology. Sixteen pairs of identical twins performed 24 maximal eccentric contractions (24MAX) using the elbow flexors. EIMD indicators were measured pre-24MAX and three days post-24MAX and included: post-exercise force deficit, maximal isometric force (ISO), plasma creatine kinase (CK), myoglobin (Mb), and joint range of motion. Force-time curves were recorded throughout the 24MAX. Twin siblings were alike for pre-exercise ISO (intraclass R = 0.89) and CK (R = 0.76) (p < 0.001), but were discordant for post-exercise force deficit (R = 0.29), CK (R = 0.15), and Mb (R = 0.17) (p > 0.05). In comparison with individuals minimally affected by the 24MAX, those who experienced the greatest force deficit 3 days post-exercise (> 50 %) were characterised by the greater application of eccentric force at longer muscle lengths (23.1 % vs 17.3 %) (p < 0.05). This study demonstrates that twins do not experience the same level of EIMD following identical exercise bouts. This suggests that the individual variability following high-force eccentric exercise cannot be attributed to genetic differences, refuting the idea that an inherited subclinical predisposition is responsible. From these results, a potential mechanism for the repeated bout effect is discussed.

Adult↗

Congenital diaphragmatic hernia: an evaluation of the prognostic value of the lung-to-head ratio and other prenatal parameters.

OBJECTIVES: A retrospective analysis of the prognostic significance of the lung-to-head ratio (LHR) and other prenatal parameters on the outcome of fetuses with left-sided congenital diaphragmatic hernia (CDH). METHODS: A total of 26 fetuses with isolated left CDH without chromosomal abnormalities were included. Twenty-one LHR measurements could retrospectively be calculated from the last available ultrasonographic recordings before birth. The relationship between LHR and fetal outcome and the gestational age dependency of this relation was tested. Cutoff levels as previously published were applied to determine their predictive value in this population. The association between other prenatal predictive variables and fetal outcome was also determined. Survival was defined as discharge from the hospital. RESULTS: The overall survival rate was 50%. There was a statistically significant difference between the mean LHR of the survivors compared to the mean LHR of the nonsurvivors (1.78 vs 1.02), whereas the mean gestational age of these two groups did not differ. LHR was not gestational age dependent in the prediction of fetal outcome. The cutoff levels LHR <1, 1-1.4, >1.4 showed a good applicability in the prediction of fetal outcome within the present study population with a 100% survival if LHR >1.4 and a 100% mortality if LHR <1. An intrathoracic position of the stomach, mediastinal shift, polyhydramnios as individual variables and early diagnosis (<25 weeks' gestation) revealed to be poor sonographic predictors for fetal outcome. CONCLUSION: LHR proved to be a good predictor for fetal outcome, independent of gestational age at the time of the measurement. To substantiate our observation, a prospective multicenter study is warranted.

Biometry↗

Factors influencing variable outcomes after ventricular fibrillation cardiac arrest of 15 minutes in dogs.

Animal experiments with cardiac arrest and cardiopulmonary resuscitation (CPR) despite controlled insult and postinsult life support, have yielded variable individual outcomes. This report concerns 10 dog experiments with a standardized model of VF cardiac arrest with no flow for 10 min followed by CPR basic life support (BLS) from VF 10 to 15 min and then CPR advanced life support (ALS) with epinephrine at 15 min. Defibrillating countershocks began at 17 min, for restoration of spontaneous circulation. After controlled ventilation to 20 h and intensive care to 96 h, outcome was evaluated using the overall performance category (OPC) 1 (normal) (n5) vs. OPC 2-4 (impaired) (n5) (P less than 0.001). We searched for correlations between normal vs. impaired outcome in various prearrest, arrest and postarrest factors that are suspected to influence postarrest neurologic deficit. Prearrest variables were similar in the normal and impaired groups. Resuscitation variables were similar in both. Coronary perfusion pressure during CPR-ALS was higher in the normal outcome group (P = 0.03). Among postarrest variables, postarrest reperfusion pressure pattern (initial hypertensive bout), blood glucose, cardiac output, Hct, pHa, PaO2 and PaCO2 were the same. Our data support the importance of maximizing coronary perfusion pressure not only for restoration of heart beat but also as a possible predictor of improved cerebral outcome.

Animals↗