Absence of coronary artery calcification and all-cause mortality.

OBJECTIVES: We sought to quantify the mortality rates associated with absent and low positive (CAC 1 to 10) coronary artery calcium (CAC). BACKGROUND: There is increasing interest in the absence of CAC as a "negative" cardiovascular risk factor. However, published event rates for individuals with no CAC vary, likely owing to differences in baseline risk, follow-up period, and outcome ascertainment. The prognostic significance of low CAC (CAC 1 to 10) is not well described. METHODS: Annualized all-cause mortality rates were assessed in 44,052 consecutive asymptomatic patients referred for CAC testing. Mean follow-up of the cohort was 5.6 +/- 2.6 years (range 1 to 13 years). RESULTS: A total of 19,898 patients (45%) had no CAC on screening electron beam tomography, whereas 5,388 (12%) had low levels of CAC (CAC 1 to 10), and 18,766 (43%) had CAC >10. There were 104 deaths in those with no CAC (0.52%), 58 deaths in those with CAC 1 to 10 (1.06%), and 739 deaths in those with CAC >10 (3.96%). Annualized all-cause mortality rates for CAC = 0, CAC 1 to 10, and CAC >10 were 0.87, 1.92, and 7.48 deaths/1,000 person-years, respectively. The hazard ratio (HR) for all-cause mortality among CAC 1 to 10 versus CAC = 0 after adjustment for traditional risk factors was 1.99 (95% confidence interval [CI]: 1.44 to 2.75). Smoking (HR: 3.97, 95% CI: 2.75 to 5.41) and diabetes mellitus (HR: 3.36, 95% CI: 2.09 to 5.41) were associated with few events observed in CAC = 0 group. CONCLUSIONS: In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%. A finding of 0 CAC might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies. Individuals with low CAC score (CAC 1 to 10) are at increased risk above individuals with a 0 score and could be considered a distinct risk group by physicians and investigators.

Inhibition of erythrocyte membrane ATPases with antisickling and anaesthetic substances and ionophoric antibiotics.

A study has been carried out into the effects of clinically important antisickling and anaesthetic substances and ionophoric antibiotics on the activities of (Na+, K+)- and (Ca+2, Mg2+)-ATPases of the human erythrocyte membrane. In general, these drugs, with the exception of nystatin, inhibit both types of enzymic activities but with varying degrees of efficacy. (Ca2+, Mg2+)-ATPases was more sensitive to the lipophilic anaesthetics and (Na+,K+)-ATPase to the ionophoric antibiotic, amphotericin B. These results are explained in the light of the partition coefficients of these drugs in erythrocyte membranes, their effects on the fluidity of the erythrocytes membranes, the changes they induce in the permeability properties of erythrocytes and the subsequent effect of procaine on sickling of erythrocytes, and their potential interaction with specific membrane components.

Development of a swine animal model for the study of sudden infant death syndrome.

An animal model with selective cardiac autonomic denervation was developed in neonatal swine for the purpose of future studies concerning the possible role of abnormal cardiac innervation in the etiology of sudden infant death syndrome. Twenty-six 4- to 8-day old piglets were randomly assigned to one of the following treatment groups: right stellate ganglionectomy (RSG), left stellate ganglionectomy (LSG), right cardiac vagotomy (RCV), and sham-operated control group. Piglets were anesthetized with Saffan and mechanically ventilated on room air. The thoracic wall was opened, and the sternum was divided, permitting exposure of pleura, heart, and lungs. After completion of one of these operative procedures, the thoracic wall was closed in layers. On successful recovery from anesthesia and extubation, piglets were returned to their sows. Postoperative administration of antibiotics was performed during the first week. Electrocardiograms were recorded once a week over an 8-week period. The sham-operated control group had a postnatal increase in QTc and decrease in heart rate. The RSG group had significantly longer QTc than the sham-operated control group QTc, whereas the RCV group had significantly shorter QTc interval than sham-operated controls. Surgical complications caused the death of two piglets (hemorrhage in one and aspiration in the other), infection caused the death of one piglet 2 weeks after surgery, and three died of unknown causes (one from the RSG group and two from the RCV group). The cause of death for these three animals could not be determined (necropsy was not revealing) because they were not monitored at the time of their demise.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of administration of oxytocin in association with gonadotropin-releasing hormone on luteinizing hormone levels in rats in vivo.

Gonadotropin-releasing hormone (GnRH) and oxytocin both stimulate the secretion of luteinizing hormone (LH), although with different characteristics. Therefore, interaction between oxytocin and GnRH in the control of LH may be postulated. We developed models for investigating whether oxytocin can modulate GnRH action on LH in vivo. Pentobarbitone is known to pharmacologically isolate the pituitary from hypothalamic GnRH. We found that after pentobarbitone anesthesia of female rats at proestrus, oxytocin caused a synergistically enhanced LH response to administered GnRH (p < 0.04). In a second series of experiments, female proestrous rats were anesthetized with althesin. This anesthetic allows transport of endogenous GnRH from the hypothalamus to the pituitary. In control animals, which received no exogenous hormone, there was a surge in the mean LH concentration on the evening of proestrus, indicating the presence of endogenous GnRH activity. Thus, the novel model enables detection of interactions of administered hormones with endogenous GnRH. Administration of GnRH plus oxytocin in the afternoon of proestrus caused a reduction (p < 0.01) in the mean level of LH observed in the evening. The reduction was larger than if GnRH alone was administered. Following althesin anesthesia, rats sometimes had low LH levels on the afternoon of proestrus. There was a statistically significant difference between the number of rats that received oxytocin plus GnRH and had low LH levels and the number with low LH levels in the control group (p < 0.02). Neither of the hormones administered alone had a significant effect. Thus, it appears that oxytocin accentuated the effect of GnRH in reducing LH concentrations in althesin-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Course of murine leukemia retrovirus infection determined in vivo by magnetic resonance imaging.

Magnetic resonance imaging was applied to measure the volumes of spleens and lymph nodes of mice infected with three different leukemia retroviruses (LP-BM5 murine leukemia virus, Friend, and Rauscher) in vivo. Anesthesia by rapid intraperitoneal injection of Saffan was sufficient for magnetic resonance imaging and could be repeated at appropriate intervals. Eleven frontal magnetic resonance images through the abdomen with a center-to-center distance of 1.5 mm between adjacent slices were acquired simultaneously. To optimally demarcate spleens from the surrounding tissues, the magnetic resonance images were mildly T2-weighted for mice infected with LP-BM5 murine leukemia virus and mildly T1-weighted for those infected with Friend and Rauscher virus. Measurements requiring only 3 to 4 hours in groups of 24 to 28 mice were accomplished by using a standardized holder (i) accommodating two animals in the supine position and (ii) ensuring reproducible positioning in the magnetic resonance-instrument, and (iii) by reducing the number of phase-encoding steps of mildly T2-weighted magnetic resonance images from 256 to 128. Volumes of spleens and inguinal lymph nodes were calculated from the respective cross-sectional areas. The weights and magnetic resonance image-derived volumes of spleens and inguinal lymph nodes correlated well (r greater than 0.95). Despite large variations in the extent of splenomegaly and lymphadenopathy at any given time, the progression of the disease could easily be followed by repeating magnetic resonance imaging at intervals. Thus, statistically relevant results can be obtained in an infection model requiring the use of only a few animals.

[Arrhythmogenic right ventricular dysplasia revealed during anesthesia]. / Révélation lors de l'anesthésie d'une dysplasie ventriculaire droite arythmogène.

Bigeminism appearing during pelvic laparoscopy led to the diagnosis of arrhythmogenic right ventricular dysplasia. It is a recently identified specific anatomical and rhythmic entity which gives rise to ventricular tachycardia in the young patient. When anti-arrhythmic drugs become inefficient, surgical treatment may be necessary (ventriculotomy). The anesthetic technique must be chosen so as to avoid setting off the abnormal rhythm. When an expected arrhythmia occurs in the operating theatre, it is inherent either to the surgery, the anaesthetic or the patient. Arguments in favour of cardiac disease are: the common occurrence of cardiac disease, preoperative abnormal ECG or chest X-ray, the mechanism of the arrhythmia (reentry) and the timing of its appearance. This arrhythmia is likely to disappear under light general anaesthesia. Functional abnormalities (anxiety, hypercapnia, hypoxia, acidosis, hypokalemia) should be treated before carrying out other specialized tests, such as cardiac ultrasonography.

Use of an emulsion of ICI 35868 (propofol) for the induction and maintenance of anaesthesia.

2,6-Diisopropyl phenol in a fat emulsion formulation (propofol) has been used to supplement 67% nitrous oxide in oxygen anaesthesia in 20 patients premedicated with morphine 0.15 mg kg-1 and atropine 0.6 mg, and undergoing body surface surgery. Following an induction dose of propofol 2.5 mg kg-1, the mean maintenance dose was 73.4 micrograms kg-1 min-1. When compared with 10 patients receiving Althesin to supplement nitrous oxide in oxygen in a similar manner, recovery was considerably faster following propofol. The only major side-effect associated with the use of propofol was pain on injection in nine out of 20 patients. When the patients receiving propofol were compared with a second control group (n = 11) in whom anaesthesia was induced with thiopentone 4 mg kg-1 and maintained with 1% halothane and nitrous oxide in oxygen, the former group showed a significant (P less than 0.01) decrease in the plasma cortisol concentration 30 min after the induction of anaesthesia. However, by 3 h after induction, the cortisol concentration in both groups was not significantly different from the baseline (preinduction) value. The mechanism of this decrease is not known. Investigation of the influence of the fat emulsion on blood coagulation and fibrinolysis revealed no differences when compared with patients receiving Althesin.

Efeitos do alfatesin sobre a atividade convulsivante da estricnina e do pentetrazol em coelhos / Effects of alphatesin on the convulsive activity of the strichinin and pentetrazol in rabbits

O uso de Alfatesin é acompanhado com freqüência de fenômenos excitatórios de natureza ainda näo esclarecida apesar de ser empregado, eventualmente, em crises de epilepsias. Por esse motivo resolvemos estudar os efeitos desse agente, isoladamente (0,1 kg1) e em associaçäo com pentetrazol (10 mg. kg-1) ou 0,1 ml de estricnina (0,2 mg.kg-1) por via venosa, em dez coelhos. As drogas foram utilizadas isoladamente e em associaçäo nos mesmos animais, em intervalos de quatro dias. Foram observadas: presença de reflexo córneo palpebral e de endireitamento, nistagmo, miose, tono muscular, ataxia, analgesia e convulsäo. A cada atributo foi conferida uma nota de 0 a 3, de acordo com a sua intensidade. Foi observado que o alfatesin, isoladamente, determina sedaçäo, hipotonia muscular, ataxia e perda do reflexo de endireitamento, mas näo induz analgesia. Associado ao pentetrazol e a estricnina reduz ou abole as manifestaçöes de estimulaçäo do sistema nervoso central características dessas drogas. Ainda é capaz de impedir o óbito induzido pela estricnina isoladamente. A explicaçäo para esses efeitos é discutida, necessitando de estudos mais sofisticados para seu esclarecimento

Althesin in high risk patients with heart disease in orthopedic surgery.

Althesin was used in 65 patients with heart diseases undergoing orthopedic surgery, alone or in association with neuroleptanalgesic drugs. Patients were classified according to four types of heart diseases: atrial fibrillation in older patients (41.53%), disorders of cardiac rhythm (23.07%), valvular diseases (9.23%), ischemic heart disease (26.15%) and according to the degree of risk (ASA 3 and 4). All patients were carefully studied before the operation, and adequately treated with cardiac drugs in order to reduce heart rate, to reduce blood pressure and to reduce heart failure, whenever necessary. Anesthesia was induced with Althesin in all patients, and maintained with Althesin/N2O/O2 in 24.61% of the cases, and Althesin/N2O/O2/NLA in 75.39% of the cases. No significant changes in heart rate or in blood pressure were observed either during surgery or in the first 24 hours after the operation. There were five deaths in the days after the operation, one of which was due to surgery. One patient was discharged while still in a coma. All the other patients were discharged from the hospital within approximately four weeks from the day of the operation in good general condition. It was concluded that Althesin is a very reliable anesthetic agent for patients with heart diseases.

Use of a continuous infusion of althesin in neuroanaesthesia. Changes in cerebral blood flow, cerebral metabolism, the EEG and plasma alphaxalone concentration.

Ten patients with small supratentorial tumours were studied during craniotomy. Cerebral blood flow (CBF) was measured in the contralateral hemisphere by a modification of the Kety and Schmidt technique using xenon-133 i.v. With an Althesin infusion rate of 0.2 ml kg-1 h-1, CBF was 24.4 +/- 5.4 ml min-1/100 g and CMRO2 1.87 +/- 0.44 ml min-1/100 g at PaCO2 4.1 +/- 0.7 kPa (mean +/- SD). During constant infusion rates of Althesin, steady values of CMRO2 were obtained, while an increase in infusion rate of 150% was associated with an increase in plasma alphaxalone concentration, a decrease in CMRO2 and a tendency of further EEG suppression. However, great inter- and intraindividual variations were present, and correlations between CMRO2, EEG activity and plasma alphaxalone concentration were weak.

The effect of althesin, ketamine or pentothal on renal function in saline loaded rats.

Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excretion rates, GFR, ERPF, ERBF and blood pressure were measured. Five groups of rats were studied: (1) control animals given saline in place of any anaesthetic agent, all parameters measured remained constant; (2) althesin (1.2 mg/kg), all parameters remained constant except for the blood pressure which decreased slightly for 5 min; (3) althesin (12 mg/kg); (4) ketamine (50 mg/kg); (5) pentothal (50 mg/kg). The above anaesthetics altered all of the measured parameters except urine output. Various mechanisms for these anaesthetic agents are discussed. In althesin anaesthetized rats, all the retarded renal parameters recovered within 30 min. It is concluded that for the study of renal function, if a brief anaesthesia is needed, althesin is a more suitable anaesthetic agent.

[Anesthetic induction with Althesin or diazepam in patients undergoing an aortocoronary bypass]. / Induction anesthésique avec Alfatésine ou diazépam chez des patients opérés pour pontage aorto-coronarien.

The haemodynamic effects of induction of anaesthesia with diazepam (group D) and Althesin (group A) were studied in 25 coronary patients under betablockers with good myocardial function. Haemodynamic variables monitored were vascular pressures, cardiac output and systolic time intervals. The effects of both drugs were observed when used alone (time I) and in combination with fentanyl, pancuronium and nitrous oxide (time II). The results seemed to show that Althesin (12.51% fall in SI and 10.79% increase in PEP/LVET) depressed myocardial function more than diazepam (no significant difference), but the introduction of fentanyl, pancuronium and nitrous oxide removed the differences between the drugs as to their effect on myocardial performance. These drugs added a depressant effect to diazepam (13.83% fall in SI and 15.77% increase in PEP/LVET) without increasing Althesin's negative inotropic effect. However, in group A at time II, the pulmonary arterial pressure, the wedge pressure and the pulmonary vascular resistance were significantly reduced, while they remained stable in the diazepam group.

Propofol ('Diprivan') for outpatient cystoscopy. Efficacy and recovery compared with althesin and methohexitone.

In two non-concurrent investigations, propofol was compared with methohexitone and with Althesin as an intravenous anaesthetic for cystoscopy in outpatients. In the comparison between propofol and methohexitone the 60 patients also received alfentanil in similar dosage; in comparison with Althesin (43 patients) the Cremophor formulation of propofol was used. During induction of anaesthesia propofol caused fewer excitatory effects than either methohexitone or Althesin, and less pain than methohexitone. There was no difference in the incidence of apnoea caused by propofol 1.5 mg/kg and Althesin 0.05 ml/kg, or propofol 2 mg/kg and methohexitone 1.5 mg/kg. Induction of anaesthesia by propofol was faster than that by Althesin. The use of alfentanil 7 micrograms/kg at induction of anaesthesia apparently increases the incidence of apnoea seen at that time and during maintenance of anaesthesia, but an overall dose of approximately 1 mg reduces the mean dose of propofol required from 0.459 mg/kg/min to 0.192 mg/kg/min and improves the quality of anaesthesia. During maintenance of anaesthesia propofol produced less myoclonia and movement than Althesin, and fewer hiccups than methohexitone, but the mean minimum systolic arterial pressure observed in the propofol group was less than that seen in the methohexitone group. Immediate recovery of consciousness was faster and better after propofol than methohexitone, and fewer complications were seen after propofol than Althesin. Recovery of coordination and perception, tested by the digit substitution test, was faster after propofol than methohexitone. Exact comparisons of recovery of ocular tone (Maddox Wing test) between the anaesthetics were not possible as both Althesin and methohexitone rendered some patients incapable of taking the tests in the early post-operative period. In response to a take-home questionnaire, patients stated that they were drowsy for a shorter time, and ate earlier after propofol than after methohexitone. No patient who received propofol vomited or was nauseated and all would wish to receive the same anaesthesia again. The studies suggest that propofol is preferable to both Althesin and methohexitone for intravenous anaesthesia for cystoscopy in outpatients.

Haematological and biochemical changes during anaesthesia with propofol ('Diprivan').

The influence of an emulsion formulation of 2,6-diisopropylphenol (propofol) on blood coagulation and fibrinolysis, and on the neuroendocrine responses to surgery has been investigated in 12 patients who received incremental doses of propofol to supplement 67% nitrous oxide in oxygen as anaesthesia for body surface surgery. The effects were compared with those in 10 patients who received Althesin to supplement nitrous oxide in oxygen in a similar manner. When pre-operative values were compared with data obtained after 30 min surgery, no significant effects on coagulation or fibrinolytic indices were found in either group. Both groups, however, showed a significant fall in haemoglobin concentration 30 min after induction of anaesthesia (P less than 0.05); and a fall in haematrocrit value was observed in those patients who received propofol (P less than 0.05). No changes in total white cell counts or platelet counts were observed. Both groups of patients showed a significant rise in blood glucose 30 min after induction of anaesthesia (P less than 0.001). After 3 h values were not significantly different from preoperative levels. The mean plasma cortisol levels fell in both groups 30 min after induction of anaesthesia, but returned to control values by 3 h. The mechanism causing this decrease is not known.

Propofol ('Diprivan') as a supplement to nitrous oxide-oxygen for the maintenance of anaesthesia.

Incremental doses of propofol (10-20 mg) have been used to supplement nitrous oxide in oxygen anaesthesia for patients undergoing body surface surgery. After premedication with morphine 0.15 mg/kg, anaesthesia was successfully induced in 21 patients with 2.5 mg/kg propofol. One patient with labile hypertension suffered a pronounced cardiovascular response to the induction of anaesthesia, but without operative sequelae. The mean maintenance rate of propofol was 73.4 micrograms/kg/min. When compared with 10 patients receiving incremental doses of Althesin, recovery to giving correct date of birth was significantly faster in patients receiving propofol (P less than 0.01); when compared with 11 patients receiving an induction of thiopentone 5 mg/kg and nitrous oxide/oxygen/halothane, more patients receiving propofol had recovered to giving correct date of birth by 10 min after the end of anaesthesia (P less than 0.001). However, use of propofol was associated with pain on injection in 9 out of 20 patients, and apnoea of greater than 30 s in 8 patients.

Efeitos hemodinâmicos do etomidato, tiopental sódico e alfatesin durante induçäo anestésica e pós-intubaçäo traqueal / Hemodymanic effects of etomidate, sodium thiopental and althesin during anesthesia induction tracheal and post intubation

Os autores comparam-se os efeitos hemodinâmicos do etomidate (0,3 mg. kg-1) durante a induçäo anestésica e após a intubaçäo traqueal com os do tiopental sódico (6-8 mg. kg-1) e Alfatesin (0,4 mg.kg-1) em 90 pacientes distribuídos em 3 grupos de 30. Foram avaliados a frequüência cardíaca, a pressäo arterial sistólica, diastólica e média e o produto da freqüência cardíaca pela pressäo arterial sistólica antes da administraçäo de cada droga, durante a mesma, um minuto após o seu término e imediatamente após a intubaçäo traqueal. O grupo do etomidate mostrou maior estabilidade da freqüência cardíaca e da pressäo arterial, assemelhando-se mais ao grupo do Alfatesin nos momentos anteriores à intubaçäo traqueal. Após a mesma, nos três grupos houve elevaçäo nos valores de todos os parâmetros. Quanto aos efeitos sobre o produto freqüência cardíaca e pressäo arterial sistólica, näo houve diferença significativa entre as três drogas

Infusäo contínua de alfatesin associado ao fentanil / Continous infusion of althesin associated with fentanyl

Vinte e cinco pacientes foram anestesiados usando-se infusäo contínua de Alfatesin associado ao Fentanil. Observou-se o consumo das drogas, os efeitos sobre a pressäo arterial e freqüência cardíaca e as características da recuperaçäo pós-anestésica. O consumo médio de Alfatesin foi de 51,5 + ou - 15 ml correspondendo a uma velocidade de infusäo de 0,0045 ml. kg-1. min-1. O consumo médio de Fentamil foi de 24 + ou - 5,6 ml. Os efeitos cardiovasculares näo foram clinicamente importantes indicando que as drogas produziram alteraçöes hemodinâmicas significativas. Observou-se náuseas e vômitos em 6 pacientes, tremores e calafrios em 11; depressäo respiratória, em 6. Nestes, foi necessário o uso de antagonistas dos narcóticos