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Biomedical subjects

C G Brown

Publications and source records attributed to C G Brown.

At least 91 records · Page 5Linked to original sources
PubMed1990

Hemodynamic effects of 1-[3,4-dihydroxyphenyl]-1,2-diaminoethane versus norepinephrine during ventricular fibrillation and cardiopulmonary resuscitation.

We hypothesized that substitution of the hydroxyl group (OH) on the beta carbon of norepinephrine (NE) with an amino group would yield a compound, 1-(3,4-dihydroxyphenyl)-1,2-diaminoethane (DHPDAE), that would maintain the hemodynamic properties of NE during CPR, but would decrease the rate of post-defibrillation dysrhythmias. Six mixed breed swine weighing greater than 28 kg were studied. The animals were instrumented for cerebral (CBF) and myocardial blood flow (MBF) measurements. Ventricular fibrillation (VF) was induced. After 10 min of VF, CPR was begun. After 3 min of CPR, 2.5 mg/kg of DHPDAE was administered and CPR continued. Defibrillation was attempted 3.5 min after drug administration. CBF, MBF and defibrillation rates were compared to an historical control group receiving 0.16 mg/kg of NE. Outcome variables were compared using a Wilcoxon Rank Sum test and Fisher-exact test. NE significantly improved CBF and MBF compared to DHPDAE. All the animals in the NE group were successfully defibrillated into a perfusing rhythm. Sixty percent of the NE treated animals experienced post-defibrillation ventricular dysrhythmias. None of the animals in the DHPDAE were successfully defibrillated into a perfusing rhythm. Substitution of the hydroxyl group on the beta-carbon of NE with an amino group significantly decreases the hemodynamic properties of the parent molecule.

Animals↗
PubMed1990

Adrenergic agonists during cardiopulmonary resuscitation.

A number of studies have suggested that following a prolonged cardiopulmonary arrest, large doses of alpha-adrenergic agonists that possess post-synaptic alpha-2 agonist properties, i.e. epinephrine and norepinephrine, may be required to enhance myocardial and cerebral hemodynamics. While initial human studies using large doses of epinephrine have shown improved hemodynamics over standard therapy, hospital discharge rates and neurological outcome have been discouraging. This probably reflects the fact that the administration of epinephrine was employed late in the resuscitation effort. Future studies using larger doses of epinephrine as the initial pharmacologic intervention during cardiopulmonary resuscitation (CPR) will help to determine whether there is any therapeutic benefit. In addition, a number of questions still remain unanswered in delineating the specific alpha and beta adrenergic agonist components which will maximally enhance hemodynamics and resuscitation rates during CPR. This will help determine whether norepinephrine or a yet unsynthesized adrenergic agonist may be more beneficial for use during cardiac arrest.

Adrenergic alpha-Agonists↗
PubMed1990

Effect of high dose norepinephrine versus epinephrine on cerebral and myocardial blood flow during CPR.

Several animal studies have demonstrated an improvement in cerebral blood flow (CBF) and myocardial blood flow (MBF) after the administration of epinephrine (E) 0.20 mg/kg during closed chest CPR. The administration of norepinephrine (NE) in doses of 0.12 and 0.16 mg/kg demonstrated a trend toward improved CBF and MBF during CPR over that seen with E 0.20 mg/kg in the same animal model. The purpose of this study was to compare the effects of a higher dose of NE 0.20 mg/kg to E 0.20 mg/kg to determine if increasing doses of NE would demonstrate further improvement in CBF and MBF during CPR. Fourteen immature swine were anesthetized and instrumented for regional blood flow and hemodynamic measurements. After 10 min of ventricular fibrillation (VF), CPR was begun using a mechanical thumper. After 3 min of CPR, the animals received either E 0.20 mg/kg (n = 7) or NE 0.20 mg/kg (n = 7) through a right atrial catheter. CPR was continued for an additional 3.5 min and defibrillation was then attempted. CBF (ml/min/100 g), MBF (ml/min/100 g), myocardial oxygen delivery (MDo2; ml O2/min/100 g), myocardial oxygen consumption (MVo2; ml O2/min/100 g), and myocardial oxygen extraction ratios (ER, MVo2/MDo2) were measured during normal sinus rhythm (NSR), during CPR, and during CPR following drug administration. Following drug administration, CBF, MBF, MDo2 and MVo2 rose while ER fell in both E and NE groups. There were no significant differences between groups in CBF, ER, or intravascular pressures following drug administration (P greater than or equal to 0.07). The NE group demonstrated significantly higher MBF (118.9 +/- 73.1 vs. 62.2 +/- 45.3, P = 0.04), MVo2 (14.2 +/- 7.7 vs. 7.0 +/- 3.8, P = 0.05), and MDo2 (19.9 +/- 13.4 versus 9.4 +/- 6.3, P = 0.05) compared to the E group following drug administration While NE improved MBF and MDo2 over E during CPR, there was a trend toward lower resuscitation rates with NE (57.1% vs. 85.7% P = 0.56). Any benefit of higher MBF and MDo2 with NE 0.20 mg/kg appears to be offset by proportionately high MVo2 and a trend toward lower resuscitation rates in the NE 0.20 mg/kg animals.

Animals↗
PubMed1990

The effectiveness of bystander CPR in an animal model.

Several clinical studies have yielded conflicting results in examining the effectiveness of bystander CPR (BCPR). The purpose of this pilot study was to determine the effectiveness of BCPR in an animal model of cardiac arrest and resuscitation. Ten swine were instrumented for hemodynamic and regional blood flow measurements with tracer microspheres. After two minutes of ventricular fibrillation (VF), the animals received eight minutes of either BCPR (five) or no-bystander CPR (NBCPR; five). Defibrillation was then attempted in both groups. If unsuccessful, CPR was begun and epinephrine 0.02 mg/kg was administered. Defibrillation was attempted again three and one-half minutes after epinephrine administration. Regional myocardial and cerebral blood flows were measured 30 seconds and five and one-half minutes after initiation of BCPR and one minute after epinephrine administration. In the BCPR group, myocardial blood flow was initially 29.0 +/- 33.2 and decreased to 15.0 +/- 21.5 mL/min/100 g during the last two and one-half minutes of BCPR. Cortical cerebral blood flow was initially 2.0 +/- 2.8 and fell to 0.6 +/- 0.8 mL/min/100 g during the last two and one-half minutes of BCPR. There were no statistical differences in myocardial blood flow and cerebral blood flow between the initial or late stages of BCPR (P greater than .14). There were no statistical differences in myocardial blood flow and cerebral blood flow between BCPR and NBCPR groups after epinephrine administration (P greater than .09).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Four case studies: high-dose epinephrine in cardiac arrest.

Animal and human studies have suggested that higher doses of epinephrine than currently recommended may improve resuscitation rates after prolonged cardiac arrest. Because of our failure to resuscitate four patients with the standard American Heart Association protocol for cardiac arrest, we used a larger dose of epinephrine in an attempt to enhance resuscitative efforts. All patients required CPR and had nonperfusing rhythms for at least 20 minutes. The four patients received from 0.12 to 0.22 mg/kg epinephrine. Within five minutes of high-dose epinephrine, all four patients developed perfusing rhythms with maximum systolic blood pressures ranging from 134 to 220 mm Hg. Cardiac dysrhythmias did not occur after these doses of epinephrine. Only one of four patients had ECG evidence of an acute myocardial infarction. In this patient, the history suggested that the myocardial infarction was a primary event, not the consequence of epinephrine. All four patients sustained severe brain injury leading to their demise. This injury was probably due to prolonged cardiopulmonary arrest and global brain ischemia. Pharmacologic and potential pathophysiologic mechanisms of high-dose epinephrine are reviewed.

Adult↗
PubMed1990

The median frequency of the ECG during ventricular fibrillation: its use in an algorithm for estimating the duration of cardiac arrest.

Recent studies have suggested that the initial therapeutic intervention for ventricular fibrillation (VF) may depend on downtime (DT), i.e., the time duration of VF. We characterized the dynamics of the frequency distribution in the power spectrum of the ECG recorded from eleven swine during VF to determine if enough information existed in this domain to estimate DT. We used the median frequency (FM) of the power spectrum to track the frequency distribution. The FM followed a dynamic repeatable course during the first 10 min of VF. Intersubject variability was small. We modeled the FM data of the eleven subjects with a set of first-order polynomial equations and tested the algorithm with data from an additional ten subjects. The algorithm predicted VF duration with an average error of -0.86 min; 71.5% of the predictions fell within the 95% confidence limits of the model. This paper has identified a signal processing tool which may be useful in the prehospital treatment of VF.

Algorithms↗
PubMed1990

Control of tropical theileriosis (Theileria annulata infection) of cattle.

Tropical bovine theileriosis caused by Theileria annulata and transmitted by ticks of the genus Hyalomma may be controlled by one or more of the following methods: i) management, with particular emphasis on movement control; ii) vector control by application of acaricides, preventing transmission of disease; iii) treatment of clinical disease using specific chemotherapeutics; iv) immunization with live vaccines; and v) the use of cattle resistant to ticks or the disease. Of these the most important and effective control method is the use of a live cell culture vaccine attenuated by prolonged culture in vitro of mononuclear cells persistently infected with macroschizonts of T. annulata. This vaccine, used chiefly in susceptible taurine dairy cattle, can now be complemented by using novel chemotherapeutic naphthoquinones--parvaquone and buparvaquone--which are very effective in treatment of the clinical disease in these valuable cattle.

Animal Husbandry↗
PubMed1989

Infection of bovine monocyte/macrophage populations with Theileria annulata and Theileria parva.

Infection and transformation of cells of the bovine immune system by Theileria annulata and T. parva were compared. Preliminary experiments with mammary gland macrophages indicated that they were permissive to infection by T. annulata but only to a limited extent by T. parva. Further experiments involved several purified subpopulations of bovine cells including bovine monocytes, T cells and MHC class II positive and negative populations. These subpopulations were incubated with T. annulata or T. parva sporozoites in limiting dilution cultures. T. annulata preferentially infected macrophage type cells and also MHC class II positive cells, whereas the frequency of MHC class II negative cells infected by this parasite was negligible. T cells also showed a very low level of infection. In complete contrast, T. parva preferentially infected T cells and did not infect cells phenotypically defined as monocytes at all. These results suggested that class II expression was necessary for T. annulata infection and not necessary for, though not a barrier to T. parva infection. T. annulata infected cell lines all expressed class II molecules to varying degrees. Other available phenotypic markers were only expressed at very low levels or no longer expressed. The immunological significance of the different cell preferences and phenotypes of infected cell lines of T. annulata and T. parva is discussed.

Analysis of Variance↗
PubMed1989

Relation between dopaminergic control of pituitary lactotroph function and deceleration of age-related changes in serum prolactin of diet-restricted rats.

Pituitary lactotroph function has been examined in diet-restricted (6 hr/day) male and female rats and compared with that in animals fed ad lib. After 12 months the age-related increase in serum prolactin concentration was significantly attenuated in diet-restricted female rats. Similar effects were not observed in male rats. Isolated superfused anterior pituitary glands removed from rats on both feeding regimens at 12 or 18 months and challenged with dopamine in vitro (5 microM) did not show differential prolactin secretion. No significant differences were observed in serum prolactin secretion in vivo after administration of bromocriptine (3 mg/kg body weight, sc) or haloperidol (1.75 mg/kg body weight, ip). These results do not support an altered dopamine receptor function in the anterior pituitary lactotrophs. In contrast, central dopamine receptor function in rats 12 months of age was altered by dietary restriction, since the frequency of cataleptic responses to haloperidol injection (2 mg/kg body weight, ip) was significantly depressed in the test animals.

Aging↗
PubMed1989

The effect of UK14,304-18 (an alpha-2 adrenergic agonist) on myocardial blood flow during cardiopulmonary resuscitation.

Several recent studies have suggested that adrenergic drugs with peripheral postsynaptic alpha-2 agonist properties increase aortic diastolic pressure (ADP), and thus in the setting of CPR, may improve myocardial blood flow (MBF). This preliminary study investigated the effect of UK14,304-18, a postsynaptic alpha-2 adrenergic agonist on ADP, MBF, myocardial oxygen delivery/utilization (MDO2/MVO2), endocardial/epicardial blood flow ratio (EN/EP), coronary sinus oxygen content (CcsO2) and extraction ratio (ER) during CPR. Five swine were instrumented for MBF measurements using tracer microspheres. Catheters were also placed to measure arterial oxygen content (CaO2) and CcsO2. ADP, MBF, MDO2/MVO2, EN/EP, ER, CaO2 and CcsO2 were measured during normal sinus rhythm (NSR), and during CPR following a 10-min cardiorespiratory arrest. Following this, each animal received 2.0 mg/kg of UK14,304-18 through a right atrial line. ADP, MBF, MDO2/MVO2, EN/EP, ER, CaO2 and CcsO2 were again determined. Defibrillation was then attempted. To determine whether UK14,304-18 improved ADP, MBF and MDO2 over MVO2, compared to CPR alone, results were compared using a paired Student t-test. Statistical significance was considered at the P less than or equal to 0.05 level. No significant improvement in ADP, MBF, MDO2 or ER was noted following the administration of UK14,304-18. The lack of improvement in ADP and MBF may be secondary to a centrally acting postsynaptic alpha-2 agonist effect because of disruption of the blood brain barrier following a prolonged cardiac arrest or because of pharmacologically or structurally distinct populations of peripheral postsynaptic alpha-2 adrenoreceptors that develop in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1989

The effect of dose and line on immunisation of cattle with lymphoblastoid cells infected with Theileria annulata.

Thirty-one Friesian calves in Morocco susceptible to tropical theileriosis were protected against a lethal sporozoite challenge by prior infection with lymphoblastoid cell lines infected and transformed in vitro by a Moroccan stock of Theileria annulata. The challenge infection of cryopreserved sporozoites killed all four susceptible control calves within 20 days. Four schizont-infected cell cultures at Passage 3 were inoculated at four different doses, 10(8), 10(6), 10(4) and 10(2), into pairs of calves. The recipient animals showed great variation in severity of disease symptoms, which did not show a linear correlation with the cell dose inoculated. The most severe disease symptoms were recorded, prior to challenge, in the 10(2) cell dose recipients; one animal died of acute theileriosis and another had to be treated. One of the four cell lines used was more virulent than the other three. Two years after the completion of this experiment, immunised animals have shown normal productivity traits.

Animals↗
PubMed1989

The effect of norepinephrine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

alpha-Adrenergic drugs improve cerebral blood flow (CBF) during cardiopulmonary resuscitation (CPR), in part, by reversing carotid artery collapse and by shunting blood from extracerebral to intracerebral vascular structures. Adrenergic drugs with beta 2-agonist properties may cause peripheral vasodilation, and thus may be less beneficial in this setting. The purpose of this study was to compare epinephrine (E), an alpha 1,2, beta 1,2-agonist, with norepinephrine (NE), an alpha 1,2, beta 1-agonist, on CBF during CPR. Twenty swine each weighing greater than 15 kg were instrumented for regional CBF measurements using tracer microspheres. Regional CBF was measured during normal sinus rhythm (NSR). Animals were then placed into ventricular fibrillation (VF). After ten minutes of VF, the animals received closed-chest CPR using a mechanical thumper. Regional CBF was measured during CPR. After three minutes of CPR, the animals were allocated to receive either E, 0.20 mg/kg (N = 5); NE, 0.08 mg/kg (N = 5); NE, 0.12 mg/kg (N = 5); or NE, 0.16 mg/kg (N = 5). Regional blood flows were again measured following drug administration. CBFs following drug administration were compared using an analysis of covariance adjusting for baseline differences during CPR. A Newman-Keuls multiple comparison was used to follow-up significant (P less than or equal to .05) differences. Statistical significance was considered at P less than or equal to .05. There was a clinically significant improvement in cerebral cortical flow with NE, 0.12 mg/kg, and NE, 0.16 mg/kg, compared with NE, 0.08 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Estimating the duration of ventricular fibrillation.

As the duration of time between the onset of ventricular fibrillation and the application of defibrillation (downtime) increases, the rate of successful resuscitation decreases. Results of recent animal studies suggest that the rate of successful resuscitation may be increased after a prolonged cardiorespiratory arrest when pharmacologic therapy is instituted before defibrillation. An accurate estimation of downtime could be critical in selecting the most appropriate therapeutic intervention. The purpose of our study was to determine whether changes in the frequency or amplitude of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate downtime. We characterized the dynamics of both total power and frequency distribution of the power in the ECG during ventricular fibrillation in 11 swine to determine whether enough information existed in either parameter to estimate downtime. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic, repeatable pattern. However, median frequency showed less intersubject variability than did total power. A mathematical model of median frequency was developed and used with data obtained from ten additional swine to estimate downtime. The model estimated downtime to within 1.3 minutes of actual downtime between one and ten minutes of ventricular fibrillation. Our study has identified a new, potentially useful parameter for studying various management strategies in ventricular fibrillation as a function of downtime.

Animals↗
PubMed1989

Substance abuse education in residency training programs in emergency medicine. NIAAA Task Force of the American College of Emergency Physicians.

The emergency department is the focal point for many social ills, not the least of which is substance abuse. We conducted a study to determine to what degree substance abuse education is taught in emergency medicine residency training programs. A set of educational objectives was developed by a task force composed of representatives of the American College of Emergency Physicians, the Society of Teachers of Emergency Medicine, and the University Association for Emergency Medicine. A questionnaire then was sent to the directors of all emergency medicine residency programs accredited by the Accreditation Council for Graduate Medical Education to determine the degree to which those objectives are covered in residency training. A 62% response rate was achieved. The data revealed that such topics as narcotic prescription law, patterns of risk, and issues pertaining to substance abuse by physicians were covered by fewer than half of the programs responding. Respondents were generally satisfied with the adequacy of training of residents and faculty in the area of substance abuse; however, they were dissatisfied with the adequacy of available training materials. Recommendations for changes in graduate curriculum as well as avenues for further research are provided.

Attitude of Health Personnel↗
PubMed1989

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR.

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of direct mechanical ventricular assistance on myocardial hemodynamics during ventricular fibrillation.

Direct mechanical ventricular assistance (DMVA) is a method of biventricular circulatory support that employs a pneumatic device to apply both systolic and diastolic forces directly to the ventricular myocardium. This study investigated the effects of DMVA on myocardial hemodynamics when applied after a prolonged cardiopulmonary arrest. Seven swine weighting 28.3 +/- 2.5 kg were instrumented for regional myocardial blood flow (MBF) measurements using tracer microspheres. Ventricular fibrillation was then induced. After 10 min of ventricular fibrillation, CPR was initiated for 3 min. DMVA was then applied through median sternotomy. Defibrillation was attempted after 3.5 min of DMVA. If unsuccessful, DMVA was instituted for another 17.5 min and a subsequent defibrillation attempt was made. Arterial oxygen content (CaO2), coronary sinus oxygen content (CcSO2), myocardial oxygen delivery/consumption (mDO2/mVO2), extraction ratio (ER), and endocardial/epicardial blood flow ratio (EN/EP) were determined during CPR, during the initial application of DMVA (DMVA1), and after the subsequent 17.5 min of DMVA in those animals not initially defibrillated (DMVA2). Three of the seven animals were successfully defibrillated during DMVA1. After the additional 17.5 min of DMVA, only one other animal was defibrillated. There was a significant improvement in CaO2, CcSO2, MBF, mDO2, mVO2, ER, and EN/EP after DMVA1 compared to CPR. Only mVO2 and ER improved significantly after DMVA2. These findings support the concept that physical diastolic augmentation may improve myocardial hemodynamics when DMVA is applied during cardiac arrest.

Animals↗