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1.
J Bioeth Inq ; 18(4): 573-587, 2021 12.
Article in English | MEDLINE | ID: mdl-34741699

ABSTRACT

Being a healthcare professional in both paediatric and adult hospitals will mean being exposed to human tragedies and stressful events involving conflict, misunderstanding, and moral distress. There are a number of different structured approaches to reflection and discussion designed to support healthcare professionals process and make sense of their feelings and experiences and to mitigate against direct and vicarious trauma. In this paper, we draw from our experience in a large children's hospital and more broadly from the literature to identify and analyse four established approaches to facilitated reflective discussions. Each of the four approaches seeks to acknowledge the stressful nature of health professional work and to support clinicians from all healthcare professions to develop sustainable skills so they continue to grow and thrive as health professionals. Each approach also has the potential to open up feelings of uncertainty, frustration, sorrow, anguish, and moral distress for participants. We argue, therefore, that in order to avoid unintentionally causing harm, a facilitator should have specific skills required to safely lead the discussion and be able to explain the nature, scope, safe application, and limits of each approach. With reference to a hypothetical but realistic clinical case scenario, we discuss the application and key features of each approach, including the goals, underpinning theory, and methods of facilitation.


Subject(s)
Health Personnel , Occupational Stress , Psychological Trauma , Humans , Health Personnel/psychology , Hospitals , Occupational Stress/psychology
2.
Hum Reprod ; 34(4): 751-757, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30865256

ABSTRACT

STUDY QUESTION: Does an informed group of citizens endorse the clinical use of mitochondrial donation in a country where this is not currently permitted? SUMMARY ANSWER: After hearing balanced expert evidence and having opportunity for deliberation, a majority (11/14) of participants in a citizens' jury believed that children should be able to be born using mitochondrial donation. WHAT IS KNOWN ALREADY: Research suggests that patients, oocyte donors and health professionals support mitochondrial donation to prevent transmission of mitochondrial disease. Less is known about public acceptability of this novel reproductive technology, especially from evidence using deliberative methods. STUDY DESIGN, SIZE, DURATION: This study comprised a citizens' jury, an established method for determining the views of a well-informed group of community members. The jury had 14 participants, and ran over one and a half days in 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Jurors were members of the public with no experience of mitochondrial disease. They heard and engaged with relevant evidence and were asked to answer the question: 'Should Australia allow children to be born following mitochondrial donation?' MAIN RESULTS AND THE ROLE OF CHANCE: Eleven jurors decided that Australia should allow children to be born following mitochondrial donation; 7 of whom added conditions such as the need to limit who can access the intervention. Three jurors decided that children should not (or not yet) be born using this intervention. All jurors were particularly interested in the reliability of evidence, licensing/regulatory mechanisms and the rights of children to access information about their oocyte donors. LIMITATIONS, REASONS FOR CAUTION: Jurors' views were well informed and reflected critical deliberation and discussion, but are not intended to be representative of the whole population. WIDER IMPLICATIONS OF THE FINDINGS: When presented with high quality evidence, combined with opportunities to undertake structured deliberation of novel reproductive technologies, members of the public are able to engage in detailed discussions. This is the first study to use an established deliberative method to gauge public views towards mitochondrial donation. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a University of Sydney Industry and Community Collaboration Seed Award (2017), which was awarded contingent on additional funding from the Mito Foundation. Additional funding was provided by the Mito Foundation. The Foundation was not involved in jury facilitation or deliberation, nor analysis of research data. TRIAL REGISTRATION NUMBER: Not applicable.


Subject(s)
Attitude , Mitochondrial Diseases/prevention & control , Mitochondrial Replacement Therapy/legislation & jurisprudence , Mitochondrial Replacement Therapy/methods , Oocyte Donation/legislation & jurisprudence , Oocyte Donation/methods , Public Opinion , Adolescent , Adult , Aged , Australia , Decision Making , Female , Humans , Male , Middle Aged , Policy Making , Young Adult
3.
Arch Dis Child ; 99(3): 216-20, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24311188

ABSTRACT

OBJECTIVE: End-of-life decision-making is difficult for everyone involved, as many studies have shown. Within this complexity, there has been little information on how parents see the role of doctors in end-of-life decision-making for children. This study aimed to examine parents' views and experiences of end-of-life decision-making. DESIGN: A qualitative method with a semistructured interview design was used. SETTING: Parent participants were living in the community. PARTICIPANTS: Twenty-five bereaved parents. MAIN OUTCOMES: Parents reported varying roles taken by doctors: being the provider of information without opinion; giving information and advice as to the decision that should be taken; and seemingly being the decision maker for the child. The majority of parents found their child's doctor enabled them to be the ultimate decision maker for their child, which was what they very clearly wanted to be, and consequently enabled them to exercise their parental autonomy. Parents found it problematic when doctors took over decision-making. A less frequently reported, yet significant role for doctors was to affirm decisions after they had been made by parents. Other important aspects of the doctor's role were to provide follow-up support and referral. CONCLUSIONS: Understanding the role that doctors take in end-of-life decisions, and the subsequent impact of that role from the perspective of parents can form the basis of better informed clinical practice.


Subject(s)
Decision Making , Parents/psychology , Professional-Family Relations , Terminal Care , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Physicians
4.
Child Care Health Dev ; 40(3): 301-8, 2014 May.
Article in English | MEDLINE | ID: mdl-23445484

ABSTRACT

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is now the most common reason for a child to present to a paediatrician in Australia. Stimulant medications are commonly prescribed for children with ADHD, to reduce symptoms and improve function. In this study we investigated the factors that influence paediatricians' decisions about prescribing stimulant medications. METHOD: In-depth, semi-structured interviews were conducted with paediatricians (n = 13) who were purposively recruited so as to sample a broad demographic of paediatricians working in diverse clinical settings. Paediatricians were recruited from public outpatient and private paediatrician clinics in Victoria, Australia. The interviews were audio-recorded and transcribed verbatim for thematic analysis. Paediatricians also completed a questionnaire describing their demographic and practice characteristics. RESULTS: Our findings showed that the decision to prescribe is a dynamic process involving two key domains: (1) weighing up clinical factors; and (2) interacting with parents and the patient along the journey to prescribing. Five themes relating to this process emerged from data analysis: comprehensive assessments that include history, examination and information from others; influencing factors such as functional impairment and social inclusion; previous success; facilitating parental understanding including addressing myths and parental confusion; and decision-making model. CONCLUSIONS: Paediatricians' decisions to prescribe stimulant medications are influenced by multiple factors that operate concurrently and interdependently. Paediatricians do not make decisions about prescribing in isolation; rather, they actively involve parents, teachers and patients, to arrive at a collective, well-informed decision.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/therapeutic use , Decision Making , Physicians/psychology , Practice Patterns, Physicians'/statistics & numerical data , Adult , Aged , Attitude of Health Personnel , Drug Prescriptions/statistics & numerical data , Female , Humans , Male , Middle Aged , Physician-Patient Relations , Professional-Family Relations , Victoria
7.
J Med Ethics ; 35(12): 722-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19948926

ABSTRACT

The concept of selecting for a disability, and deafness in particular, has triggered a controversial and sometimes acrimonious debate between key stakeholders. Previous studies have concentrated on the views of the deaf and hard of hearing, health professionals and ethicists towards reproductive selection for deafness. This study, however, is the first of its kind examining the views of hearing children of deaf adults towards preimplantation genetic diagnosis and prenatal diagnosis to select for or against deafness. Hearing children of deaf adults (or CODAs, as they call themselves, and are widely known in the deaf community) straddle both the deaf and hearing worlds, and this dual perspective makes them ideally placed to add to the academic discourse concerning the use of genetic selection for or against deafness. The study incorporated two complementary stages, using initial, semistructured interviews with key informants (CODAs and health professionals) as a means to guide the subsequent development of an electronic survey, completed anonymously by 66 individuals. The participants shared many of the same views as deaf individuals in the D/deaf (or "culturally deaf") community. The similarities extended to their opinions regarding deafness not being a disability (45.5% believed deafness was a distinct culture rather than a disability), their ambivalence towards having hearing or deaf children (72.3% indicated no preference) and their general disapproval of the use of genetic technologies to select either for or against deafness (60% believed that reproductive technologies, when used to select for or against deafness, should not be available to the community).


Subject(s)
Attitude to Health , Deafness/genetics , Genetic Testing/psychology , Patient Acceptance of Health Care/psychology , Prenatal Diagnosis/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Deafness/diagnosis , Deafness/psychology , Female , Genetic Counseling , Genetic Testing/ethics , Humans , Interviews as Topic , Male , Middle Aged , Parents/psychology , Prenatal Diagnosis/ethics , Selection, Genetic , Young Adult
8.
J Perinatol ; 29(10): 662-7, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19626028

ABSTRACT

OBJECTIVE: Prenatal ultrasound has led to the early diagnosis of major anomalies. However, the ready availability of this technology has led to increasing challenges for physicians counseling affected parents, which is all the more difficult in a twin pregnancy with only one affected fetus. This paper reviews the medical and ethical considerations in twin pregnancies discordant for a serious cardiac condition. STUDY DESIGN: Six recent twin pregnancies discordant for a serious cardiac condition and their outcomes are presented. Options considered in the management of the pregnancy were to continue or terminate the pregnancy, selectively terminate the affected twin or to decide whether to treat the affected twin once delivered. An approach to decision making in such situations has been formulated after critical analysis of the factors involved. RESULTS: Four of the six pregnancies were monochorionic twins. Two sets of parents decided to terminate the pregnancy. In the four that continued, two opted for the affected twin to be appropriately managed once delivered. A further two considered selective termination but opted to continue the pregnancy because of the risk of premature labor and/or cerebral hypoxia following such intervention. They sought a commitment, however, that they be given the option whether to treat the affected twin following delivery. Eventually both elected to have their babies treated, one of whom died in the postoperative period. DISCUSSION: Medical considerations included the risks of continuation of the pregnancy for the mother and her twins, the safety of termination (total or selective), and the risks to the unaffected fetus. Ethical issues revolved around concepts of autonomy, beneficence and justice from the standpoint of the family and the twins. The gestation and the viability of the twins played an important role in decision making and approaches, taking into account the local legal and other considerations. CONCLUSION: Attention is drawn to the complexities of the issues involved in twin pregnancies complicated by a serious cardiac condition in one of the twins. Optimal counseling requires sound clinical knowledge about the medical risks to the mother and her twins, and a clear understanding of the key ethical considerations. Such an approach will assist parents in their very difficult decision making.


Subject(s)
Abortion, Eugenic/ethics , Abortion, Eugenic/psychology , Decision Making/ethics , Heart Defects, Congenital/diagnostic imaging , Physician-Patient Relations/ethics , Twins, Monozygotic , Abortion, Eugenic/adverse effects , Adult , Female , Heart Defects, Congenital/surgery , Humans , Magnetic Resonance Imaging , Parents , Patient Participation , Pregnancy , Ultrasonography, Prenatal
9.
J Anat ; 213(3): 325-35, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18624829

ABSTRACT

Human 2D : 4D ratios (measures of the relative lengths of index and ring fingers) attract considerable research interest because they exhibit sexual dimorphism and are associated with various morphological, physiological and behavioural traits as well as sporting abilities and medical conditions. In an attempt to identify potential confounding factors in such studies, we have examined how relative and absolute digit lengths vary with gender and tested whether they are influenced by age, right-left asymmetry and hand preference. Participants between 4 and 60 years of age were recruited from local educational sites. Hand photocopies and calliper measurement were used to obtain digit lengths. We employed linear regression analysis to examine the growth trajectories of individual digits, analyses of variance to isolate main and interaction effects of age, gender and hand preference, and paired t-tests to identify lateral asymmetries. Both digits exhibited biphasic growth with an early growth phase followed by a stable length phase. Digits in females attained their maximum length about 2.2 years (dextral subjects) or 5.1 years (sinistral subjects) earlier than those in males. Sexual dimorphism in 2D : 4D ratios was apparent by 4 years of age and age changes in ratios depended on gender, side and hand preference. Relative and absolute lengths displayed age, gender, hand-preference and age x gender interaction effects. Lengths tended to be greater in females in younger subjects and greater in males in older subjects. Ratios tended to be greater in sinistral subjects. In dextral subjects, significant lateral asymmetries in 2D lengths were seen at all ages but asymmetries in males and 4D lengths seemed to be age-dependent. We conclude that age, lateral asymmetry and hand preference are potential confounding factors and that future study designs should take account of these as well as other known confounders such as ethnicity, birth order, menstrual cycle phase and sexual preference.


Subject(s)
Aging/physiology , Fingers/anatomy & histology , Sex Characteristics , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Fingers/growth & development , Functional Laterality , Humans , Linear Models , Male , Middle Aged
10.
Mol Genet Metab ; 94(2): 143-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18395481

ABSTRACT

Non-ketotic hyperglycinaemia (NKH) is a devastating neurometabolic disorder leading, in its classical form, to early death or severe disability and poor quality of life in survivors. Affected neonates may need ventilatory support during a short period of respiratory depression. The transient dependence on ventilation dictates urgency in decision-making regarding withdrawal of therapy. The occurrence of patients with apparent transient forms of the disease, albeit rare, adds uncertainty to the prediction of clinical outcome and dictates that the current practice of withholding or withdrawing therapy in these neonates be reviewed. Both bioethics and law take the view that treatment decisions should be based on the best interests of the patient. The medical-ethics approach is based on the principles of non-maleficence, beneficence, autonomy and justice. The law relating to withholding or withdrawing life-sustaining treatment is complex and varies between jurisdictions. Physicians treating newborns with NKH need to provide families with accurate and complete information regarding the disease and the relative probability of possible outcomes of the neonatal presentation and to explore the extent to which family members are willing to take part in the decision making process. Cultural and religious attitudes, which may potentially clash with bioethical and juridical principles, need to be considered.


Subject(s)
Decision Making , Ethics, Medical , Hyperglycinemia, Nonketotic/therapy , Neonatology/ethics , Neonatology/legislation & jurisprudence , Humans , Hyperglycinemia, Nonketotic/diagnosis , Infant, Newborn , Liability, Legal , Life Support Care , Withholding Treatment/legislation & jurisprudence
11.
J Anat ; 211(5): 630-8, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17764524

ABSTRACT

It is known that there are sexually dimorphic differences in relative and absolute lengths of the index (2nd) and ring (4th) fingers and that the sizes of laterally-paired soft tissues (e.g. ears and fingers) show changes across the menstrual cycle. The aim of the present study was to determine whether cyclical changes in the digit lengths of the index and ring fingers also occur and, if so, to what extent these are related to changing patterns of circulating sex steroids. Digit lengths were assessed over two cycles in groups of right-handed females (19-21 years of age) who were divided on the basis of whether or not they were taking oral contraceptive pills (n = 13 and n = 6 respectively). Using callipers, finger lengths were measured on photocopy images of both hands taken at 4-day intervals for a total of 56 days. We tested the following null hypotheses: (1) digit length measurements do not exhibit fluctuations across the menstrual cycle; (2) there is no evidence of lateral asymmetry between measurements made on both hands; (3) the lengths of digits 2 and 4 do not differ in either hand. Null hypotheses were tested using Page's L trends test for related samples (cyclical fluctuations) and paired Student's t tests (left-right asymmetries and within-hand digital differences). In those not taking oral contraceptives, finger lengths and 2D:4D digit ratios fluctuated across the cycle with values tending to increase in the pre-ovulatory period and decline thereafter. Left-right asymmetries varied in a similar fashion with lengths generally being larger, and lateral asymmetries smaller, in the dominant hand. Although sample sizes were smaller, some of these patterns were retained but others were perturbed in those practising oral contraception. We conclude that finger lengths are cycle-dependent and that account should be taken of this, and of oral contraceptive usage, in future studies on female digit lengths and their ratios.


Subject(s)
Fingers/anatomy & histology , Menstrual Cycle/physiology , Adult , Anthropometry/methods , Contraceptives, Oral, Hormonal/administration & dosage , Female , Functional Laterality , Humans
12.
J Med Ethics ; 32(9): 537-41, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16943337

ABSTRACT

Clinical genetic research is often regarded as more ethically problematic than other forms of research, and in some countries is subject to specific regulation, requiring researchers to follow specialised guidelines. In this paper, an approach to enhancing the ethical conduct of genetic research is proposed, which is believed to be more effective than simply attempting to follow general guidelines. The potential concerns, likely areas of misunderstanding and negative reactions of the participant group are systematically investigated before starting a study on genetics. This would constitute, in effect, an ethical pilot study, similar to a feasibility pilot study to test equipment, procedures and logistics. The findings of the ethical pilot study would be used to help in designing ethically important aspects of research protocol, such as recruitment procedures, written and other information for potential participants, informed consent processes and reporting of results including ambiguous or uncertain results.


Subject(s)
Ethics, Research , Hearing Loss, Sensorineural/genetics , Parents/psychology , Patient Selection/ethics , Child , Female , Genetic Techniques/ethics , Genetic Techniques/psychology , Health Knowledge, Attitudes, Practice , Humans , Male , Parent-Child Relations , Pilot Projects , Privacy/psychology
13.
J Med Genet ; 43(11): 850-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16840571

ABSTRACT

BACKGROUND: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. METHODS: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. RESULTS: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. DISCUSSION: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.


Subject(s)
Connexins/genetics , Hearing Loss, Bilateral/genetics , Hearing Loss, Sensorineural/genetics , Mutation , Alleles , Australia , Child , Connexin 26 , DNA Mutational Analysis , Female , Genetic Testing , Humans , Male , Polymorphism, Single Nucleotide , Schools
14.
J Am Soc Echocardiogr ; 14(12): 1212-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11734789

ABSTRACT

The impact of echocardiography on the continuum of cardiovascular health care is well established. Ongoing concerns regarding costs, accessibility, quality, and appropriateness of services rendered by practitioners of echocardiography have prompted various legislative proposals and regulatory policies from government, medical professional groups, and health plans. Specifically, there continues to be a drive to enact law for licensure of sonographers. These activities require continuing advocacy for the profession with active leadership. As part of its mission statement, the American Society of Echocardiography (ASE) states, "ASE strives to be a leader in public policy in order to create a favorable environment for excellence in the practice of echocardiography." As such, the ASE is committed to an increase in their interaction with legislators, payers, and policy makers. This article describes the historical perspective of state, federal, and provincial sonographer licensure issues to provide an understanding of the political perspectives.


Subject(s)
Allied Health Personnel/legislation & jurisprudence , Echocardiography/standards , Licensure/legislation & jurisprudence , Allied Health Personnel/organization & administration , Allied Health Personnel/standards , Canada , Humans , Lobbying , United States
15.
Med J Aust ; 175(4): 205-10, 2001 Aug 20.
Article in English | MEDLINE | ID: mdl-11587281

ABSTRACT

Teaching ethics incorporates teaching of knowledge as well as skills and attitudes. Each of these requires different teaching and assessment methods. A core curriculum of ethics knowledge must address both the foundations of ethics and specific ethical topics. Ethical skills teaching focuses on the development of ethical awareness, moral reasoning, communication and collaborative action skills. Attitudes that are important for medical students to develop include honesty, integrity and trustworthiness, empathy and compassion, respect, and responsibility, as well as critical self-appraisal and commitment to lifelong education.


Subject(s)
Curriculum , Education, Medical, Undergraduate , Ethics, Medical/education , Schools, Medical , Teaching , Australia , Humans , New Zealand
16.
Med J Aust ; 174(6): 296-7, 2001 Mar 19.
Article in English | MEDLINE | ID: mdl-11297119

ABSTRACT

Issues of confidentiality are complicated by the relationships we have to patients and others who have valid interests in the confidential information. There are no straightforward answers to problems which involve complex relationships and sensitive information. The best we can do is to think thoroughly and carefully about the issues in each case, and use our knowledge of the people involved to reach a decision. Doctors faced with difficult decisions of this kind should be assured that everyone finds them difficult. Sharing the burden with experienced colleagues can be helpful.


Subject(s)
Adolescent Health Services/standards , Confidentiality , Ethics, Medical , Professional-Family Relations , Adolescent , Australia , Contraceptive Agents, Female , Decision Making , Female , Humans , Third-Party Consent
17.
Am J Cardiol ; 86(6): 669-74, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-10980221

ABSTRACT

Suboptimal left ventricular (LV) cavity visualization and endocardial border delineation often compromise the clinical utility of echocardiography. This study examines the safety and efficacy of perflutren, a novel ultrasound contrast agent, for LV cavity opacification and endocardial border delineation in patients with suboptimal baseline echocardiograms. In a multicenter, randomized, placebo-controlled, double-blind trial, 211 patients with suspected cardiac disease and suboptimal baseline echocardiograms were enrolled at 17 sites. Two intravenous injections of either placebo (saline) or perflutren (5 or 10 microl/kg) were given approximately 30 minutes apart. Images of the apical 4- and 2-chamber views were acquired and scored. Perflutren opacified the LV cavity after both dosages (5 and 10 microl/kg dosages). Clinically useful contrast was observed in 89% of patients who received perflutren and in 0% of patients who received placebo (p < 0.01). Quantitative assessment of LV opacification with videodensitometry showed similar results. The mean duration of clinically useful contrast was 90 seconds. Improvement in endocardial border delineation was demonstrated in 91% of patients who received perflutren and in 12% of those who received placebo (p < 0.001). Following perflutren, an average of 4 more segments per patient were evaluable compared with baseline. Salvage of nondiagnostic baseline examinations by perflutren was demonstrated in 48% of eligible subjects. The safety profile of perflutren was similar to placebo. These data indicate that administration of perflutren to patients with suboptimal baseline images is well tolerated and provides substantial LV cavity opacification and improvement in endocardial border delineation.


Subject(s)
Contrast Media , Echocardiography/methods , Fluorocarbons , Heart Ventricles/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Densitometry , Diagnosis, Differential , Double-Blind Method , Female , Humans , Injections, Intravenous , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Safety , Video Recording
19.
Cardiovasc Pathol ; 9(2): 67-84, 2000.
Article in English | MEDLINE | ID: mdl-10867357

ABSTRACT

UNLABELLED: This study examined the effect of delayed reperfusion of myocardial hibernation from 24 hours to 7 days on myocardial ultrastructural and functional changes and their recoveries after reperfusion. BACKGROUND: We have previously shown in pigs that after reperfusion the functional and structural alterations in short-term myocardial hibernation which was reperfused in 24 hours can recover in 7 days. The effect of delayed reperfusion of hibernating myocardium on the extent and severity of cellular and extracellular structural changes of hibernating myocardium, and their recoveries after reperfusion is not known. METHODS AND RESULTS: A severe LAD stenosis was created in 27 pigs, reducing resting flow by 30-40% immediately after placement of the stenosis and producing acute ischemia as evidenced by regional lactate production, a decrease in regional coronary venous pH, reduced regional wall thickening (from 38.5 +/- 5.1% to 10.4 +/- 8.0%) and a 33% reduction of regional oxygen consumption. The stenosis was maintained either for 24 hours in 9 pigs (group 1) with LAD flow of 0.65 +/- 0.13 ml/min/g (38% reduction), or for 7 days in 17 pigs (group 2) with LAD flow of 0.67 +/- 0.14 ml/min/g (36% reduction). There were no differences (p = NS) in the reduction of wall thickening, rate-pressure product, lactate production, or regional oxygen consumption between group 1 and group 2. Quantitative morphometric evaluation of the ultrastructure on electromicrographs revealed a greater decrease in sarcomere volume and a higher incidence of myocytes with reduced sarcomere volume in 7-day than in 24-hour hibernating regions (53 +/- 19% versus 33 +/- 14%, p < 0.05). Patchy myocardial necrosis with replacement fibrosis was common, but 6 of the 18 pigs had no myocardial necrosis or replacement fibrosis in the 7-day hibernating group, and 4 of 9 pigs had no patchy myocyte necrosis in the 24 hour hibernating group. In 6 pigs in group 1 in which the stenosis was then released and hibernating myocardium reperfused in 24 hours, regional wall thickening recovered to 30 +/- 6% (p = NS compared to baseline) after one week of reperfusion. In 12 pigs in group 2 in which the stenosis was released and hibernating myocardium reperfused in 7 days, regional wall thickening recovered slowly, from 10.1 +/- 7.2% to 18.1 +/- 8.3% at one week (n = 5) and to 28.0 +/- 3.6% at 3-4 weeks of reperfusion (n = 7, p < 0.05 compared to baseline). Similarly, the sarcomere volume or myofilament recovered significantly (p < 0.01) and was not different compared to the normal region (p = NS) in the 24-hour hibernating region of group 1, but the recovery was much slower and was incomplete at 4 weeks (p < 0.01) compared to baseline in the 7-day hibernating region of group 2. Recovery of regional wall thickening correlated with ultrstructural recovery (p < 0.01). By multivariate stepwise regression analysis, the degree of LAD flow reduction, the extent of fibrosis, and myofilament loss were independent predictors of the extent of functional recovery. CONCLUSIONS: In a porcine model of myocardial hibernation with myocardial hypoperfusion, systolic dysfunction, and metabolic adaptations, a longer period of myocardial hibernation with delayed reperfusion was associated with more severe abnormalities of myocytes. an increasing interstitial fibrosis, and more protracted myofibrillar and functional recoveries after reperfusion. The extent of functional recovery is related to the degree of coronary flow reduction, the severity of the ultrastructural changes, and the extent of interstitial fibrosis.


Subject(s)
Heart/physiopathology , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardial Stunning/pathology , Myocardial Stunning/physiopathology , Myocardium/ultrastructure , Animals , Coronary Circulation , Coronary Disease/pathology , Echocardiography , Myocardial Reperfusion Injury/diagnostic imaging , Myocardial Stunning/diagnostic imaging , Myocardial Stunning/metabolism , Myocardium/metabolism , Necrosis , Oxygen Consumption , Swine , Systole , Time Factors
20.
Am Heart J ; 139(3): 399-404, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10689253

ABSTRACT

BACKGROUND: In current practice, contrast echocardiography is performed with single or multiple bolus injections, which often result in an uncontrolled period of attenuation followed by transient left ventricular opacification (LVO). Because a "slow bolus" appears to reduce attenuation and prolong LVO, we hypothesized that a controlled infusion of contrast might provide a more uniform contrast effect with less attenuation and longer contrast duration. METHODS AND RESULTS: We sought to test the hypothesis by using an infusion of contrast (DEFINITY [perflutren], The DuPont Pharmaceuticals Co, Medical Imaging, North Billerica, Mass) that is stable when diluted in saline in a randomized, multicenter, controlled, crossover trial. Sixty-four patients with poor noncontrast images were recruited at 3 centers and randomly assigned to 2 single "slow" bolus injections of contrast (10 microL/kg each over a period of 30 to 60 seconds) or an infusion (1. 3 mL in 50 mL normal saline initially at 4.0 mL/min) of contrast. Patients then returned within 24 to 72 hours for the alternative form of contrast delivery. Three independent experienced echocardiographers viewed 30 seconds of videotape for all optimal baseline and optimal contrast images to score LVO and qualitatively assessed endocardial border evaluability. The duration of adequate LVO then was independently assessed by review of the entire videotape. Three independent sonographers traced single-frame, digitally captured images to measure the length of the contiguous endocardial border visualized. Both bolus and infusion administration demonstrated improved LVO (>90% by all blinded readers, P <.01) and endocardial border visualized (mean increase of 1.8 to 4.7 cm at both end-diastole and end-systole, all P <.05) as compared with baseline images. However, contrast infusion resulted in a longer duration of LVO (range of mean durations for each reader, 158 to 174 seconds longer, P <.05) and a shorter duration of attenuation (18 to 54 seconds, P <.05) compared with either bolus injection. There were no severe adverse events with contrast infusion. CONCLUSIONS: Contrast echocardiography delivered as an infusion optimizes the contrast effect by decreasing the attenuation period, extending the LVO duration, and providing a uniform contrast effect that may be useful in obtaining multiple echocardiographic views, stress echocardiography, myocardial perfusion imaging, and applications in which blood flow must be quantified.


Subject(s)
Contrast Media/administration & dosage , Echocardiography/methods , Heart Diseases/diagnostic imaging , Adult , Aged , Aged, 80 and over , Cross-Over Studies , Echocardiography/adverse effects , Endocardium/diagnostic imaging , Evaluation Studies as Topic , Female , Heart Ventricles/diagnostic imaging , Humans , Infusions, Intravenous , Injections, Intravenous , Male , Middle Aged , Predictive Value of Tests , Time Factors
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