The feasibility of delivering cardiac brief intervention to patients following ST-elevation myocardial infarction: Protocol for a pilot randomised controlled trial.

BACKGROUND: Patients experience emotional distress and hold cardiac misconceptions following ST-elevation myocardial infarction. These issues informed the co-production of Cardiac Brief Intervention with patients and clinicians. The current study will establish a knowledge base for the feasibility of delivering this intervention to patients following ST-elevation myocardial infarction, with a preliminary exploration of impact on associated outcomes (ClinicalTrials.gov: NCT05848674). METHODS: A pilot randomised controlled trial incorporating a mixed-methods design will be conducted. Patients with ST-elevation myocardial infarction (number = 40) will be recruited from coronary care units at two hospital centres in Northern Ireland, with participants randomised (1:1) to the intervention or control group. Cardiac Brief Intervention constitutes a nurse-led, short (20 minutes) emotional and educational support discussion with a patient, with a leaflet that serves as a memory-aid. It will be delivered to the intervention group prior to discharge from a coronary care unit. The control group will receive standard care information. Data will be collected at baseline, post-intervention, 4 weeks from diagnosis, and 14 weeks from diagnosis. Feasibility measurements and process evaluation (quantitative and qualitative) will assess the viability of the research design and intervention delivery. Cardiac rehabilitation attendance data will be collected, and participants will complete questionnaires related to associated outcomes. Quantitative data will be reported with descriptive statistics and qualitative data will be analysed using framework analysis, with data integrated to achieve triangulation of findings. DISCUSSION: Educational and emotional difficulties following ST-elevation myocardial infarction may impede patient outcomes and cardiac rehabilitation participation. These issues informed the co-production of Cardiac Brief Intervention with patients and clinicians. This study will evaluate the feasibility of delivering Cardiac Brief Intervention to patients. These results will inform large-scale definitive testing of the intervention, which may lead to adoption in clinical practice to improve cardiac rehabilitation uptake and patient outcomes.

"No more couch-potato!" Patients' experiences of a pre-operative programme of cardiac rehabilitation for those awaiting coronary artery bypass surgery.

BACKGROUND: The waiting period for coronary artery bypass surgery is a difficult time for patients and families. Pre-operative cardiac rehabilitation may be safe and effective, but there is limited evidence regarding patients' experience and perceptions of such intervention. AIM: To describe patients' experiences of a pre-operative programme of cardiac rehabilitation developed specifically for those awaiting coronary artery bypass surgery. METHOD: A convenience sample of eight patients awaiting non-urgent surgery who had completed a 12 week pilot programme of cardiac rehabilitation were invited to be interviewed using a descriptive phenomenological approach. Domicillary interviews using an open technique were taped, transcribed and analysed using Colaizzi's framework. RESULTS: Participants described this programme as a useful means of improving exercise capacity and decreasing anxiety. Through the combination of exercise, advice and support participants stated that their initial fear that exercise would cause a heart attack was replaced with confidence, enabling them to become fitter and modify other risk factors. CONCLUSIONS: Findings of this study suggest that the programme was acceptable and perceived as beneficial by participants. Further research is required to evaluate the efficacy of pre-operative rehabilitation on risk factor modification.

Protection from lethal endotoxic shock after testosterone depletion is linked to chromosome X.

Men are considered more susceptible to sepsis after severe injury than are women, which has been attributed to a suppressing effect of male sex steroids on the inflammatory response. Moreover, the effect of sex steroids on the inflammatory process depends on the genetic background. The present study examined the genetic contribution to survival after endotoxic shock in mice depleted of testosterone by surgical castration. Six-week-old male mice, from strains A/J, AKR/J, C57BL/6J (B6), BALBc/J, DBA/2J, and C3H/HeN, were castrated (CX) or nonoperated (NoOp). Two weeks after surgery, mice were injected intraperitoneally with Escherichia coli lipopolysaccharide (15 mg/kg) and the frequency of mortality was monitored. CX A/J mice showed a significantly higher survival rate than NoOp mice, but this protective effect was not observed in the other strains. Administration of 5-alpha-dihydrotestosterone to CX A/J mice reverted the protection by CX. The protective effect of CX was also observed in crosses of female A/J and male B6 (AXB), but not female B6 and male A/J (BXA), suggesting that protection is linked to the A/J X chromosome. This possibility was corroborated by using consomic mice containing A/J chromosome X and the remaining chromosomes from B6. These results suggest that testosterone is a negative factor in the recovery from endotoxic shock, depending on the genetic background.

Design and synthesis of poly ADP-ribose polymerase-1 inhibitors. 2. Biological evaluation of aza-5[H]-phenanthridin-6-ones as potent, aqueous-soluble compounds for the treatment of ischemic injuries.

A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphthyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure-activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.

Accelerated recovery after endotoxic challenge in heat shock-pretreated mice.

The inflammatory response induced by bacterial lipopolysaccharide (LPS) has profound metabolic and physiological effects. Thus hepatic glucose production is depressed after LPS administration, which is, at least in part, due to the downregulation of phosphoenolpyruvate carboxykinase (PEPCK) expression. PEPCK is a key regulatory enzyme of the gluconeogenic pathway. Expression of heat shock proteins (hsps) is a well-conserved response to stress correlated with protection from subsequent insults including inflammation. In this study, the expression of PEPCK was observed to be preserved after injection of LPS in heat shock-pretreated mice. Protection of PEPCK expression was limited to the time after heat shock treatment that displayed hsp70. Comparison of the transcription rate and mRNA levels of PEPCK after LPS injection between mice that were heat shock pretreated or not indicated that the preservation of PEPCK expression was not due to initial protection from the LPS challenge. On the contrary, it was mediated by a rapid recovery after the LPS insult at the level of transcription. These observations suggest that the mechanism of heat shock-mediated protection (stress tolerance) after LPS challenge is due to an increase in the capacity of the organism to recover rather than deterrence from the insult.