The Safety of Simultaneous Arterial and Coronary Sinus Perfusion: Experimental Background and Initial Clinical Results

Concern over myocardial damage from simultaneous arterial (antegrade) and coronary sinus (retrograde) perfusion has led to alternating between these delivery routes to maximize their individual benefits. Based upon predominant retrograde drainage via Thebesian veins, this study: (1) confirms experimentally the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports initial clinical application of this combined strategy in 155 consecutive patients. Experimental: Five mini-pigs (25 to 30 kg) underwent 1 hour of aortic clamping with simultaneous aortic and coronary sinus perfusion at 200 mUmin with normal blood (37°C) before and after 30 minutes of perfusion with either warm (37°C) or cold (4°C) blood cardioplegia. Coronary sinus pressure was always less than 30 mmHg. There was no right or left ventricular edema, lactate production, or lipid peroxidation as transmyocardial and myocardial conjugated dienes were unaltered, and postbypass recovered left ventricular end-systolic elastance (conductance catheter) and preload recruitable stroke work Index 101%± 3% and 109%± 90%, respectively. Clinical: Simultaneous arteriaVcoronary sinus perfusion was used in 155 consecutive high risk patients (New York Heart Association Class III to IV) undergoing isolated coronary artery bypass grafting (CABG) (n = 109) and CABG + valve replacementlrepair or aneurysm (n = 46). Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 ± 4 minutes (range 30 to 207), with 3.5 ± 0.1 grafts per patient; all anastomoses were performed with the aorta clamped. Cold intermittent blood cardioplegia was used for distal anastomoses and valve implantationhepair in 123 patients, and warm continuous blood cardioplegia was used in 32 patients. Following a warm cardioplegic reperfusate, all patients received warm non-cardioplegic blood perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic shock. There were three postoperative myocardial infarctions (2%), and six patients died (3.9% mortality). Conclusion: These experimental and clinical findings overcome perceived concerns about myocardial damage from simultaneous arterial and coronary sinus perfusion, and suggest this approach may add to the armamentarium of cardioprotective strategies. (J Card Surg 1994;9:15–25)     

Pharmacovigilance-related topics at the level of the International Conference on Harmonisation (ICH)

Marketing authorisations for medicines need to be based on the universal criteria quality, safety and efficacy, whilst taking into account local public health needs. With view to using resources efficiently and avoiding delay in access to medicines, scientific standards for investigating quality, safety and efficacy should be universal too. A major step to achieve this was taken in 1990 when the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was established between authorities and industry in the European Union (EU), Japan and the United States. Since then more than 50 ICH Guidelines have been published, out of which six are specific to pharmacovigilance. They refer to management and expedited reporting of individual adverse drug reaction (ADR) cases, including electronic formats, periodic reporting of worldwide data and planning of pharmacovigilance. Their development has to be seen in the context of initiatives taken in the three ICH Regions to strengthen pharmacovigilance. Most recently this involves making use of risk management concepts, reflecting new thinking of proactivity in pharmacovigilance. Moreover, consideration is given to regional and international cooperation beyond the ICH Regions.     

The effects of dopamine agonists on prepulse inhibition in healthy men depend on baseline PPI values

Rationale and objectives Dopamine (DA) agonists reliably disrupt prepulse inhibition (PPI) of the startle reflex in animals but less so in humans despite cross-species similarities in the neural regulation of PPI. This study examines whether individual variation in baseline PPI may account for the inconsistencies in DA agonist-induced PPI disruption in humans. Methods Baseline PPI measures were obtained from 32 healthy adult men. Subjects were subsequently tested in three sessions after ingestion of placebo or active drug in a balanced double-blind design. Seventeen subjects were given 0.05 and 0.1 mg of pergolide (a direct DA agonist) and 15 subjects were given 100 and 200 mg of amantadine (an indirect DA agonist). In each treatment group, subjects were assigned to “high” and “low” PPI subgroups based on the median split of their baseline PPI. Results Amantadine and pergolide disrupted PPI in high- but not in low-PPI subjects. In contrast, low-PPI subjects showed a trend towards PPI facilitation especially with pergolide. Conclusions Our results suggest that baseline PPI is an important determinant of the effect of DA agonists on PPI.     

Friedreich ataxia: from genes to therapies?

Most cases are caused by a single mutation, paving the way for therapeutic advances for this fatal disease.     

Catastrophic antiphospholipid syndrome in a 14-year-old child

Antiphospholipid syndrome (APS) is an autoimmune disease. Less than 1% of patients with APS present with life-threatening catastrophic APS (CAPS). We report here a case of CAPS in a young girl with cardiac, gastrointestinal and renal involvement. Although the management was complicated, the outcome was better than expected. We suggest that CAPS be included in the differential diagnosis of acute renal failure in children with multi-organ involvement and prolonged phospholipid-dependent coagulation time and promptly treated with immunomodulating agents and anticoagulants.     

Amino-terminal pro-brain natriuretic peptide predicts ventricular arrhythmogenesis in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators

STUDY OBJECTIVES: Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs). DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction < 35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria. INTERVENTIONS: Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit. MEASUREMENTS AND RESULTS: During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events. CONCLUSION: To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.     

Group crisis intervention for children during ongoing war conflict

The aim of this study was to evaluate the short-term impact of a group crisis intervention for children aged 9-15 years from five refugee camps in the Gaza Strip during ongoing war conflict. Children were selected if they reported moderate to severe posttraumatic stress reactions, and were allocated to group intervention (N=47) encouraging expression of experiences and emotions through storytelling, drawing, free play and role-play; education about symptoms (N=22); or no intervention (N=42). Children completed the CPTSD-RI and the CDI pre- and post-intervention. No significant impact of the group intervention was established on children's posttraumatic or depressive symptoms. Possible explanations of the findings are discussed, including the continuing exposure to trauma and the non-active nature of the intervention.     

Surgical and radiological management of uterine fibroids--a UK survey of current consultant practice

BACKGROUND: The aim of this study was to determine the current surgical and radiological management of uterine fibroids by consultants working in the UK. METHODS: A structured questionnaire was posted to all 1439 UK consultants. Non-responders were sent one reminder. The main outcome measures were surgical route and technique used for myomectomy, and the use and availability of uterine artery embolization (UAE). RESULTS: Eight hundred fifty-two (59%) consultants replied. Seven hundred thirty-five (86%) admitted to regular sessions of gynecologic surgery, and 75% of this group performed open myomectomy, 16% laparoscopic myomectomy, and 66% hysteroscopic myomectomy. Open myomectomy: Forty-one percent of consultants performed open surgery on uteri equivalent to 12-week gestational age or less, 87% prescribed preoperative gonadotrophin-releasing hormone agonists (GnRHa) in order to reduce surgical bleeding, with 35% using myomectomy clamps, 23% tourniquets, and 19% vasoconstrictors. Laparoscopic myomectomy: The largest uterine size the majority would attempt was equivalent to a 12-week gestation, 58.6% used preoperative GnRHa, 21% used intraoperative vasoconstrictors, and 1.4% tourniquets in order to minimize bleeding. Hysteroscopic myomectomy: As with laparoscopic myomectomy, the largest uterine size the majority would attempt was equivalent to a 12-week pregnancy. Blood transfusion: Twenty per cent, 10%, and 7% reported the need for blood transfusion in up to 10% of patients undergoing open, laparoscopic, or hysteroscopic myomectomy, respectively. UAE: Fifty-one percent have access to UAE and 40% have referred at least one patient in 2001. CONCLUSIONS: Open and hysteroscopic myomectomy are frequently utilized in contrast to laparoscopic myomectomy. The reported rate of blood transfusion appears low. Although UAE is widely available, the majority of patients are still managed surgically.