Decreased sensitivity of neonatal rabbit sarcoplasmic reticulum to anthracycline cardiotoxicity.

Anthracyclines are useful chemotherapeutic agents whose utility is limited by the development of irreversible cardiotoxicity. When tested, the pediatric population demonstrates an increased sensitivity to the cardiotoxicity of this class of agents, although the reasons for this increased sensitivity are unclear. The sarcoplasmic reticulum (SR) is a target for anthracycline cardiotoxicity in adults, but the effects of anthracycline on the SR in developing myocardium have not been examined.

Doxorubicin and C-13 deoxydoxorubicin effects on ryanodine receptor gene expression.

Chronic anthracycline administration to rabbits causes impairment of cardiac contractility and decreased gene expression of the calcium-induced calcium release channel of sarcoplasmic reticulum (SR), the ryanodine receptor (RYR2). The C-13 hydroxy metabolite (doxorubicinol), formed in the heart, has been hypothesized to contribute to anthracycline cardiotoxicity. C-13 deoxydoxorubicin is an analog unable to form the C-13 hydroxy metabolite.

Sarcoplasmic reticulum calcium release is stimulated and inhibited by daunorubicin and daunorubicinol.

Cardiac effects of anthracyclines or their metabolites may include both the stimulation and inhibition of Ca(2+) release from sarcoplasmic reticulum. In this study, the ability of daunorubicin and its primary metabolite, daunorubicinol, to stimulate and inhibit Ca(2+) release from canine sarcoplasmic reticulum (SR) vesicles was investigated. It was observed that both daunorubicin and daunorubicinol were several fold more potent at inhibiting than they were at stimulating SR Ca(2+) release.

Daunorubicin cardiotoxicity: evidence for the importance of the quinone moiety in a free-radical-independent mechanism.

Anthracyclines, such as daunorubicin (Daun), and other quinone-containing compounds can stimulate the formation of toxic free radicals. The present study tests the hypothesis that the quinone moiety of Daun, by increasing free-radical production, disrupts sarcoplasmic reticulum (SR) function and thereby inhibits myocardial contractility in vitro. We compared Daun with its quinone-deficient analogue, 5-iminodaunorubicin (5-ID), using experimental interventions to produce various contractile states that depend on SR function.

Transcutaneous PCO2 monitoring during laparoscopic cholecystectomy in pregnancy.

Purpose: Respiratory acidosis during carbon dioxide (CO2) insufflation has been suggested as a cause of spontaneous abortion and preterm labour following laparoscopic cholecystectomy during pregnancy. Capnography may not be adequate as a guide to adjust pulmonary ventilation during laparoscopic surgery and hence arterial carbon dioxide (PaCO2) monitoring has been recommended. We report the feasibility and benefits of transcutaneous carbon dioxide monitoring (PtcCO2) as an approach to optimise ventilation during laparoscopic surgery in pregnancy.

Labour pain management in a parturient with an implanted intrathecal pump.

Purpose: We report the peripartum anaesthetic management for vaginal delivery of a chronic pain patient with an implanted intrathecal pump. This is the first report describing labour analgesia in a patient with such a device. As intrathecal systems become more popular for the management of nonmalignant pain, this situation is likely to be encountered with increasing frequency in the future.

Anaesthesia in Barbados.

Purpose: To describe the anaesthesia services in Barbados: to present the major challenges confronting the Anaesthesia Department of the government-owned Queen Elizabeth Hospital (QEH): and to describe the Department's approaches to optimise safety and cost-effectiveness of anaesthesia at QEH.

Source Of Information: Authors (KBS, HSLM, RAH), who collectively provided more than 50 yr of anaesthesia at QEH; the Dean (ERW) of the University of West Indies Medical School (Barbados campus); archives of Barbados; and records of QEH.

Principal Findings: The government of Barbados provides modern health care services to all of its citizens, primarily at QEH.

Negative pressure induced airway and pulmonary injury.

Purpose: To describe negative pressure injury occurring during the use of a laryngeal mask airway (LMA) in which airway bleeding rather than pulmonary oedema was the major complication.

Clinical Features: A patient presented to the day surgery unit for resection of a ganglion cyst on her right wrist. She underwent general anaesthesia using an LMA, and experienced severe laryngospasm and transient hypoxaemia (oxygen saturation to 66%) seven minutes after incision.

Aging increases the cardiotoxicity of daunorubicin and daunorubicinol in the rat.

This study examined effects of aging on the cardiac response in vitro to daunorubicin, a cancer chemotherapeutic agent that causes cardiotoxicity. Left ventricular trabeculae carneae from adult (aged 6-9 months) and old (aged 24-28 months) Fischer 344 rats were placed in oxygenated, physiological buffer. Preparations were treated with daunorubicin (175 microM) or saline (controls) over a 210-minute study period.

Time-related increases in cardiac concentrations of doxorubicinol could interact with doxorubicin to depress myocardial contractile function.

1. The present study evaluated the time-dependency of acute anthracycline cardiotoxicity by varying the duration of exposure of rabbit isolated atria to doxorubicin and determining changes (1) in contraction and relaxation and (2) in atrial concentrations of doxorubicin and its C-13 hydroxy metabolite, doxorubicinol. 2.

Daunorubicin-induced cardiac injury in the rabbit: a role for daunorubicinol?

This study evaluated potential contributions of daunorubicin and its principle metabolite, daunorubicinol, to the cardiotoxicity of daunorubicin therapy. Daunorubicin (15 mg/kg) or placebo (normal saline) was administered by iv bolus to New Zealand white rabbits and 3 to 4 days later, hearts were removed to measure contractility (dF/dt), concentrations of daunorubicin and daunorubicinol, and evidence of oxidative stress on glutathione and glutathione peroxidase. Contractile function of isolated atria and papillary muscles was depressed (p < 0.

Aging alters the force-frequency relationship and toxicity of oxidative stress in rabbit heart.

Adult (6 months) and senescent (greater than 5 years) rabbit atria were studied under conditions known to increase cytoplasmic calcium (increased frequency of contraction and oxidative stress). At a contraction frequency of 1/sec, cardiac relaxation (90% relaxation time) was similar in senescent and adult atria but at a frequency of 2 or 3/sec, relaxation was significantly slower in senescent preparations (P less than 0.05).

Doxorubicin cardiotoxicity: analysis of prevailing hypotheses.

Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents that produce a well-described but incompletely understood cardiac toxicity. According to a popular hypothesis, anthracyclines injure the heart by generating oxygen-centered free radicals. This free radical hypothesis, however, appears to be inconsistent with many observations, such as the frequent failure of anthracyclines at cardiotoxic doses to produce evidence of increased free radical generation.

Reversal of bupivacaine epidural anesthesia by intermittent epidural injections of crystalloid solutions.

This study was designed to determine whether epidural motor blockade could be reversed by postoperative injections of crystalloid solutions via the epidural catheter. Twenty-seven patients (ASA physical status I, nonlaboring) had epidural anesthesia with 0.75% bupivacaine for elective cesarean delivery.

Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial.

Forty postpartum patients with postdural puncture headache (PDPH) were randomly assigned to receive oral caffeine (300 mg) or a placebo. Intensity of headache, quantitated using a visual analogue pain scale (VAS), was assessed immediately before drug administration and 4 and 24 h later. Relief of PDPH measured as delta VAS (initial VAS - VAS at 4 h) was significantly better in the caffeine than in the placebo group (P = 0.

Monitored anesthesia care for dental implant surgery: analysis of effectiveness and complications.

The optimal method of providing safe and effective sedation for outpatients undergoing lengthy dental operations is unclear. We provided monitored anesthesia care (conscious sedation) for 102 consecutive dental implant procedures, using intravenous midazolam and fentanyl as primary pharmacologic agents. Midazolam was administered by multiple, intermittent injection or via continuous infusion.