Intracellular calcium mishandling leads to cardiac dysfunction and ventricular arrhythmias in a mouse model of propionic acidemia.

Propionic acidemia (PA) is a rare metabolic disease associated with mutations in genes encoding the α and ß subunits of the enzyme propionyl-CoA carboxylase. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species production and oxidative damage, which have been associated with the disease pathophysiology. Clinical symptoms are heterogeneous and include cardiac complications, mainly cardiac dysfunction and arrhythmias, which are recognized as one of the major life-threatening manifestations in patients. We aimed to investigate the molecular mechanisms underlying the cardiac phenotype using a hypomorphic mouse model (Pcca-/-(A138T)) that recapitulates some biochemical and clinical characteristics of PA. We demonstrate that Pcca-/-(A138T) mice present with depressed cardiac function along with impaired cell contractility when compared to the wild-type mice. Cardiac dysfunction in Pcca-/-(A138T) mice was associated with lower systolic Ca2+ release ([Ca2+]i transients), impairment in the sarcoplasmic reticulum (SR) Ca2+ load and decreased Ca2+ re-uptake by SR-Ca2+ ATPase (SERCA2a). These functional changes correlated well with the depressed activity of SERCA2a, the elevated ROS levels and SERCA2a oxidation rate in cardiomyocytes isolated from Pcca-/-(A138T) mice. In addition, decreased SR-Ca2+ load in Pcca-/-(A138T) cardiomyocytes was associated with increased diastolic Ca2+ release. The increase in Ca2+ sparks, Ca2+ waves and spontaneous [Ca2+]i transients in Pcca-/-(A138T) cardiomyocytes could be responsible for the induction of ventricular arrhythmias detected in these mice. Overall, our results uncover the role of impaired Ca2+ handling in arrhythmias and cardiac dysfunction in PA, and identify new targets for the development of therapeutic approaches for this devastating metabolic disease.

[Pulmonary edema related to administration of 15-methyl-prostaglandin F2alpha during a cesarean section]. / Edema pulmonar en una cesárea relacionado con la administración de 15-metil prostaglandina F2alpha.

An 18-year-old woman pregnant at 37 weeks gestation and with a history of recurrent urinary tract infection was admitted with a clinical picture of pyelonephritis that responded favorably to antibiotic treatment. After 2 days, cervical ripening was induced with prostaglandin E2 gel and labor was induced with oxytocin. The patient requested epidural analgesia. Six hours after induction, cesarean delivery was indicated owing to risk of fetal distress. The operation was carried out under epidural anesthesia with 10 mL of 0.5% bupivacaine without a vasoconstrictor. After delivery, uterine atony was treated unsuccessfully with oxytocin and methylergometrine maleate; the obstetrician then gave an intramyometrial injection of 0.25 mg of 15-methyl-prostaglandin F2alpha (PGF2alpha). After 5 minutes, SpO2 fell to 89%, accompanied by dyspnea and sinus tachycardia of 130-140 beats/min, with normal cardiorespiratory sounds. The patient was transferred to the postoperative recovery unit, where a chest radiograph led to a diagnosis of acute pulmonary edema. Treatment to reduce edema was successful. PGF2alpha and its analogs are useful for treating uterine atony that does not respond to other drugs, but side effects are not unknown. Caution in prescribing PGF2alpha and care in monitoring the patient's reaction are therefore recommended during and after anesthesia. Unnecessary overhydration should be avoided.

[Evoked potentials and psychometric tests in the diagnosis of subclinical neurological damage in a group of workers exposed to low concentrations of mercury vapor]. / Potenciales evocados y test psicométricos en el diagnóstico de daño neurológico subclínico de un grupo de trabajadores expuestos a bajas concentraciones de vapores de mercurio.

We study the effects of low concentrations of mercury vapour on the nervous system of a group of eleven workers of a chloroalkali plant exposed to it. Twenty-three non-exposed workers in the same factory were used as control group. We used clinical and analytic explorations, psychometric tests and evoked potentials to evaluate the subjects. The average Hg in urine of the exposed group was 41.74 micrograms/gr creatinine and the average of the non-exposed group as 9.71 mu/yr. In the exposed group the evoked potentials have found a slowing-down of conduction in all the nervous paths studied (optical, auditive and somatosensory) and in the latency of P300 wave, although this was not statistically significant compared to the control group. Of the psychometric test used, only Rey's Complex Figure Test showed deterioration in the visual memory subtest of the exposed group (p < 0.05) compared to the control group, although in Wechsler's digit span test lower scores were obtained which were close to being statistically significant comparing the averages of the two groups (0.05 < p < 0.051). Bearing in mind these results we think that the amounts of Hg in urine and TLV-TWA (50 micrograms/gr creatinine and 50 micrograms/m3 respectively) accepted by most authors as innocuous should be reduced.