One-year follow up of cardiac anxiety after a myocardial infarction: a latent class analysis.

INTRODUCTION: Longitudinal elevated depressive symptom scores are associated with a less favorable cardiac outcome. Although anxiety has received less attention, meta-analysis suggests that high baseline levels of general anxiety might worsen cardiac outcome. The objective of this study was to explore the longitudinal course of cardiac anxiety after a myocardial infarction (MI). METHODS: The Cardiac Anxiety Questionnaire (CAQ) was administered to 194 patients hospitalized for MI after admission, and one, three, six and twelve months after discharge. Latent class growth analysis (LCGA) was performed to identify groups based on cardiac anxiety course. Between group differences were checked on relevant socio-demographic, cardiac and psychiatric variables. RESULTS: LCGA identified three groups with stable CAQ levels over time, indicative of high (7.7%), intermediate (45.4%) and low (30.4%) levels of cardiac anxiety, respectively. A fourth group (16.5%) reported high levels of cardiac anxiety that decreased over time. Between group differences were of particular interest for the two subgroups that started high in cardiac anxiety, since these may differentiate patients with spontaneous remission from those who might be in need of treatment. Patients in whom cardiac anxiety persisted were less often employed, had more diabetes mellitus, a history of acute coronary syndrome, depressive symptoms, anxiety and avoidance at baseline and a lower quality of life at follow-up. CONCLUSION: This first study addressing cardiac anxiety after an MI identified four trajectories. Future studies should focus on cardiac outcome and treatment strategies for cardiac anxiety in the subgroup with persistent high anxiety levels.

Cellular and subcellular studies of the biotransformation of hexamethylmelamine in rat isolated hepatocytes and intestinal epithelial cells.

The antitumor agent hexamethylmelamine is subject to oxidative metabolic conversion in rat isolated liver and small intestinal cells (conversion 40 times higher in hepatocytes). This N-demethylation is mediated by cytochrome P-450 in the microsomal fractions, and in mitochondrial preparations it has been found to occur via N- methylolpentamethylmelamine . Somehow, pentamethylmelamine, hydroxymethylpentamethylmelamine , or an intermediary metabolite becomes trapped in the intact cell, but the nature of the adduct formed is still unresolved. Pretreatment of rats with 3-methylcholanthrene p.o. caused a 5-fold increase in hexamethylmelamine turnover. Phorone administered in vivo prior to cell preparation (liver and gut) caused an increase in pentamethylmelamine production. The latter results together with results of adding glutathione to cell incubations demonstrate that glutathione contributes to the regulation of cytochrome P-450-mediated N-demethylation of hexamethylmelamine.

Rapid formation of N-hydroxymethylpentamethylmelamine by mitochondria from rat small intestinal epithelium.

Isolated rat intestinal mitochondria showed a considerable capacity to convert hexamethylmelamine to its monodemethylated metabolite pentamethylmelamine. Mitochondrial turnover rate is about the same as compared with microsomal preparations. Only in mitochondrial incubations N-hydroxymethylpentamethylmelamine could be identified as a metabolic intermediate. The known chemical reactivity of carbinolamines means that this activation pathway in mitochondria could be involved in the pharmacological or toxic effects of hexamethylmelamine.

Low oral bioavailability of hexamethylmelamine in the rat due to simultaneous hepatic and intestinal metabolism.

The disposition of both hexamethylmelamine (HMM) after intraarterial, i.v., portal vein, and intraduodenal administration and of pentamethylmelamine following its i.v. administration was studied in male Wistar rats. HMM (5 and 10 mg/kg) and pentamethylmelamine (5 mg/kg) were infused via implanted cannulas into conscious animals (n greater than or equal to 4). Plasma levels of parent compound and of metabolites were determined by gas chromatography. The areas under the plasma concentration-time curves of HMM following its intraarterial and i.v. administration were not significantly different, indicating that HMM was not appreciably metabolized in the lung. Areas under plasma-concentration-time curves of HMM following portal vein and intraduodenal administration were 27 and 8% of the area under the plasma concentration-time curve after i.v. administration, respectively. Absorption of HMM was complete as judged from metabolite data. The reduced bioavailability of HMM intraduodenally was thus a consequence of presystemic elimination in the liver and the gut wall. Extraction ratios (or first-pass effects) of the liver and the gut wall were 73 and 71%, respectively. Linear kinetic behavior of HMM i.v. was observed in the 5- to 10-mg/kg dose range. Extensive gut wall metabolism may have important implications for the antitumor activity mechanism of HMM.