Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: increase in gradient after exercise.

To define alterations in the magnitude of the left ventricular outflow tract gradient during supine exercise, 10 patients with hypertrophic obstructive cardiomyopathy were studied under basal conditions and during exercise and recovery with simultaneous invasive hemodynamic measurements, particularly of the peak to peak systolic pressure gradient across the left ventricular outflow tract. Basal outflow pressure gradient ranged from 0 to 89 mm Hg (average 37.4 +/- 9.6). No increase was observed during 5 min of exercise (average 29.6 +/- 10 mm Hg, range 0 to 91; p = NS), even though arterial blood pressure, heart rate and cardiac index increased significantly in association with a decrease in peripheral vascular resistance. However, a rapid and highly significant increase in left ventricular outflow gradient occurred after exercise was completed (average 83.5 +/- 11.4 mm Hg, range 10 to 130; p less than 0.001), while arterial blood pressure, heart rate and cardiac index closely approached basal levels and total peripheral vascular resistance increased. In contrast to previous assumptions regarding the behavior of the outflow gradient in hypertrophic cardiomyopathy, obstruction to left ventricular outflow increases after rather than during supine exercise. Rapid changes in preload during recovery represent the most likely explanation for the postexercise development of outflow obstruction. New considerations regarding the mechanisms of sudden cardiac death and the therapeutic approach in patients with hypertrophic cardiomyopathy may result from this pathophysiologic observation.     

Effect of transcoronary ablation of septal hypertrophy on clinical outcome in hypertrophic obstructive cardiomyopathy associated with atrial fibrillation

Summary Background Relatively few reports on the clinical impact of atrial fibrillation (AF) in hypertrophic obstructive cardiomyopathy (HOCM) are available. The aims of our study are to report the effect of transcoronary ablation of septal hypertrophy (TASH) on clinical outcome in HOCM associated with AF and to evaluate the influence of AF on symptoms and quality of life in HOCM. Patient and methods In 80 consecutive patients (38 f, mean age 56 ± 17 years) with severely symptomatic HOCM referred for interventional treatment, we analyzed the prevalence of AF based on 240 Holter ECG recordings and patients’ history, retrospectively. Symptoms, quality of life, number of hospital admissions and hemodynamic performance were obtained in all patients before and after TASH. Mortality was additionally investigated by letter and telephone contact. Results The overall prevalence of AF was 29%. Paroxysmal AF was detected in 17 pts (21.3%), persistent AF in 5 pts (6.3%). Only 1 pt (1.3%) suffered from permanent AF. Symptoms due to AF were present in 52.6% of the AF patients. Quality of life score was markedly improved after TASH (15.9 ± 3.8 vs. 20.7 ± 3.8, p < 0.001) with no difference between sinus rhythm and atrial fibrillation. However, hospital admissions were more frequent in the AF group (0.85 ± 1.84 vs. 0.28 ± 0.81, p = 0.03) in 32 ± 13 months. AF patients suffered more often from syncope before TASH (30 ± 70% vs. 10 ± 30%, p = 0.008). Two patients with sinus rhythm at baseline died after 32 ± 13 months from cardiovascular cause. Conclusions Atrial fibrillation is the major cardiac arrhythmia in severe HOCM. The majority of AF patients demonstrate AF specific symptoms. The paroxysmal type of atrial fibrillation dominates by far. Both patients with and without atrial fibrillation showed similar quality of life with marked improvement after TASH.     

Gestational stress induces persistent depressive‐like behavior and structural modifications within the postpartum nucleus accumbens

Postpartum depression (PPD) is a common complication following childbirth experienced by one in every five new mothers. Pregnancy stress enhances vulnerability to PPD and has also been shown to increase depressive‐like behavior in postpartum rats. Thus, gestational stress may be an important translational risk factor that can be used to investigate the neurobiological mechanisms underlying PPD. Here we examined the effects of gestational stress on depressive‐like behavior during the early/mid and late postpartum periods and evaluated whether this was accompanied by altered structural plasticity in the nucleus accumbens (NAc), a brain region that has been linked to PPD. We show that early/mid (postpartum day 8) postpartum female rats exhibited more depressive‐like behavior in the forced swim test as compared with late postpartum females (postpartum day 22). However, 2 weeks of restraint stress during pregnancy increased depressive‐like behavior regardless of postpartum timepoint. In addition, dendritic length, branching and spine density on medium spiny neurons in the NAc shell were diminished in postpartum rats that experienced gestational stress although stress‐induced reductions in spine density were evident only in early/mid postpartum females. In the NAc core, structural plasticity was not affected by gestational stress but late postpartum females exhibited lower spine density and reduced dendritic length. Overall, these data not only demonstrate structural changes in the NAc across the postpartum period, they also show that postpartum depressive‐like behavior following exposure to gestational stress is associated with compromised structural plasticity in the NAc and thus may provide insight into the neural changes that could contribute to PPD.     

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Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice

Recent evidence suggests mitochondrial dysfunction as a common early pathomechanism in Alzheimer's disease integrating genetic factors related to enhanced amyloid-beta (Ass) production and tau-hyperphosphorylation with aging, as the most relevant sporadic risk factor. To further clarify the synergistic effects of aging and Ass pathology, we used isolated mitochondria of double Swedish and London mutant APP transgenic mice and of non-tg littermates. Pronounced mitochondrial dysfunction in adult Thy-1 APP mice, such as a drop of mitochondrial membrane potential and reduced ATP-levels already appeared at 3 months when elevated intracellular but not extracellular Ass deposits are present. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species, an altered Bcl-xL/Bax ratio and reduction of COX IV activity. We observed significant decreases in state 3 respiration and FCCP-uncoupled respiration in non-tg mice after treatment with extracellular Ass. Similar deficits were seen only in aged Thy-1 APP mice, probably due to compensation within the respiratory chain in young animals. We conclude that Ass dependent mitochondrial dysfunction starts already at 3 months in this AD model before extracellular deposition of Ass and progression accelerates substantially with aging.     

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