Diminished posttetanic potentiation in failing human myocardium

In heart failure a decreased function of SERCA2 has been demonstrated. The present study aimed at investigating the relation between sarcoplasmic reticulum-Ca²⁺-load (SR-Ca²⁺-load) and the activity of the SERCA2. SR-Ca²⁺ load was evaluated by measuring posttetanic potentiation (PTP) in human nonfailing (NF, n=10) and endstage failing myocardium (DCM, n=11). In addition, the effect of cyclopiazonic acid (CPA), a specific inhibitor of SERCA2, on PTP was studied in both NF and DCM. In crude membrane preparations from the same hearts the maximal SERCA2 activity was determined and correlated with the PTP. In failing myocardium the PTP was significantly reduced compared to nonfailing myocardium (13.7±0.75 mN/mm² vs. 17.1±1.55 mN/mm², p<0.05, ±SEM). When PTP was studied in the presence of increased extracellular Ca²⁺-concentrations, the difference between NF and DCM was further pronounced. CPA decreased PTP in both nonfailing and failing human tissue. The maximal SERCA2 activity was significantly reduced in failing myocardium (NF 267±18.5 nmol ATP/mg protein · min⁻¹ vs. DCM 191±13.4 nmol ATP/mg protein · min⁻¹, p<0.05, ± SEM). Correlation of the PTP and maximal SERCA2 activity revealed a close correlation between both parameters in NF and DCM. In summary, the presented results suggest that reduced SERCA2 activity in DCM influences posttetanic force potentiation probably through a reduced SR-Ca²⁺-load. Received: 30 July 1999 Returned for 1. revision: 9 September 1999 1. Revision received: 24 November 1999 Returned for 2. revision: 26 January 2000 2. Revision received: 26 April 2000 Accepted: 9 May 2000     

Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower levels of non-SHBG-bound testosterone in male newborns and healthy adult men

OBJECTIVE: It is generally accepted that SHBG decreases the bioavailability and activity of testosterone (T). In in vitro experiments increased levels of SHBG will be associated with decreased levels of non-SHBG bound testosterone (non-SHBG-T). However, in vivo SHBG can alter both production and clearance rates and thus plasma levels of T. DESIGN AND PATIENTS: In order to study the effect of SHBG on the levels of non-SHBG-T in vivo in the presence of an active hypothalamo-pituitary-gonadal (HPG) axis we conducted a cross sectional study in 400 healthy adult men with an age range of 40-80 years and in 106 newborn boys. MEASUREMENTS: In both groups, regression coefficients (beta) and partial correlation coefficients (r) were calculated for the relationship between SHBG and T or non-SHBG-T. Adult men were divided into age groups per decade (40-50 years, 51-60 years, 61-70 years and 71-80 years) to study possible differences in the impact of SHBG on the level of non-SHBG-T throughout ageing. RESULTS: Higher levels of SHBG were associated with higher levels of total testosterone in neonates (beta = 0.02 +/- 0.004, r = 0.44, P < 0.001) but not with non-SHBG-T (beta = -0.001 +/- 0.001, r = 0.05, P = 0.52). In adult men there was a significant age related increase in levels of SHBG and an age-related decrease of both total and non-SHBG-T. Higher SHBG was strongly associated with higher total testosterone in all age groups (beta = 0.26, 0.26, 0.26 and 0.23 for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively, P < 0.001 for all age groups). Higher SHBG was not or only slightly associated with higher non-SHBG-T beta = 0.02 (P = 0.32), beta = 0.04 (P = 0.03), beta = 0.04 (P = 0.02) and beta = 0.02 (P = 0.16) for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively. CONCLUSIONS: In contrast to general belief, SHBG levels barely influence levels of non-SHBG-bound testosterone both in male newborns and healthy adult men: the influence, if any, is positive. Consequently the age related increase of SHBG does not account for the age related decline in non-SHBG-T in healthy adult men.     

Results of anorectal manometry for the determination of age- and sex-dependent pressure differences

Manometric findings in 88 anorectal healthy probands are reported. Basal (PAC) and maximal squeeze (PAC max) pressures in the anal canal as well as rectal pressure at rest (PAR) and the pressure increase in the anal canal after dilatation of the ampulla recti (delta PAC) were registered with a 2 balloon catheter and statistically analysed in the 52 male and 36 female probands, divided in three age groups (group I under 40 years, group II 40-60 years and group III over 60 years). PAC showed for all three groups a statistically significant difference for men and women as well as a statistically significant decrease with age in both sex groups. PAC max, PAR and PAC decreased statistically significantly with age in both sex groups whereas in the three age groups, men and women showed nearly equal values. These age- and sex correlated differences in the anorectal pressure profile must be considered in the evaluation of the continence function.     

Value and limitations of Holter monitoring and electrophysiologic testing in the evaluation of the treatment of sustained monomorphic ventricular tachycardia

The authors studied the value and limitations of Holter monitoring and electrophysiological investigation in the evaluation of treatment of sustained monomorphic ventricular tachycardia (VT). One hundred and twenty-four consecutive patients were included in the study from January 1981 to February 1988. The etiologies were chronic myocardial infarction (N = 54), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31), and idiopathic VT (N = 15). All the tachycardias could be induced during baseline electrophysiological investigations and presented as complex ventricular arrhythmias on the Holter recordings. The investigations were repeated after treatment which was maintained irrespective of the results, unless the tachycardia which was induced or recorded was over 130 cycles/min and/or poorly tolerated. Recurrence was defined as the recording of VT in the absence of a change of treatment and/or the occurrence of sudden death. The follow-up period averaged 29 +/- 21 months. The Kaplan-Meier method was used to study the prevalence of absence of recurrence and survival rates. We observed 28 recurrences of VT and there were 21 deaths. Eighty-five per cent of patients had normal Holter monitoring after treatment. The prevalence of absence of recurrence was 0.751 when the Holter was normal and 0.485 when an arrhythmia was recorded (p = 0.03). The sensitivity was 25 per cent and the specificity 88 per cent. The survival rates were 0.66 and 0.585 respectively (p = 0.008). Fifty-three per cent of patients remained inducible after treatment with a prevalence of absence of recurrence of 0.572. This value rose to 0.877 when VT could not be induced (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epac signaling is required for hippocampus-dependent memory retrieval

Previously we uncovered a critical role for norepinephrine and β₁-adrenergic signaling in hippocampus-dependent memory retrieval. Because the β₁ receptor couples to G_s, we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cAMP and downstream signaling, we demonstrate that cAMP and two of its targets, protein kinase A (PKA) and exchange protein activated by cAMP (Epac), are both required for retrieval. These findings demonstrate that cAMP signaling through Epac (as well as PKA) plays an essential role in cognition.     

Safety of cardiac catheterization via peripheral vascular grafts

There are few data concerning the complications and technical difficulties encountered when cardiac catheterization is performed using peripheral bypass grafts for vascular access. All cardiac catheterizations performed at our institution from January 1, 1984 to April 1, 1991 were retrospectively reviewed to assess the in-hospital clinical outcomes in patients who had arterial access for catheterization achieved via prosthetic graft puncture. Seventeen procedures had percutaneous puncture of a vascular graft from a total of 2,929 arterial catheterizations performed. The interval from graft placement to catheterization was 7.5 ± 1.1 years. Arterial sheaths were employed in all cases and corresponded to the catheter size, with 5F systems used in 53% and 7F or larger systems used in the remaining patients. No intraprocedural or postprocedural complications were recognized. Technical difficulties were limited to the inability to selectively cannulate a nondominant right coronary artery in 1 patient. We conclude that percutaneous introduction of an arterial sheath and left heart catheterization via remotely implanted vascular bypass grafts is not associated with an increased risk of procedural complications or technical difficulties. © 1993 Wiley-Liss, Inc.