Lidocaine and Nisoldipine Attenuate Almokalant-Induced Dispersion of Repolarization and Early Afterdepolarizations In Vitro

Attenuation of Almokalant-Induced Proarrhythmias In Vitro. Introduction: Treatment with Class III antiarrhythmic agents may lead to increased dispersion or repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na⁺ or Ca²⁺-blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro. Methods and Results: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent almokalant (0.1 μM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33%± 4.2%, n = 18) than in the VM (17%± 5.9%, n = 18. P < 0.05). In six of the preparations, addition of 1, 5, and 25 μM lidocaine reduced the almokalant-induced prolongation in a concentration-dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 μM lidocaine, the remaining prolongation was 7%± 12.2% (P < 0.05 vs time controls) in the PF and 14%± 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 μM nisoldipine did not reduce the almokalant-induced prolongation in the PF and VM, hut attenuated the spike-and-dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with almokalant (0.3 and 1 μM, respectively) at an API) of 828 ± 41.4 msec. In six separate preparations pretreated with lidocaine (5 μ) the almokalant-induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 μM) did not influence the response to almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear. Conclusion: At concentrations that did not affect the APD in the VM hut reduced the APD in the PE. lidocaine suppressed almokalant-induced dispersion and the development of EADs. Nisoldipine, (m the other hand, inhibited almokalant-induced EADs directly. Hence, (he primary APD-prolonging effect of a Class III agent may he preserved, but the risk of proarrhythmary reduced, during concomitant treatment with low concentrations of a Na⁺- or Ca²⁺ blocking agent.     

Autonomic Denervation After the Maze Procedure

LÖNNERHOLM, S., et al .: Autonomic Denervation After the Maze Procedure. The Maze III procedure is a surgical operation for curative treatment of AF. The procedure is extensive, however, with multiple incisions in both atria, and its effects on autonomic regulation of the heart rhythm are not known. This study comprises 17 patients, 10 with paroxysmal AF and 7 with chronic AF, who had no concurrent cardiac disease known to affect heart rate variability (HRV). A 24-hour Holter recording was performed preoperatively and 2 months (early) and 7 months (late) after surgery, for analysis of HRV in the time and frequency domains. Early after the Maze procedure all HRV components were markedly reduced compared to baseline (mean ± 1 SD): SDNN   73 ± 13   versus   148 ± 50   (ms), total power   168 ± 126   versus   560 ± 1567   (ms²), low frequency (LF) power   47 ± 67   versus   826 ± 677   (ms²), high frequency (HF) power   47 ± 40   versus   678 ± 666   (ms²), and LF:HF   1.22 ± 0.9   versus   2.55 ± 1.4   . Late after the Maze procedure all variables were still reduced. Only total power increased significantly between early and late follow-up (   168 ± 126   vs   496 ± 435   ms²). Late after Maze surgery, values of the different HRV components did not differ between the patients with paroxysmal AF and chronic AF. Early after the Maze procedure there is a marked decrease of all HRV components, which is maintained 7 months after surgery, a pattern consistent with denervation of the heart. (PACE 2003; 26[Pt. I]:587–592)     

Tissue concentration and release of substance P-like immunoreactivity in the dental pulp

The concentration of substance P-like immunoreactivity (SPLI) was determined in dental pulps from cat, dog and man by radioimmunoassay. Pulps from mature cats showed the highest SPLI-levels (mean 32 pmol/g); these are comparable to or higher than those found in any other organ outside the central nervous system. The SPLI concentrations were lower in pulp from immature teeth. The immunological and chromatographic behav behaviour of the pulpal SPLI from cat and man resembled that of synthetic substance P (SP), indicating that the assayed substance is closely related to or identical with SP. Release of pulpal SPLI in canine teeth ws evoked by stimulation of the inferior alveolar nerve in anaesthetized cats. In 9 of 16 experiments the amounts of SPLI found in pulp suprafusates following stimulation (4–31 fmol) were larger than those in unstimulated controls (0–7 fmol). Stimulation also reduced the pulpat tissue concentration of SPLI to 60% of that in homologous control pulps. The high concentration of SPLI found in the dental pulp and the demonstration of nerve-induced release strengthen the hypothesis that SP serves some function in the dental pulp.     

Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries

Objective. Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q⁵⁰⁶). To test the importance of the FV:Q⁵⁰⁶ mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years.
Design, setting and subjects. In a retrospective case-control study, the FV:Q⁵⁰⁶ mutation was investigated in 101 survivors of MI (79 men, 22 women) and in 101 healthy sex- and age-matched controls.
Main outcome measure. The prevalence of FV:Q⁵⁰⁶ mutation.
Results. The FV:Q⁵⁰⁶ mutation was found in 18% of patients versus 11% of controls ( P =0.16). The mutation was significantly more frequent amongst male patients than amongst controls (23 vs. 10%; P =0.03), the calculated odds ratio being 2.6 (95% CI, 1.1–6.4).
Conclusion. The high prevalence of the FV:Q⁵⁰⁶ mutation found amongst Swedish MI patients, especially amongst men, is noteworthy, and calls for further studies on the outcome of MI in APC-resistant patients. The prevalence of the FV:Q⁵⁰⁶ mutation in controls is higher than figures reported from other countries, suggesting that at least 10% of the Swedish population are carriers of a congenital prothrombotic disorder.     

Paradoxical Esterification of Plasma Cholesterol in Fish Eye Disease

ABSTRACT. Carlson LA, Holmquist L. (King Gustaf V Research Institute and Department of Internal Medicine, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden.) Paradoxical esterification of plasma cholesterol in fish eye disease. The activity of lecithin: cholesterol acyl transferase (LCAT), the enzyme which catalyses the esterification of human plasma cholesterol, has been measured by two independent methods in plasma from the two known living Swedish patients with fish eye disease. The enzyme activity was in both cases about 15% of that of normal plasma. Paradoxically, however, the percentage of plasma cholesterol which was esterified was almost normal in both patients. In addition, a normal spectrum of the fatty acids of the cholesteryl esters was present indicating a normal cholesterol esterification pathway in vivo. Incubation experiments in vitro of plasma from the two patients also yielded normal cholesterol esterification rates when measured by two different methods. These paradoxical results for cholesterol esterification are discussed on the basis of the present biochemical knowledge of fish eye disease and LCAT deficiency.     

Response from a disadvantaged, rural population to a subsidized dental program

abstract – The present report deals with the first part of an investigation concerning the dental treatment in a disadvantaged, rural population in Norway. A state-supported dental program was introduced, and the response of the recipients was recorded. In a community of 5,214 inhabitants (Nord-Odal) all persons (280) between 20–60 years of age receiving economic support under different welfare programs were sent a short questionnaire and an accompanying letter offering subsidized dental services. After a follow-up letter, remaining non-respondents were visited in their homes for collection of the questionnaires. Finally, completely or partially answered questionnaires totalled 265, representing 97 % of all recipients excluding 7 with residence outside the community. Of the respondents, 78 % agreed to participate in the program, 12 % refused, and 10 % were uncertain. In general, those who refused were most likely to be found in the oldest age group and among people with a minimum income. Persons wearing dentures in both jaws refused the program more frequently than did persons with 15 or more teeth. The most common reason for refusing participation was satisfaction with their present dental condition.