Action potential duration (APD) in rabbit ventricular myocardium shortens after a rest period (postrest shortening). However, the effects of preceding stimulus frequency on the postrest shortening have not been elucidated. We recorded transmembrane action potentials (TAPs) and monophasic action potentials (MAPs) from the rabbit ventricle. In in vitro experiments, repetitive regular stimuli (S1) at cycle lengths ranging between 500 to 3000 ms were followed by a single extrastimulus (S2) at a coupling interval of 5000 ms. A decrease in S1S1 interval resulted in a progressive shortening of the duration of TAP (TAPD) elicited by S2 (S2-TAPD), which was potentiated by increasing extracellular calcium concentration ([Ca2+] o) or application of ouabain and was inhibited by lowering [Ca 2+]o or verapamil. Application of ryanodine was most effective in lengthening S2-TAPD following a short S1S1 interval. 4-aminopyridine and E4031 caused marked lengthening of S2-TAPD when S1S1 was long. However, the lengthening effect was attenuated and disappeared with a shorter S1S1 interval. In in vivo experiments, regular ventricular pacing (S1) at cycle lengths ranging between 250 to 1000 ms was followed by a single extrastimulus (S2) with a coupling interval (S1S2) of 1500 ms. A decrease in the S1S1 interval also resulted in progressive shortening of the duration of MAP elicited by S2. Our results indicate that the postrest shortening is potentiated by an increase in the preceding stimulus frequency in the rabbit ventricle, in which the function of sarcoplasmic reticulum may play a significant role.
INTRODUCTION Most of the symptoms in hyperthyroidism, such as an augmented metabolism, tachyarrhythmias and increased myocardial contractility, resemble those of increased sympathetic beta-adrenergic receptor are a major concern, but the exact mechanisms of the effects remain to be clarified. In the present study, the direct effects of triiodothyronine(T3) on the spontaneous beating and beta-receptor in relation to protein synthesis of the cultured ventricular myocytes were investigated. METHODS The cardiac myocytes were prepared from neonatal rat ventricle by enzymatic digestion and incubated at 37 degrees C in the atmosphere of 5% CO2 in air. The culture medium used was DME containing 5% fetal bovine serum and was renewed daily. The spontaneous beating frequencies of the myocytes were measured by the use of optical-video system. The cultured myocytes showed spontaneous beating dependent on Ca2+ concentration about 48 hours after the isolation. Although the beating was irregular and unstable at the beginning, it became regular and steady on the 3rd culture day. The experiments measuring spontaneous beating frequency were performed using the cells of this stage. In these experiments, the effects of T3 on the spontaneous beating frequency were studied after a 15-20 minute incubation with various concentrations of T3 (1 x 10(-10)-1 x 10(-7)M). The spontaneous beating was enhanced by isoproterenol and suppressed by Ca antagonists. The cardiac beta-receptors were identified using the hydrophilic radioligand 3H-CGP-12177 which labels specifically cell surface bound beta-receptors. The effects of T3 on protein synthesis in cultured myocytes were studied by measuring 3H-leucine uptake. RESULTS I. The effects of T3 on the spontaneous beating The effects of T3 on the spontaneous beating were investigated in two different ways. Firstly, the direct effect of T3 was studied by incubating the cells in the medium containing variable concentration of T3. T3 increased the beating frequency dose-dependently, and the maximal accelerating action was observed at the concentration of 10(-8)M. T3 at this concentration increased the spontaneous beating frequency from 131 +/- 25 min to 157 +/- 35 min after the treatment. Higher concentration of T3 induced arrhythmias and seemed to be toxic. Therefore, in the following experiments the concentration of 10(-8)M was used. The cardiac myocytes were incubated in either T3 containing or T3 free medium for 10 days. The incubation medium was renewed every day, and the change in the beating frequency was monitored continuously.(ABSTRACT TRUNCATED AT 400 WORDS)
The mechanisms of sustained ventricular tachycardia (VT) induced by large cumulative dose of cesium chloride (Cs) remains unclear. Seven anesthetized rabbits were intravenously injected with Cs (1 mmol/kg) 3 times at 20-min intervals. The surface ECG and monophasic action potential of the left ventricular endocardium were simultaneously recorded. In another 12 rabbits, transmembrane action potentials of right ventricular muscles were recorded with glass microelectrodes. In experiments in vivo, sustained monomorphic VT was induced after the third injection of Cs, whereas the early afterdepolarization (EAD)-related nonsustained polymorphic VT was induced after the second injection. Overdrive pacing during the sustained VT resulted in postdrive acceleration. The pacing and recovery cycle lengths showed an inverse relation. In experiments in vitro, preparations were superfused with Tyrode's solution containing 7.5 mM Cs. Cs initially induced EADs. Additional exposure to Cs depolarized the membrane potential, which consequently attained threshold, producing spontaneous activities. Further exposure resulted in an induction of sustained rhythms that were accelerated by overdrive pacing. Our results indicate that the sustained rhythms at low membrane potential induced by a long exposure to Cs in vitro may underlie an electrophysiologic mechanism for the sustained VT induced after large cumulative dose of Cs in vivo.
The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients.The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis.The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index.Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.
Previous evidence has shown that the action potential duration of rabbit ventricular muscle cells shortens after a rest period (postrest shortening). However, there has not been much research on postrest shortening in the intact heart. We recorded transmembrane action potentials (TAPs) of isolated papillary muscle from rabbit ventricle with glass microelectrodes and monophasic action potentials (MAPs) of the rabbit left ventricular endocardium with contact electrodes. In the in vitro experiments, repetitive regular stimuli (S1) at a cycle length of 1 sec were followed by a single extrastimulus (S2) at coupling intervals (S1S2) ranging between 0.5 sec and 8 sec. The increase in the S1S2 interval resulted in a progressive shortening of the duration of TAP elicited by the S2, which was abolished by the simultaneous application of 1 mmol/L 4-aminopyridine and 2 micromol/L ryanodine. In the in vivo experiments, regular right ventricular pacing (S1) at a cycle length of 0.35 sec was followed by a single extrastimulus (S2) with coupling intervals (S1S2) ranging between 0.25 sec and 3 sec. The increase in the S1S2 interval also resulted in a progressive shortening of the duration of MAP elicited by the S2. This is the first report to demonstrate postrest shortening in the intact heart, which probably occurs because of a mechanism analogous to that observed in the isolated ventricular muscle.
