Sodium-calcium exchange in Purkinje fibers: Electrical and mechanical effects

Summary The role of Na and Ca in the modulation of electrical and mechanical events was studied in canine cardiac Purkinje fibers perfusedin vitro. The results show that: 1) A low Na–Ca solution (Na 80.8 mM, Ca 1.08) increased contractile force and shortened the action potential transiently; during the recovery, the force decreased below and increased transiently above control; the action potential lengthened transiently. 2) A low Na solution increased force and transiently shortened the action potential; during the recovery, the force transiently decreased and the action potential lengthened again. 3) A low Ca solution decreased force and prolonged the action potential; during the recovery, the force increased transiently and the action potential shortened. 4) In low Na–Ca solution, verapamil, manganese or a fast driving rate did not prevent the transient increase in force but in the steady state the force was lower. 5) If the low Na–Ca solution was begun during quiescence resuming activity after one minute already resulted in a higher force. 6) Caffeine and high K decreased force but only caffeine markedly decreased the inotropic effects of low Na. 7) The initial increase in force was reversed in calcium-overloaded fibers. And 8) The Na–Ca ratio necessary to maintain force is smaller for Purkinje than myocardial fibers. It is concluded that a low Na–Ca solution increases force by increasing cellular calcium stores probably in the sarcoplasmic reticulum, that the maintenance of force is critically dependent on a smaller slow inward current, and that there are substantial differences between Purkinje and ventricular muscle fibers.Supported by grants HL17451 and 27038 from the National Institutes of Health, Heart and Lung Institute.During this work Dr. Li was a New York Heart Postdoctoral Fellow. Dr. Li's present address is Searl Research and Development, 4901 Searl Parkway, Skokie, Ill. 60077.     

Effects of prostaglandins E2 and F2α on electromyogram of cat colonin vitro

Prostaglandins cause diarrhea, and their production by the gut increases in diarrheal states. We studied the effects of PGF₂ and PGE₂ on the electromyogram recorded from the cat colonin vitro to determine if these prostaglandins might produce electromyographic changes similar to those seen in diarrheal states. PGF₂ decreased slow wave frequency and uncoupled slow wave propagation in the proximal colon. It increased the frequency of migrating spike bursts. PGE₂ had no effect on slow waves, but increased the frequency of the migrating spike burst. PGF₂ produced electromyographic changes similar to those recorded from the colon of cats with spontaneous diarrhea or after exposure to diarrhea-producing agents such as ricinoleate or quinidine. Some diarrhea-producing agents are likely to act by increasing prostaglandin production.     

Organ-cultured chick embryonic hearts of various ages. I. Electrophysiology

Tetrodotoxin (TTX)-insensitive slow Na⁺ channels are converted or replaced by TTX-sensitive fast Na⁺ channels during normal embryonic development of the chick heart, and rapid reversion occurs in monolayer cell culture (denervated). Fast Na⁺ channels first appear at 4 to 5 days, which is about the time of innervation. Studies were done to determine whether changes in cation channels will occur while hearts are in organ culture. To test whether fast Na⁺ channels will develop in the absence of innervation, hearts from chick embryos 2 to 3 days old were placed into culture for 6 to 8 days. Although the resting potentials of the ventricular cells were about the same as those obtained from fresh 8 to 10 day old hearts, the maximum rate of rise of the action potentials ($\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$) did not reach the high value (about 80 V/s) expected from the calendar age. Instead $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ remained at about the same value (12 V/s) that the hearts had when placed into culture. The action potentials were completely insensitive to TTX. The slow channels admit primarily Na⁺ and not Ca²⁺ because Mn²⁺ (1 mm) and lowering [Ca²⁺]₀ to nearly zero by EGTA did not diminish $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$. To test whether the fast Na⁺ channels disappear in organ culture, hearts from embryos 15 to 19 days old were cultured as whole hearts or minced hearts. The whole hearts survived well for 1 to 6 days; the $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ values remained high (～ 100 V/s), and TTX completely blocked the action potentials. The minced hearts had variable $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ values, depending on the piece. Those pieces which had a low $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ were insensitive to TTX, and those which had a high or intermediate $\text{+}\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$, were reduced to 5 to 20 V/s by TTX; these persisting responses in TTX were not blocked by Mn²⁺ or zero [Ca²⁺]₀. The results suggest that, while in organ culture, young hearts do not gain fast Na⁺ channels or lose the slow Na⁺ channels that would normally occur in situ. Organ-cultured old hearts left intact do not lose their fast Na⁺ channels. Thus, young or old hearts retain the channels that they originally possessed when placed into culture. Mincing initiates a gain of slow Na⁺ channels, and in some pieces, a partial loss of fast Na⁺ channels.     

血清脂联素水平与冠状动脉慢血流现象的相关性研究

目的：观察冠状动脉慢血流现象（CSFP）患者血清脂联素（APN）水平的变化,探讨两者的相关性。方法采用TIMI计帧法（TFC）作为测定CSFP的指标,将入选病例分为CSFP组（观察组）及无CSFP现象（对照组）两组。观察组106例,对照组100例,均排除既往冠心病及其他类型心脏病。采用酶联免疫吸附试验（ELISA）法测定血清APN的含量。分析血清APN与冠状动脉血流TFC之间的相关性。结果观察组的血清APN水平[（8.2±2.74）mg/L]明显低于对照组[（11.3±3.0）mg/L],差异有显著统计学意义（P＜0.01）。血清APN与CSFP呈负相关（r=-0.56,P＜0.01）,高血压、吸烟占比观察组明显高于对照组（均P＜0.05）。结论血清APN水平与CSFP之间存在相关性,同时发现高血压及吸烟也与CSFP有关。     

内脏脂肪指数与冠状动脉慢血流相关性分析

目的 探讨内脏脂肪指数(visceral adiposity index,VAI)与冠状动脉慢血流现象(coronary slowflow phenomenon,CSFP)的相关性,分析CSFP的病理生理特征。方法 选取2021年1月至2022年12月在东营市人民医院行冠状动脉造影显示心外膜冠状动脉无明显病变的慢血流患者75例,为CSFP组;另选取同期因心脏症状行冠状动脉造影显示冠状动脉正常的患者65例,为正常组。测量两组患者身高、体质量、腰围(WC)等一般资料,并采集血液,检测总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇(HDL-C)、三酰甘油、空腹血糖等指标。结果 CSFP组和正常组体质量指数[(27.65±2.90) kg/m² vs (23.99±2.3) kg/m²,P<0.001]、WC[(94.25±11.65)cm vs (83.20±5.7)cm,P<0.001]、高血压病(66.7%vs 41.5%,P=0.003)、吸烟(38.7%vs 12.3%,P<0.001)、三酰甘油[(2.49±1.04)...     

Novel TPM3 mutation in a family with cap myopathy and review of the literature

Cap myopathy is a rare congenital myopathy characterized by the presence of caps within muscle fibres and caused by mutations in ACTA1, TPM2 or TPM3. Thus far, only three cases with TPM3-related cap myopathy have been described. Here, we report on the first autosomal dominant family with cap myopathy in three-generations, caused by a novel heterozygous mutation in the alpha-tropomyosin-slow-encoding gene (TPM3; exon 4; c.445C>A; p.Leu149Ile). The three patients experienced first symptoms of muscle weakness in childhood and followed a slowly progressive course. They presented generalized hypotrophy and mild muscle weakness, elongated face, high arched palate, micrognathia, scoliosis and respiratory involvement. Intrafamilial variability of skeletal deformities, respiratory involvement and mild cardiac abnormalities was noted. Muscle MRI revealed a recognizable pattern of fatty muscle infiltration and masseter muscle hypertrophy. Subsarcolemmal caps were present in 6–10% of the fibres and immunoreactive with anti-tropomyosin antibodies. We conclude that the MRI-pattern of muscle involvement and the presence of masseter muscle hypertrophy in cap myopathy may guide molecular genetic diagnosis towards a mutation in TPM3. Regular respiratory examinations are important, even if patients have no anamnestic clues. We compare our findings to all cases of cap myopathy with identified mutations (n = 11), thus far reported in the literature.     

Morphological variability is greater at developing than mature mouse neuromuscular junctions

The neuromuscular junction (NMJ) is the highly specialised peripheral synapse formed between lower motor neuron terminals and muscle fibres. Post-synaptic acetylcholine receptors (AChRs), which are found in high density in the muscle membrane, bind to acetylcholine released into the synaptic cleft of the NMJ, thereby enabling the conversion of motor action potentials to muscle contractions. NMJs have been studied for many years as a general model for synapse formation, development and function, and are known to be early sites of pathological changes in many neuromuscular diseases. However, information is limited on the diversity of NMJs in different muscles, how synaptic morphology changes during development, and the relevance of these parameters to neuropathology. Here, this crucial gap was addressed using a robust and standardised semi-automated workflow called NMJ-morph to quantify features of pre- and post-synaptic NMJ architecture in an unbiased manner. Five wholemount muscles from wild-type mice were dissected and compared at immature (post-natal day, P7) and early adult (P31−32) timepoints. The inter-muscular variability was greater in mature post-synaptic AChR morphology than that of the pre-synaptic motor neuron terminal. Moreover, the developing NMJ showed greater differences across muscles than the mature synapse, perhaps due to the observed distinctions in synaptic growth between muscles. Nevertheless, the amount of nerve to muscle contact was consistent, suggesting that pathological denervation can be reliably compared across different muscles in mouse models of neurodegeneration. Additionally, mature post-synaptic endplate diameters correlated with fibre type, independently of muscle fibre diameter. Altogether, this work provides detailed information on healthy pre- and post-synaptic NMJ morphology from five anatomically and functionally distinct mouse muscles, delivering useful reference data for future comparison with neuromuscular disease models.     

Fast pathway ablation in a patient with PR prolongation

The classical form of typical atrioventricular node reentrant tachycardia (AVNRT) is a “slow-fast” pathways tachycardia, and the usual therapy is an ablation of the slow pathway since it carries a low risk of atrioventricular (AV) block. In patients with long PR interval and/or living on the anterograde slow pathway, an alternative technique is required. We report a case of a 42-year-old lady with idiopathic restrictive cardiomyopathy, persistent atrial fibrillation status post pulmonary vein isolation, and premature ventricular complex ablation with a systolic dysfunction, who presented with incessant slow narrow complex tachycardia of 110 bpm that appeared to be an AVNRT. Her baseline EKG revealed a first-degree AV block with a PR of 320 ms. EP study showed no evidence of anterograde fast pathway conduction. Given this fact, the decision was to attempt an ablation of the retrograde fast pathway. The fast pathway was mapped during tachycardia to its usual location into the anteroseptal region, then radiofrequency ablation in this location terminated tachycardia. After ablation, she continued to have her usual anterograde conduction through slow pathway and the tachycardia became uninducible. In special populations with prolonged PR interval or poor anterograde fast pathway conduction, fast pathway ablation is the required ablation for typical AVNRT.     

丹红注射液对冠状动脉慢血流现象的疗效观察

目的:观察丹红注射液治疗冠状动脉慢血流现象(CSFP)的临床疗效,探讨丹红注射液改善冠脉微循环障碍的可能机制。方法:64例冠脉造影有CSFP及运动负荷试验阳性患者,随机分为观察组(n=32)和对照组(n=32)进行治疗,对照组给予常规药物,观察组在对照组治疗基础上加用丹红注射液。治疗10天后,观察两组临床疗效及血清内皮素-1(ET-1)、血栓调节蛋白(TM)及超敏C-反应蛋白(hs-CRP)水平变化。结果:治疗前,两组各项观察指标差异无统计学意义(P0.05)。治疗10天后,观察组心绞痛缓解总有效率、心电图改善总有效率及运动负荷试验的运动总时间及运动至ST段压低0.1mV的时间均明显高于对照组(90.62%vs 68.75%、84.37%vs 59.37%、441.06±50.61svs 405.03±49.25s、304.53±43.24svs 260.53±49.02s)(P0.01);两组患者治疗后的血清ET-1、TM、hs-CRP水平均较同组治疗前显著降低(P0.01),观察组各项指标较对照组下降更明显(P0.01)。结论:丹红注射液可通过改善血管内皮功能及减轻炎症反应,有效治疗CSFP。     

Dietary Complex and Slow Digestive Carbohydrates Promote Bone Mass and Improve Bone Microarchitecture during Catch-Up Growth in Rats

Catch-up growth is a process that promotes weight and height gains to recover normal growth patterns after a transient period of growth inhibition. Accelerated infant growth is associated with reduced bone mass and quality characterized by poor bone mineral density (BMD), content (BMC), and impaired microarchitecture. The present study evaluated the effects of a diet containing slow (SDC) or rapid (RDC) digestible carbohydrates on bone quality parameters during the catch-up growth period in a model of diet-induced stunted rats. The food restriction period negatively impacted BMD, BMC, and microarchitecture of appendicular and axial bones. The SDC diet was shown to improve BMD and BMC of appendicular and axial bones after a four-week refeeding period in comparison with the RDC diet. In the same line, the micro-CT analysis revealed that the trabecular microarchitecture of tibiae and vertebrae was positively impacted by the dietary intervention with SDC compared to RDC. Furthermore, features of the cortical microstructure of vertebra bones were also improved in the SDC group animals. Similarly, animals allocated to the SDC diet displayed modest improvements in growth plate thickness, surface, and volume compared to the RDC group. Diets containing the described SDC blend might contribute to an adequate bone formation during catch-up growth thus increasing peak bone mass, which could be linked to reduced fracture risk later in life in individuals undergoing transient undernutrition during early life.