[Preliminary exploration of modified side overlap with fundoplication by Yamashita (mSOFY) anastomosis technique in laparoscopic proximal gastrectomy].

Objective: To discuss the feasibility and safety of modified side overlap with fundoplication by Yamashita (mSOFY) in laparoscopic proximal gastrectomy. Methods: Using the method of descriptive case series study, the clinical data of 9 patients with upper gastric cancer who successfully performed mSOFY anastomosis from March 2022 to October 2022 in the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University were retrospectively analyzed.The reconstruction steps of mSOFY anastomosis are as follows: (1) Make a small incision on the right side of the esophageal stump and in front of the anterior wall of the gastric stump; (2) The 45mm linear cutting stapler is placed into the preset anastomosis of the esophagus and the remnant stomach, and the esophagus is rotated 90° counterclockwise along the axis, so that the right wall of the esophagus is anastomosed with the remnant stomach, and the stomach wall is sutured to the left side of the esophagus; (3) The common opening of esophagus and remnant stomach was sutured with inverted suture; (4)Suture the left and lower sides of the esophagus with the remnant stomach to make the esophagus flat against the stomach wall; (5) Open the sutured common opening: due to the pressure of the false dome, the posterior wall of the lower esophageal segment was compressed into a valve-like structure. We mainly observing the postoperative reflux and nutritional improvement of the patients, and recording the intraoperative situation and postoperative complications. Results: Nine patients with upper gastric cancer who completed laparoscopic proximal gastrectomy (mSOFY anastomosis) did not have conversion to laparotomy or intraoperative / postoperative complications. The operation time was (169.4±10.4) minutes, the anastomotic reconstruction time was (51.7±7.1) minutes, the intraoperative bleeding volume was (98.9±43.4) ml, and the number of lymph nodes dissected was (27.2±6.7). The patient recovered well after operation, without any complaints related to reflux esophagitis. Postoperative gastrointestinal radiography showed that the anastomosis was smooth, without stenosis and leakage. The serum albumin [(41.6±3.4) L vs. (39.9±2.6) L], prealbumin [(211.3±38.6) mg/L vs. (205.3±36.0) mg/L], and hemoglobin levels [(126.7±13.2) g/L vs. (121.0±9.7) g/L] of patients before and one month after surgery have no statistically significant differences (all P>0.05). Conclusion: mSOFY anastomosis can be used as one of the safe and feasible reconstruction methods in laparoscopic proximal gastrectomy.

Absence of Magnetic Thermal Conductivity in the Quantum Spin Liquid Candidate EtMe_{3}Sb[Pd(dmit)_{2}]_{2}.

We present the ultralow-temperature specific heat and thermal conductivity measurements on single crystals of triangular-lattice compound EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, which has long been considered as a gapless quantum spin liquid candidate. In specific heat measurements, a finite linear term is observed, consistent with the previous work [S. Yamashita et al., Nat. Commun. 2, 275 (2011)NCAOBW2041-172310.1038/ncomms1274]. However, we do not observe a finite residual linear term in the thermal conductivity measurements, and the thermal conductivity does not change in a magnetic field of 6 T. These results are in sharp contrast to previous thermal conductivity measurements on EtMe_{3}Sb[Pd(dmit)_{2}]_{2} [M. Yamashita et al., Science 328, 1246 (2010)SCIEAS0036-807510.1126/science.1188200], in which a huge residual linear term was observed and attributed to highly mobile gapless excitations, likely the spinons of a quantum spin liquid. In this context, the true ground state of EtMe_{3}Sb[Pd(dmit)_{2}]_{2} has to be reconsidered.

Depressed calcium-handling proteins due to endoplasmic reticulum stress and apoptosis in the diabetic heart are attenuated by argirein.

Diabetic cardiomyopathy (DC) is a unique disease frequently complicated to diabetes mellitus, manifesting endoplasmic reticulum (ER) stress and depressed calcium-handling proteins. We hypothesized that the abnormal FKBP12.6, SERCA2a, and CASQ2 are consequent to ER stress and apoptosis that are likely due to an entity of inflammation. These abnormalities may be attributed to reactive oxygen species genesis from activated NADPH oxidase which could respond to argirein (AR) through its anti-inflammatory activity. Sprague Dawley rats were randomly divided into six groups. Except the normal group, rats were injected with streptozotocin (STZ; 60 mg/kg, i.p.) once. During weeks 5 to 8 following STZ injection, rats were treated (in milligrams per kilogram per day, i.g.) with aminoguanidine (AMG, 100; an inducible nitric oxide synthase and AGEs inhibitor) or three doses of AR (50, 100, and 200). FKBP12.6, SERCA2a, and CASQ2 and ER stress chaperones Bip and PERK and apoptotic molecules were monitored in vivo and in vitro. Impaired cardiac performance and downregulated FKBP12.6, SERCA2a, and CASQ2 were significant in DC in vivo, and abnormal calcium-handling proteins were also found in high-glucose-incubated myocytes in vitro. ER stress manifested by upregulated Bip and PERK was predominant in association with DNA ladder and upregulated Bax and downregulated BCL-2 in vivo and in vitro. AR is effective to attenuate these abnormalities compared to AMG. Diabetic myocardium has inflammatory entity expressed as ER stress contributing to downregulated calcium-handling proteins. AR has potential in managing DC through attenuating depressed calcium-handling proteins, activated ER stress, and apoptosis in the myocardium.

Upregulated NADPH oxidase contributes to diabetic testicular complication and is relieved by strontium fructose 1,6-diphosphate.

Diabetes is frequently associated with declining sexual function resulting from oxidative damage. NADPH oxidase is a major resource of reactive oxygen species (ROS) in the testes and is likely related to an activated endothelin-1 (ET-1) system. An activation of NADPH oxidase-ET-1 pathway was hypothesized in diabetic testopathy. We verified the hypothesis and tested if strontium fructose 1,6-diphosphate (FDP-Sr) could relieve these changes in diabetic testis as compared to testosterone propionate (TP) and sildenafil. Diabetes was produced in male Sprague-Dawley rats 8 weeks after a single injection of streptozotocin (STZ), and interventions with testosterone propionate (TP), sildenafil and FDP-Sr were conducted in the last 4 weeks. Blood glucose, testosterone, follicle stimulating hormone (FSH) , luteinizing hormone (LH) and expressions of NADPH oxidase subunits and the ET system were measured. Decreased insulin, FSH, LH and testosterone in serum were found associating with testicular oxidative stress in STZ-injected rats. Additionally, over-expressions of NADPH oxidase p22, p47, p67 subunits and the ET pathway were significant in the diabetic testis relative to normal and were completely abolished by FDP-Sr. Both TP and sildenafil were not beneficial to diabetic testopathy except serum androgen raised by TP. Activated NADPH oxidase and ET system are significant contributing to testis injury and are responded to FDP-Sr only, against both TP and sildenafil, by restoring the testis function and the hypothalamus-pituitary-testis axis. It is due to its extra-energy supply and an antioxidant activity of FDP-Sr.

Upregulation of leptin pathway correlates with abnormal expression of SERCA2a, phospholamban and the endothelin pathway in heart failure and reversal by CPU86017.

Emerging evidence indicates that leptin may be a potential new target in chronic heart failure (CHF) treatment. We hypothesized that hyperleptinemia may correlate with abnormal expression of SERCA2a, PLB (phospholamban), and the endothelin (ET) pathway in CHF. An activated ET pathway is involved in CHF that is suppressed by CPU86017 (p-chlorobenzyltetrahydroberberine chloride), a complex class III antiarrhythmic agent with an antioxidant effect. Thus, relief of CHF may be mediated by a reversal of abnormalities of the leptin system, the ET-reactive oxygen species (ROS) pathway, SERCA2a, and PLB by CPU86017. CHF was produced by coronary artery ligation for 6 weeks in rats. The rats were divided into 3 groups: sham, CHF untreated, and CHF+CPU86017 (4 mg/kg per day, s.c.). Hemodynamic changes, cardiac morphology, serum biochemistry, messenger ribonucleic acid (mRNA) and protein expression of the leptin pathway, ET pathway, and redox were measured. In CHF rats, hemodynamic abnormalities, cardiac remodeling, and histological changes with features of cardiac failure were associated with hyperlipidemia accompanied by oxidative stress and upregulated OB-Rb, ECE, pp-ET-1, ET(A)R, and ET(B)R mRNA expression in the myocardium. Protein expression of leptin and ET(A)R in the myocardium was markedly increased in CHF rats. An activated leptin pathway was associated with downregulation of SERCA2a and upregulation of PLB in mRNA and protein expression in CHF. CPU86017 downregulated the leptin system and reversed the above changes in the myocardium. An activated leptin pathway correlates with abnormal expression of SERCA2a and PLB and an activated ET-ROS system in the affected myocardium. The multi-ion-channel-blocking and antioxidative effects of CPU86017 downregulate the leptin pathway and ET system, resulting in reversal of the abnormalities of expression of SERCA2a and PLB and cardiac performance in CHF.

Frequency dependent prolongation of effective refractory period by a complex class III antiarrhythmic agent CPU-86017.

AIM: To compare the prolongation of the effective refractory period (ERP) of a novel complex Class III agent CPU-86017 with compounds blocking INa (lorcainide, Lor), IK (dofetilide, Dof), ICa (verapamil, Ver) and a complex Class III multiple channel blocking agent (amiodarone, Ami) at different frequency levels. METHODS: The ERP of the guinea pig right papillary muscle and the anoxic left atrial muscle treated with high K+ at pH 6.6-6.8, in concentrations ranging 0.03-30 micromol/L was compared at frequency levels ranging from 0.5-4.0 Hz. RESULTS: CPU-86017 showed a positive frequency dependence (PFD) with respect to ERP in the papillary muscles and a mild reverse frequency dependence (RFD) in the diseased atrium. The potency of ERP prolonging effect of various agents at 4.0 Hz was Dof > CPU-86017 > Ver > Ami > Lor, and Dof > CPU-86017 > Ami > Lor > Ver in the normal papillary and diseased atrial muscle, respectively. CONCLUSION: The profile and potency of prolonging the ERP by CPU-86017 is similar to Dof which blocks IKr in the diseased atrium, and to Ver which blocks ICa in guinea pig ventricle.

Puerarin blocks transient outward K+ current and delayed rectifier K+ current in mice hippocampal CA1 neurons.

AIM: To study the effects of puerarin (Pue) on IA and IK in mouse hippocampal neurons. METHODS: The whole cell patch clamp techniques were used. RESULTS: Pue reduced the amplitude of IA and IK, in a concentration-dependent, but not rate- or use-dependent manner (IC50 were 461 micromol/L and 215 micromol/L, respectively). Pue (0.5 mmol/L) shifted the steady state activation curves of IA and IK to positive and negative potentials (Vh about 20.6 mV and 28.6 mV) respectively, but inactivation curves of IA were not affected by Pue. CONCLUSION: Pue inhibited IA and IK in mouse hippocampal CA1 neurons and its blocking effect on I(K) was much stronger than on IA.

[Bepridil inhibition on the delayed rectifier K+ currents in thyroxine induced hypertrophied guinea pig ventricular myocytes].

AIM: To study the effects of bepridil on the rapidly activating component (IKr), the slowly activating component (IKs) of the delayed rectifier potassium current and the inward rectifier potassium current (IK1) in hypertrophied guinea pig ventricular myocytes. METHODS: The whole cell patch clamp techniques were used. RESULTS: In hypertrophied guinea pig ventricular myocytes, bepridil 30 mumol.L-1 markedly inhibited IKr and IKs (by 20.9% and 27.2% at 0 mV and mV, respectively). The effect of bepridil on IKs was larger than on IKr. Bepridil 30 mumol.L-1 also significantly inhibited the inward component of IK1 (by 15.1% at +100 mV), but the reverse potential of IK1 was unaffected. Bepridil (1-100 mumol.L-1) was shown to inhibit IKr and IKs in a concentration-dependent manner. Their IC50 were 46.7 mumol.L-1 and 23.8 mumol.L-1, respectively. CONCLUSION: Bepridil inhibit IKr, IKs and IK1 in hypertrophied guinea pig ventricular myocytes, which may be important in understanding the antiarrhythmic effects of this drug.

Vulnerable substrate and multiple ion channel disorder in a diseased heart will be new targets for antiarrhythmic therapy.

Life-threatening arrhythmia remains a problem contributing to major death in cardiovascular diseases. Till date the antiarrhythmic drugs (AAD) including the Class I and the pure Class III agents have not been recommended for controlling malignant ventricular arrhythmias in a diseased heart, not because of low efficacy but because of an increase in mortality due to their toxic effects. A vulnerable substrate (VS) possessing some properties such as reduced NE and SOD activity, hypertrophied myocardium, and an increase in QT dispersion, is reported to develop in non-infarcted zone of an infarcted heart. Hypertrophied ventricle and exaggerated cardiac arrhythmia can be produced on chronic medication with levothyroxin and this model shares some properties of VS. There is a significant difference in the pattern of disordered ion channels between the congenital long QT syndrome(LQTS) and the acquired heart disease. The affected ion channel in congenital LQTS is single. A novel mutation causing an early appearance of stop codon was discovered in HERG gene resultant with a single disarranged IKr channel leading to a prolonged QT interval. In contrast it is characterised with multi-channels and non-specific disorder in the hypertrophied myocardium in the acquired heart disease. The disordered ion channel is the consequence of the VS lesion influencing the lipid membrane in a diseased heart. The VS and multiple ion channel disorder are provided as new targets to treat cardiac arrhythmias in a diseased heart.

Plasma CPU-86017 concentrations regarding suppression of ouabain-induced cardiac arrhythmias and decrease of heart rate in guinea pigs.

AIM: To determine the effective plasma levels of CPU-86017 which could suppress the cardiac arrhythmias induced by i.v. ouabain in guinea pigs. METHODS: The cardiac arrhythmias and the heart rate were monitored by ECG traces. Blood samples were collected to determine plasma levels using HPLC assay. TXB2 and 6-keto-PGF1 alpha were measured in plasma. RESULTS: The plasma concentrations of CPU-86017 which were effective to suppress ventricular fibrillation (VF) and heart rate were 0.13-0.23 mg/L and 0.13-0.31 mg/L, respectively. A reduction of TXB2 levels and an elevation of 6-keto-PGF1 alpha levels were observed after CPU-86017 i.v. administration. CONCLUSION: The arrhythmia-suppressing and heart rate-slowing effect of CPU-86017 followed a linear relationship with its concentrations in plasma.

Chronic levothyroxin treatment is associated with ion channel abnormalities in cardiac and neuronal cells.

1. We investigated the ion currents responsible for repolarization of guinea-pig isolated myocytes (ICa) and rat hippocampal CA1 neurons (IA and IK) by means of the whole-cell holding technique. 2. The rat hypertrophied heart, induced by levothyroxin, caused exaggerated cardiac arrhythmias after coronary ischaemia-reperfusion. 3. We found an enhanced ICa in guinea-pig isolated myocytes and decreased IA and IK in rat hippocampal CA1 neurons following levothyroxin treatment. Blockade of the outward K+ current and an increment in inward Ca2+ current by chronic levothyroxin treatment contributed to the delayed repolarization and aggravated cardiac arrhythmias. 4. Animals treated with chronic levothyroxin may serve as pathological models for the investigation of the pattern of ion channel disorders with regard to impaired repolarization and aggravated cardiac arrhythmias.

Reduction in QT dispersion and ventricular arrhythmias by ischaemic preconditioning in anaesthetized, normotensive and spontaneously hypertensive rats.

QT dispersion is a marker for dispersion of ventricular repolarization and electrical instability of the heart. However, QT dispersion remains undocumented in both normotensive rats (NTRs) and spontaneously hypertensive rats (SHRs), in particular in conditions of myocardial ischaemia/reperfusion (isch./rep.) and ischaemic preconditioning (IP). Therefore, we assessed the effects of IP on the dynamic change of QT and QTc dispersion during isch./rep., and on isch.- and rep.-induced ventricular arrhythmias in both NTRs and SHRs. Isch. and rep. were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of IP (three cycles of 3 min coronary artery occlusion and 5 min rep.) on myocardial repolarization and on development of isch.- and rep.-induced ventricular arrhythmias was studied in 12 NTRs and 12 SHRs. Another 12 NTRs or 12 SHRs were subjected to 10 min of isch. followed by 10 min rep. without IP. SHRs have significantly longer QT- and QTc-intervals as well as QT and QTc dispersion before isch. compared to NTRs. Myocardial isch. and early rep. largely increased QT and QTc dispersion in both NTRs and SHRs and resulted in a high incidence of isch.- and rep.-induced ventricular tachycardia (VT) and fibrillation (VF). IP significantly reduced QT and QTc dispersion in SHRs before isch., and remarkably reduced the elevation of QT and QTc dispersion during a prolonged period of isch. and rep. in all rats. This protective effect on electrophysiology of IP was associated with an antiarrhythmic effect against both isch.- and rep.-induced ventricular arrhythmias in NTRs and SHRs. Our data indicate that: 1) SHRs have a significantly higher baseline dispersion of ventricular repolarization than NTRs; 2) IP provides protection against ventricular arrhythmias in SHRs; 3) the increasing QT dispersion provoked by myocardial isch. and rep. is associated with a high incidence of isch.- and rep.-induced ventricular arrhythmias and; 4) the reduction of QT dispersion by IP may be involved in its protective effect against isch.- and rep.-induced arrhythmias in both NTRs and SHRs.

Ischemia/reperfusion-induced arrhythmias in anaesthetized rats: a role of Na+ and Ca2+ influx.

We hypothesized that by limiting the Na+ and Ca2+ loading by a blocker/inhibitor of the Na+ channel (lidocaine), Na+ overload (R56865: N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine), Ca2+ channel (verapamil), Na+ -H+ exchange (ethylisobutyl amiloride) or of Na+ -Ca2+ exchange (No. 7943: 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), it should be possible to reduce ischemia/reperfusion-induced arrhythmias. To test this hypothesis, we used anaesthetized rats subjected to 5 min of coronary artery occlusion followed by 10 min of reperfusion to study antiarrhythmic effects of above compounds on reperfusion-induced ventricular premature beats, ventricular tachycardia, and reversible and irreversible ventricular fibrillation. Compound or saline was administered as an intravenous bolus injection at 5 min before ischemia. Pretreatment with lidocaine (5 mg/kg), verapamil (0.63 mg/kg), R56865 (0.63 mg/kg) or ethylisobutyl amiloride (1.25 mg/kg) significantly reduced or abolished all types of ventricular arrhythmias. However, pretreatment with verapamil was associated with second or third degree heart block in 3 out of 12 animals. Pretreatment with No. 7943 did not significantly influence the ischemia/reperfusion-induced ventricular arrhythmias. The present results suggest that both intracellular Na+ -and Ca2+ -loading play important roles in reperfusion-induced ventricular arrhythmias and the inhibition of Na+ -Ca2+ exchange to limit Ca2+ loading probably does not play any important role in ischemia/reperfusion-induced arrhythmias in anaesthetized rats.

Bepridil inhibition of sodium current in rat hippocampal CA1 neurons.

AIM: To study the effects of bepridil on sodium current in rat hippocampal neurons. METHODS: All experiments were performed on acutely isolated hippocampal pyramidal neurons by means of whole-cell patch-clamp techniques. Recording media contained ion channel blockers to allow the selective activation of voltage-dependent sodium currents. RESULTS: Bepridil reduced the amplitudes of sodium current in time- and concentration-dependent manners. The half-blocking time was about 10 min in bepridil 10 micromol.L-1, and IC50 was 2.6 (2.3-2.9) micromol.L-1. Bepridil 10 micromol.L-1 shifted the maximal activation of sodium current from -50 mV to -40 mV, and the characteristic voltage of inactivation from -71 mV to -89 mV without changing the slope factor. CONCLUSION: Bepridil blocked voltage-dependent sodium current of hippocampal CA1 neurons and might have therapeutic actions for ischemia-induced brain damage.

p-Chlorobenzyltetrahydroberberine inhibits vascular smooth muscle contractions caused by Ca2+.

AIM: To investigate influences of p-chlorobenzyltetrahydroberberine (CPU-86017) and levothyroxin (Lev) on vascular smooth muscle (VSM) contractions by intracellular Ca2+ release and calcium entry. METHODS: Three kinds of contractions of rat thoracic aortic rings were used to compare suppression by CPU-86017, bepridil (Bep), verapamil (Ver), and nimodipine (Nim) in euthyroid- and Lev-induced hyperthyroidism rats. RESULTS: The IC50 of CPU-86017 on KCl-induced contractions of euthyroid and hyperthyroid VSM were 80 (36-179) and 121 (62-236) mumol.L-1, respectively. The potency of CPU-86017 was approximate to 1/10 of Bep and 1/100 of Ver and Nim. Suppressions of Ver and Nim on hyperthyroid VSM in Ca(2+)-free solution were greatly attenuated by -86% and -95%, respectively. Slight or no change in activity of CPU-86017 and Bep was found. Contractions on adding Ca2+ into Ca(2+)-free medium were suppressed by CPU-86017 and its potencies in euthyroid and hyperthyroid rats were not different. CONCLUSION: CPU-86017 is more potent to suppress Ca2+ entry than intracellular calcium mobilization and Lev enhances both.

Histamine aggravated levothyroxine-induced cardiomyopathy in guinea pigs.

AIM: To study effects of histamine on cardiomyopathy. METHODS: Cardiomyopathy model was developed in guinea pig by i.p. levothyroxine 0.5 mg.kg-1.d-1 for 10 d. Langendroff's hearts were perfused. ECG and contractile force were recorded. Histamine (5 micrograms) was given by intra-aortic injection. Histamine content of coronary venous effluent was determined fluorometrically. RESULTS: Attack of histamine on cardiomyopathy was severer than that in normal hearts. Tachycardia was more prominent; atrioventricular conduction block occurred earlier; decrease in coronary flow was more marked. Uptakes of histamine were 37% in the model and 19% in the normal hearts (P < 0.01). CONCLUSION: Histamine aggravated levothyroxine-cardiomyopathy.

Heart hypertrophy induced by levothyroxine aggravates ischemic lesions and reperfusion arrhythmias in rats.

AIM: To develop a cardiac hypertrophic model in rats. METHODS: Rats were i.p. levothyroxine 0.5 mg.kg-1.d-1 x 10 d. The action potentials of right papillary muscles were recorded by standard glass-microelectrode technique. The left coronary artery was ligated followed by reperfusion and the apparent infarcted zone (AIZ) was determined by tetracycline fluoresence, and the superoxide dismutase (SOD) activity and malondialdehyde (MDA) product in myocardium were also measured. RESULTS: In the rats treated by levothyroxine, the heart was hypertrophic and the action potential duration (APD) and effective refractory period (ERP) were prolonged, the APD20, APD50, APD90, and ERP were prolonged by 80%, 79%, 74%, and 68%, respectively. No changes in resting potential (RP), action potential amplitude (APA), and Vmax were produced. The incidence of heart arrest (8/8) and the risk of death (67 +/- 0) induced by ischemia-reperfusion in rats with hypertrophic heart was higher than those in normal rats (4/10 and 44 +/- 19, respectively). The AIZ was expanded markedly in hypertrophic heart, and attenuated by lidocaine and propranolol. CONCLUSION: Levothyroxine-induced heart hypertrophy is a suitable model for severe ischemia and arrhythmias in rats.

Propranolol and bepridil attenuating levothyroxine-induced rat cardiac hypertrophy and mitochondrial Ca2+ Mg(2+)-ATPase activity elevation.

AIM: To study the effects of propranolol and bepridil on levothyroxine-induced rat cardiac hypertrophy and mitochondrial Ca2+ Mg(2+)-ATPase activity elevation. METHODS: Rat heart hypertrophy was induced by i.p., levothyroxine 1 mg.kg-1.d-1 x 10 d. Then rats were treated by ig propranolol (Pro) or bepridil (Bep) 10 mg.kg-1 daily. Ca2+ Mg(2+)-ATPase activity and enzyme kinetic parameters were assayed. RESULTS: The activity and Vmax of mitochondrial Ca2+ Mg(2+)-ATPase isolated from hypertrophic left ventricle were 25 +/- 4 and 35.1 +/- 0.8 mumol Pi.h-1/mg protein, respectively, those of normal were 6.7 +/- 1.8 and 10 +/- 4 mumol Pi.h-1/mg protein, respectively. Apparent K(m) of the hypertrophic group Ca2+ Mg(2+)-ATPase was 0.4 +/- 0.12 mmol.L-1 ATP, and that of normal was 0.59 +/- 0.22 mmol.L-1 ATP. The total protein quantity of hypertrophic left ventricle was 80 +/- 30 mg, and that of normal was 47 +/- 9 mg. After treated with Pro or Bep (both 10 mg.kg-1 ig), the cardiac hypertrophy was attenuated, the enzyme activity and Vmax as well as total protein quantity of hypertrophic left ventricle were reduced to normal level, but apparent K(m) was not affected. CONCLUSION: Both Pro and Bep prevented the myocardium and its mitochondria from ischemia and overload calcium injury.

Bepridil reducing levothyroxine-induced enhancement of mitochondria Ca2+ Mg(2+)-ATPase activity in rat cerebrum.

AIM: To study if bepridil (Bep) could affect the enhancement of activity of cerebral mitochondria Ca2+ Mg(2+)-ATPase caused by levothyroxine (Lev) in relation to ischemic overload calcium cerebrum injury. METHODS: The experimental hyperthyroidism model with ischemic cerebrum was developed in rats by ig Lev 1 mg.kg-1.d-1 for 7 d. Ca2+ Mg(2+)-ATPase activity and its kinetic parameters were assayed. RESULTS: The activity, Vmax and Km of cerebral mitochondria Ca2+ Mg(2+)-ATPase in control rats were 3.1 +/- 0.8, 5.1 +/- 2.3 mmol.P(i).h-1/g protein and 0.81 +/- 0.08 mmol.L-1 (ATP) respectively, whereas those of hyperthyroid rats were significantly altered to 4.6 +/- 0.5, 8.5 +/- 1.9 mmol.P(i).h-1/g protein and 0.49 +/- 0.11 mmol.L-1 (ATP) respectively. After treated with Bep 10 or 20 mg.kg-1.d-1 ig for 3 d, allabove 3 parameters of the enzyme were very significantly reduced vs those of either control or hyperthyroid. CONCLUSION: Bep, via decreasing Ca2+ Mg(2+)-ATPase activity and increasing the affinity of Ca2+ Mg(2+)-ATPase to ATP, could prevent rat cerebrum from ATP depletion and ischemic overload calcium injury.

Orthogonal analysis of aggravating effects of alpha-, beta-agonists and leukocytes on reperfusion-induced arrhythmias and ventricular fibrillation in Langendorff's rat heart.

AIM: To study the effect of leukocyte (Leu), alpha-agonist (alpha-Ago), and beta-agonist (beta-Ago) on the arrhythmias induced by ischemia and reperfusion to determine which of the 3 factors was the most important one in exacerbating arrhythmias. METHODS: Arrhythmias were induced by the reduction and subsequent resumption of perfused flow in Langendorff's perfused rat hearts. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded on ECG, and the results were orthogonally analyzed. RESULTS: When Leu was present, the incidence of VF induced by ischemia-reperfusion was 80%. The incidence in Leu-depleted hearts was 20%, alpha-Ago and beta-Ago elevated it to 60% and 100%, respectively. The results by orthogonal analysis demonstrated Leu or alpha-Ago+ beta-Ago increased VF incidence. With regard to arrhythmias, arrhythmia score was remarkedly increased by all of 3 factors and various combinations except beta-Ago + Leu. CONCLUSION: Among these 3 factors, Leu was the most important one in facilitating reperfusion-induced arrhythmias.