Objective To evaluate the effect of combination therapy with milrinone and esmolol on hemodynamics and cardiac function in patients with septic myocardial depression. Methods From October 2010 to October 2013,after the hemodynamics and cardiac function were evaluated by pulse indicator continuous cardiac output (PICCO),74 sepsispatients withCI < 2.2 L/min · m2 after fluid resuscitation were enrolled in the study and were divided into group A with intravenous injection of dobutamine hydrochloride ,and group B with intravenous injection of milrinone and esmolol,with 37 cases in each group. The patients'PICCO indicators, echocardiography and cardiac biomarker(CK,CK-MB,MYO,cTnI and ProBNP)in two groups were compared before and after 3-day treatment. Results (1)CI and GEF were significantly increased in group B after 3-day treatment when compared with those in group A.(2)Compared with those in group A,early diastolic mitral flow velocity/end diastolic mitral velocity (E/A) and right ventricular diastolic diameter(RVD) in group B had statistical significance.(3) CK-MB,cTnI and ProBNP decreased significantly in group B when compared with those in group A. Conclusion Combination therapy with milrinone and esmolol can increase cardiac ejection function,slow down the heart rate,reduce the heart blood and vascular preload,lessen the injury of myocardial and improve heart function.

The present study was to investigate the effects of aminoglycoside antibiotics, changes in extracellular Ca2+ concentration and antagonists of L-type Ca-channels on the activity of rabbit carotid sinus baroreceptors (CS-BRA) in isolated and superperfused carotid sinus-carotid sinus nerve (CS-CNS) preparations, using extracellular recording technique. The results are as follows. (1) Streptomycin (0.25～0.75 mmol/L) and gentamycin (0.43～1.29 mmol/L) inhibited CS-BRA in a dose-dependent manner, which recovered after the drugs were washed out. (2) Perfusion with high Ca2+ (3.3 mmol/L) solution inhibited CS-BRA, while perfusate with trace Ca2+ (in the order of 10－5 mol/L) increased it. (3) Verapamil and diltiazem had no effect on CS-BRA at a concentration of 10－7mol/L, but inhibited it at higher concentrations (>10－6 mol/L). These results suggest: (1) aminoglycoside antibiotics can inhibit CS-BRA specifically, thus providing a new tool for the study of baroreceptors; (2) calcium ions are not necessary for producing generator potentials of baroreceptors, and the L-type calcium channel does not seem to be involved in CS-BRA per se; and (3) the inhibitory effects of aminoglycoside antibiotics on CS-BRA may not be related to the blocking of L-type calcium channels.

Objective To study adrenomedullin (AM) mRNA and protein expression level in myocardium of autoimmune myocarditis animal models induced by immunization of mice with lactobacillus casei cell wall element(LCWE). Methods Forty-five Balb/c male mice were randomly divided into experimental group (n = 30) and control group (n = 15), which were intraperitoneally injected with LCWE and phosphate buffered solution(PBS) at day 0,3,5 and 10,respectively. Sera and myocardium samples were gained 14,21 and 28 days after the first immunization. AM expression levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction(RT- PCR) and immunchistochemistry,and mycardial histopathological lesions were observed. The anti- myosin antibodies in different stages were examined by an ELISA. Results There were myocardial necrosis or inflammatory infiltration in the experimental group, but myocardial lesions were not found in the control group. Anti - myosin antibodies were detected in sera of experimental mice,but not in control group. Immunchistochemistry findings demonstrated that AM expression level was higher in the experimental group than in the control group( P

AIMTo observe the effect of stretching left ventricles in the end of action potential on rabbit cardiac activity, and to investigate its possible mechanisms.

METHODSStretch (120 mmHg, 50 ms) was applied in the end of action potential by the pressure-clamp technique to observe if there would be any changes in rabbit cardiac activity and streptomycin (500 micromol/L) was used to identify the mechanism.

RESULTSStretch in the end of action potential caused arrhythmia (P < 0.05) and streptomycin blocked the above effect (P < 0.05).

CONCLUSIONStreptomycin could block the effect of stretching left ventricles in the end of action potential on rabbit cardiac activity, which indicates that stretch-activated ion channels involve it.

Action Potentials ; physiology ; Animals ; Arrhythmias, Cardiac ; etiology ; physiopathology ; Female ; Heart Ventricles ; physiopathology ; In Vitro Techniques ; Ion Channels ; physiology ; Male ; Mechanoreceptors ; drug effects ; Proprioception ; Rabbits ; Streptomycin ; pharmacology

The purpose of this study was to investigate the effects of calcitonin gene-related peptide (CGRP) on the repolarization process in isolated guinea-pig atrial cells and to determine the contribution of K(+) channels to the CGRP-induced changes in action potential using conventional microelectrode method at the physiological temperature. We found that: (1) CGRP (16 nmol/L) antagonized the influences of potassium channel blockers, 4-AP and BaCl2, on action potential; (2) CGRP (16 nmol/L) increased the amplitude and maximum depolarizing velocity of slow action potential and shortened the conducting time in guinea pig atrial myocardium at extracellular K(+) concentration of 18.5 mmol/L; (3) CGRP (16 nmol/L) alleviated triggered activity induced by superfusion with solution containing CsCl and no potassium ion; and (4) the effects of CGRP on the configuration of action potential were temperature-dependent. At the temperature of 36.5+/-0.5 degrees C, CGRP (5, 16, and 50 nmol/L) increased the amplitude of the action potential and shortened APD(20), APD(50) and APD(90). The CGRP effects on APD(20) and APD(50) were dose-dependent and reversible. On the contrary, CGRP prolonged APD(20), APD(50) and APD(90) at the temperature of 25.5+/-2.1 degrees C. The present study suggests that CGRP possesses multiple effects on various ionic channels. Among them the effects on potassium currents are major determinants in the changes in action potential induced by CGRP under physiological temperature. It is necessary to further study the influences of CGRP on different types of potassium channels.
Action Potentials ; drug effects ; physiology ; Animals ; Body Temperature ; Calcitonin Gene-Related Peptide ; pharmacology ; Cells, Cultured ; Female ; Guinea Pigs ; Heart Atria ; cytology ; drug effects ; Male ; Potassium Channels ; physiology

Aim To investigate the effect of dihydromyricetin on canine carotid artery and the underlying mechanism.Methods The in vitro isometric tension measurement technique was employed to investigate the effect of dihydromyricetin on canine carotid artery rings.Laser scanning confocal microscope technique was used to measure the dynamic change of intracellular calcium concentration in single VSMC.Results Dihydromyricetin(1～300 ?mol?L-1)caused a concentration-dependent contraction of both endothelium-intact and endothelium-denuded rings.This constrictive effect was attenuated in Ca2+-free solution(P

Objective: To investigate the effect and related mechanisms of RTA-408 on rat vascular smooth muscle cells (VSMCs) calcification induced by advanced glycation end products(AGE). Methods: VSMCs were isolated from the aorta of Sprague Dawley rats and cultured in vitro. The fifth generation of VSMCs were randomly divided into 4 groups with random number table including control group(cells were incubated with normal medium for 2 days, then incubated with bovine serum albumin for 5 days),AGE group (cells were incubated with normal medium for 2 days, then incubated with 200 mg/L AGE for 5 days), experimental group(cells were incubated with 100 nmol/L RTA-408 for 2 days,then incubated with 200 mg/L AGE for 5 days),and RTA group(cells were incubated with 100 nmol/L RTA-408 for 2 days,then incubated with bovine serum albumin for 5 days). Cytosolic calciumin VSMC was measured using arsenazo Ⅲ assay. Von Kossa staining was utilized to detect the calcium deposition.The contents of malondialdehyde(MDA) and superoxide dismutase(SOD) in VSMCs were tested by appropriate kits.The protein expressions of osteopontin (OPN), alkaline phosphatase (ALP), nuclear factor E2 related factor 2(Nrf2), and NAD(P)H: quinone oxidoreductase 1(NQO1) were examined using Western blot. Results: (1) Cytosolic calciumconcentration was significantly higher in AGE group than in control group((2.43±0.15) mmol/L vs. (1.23±0.09) mmol/L, P<0.01), which was significantly reduced in experimental group((1.62±0.18) mmol/L,P<0.01 vs. AGE group). (2) Calcium deposition in VSMCs was significantly upregulated in AGE group than in control group(3.64±0.50 vs. 1.00±0.12, P<0.01), and was downregulated in experimental group (1.56±0.37, P<0.01 vs. AGE group). (3) The MDA contents were higher((3.79±0.27) nmol/mg prot vs.(1.99±0.15) nmol/mg prot, P<0.01), while the SOD activities were lower((308.45±14.28) U/mg prot vs. (428.58±11.00) U/mg prot, P<0.01) in AGE group than in control group. The MDA contents were lower((2.37±0.19) nmol/mg prot vs. (3.79±0.27) nmol/mg prot, P<0.01),while the SOD activities were higher((391.03±22.92) U/mg prot vs. (308.45±14.28) U/mg prot, P<0.05)in experimental group compared with AGE group. (4) The relative expressions of OPN and ALP were higher in AGE group than in control group(3.06±0.21 vs. 1.00±0.07, and 2.89±0.29 vs. 1.00±0.10,both P<0.01), both (OPN(1.15±0.12) and ALP(1.45±0.15)) were downregulated in experimental group (both P<0.01 vs. AGE group). (5) The relative protein expressions of Nrf2 and NQO1 in experimental group were higher than AGE group(2.37±0.17 vs. 1.17±0.09, and 3.91±0.18 vs. 1.05±0.08, both P<0.01). Conclusion Activation of nrf2/NQO1 signaling pathway by RTA-408 can reduce the AGE-induced VSMC calcification through attenuating oxidative injury.

The purpose of this study was to examine the effects of calcitonin gene-related peptide (CGRP) on coronary flow and various parts of cardiac conduction system (CCS) in the isolated guinea pig heart by recording the cardiac electrogram and His bundle activity simultaneously. The coronary flow (CF) was measured and the right atrium was paced at incremental frequencies periodically. Perfusing heart with CGRP at the concentrations of 3～30 nmol/L increased CF strikingly and dose-dependently. CGRP (30 nmol/L) caused a moderate and significant increase in the spontaneous heart rate, but failed to influence the atrioventricular nodal and His bundle-Purkinje fiber conduction time and the longest atrial pacing cycle length inducing 3∶2 Wenckebach and 2∶1 AV nodal conduction. The results indicate that CGRP in the guinea pig heart might act mainly on coronary vessels and then the sinus node, but did not affect the conductivity and refractoriness of the AV conduction system.

It is necessary to control the mechanical stimuli precisely in the studies of cardiac mechano-electrical feedback (MEF). In the present study a ventricular pressure-clamping system has been developed, which can be applied to isolated-perfused rabbit hearts. Controlled by a computer, this system not only can make the left ventricle follow a command defining the same pressure wave as that during a beating cycle under physiological condition, but also deliver mechanical stimuli with a proper waveform to the ventricle at a particular time phase. This system integrates multiple functions, including perfusing, pacing, recording of electrocardiogram and monophasic action potentials, and clamping and measuring of ventricular pressures in isolated-perfused hearts. Thus, it is a distinct system for investigating the phenomena and mechanisms of cardiac MEF at organ level.
Action Potentials ; Animals ; Constriction ; Electrocardiography ; Feedback ; Heart ; physiology ; In Vitro Techniques ; Rabbits ; Ventricular Pressure

OBJECTIVETo develop a system for automatically controlling carotid sinus pressure in the study on baroreceptors.

METHODSThe preparation containing carotid sinus with parts of the connected vessels and carotid sinus nerve (CS-CSN) were isolated and perfused. A critical pressure controlling component (PRE-U, Hoerbiger, Deutschland) dictated by a computer was integrated into the system to clamp the intrasinus pressure. The pressure command and the relevant intrasinus pressure were compared to evaluate the validity of the pressure controlling system.

RESULTSA variety of sinus pressure-controlling patterns, including pulsation, ramp and step pressures, could be achieved accurately by using the system, and the pressure-dependent discharge activities of sinus nerve were confirmed.

CONCLUSIONThis system for clamping carotid sinus pressure could realize multiple pressure-controlling patterns and is a useful and flexible pressure controlling method that could applied in the study on mechano-electric transduction of baroreceptors.

Animals ; Blood Pressure ; Carotid Sinus ; innervation ; physiology ; Nerve Fibers ; physiology ; Pressoreceptors ; physiology ; Rabbits