Characterisation of left ventricular relaxation in the isolated guinea pig heart

The time constant of left ventricular pressure fall, τ, has frequently been used as a measure of myocardial relaxation in the blood-perfused, ejecting heart. The aim of the present study was to characterise τ in relation to β-adrenergic activation, coronary perfusion pressure and flow as well as cardiac oxygen supply and demand in the isolated, isovolumically beating heart. Therefore, τ was analysed from digitised left ventricular pressure data in a total of 23 guinea pig hearts perfused with saline at constant pressure (60 cmH₂O). The coronary venous adenosine concentration ([ADO]) served as an index of myocardial oxygenation. Isoprenaline (0.4–3.2 nmol l⁻¹) decreased and propranolol (3–9 μmol l⁻¹) increased τ dose-dependently (linear regression τ vs lg ([isoprenaline]),r=0.74; τ vs. lg([propranolol]),r=0.66, bothP<0.05). During graded reductions in cardiac oxygen supply from 96.1±12.6(SEM) to 44.4±4.4 μl min⁻¹ g⁻¹, τ was prolonged from 61.5±12.7 to 109.9±22.6 ms while left ventricular developed pressure (LVDP) decreased from 90.7±7.2 to 40.7±5.1 mmHg. In parallel, [ADO] increased from 23.7±9.1 to 58.0±19.1 pmol ml⁻¹ (P<0.05). Increasing oxygen supply to 165.4±32.4 μl min⁻¹ g⁻¹ augmented LVDP to 102.7±7.3 mmHg but did not change τ or [ADO]. There was a dual response of τ to changes in cardiac oxygen supply or demand. As long as oxygen supply and demand matched, τ remained constant. However, when the oxygen supply was less than 100 μl min⁻¹g⁻¹, left ventricular relaxation was prolonged in parallel to the reduction in oxygen supply. In addition, a close relationship was observed between [ADO] as an indicator of myocardial oxygenation and τ (Spearman correlation,r=0.99,P<0.005). We conclude that the time constant of left ventricular pressure fall, τ, sensitively reflects myocardial relaxation in the isolated, isovolumically beating guinea pig heart. Moreover, in this model left ventricular relaxation is not influenced by alterations in coronary perfusion pressure or flow as long as cardiac oxygen demand is matched by an adequate supply. Rather, relaxation is strictly coupled to myocardial oxygenation as reflected by coronary venous adenosine concentrations.     

Effects of milrinone on contractile responses of guinea pig trachea, lung parenchyma and pulmonary artery

The effects of milrinone, a bipyridine with known vasodilator activity, on guinea pig tracheal-spirals, lung parenchymal strips and pulmonary artery rings in vitro were compared with the effects of isoproterenol and aminophylline on these tissues. The concentration of milrinone that produced 50% relaxation (IC50) of tracheal spirals constricted by carbachol was 3.6 X 10(-5) M. Isoproterenol (IC50, 9.5 X 10(-8) M) was significantly (P less than .001) more potent and aminophylline (IC50, 1.2 X 10(-4) M) was significantly (P less than .001) less potent than milrinone in this effect. The IC50 for milrinone for lung parenchymal strips contracted by histamine was 3.2 X 10(-5) M, whereas the IC50 for isoproterenol was significantly (P less than .001) less, 1.4 X 10(-7) M; aminophylline produced only limited relaxation of lung parenchymal strips. Milrinone relaxed pulmonary artery rings constricted by norepinephrine with an IC50 of 3.8 X 10(-6) M, whereas neither isoproterenol nor aminophylline produced a 50% relaxation. Pretreatment of tracheal spirals, lung parenchymal strips and pulmonary artery rings with 1.6 X 10(-4) M milrinone inhibited subsequent contraction by carbachol, histamine and norepinephrine, respectively. The relaxant effects of milrinone were not influenced by treatment with atropine, cimetidine, mepyramine, phentolamine or propranolol. However, indomethacin blocked milrinone's relaxant effects on tracheal spirals effectively, but not on pulmonary artery rings or lung parenchymal strips, suggesting distinct modes of action on various tissue types.     

Potent and reversible effects of ATI-2001 on atrial and atrioventricular nodal electrophysiological properties in guinea pig isolated perfused heart

We recently demonstrated that the short-acting analog of amiodarone, ATI-2001, caused favorable effects in guinea pig ventricular myocardium on electrophysiological substrates underlying tachyarrhythmia initiation, perpetuation, and termination. Here, the acute effects of 1.0 microM ATI-2001 and 1.0 microM amiodarone (90-min infusion followed by 90-min washout period) on atrial and atrioventricular (AV) nodal electrophysiological properties were studied in guinea pig isolated hearts. Neither ATI-2001 nor amiodarone significantly prolonged atrial conduction time. Compared with amiodarone, ATI-2001 caused significantly more rapid and greater prolongation of atrial monophasic action potential duration at 90% repolarization (maximal change 21.4 +/- 3.7 versus 19.0 +/- 4.0 ms) and atrial effective refractory period (ERP, 27.8 +/- 6.1 versus 9.2 +/- 2.3 ms). Shortening of the atrial cycle length from 250 to 200 ms did not significantly alter drug-induced changes in atrial repolarization and refractoriness. ATI-2001 prolonged the atrium-to-His bundle interval (22.1 +/- 2.6 versus 8.8 +/- 2.3 ms), His bundle-to-ventricle interval (2.8 +/- 0.4 versus 0.9 +/- 0.3 ms), AV nodal ERP (72.5 +/- 7.3 versus 31.4 +/- 4.1 ms), and Wenckebach cycle length (69.6 +/- 5.2 versus 35.8 +/- 4.1 ms) significantly more than did amiodarone. Unlike amiodarone, the effects of ATI-2001 were markedly reversed upon discontinuation of drug infusion. Given these data, ATI-2001 should not only be useful for terminating ongoing and preventing reoccurrence of atrial tachyarrhythmias but also to treat supraventricular tachycardias involving the AV node and to control ventricular rate during atrial tachyarrhythmias. Whether the observed differences in the pharmacokinetic properties render ATI-2001 superior to amiodarone in acute tachyarrhythmia management and less likely to accumulate into tissues during chronic therapy remains to be established.     

Comparison of contractile responses of the guinea pig ileum longitudinal muscle to ethanol and GABAA agonists

The guinea pig ileum myenteric plexus contains GABAA receptors linked to chloride ion channels which are pharmacologically similar to those in the central nervous system. The present study examined the reported ability of acute ethanol treatment to directly activate GABAA receptors or to increase GABAA agonist-mediated activation of the GABAA receptor in the myenteric plexus. Direct addition of ethanol to preparations of the guinea pig ileum longitudinal muscle had two effects. Immediately after ethanol (10-300 mM) was added to the tissue bath a concentration-related contractile response was observed which became maximal within 10 sec and then decayed over the next 60 sec. Contractile responses to higher concentrations of ethanol (greater than 100 mM) also were followed by a sustained reduction of longitudinal muscle tone. Contractions evoked by gamma-aminobutyric acid (GABA) and GABAA agonists, 3-aminopropane sulfonic acid (APSA) (3-100 microM) or muscimol (0.3-30 microM) developed maximally and decayed within 20 sec. Acetylcholine (0.01-10 microM) induced contractions were sustained over several minutes. Preincubation of tissue strips in ethanol (30 mM) for 1 min did not alter concentration relationships for GABA, muscimol or APSA contractile responses. Furthermore, addition of ethanol (10-100 mM) simultaneously with APSA, or 0.5, 2 or 5 min before the addition of APSA, also failed to consistently enhance contractile responses. Ethanol (30 mM) also did not alter desensitization-induced reductions in contractile responses to muscimol (3 microM) caused by preincubation of tissues with muscimol (1 microM). Finally, contractile responses to ethanol and APSA were completely blocked by atropine (0.1 microM) and tetrodotoxin (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential modulation by beta adrenoceptors of inward calcium and delayed rectifier potassium current in single ventricular cells of guinea pig heart

This study was designed to investigate the modulation of the high-threshold (L-type) inward calcium current (ICa) and the delayed rectifier potassium current (IK) by beta adrenoceptor stimulation in single ventricular cells of guinea pig heart. Single ventricular cells were prepared by the collagenase dispersion procedure, and membrane currents were recorded with a patch electrode by use of the whole-cell voltage clamp method. ICa was obtained by intra- and extracellular perfusion with the Cs(+)-solutions that suppressed potassium currents. IK was evaluated in Co+(+)-Tyrode's solution in which 0.9 mM Co+(+) was substituted for equimolar Ca+(+) to abolish ICa. Isoproterenol, a nonselective beta adrenoceptor agonist, increased not only ICa but also IK at the same threshold concentration (1 nM). In contrast, the threshold concentration of T-1583, a selective beta-1 adrenoceptor agonist, for increasing ICa (1 nM) was distinctly lower than that for increasing IK (100 nM). These results suggest that ICa and IK can be differentially modulated by beta adrenoceptors.     

Intrathecal somatostatin in the guinea pig: effects on spinal cord blood flow, histopathology and motor function.

In the present investigation, the vasoconstrictive, motor and neurodegenerative effects of intrathecal somatostatin (SST) were assessed in guinea pigs implanted with lumbar intrathecal catheters. Five consecutive dose increments of SST (5, 10, 15, 30 and 60 micrograms) to a total of 120 micrograms during the period of 16 +/- 3 min, resulted in a moderate (< 20%), gradual decrease of the spinal blood flow monitored with the laser-doppler method. A subsequent injection of clonidine (50 micrograms) or norepinephrine (10 micrograms) resulted in a more pronounced decrease of spinal blood flow (35% and 79%, respectively). Three consecutive, daily intrathecal injections of 30 or 60 micrograms SST did not cause any loss of weight support or paralysis of the hind limbs. There were no histopathological changes in the white or gray matter of the thoracic and lumbar sections of the spinal cords. It is concluded that SST, in the doses studied, is not neurodegenerative in guinea pigs. These findings are in contrast to those previously seen in rats. The implication of this study may be the necessity to use several alternate animal species in order to evaluate the antinociceptive and neurodegenerative properties of the peptides administered by the intrathecal route and the choice of dose to be compared across species.     

An examination of the influence of the epithelium on contractile responses to peptidoleukotrienes and blockade by ICI 204,219 in isolated guinea pig trachea and human intralobar airways

The influence of the epithelium on antagonism by ICI 204,219 of contractile responses to peptide leukotriene (LT) agonists was examined in guinea pig tracheal and human bronchial rings. The -log molar KB values for ICI 204,219 were found to be independent of the epithelium in both tissues. Even though uninfluenced by the epithelium, the -log molar KB values for ICI 204,219 were about 10-fold smaller in human airways than in guinea pig trachea. Removal of the epithelium from guinea pig trachea resulted in small leftward shifts of the concentration-response curves to LTC4 and LTD4 and rightward shifts of the concentration-response curves to LTE4 when examined in the presence of indomethacin. The potentiation of LTC4 and LTD4 by epithelium removal was not seen in the presence of inhibitors of the transformation of LTC4 to LTD4 and LTD4 to LTE4. The influence of the epithelium on responses to LTE4 remained in the presence of these metabolic inhibitors. The lipoxygenase inhibitors nordihydroguaiaretic acid, B755C, Rev 5901 and AA861 antagonized responses to LTE4 in the presence, but not in the absence of epithelium. In human airways, epithelium removal resulted in a small leftward shift of the concentration-response curve to LTD4 whereas responses to LTC4 and LTE4 were unaltered. This effect was not observed in the presence of indomethacin, relating it to reduced release of cyclooxygenase products. These data suggest that contractile responses of guinea pig trachea to LTE4 are modulated by LTE4-induced release of 5-lipoxygenase product(s) only when the epithelium is present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of pharmacodynamic interactions between quinidine and digoxin in isolated atrial muscle of guinea pig heart

Quinidine has been reported to have no effect on the positive inotropic action of digoxin observed in isolated cardiac muscle preparations. This is surprising because quinidine has been shown to reduce Na+ influx in cardiac muscle. The conditions which increase Na+ influx stimulate the glycoside binding to Na+- and K+-activated Mg++-dependent ATP phosphohydrolase (Na+,K+-ATPase), and therefore quinidine may be expected to have an opposite effect. Thus, the effects of quinidine on cardiac muscle and its possible interactions with digoxin were re-evaluated using electrically paced left atrial muscle preparations of guinea pig heart. Quinidine caused a frequency- and concentration-dependent decrease in maximal upstroke velocity and amplitude of the action potential without altering resting membrane potential. In addition, quinidine prolonged action potential duration markedly in a frequency-dependent manner. Despite action potential prolongation, the alkaloid reduced net Na+ influx as determined by a decrease in steady-state ouabain-sensitive 86Rb+ uptake. Under these conditions, however, quinidine failed to reduce the rate of onset or the maximal positive inotropic effect of digoxin; or did it reduce digoxin binding to Na+,K+- ATPase in beating atrial muscle preparations. Benzocaine, which reduced net Na+ influx without increasing the action potential duration, also failed to affect the peak inotropic effect of digoxin or the glycoside binding. Quinidine had no direct effects on glycoside binding to isolated cardiac Na+,K+-ATPase. Moreover, [3H]ouabain binding to isolated enzyme was relatively insensitive to changes in Na+ concentrations between 1 and 8 mM although binding was stimulated clearly by Na+ above 8 mM. These results indicate that quinidine, at therapeutic concentrations, does not interact pharmacodynamically with digoxin in isolated cardiac muscle.     

Antigen-induced enhancement of noncholinergic contractile responses to vagus nerve and electrical field stimulation in guinea pig isolated trachea.

Nonadrenergic, noncholinergic contractions were elicited by electrical field stimulation (EFS) (2 Hz, 1 msec, 12 V for 15 sec) of the distal aspect of guinea pig trachea pretreated with atropine (1 microM), propranolol (1 microM) and indomethacin (3 microM). The contractions were abolished by pretreatment with the sensory C-fiber toxin capsaicin or by a combination of the neurokinin (NK)1 receptor antagonist, CP 96,345 (0.1 microM), and the NK2 receptor antagonist, MEN 10376 (3 microM), and were markedly attenuated by tetrodotoxin. In animals actively sensitized to ovalbumin, the addition of threshold concentrations of antigen markedly increased the noncholinergic contractile responses to EFS (approximately 3- to 6-fold). This potentiation was long lasting, persisting virtually unchanged for 60 min, whereas the antigen-induced contractions were shorter lived, usually lasting less than 30 min. The ovalbumin-induced potentiation of the neuronal response was not observed in tissues pretreated with capsaicin or treated with tetrodotoxin. This antigen-induced potentiation of capsaicin-sensitive, EFS-induced contractions was not mimicked by serotonin or prostaglandin D2. However, it was mimicked by histamine. Moreover, the histamine H1 receptor antagonist pyrilamine (0.3 microM) reversed the potentiation elicited by ovalbumin. The effect of ovalbumin challenge was also examined on the distal trachea with the right vagus nerve intact. Noncholinergic contractions to EFS and vagus nerve stimulation were enhanced equally by threshold concentrations of antigen. The results support the hypothesis that antigen challenge releases histamine which acts via H1 receptors to enhance noncholinergic contractions due to the release of tachykinins from capsaicin-sensitive fibers in the guinea pig trachea.     

Differential effects of reactive oxygen metabolites on neurally stimulated and nonstimulated guinea pig ileum.

Large numbers of polymorphonuclear leukocytes which generate reactive oxygen metabolites are found in mucosa and submucosa of the intestinal wall of subjects suffering from inflammatory bowel disease. We have, therefore, examined the relative influences of hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and N-chloramines such as NH2Cl, on the neurally stimulated and nonstimulated guinea pig ileum. In separate experiments the oxidants were tested in the presence and absence of the cyclooxygenase inhibitor piroxicam and the antioxidant glutathione. All three oxidants, in concentrations produced by activated neutrophils, increased the muscle tone (concentration-dependent, peak at 0.3 mM for NH2Cl and H2O2 and 1 mM for HOCl). Tetrodotoxin (0.5 microM) inhibited the NH2Cl and H2O2 effects by 50% and 70%, respectively. Piroxicam (5 microM) partially blocked maximal contractions induced by all three oxidants. The contractile response to carbachol (10 microM) was blocked by 0.3 mM NH2Cl, but not by H2O2 and HOCl. In electrically stimulated ileum the oxidants produced a concentration-dependent biphasic response (transient enhancement of neurally mediated twitch contraction followed by marked inhibition). This response was not modified by piroxicam, hexamethonium, atropine and pyrilamine. The inhibition of twitch contraction was irreversible for NH2Cl and HOCl, in contrast to H2O2, which was reversed by repeated washing. Neither the contractile effect nor the effects on nerve stimulation-induced contraction were affected by preincubation of the tissue with glutathione, whereas prior combination of NH2Cl with glutathione prevented the effects of NH2Cl. Oxidant-induced contraction of guinea pig ileum appears to be via release of prostaglandins and one or more neurotransmitters. High concentrations of reactive oxygen metabolites may alter receptor function.(ABSTRACT TRUNCATED AT 250 WORDS)     

豚鼠离体右心房自律性及收缩特性与葛根素的影响

目的:观察葛根素对豚鼠离体右心房自律性及收缩特性的影响,并探讨其作用机制。方法:实验于2005-07在赣南医学院药理实验室(省级重点实验室)完成。健康豚鼠6只,用锤子击打头部至昏迷,剖开胸腔迅速取出心脏,在持续充纯氧的条件下,分离右心房。将右心房肌悬挂在含20mLKrebs液的麦氏浴槽中,恒温(37±0.5)℃,持续通入纯氧。右心房稳定45min后,测定其正常自动节律、收缩幅度、收缩速度和舒张速度作为给药前对照,然后累积加入葛根素(终浓度为0.0036,0.012,0.036,0.12,0.36,1.2,3.6mmol/L),每次给药间隔5min,测定其自动节律、收缩幅度、收缩速度、舒张速度的变化。结果:葛根素可降低豚鼠离体右心房的自律性、收缩幅度、收缩速度、舒张速度,且有明显的剂量依赖性。结论:葛根素可抑制豚鼠离体右心房的自律性,明显降低豚鼠离体右心房的收缩幅度、收缩速度、舒张速度,且有明显的剂量依赖性,其作用机制可能与抑制钙离子通道及钠离子通道有关。     

Characterization of the contractile serotonergic receptor in guinea pig trachea with agonists and antagonists.

5-Hydroxytryptamine (5-HT)2 receptors can be partially characterized by their sensitivity to ketanserin blockade and increase in phosphoinositide turnover upon stimulation. Previously, the contraction of guinea pig trachea to 5-HT was shown to be antagonized by the 5-HT2 receptor antagonists ketanserin and LY53857. However, 5-HT did not dramatically increase phosphoinositide turnover in guinea pig trachea, suggesting that the contractile receptor may be different from the classically defined 5-HT2 receptor. The present in vitro studies better characterize this receptor, using diverse serotonergic agonists and antagonists to profile in more detail the contractile serotonergic receptor in guinea pig trachea. With regard to agonists, the 5-HT2 receptor agonists DOI and alpha-methyl-5-HT contracted guinea pig trachea with greater potency than quipazine, 5-methoxytryptamine, 5-carboxamidotryptamine, 8-hydroxy-2-(di-N-propylamino)tetralin and 2-methyl-5-HT. Sumatriptan and 1-(3-chlorophenyl)-piperazine (10 nM-100 microM) were inactive as agonists. A strong correlation between agonist potency (EC50) and reported 5-HT receptor binding affinities was found for both the 5-HT1C (r = 0.890) and 5-HT2 (r = 0.831) receptor. Ketanserin, spiperone, ritanserin, LY53857, 1-napthylpiperazine, 1-(3-chlorophenyl)-piperazine, rauwolscine, ICS 205-930, cyanopindolol and sumatriptan all blocked 5-HT-induced contractions in guinea pig trachea. As occurred with agonist potencies, strong correlations were found between reported 5-HT1C (r = 0.814) and 5-HT2 (r = 0.912) receptor binding affinities in brain membranes and apparent dissociation constants (KB) for the 10 antagonists of 5-HT induced contraction in guinea pig trachea.(ABSTRACT TRUNCATED AT 250 WORDS)     

Structure-activity relationships and electrophysiological effects of short-acting amiodarone homologs in guinea pig isolated heart

Antiarrhythmic agents with amiodarone-like electrophysiological actions, but with a more favorable pharmacokinetic profile than amiodarone would be extremely useful for the treatment of many tachyarrhythmias. We designed a series of amiodarone homologs with an alkyl ester group at position 2 of the benzofurane moiety. It was hypothesized that the electrophysiological and pharmacokinetic properties of these compounds are closely related to the size and branching of the ester group. The magnitude and time course of electrophysiological effects caused by methyl (ATI-2001), ethyl (ATI-2010), isopropyl (ATI-2064), sec-butyl (ATI-2042), and neopentyl (ATI-2054) homologs, and their common metabolite (ATI-2000) were investigated in guinea pig isolated heart. In paced hearts (atrial cycle length = 300 ms), each homolog (1 microM) was infused for 90 min followed by a 90-min washout. The stimulus-to-atrium (St-A), atrium-to-His bundle (AH), His bundle-to-ventricle (HV), QRS, and QT intervals, and ventricular monophasic action potential duration at 90% repolarization (MAPD(90)) were measured every 10 min. ATI-2001 and ATI-2064 significantly lengthened the St-A, HV, and QRS intervals, whereas ATI-2042 and ATI-2054 prolonged only the St-A interval. All compounds except the metabolite prolonged the AH interval. The relative rank order for the homologs to lengthen ventricular repolarization (MAPD(90)) was ATI-2042 > or = 2001 = 2010 = 2064 > 2054 > or = 2000. The metabolite was electrophysiologically inactive. Thus, modification of the benzofurane moiety ester group size and branching markedly altered the magnitude and time course of the electrophysiological effects caused by the ATI compounds. The different structure-activity relationships among the amiodarone homologs may have important consequences for further development of amiodarone-like antiarrhythmic agents.     

Effects of mitoxantrone on excitation-contraction coupling in guinea pig ventricular myocytes

The mechanisms of the inotropic effect of mitoxantrone (MTO), a synthetic dihydroxyanthracenedione derivative with antineoplastic activity, was investigated in guinea pig ventricular myocytes using whole-cell patch-clamp methods combined with fura-2 fluorescence and cell-edge tracking techniques. In right ventricular papillary muscles, 30 microM MTO increased isometric force of contraction as well as action potential duration (APD) in a time-dependent manner. The force of contraction was increased approximately 3-fold within 4 h. This positive inotropic effect was accompanied by a prolongation of time to peak force and relaxation time. In current-clamped single myocytes treated with 30 microM MTO for 30 min, an increase of cell shortening by 77% and a prolongation of APD by 19% was observed. Peak amplitude of the intracellular Ca(2+) transients was also increased by 10%. The contribution of APD prolongation to the enhancement of cell shortening induced by MTO was assessed by clamping control myocytes with action potentials of various duration. Prolongation of APD(90) (ADP measured at 90% of repolarization) by 24% led to an increase of cell shortening by 13%. When the cells were clamped by an action potential with constant APD, MTO still caused an increase of cell shortening by 59% within 30 min. No increase of the peak intracellular Ca(2+) transients, however, was observed under this condition. We conclude that both the APD prolongation and a direct interaction with the contractile proteins contributed to the positive inotropic effect of MTO.     

The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig.

The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials.     

葛根素注射液联合厄贝沙坦对心室快速起搏心力衰竭实验犬心房颤动及心房纤维化的影响

目的观察葛根素注射液联合厄贝沙坦对心室快速起搏致充血性心力衰竭（congestive heartfailure,CHF）实验犬心房颤动及心房纤维化的影响。方法选择健康成年杂种犬21只,随机令为正常组对照组、cI—IF模型组和TMP治疗组。采用右心室快速起搏建立实验犬CHF模型。Butst刺激诱发心房颤动（atrial fibrin;tripn,LVEF）。超声心动图仪检测实验犬左心室射血分数（1eft ventricular ejection fraction,LVEF）。Mallory’s三色法染色检测心房组织纤维比程度。采用放射免疫法测定血桨血管紧张素1[和醛固酮的浓度,测定血清m型前肢原氨基末端肽（amino．tedllldall～eptldcoflype Ⅲ procollagen,PⅢNP）、层粘连蛋白（lalTlmln,I．N）和透明质酸（hyaltlronlcacid,HA）的水平。结果CHF模型组LVEF较正常对照组明显下降（P〈0．01）;AF发生率、持续性AF发生率及AF持续时间较正常对照组均明显增加（P〈0．01）;左右心房纤维化程度较正常对照组亦有明显增加（P〈0．01）;AF持续时间与左心房纤维比程度呈密切正相关（r=0．84,P=0．018）;血浆血管紧张素Ⅱ、醛固酮以及血清PⅢNP、HA水平较正常对照组均有明显升高（P〈0．05或P〈0．01）;LN比较则无统计学差异;血浆血管紧张素Ⅱ水平与醛固酮水平均呈密切正相关（r=0．759,P=0．182）。治疗组LVEF较亡I-IF;模型组有明显改善（P〈0．05）;持续性AF发生率较CHF模型组有明显降低（P〈G．05）;左右心房纤维化程度较CHF模型组均有明显减轻（P〈0．01）。结论葛根素注射液联合厄贝沙坦可减轻Ⅱ-IF时心房纤维比的程度,这可能是其减少CHF时AF发生率及持续时间的机制之一。     

缬沙坦对慢性充血性心力衰竭合并慢房颤患者室性心律失常的影响

目的观察短期应用缬沙坦对慢性充血性心力衰竭(CHF)合并慢房颤患者室性心律失常的影响。方法选择45例CHF合并慢房颤室性心律失常患者,均给予常规治疗,加用缬沙坦胶囊80 mg,每天1次,治疗8周。治疗前后分别行动态心电图检查,测量左室射血分数(LVEF),测定血清钾浓度。结果经8周缬沙坦治疗后室性早搏、室性心动过速发生率明显降低(P0.01);缬沙坦治疗前后LEVF比较差异有统计学意义(P0.05)。结论短期应用缬沙坦可能对CHF患者室性心律失常有效。