中国萝芙木碱Verticillatine对麻醉狗和猫心功能与血流动力学的影响

Verticillatine(Vt)0.5～1.0mg/kg iv,能使麻醉狗的血压下降,心率减慢,cl,LVSP LV dp/dt max,LVWI,TPR降低,作用随剂量增加而加强。冠脉阻力稍降低,但心肌氧利用率和氧耗减少。颈内动脉和股动脉血流增加,阻力减少。给麻醉猫iv Vt和六羟季铵1.0 mg/kg后,BP,LVP和LV dp/dt max降低,但LV dp/dt/p和LVEDP无明显变化。说明Vt能降低心脏后负荷,对前负荷无明显影响。     

中国萝芙木碱Verticillatine对麻醉狗和猫心功能与血流动力学的影响

Verticillatine(Vt)0.5～1.0mg/kg iv,能使麻醉狗的血压下降,心率减慢,cl,LVSP LV dp/dt max,LVWI,TPR降低,作用随剂量增加而加强。冠脉阻力稍降低,但心肌氧利用率和氧耗减少。颈内动脉和股动脉血流增加,阻力减少。给麻醉猫iv Vt和六羟季铵1.0 mg/kg后,BP,LVP和LV dp/dt max降低,但LV dp/dt/p和LVEDP无明显变化。说明Vt能降低心脏后负荷,对前负荷无明显影响。     

人参茎叶黄酮对狗心脏血流动力学的影响

人参茎叶黄酮20mg/kg(iv)能明显降低麻醉狗的 LVP、(dp/dt)max、TPVR、BP和耗氧量。对心脏泵功能指标 CI、SI 和心肌收缩性指标 dp/dt/CPIP 无显著影响。对反映心肌收缩敏捷度的 t-(dp/dt)max 明显延长(1～40min)。对 CO、PF 无明显影响。     

小檗碱对清醒大鼠血液动力学的影响

静脉注射小檗碱(berberine,Ber)能引起清醒大鼠血压、左室压、及左室舒张末期压的降低。其下降程度DAp>SAP>LVSP心率先反射性加快后缓慢而持久下降。在后负荷及心率下降的同时并不伴有±(dp/dt)max,(dp/dt)p~(-1)的降低或LVP(dp/dt)p~(-1)环及其斜率的缩小,甚至还略有增加。这表明Ber对心肌的收缩性能有增强作用。因此降压效应主要为降低心率及外周血管阻力所致。     

心喘灵(XC-1)及其衍生物XC-2对麻醉犬血流动力学的作用

本工作比较研究了心喘灵(XC-1)及其衍生物XC-2(8204) 对麻醉开胸犬心脏血流动力学的作用。用递加剂量法静注心喘灵0.5,1.0,2.0和4.0 mg/kg,每二个剂量之间的间隔为5 min,给药后MAP和LVP下降,HR减慢,CI和SI增加,TPR降低,冠状、颈内和股动脉血流增加,血管阻力下降,±LVdp/dt max增加,而LV dp/dt/p改变不明显,LVW,CVP和MVO₂无明显变化。用同法静注同样剂量XC-2的作用和心喘灵相似,但较弱;一次静注5 mg/kg也出现柑似但较弱的作用。它们的作用是通过阻断α和β受体及直接扩张血管所引起。     

小檗碱对清醒大鼠血液动力学的影响

静脉注射小檗碱(berberine,Ber)能引起清醒大鼠血压、左室压、及左室舒张末期压的降低。其下降程度DAp>SAP>LVSP心率先反射性加快后缓慢而持久下降。在后负荷及心率下降的同时并不伴有±(dp/dt)max,(dp/dt)p^-1的降低或LVP(dp/dt)p^-1环及其斜率的缩小,甚至还略有增加。这表明Ber对心肌的收缩性能有增强作用。因此降压效应主要为降低心率及外周血管阻力所致。     

异钩藤碱的降压及血流动力学作用(英文)

在清醒正常血压大鼠,iv Isorhy2.5 mg/kg对BP及HR均无明显影响,iv5 mg/kg则使DAP和HR降低,但SAP无变化,剂量加大至10 mg/kg时,上述各项指标均明显降低。经十二指肠内给Isorhy10 mg/kg后20 min出现BP及HR降低,而20mg/kg剂量组于10 min开始出现BP及HR的进一步下降.Isorhy(10mg/kg和2 mg/kg,iv)亦能分别降低肾性高血压清醒大鼠和麻醉犬的BP。icv表明中枢不是降压作用的主要部位,在体条件下无α-受体和神经节阻断作用。Isorhy使清醒大鼠和麻醉犬的LVSP,dP/dt_(max),V_(max)等左室收缩性能指标短暂下降,而BP呈持久性降低。在麻醉犬给药后CO,CI,HR及LVWI下降的同时SV和SI不变,TPVR降低,反映心肌氧耗的TTI明显减少.结果提示Isorhy具有肯定的降压作用,其持续降压与扩张血管及减慢心率导致CO下降有关,而其负性肌力作用亦可能参与了早期的降压机理.Isorhy能减少心肌氧耗对高血压心肌劳损可能有保护意义。     

硅酸钠对犬血流动力学的作用

麻醉犬8只,iv硅酸钠10～20mg/kg,观察血流动力学各参数的影响。结果表明Na_2SiO_3可使LVSP,+dp/dt max和VCE-+dp/dtmax增加,-dp/dt max增加而T值缩短,可使SBP,DBP和MAP增加,CI增加而对HR及THR影响不大。认为升压作用与CI增加,心脏作功增加有关。     

汉防己甲素对左心室功能及外周血管的影响

麻醉狗急性实验表明,静脉注射汉防己甲素引起降压的同时,伴有LVP、±dp/dt max(左心室压正负向变化最大速率)的降低。但LVP和±dp/dt max的恢复先于血压的恢复。提示其对左心室收缩功能的抑制仅与初期降压效应部分有关。本品降低血压和外周阻力以及减慢心率的作用较持久,其对舒张压的降低作用大干对收缩压的影响。结果表明汉防己甲素的降压效应主要系通过扩张阻力血管所致。     

人参茎叶皂甙对狗心脏血流动力学的影响

实验表明人参茎叶皂甙(GSL)50mg/kg i.v.可使狗左室泵功能和心肌收缩性发生程度不同的改变,可使 LVP,CO,CI,TPVR,BP,HR,耗氧量,(dp/dt)max,(dp/dt)/CPIP等下降,PF,SI,t-(dp/dt)max 等上升。这些结果与目前掌握的人参根总皂甙对狗血流动力学的影响基本一致。     

Renal vascular effects of dilazep antagonized by 3-isobutyl-1-methyl-xanthine

The effects of different doses of dilazep on renal hemodynamics, urine formation, and renin release were studied in anesthetized dogs. Intrarenal arterial infusion of dilazep (1 microgram/kg/min) increased renal blood flow, with no change in systemic arterial blood pressure and renal venous plasma renin activity. Renal vasodilation induced by dilazep was completely inhibited by intrarenal arterial infusion of 3-isobutyl-1-methyl-xanthine (IBMX; 11.1 micrograms/kg/min), a potent adenosine receptor antagonist, but not by indomethacin (13 mg/kg i.v.). These results suggest that dilazep has a vasodilatory action in the kidney--one that is independent of the renal renin-angiotensin system. The inhibitory action of IBMX on the dilazep-induced renal vasodilation indicates that the renal vascular effects of dilazep may be exerted by augmentation of endogenous adenosine and mediated through adenosine receptors.     

General pharmacological actions of traxanox sodium. II. Effects on the cardiovascular system

The effects of traxanox, an anti-allergic drug, on the cardiovascular system were studied in both anesthetized dogs and cats and in isolated heart preparations from guinea-pigs. In anesthetized dogs, a very small dose of traxanox (0.01 mg/kg, i.v.) had no effect, but 0.1--30 mg/kg caused an increase in respiratory rate, hypotension, bradycardia, a transient decrease followed by an increase in renal blood flow, and a decrease in femoral blood flow. These effects were abolished by vagal block, indicating they are mediated via vagal afferents. In contrast, oral administration of traxanox (100 mg/kg) had no effect on the blood pressure or heart rate of anesthetized dogs. In anesthetized cats, traxanox (3 and 30 mg/kg, i.v.) caused a slight increase in blood pressure, but showed no effect on respiratory rate and heart rate. Both traxanox and theophylline (10(-4)M) caused increases in the beat rate of the atria and the contractile force of the papillary muscle in isolated preparations from guinea-pigs, and they potentiated the positive chronotropic and inotropic responses induced by isoproterenol. On the other hand, in anesthetized and vagotomized dogs, traxanox (3 and 10 mg/kg, i.v.) affected neither the left ventricular contractile force nor the hypotension and positive inotropic and chronotropic responses produced by isoproterenol. Administration of theophylline alone (3 and 10 mg/kg, i.v.) caused hypotension and increases in contractile force and heart rate, but it did not enhance the responses produced by isoproterenol. At doses of 1 and 10 mg/kg (i.v.), traxanox had little effect on either pressor or chronotropic responses to norepinephrine, epinephrine, DMPP and stellate cardiac nerve stimulation. The same doses of traxanox slightly reduced the depressor and chronotropic responses to isoproterenol, acetylcholine and vagus nerve stimulation. These findings suggest that traxanox had no effect on the cardiovascular systems of the animals studied in the dose range (1--5 mg/kg, p.o.) showing anti-allergic activity.     

Modification of cardiovascular responses to intravenous phenytoin by dopamine in dogs: Evidence against an adverse interaction

Phenytoin (sodium diphenylhydantoin) was studied for its blood pressure and heart rate effects in conscious and anesthetized dogs, alone and in combination with dopamine HCl. In conscious dogs phenytoin administered intravenously (0.15–1.0 mg/kg/min) at different infusion rates (total dose, 25 mg/kg) produced consistent central nervous system (CNS) excitation (agitation, emesis, incoordination) at doses below those required to produce hypotension. Concomitant administration of phenytoin (total dose, 23–32 mg/kg) and dopamine (2.5, 10, or 25 μg/kg/min) did not produce adverse effects on blood pressure and heart rate. In the anesthetized dog, iv infusions of phenytoin (0.88–1.0 mg/kg/min for 70 min) produced a progressive lowering of blood pressure and heart rate, and four of seven dogs died (total dose, 55–70 mg/kg). When dopamine (25 μg/kg/min) and phenytoin were infused simultaneously, the blood pressure and heart rate changes were reduced, and only one of seven dogs died (total dose, 71 mg/kg). When the dopamine infusion was started after phenytoin had already produced a severe hypotension or after the total dose of phenytoin had been given, dopamine raised the blood pressure and heart rate in four of seven dogs. Three dogs failed to respond and died (total dose, 65–77 mg/kg). These experiments show that phenytoin and dopamine do not adversely interact to produce cardiovascular collapse in dogs and suggest that dopamine may be supportive in phenytoin-induced hypotension, thus supporting the simultaneous use of these agents where clinically indicated in man.     

A novel orally active dopamine (DA) prodrug TA-870. IV. Renal vasodilatory and negative chronotropic effects in anesthetized dogs: influence of DA1 and DA2 dopamine receptor selective antagonists.

We investigated the involvement of the activations of dopamine (DA) receptors DA1 and DA2 in the effects of a novel DA prodrug TA-870 in anesthetized dogs and compared the effects with those of DA. Intravenous (i.v.) administration of TA-870 in anesthetized dogs produced a dose-dependent increase in free DA in blood and caused a decrease in renal vascular resistance (RVR) and an increase in renal blood flow (RBF). It also produced a bradycardia at high doses. In phenoxybenzamine-treated anesthetized dogs, the renal vasodilatory action of intrarenally administered TA-870 was less than or equal to that of i.v. TA-870, whereas that of intrarenally administered DA was greater than that of i.v. DA. The renal vasodilatory effects of TA-870 and DA were almost completely inhibited by the DA1 selective antagonist SCH-23390 but were not affected by the DA2 selective antagonist domperidone. In bilaterally vagotomized dogs, both TA-870 and DA at high doses partially reduced the positive chronotropic responses to the right postganglionic cardioaccelerator nerve stimulation; this effect was abolished after treatment with domperidone. In isolated guinea pig right atria, unchanged TA-870 and deethoxycarbonyl metabolite of TA-870, the intermediate from TA-870 to DA, did not affect the spontaneous atrial rate even at high concentrations, whereas DA produced a concentration-dependent increase in the rate. In addition, neither compound showed antagonistic action to the positive chronotropic effect of DA, which was competitively inhibited by propranolol. We conclude that the renal vasodilatory effect of TA-870 results simply from the activation of DA1 receptors by DA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenoceptor blocking hemodynamic and coronary effects of YM-09538, a new combined alpha- and beta-adrenoceptor blocking drug, in anesthetized dogs

In anesthetized dogs. YM-09538, a new sulfonamide-substituted phenylethylamine, competitively antagonised the phenylephrine-induced vasopressor response with a DR10 of 0.50 mg/kg i.v. and the isoproterenol-induced positive chronotropic response with a DR10 of 0.66 mg/kg i.v., indicating that YM-09538 blocks both alpha 1- and beta 1-adrenoceptors and almost to the same extent. YM-09538 was 4 times more potent than phentolamine in blocking alpha 1-adrenoceptors and 3 times less potent than propranolol in blocking beta 1-adrenoceptors. YM-09538 non-selectively blocked cardiac beta 1- and vascular beta 2-receptors and was devoid of intrinsic beta-sympathomimetic and local anesthetic activities. In anesthetized closed-chest dogs, YM-09538 resembled propranolol in reducing heart rate, cardiac output, max. dLVP/dt and left ventricular cardiac work but differed from propranolol in decreasing total peripheral resistance, in increasing femoral blood flow, in causing larger falls in arterial blood pressure and in decreasing pulmonary arterial pressure. In anesthetized open-chest dogs, YM-09538 reduced heart rate, myocardial contractile force and arterial blood pressure. In non-ischemic myocardium, transmural flow and coronary vascular resistance were respectively strongly increased and decreased and the endo/epi flow ratio was slightly but not significantly reduced. In ischemic myocardium, YM-09538 also increased transmural flow and since endocardial and epicardial flows were augmented to the same extent, the endo/epi flow ratio remained unchanged. All these hemodynamic and coronary effects of YM-09538 can be accounted for the drug's combined alpha- and beta-adrenoceptors blocking properties.     

Cardiovascular effects of nicorandil and nitroprusside in furosemide plus digoxin pretreated dogs

In support of human congestive heart failure (CHF) trials, the cardiovascular effects of the vasodilators nicorandil (NIC) and nitroprusside (NP) were examined in anesthetized and conscious dogs pretreated with the diuretic furosemide (FURO) and the cardiac glycoside digoxin (DIG). In anesthetized control dogs, iv NP (2–19 μg/kg/min) and NIC (24–105 μg/kg/min) maximally reduced mean arterial pressure (MAP) by 43 and 40 mmHg, respectively, with moderate increases in heart rate (HR). These hypotensive responses to NP and NIC were unmodified by iv FURO (2.65 mg/kg) + DIG (0.075 mg/kg) pretreatment (PT). FURO + DIG reduced central venous pressure (CVP) BY 3 mmHg, masking the separate effects of NP and NIC. In a third group, FURO's fluid volume depletion and DIG's plasma concentrations were unaffected by adjunctive NIC infused for 2.5 h at a mean 17 μg/kg/min iv. No untoward interactions were seen with any combination. In conscious dogs, the hypotension and tachycardia seen with iv NP (2–20 μg/kg/min) and NIC (20–160 μg/kg/min) were also unchanged after 5 days of oral FURO (5 mg/kg/day) and DIG (0.0125 mg/kg/day), with no intolerance. Repeated oral NIC (7.5 mg/kg/day × 3 days) in these chronic FURO + DIG dogs ws consistently hypotensive but steadily more tachycardiac. This study offers a prototype of 3-way CHF drug interaction, demonstrates that NIC and NP can be safely combined with acute and chronic FURO and DIG, and shows that these CHF agents minimally affect the cardiovascular responses to NIC and NP in dogs.     

Effect of propranolol on cortical electrical activity in conscious and anesthetized rats

The effect of propranolol on electrocorticographic (ECoG) activity was studied in conscious and anesthetized rats. Cortical electrodes and femoral venous cannulae were implanted 5 days before the experiments. The ECoG was recorded continuously and analyzed to different frequency bands, 2 hr before and 4 hr after the administration of propranolol. After a single infusion of 2 and 5 mg/kg or 5 consecutive daily doses of 2 mg/kg propranolol, frequent bursts of large amplitude 6-7 c/sec wave in the ECoG were observed. This ECoG phenomenon lasted between 60-100 min after the infusion of propranolol and was entirely abolished by pentobarbital anesthesia. Frequency analysis of the ECoG showed an immediate shift from predominantly delta (delta 0.5-4 c/sec) activity to overwhelmingly theta (theta 4-8 c/sec) activity following the infusion of propranolol. It is suggested that these changes in ECoG induced by propranolol are related to the sleep-enhancing and tranquilizing effects of propranolol.     

Pharmacological studies of celiprolol: III. Effects of celiprolol on the cardiovascular system and renal function, and its antiarrhythmic effects

Effects of celiprolol on the cardiovascular system and renal function, and its antiarrhythmic effects were studied. 1. In anesthetized dogs, celiprolol (0.01-3 mg/kg, i.v.) dose-dependently depressed the maximum rate of rise of left ventricular pressure, cardiac output and cardiac work less severely than propranolol and atenolol. 2. Celiprolol (0.01 mg/kg, i.v.) decreased the myocardial oxygen consumption in anesthetized dogs as potently as propranolol. 3. Celiprolol (0.03-3 mg/kg, i.v.) tended to increase femoral blood flow. Celiprolol (1 mg/kg, i.v.) increased common carotid blood flow. 4. Celiprolol decreased urine volume and urinary excretion of Na+ and Cl- at doses of 1 and 10 mg/kg and increased the sodium reabsorption rate at a dose of 10 mg/kg in anesthetized dogs, whereas it produced no change in plasma renin activity. 5. Celiprolol inhibited both halothane-adrenaline arrhythmia in dogs and ouabain-induced arrhythmia in rabbits. Its antiarrhythmic effects were 1/10-1/3 as potent as those of propranolol. 6. Celiprolol suppressed the maximum rate of rise of action potential at a concentration of 3 x 10(-4) M, which was 30 times as high as that of propranolol. Celiprolol (3 x 10(-5)-3 x 10(-4) M) dose-dependently shortened the effective refractory period (ERP), but it produced no change in the ratio of ERP to action potential duration. 7. These results suggest that celiprolol may be a useful drug for the treatment of ischemic heart disease and some types of arrhythmia, and that it has only a little influence on renal function.     

CK-2289 and milrinone in dogs with propranolol-induced heart failure: Effect of ouabain

We examined the interaction between ouabain and CK-2289, a new bivalent inodilator, and compared their effect with that of milrinone on the hemodynamic and myocardial energetic parameters of anesthetized dogs with propranolol-induced heart failure (PIHF). Mongrel dogs (13–19 kg) of either sex were anesthetized with pentobarbital sodium (35 mg/kg, i. v.) and instrumented for routine hemodynamic measurements using an open-chest, artificially ventilated preparation. PIHF was produced by decreasing left ventricular (LV) dP/dT_max by 50% from control values with an initial infusion of 0.5 mg/kg of propranolol followed by continuous infusion of 0.02 to 0.08 mg/kg of propranolol to maintain PIHF. This was followed by infusion of saline (2 ml, i. v., n = 12/group) or ouabain (25 μg/kg, i. v., n = 12/group). Thirty min later saline and ouabain-treated animals (4/group) were given 2 doses of saline (1 and 2 ml, i. v.), CK-2289 (0.01 and 0.03 mg/kg, i. v.) or milrinone (0.03 and 0.1 mg/kg, i. v.) 30 min apart. Hemodynamic parameters were monitored continuously. Myocardial oxygen consumption (MVO₂) was monitored 15 and 30 min after each dose of drug. CK-2289 increased LV dP/dT_max and LV dP/dT_min by 60 and 120% and 42 and 43%, respectively. Mean arterial pressure decreased by 12% after the high dose of CK-2289. CK-2289 did not affect heart rate, while LV end diastolic pressure decreased by 5 mmHg. CK-2289 increased LV work and did not affect or decrease LV contractile efficiency. Ouabain enhanced the myocardial energetic profile of CK-2289 by allowing CK-2289 to stimulate more work at a lower MVO₂, thereby increasing myocardial efficiency. Milrinone had a profile similar to CK-2289 but in ouabain-pretreated animals with PIHF milrinone stimulated less work at the same MVO₂, thus decreasing contractile efficiency. Thus, ouabain may enhance the myocardial energetic effects of CK-2289.     

Differential action of KR‐31378, a novel potassium channel activator,on cardioprotective and hemodynamic effects

The cardioprotective and hemodynamic effects of KR‐31378, a highly cardioselective ATP‐sensitive potassium channel activator with minimal hypotensive effect, were evaluated in rats and dogs, and compared with those of BMS‐191095 and lemakalim. KR‐31378 did not show any significant effect on methoxamine‐induced aortic constriction up to doses of 300 μM, whereas BMS 191095 produced a moderately potent relaxant effect (IC₅₀: 9.0 μM). In conscious rats, KR‐31378 slightly increased blood pressure only at high dose (100 mg/kg, iv), unlike BMS‐191095 that dose‐dependently decreased blood pressure (ED₂₀: 2.03 mg/kg). In anesthetized beagle dogs, KR‐31378 was approximately 100‐fold less potent than BMS‐191095 for most hemodynamic parameters (iv ED₂₀ for blood pressure lowering: 33.7 and 0.37 mg/kg, respectively). In anesthetized rats subjected to 45‐min coronary occlusion and 90‐min reperfusion, KR‐31378 (iv) dose‐dependently reduced the infarct zone from 58.6% to 42.1%, 36.6%, and 34.3% for 0.1, 0.3, and 1.0 mg/kg, respectively (P < 0.05), the effects being comparable to those of BMS 191095. In anesthetized beagle dogs that underwent 2‐h occlusion followed by 4.5‐h reperfusion, KR‐31378 (2 mg/kg, iv infusion) markedly reduced the infarct zone from 48.7% in controls to 19.1% at a dose of 2 mg/kg (P < 0.05). The reduction in infarct zone afforded by KR‐31378 in rats was inhibited by pretreatment with selective ATP‐sensitive potassium channel blockers, sodium 5‐hydroxydecanoate and glibenclamide. These results indicate that KR‐31378 is a potent cardioprotective agent with potentially minimal hypotensive effects. Thus, it could be potentially useful in the prevention and treatment of acute myocardial infarction. Drug Dev. Res. 54:182–190, 2001. © 2002 Wiley‐Liss, Inc.