蝙蝠葛酚性碱对犬血流动力学及冠脉循环的影响蝙蝠葛酚性碱对犬血流动力学及冠脉循环的影响

目的研究蝙蝠葛酚性碱（PAMD）对正常麻醉犬血流动力学、冠脉循环及心肌氧代谢的影响。方法设立生理盐水阴性对照组及PAMD 3.5和7.0 mg·kg^-1两剂量组，在不同时间点观察各组犬血流动力学、冠脉循环及心肌氧代谢的相关指标的改变。结果与药前相比，PAMD两剂量组均可降低左心室收缩压（LVSP）和±dP/dt_max，减慢心率，增加心肌氧含量、降低心肌氧利用率，且具有增加冠状动脉血流量，降低冠状动脉阻力和外周阻力的作用。对血压、心输出量和左室舒张末压（LVEDP）无显著影响。结论PAMD能改善血流动力学、冠脉循环及心肌氧代谢。     

Comparative study of the activity of boric, benzene-boronic and methyl-benzene-boronic acids upon respiration, general metabolism and systemic hemodynamics of the anesthetized dog.

The authors compared the action of boric, benzene-boronic and p-methyl-benzene-boronic acids on respiration and general metabolism and on systemic hemodynamics of the anesthetized dog. They further investigated the effects on the arterial blood pressure in the rat and on the isolated rabbit heart. In the dogs, the three acids were shown to have no significant action on the systolic, diastolic and mean arterial blood pressures and a slight stimulating action on the differential arterial blood pressure. On the contrary, in the rat, all the acids were hypotensive. This action was dose dependent. In the entire animal, as well as in the isolated rabbit heart, benzene-boronic and p-methyl-benzene-boronic acids depressed the myocardial contractility. Whereas boric acid did not act on the heart contractility in situ in anesthetized dogs, it slightly stimulated the myocardial contractility of the isolated rabbit heart. The two acids seemed to be directly active on the myocardial cell. In the anesthetized dog, cardiac performances were first depressed then stimulated. Both benzene-boronic and p-methyl-benzene-boronic acids were ventilatory depressors: they reduced ventilatory output and rhythm, they first decreased then increased total O2 consumption and CO2 production.     

The effect of prazosin on the hemodynamics of the anesthetized dog

Effect of prazosin (0.1 and 1.0 mg/kg b.w. i.v.) on the cardiovascular system was investigated in six anaesthetized Beagles (Na-pentobarbital 35 mg/kg i.p.) using the thermodilution and catheter methods. The following parameters were measured: a) mean arterial blood pressure, b) heart rate, c) total peripheral resistance, d) cardiac output, e) cardiac work, f) stroke volume and g) cardiac contractility. Results can be summarized as follows: 1. Prazosin in dose of 0.1 mg/kg i.v. caused a slight drop in arterial blood pressure; prazosin administered in dose of 1.0 mg/kg i.v. decreased blood pressure significantly. 2. Following doses of 0.1 and 1.0 mg/kg i.v. of prazosin, heart rate was significantly increased in each of six dogs. 3. When prazosin was given i.v. (0.1 and 1.0 mg/kg), an initial increase in cardiac output occurred. Later, a reduction in cardiac index below the control values could be observed. 4. The contractility parameters of the left ventricle--dp/dtmax and VCE--were increased after i.v. administration of 0.1 and 1.0 mg/kg b.w. of prazosin.     

Effects of nisoldipine on coronary collateral perfusion and hemodynamics in chronically instrumented dogs

The effect of a new dihydropyridine slow-channel calcium blocking agent, nisoldipine, on hemodynamics and myocardial blood flow in normal and collateral-dependent areas distal to a chronic coronary artery occlusion were studied in chronically instrumented, conscious dogs. Nisoldipine produced significant and dose-related decreases in arterial blood pressure, an elevation of heart rate and large increases in coronary blood flow velocity. In dogs with an Ameroid constrictor previously implanted to enhance coronary collateral development, this agent produced large increases in perfusion distal to a chronic coronary artery occlusion. In addition, despite a reduction in arterial pressure, nisoldipine preserved renal cortical, intestinal and skeletal muscle blood flow while increasing tissue flow within liver and cerebral cortex. Thus, nisoldipine increases oxygen supply to collateral-dependent myocardium in the presence of reduced driving pressure for collateral perfusion.     

蛇床子素对麻醉开胸犬心电图和血流动力学的影响

麻醉开胸犬，ｉｖ７．５－１５ｍｇ·ｋｇ￣（－１）蛇床子素后，收缩期血压，舒张期血压，平均血压，左室收缩压，室内压最大上升速率及心输出量，总外周阻力均降低，在１０ｍｉｎ时为作用高峰；ｉｖ７．５ｍｇ·ｋｇ￣（－１），心电困无影响，但ｉｖ１５ｍｇ·ｋｇ￣（－１），心电图的Ｐ－Ｒ间期略延长。且室内压最大下降速率也降低。提示蛇床子素有抑制心脏作用，且外周阻力降低，血压下降，故在临床应用时应引起注意。     

Effect of ouabain on insulin secretion in the anesthetized dog

The effect of ouabain on insulin secretion has been studied in the anesthetized dog. Blood glucose, plasma free fatty acids and plasma amino nitrogen were determined simultaneously. When infused at a dose of 1 μg/kg/min, ouabain significantly reduces blood glucose and plasma free fatty acid levels and increases plasma amino nitrogen. Plasma insulin concentrations are significantly increased in both arterial and pancreaticoduodenal venous blood. The pancreaticoduodenal vein blood flow is not significantly modified. Calculated pancreatic insulin production is markedly increased during ouabain infusion. These findings were confirmed using “one shot” injections of ouabain. The mechanism of the marked in vivo effect of ouabain on insulin production is discussed.     

注射用红景天苷对麻醉犬血流动力学的影响

目的:观察注射用红景天苷对麻醉犬血流动力学的影响。方法:杂种犬36只,人工呼吸下开胸,给药后观察其心率(HR)、血压(MAP)、心输出量(CO)、冠脉血流量(CBF)、左室压(LVP)、左心室舒张末期压(LVEDP)、左室等容收缩期压力最大变化率(±LVdP/dtmax)等指标,计算冠脉阻力(CVR)和体循环总外周阻力(TPR)等血流动力学指标。结果:红景天苷(2,4,8 mg.kg-1)对MAP,HR和LVP无明显影响,能显著增加CBF和CO,±LVdP/dtm ax也出现不同程度的增加,同时LVEDP,CVR和TPR降低。结论:注射用红景天苷能明显改善麻醉开胸犬的血流动力学指标。     

Effects of a 2',3',5'-substituted adenosine derivative on systemic and coronary hemodynamics and on cardiac metabolism in the anesthetized dog

Hemodynamic and metabolic effects of 2',3'-O-methoxyethylidene-adenosine-5'-(Nethyl-carboxamide) (744-98), an adenosine analogue with long-lasting coronary dilator activity, were studied in the anesthetized, closed-chest dog. The coronary sinus outflow increased 5fold following administration of the compound (5 microgram/kg i.v.) and still remained three thimes higher than the control level after 4 h. Total peripheral resistance decreased markedly, accompanied by a baroreceptor-mediated increase in heart rate, left ventricular dp/dtmax and myocardial oxygen consumption. Blood glucose levels and glucose uptake by the heart increased concomitantly, whereas plasma free fatty acid (FFA) levels decreased markedly, without consistent changes in myocardial FFA balance. These effects are explained by antilipolytic and glucagon-releasing activities of the adenosine analogue. The myocardial oxygen extraction ratio for glucose greatly exceeded the aerobic metabolic requirement, a finding already previously obtained with coronary dilators.     

The effect of the cardiotonic imazodan (CI-914) on myocardial and peripheral hemodynamics in the anesthetized dog

The purpose of this study was to evaluate the effect of the new cardiotonic, imazodan (CI-914), on myocardial hemodynamics and oxygen consumption, and peripheral blood flow distribution. Organ blood flow was measured by the radiolabeled-microsphere-reference-withdrawal technique and myocardial oxygen consumption calculated from arterial and coronary sinus O2 content and blood flow. At inotropic levels, CI-914 decreases mean arterial pressure with a minimal increase in heart rate. CI-914 decreases coronary vascular resistance and increases supply to demand ratio, indicating an active coronary vasodilation. CI-914 does not alter peripheral blood flow distribution, thus suggesting equivalent organ vasodilation. These data suggest that CI-914 may be useful in the treatment of congestive heart failure because of its positive inotropic, coronary vasodilator, and peripheral vasodilator properties.     

Effect of dopamine on renin secretion in the anesthetized dog.

Intrarenal perfusion of dopamine (6 mug/kg/min for 10 min) caused a significant increase of renin secretion, together with a significant increase in renal blood flow. This renin hypersecretion is not accompanied by any significant alteration in renal perfusion pressure, kalemia or natriuresis. The role of intrarenal dopaminergic receptors has been studied: (a) Haloperidol (intrarenal perfusion of 50 mug/kg/min for 20 min) suppresses the renal vasodilation and renin hypersecretion induced by dopamine. (b) Propranolol (intrarenal perfusion of 1 mg/kg in 15 min, then of 4 mg/kg/hr) alters neither the renal vasodilation nor the renin hypersecretion induced by dopamine. These observations support the assumption that the dopaminergic receptors are brought into play in the two renal responses to dopamine studied by us.     

Comparison of vasodilating effects of nisoldipine and nifedipine in anesthetized open-chest dogs

Hemodynamic effects of nisoldipine (Bay k 5552) were compared with those of nifedipine in anesthetized open-chest dogs. Both nisoldipine and nifedipine produced a fall in aortic pressure and increases in aortic, vertebral and coronary blood flows. After administration of nisoldipine, renal blood flow, heart rate and left ventricular enddiastolic pressure were not changed, but left ventricular dP/dt was increased. After administration of nifedipine, renal blood flow and left ventricular dP/dt were decreased, and left ventricular enddiastolic pressure was elevated. Heart rate was hardly changed. Durations of increases in aortic, vertebral and coronary blood flows were about 3 times longer after nisoldipine than after nifedipine. Percent decrease in coronary vascular resistance was greater and percent decrease in renal vascular resistance was smaller than that in total peripheral vascular resistance with both nisoldipine and nifedipine. Results indicate that nisoldipine and nifedipine produce marked coronary vasoldilation and the vasodilating effect of nisoldipine lasts longer than that of nifedipine.     

Effect of kavinton on systemic and regional hemodynamics in waking and anesthetized rats

The effect of cavinton (vinpocetine) on the systemic and regional hemodynamic parameters was studied by the radioactive microsphere technique in experiments on conscious and anesthetized rats. Intravenous administration of cavinton (10 mg/kg) was followed by the development of hypotension and bradycardia in conscious and anesthetized animals. Administration of cavinton to anesthetized rats increased the blood flow both in the brain and in most internal organs. In conscious animals the drug failed to increase the cerebral blood flow but increased the blood flow in the internal organs. It is suggested that dilation of the cerebral vessels under the influence of cavinton only in anesthetized rats could be related to a higher initial resistance of the cerebral vessels in anesthetized animals as compared with conscious ones.     

Inhibitory effect of nisoldipine on angiotensin-II-induced renal actions in anesthetized dogs

Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anesthetized dogs. Intrarenal arterial infusion of nisoldipine (2, 10, and 50 ng/kg per min) had no effect on mean systemic blood pressure and heart rate and there was no significant change in renal hemodynamics during infusion of various doses of the drug. Urine flow and urinary excretions of sodium, chloride, and potassium were increased by nisoldipine in a dose-related manner. Fractional excretions of sodium and chloride were markedly elevated with the highest dose given thereby indicating that tubular reabsorptions of sodium and chloride were inhibited by nisoldipine. Nisoldipine (50 ng/kg per min) abolished the decreasing effects of angiotensin-II on glomerular filtration rate, urine flow, and urinary excretion of electrolytes but not the decrease in renal blood flow by the peptide. Angiotensin-II-induced reduction of fractional excretion of electrolytes was completely blocked by nisoldipine. Renal responses to norepinephrine were unaffected by nisoldipine. Thus, nisoldipine administered intrarenally to anesthetized dogs exerts a diuretic action by way of tubular effects, as is the case with other dihydropyridine calcium channel blockers. Nisoldipine seems to effectively antagonize the renal response to angiotensin-II. Thus, the preferential inhibition of angiotensin-II-induced antidiuresis may mean that nisoldipine interferes with stimulatory effects of angiotensin-II on the renal tubular reabsorption of electrolytes and water.     

Pharmacokinetics of nisoldipine. III. Biotransformation of nisoldipine in rat, dog, monkey, and man

After intraduodenal administration of 14C-labelled (+/-) 3-isobutyl-5-methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylate (nisoldipine, Bay k 5552) to rats approx. 68% of the dose was excreted in the bile in the first 6 h. In an isolated perfused rat liver model the excretion with the bile was 56% of the total dose within 3 h. The recovery of radioactivity from orally administered [14C] nisoldipine was approx. 32% (rat), 23% (dog), 73% (monkey) and 74% (man), resp., in the urine. The unchanged drug was neither detected in the urine nor in the bile, but nisoldipine was present in plasma of the rat 30 min after dosing and up to 24 h in man. The drug was extensively metabolized: 18 biotransformation products were identified by comparison with synthetic reference compounds using combined GC-MS, 1 NMR-spectroscopy, mass spectrometry, gas chromatography/radio-gas chromatography and two-dimensional thin layer chromatography, 6 of them being quantitatively important (about 80% of the radioactivity excreted in urine). The metabolites identified accounted for approx. 82% (rat: bile and urine), 19% (dog, due to the low renal excretion), 58% (monkey: urine) and 64% (man: urine) of the excreted dose, resp. The following biotransformation steps occurred: hydroxylation of the isobutyl moiety, dehydrogenation of the 1,4-dihydropyridine system, oxidative ester cleavage, hydroxylation of one of the methyl groups in 2- or 6-position and subsequent oxidation to the carboxylic acid, oxidation of one of the methyl groups of the isobutyl moiety to the carboxyl group reduction of the aromatic nitro group (minor biotransformation reaction) and glucuronidation as phase II reaction.     

Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs

Inhibitory effects of the calcium channel blocker nisoldipine on angiotensin II-induced antidiuresis were investigated in anesthetized dogs, and the findings were compared with those of saralasin. Intrarenal arterial infusion of 10 ng/kg/min angiotensin II resulted in marked decreases in renal blood flow (RBF) and urine formation, with a relatively moderate decrease in glomerular filtration rate. There were marked reductions in the fractional excretion of lithium, which is used as an index of the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. Nisoldipine (50 ng/kg/min) administered intrarenally produced a partial inhibition on the decreased response of RBF to angiotensin II. The peptide-induced decreases in urine flow, urinary excretion of electrolytes and fractional excretion of electrolytes were abolished by nisoldipine. In contrast, when saralasin was administered intrarenally at 10 ng/kg/min, a dose which could partially inhibit the angiotensin II-induced decrease in RBF to the same extent as seen with nisoldipine, the antagonist attenuated, but did not abolish, the antidiuretic action of angiotensin II. Significant decreases in urine formation by angiotensin II were observed, even in the presence of saralasin. These results suggest that nisoldipine, unlike saralasin, preferentially interferes with the stimulatory effect of angiotensin II, as related to the renal tubular reabsorption of sodium and water.     

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。