牡荆素对麻醉犬血流动力学及心肌耗氧量的影响

目的研究牡荆素对麻醉犬血流动力学及心肌耗氧量的影响。方法杂种犬30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）及血氧含量。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。采用多普勒超声血流仪测定麻醉犬冠脉流量和心输出量,用血气分析仪测定血氧含量。结果牡荆素可减慢心率和左心室内压,并显著增加麻醉犬冠脉血流量和心输出量,降低总外周血管阻力和冠脉阻力,提高心搏出量、心搏指数及心脏指数。结论牡荆素可显著改善麻醉犬血流动力学参数。     

Chronic cardiovascular effects of bepridil in anesthetized and conscious dogs

The chronic cardiovascular effects of bepridil were investigated in pentobarbital-anesthetized dogs following chronic administration for 2 weeks and in awake instrumented dogs for 5 days. Prolonged administration of bepridil, 10 mg/kg, p.o., twice a day for 14 days produced a significant reduction in heart rate, cardiac output, and left ventricular minute work in dogs anesthetized approximately 12 hr following the last dose of the compound. Bepridil significantly increased coronary blood flow, whereas renal and mesenteric flows were not altered. Myocardial contractility was not significantly altered; however, left ventricular stroke work curves obtained during acute volume loading shifted to the left, indicating enhanced myocardial performance. Oral administration of bepridil twice daily produced a significant reduction in mean arterial blood pressure, a significant decrease in left ventricular stroke work and minute work, and myocardial oxygen consumption in awake animals. In addition, the compound decreased total peripheral resistance (TPR) in awake animals, whereas TPR was increased in anesthetized dogs.     

生脉输液对麻醉犬血流动力学及心肌耗氧量的影响

目的研究生脉输液对麻醉犬血流动力学及心肌耗氧量的影响。方法将杂种犬36只,随机分为6组(每组6只):对照组、阳性药组(硝酸甘油注射液组和生脉注射液组)、生脉输液高、中、低三个剂量组。人工呼吸下开胸,观察用药前后不同时间点麻醉犬的冠脉流量(CBF)、心输出量(CO)、冠脉阻力(CAVR)、总外周阻力(TPVR)、心搏出量(SV)、心搏指数(SI)、心脏指数(CI)、左室作功(LVSW)、心肌血流量(MBF)、心肌耗氧指数(MOCI)、耗氧量(VO2)、心肌氧利用率(MOUR)等指标的变化。结果与对照组比较,生脉输液(200,100 mg生药.kg-1)能显著增加麻醉犬冠状动脉和主动脉的血流量、增加心肌血流量,降低总外周血管阻力和冠状动脉阻力,提高心搏出量和心肌氧利用率。结论生脉输液对麻醉犬血流动力学参数有改善作用,具有良好的抗心肌缺血作用。     

益气通脉口服液对麻醉犬心脏血流动力学的影响

研究了益气通脉口服液对麻醉犬心脏血流动力学的影响。结果表明,益气通脉口服液可显著增加冠脉血流量、降低冠流阻力、明显增加心输出量、心搏出量、降低外周阻力、增加左室作功     

Cardiovascular Haemodynamics of Oriental Hornet Venom Sac Extract

Abstract: The effects of hornet venom sac extract on the functioning of the cardiovascular system was assessed in dogs by concomitant examination of the following parameters: Systemic blood pressure, blood pressure and the dp/dt derivative of the left ventricle of the heart, heart rate, direct measurement of the left ventricular wall thickness, cardiac output, and body temperature. The effect of adult hornet venom sac extract on the canine cardiovascular system was rapid and led to a sharp drop in the systemic blood pressure, a similar drop in the pressure and dp/dt derivative in the left ventricle, to bradycardia, immediate thickening of the left ventricular wall and to an immediate rise in the cardiac output. As for the canine temperature, this dropped immediately following the administration of venom sac extract and remained at the new low level for at least 30 min. The smaller molecular weight components (less than 10 kilodalton) in venom sac extract have been found to be responsible for the immediate effects of venom sac extract on the cardiovascular system. On the other hand the high-molecular weight components exert more delayed effects which lead to a cumulative disturbance of cardiac function.     

Cardiovascular alterations in the hypothyroid rat.

We conducted the present studies in intact animals to assess alterations in integrated cardiovascular function due to hypothyroidism. Rats were surgically thyroidectomized or sham operated. Most obvious among the alterations detected under resting conditions was the bradycardia present in hypothyroid animals. Cardiac output was significantly reduced by slower heart rate; however, mean arterial blood pressure and left ventricular +dP/dt were maintained. Total peripheral resistance was increased in hypothyroid animals. Functional responsiveness to hemodynamic challenges unmasked additional characteristics. Thyroidectomized animals had normal stroke index-left ventricular end diastolic pressure relationships in response to rapid volume infusion. Peak left ventricular +dP/dt response to brief aortic occlusion was attenuated in thyroidectomized animals. Hypothyroid rats failed to augment left ventricular -dP/dt in response to isoproterenol challenge. Moreover, isoproterenol failed to reduce total peripheral resistance in the hypothyroid rat. Therefore, the hemodynamic responses observed in the intact, hypothyroid animal are consistent with the presence of (a) decreased cardiac contractile protein ATPase, (b) reduced calcium uptake by cardiac sarcoplasmic reticulum and (c) altered vascular adrenergic receptors. Many cellular and subcellular defects are compensated by integrative mechanisms operating under resting conditions, while other defects are unmasked only when examined in the intact, functional cardiovascular system undergoing hemodynamic challenge.     

Hemodynamic effects of the serotonergic agent quipazine in the anesthetized dog

The hemodynamic effects of quipazine, a serotonergic agent, were determined in pentobarbital-anesthetized, open-chest dogs administering the drug IV, either by bolus injection or by continuous infusion. Bolus injections of 0.1 and 1 mg/kg elicited transient increases in blood pressure, peripheral resistance, aortic flow, and stroke volume. Administration of 10 mg/kg decreased blood pressure, aortic flow, heart rate, cardiac contractility, and venous pressure, and increased stroke volume. Infusion of quipazine at a rate of 0.5 mg/kg/min for 30 min initially increased blood pressure and peripheral resistance and subsequently produced hypotension and decreased cardiac function. From the beginning of infusion, heart rate and venous pressure decreased, while stroke volume increased. Pretreatment with methysergide antagonized the hypotension and bradycardia, as well as the changes in venous pressure and stroke volume. It was concluded that quipazine elicits complex, dose-related cardiovascular effects, some of which (hypotension, venodilatation, bradycardia) are mediated through methysergide-sensitive central serotonin receptors. The arterial vasoconstriction produced by low doses of the drug was not mediated through these receptors and was probably the result of activation of a cardiogenic reflex.     

Factors influencing cadmium toxicity in A-V conduction system of isolated perfused rat heart.

The hemodynamic effects of successive intravenous infusions of 20% methanol in anesthetized, mechanically ventilated dogs were assessed against any spontaneous changes occurring during saline infusions. Preinfusion parameters, including pentobarbital-induced tachycardia and reduced stroke volume, were similar for test and control groups, which both maintained normal blood gases and pH during subsequent infusions. Systemic blood pressures of control dogs fell 10–20% during the saline-infusion regimen. Methanol quickly distributed in total body water. Clinical (130–200 mg/100 ml) and higher blood alcohol concentrations progressively decreased stroke volume and cardiac output, systemic blood pressure, and flow through femoral and common carotid arteries, while total peripheral resistance increased. Death by cardiac arrest occurred at blood concentrations exceeding 400 mg/100 ml. Other studies suggest that the dose-related decreased stroke volume, bradycardia, and elevated total peripheral resistance may be direct alcohol effects.     

Influence of an antispastic, analgesic combination on blood pressure, dynamics and contractility of the left ventricle in the dog]

The following cardiovascular parameters were continuously measured in 12 dogs anaesthetized with sodium pentobarbital following i.v. application of Baralgin, a combination of 1-beta- piperidino-ethoxycarbmethoxy-benzophenone-hydrochloride with diphenylpiperidino-ethyl-acetamide-bromomethylate and 2.3-dimethyl-4-methylamino-1-phenyl-5-pyrazolone-N-methanesulfonic acid: Mean arterial blood pressure, left ventricular pressure, dp/dt-value in the left ventricle, the parameter (see article), told peripheral resistance, cardiac work, heart rate, cardiac output and stroke volume, flow rate in the A. femoralis and the repiration volume. In this experimental series dosages of 0.1, 0.25, 0.625 and 1.56 ml Baralgin/kg i.v. were tested and the subsequent cardiovascular activity was recorded for a period of 90 min following application. 1. The mean arterial blood pressure remained practically unaltered following low doses of Baralgin (0.1 and 0.25 ml/kg i.v.), whereas higher doses (0.625 and 1.56 ml/kg) led to an initial drop in blood pressure corresponding to the fall in total resistance. 2. The cardiac output rose slightly in correlation with rise in stroke volume. In the dosage range of 0.25 ml Baralgin/kg i.v. the rise in cardiac output was accentuated by an increase in heart rate. 3. The cardiac work remained relatively stable following small Baralgin doses, however, a slight diminution in cardiac work due to the fall in blood pressure and decrease in cardiac output, resulted from application of 1.56 mg/kg i.v. 4. A slight positive inotropic stimulation of the heart became apparent in the initial period following small doses of Baralgin (0.1 and 0.25 ml/kg i.v.), higher i.v. dosages caused a marginal reduction in cardiac contractility.     

Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and prostaglandin E2 in anaesthetized dogs.

1 The aim of the study was to determine the mechanism of the hypotension and bradycardia produced by prostacyclin (PGI2). 2 Haemodynamic studies were carried out in nineteen open-chest beagle dogs anaesthetized with chloralose. PGI2 was infused intravenously or into the left atrium. 3 Infusions of PGI2 either intravenously or into the left atrium equally reduced arterial pressure and total peripheral resistance but bradycardia was greater after infusion into the left atrium. 4 Comparison of effects of PGI2 with those of prostaglandin E2 (PGE2) showed that although left atrial infusions both reduced aortic pressure and total peripheral resistance, PGE2 always increased heart rate, cardiac output and maximum acceleration. 5 Similar effects were observed with sodium nitroprusside except that it always caused tachycardia and reduced stroke volume. 6 Atropine (0.05 or 1 mg/kg i.v.) reduced or reversed the bradycardia induced by PGI2 but its hypotensive effects were reduced only after 1 mg/kg atropine. After vagotomy changes in cardiac output, stroke volume and maximum acceleration were increased, the hypotensive effects of PGI2 were reduced and the bradycardia was reversed; effects induced by PGE2 were not significantly altered. 7 The hypotension induced by prostacyclin is due to two components, a direct relaxation of vascular smooth muscle and a reflex, non-cholinergic vasodilatation. The bradycardia is reflex in nature and is partially mediated by the vagus pathway.     

Cardiovascular effects and plasma levels of denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs

Cardiovascular effects of denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs were investigated following intravenous and oral administration. In the conscious state, denopamine (0.5-4 micrograms/kg/min, i.v. infusion) increased LV dp/dtmax, cardiac output, stroke volume in a dose-dependent manner, and it decreased left ventricular end-diastolic pressure, total peripheral resistance and PQ interval. Denopamine produced an increase in LV dp/dtmax by 90% at a rate of 4 micrograms/kg/min with slightly increasing systemic blood pressure and heart rate. In the same dogs after anesthetizing with pentobarbital, denopamine in the same dose range showed more marked positive inotropic effects and less changes in cardiac output and total peripheral resistance than in conscious dogs. Other cardiovascular effects of denopamine were qualitatively similar to conscious dogs. These effects of denopamine were diminished by treatment with propranolol. Oral administration of denopamine to conscious dogs (0.1-0.4 mg/kg) produced a rise in LV dp/dtmax dose-dependently, and denopamine at a dose of 0.4 mg/kg increased LV dp/dtmax by 66%, this effect lasting for 7 hr. Heart rate and blood pressure were not affected significantly. Effects on other cardiovascular parameters were changed in the same direction as intravenous administration. The increase in LV dp/dtmax corresponded well with the changes in plasma levels of denopamine in conscious dogs by both intravenous and oral administration. Denopamine showed a selective positive inotropic effect in chronically instrumented dogs, and its positive inotropic action was more marked in the myocardium depressed with an anesthetizing dose of pentobarbital than in the conscious state.     

Centrally mediated hypotension and bradycardia by methysergide in anesthetized dogs.

In anesthetized dogs, methysergide (1 and 3 mg/kg i.v.) caused reductions in systolic and diastolic blood pressure, heart rate, left ventricular pressure and peripheral resistance. Caardiac output was unchanged because of an increase in stroke volume. Methysergide exhibited no alpha-receptor, ganglion, or adrenergic neuron-blocking properties nor did it have marked direct vasocilator action. The BCO, but not the orthostatic, reflex was severely inhibited by the drug, evidence for a central inhibitory action. Atropine, vagotomy or carotid sinus debuffering had little or no effect on the hypotension and bradycardia produced by methysergide, whereas guanethidine pretreatment essentially abolished these effects. Direct intracerebronventricular administration of small doses of methysergide (0.2 mg/kg) caused significant hypotension and bradycardia. It is concluded that methysergide causes centrally mediated hypotension and bradycardia, the mechanism of which is not clearly understood.     

The effect of (minus)-delta 9-trans-tetrahydrocannibinol on myocardial contractility and venous return in anesthetized dogs

Administration of (?)-Δ⁹-trans-tetrahydrocannabinol (Δ⁹-THC, 2.5 mg/kg i.v.) to pentobarbital-anesthetized dogs in which heart rate was maintained constant by electrical pacing, decreased aortic blood pressure, cardiac output, left ventricular peak pressure and left ventricular end diastolic pressure and dP/dt. However, the contractility index (max. dP/dt)/I.P. was not altered by the compound. Furthermore, it was shown that the decrease in cardiac output due to Δ⁹-THC could be restored to original levels by an infusion of saline-dextran in quantities sufficient to elevate the left ventricular end diastolic pressure to pre-Δ⁹-THC level.In dogs in which cardiac output was maintained constant by a right heart bypass procedure Δ⁹-THC decreased blood pressure and total peripheral resistance and augmented intravascular blood volume. This increase in intravascular blood volume was significantly less (74%) in animals in which the splanchnic (superior, inferior and celiac) arteries were ligated prior to the administration of Δ⁹-THC. On the other hand, in spinal dogs Δ⁹-THC was devoid of any measurable cardiovascular effects.These observations clearly support the hypothesis that the diminution of cardiac output induced by Δ⁹-THC in animals with constant cardiac rate is primarily due to diminished venous return to the heart and not to an impaired ability of the myocardium.     

Role of peripheral vascular resistance as an indicator of cardiovascular abnormalities in patients with Parkinson's disease

The aim of this study was to evaluate cardiovascular autonomic modulation in response to an orthostatic stress in healthy subjects and Parkinson's disease (PD ). The study included 47 controls and 56 PD patients divided into groups (vasoconstrictor PD , vasodilator PD , control) according to vasodilation/vasoconstriction response during 70° head up tilt test. Using impedance cardiography (ICG ) and electrocardiography (ECG ) we measured stroke volume, cardiac output, left ventricular work index, left ventricular ejection time, acceleration index, index of contractility, Heather index, thoracic fluid content, total peripheral resistance, total arterial compliance. We also analyzed heart rate variability (HRV ), using spectral analysis and continuous blood pressure (contBP). At rest, the vasodilator PD group showed significantly higher values of total peripheral resistance and lower values of stroke volume and cardiac output, compared to the vasoconstrictor PD and the control groups. A post‐tilt drop in ? (change rest – tilt) systolic blood pressure, ?mean blood pressure, ?total peripheral resistance and ?Heather index, and a significantly lower increase in ?diastolic blood pressure was observed in subjects from the vasodilator PD group compared to the vasoconstrictor PD and the control groups. No statistically significant differences were observed for HRV parameters between the vasoconstrictor and vasodilator PD groups, P  > .05. Longer duration and higher disease stage of PD correlated with a reduction in post‐tilt systolic blood pressure changes in vasodilator group. Positive inotropy of the cardiac muscle represents a significant factor preventing orthostatic hypotension in PD subjects with a concurrent drop in peripheral vascular resistance during orthostatic stress.     

Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog

The cardiac and hemodynamic effects of increasing doses (0.1-3 mg/kg i.v.) of the novel cardiotonic agent, DPI 201-106 (DPI), were investigated over a 60 min period in conscious dogs chronically instrumented for the measurement of arterial pressure, heart rate, left ventricular pressure (LVP), LV (+) dP/dtmax and cardiac output. LV (+) dP/dtmax, cardiac output and stroke volume were significantly increased by DPI whereas the total peripheral resistance was significantly decreased. These effects were dose-dependent in intensity and in duration. The mean arterial pressure and heart rate remained unaffected, except by the 3 mg/kg dose, which increased them slightly. Autonomic blockade with hexamethonium, atropine and propranolol did not alter the positive inotropic properties of DPI but unmasked its intrinsic bradycardic effect. At equipotent positive inotropic doses, DPI (0.3 mg/kg), milrinone (40 micrograms/kg) and dobutamine (5 micrograms/kg per min) induced similar increases in cardiac output and similar decreases in total peripheral resistance, but only dobutamine and milrinone accelerated the heart rate, whereas ouabain (17.5 micrograms/kg) induced a strong rise in the total peripheral resistance and markedly lowered the heart rate and cardiac output. After coadministration of DPI and ouabain, LV (+) dP/dtmax was further increased whereas the ouabain-induced bradycardia, the rise in the total peripheral resistance and the decrease in cardiac output were reinforced, halved and unaltered, respectively. We conclude that (a) DPI exhibits potent and direct positive inotropic properties, associated with a peripheral vasodilating action, and almost no positive chronotropic effects, and (b) coadministration of DPI and ouabain results in synergistic positive inotropic effects.     

Comprehensive evaluation of cardiovascular function in the anesthetized rat.

The present report describes methods and procedures which have been developed and used in the intact, anesthetized rat for cardiovascular functional evaluation. Integrative hemodynamic mechanisms are ascertained under resting conditions by measuring arterial blood pressure, cardiac output and heart rate. Stroke volume and total peripheral resistance are derived from the above measurements. In addition, left ventricular pressure is determined by direct cardiac puncture. Derived rates of left ventricular pressure development (+dP/dt) and left ventricular pressure decline (-dP/dt) provide estimates of myocardial contractility and cardiac relaxation, respectively. Hemodynamic responses to isoproterenol infusion test the functional adequacy of the beta-adrenergic receptor, adenylate cyclase, cyclic AMP system. Ventricular function curves relating stroke volume and end-diastolic pressure during rapid volume infusion provide useful indices of cardiac pump performance in the intact heart. Peak left ventricular +dP/dt in response to brief aortic occlusion provides an index of cardiac contractile performance. Cardiac cellular/subcellular mechanisms relating (a) myofibrillar ATPase with heart contractility and (b) sarcoplasmic reticulum calcium handling properties with myocardial relaxation can be assessed. Thus, the methods and procedures described represent an experimental animal preparation which should prove useful for comprehensive evaluation of cardiovascular function.     

Acute cardiovascular effects of methyl methacrylate monomer: characterization and modification by cholinergic blockade, adrenergic stimulation and calcium chloride infusion.

1. Methyl methacrylate monomer (MMA) given by i.v. infusion to anesthetized dogs caused a sustained hypotension, bradycardia, reduction of cardiac output and stroke volume, and increased peripheral resistance. 2. Epinephrine i.v. could reverse the hypotension but not the bradycardia; isoproterenol i.v. could reverse the bradycardia but not the hypotension. 3. Bilateral cervical vagotomy prevented bradycardia but not other cardiovascular effects of MMA, and prevented all respiratory effects except hypoxemia. 4. Calcium chloride i.v. reversed all circulatory changes except bradycardia; a combination of atropine and calcium reversed all cardiovascular changes from MMA.     

Effect of bromocriptine on cardiac function and coronary blood flow

The present study was designed to investigate the effects of bromocriptine, a dopamine receptor agonist, on systemic and coronary hemodynamics and to determine the mechanisms involved in the action of this compound. Intravenous infusion of bromocriptine (1 microgram/kg/min for 20 min) to pentobarbital-anesthetized dogs produced significant decreases in blood pressure, heart rate, total peripheral resistance, peak dP/dt, left ventricular pressure, and coronary blood flow. There were significant increases in stroke volume and coronary vascular resistance, whereas the index of contractility was unaffected. Cardiac output was decreased 30 min after the termination of bromocriptine infusion. The cardiovascular actions of bromocriptine were significantly antagonized by the dopamine receptor antagonist, sulpiride. Bromocriptine also failed to exert these effects when administered to animals that were treated with ganglionic blocking agents. These results suggest that the hypotensive action of bromocriptine is mainly due to a decrease in total peripheral resistance. In addition, the actions of bromocriptine on cardiac function are the result of activation of presynaptic dopamine receptors and the drug does not have any direct action on the myocardium.     

The effect of Bitis gabonica (gaboon viper) snake venom on blood pressure,stroke volume and coronary circulation in the dog

The effects of Gaboon Viper (Bitis gabonica) venom on cardiac output, arterial blood pressure, coronary flow and total peripheral resistance were investigated in eight anaesthetized dogs. Venom doses in the range of 0·125–0·50 mg/kg produced an abrupt fall in arterial blood pressure which recovered to near normal after 30 min. Stroke volume and cardiac output both rose during the hypotensive response and then declined to below control values. Heart rate and electrocardiogram were essentially unaltered. Coronary blood flow increased after venom and total peripheral resistance decreased. These responses tended to diminish as venom dose was increased, indicating some form of tachyphylaxis. The results indicate the presence of two different components affecting the cardiovascular system: a vasodilatory component responsible for the fall in peripheral resistance and hence arterial blood pressure and a cardiotoxic component responsible for the progressive reduction in stroke volume.     

Role of vagal activity in the cardiovascular responses to phenylephrine in man.

The effects of phenylephrine on blood pressure (BP), left ventricular function and total peripheral resistance (TPR) were evaluated in six normotensive male volunteers before and after vagal blockade with atropine. Before atropine, phenylephrine dose-related increased TPR, systolic and diastolic BP and decreased cardiac output by decreases in both stroke volume and heart rate. Post-atropine, the BP (but not TPR) responses to phenylephrine were markedly potentiated, related to an increase in stroke volume despite the higher afterload. Thus vagal tone may regulate cardiac output via effects on both heart rate and venous return.