EFFECTS OF ACUTE VERSUS CHRONIC DELETION OF ARTERIAL BARORECEPTOR INPUT ON THE CARDIOVASCULAR RESPONSES TO EXERCISE IN THE RABBIT

These experiments were designed to confirm that at the onset of treadmill exercise in rabbits the tonic reflex depressor effects of input to the central nervous system from arterial baroreceptors is abolished, thus contributing to the rise of systemic arterial pressure (SAP) and heart rate (HR). An inflatable cuff was placed around one common carotid artery after the remaining arterial baroreceptors had been surgically denervated. Transient inflation of the cuff caused reflex rises of SAP and HR, which were much reduced during the first minute of exercise. Deflation of the cuff caused a brisk fall of HR, which was completely abolished by exercise. A snare was placed around one carotid sinus nerve after the remaining arterial baroreceptors had been surgically denervated. Where the snare was tightened all arterial baroreceptor reflexes were immediately and permanently abolished. This allowed the reflex effects of baroreceptor input to be calculated by difference. The magnitude of these calculated effects, at rest and during exercise, diminished according to how long after barodenervation the observations were made. We conclude from the above experiments that the resting tonic reflex depression of SAP and HR caused by baroreceptor input is much reduced, rather than completely abolished, at the onset of exercise. We also conclude, from the effects of partial surgical barodenervation, and of unloading the carotid baroreceptors prior to exercise by inflating the carotid cuff, that resting input from the arterial baroreceptors must be near zero before the cardiovascular response to exercise is grossly altered.     

Aortic baroreceptors exert a tonically active restraining influence on centrally mediated depressor responses.

This study tested the hypothesis that aortic baroreceptors exert a central restraining influence on centrally mediated depressor responses and that this mechanism is tonically active and is independent of their modulation of basal arterial pressure. The effects of short-term (48-72 h) aortic baroreceptor deafferentation (ABD) on the acute hemodynamic (peripherally mediated pressor and centrally mediated depressor) effects of clonidine were investigated in conscious and anesthetized normotensive rats. ABD caused an immediate increase in basal arterial pressure and heart rate and a significant attenuation of the baroreceptor reflex control of heart rate. Since only arterial pressure subsided to control levels by 48-72 h, the data suggest that central reorganizational changes were potent enough to overcome the tonically active restraining influence of aortic baroreceptors on basal arterial pressure but not heart rate. Clonidine produced a similar pressor effect in conscious ABD and sham rats but its depressor effect was significantly greater in ABD rats whose baroreceptor reflex control of heart rate was significantly attenuated. Intracisternal (i.c.) administration of 0.1 microgram of clonidine, a dose that had no effect when administered i.v., produced a near-maximal depressor effect in conscious ABD rats vs. no effect in sham rats (-16.7 +/- 4.1 vs. -0.3 +/- 2 mm Hg; p less than 0.001). The depressor effect of clonidine was also enhanced in chloralose-anesthetized rats and coincided with an anesthesia-induced attenuation of the baroreceptor reflex control of heart rate. It is concluded that aortic baroreceptors exert a potent restraining influence on the centrally mediated depressor effect of clonidine. Since ABD had no significant effect on the depressor response to nitroprusside, but enhanced the depressor response to ganglion blockade by hexamethonium, the data suggest that a higher peripheral sympathetic neural activity existed in ABD rats. The reorganizational changes that occurred within 48-72 h after ABD were potent enough to overcome the tonically active restraining influence of aortic baroreceptors on basal arterial pressure but not on the centrally mediated depressor responses. Thus, the buffering influence of aortic baroreceptors and their central projections on centrally mediated depressor responses seems to be tonically involved in blood pressure control.     

CHARACTERIZATION OF THE BARORECEPTOR HEART RATE REFLEX DURING DEVELOPMENT IN SPONTANEOUSLY HYPERTENSIVE RATS

1. We have examined the baroreceptor-heart rate (HR) reflex in weight-matched conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats during development. 2. Graded steady-state changes in mean arterial pressure (MAP) and the corresponding HR responses before and after vagal blockade with methylatropine were fitted to an S-shaped logistic function. 3. At 6 weeks of age, SHR had a 17% higher MAP than WKY and an increased baroreflex gain (slope) compared with WKY due to an increased curvature of the MAP-HR relationship. The HR range (the difference between the upper and lower HR plateaus) was similar in the two strains at this time. 4. From 9-14 weeks of age, the baroreflex gain progressively increased in WKY and decreased in SHR due to corresponding alterations in HR range. 5. By 20 weeks the baroreflex gain was 23% lower in SHR than WKY due to a 37% lower HR range. 6. There were no differences between the two strains in the sympathetic component of the baroreflex at any age, suggesting that the changes to baroreflex properties were confined to the cardiac vagus. 7. Pretreatment with enalapril from 4-9 weeks reduced the hypertension of SHR at 14 and 20 weeks by 38% and abolished all baroreceptor-HR reflex differences between the two strains. 8. These studies suggest that the major alteration to the baroreceptor-heart rate reflex in the SHR during development was a reduction in the maximum vagal capacity to respond to changes in blood pressure. This effect developed after the onset of hypertension and was prevented by antihypertensive treatment early in life. The lack of effect on the cardiac sympathetic component suggests that altered arterial baroreceptor afferents are not unlikely to be responsible.     

COMPARISON OF METHODS FOR ELICITING THE BARORECEPTOR-HEART RATE REFLEX IN CONSCIOUS RABBITS

1. Two methods were used for altering blood pressure in conscious rabbits by up to ± 30 mmHg from the resting level in order to characterize the barorecep-tor-heart rate reflex. These were to inflate descending aortic or inferior vena caval cuffs, or to give brief intravenous infusions of phenylephrine or glycerol trinitrate. The relation of change in blood pressure to change in heart interval was examined, both during the initial ‘ramp’ changes of these variables and when they had reached a ‘steady-state'. 2. Both methods allowed the construction of'steady-state’ sigmoid stimulus-response curves whose parameters were reproducible within animals, and which were attended by a relatively small variance between animals. The inflatable-cuff method gave a higher average value for maximum gain than the vasoactive drug method (10.0 v 5-4 ms/mmHg) and a narrower pressure range between the threshold and saturation points of the response, but values for the other parameters were similar. Corresponding parameters obtained by the two methods correlated closely. 3. After denervating all arterial baroreceptors except one carotid sinus, ‘steady-state’ maximum gain by cuff-inflation was reduced to 3.1 ms/mmHg, and to 2-6 ms/mmHg by the vasoactive drug method. The heart interval range between upper and lower plateau levels was reduced, but the pressure range between threshold and saturation points was widened, with both methods. 4. During the initial ‘ramp’ changes of blood pressure the sensitivity of the reflex was described by the slope of the linear regression of heart interval on ‘mean blood pressure. The slopes obtained by aortic cuff inflation, and by infusion of either vasoactive drug, correlated positively with ‘steady-state’ maximum gain. However, the reproducibility of the ‘ramp’ method was inferior to that of the ‘steady-state’ method with respect to reflex sensitivity, and other parameters of the stimulus-response relation cannot be estimated. 5. Complete baroreceptor denervation virtually eliminated heart rate changes over the range of blood pressures usually employed. However, when blood pressure was increased by more than 40 mmHg a profound reflex bradycardia and hypopnoea were then evoked.     

Modulation of the baroreceptor reflex by alpha 2A-adrenoceptors: a study in alpha 2A knockout mice

1. Our objective was to determine whether alpha(2A)-adrenoceptors modulate the baroreceptor reflex. The efficacy of the reflex was evaluated by measuring the spontaneous blood pressure and heart rate variability at rest and the heart rate responses to evoked changes in blood pressure. Experiments were carried out in conscious, unrestrained, and anaesthetized alpha(2A)-adrenoceptor-deficient (alpha(2A)-KO) mice and WT mice. 2. In conscious alpha(2A)-KO mice, the spontaneous blood pressure variability was greater, and the spontaneous heart rate variability was lower than in conscious WT mice. This was also observed in anaesthetized animals. 3. The reflex bradycardia after intravenous injection of phenylephrine was greatly attenuated in conscious alpha(2A)-KO compared to conscious WT mice; the baroreceptor reflex gain (ratio maximal change in heart rate/maximal change in mean arterial pressure) was decreased by 40%. 4. Similar results were obtained when reflex bradycardia was elicited by intra-arterial volume loading of conscious WT and alpha(2A)-KO mice. The baroreceptor reflex gain upon volume loading was also low in anaesthetized alpha(2A)-KO mice. 5. The reflex tachycardia evoked by intravenous sodium nitroprusside injection was also significantly less in alpha(2A)-KO mice as compared to WT, conscious as well as anaesthetized; the baroreceptor reflex gains were decreased by 50 and 65%, respectively. 6. Direct stimulation of cardiac beta-adrenoceptors by the agonist isoprenaline produced similar cardioacceleration in alpha(2A)-KO and WT animals. 7. Our results show that the baroreceptor reflex function is impaired in mice lacking alpha(2A)-adrenoceptors. We conclude that central alpha(2A)-adrenoceptors facilitate the reflex response to both loading and unloading of the arterial baroreceptors.     

Vasodilators in myocardial infarction: rationale and current status.

While digitalis and diuretics constitute conventional therapy of congestive heart failure due to acute myocardial infarction, systemic vasodilator drugs offer an innovative approach of decreasing left ventricular systolic wall tension (afterload) by reducing aortic impedance and/or by reducing cardic venous return. Thus, vasodilators increase lowered cardiac output by diminishing peripheral vascular resistance and/or decreasing increased left ventricular end-diastolic pressure (ventricular preload) by reducing venous tone. Concomitantly, there is a reduction of myocardial oxygen demand thereby potentially limiting infarct size and ischaemia. The vasodilators produce disparate modifications of cardiac function depending on their differing alterations of preload versus impedance: nitrates principally cause venodilatation (decrease left ventricular end-diastolic pressure); sodium nitroprusside, phentolamine and prazosin produced relatively balanced arterial and venous dilatation (decrease left ventricular end-diastolic pressure while increasing cardiac output, provided upper limits of normal left ventricular end-diastolic pressure are maintained); and hydrallazine solely effects arteriolar dilatation (increases cardiac output). Combined sodium nitroprusside and dopamine therapy synergistically enhances cardiac output and decreases left ventricular end diastolic pressure. In addition, sodium nitroprusside is aided by mechanical counterpulsation which sustains myocardial perfusion pressure in acute myocardial infarction.     

Effect of diazoxide on left ventricular performance in hypertension

Summary The effect of diazoxide on left ventricular performance during rest and isometric exercise (handgrip) was examined in 16 unselected hypertensive patients, 6 of whom had been pretreated with the beta-adrenergic blocking agent pindolol. Diazoxide regularly and promptly produced a fall in left ventricular systolic and end diastolic pressures, and an increase in heart rate and left ventricular dp/dt_max. Haemodynamic changes were maximal 2 minutes after injection of the drug and decreased little over the next 8 minutes. After beta-adrenergic blockade, diazoxide caused a more pronounced reduction in left ventricular systolic pressure and a less marked fall in end-diastolic pressure, whilst the diazoxide-induced rise in heart rate was partially and the increase of dp/dt_max was completely inhibited. The increase in systolic pressure during isometric exercise was not influenced by diazoxide, but the positive inotropic reaction was augmented. The findings appear to show that cardiac stimulation by diazoxide is due to a reflex mechanism transmitted by baroreceptors, and that improvement of cardiac performance is mainly due to a reduction of left ventricular after-load.     

Cardiovascular sensory receptors and their regulatory mechanisms

The role of cardiovascular receptors in the neural regulation of circulatory system is now well established. Atrial type B receptors located in the two atria and veno-atrial junctions, which are stimulated by atrial filling are believed to play an important role in the regulation of body fluid volume and heart rate. Heart rate is influenced also by other sensory receptors e.g. arterial baroreceptors, ventricular receptors, pulmonary stretch receptors and chemoreceptors. Of all these visceral receptors, arterial baroreceptors located mainly in the aortic arch and the carotid sinus region are stimulated by intravascular pressure; play a major role in the regulation of blood pressure by changes in heart rate and vascular tone. The vascular tone is also affected by the circulatory levels of various neurotransmitters and hormones. Vasodilatory response to adenosine and acetylcholine is partly mediated through endothelium-derived relaxing factors (EDRF), hyperpolarizing factors (EDHF) and contracting factors (EDCF). The endothelium-dependent mechanisms are altered during hypertension and diabetes. The autonomic control of blood pressure is primarily through arterial baroreceptors. The sensitivity of the baroreceptor heart rate reflex is significantly attenuated on occlusion of left anterior descending coronary artery (LAD) of anaesthetised dogs taken as an experimental model of coronary insufficiency in-patients of coronary heart disease. The fall in the sensitivity of baroreflex on LAD occlusion is mediated primarily by sympathetic limb of the autonomic nervous system. Acute fall in hemoglobin level by hemodilution in dogs produced an increase in cardiac output by increasing the heart rate through inhibition of parasympathetic tone. After parasympathetic blockade the increase in cardiac output on fall in hemoglobin was due to a rise in the stroke volume. Acute fall in hemoglobin level attenuated the baroreflex response. Sustained changes in blood pressure cause resetting of baroreflex i.e. increase in arterial pressure involves reduced activity of baroreceptors at equivalent pressure and vascular stretch. Like in acute hypoxia the altered responsiveness of baroreceptor heart rate reflex during oxygen deficiency due to acute occlusion of LAD or acute normovolemic hemodilution may involve both peripheral and central components and possibility of modulation by circulating hormones also exists.     

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.     

Cardiovascular profile of 5 novel nitrate-esters: a comparative study with nitroglycerin in pigs with and without left ventricular dysfunction.

1. Four cumulative 10 min intravenous infusions of 0.05, 0.2, 0.5 and 2.0 mg min-1 were used to compare the cardiovascular profile of 5 novel nitrate-esters dissolved in Intralipid 10% to that of nitroglycerin (GTN) in conscious pigs. 2. Infusion of Intralipid 10% alone had no effect on any of the systemic haemodynamic parameters. GTN infusions decreased mean arterial blood pressure dose-dependently from 94 +/- 2 mmHg to 79 +/- 3 mmHg (P less than 0.05) and raised cardiac output from 2.74 +/- 0.09 l min-1 to 3.40 +/- 0.18 l min-1 (P less than 0.05) due to an increase in heart rate (by up to 43 +/- 3%), as stroke volume decreased slightly. Systemic vascular resistance decreased (by 32 +/- 3%) and left ventricular end-diastolic pressure fell from 5.2 +/- 0.4 mmHg to 2.2 +/- 0.5 mmHg (both P less than 0.05). 3. The novel compounds CEDO 8811, CEDO 8834 and CEDO 8901 increased cardiac output only at the highest dose (7%, 8% and 9%, respectively). There was no change in mean arterial blood pressure as the increase in cardiac output was counterbalanced by arterial vasodilatation. All three compounds reduced left ventricular end-diastolic pressure slightly. 4. CEDO 8816 was a more potent arterial and venodilator than the aforementioned CEDO compounds, as the decreases in systemic vascular resistance and left ventricular end-diastolic pressure were already significant at lower doses. The fall in stroke volume was fully compensated by the increase in heart rate and as a result cardiac output increased by 11 +/- 3% (P less than 0.05) at the highest dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rilmenidine prevents blood pressure increase in rats with compromised nitric oxide production

AIM: To search tools of high blood pressure in the model of nitric oxide (NO)-defective hypertension, and thestudy focused on the effect of rilmenidine, agonist of imidazoline receptors, which was suggested to modulatecentral sympathetic outflow. METHODS: Three experimental groups, each consisting of 7 rats, were used: (I) ratswith inhibition of NO synthase (NOS) by Nr-nitro-L-arginine methyl ester (L-NAME) 40 mg.kg-~.d~ for 4 weeks indrinking water, (II) rats with inhibited NOS as in group I, plus agonist of imidazoline receptors rilmenidine 3mg.kg^-1.d^-1 for 4 weeks by garage, and (Ⅲ) control rats. Systolic blood pressure was measured weekly noninvasively.At the end of experiment aortic ring isometric tension was followed, NOS expression (aorta, left ventricle), andNOS activity (left ventricle and brain) were determined. RESULTS: In the group I systolic blood pressure in-creased significantly, aortic ring relaxation to acetylcholine was significantly attenuated. Rilmenidine administeredsimultaneously with L-NAME (group II) prevented the increase of blood pressure which did not differ significantlyfrom control values; aortic ring relaxation to acetylcholine did not differ from control. No change in NOS expres-sion (aorta and left ventricle) was found in groups I and II. Significant decline in NOS activity (left ventricle andbrain) was found in groups I and II. CONCLUSION: Rilmenidine has a remarkable role in NO-defective hypertension,possibly by inhibiting central sympathetic outflow and by affecting receptors in vascular smooth muscle also. Theprime cause of hypertension in this experimental model - the compromised production of NO due to inhibition ofNOS - was not affected by rilmenidine.     

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。     

AN ANALYSIS OF THE HAEMODYNAMIC EFFECTS OF TOLBUTAMIDE IN CONSCIOUS DOGS

1. In conscious chronically instrumented dogs, tolbutamide (5-45 mg/kg) induced significant dose-related increases in mean arterial pressure and left ventricular end-diastolic pressure. 2. Cardiac output was decreased while heart rate, d(LVP)/dt, and regional myocardial performance at the left ventricle were not significantly affected. Computed total peripheral resistance was increased. 3. Pretreatment with the alpha-antagonist phentolamine (1-1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 microgram/kg) was enhanced by pretreatment with tolbutamide (45 mg/kg). 4. In an isolated tissue preparation using ring segments of canine femoral arteries, neither tolbutamide nor its major hepatic metabolites (carboxytolbutamide, p-toluene-sulfonamide and p-toluene-sulfonylurea) caused any smooth muscle contraction. However, pretreatment of these tissues with 10(-4), 10(-3), or 10(-2) mol/l tolbutamide potentiated the contractile response to norepinephrine by up to 19% and to phenylephrine by up to 8%. 5. It was concluded that the pressor effect of tolbutamide arises by potentiating the alpha-adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines.     

The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations

We investigated in conscious, freely moving rats whether the release of GABA, taurine and arginine in the hypothalamus is influenced by impulses originating from peripheral baroreceptors. The posterior hypothalamic nucleus was superfused with artificial cerebrospinal fluid through a push-push cannula and the release of amino acids was determined in the hypothalamic superfusate of control rats, as well as of rats after bilateral aortic denervation (AD). AD led to hypertension and increased the lability of arterial pressure. In sham-operated rats, intravenous infusion of phenylephrine increased blood pressure and the hypothalamic release of GABA and taurine. AD almost abolished the phenylephrine-induced release of the inhibitory amino acids. Similarly, the pressor response to hypervolaemia, elicited by blood injection, enhanced the release rates of GABA and taurine only in sham-operated rats. Baroreceptor unloading evoked either by intravenous infusion of nitroprusside, or by haemorrhage, decreased the release rates of GABA and taurine in sham-operated rats but not in AD rats. Electrical stimulation of the afferent aortic depressor nerve enhanced extracellular GABA and taurine in the posterior hypothalamic nucleus. The release rate of arginine was not influenced by alterations in baroreceptor activity either in sham-operated or in AD rats. The findings support the idea that, in the hypothalamus,GABA and taurine are involved in central blood pressure regulation. The release of these two amino acids seems to be driven tonically by baroreceptor impulses. Moreover, the findings indicate that the baroreceptors of the aortic arch play a crucial role in the mediation of changes in hypothalamic GABA and taurine outflow so as to counteract blood pressure fluctuations. Received: 23 December 1996 / Accepted: 2 May 1997     

新型内皮素受体拮抗剂CPU0214与正常大鼠心肌ET受体结合特点及对清醒DOCA-盐型高血压大鼠的降压作用

目的　研究新型内皮素受体拮抗剂CPU0 2 1 4与正常大鼠心肌内皮素 (ET)受体结合特点 ,对血管收缩的拮抗作用及对高血压大鼠血压的降低作用。方法　采用放射配体竞争抑制结合法和ET 1引起的胸主动脉环收缩法分别研究CPU0 2 1 4与正常大鼠心肌ET受体结合的特性和对血管收缩功能的拮抗作用 ;采用放射配体结合法观察注射醋酸脱氧皮质酮 (DO CA)和饮用盐水造成的高血压模型大鼠的心肌ET受体的改变及其股动脉平均动脉压的变化 ,研究CPU0 2 1 4的降压作用。结果　CPU0 2 1 4在正常心肌膜上竞争性结合1 2 5I ET1 ,其IC50 为1 6nmol·L-1 ;抑制ET 1所致胸主动脉环收缩。DOCA 盐型高血压大鼠表现内皮素受体的Bmax值和Kd 值升高 ;CPU0 2 1 4使清醒高血压大鼠的平均动脉压明显降低 ,在 6 0～ 90min时最为明显。结论　CPU0 2 1 4在正常大鼠竞争结合内皮素受体、拮抗血管收缩 ,在内皮素异常高血压大鼠可降低其血压 ,表明CPU0 2 1 4对治疗高血压有良好的研究价值     

Comparative effects of inotropic agents on coronary and systemic hemodynamics of conscious dogs: actions of milrinone, dopamine, ouabain and MCI-154

The hemodynamic actions of a new inotropic agent, MCI-154, were compared to dopamine, ouabain and milrinone in conscious, chronically instrumented dogs. MCI-154 and milrinone produced similar hemodynamic changes: increases in heart rate, diastolic coronary blood flow velocity and peak positive dP/dt. Neither agent had significant effects on arterial pressure while both drugs reduced left ventricular end-diastolic pressure in a dose-related fashion and myocardial segment length, indicating a decrease in diastolic left-ventricular size. MCI-154 was found to be approximately twice as potent as milrinone. In contrast, dopamine and ouabain produced little change in left ventricular end-diastolic pressure or myocardial segment length during diastole, while both drugs produced increases in arterial and left ventricular systolic pressures. An increase in left ventricular afterload was not observed with either MCI-154 or milrinone, highlighting an important advantage of the latter compounds.     

Myocardial and ventricular mechanics as influenced by disopyramide

The effects of disopyramide (D) on the mechanics of isolated myocardium as well as on the whole ventricle were examined in the rat model. Moreover bipolar leads of the apex and an area at the base of the left ventricle were set up to get indications for changes in the spread of excitation. D in concentrations of 10(-8) to 10(-4) mol/l did not affect the diastolic elastic properties of isolated myocardium. Isometric contraction amplitude was nearly unaltered, while rate of isometric contraction and relaxation were slightly increased. In the whole ventricle in situ D (2 to 10 mg/kg b.w. administered i.v.) induced a dose-dependent decrease in left ventricular isovolumetric peak pressure (16%), max.pos. dP/dt (40%) and max.neg. dP/dt (30%; for highest doses respectively), while time to peak pressure and relaxation time 90% were prolonged. Therapeutic dose of D (2 mg/kg b.w.i.v.) induced no decrease in essential systolic parameters of the whole ventricle under auxotonic conditions. Left ventricular pressure, dP/dt max.pos. and neg., left ventricular end-diastolic pressure and cardiac output were nearly unaltered. Heart rate showed a tendency to decrease, while total time of contraction and left ventricular ejection time increased. Higher doses of D led to marked cardiac depressant effects. The time interval between the excitation of the apex and an area at the base of the heart was increased. It was concluded that the negative dromotropic effect of D and thereby an altered pattern of left ventricular contraction are essential components in the elimination of the pressure gradient between left ventricle and aorta, observed in patients with muscular subaortic stenosis, and are presumably involved in the cardiac depressant effect of the drug in over-therapeutic doses.     

Comparative haemodynamic effects of lidocaine, mexiletine, and disopyramide

The effect of intravenous boluses of lidocaine (5 mg/kg), mexiletine (3.5 mg/kg), and disopyramide (5 mg/kg) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance, left ventricular end-diastolic pressure, and peak rate of change of left ventricular pressure (peak LV dP/dt) were assessed in the conscious rabbit. Plasma levels for the three drugs corresponded to the human therapeutic range 3 min after administration. All three drugs had negative inotropic effects and reduced HR. Lidocaine reduced peak LV dP/dt by 26%, mexiletine by 41%, and disopyramide by 53%. The three drugs had quite different effects on CO as a result of differences in their actions on peripheral blood vessels: disopyramide caused a 21% fall in CO, associated with a significant vasoconstriction; mexiletine did not lower CO, as it caused a substantial vasodilation; and lidocaine did not produce any substantial change in either CO or vascular resistance. Cardiac autonomic blockade did not alter these changes. These results confirm that disopyramide has a marked cardiodepressant effect, and demonstrate that, although lidocaine depresses myocardial contractility in the conscious rabbit, it has little effect on other haemodynamic parameters. The experiments also show that mexiletine is a more profound negative inotrope than lidocaine, but that, as it produces a significant fall in MAP and thus a reduction in afterload, the CO is maintained.     

用重建心阻抗图观察冠心病患者心功能的血流动力学变化

目的用重建心阻抗图观察冠心病患者心功能的改变。方法实验分患者组和健康对照组,用重建非线性公式分别计算并统计两组的心搏出量(SV)、每分心排血量(CO)、心排血指数(CI)、左室心功指数(CWI)、左室射血分数(LVEF)、左室心收缩指数(LHI)、总外周阻力(TPR)、主动脉顺应性(AC)、左室舒张指数(LDI)、左室舒张末压(LVEDP)。结果重建心阻抗法监测的心功能不全组中TPR、LDI、LVEDP均明显高于对照组,而CWI两者则无明显差异(P>0.5),其余指标明显降低。结论上述结果符合患者及健康人的病理生理变化及血流动力学特点,重建心阻抗图应用于冠心病患者时应结合临床,能提供一定的参考价值。     

Influence of baroreceptor reflexes on the capacitance vessel's response to acetylstrophanthidin

The importance of the reflexes in the effects of acetylstrophanthidin on capacitance vessels was evaluated in the present study using chloralose-anesthetized dogs with intact and denervated baroreceptors. In each animal left ventricular bypass was instituted by draining all pulmonary venous blood into a reservoir from which it was pumped into a T-tube inserted into the descending thoracic aorta. Shifts of blood into or out of the reservoir reflected alterations in systematic vascular capacity. Femoral artery and central venous pressures as well as reservoir level, were continuously monitored. Acetylstrophanthidin (12.5 and 25.0 μg/kg) was administered by rapid i.v. injection. In 6 animals with intact baroreceptors, both doses of acetylstrophanthidin were followed by an increase in intravascular blood volume (average 86 and 228 ml, respectively). The small dose had no effect on arterial blood pressure while the large dose produced a significant rise in the pressure. Acetylstrophanthidin administration in 6 denervated dogs was not associated with a significant change in intravascular volume, but both doses produced significant increases in arterial pressure. These results indicate that the increase in systematic vascular capacity observed in animals with intact baroreceptors was due to venodilation resulting from a withdrawal of sympathetic activity to the systemic veins rather than from a direct action of acetylstrophanthidin on these vessels.