Baroreflex responses to the stress of severe hemorrhage in the rat

In two groups of anesthetized (sodium pentobarbital), mature Sprague-Dawley rats, 1) aged 2 years and weighing 300–400 grams, 2) aged 6 months weighing 200–300 grams, baroreflex-induced circulatory responses to pressor (graded doses phenylephrine) and depressor (graded doses nitroglycerine) agents were compared to those occurring during progressive hemorrhage in the same animals. Graded withdrawals of blood from the femoral artery elicited progressive hypotension accompanied by bradycardia rather than expected tachycardia. Graded doses of phenylephrine (2.5 ug to 40 ug bolus, via femoral vein) regularly induced elevations in arterial blood pressurewith associated reflex bradycardia. Similarly graded doses of nitroglycerine induced a marked decline in arterial blood pressure,without expected tachycardia. As hypotension became more severe (during hemorrhage), atrioventricular conduction slowed and A-V block developed, resulting in statistically greater slowing in ventricular than in atrial excitation and contractile cycles. Heart failure during hemorrhage in the rat is characterized sequentially by severe bradycardia, depressed atrial contractile force, impaired conduction and A-V block, terminating in ventricular, atrial, and finally, in pacemaker failure. Baroreceptor reflexes were blunted or even absent in both young and old animals during induced hypotension.     

Treatment of PAT

It has been suggested that the dive reflex (elicited by face immersion in water with breath-hold) may be employed to induce vagally-mediated bradycardia in individuals with paroxysmal atrial tachycardia. However, in several cases the use of this reflex is reported to have led to exacerbation of the cardiac dysfunction. Examination of heartrate and EKG T-wave amplitude changes during the dive in healthy, college-aged individuals indicated that warming the water (10° through 20° C to 40° C) decreased the bradycardia, but did not alter theattenuation (approximately 100 μv) of the T-wave. The latter effect was taken to indicate that sympathetic activity, as indexed by T-wave amplitude, was not reduced by increases in water temperature. On the other hand, a 90° head-up to head-down body tilt produced a bradycardia response of some 30 bpm as well as a T-wave amplitudeincrease (sympathetic withdrawal) in the order of 100 μv. These data suggest that individuals who exhibit symptoms of ventricular sympathetic irritability may be adversely affected by the dive maneuver, regardless of water temperature. The body-tilt induced reflex in such individuals may thus be more appropriate given the large-magnitude bradycardia and absence of T-wave attenuation. At the present, however, the body-tilt preparation has been used only with healthy normal subjects, so this suggestion remains to be directly tested.     

Brain mechanisms in fatal cardiac arrhythmia.

Intravenous injection of histamine to rabbits was used as a prototype in an investigation of the mechanism of sudden death due to anaphylaxis and other causes. The "dive" reflex, bradycardia due to activation of the ophthalmic branch of the fifth cranial nerve, was induced in thirty-seven of the animals while they inhaled a very small amount of cigarette smoke. Associated with the resulting bradycardia were lowered blood pH and increased serum content of lactic acid and potassium and increased peripheral arterial constriction with elevation of diastolic blood pressure. Intravenous injection of 1 ml of histamine in the presence of the dive reflex induced potentially fatal ventricular arrhythmia, but no cardiac disturbance when administered while the dive reflex was inactive, thereby strongly suggesting that sudden death in anaphylaxis may involve an overzealous response to a normally protective neural reflex.     

心律失常发生的别差异

临盘床中某些心律失常的发生具有性别差异。女性同男性相比,其平均静息心率快,QT间期长,QRS波群时间短,QRS电压低。女性有更高的病态窦房结综合征、不适当性窦性心动过速、房室结折返性心动过速、右室特发性室速和长QT间期综合征引起的心律失常事件的发生率。而男性房室传导阻滞、颈动脉窦综合征、房颤、旁路导致的室上性心动过速、预激综合征、室颤、猝死、Brugada综合征和触发型室速的发生率高。这些差异有的与心律失常伴发的器质性心脏病男女发生率不同有关,另外性激素对离子通道的功能、表达的影响以及自主神经张力的差异在这些差异的产生中也具有重要作用。了解这些差异对女性心律失常处理具有重要的指导作用。     

Selective autonomic blockade of conditioned and unconditioned cardiovascular changes in rhesus monkeys (Macaca mulatta).

Changes in heart rate and in systolic and diastolic blood pressures were examined in eight rhesus monkeys during six sessions of differential classical conditioning. The conditioned stimuli consisted of tones differing in frequency and the unconditioned stimuli consisted of tail shock. Both the conditioned responses (CRS) and unconditioned responses (UCRs) consisted of increases in heart rate and in systolic and diastolic pressures, but blood pressure CRs sometimes occurred in the absence of heart rate CRs. Graded doses of the selective blocking agents propranolol, phentolamine, and atropine methylnitrate were systemically administered to four of the monkeys prior to additional conditioning sessions. The results suggested that the CRs and UCRs were mediated by both sympathetic and parasympathetic influences.     

Brain mechanisms in fatal cardiac arrhythmia

Intravenous injection of histamine to rabbits was used as a prototype in an investigation of the mechanism of sudden death due to anaphylaxis and other causes. The “dive” reflex, bradycardia due to activation of the ophthalmic branch of the fifth cranial nerve, was induced in thirty-seven of the animals while they inhaled a very small amount of cigarette smoke. Associated with the resulting bradycadia were lowered blood pH and increased serum content of lactic acid and potassium and increased peripheral arterial constriction with elevation of diastolic blood pressure. Intravenous injection of 1 ml of histamine in the presence of the dive reflex induced potentially fatal ventricular arrhythmia, but no cardiac disturbance when administered while the dive reflex was inactive, thereby strongly suggesting that sudden death in anaphylaxis may involve an overzealous response to a normally protective neural reflex.     

IABP在心脏直视手术围术期低心排的应用

为了探讨主动脉内球囊反搏（IABP）治疗心脏手术围术期低心输出量综合征（LCOS）的临床疗效,对16例心脏手术围术期LCOS患者,经过股动脉放置IABP导管于降主动脉内进行左心辅助治疗,IABP治疗前、后监测患者连续有创动脉收缩压（SABP）、有创平均动脉压（MABP）、中心静脉压（CVP）、动脉血氧分压（PaO2）、心率（HR）、尿量和血管活性药物的使用。结果显示,IABP辅助治疗时间25h～116h,平均（78．5±40．5）h。行IABP治疗后,SABP、MABP、PaO2较术前明显提高（P〈0．05）,HR、CVP明显下降（P〈0．05）,尿量增加,血管活性药物使用量明显减少（P〈0．05）,12例患者心功能好转而脱离IABP,11例（69．3％）存活,4例死于心源性休克,1例死于多器官功能不全综合征（MODS）。提示正确及时地使用IABP能明显改善心脏手术围术期LCOS患者的血流动力学指标,减少血管活性药物的使用,建议对有适应证者应尽早应用,适时撤离。     

Drug discrimination under concurrent variable-ratio variable-ratio schedules

Pigeons were trained to discriminate 5 mg/kg pentobarbital from saline under concurrent variable-ratio (VR) VR schedules, in which responses on the pentobarbital-biased lever were reinforced under the VR schedule with the smaller response requirements when pentobarbital was given before the session, and responses on the saline-biased key were reinforced under the VR schedule with the larger response requirements. When saline was administered before the session, the reinforcement contingencies associated with the two response keys were reversed. When responding stabilized under concurrent VR 20 VR 30, concurrent VR 10 VR 40, or concurrent VR 5 VR 50 schedules, pigeons responded almost exclusively on the key on which fewer responses were required to produce the reinforcer. When other doses of pentobarbital and other drugs were substituted for the training dose, low doses of all drugs produced responding on the saline-biased key. Higher doses of pentobarbital and chlordiazepoxide produced responding only on the pentobarbital-biased key, whereas higher doses of ethanol and phencyclidine produced responding only on this key less often. d-Amphetamine produced responding primarily on the saline-biased key. When drugs generalized to pentobarbital, the shape of the generalization curve under concurrent VR VR schedules was more often graded than quantal in shape. Thus, drug discrimination can be established under concurrent VR VR schedules, but the shapes of drug-discrimination dose-response curves under concurrent VR VR schedules more closely resemble those seen under interval schedules than those seen under fixed-ratio schedules. Graded dose-response curves under concurrent VR VR schedules may relate to probability matching and difficulty in discriminating differences in reinforcement frequency.     

Acceleration model in the heterogeneous case of the general graded response model

A new model, called acceleration model, is proposed in the framework of the heterogenous case of the graded response model, based on processing functions defined for a finite or enumerable number of steps. The model is expected to be useful in cognitive assessment, as well as in more traditional areas of application of latent trait models. Criteria for evaluating models are proposed, and soundness and robustness of the acceleration model are discussed. Graded response models based on individual choice behavior are also discussed, and criticisms on model selection in terms of fitnesses of models to the data are also given.This research was supported by the Office of Naval Research (N00014-90-J-1456).     

Successive-beat analysis of cardiovascular orienting and conditional responses

We have shown that prominent changes in heart rate (HR) and blood pressure (BP) occur in dogs during classical defensive conditioning. These changes are usually analyzed as average HR and BP during control periods versus averages during conditional stimulus (CS) and unconditional stimulus (US) periods. A new method has been developed for evaluation of these functions, viz., analysis across many trials of successive beats beginning at onset of CS and working backward (control period) and forward (CS period). Nine awake dogs were continuously studied: six with HR and intra-arterial BP measurements and three with HR measurements only. A drop in HR occurs 1 to 2 beats after CS onset (often noted as a “dropped” beat on individual trials). In some dogs, on the third to fifth beat HR reaches its maximum during the CS period, thereafter falling slightly, but still above baseline; other dogs show progressively increasing HR throughout the whole CS period. At US onset (foreleg shock) HR usually rises rapidly to a peak greater than that at CS maximum. BP follows HR changes fairly closely, diastolic better than systolic. These results indicate that I) this method can reveal transients previously unsuspected, 2) a prominent initial sudden bradycardia followed by tachycardia commonly occurs in conditioning in dogs, 3) the latent period of prominent HR increase is usually quite short (1.3 to 1.6 secs.), and 4) BP follows HR directly during the early part of the CS.     

Mental and physical stress as moderators of the postural response in insulin-dependent diabetic patients

Two simple stressors, mental arithmetic and isometric handgrip, were studied as moderators of the physiological response to standing in insulin-dependent diabetic patients and in healthy controls. Continuous (beat-to-beat) measures were taken of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and skin conductance (SC) during postural change under baseline and stressor conditions. Diabetic patients without symptoms of neuropathy and healthy controls showed generally similar responses to postural change and to the stressor conditions. SBP and DBP were more responsive to the mental and physical stressors than were HR or SC, especially after standing. Two diabetic patients with postural hypotension showed significant increases in overall BP levels and less of a fall in BP during postural change under the stressor conditions, despite minimal HR or SC responses. Results indicate that these strategies are effective in increasing BP during postural change in both diabetic and nondiabetic individuals and may be useful in the management of orthostatic hypotension.     

重视非抗心律失常药物的致心律失常作用

抗心律失常药物的致心律失常作用近年来已得到心血管科医生的广泛关注,但在临床实践中观察,对于一些非抗心律失常药,如抗生素、精神类药物等,在发挥他们相应的药理效应同时,可引起心动过缓、心动过速、传导阻滞,甚至致命性心律失常,而其致心律失常效应往往没有引起关注,强化非心脏药物致心律失常作用的意识,了解其可能的机制及促发因素都是必要的。     

An animal analogue to systematic desensitization and elimination of avoidance

Rats first acquired a two-way avoidance response to a discrete warning signal (80 db white noise.) The effects of 3 experimental and 3 control treatments on elimination of the response were evaluated on a nonshock posttreatment extinction test. Group Systematic Desensitization (SD) received graded exposure to the warning signal while they were eating. Rats in Graded Hierarchy (GH) and Extinction (Ext) groups were yoked to Ss in the SD group such that GH and Ext treatment was identical with that of SD except that neither group ate and the Ext group was exposed to the full intensity warning signal (nongraded exposure) on all trials. None of the control groups was exposed to the warning signal between acquisition and the posttreatment test. Results indicated that SD, while interfering with avoidance during treatment, did not differ in effectiveness from control treatment and was significantly less effective than GH and Ext, when avoidance was tested in extinction. It was suggested that the present analogue SD technique impaired S's reception of (exposure to) the warning signal during treatment.     

Mechanism of the human diving response

The diving response in human beings is characterized by breath-holding, slowing of the heart rate (diving bradycardia), reduction of limb blood flow and a gradual rise in the mean arterial blood pressure. The bradycardia results from increased parasympathetic stimulus to the cardiac pacemaker. The reduction in limb blood flow is due to vasoconstriction resulting from increased activity of the sympathetic nerves supplying arteries in the arms and legs. Essentially the response is produced by the combination of water touching the face and either voluntary or involuntary (reflex) arrest of breathing. The nervous inputs and outputs for the response are coordinated in the brain stem by the respiratory, vasomotor and cardioinhibitory “centers.” The diving response in human beings can be modified by many factors but the most important are water temperature, oxygen tension in the arterial blood and emotional factors.     

A mechanical method for changing heart rate and blood pressure

The investigation of afferent cardiovascular influences upon central nervous processes needs a methodology which allows for independent and systematic manipulation of circulatory processes. By mechanical manipulation of posture (tilt table, orthostasis) and compression of lower body parts (by anti-G-suit) reliable changes in heart rate and blood pressure can be induced. In fourty subjects (study 1) it could be shown that sustained (30 min.) changes in heart rate (e.g. orthostatic tachycardia, decrease of heart rate during compression) and mean arterial blood pressure (increase during orthostasis with and without compression) occur. Although changes in heart rate could be achieved irregardless of whether the venous "pooling" was suppressed by an air- or water-filled pressure suit, the pressor effect did differ quite considerably. In fourty-four subjects (study 2) it could be demonstrated that only by means of an water-filled suit further increases in mean arterial blood pressure could be evoked during orthostasis. Changes in hemodynamic also lead to changes in sympatho-vagal control of cardiac activity. In study 3 (ten subjects) it could be shown, that orthostasis mainly evokes alterations in sympathetic activity whereas lower body compression leads to additional increases of vagal activity and respiratory sinus arrhythmia during orthostasis.     

Shortening of the QT interval of the EKG is associated primarily with increased ventricular contractility rather than heart rate

The objective of this study was to gather direct evidence on whether the duration of the QT interval relates primarily to heart rate or to ventricular contractility. The electrocardiographic and cardiodynamic consequences of electrical stimulation (15 V, 5 ms, 10Hz) of various intrathoracic sympathetic efferent neuronal structures were studied in 10 anesthetized mongrel dogs. Stimulation of efferent sympathetic axons in the right intraganglionic nerve, which innervates the sinoatrial node, induced tachycardia (110±5 - 133±6 bpm; p<0.01) without significantly altering right or left ventricular intramyocardial ventricular chamber pressures. The QT interval, as determined by leads I, II and III of the EKG and a transthoracic lead, was not affected by this intervention (310±8 - 302±ms). Increasing heart rate to a similar degree (111±3 - 131±3 bpm) by right atrial pacing did not induce changes in the QT interval. When right (23±3 - 49±8 mm Hg; p<0.01) and left (81±10 - 127±19 mm Hg; p<0.01) ventricular forces were augmented without concomitant increases in heart rate by stimulating efferent sympathetic axons in the left caudal pole cardiopulmonary nerve the QT interval shortened (322±11 - 290±12 ms; p<0.01). Only when an efferent sympathetic nerve, that contains fibers destined for both the sinoatrial node and the ventricles was stimulated did both heart rate and ventricular contractility augment and QT shorten (318±10 - 290±11 ms; p<0.01). These results indicate that QT interval shortening induced by efferent sympathetic neurons is primarily associated with augmentation of ventricular contractility rather than heart rate.     

Potentiation of the pressor response to stress by tolbutamide in dogs

Tolbutamide has previously been shown to amplify the pressor effects of “exogenous” catecholamines in conscious dogs, possibly due to sensitization of the α₁-adrenoreceptor-mediated vasoconstriction. The objective of this study was to examine if tolbutamide also amplifies the pressor effects of “endogenous” catecholamines released during psychological stress (classical Pavlovian aversive conditioning). Experiments were conducted in β-adrenoreceptor-blocked (propranolol, 1 mg/kg, i.v.) conscious dogs (n=4) trained in classical aversive conditioning. Conditioning was accomplished by following a tone (CS+) with a 1/2 second shock; another tone (CS-) was not followed by any shock and served as control. With saline pretreatment, aversive conditioning (i.e., CS+) increased mean arterial pressure (MAP) only by approximately 4.7% when compared to CS-, whereas with tolbutamide (45 mg/kg, i.v.) pretreatment, the increase in MAP induced by CS+ beyond what was induced by the CS- (approximately 6.2%) was significantly (p<0.05) larger than that with saline pretreatment. In isolated canine femoral arterial segments (n=4), the vasoconstrictor effect of phenylephrine (an α₁-agonist) at 5×10^?6M (which was the EC₅₀ value) was amplified by 2×10^?2M of tolbutamide from 54.0±2.0% to 66.9±2.1%. In conclusion, tolbutamide amplifies the pressor effects of “endogenous” catecholamines in conscious dogs, possibly by sensitization of the α₁-adrenoreceptor-mediated vasoconstriction. This mechanism of action is novel and has not been reported with other agents.     

Failure to develop a conditional reflex by stimulation of the cephalad portion of the severed vagosympathetic trunk: Its significance in terms of the central connections of the vagus

Stimulation of the central stump of either vagosympathetic trunk in the dog, the contralateral nerve remaining intact, regularly provoked deep respiratory movements with forceful expiration, followed by a period of apnea, and a fall in blood pressure, systolic and diastolic, of 20–60 mm/Hg. Stimulation of the cephalad portion of the left nerve provoked brief acceleration of heart rate during the period of hyperventilation, followed by bradycardia; when the stimulus was applied to the central stump of the right nerve heart rate remained relatively unchanged. When a 12-second tone as a conditional stimulus (CS) was reinforced during its last six seconds with such stimulation of the vagosympathetic trunk as an unconditional stimulus (US), despite the striking visceromotor responses elicited by the US, no conditional reflex was established even after more than 3,400 trials in 16 dogs (34–781 trials per animal).     

Regulation of exercise intensity using ratings of perceived exertion during passive visual distraction

The purpose of this investigation was to determine if passive visual distraction altered ability to regulate exercise intensity as, assessed by ratings of perceived exertion during a 30-min. treadmill run. 10 trained females (VO2max, 52.7 ml.kg-1.min.-1) performed a graded exercise test on a treadmill to assess maximal aerobic power and rating of perceived exertion, oxygen uptake (VO2), heart rate, and running velocity at the 2.5 mmol.L-1 blood lactate concentration. Subjects then used the target rating of perceived exertion to regulate exercise intensity during a control condition, and two treatment runs with passive visual distractions. During the treatment sessions, the subjects ran on a treadmill while viewing a high-action or a low-action video with no audio. The subjects were allowed to adjust the treadmill speed throughout the run to maintain the target rating of perceived exertion; however, subjects were not allowed to view the speed setting. There were no significant differences in blood lactate concentration among the conditions for the control, low action, high action, or graded exercise test (p < or = .05). No significant differences in VO2 or running velocity were found within or among the 30-min. treatment runs and the graded exercise test. Heart rate at 5 min. of exercise during control (158 +/- 3 b.min.-1), low action (158 +/- 3 b.min.-1), and high action (159 +/- 2 b.min.-1) was significantly lower than the graded exercise test (169 +/- 3 b.min.-1). Based on the data collected, visual passive distraction did not alter regulation of intensity using ratings of perceived exertion during a 30-min. treadmill run.     

Isatin: role in stress and anxiety

(Indoledione 2,3) isatin is an endogenous indole found both in mammalian brain and peripheral tissues. Isatin concentration in blood can exceed 1 microM and tissue concentrations vary from < 0.1 to 10 microM. Its level in the brain and periphery is increased by stress. Isatin has a wide spectrum of behavioural and metabolic effects. It is anxiogenic at lower doses and sedative at higher doses. Its most potent known in vitro actions are as an antagonist of atrial natriuretic peptide (ANP) function and NO signaling. In this review, we discuss isatin and stress in animal models, the few human studies, and also what it is known to date about the molecular mechanisms of its action. We suggest the possibility that isatin and its analogues may be interesting new pharmacological agents; Isatin antagonists may be anxiolytic, and isatin agonists may activate the HPA axis.