Comparison of the exercise pressor reflex between forelimb and hindlimb muscles in cats.

In thirteen cats anesthetized with alpha-chloralose, we compared the cardiovascular and ventilatory responses to both static contraction and tendon stretch of a hindlimb muscle group, the triceps surae, with those to contraction and stretch of a forelimb muscle group, the triceps brachii. Static contraction and stretch of both muscle groups increased mean arterial pressure and heart rate, and the responses were directly proportional to the developed tension. The cardiovascular increases, however, were significantly greater (P < 0.05) when the triceps brachii muscles were contracted or stretched than when the triceps surae muscles were contracted or stretched, even when the tension developed by either maneuver was corrected for muscle weight. Likewise, the ventilatory increases were greater when the triceps brachii muscles were stretched than when the triceps surae muscles were stretched. Contraction of either muscle group did not increase ventilation. Our results suggest that in the anesthetized cat the cardiovascular responses to both static contraction and tendon stretch are greater when arising from forelimb muscles than from hindlimb muscles.

Coronary-bronchial blood flow and airway dimensions in exercise-induced syndromes.

1. We have an incomplete understanding of integrative cardiopulmonary control during exercise and particularly during the postexercise period, when symptoms and signs of myocardial ischaemia and exercise-induced asthma not present during exercise may appear. 2. The hypothesis is advanced that baroreflex de-resetting during exercise recovery is normally associated with (i) a dominant sympathetic vasoconstrictor effect in the coronary circulation, which, when associated with obstructive coronary disease, may initiate a potentially positive-feedback cardiocardiac sympathetic reflex (variable myocardial ischaemia with symptoms and signs); and (ii) a dominant parasympathetic bronchoconstrictor effect in the presence of bronchovascular dilatation, which, when associated with raised mediator release in the bronchial wall, reinforces the tendency for airway obstruction (variable dyspnoea results). 3. There is a need for new techniques to examine hypotheses concerning autonomic control, during and after exercise, of the coronary and bronchial circulations and the dimensions of airways. Accordingly, a new ultrasonic instrument has been designed named an 'Airways Internal Diameter Assessment (AIDA) Sonomicrometer'. It combines pulsed Doppler flowmetry with transit-time sonomicrometry of airway circumference and single-crystal sonomicrometry of airway wall thickness. Initial evaluation suggests it is relatively easy to apply during thoracotomy in recovery animals. The component devices are linear and will measure target variables with excellent accuracy. 4. In anaesthetized sheep, intubated with controlled ventilation, intravenous isoproterenol causes large increases in bronchial blood flow, a fall in arterial pressure and a reduction in airway circumference. This may reflect the dominant action of reflex vagal activity over direct beta-adrenoceptor inhibition of bronchial smooth muscle, the reflex source being baroreflex secondary to the fall in arterial pressure. These findings provide insight into the integrative mechanisms underlying the paradoxical negative effects sometimes observed when beta-adrenoceptor agonists are used in asthma.

Gadolinium attenuates exercise pressor reflex in cats.

The exercise pressor reflex, which arises from the contraction-induced stimulation of group III and IV muscle afferents, is widely believed to be evoked by metabolic stimuli signaling a mismatch between blood/oxygen demand and supply in the working muscles. Nevertheless, mechanical stimuli may also play a role in evoking the exercise pressor reflex. To determine this role, we examined the effect of gadolinium, which blocks mechanosensitive channels, on the exercise pressor reflex in both decerebrate and alpha-chloralose-anesthetized cats. We found that gadolinium (10 mM; 1 ml) injected into the femoral artery significantly attenuated the reflex pressor responses to static contraction of the triceps surae muscles and to stretch of the calcaneal (Achilles) tendon. In contrast, gadolinium had no effect on the reflex pressor response to femoral arterial injection of capsaicin (5 microg). In addition, gadolinium significantly attenuated the responses of group III muscle afferents, many of which are mechanically sensitive, to both static contraction and to tendon stretch. Gadolinium, however, had no effect on the responses of group IV muscle afferents, many of which are metabolically sensitive, to either static contraction or to capsaicin injection. We conclude that mechanical stimuli arising in contracting skeletal muscles contribute to the elicitation of the exercise pressor reflex.

Both central command and exercise pressor reflex reset carotid sinus baroreflex.

In decerebrate unanesthetized cats, we determined whether either "central command," the exercise pressor reflex, or the muscle mechanoreceptor reflex reset the carotid baroreflex. Both carotid sinuses were vascularly isolated, and the carotid baroreceptors were stimulated with pulsatile pressure. Carotid baroreflex function curves were determined for aortic pressure, heart rate, and renal vascular conductance. Central command was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) in cats that were paralyzed. The exercise pressor reflex was evoked by statically contracting the triceps surae muscles in cats that were not paralyzed. Likewise, the muscle mechanoreceptor reflex was evoked by stretching the calcaneal tendon in cats that were not paralyzed. We found that each of the three maneuvers shifted upward the linear relationship between carotid sinus pressure and aortic pressure and heart rate. Each of the maneuvers, however, had no effect on the slope of these baroreflex function curves. Our findings show that central command arising from the MLR as well as the exercise pressor reflex are capable of resetting the carotid baroreflex.

Acetazolamide in bipolar affective disorders.

Acetazolamide is a carbonic anhydrase inhibitor used for a variety of purposes, including adjunctively in the management of various types of epilepsy. A previous study on its psychotropic effects suggested the possibility of efficacy in atypical psychotic states, especially those characterized by cyclicity. In the present investigation, 16 patients with refractory affective symptomatology were treated with acetazolamide in a prospective open trial after exhaustive trials with antidepressants, lithium, carbamazepine, divalproex, and other anticonvulsants. Seven of the 16 (44%) responded positively, in some cases dramatically, for as long as 2 years. Analysis revealed that all of the responders were either in a depressive phase or in a rapid-cycling phase of a bipolar illness and that all had experienced partial positive response to at least one other anticonvulsant and were being maintained on anti-convulsant therapy when the response occurred. Salient theoretical issues are explored.

Barbiturate anticonvulsants in refractory affective disorders.

Despite an increasing literature demonstrating both acute and long-term positive psychopharmacological effects of both valproate and carbamazepine, phenytoin has remained a controversial intervention, and barbiturate anticonvulsants have generally received poor press with regard to psychotropic effects. In the present investigation, 27 seizure-free, affectively ill patients who received therapeutic trials of primidone and/or mephobarbital after failing on antidepressants, lithium, carbamazepine, valproate, and phenytoin were analyzed with regard to effects on illness severity and affective cycle rate over a period of as long as four years. Nine (33%) of the patients had a sustained positive therapeutic effect on affective state and/or psychotic symptoms to primidone and three (11%) had positive effects on mephobarbital after primidone failure. Four (15%) had brief positive effects that were not sustained, and the remaining 11 (41%) had no effects or negative effects to these agents. The theoretical and practical implications of this new and unexpected finding are discussed.

Long-term use of valproate in primary psychiatric disorders.

Thirty-five patients, all with major depressive illness, bipolar disorder, or schizoaffective disorder, were retrospectively identified as having received valproate either alone or in combination with lithium, after having failed to adequately respond to previous lithium and/or carbamazepine treatment. Clinical evaluation and Global Assessment Scale (GAS) scores indicated that at baseline all but 3 of the patients experienced serious psychiatric symptoms, serious impairment in social or professional functioning, or significant impairment in reality testing. Mean GAS scores after a mean duration of at least 1 year of valproate administration improved in 7 of 9 depressed patients, 12 of 12 patients with bipolar disorder, and 11 of 14 patients with schizoaffective states. Mean increases in GAS scores were 27.7 points for depressive disorder patients, 34.5 points for mixed bipolar disorder patients, and 17.1 points for patients with schizoaffective states. For patients with either depressive disorders or mixed bipolar disorders, that mean change represented a level of improvement sufficient to elevate the majority of the patients into the mild symptom range or the virtually asymptomatic state. That improvement was confirmed by the investigator's global evaluation of patient response with regard to affect: valproate administration produced significant affective responses in 7 of 9 depressed patients, 12 of 12 patients with mixed bipolar disorders, and 11 of 14 patients with schizoaffective states. The responses of patients with bipolar and schizoaffective disorders to valproate treatment compared with valproate plus lithium treatment were also evaluated. Patients in both diagnostic categories demonstrated very similar and quite substantial improvement in mean change in GAS ratings and global evaluations, regardless of whether valproate was administered alone or in combination with lithium.