Characterisation and constitutive modelling of biaxially stretched poly(L-lactic acid) sheet for application in coronary stents.

A poly(L-lactic acid) stent is exposed to a variety of processing techniques, temperatures and environmental conditions during its lifecycle, from the manufacturing process, to crimping through to deployment within the body. The effect of the biaxial stretching procedure and the effects of temperature and extension rate (post-processing) on the mechanical response of poly(L-lactic acid) are hereby investigated, and a constitutive model calibrated against experimental data is proposed. Dumb-bell specimens were punched from biaxially stretched sheets subjected to different processing histories, and tested under uniaxial tension at various temperatures (20, 37 and 55 °C) and extension rates (1, 5 and 10 mm/min). A Design of Experiments methodology was employed to identify the parameters that had the most significant effect on the mechanical response of the polymer. Results show that the elastic modulus and yield strength of the stretched sheets are strongly dependent on the aspect ratio of the biaxial deformation, along with the temperature during uniaxial deformation (post-processing). In contrast, these mechanical properties were not heavily dependent on extension rate (post-processing). A transversely isotropic, elastic-plastic constitutive model for finite element implementation is proposed, with the intention that it may be used as a design tool for developing high stiffness, thin-strut polymeric stents that contend with the performance of their metallic counterparts.

Processing-property relationships of biaxially stretched poly(L-lactic acid) sheet for application in coronary stents.

The development of coronary stents from poly(L-lactic acid) requires knowledge of its mechanical properties and the effects of manufacturing processes on those properties. The effects of the biaxial stretching procedure on the mechanical and microstructural properties of poly(L-lactic acid) are hereby investigated. The mechanical properties were evaluated before and after biaxial stretching, with a Design of Experiments methodology employed to identify processing parameters that had the most significant effect on the elastic modulus and yield strength of the biaxially stretched sheets. Microstructural characterisation was performed using differential scanning calorimetry to evaluate crystallinity and thermal transitions of the biaxially stretched sheets. The results show that the mechanical properties of the stretched sheets are highly dependent on the extent of stretch ratio applied during processing; however, neither the elastic modulus nor yield strength are directly attributable to crystallinity, but are affected by the degree of amorphous orientation. The results of this study have the potential to be applied in the design of high stiffness, thin-strut polymeric expandable scaffolds for the application of coronary stents.

The expression of Fos-labeled spinal neurons in response to colorectal distension is enhanced after chronic spinal cord transection in the rat.

The present study used Fos-like immunoreactivity to examine neuronal activation in response to colorectal distension in rats at 1 day or 30 days following spinal cord transection or sham transection. Fifty-five Wistar rats were anesthetized and an incision was made to expose the T(5) spinal segment. The dura was reflected away in all rats and a complete transection at the rostral end of the T(5) segment was given to the lesioned group. At 1 day (acute) or 30 days (chronic) post-surgery, conscious rats were subjected to a 2 h period of intermittent colorectal distension. Rats were perfused and spinal segments L(5)-S(2) were removed and processed for Fos-like immunoreactivity. Spinal cord transection alone had no effect on Fos-labeling in either acute or chronic rats. In acute rats, colorectal distension produced significant increases in Fos-labeling in the superficial and deep dorsal horn regions. In chronic rats, colorectal distension produced a three-fold increase in Fos-labeled neurons that was manifest throughout all laminar regions. These results indicate that the number of neurons expressing Fos in response to colorectal distension is much greater after a chronic spinal cord transection than after an acute transection. Since Fos is an indicator of neuronal activation, the results show that many more neurons become active in response to colorectal distension following a chronic spinal injury. This suggests that a functional reorganization of spinal circuits occurs following chronic spinal cord transection. This may ultimately result in altered visceral and somatic functions associated with spinal cord injury in humans.

Correlation of ventricular mechanosensory neurite activity with myocardial sensory field deformation.

The mechanosensory activity generated by ventricular epicardial sensory neurites associated with afferent axons in thoracic sympathetic nerves was correlated with sensory field deformation (long axis, short axis, and transmural dimension changes), regional intramyocardial pressure, and ventricular chamber pressure in anesthetized dogs. Ventricular mechanosensory neurites generated activity that correlated best with strain developed along either the long or short axis of their epicardial sensory fields in most instances. Activity did not correlate normally to local wall thickness or to regional wall or chamber pressure development in most cases. During premature ventricular contractions, the activity generated by these sensory neurites correlated best with maximum strain developed along at least one sensory field epicardial vector. Identified sensory neurites were also activated by local application of the chemical bradykinin (10 microM) or by local ischemia. These data indicate that the activity generated by most ischemia-sensitive ventricular epicardial sensory neurites associated with afferent axons in sympathetic nerves is dependent on not only their local chemical milieu but on local mechanical deformation along at least one epicardial vector of their sensory fields.

Does postsynaptic alpha 1-adrenergic receptor supersensitivity contribute to autonomic dysreflexia?

Quadriplegics often experience periods of severe hypertension known as autonomic dysreflexia. Clinically, these events have been well documented, but the mechanisms for mediating autonomic dysreflexia remain unclear. We used a chronic rat model to investigate the potential development of supersensitivity at postsynaptic alpha 1-adrenergic receptors as a contributing factor to the exaggerated sympathetic response characteristic of autonomic dysreflexia. Adult male Wistar and Sprague-Dawley rats were anesthetized and given spinal transection at T5. After 30 days, rats were reanesthetized and arterial and venous catheters implanted. Twenty-four hours later, colorectal distension (CRD) was used to evoke autonomic dysreflexia in conscious, spinalized rats. To gauge changes in alpha 1-receptor sensitivity, we assessed mean arterial pressure (MAP) in response to intravenous phenylephrine (PE) infusions. No consistent differences were observed between intact and spinalized rats. Therefore, supersensitivity of alpha 1-receptors cannot completely account for the hypertensive bouts associated with autonomic dysreflexia. In addition, while attempting to develop an appropriate model for autonomic dysreflexia, we discovered that spinalized Wistar rats exhibited MAP responses characteristic of autonomic dysreflexia, whereas lesioned Sprague-Dawley rats did not, when subjected to CRD. Thus Wistar rats provide a better animal model for autonomic dysreflexia.

Convergence of multiple sensory inputs onto neurons in the dorsolateral medulla in cats.

The dorsolateral medulla, including the nucleus reticularis parvicellularis, the cuneate nucleus, and the external cuneate nucleus, is an integrative region for a variety of sensory inputs. The purpose of this study was to determine whether individual neurons respond to a variety of different sensory modalities. To this end, responses of 40 neurons in the dorsolateral medulla to multiple sources of sensory input were assessed in cats anesthetized with alpha-chloralose. Neurons were located in the nucleus reticularis parvicellularis (24 cells, 60%), the cuneate nucleus (10 cells, 25%), and the external cuneate nucleus (6 cells, 15%). All neurons were tested for responses to: electrical stimulation of afferents coursing through the left stellate ganglion and afferents in the left cervical vagus nerve, and somatic, auditory, and visual stimulation. No neurons responded to all five stimuli. Three cells (7.5%) responded to four stimuli, 11 (27.5%) responded to three stimuli, 10 (25.0%) responded to two stimuli, and 15 (37.5%) responded to only a single stimulus. The remaining cell was unresponsive to any stimulus. As a group, neurons in the nucleus reticularis parvicellularis received input from the greatest number of sensory modalities, and cuneate nucleus neurons received input predominantly from somatosensory afferents. External cuneate nucleus neurons displayed response profiles intermediate between nucleus reticularis parvicellularis and cuneate nucleus. In addition, eight neurons (20% of the total) were sensitive to changes in blood pressure. Results of the present study support the hypothesis that neurons in the nucleus reticularis parvicellularis receive convergent inputs from different sensory modalities.2+ behaviors.

Noxious heat-evoked Fos-like immunoreactivity in the rat medulla, with emphasis on the catecholamine cell groups.

The objectives of the present study were 1) to utilize Fos immunohistochemistry as a marker for neuronal activity in order to examine the population of neurons in the medulla that is engaged by activation of nociceptive peripheral afferents and 2) to determine whether catecholamine-containing neurons in the medulla also express noxious heat-evoked Fos-like immunoreactivity. Noxious heating of the hindpaw evoked specific patterns of Fos-like immunoreactivity in the medulla in regions known to be involved in both nociceptive processing and cardiovascular regulation. Noxious heating of the hindpaw significantly increased the mean number of neurons expressing Fos-like immunoreactivity in the contralateral ventrolateral medulla. Increased numbers of Fos-positive neurons also were observed in both the ipsilateral and the contralateral A1 catecholamine cell groups. Similarly, in the contralateral medullary dorsal reticular fields, noxious heating of the hindpaw significantly increased the mean number of neurons expressing Fos-like immunoreactivity. In contrast, in the paramedian reticular nucleus, noxious heating of the hindpaw resulted in a significant decrease in the mean number of neurons expressing Fos-like immunoreactivity. No significant differences in the mean numbers of neurons expressing Fos-like immunoreactivity were noted in the A2, C1, or C2/C3 medullary catecholamine cell groups. These results suggest that noxious stimuli affect pools of neurons in the medulla with multiple physiological functions.

Effects of vagal afferent nerve stimulation on noxious heat-evoked Fos-like immunoreactivity in the rat lumbar spinal cord.

Electrophysiological and behavioral studies have described modulation of nociception by vagal afferent fibers. The objectives of this study were to 1) use Fos-like immunoreactivity as a marker for neuronal activity to examine populations of neurons in the spinal cord that are activated by a noxious heat stimulus, 2) determine whether heat-evoked Fos-like immunoreactivity can be modulated by vagal afferent stimulation, and 3) determine whether vagally-mediated effect on heat-evoked Fos-like immunoreactivity can be blocked by intrathecally administered serotoninergic receptor and alpha-adrenergic receptor antagonists. Neurons demonstrating Fos-like immunoreactivity were located in the ipsilateral superficial and deep dorsal horn laminae extending from the caudal L3 through the rostral L6 region of the spinal cord. Stimulation of the right cervical vagus nerve attenuated significantly (42%) heat-evoked Fos-like immunoreactivity in the superficial laminae. The reduction in Fos-like immunoreactivity by vagal stimulation was abolished by intrathecal administration of methysergide, a nonselective serotoninergic receptor antagonist, but not by phentolamine, a nonselective alpha-adrenoceptor antagonist. These results suggest that vagal afferent modulation of spinal nociceptive transmission is mediated, at least in part, by serotonin receptors.

Responses of medullary raphe neurons to electrical and chemical activation of vagal afferent nerve fibers.

1. Various intensities, frequencies, and pulse widths of electrical stimulation of vagal afferent fibers were used to assess the responses of 87 medullary raphe neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized, barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be antidromically activated. Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not found; however, their locations were comparable in depth and position on the midline with other neurons in the same animals whose locations were identified. 2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed responses were characterized by excitation at one frequency or intensity and inhibition at another frequency or intensity. The remaining 27 neurons did not clearly respond. 3. The excitatory responses to electrical stimulation of the cervical vagus nerve were intensity and frequency dependent. Inhibitory responses were frequency dependent at lower frequencies of stimulation and both frequency and intensity dependent at higher frequencies. The mixed responses were frequency dependent. Overall, longer pulse widths produced significantly greater responses than shorter pulse widths. 4. Thirty-three neurons were tested for responses to chemical stimulation of vagal afferents with intra-atrial injections of three doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6% had mixed responses. For the mixed responses, excitation occurred at one dose and inhibition at another. The remaining 18% of the neurons were unresponsive to veratridine. The excitatory responses were dose dependent, but the inhibitory responses were not. Three doses of phenybiguanide (PBG) were also used to chemically activate vagal afferents in 27 neurons. Eleven percent were excited, 44% were inhibited, and 4% had mixed responses. The remaining 41% were unresponsive to PBG. The excitatory and inhibitory responses were dose dependent. 5. When comparing responses in projection and nonprojection neurons, inhibition was seen significantly more often in projection neurons and excitation in nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical stimulation were raphespinal neurons, and 78% of the neurons excited by vagal stimulation were nonprojection neurons. Similar observations were made with the responses to chemical activation of the vagus. 6. Neurons with lower spontaneous discharge rates were more often excited by vagal stimulation and neurons with higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of anesthetic agents on somatosensory responses of raphespinal neurons in the cat.

The goal of this study was to examine the effects of alpha-chloralose and pentobarbital on the somatosensory responses of medullary raphespinal neurons. With alpha-chloralose, 98% of neurons responded to innocuous stimuli, particularly tapping, but only 1/64 responded selectively to nociceptive stimuli. In contrast, 73% of neurons responded selectively to noxious stimuli with pentobarbital, and none responded selectively to innocuous stimuli. In addition, raphespinal neurons studied with pentobarbital had higher spontaneous discharge rates, and a higher incidence of spontaneity, than neurons studied with alpha-chloralose. Thus, different anesthetics produce raphespinal neurons with different somatosensory response characteristics.

Intracardiac phenylbiguanide causes excitation of spinal neurons by activation of cardiac sympathetic afferents.

The responses of spinothalamic, spinoreticular, and unidentified spinal neurons to intracardiac administration of phenylbiguanide, a 5-HT3 receptor agonist, were examined in anesthetized cats and monkeys. Eighteen neurons were excited, 5 were inhibited, and 12 were unresponsive to this stimulus. Results suggest that cardiac sympathetic afferents mediate the excitatory responses produced by phenylbiguanide, because bilateral cervical vagotomy failed to block these responses, and aortic injections of phenylbiguanide had little effect on cell activity.

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.

Responses of medullary raphespinal neurons to electrical stimulation of thoracic sympathetic afferents, vagal afferents, and to other sensory inputs in cats.

1. Medullary raphespinal neurons antidromically activated from the T2-T5 segments were tested for responses to electrical stimulation of cervical vagal and thoracic sympathetic afferents (by stimulating the left stellate ganglion), somatic probing, auditory stimuli, and visual stimuli in cats anesthetized with alpha-chloralose. A total of 99 neurons in the raphe nuclei were studied; the locations of 76 cells were histologically confirmed. Neurons were located in raphe magnus (RM, 65%), raphe obscurus (RO, 32%), and raphe pallidus (RPa, 4%). The mean conduction velocity of these neurons was 62 +/- 2.9 (SE) m/s with a range of 1.1-121 m/s. 2. A total of 60/99 tested neurons responded to electrical stimulation of sympathetic afferents. Quantitation of responses was obtained for 55 neurons. With one exception, all responsive neurons were excited and exhibited an early burst of spikes with a mean latency of 16 +/- 1.2 ms. From a spontaneous discharge rate of 5.2 +/- 1.2 spikes/s, neuronal activity increased by 2.9 +/- 0.3 spikes/stimulus. In addition to an early peak, 15 neurons (25%) exhibited a late burst of spikes with a latency of 182 +/- 12.9 ms; neuronal activity increased by 5.0 +/- 1.3 spikes/stimulus. Duration of the late peak (130 +/- 18.5 ms) was longer than for the early peak (18 +/- 0.7 ms), but threshold voltages for eliciting each peak were comparable. Sixteen of 29 spontaneously active neurons exhibited a postexcitatory depression of activity that lasted for 163 +/- 19.1 ms. All but one tested neuron in RO responded to stimulation of sympathetic afferents, but 65% of neurons in RM responded to this stimulus. 3. In response to vagal afferent stimulation, 19% of 57 neurons exhibited inhibition only, 11% were only excited, and 9% were either excited or inhibited, depending on the stimulus paradigm used; the remaining 61% of neurons were unresponsive. From a spontaneous rate of 7.9 +/- 3.8 spikes/s, excited cells increased their discharge rate by 1.6 +/- 0.3 spikes/stimulus. Activity of inhibited cells was reduced from 21.3 +/- 5.8 to 7.8 +/- 3.1 spikes/s. The conditioning-test (CT) technique was used to assess 11 neurons' responses. Stellate ganglion stimulation was the test stimulus, and vagal stimulation the conditioning stimulus. Vagal stimulation reduced the neuronal responses to stellate ganglion stimulation by an average of 50% with a CT interval of 60-100 ms, and cell responses returned to control after 300 ms. With spontaneous cell activity, low frequencies of vagal stimulation were generally excitatory, and high frequencies (10-20 Hz) inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of medullary raphespinal neurons to coronary artery occlusion, epicardial bradykinin, and cardiac mechanical stimuli in cats.

1. A total of 59 medullary raphespinal neurons antidromically activated from the T2-T5 segments were tested for responses to coronary artery occlusion, epicardial application of bradykinin, and mechanical probing of the epicardium in cats anesthetized with alpha-chloralose. With the exception of five neurons, only those neurons that were responsive to electrical stimulation of the left stellate ganglion were tested for responses to these stimuli. Neurons in this study are a subset of those in the companion report. 2. Six neurons (12%) responded to epicardial bradykinin. Five cells were excited, and one was inhibited. Nine neurons (18%) had cardiac receptive fields, and one neuron (2%) had a field confined to the pericardium. 3. Neurons were tested for responses to separate occlusions of the left anterior descending (LAD) and circumflex (CX) coronary arteries. Overall, 13/34 (38%) of tested raphespinal neurons were responsive to coronary artery occlusion. Responses to coronary artery occlusion consisted of two major patterns. One pattern consisted of either an increase or decrease in neuronal firing rate after the heart became ischemic; this pattern was termed an ischemic (IS) response. Ten neurons (29%) exhibited an IS response to occlusion of the LAD and/or CX coronary arteries. Because four neurons exhibited IS responses to occlusion of each artery, there were a total of 14 IS responses. Of these, 10 were inhibitory, and 4 were excitatory. The second pattern of response consisted of a rapidly adapting excitation or inhibition at the onset or release of occlusion, but cell activity was unchanged during cardiac ischemia; this pattern was termed an onset (ON) response. Three neurons (9%) exhibited ON responses; two were excited, and one was inhibited. No neurons demonstrated both ON and IS responses during occlusion. 4. Twenty-one neurons were tested for responses to occlusion of each artery. Seventeen neurons (81%) exhibited similar patterns of responses to occlusion of each artery; that is, they either showed the same pattern of response to occlusion of each artery or they were unresponsive to either occlusion. For the 5 of these 17 neurons that were responsive, direction of change in neuronal activity (excitation or inhibition) was the same for occlusion of each artery. 5. All raphespinal neurons tested for responses to epicardial bradykinin and coronary artery occlusion were responsive to electrical stimulation of the left stellate ganglion. In addition, 16/28 (57%) of neurons tested for responses to occlusion were responsive to electrical stimulation of the right cervical vagus nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

Convergence of sympathetic, vagal, and other sensory inputs onto neurons in feline ventrolateral medulla.

Responses of 80 neurons in rostral and caudal ventrolateral medulla to multiple sources of sensory input were assessed in cats anesthetized with alpha-chloralose. Sixty-one of eighty-one neurons (76%) were excited by stimulation of the stellate ganglion, and one neuron exhibited inhibition followed by excitation. In response to vagal stimulation, 12% of the neurons were excited and 29% inhibited. Vagal stimulation reduced the responses of 13 of 39 (33%) neurons to sympathetic stimulation. Overall, one-third of the neurons responded to both sympathetic and vagal stimulation. There was no difference in proportion of responsive neurons in rostral versus caudal ventrolateral reticular formation. Cells were also tested for auditory, visual, and natural somatic stimuli. Ten percent of the neurons responded to all five stimuli, and another 25% responded to four stimuli. Twelve percent of neurons were unresponsive to any stimulus. Twenty cells were tested for responses to changes in blood pressure elicited with phenylephrine and nitroglycerin. Seven neurons were inhibited by increases or excited by decreases in pressure, four had the opposite responses, and nine were unresponsive. In general, blood pressure-sensitive cells exhibited comparable convergence of other inputs as the overall cell population. However, three times as many pressure-insensitive neurons received vagal input as did pressure sensitive neurons. In conclusion, neurons in the ventrolateral medulla, including the vasopressor and vasodepressor regions, receive and integrate convergent input from multiple sensory origins. Since the regions of the reticular formation studied are functionally heterogeneous, the precise functions of these neurons are not known.

Dioxin contamination and growth and development in great blue heron embryos.

A great blue heron colony located near a pulp mill in British Columbia failed to fledge young in 1987, with a concurrent sharp increase in polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in their eggs. In 1988 we tested the hypothesis that the PCDD and PCDF contamination caused reproductive failure by increasing mortality of the heron embryos in ovo. Pairs of great blue heron eggs were collected from three British Columbia colonies with low, intermediate, and high levels of dioxin contamination: Nicomekl, Vancouver, and Crofton, respectively. One egg of each pair was incubated under laboratory conditions at the University of British Columbia (UBC) while the other egg was analyzed for PCDDs and PCDFs. All incubated eggs were fertile. All eggs from the Nicomekl colony hatched, while 13 of 14 eggs from Vancouver and 12 of 13 eggs from Crofton hatched. Subcutaneous edema was observed in 4 of 12 chicks from Crofton and 2 of 13 chicks from Vancouver. No edema was seen in the chicks from Nicomekl. There was a small, but significant, negative regression of plasma calcium concentration, yolk-free body weight, tibia length, wet, dry, and ash weight, beak length, and kidney and stomach weight of the hatched chicks on the tetrachlorodibenzo-p-dioxin (TCDD) level of the paired eggs. Fewer down follicles were present on the heads of TCDD-contaminated chicks. Hence while dioxins did not cause mortality of the heron embryos in ovo, the depression of growth and the presence of edema are suggestive that dioxins at the levels found in the environment have an adverse effect on the development of great blue heron embryos.

Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation.

The effect of daily exercise on the coronary resistance vessel sensitivity to intracoronary infusion of several pharmacological agents was assessed in 12 conscious adult mongrel dogs. alpha-Adrenergic receptor agonists (norepinephrine and phenylephrine) significantly decreased coronary blood flow velocity. beta 2-Adrenergic receptor agonists (isoproterenol and zinterol) and a metabolic vasodilator (adenosine) significantly increased coronary blood flow velocity. These responses occurred without altering factors that influence myocardial metabolism. Daily exercise significantly enhanced the coronary vascular sensitivity to each of the pharmacological agents. These results suggest that a nonspecific potentiation to pharmacological activation occurs after daily exercise. After left stellate ganglionectomy, intracoronary infusions of each pharmacological agent had similar effects on coronary blood flow velocity as presented for the intact dogs; however, daily exercise did not enhance the coronary vascular sensitivity to the pharmacological agents. These results demonstrate the need for an intact nervous system for the vascular adaptations associated with daily exercise.

Activation of feline spinal neurones by potentiated ventricular contractions and other mechanical cardiac stimuli.

1. Neurones in the spinal cord were tested for responses to premature ventricular contractions (PVCs), produced by controlled electrical extra stimuli, and other mechanical stimuli applied to the heart. Thirty-eight neurones were antidromically activated from the medial medullary reticular formation and/or the caudal thalamus, and twenty-four neurones did not project to these sites. 2. Only those neurones excited by electrical stimulation of the left stellate ganglion were tested for responses to PVCs. A total of twenty neurones (32%) responded to electrically induced PVCs. Three major patterns of responses occurred. Three neurones exhibited an early burst and a late burst (or bursts) during the arrhythmia, one neurone fired only an early burst, and sixteen neurones responded with only a late burst. The early bursts occurred shortly after the onset of the compensatory pause accompanying the PVC; the late bursts were usually associated with the subsequent potentiated contraction, although the stimulus eliciting the burst must often have occurred late in the compensatory pause. 3. Responses to PVCs were only seen in neurones receiving C fibre and A delta fibre input. However, there were some neurones with both A delta and C input that did not respond to PVCs. No neurones with only A delta input responded to PVCs. 4. Neurones projecting to thalamus were less likely to respond to PVCs than either spinoreticular neurones or neurones with unidentified projections. 5. Neurones responsive to PVCs were likely to exhibit a cardiac rhythmicity in their spontaneous or evoked activity. 6. A total of 42% of tested neurones responded to a rapid infusion of saline into the heart, 52% had a cardiac receptive field, and 74% responded to aortic occlusion. A given neurone might respond to one or more of these stimuli, without responding to every mechanical stimulus tested. 7. Cervical vagotomy never abolished a response to PVCs, although either the spontaneous discharge rate or magnitude of response was sometimes altered. 8. Neurones responsive to PVCs were also responsive to intracardiac bradykinin. In addition, 95% of the neurones received convergent somatic input. 9. We conclude that about a third of spinal neurones excited by electrical stimulation of the left stellate ganglion receive information regarding mechanical, presumably innocuous, events in the heart. Most responsive neurones also receive somatic input and noxious cardiac input, and this information is transmitted to the thalamus, reticular formation, and probably to other spinal segments.

Role of beta 2-adrenergic receptors on coronary resistance during exercise.

The effects of regional alpha- and specific beta 2-adrenergic receptor blockade on measurements of late diastolic coronary resistance (LDCR) and mean coronary blood flow velocity (CBFV) during exercise were examined in 14 conscious adult mongrel dogs. Specific beta 2-adrenergic receptor blockade (ICI 118.551) significantly decreased CBFV and increased LDCR by blockade of beta 2-vasodilator tone independent of alpha-adrenergic receptor-mediated tone and independent of altering myocardial metabolism. alpha-Adrenergic receptor blockade (phentolamine, 1 mg) significantly increased CBFV and decreased LDCR by blocking sympathetically mediated vasoconstrictor tone. There was no significant difference in the magnitude of response between alpha- and beta 2-adrenergic receptor blockade. These results demonstrate that alpha- and beta 2-adrenergic receptors have a significant and evidently equal influence on CBFV and LDCR during exercise. Four weeks of daily exercise and left stellate ganglionectomy (LSGx) prevented phentolamine-induced vasodilation but not ICI 118.551-induced vasoconstriction. This suggests that daily exercise and LSGx significantly decreased the alpha-adrenergic receptor-mediated vasoconstrictor tone on the coronary circulation, resulting in an apparently greater role for the coronary vascular beta 2-adrenergic receptor on the control of CBFV and LDCR during exercise.

Central organization of sympathetic cardiovascular response to pain.

Figure 1 summarizes the pathways discussed in this review. Noxious and innocuous cardiac and somatic information converge on SRT neurons in the upper thoracic spinal cord; the third thoracic segment (T3) is shown in Figure 1. The SRT pathway and collaterals of the STT convey this information to the MRF (mainly RGC). This input is integrated with other inputs (eg. auditory and visual) by MRF neurons, some of which project to the spinal cord. RS motor neurons (dotted pathway) might mediate motor responses to cardiac pain, as well as motor responses associated with escape or alerting behavior. RS neurons (cross-hatched and clear pathways) can also modulate ascending traffic by altering activity of SRT and STT cells. Finally, RS neurons (dotted pathway) might modify sympathetic function via collaterals to IML or to interneurons, or MRF cells could project to medullary areas possessing neurons (solid pathway) that project directly to IML. The small figurines represent the heart (top), blood vessels (middle right) and muscle (bottom).