Abbott J. Krieger

M2 muscarinic receptors mediate pressor responses to cholinergic agonists in the ventrolateral medullary pressor area

Microinjections of cholinergic agonists into the ventrolateral medullary pressor area (VLPA) evoke increase in blood pressure (BP) and heart rate (HR). Recently two major subtypes of muscarinic receptors (M1 and M2) have been identified. This investigation was designed to study the role of these muscarinic receptor subtypes in pressor responses of cholinergic agonists in the VLPA. Male Wistar rats were anesthetized with pentobarbital or decerebrated at mid-collicular level. The rats were artificially ventilated and BP and HR were recorded. Ventral medulla was exposed and the VLPA identified bilaterally by microinjections of L-glutamate. Microinjections of cis-methyldioxolane (CD, a specific agonist of M2 receptors) in the doses of 0.004-4 nanomol (nmol)/site into the VLPA evoked an increase in BP (13-56 mm Hg) and HR (7-24 bpm) which lasted for 10-50 min. Intravenous injections of the same doses of this agent failed to evoke a response. AFDX-116 (a specific M2 muscarinic receptor antagonist) microinjected into the VLPA (0.2-1.6 nmol-/site) evoked depressor responses (6-20 mm Hg). Microinjections of this agent into the VLPA prevented the pressor responses to subsequent microinjections of CD at the same sites, indicating that AFDX-116 blocked M2 receptors. AFDX-116 rendered neurons in the VLPA unresponsive to L-glutamate but this effect lasted for 30-40 min while the hypotensive and M2 receptor blocking effect lasted for 60-150 min. McN-A343 (a specific agonist for M1 receptors) or pirenzepine (PZ, a specific antagonist of M1 receptors) injected into the VLPA (0.4-4 nmol/site) failed to evoke any response.(ABSTRACT TRUNCATED AT 250 WORDS)

Microinjections of cholinergic agonists into the intermediolateral cell column of the spinal cord at T1-T3 increase heart rate and contractility.

Cardiovascular responses to the microinjections of cholinergic agonists into the intermediolateral cell column (IML) of the spinal cord at T1-T3 level were studied. Mean arterial pressure (MAP), heart rate (HR), the rate of increase in the left ventricular pressure (dp/dt) and contractility index (CI) were monitored in immobilized and artificially ventilated male Wistar rats either anesthetized with pentobarbital or decerebrated at mid-collicular level. Microinjections (20 nl) of carbachol (110-660 pmol) into the right IML elicited a marked increase in HR and a small increase in CI. A marked increase in the CI with relatively little effect on the HR was observed when carbachol was injected into the left IML. The cardioacceleratory effects of carbachol, but not those of L-glutamate, were blocked by prior microinjections of scopolamine (18 nmol) into the IML. Intravenous injections of chlorisondamine (a ganglion blocker) also blocked these effects of carbachol. Spinal transections at C4 or T6 level did not alter these responses. Microinjections of acetylcholine (0.01-1 nmol) into the right IML also produced tachycardic effects. The responses to acetylcholine were blocked by prior injections of a muscarinic receptor blocker (atropine hemisulfate, 0.2 nmol). Microinjections of a selective M2 muscarinic receptor agonist, cis-methyldioxolane (CD; 0.2-0.8 nmol), but not those of a relatively selective M1 receptor agonist (McN-A343; 2-3 nmol), into the right IML elicited an increase in HR. Previous microinjections of a selective competitive M2 receptor antagonist (AFDX-116; 0.8 nmol), but not those of a potent selective M1 receptor antagonist (pirenzepine; 2 nmol), into the IML blocked the effects of CD. Nicotine (0.25-1 nmol) when injected into the right IML also produced positive chronotropic effects. These responses were blocked by prior microinjections of hexamethonium (5 nmol). The above-mentioned results suggest that cholinoceptive neurons, interneurons or terminals are located in the areas of IML which control cardiac functions. Muscarinic as well as nicotinic receptors are present in this area. Muscarinic receptors are predominantly of the M2 type. The physiological significance of the presence of cholinergic receptors in this area in controlling cardiac functions remains to be established.

MRI-documented regression of a herniated cervical nucleus pulposus: A case report

Abstract An MRI-documented case of regression of a herniated cervical nucleus pulposus in a neurologically intact patient is presented.

Cardiovascular effects of substance P receptor stimulation in the ventrolateral medullary pressor and depressor areas

The pressor (VLPA) and the depressor (VLDA) areas in the ventrolateral medulla were identified with the microinjection of L-glutamate (1.77 nmol/site) in artificially ventilated urethane-anesthetized male Wistar rats. Bilateral microinjection of a stable substance P (SP) agonist [pGlu5, MePhe8, Sar9]-SP(5-11)], abbreviated as DiMe, into the VLPA (6-600 pmol/site) produced a dose-dependent increase in blood pressure (BP). The effects on heart rate (HR) were variable. Intravenous pretreatment with a ganglionic blocker chlorisondamine (3.0 mg/kg, i.v.), but not with a vasopressin antagonist, blocked these responses. Similar microinjection of DiMe (6-600 pmol/site) into the VLDA produced a dose-dependent decrease in HR but had no effect on BP levels. The DiMe-induced bradycardic response elicited from the VLDA was blocked by i.v. pretreatment with atropine methylbromide (0.5 mg/kg, i.v.). These findings indicate that there are SP receptors localized on sympathoexcitatory neurons in the VLPA and that SP may be an excitatory neurotransmitter in this area. In the VLDA, the SP receptors appear to be localized on a subpopulation of neurons that affect vagal, but not sympathetic, outflow to the heart.

Relative effects of different spinal autonomic nuclei on cardiac sympathoexcitatory function

Mean arterial pressure and heart rate were monitored in immobilized and artificially ventilated male Wistar rats either anesthetized with pentobarbital or decerebrated at midcollicular level. The rate of increase in the left ventricular pressure was also monitored in order to compute contractility index. L-glutamate (1.77 nmole) was microinjected (10 nl) into the following autonomic nuclei of the spinal cord at C8 to T4 levels: 1) intermediolateral column (IML), 2) n. intercalatus spinalis (IC) and 3) n. intercalatus pars paraependymalis (ICpe); this region is commonly known as the central autonomic area (CA). The site of microinjection was marked by injection of a dye; these studies suggested that microinjections of glutamate into the IML are likely to encompass the neurons in the nucleus (n.) intermediolateralis thoracolumbalis pars principalis (ILp) and n. intermediolateralis thoracolumbalis pars funicularis (ILf). Sympathoexcitatory cardiac responses to glutamate microinjections were elicited from T1 to T3 levels; these responses could not be evoked at C8 and T4 levels. In each of these segments, maximum responses were obtained from the IML while the responses evoked from the IC and the CA were minimal. These results suggest that at T1 to T3 levels of the spinal cord, IML is the main cell group regulating sympathetic cardiac function; CA and IC may play a relatively minor role in this function.

HIV status does not affect microbiologic spectrum or neurologic outcome in spinal infections

The impact of human immunodeficiency virus (HIV) on the clinical presentations, causative organisms, and neurologic outcomes of patients with spinal infections is reviewed. Thirty-two patients with spinal epidural abscesses, vertebral osteomyelitis, or both were treated at an urban hospital over a 42-month period. Thirteen of these patients were confirmed by serologic analysis to be HIV seropositive. The diagnoses were confirmed by 30 open surgical procedures (14 anterior, 16 posterior) and seven percutaneous biopsies. Twenty-seven intraoperative cultures were positive and the remaining three patients had positive blood cultures prior to the surgical procedure. In both the HIV (+) and HIV (-) groups, Staphylococcus aureus predominated as the causative organism (overall rate: 72%). Mycobacterium tuberculosis was the second most common organism. The clinical presentations in both groups were similar with pain as the most frequent symptom and objective neurologic abnormalities on physical examination in 29 of the 32 patients (91%). The results of this analysis show that the clinical presentations and organisms cultured do not differ depending upon a concurrent HIV infection. Furthermore, the ultimate neurologic outcome of patients with spinal infections depends on their neurologic status at the time of treatment and not on their HIV status.

Electrophrenic Respiration after Intercostal to Phrenic Nerve Anastomosis in a Patient with Anterior Spinal Artery Syndrome

Long-term positive pressure mechanical ventilation has been the standard of care for patients with respiratory insufficiency caused by high cervical spine injury. Stimulation of the phrenic nerves, and thus the diaphragm, with an implanted phrenic nerve pacemaker has provided adequate ventilation and an alternative to the standard. Diaphragmatic pacing, also known as electrophrenic respiration, requires an intact phrenic nerve to act as a conduit for the applied stimulus. Propagation of the stimulus is impossible if the injury sustained has led to axonal loss in the phrenic nerve. This may be expected if the damage to the spinal cord is at the C3-C5 level. If the cell bodies of the motor neurons in this region have been damaged, or direct injury to the phrenic nerve has occurred, then diaphragmatic pacing is not feasible by the traditional method. Microsurgical repair of peripheral nerves and nerve grafting have provided the impetus for research into anastomosis of a viable intercostal nerve to a nonfunctional phrenic nerve, with subsequent reinnervation of the diaphragm. Once successful axonal regeneration and diaphragmatic reinnervation have occurred, the distal phrenic nerve may then be paced. This case documents the first successful institution of electrophrenic respiration after intercostal to phrenic nerve anastomosis.