Spontaneous pneumothorax in 35 cats (2001-2010).

Thirty-five cases of spontaneous pneumothorax were reviewed. In contrast to dogs, cats with an established etiology all had spontaneous pneumothorax associated with lung disease. Underlying diseases identified in affected cats included inflammatory airway disease, neoplasia, heartworm infection, pulmonary abscess and lungworm infection. Many cats were managed successfully with observation alone or needle thoracocentesis and specific therapy for their primary lung disease. Cats who present with spontaneous pneumothorax may be treated successfully with non-surgical therapies and appear to have a better prognosis than previously extrapolated from canine studies.

Use of a flow-mediated vasodilation technique to assess endothelial function in dogs.

OBJECTIVE: To develop and assess the reproducibility of a protocol to noninvasively test endothelial function in dogs on the basis of the flow-mediated vasodilation (FMD) procedure used in humans. ANIMALS: 5 healthy spayed female dogs. PROCEDURES: Luminal arterial diameter and blood flow velocity in the brachial and femoral arteries were measured with ultrasonography. The within-dog reproducibility of these ultrasonographic measurements was tested. An occlusion period of 1, 3, or 5 minutes with an inflatable cuff was used to create the FMD response. Measurements made at 15, 30, and 60 seconds following release of the occlusion were compared with measurements made immediately prior to each occlusion to assess the FMD response. RESULTS: Within-dog reproducibility of measurements revealed moderate to high correlations. Change from baseline in luminal arterial diameter was most substantial when measured at 30 seconds following release of occlusion, whereas blood flow velocity changes were maximal when measured at 15 seconds following release. The brachial imaging site provided a larger number of significant FMD responses than the femoral site. The 3-minute occlusion period provided equal or better responses than the 5-minute occlusion period. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonographic measurement of the FMD responses was a feasible and reproducible technique and significant changes from baseline were detected. The FMD responses in dogs were most substantial when performed at the brachial artery with blood flow velocity and luminal arterial diameter changes from baseline measured at 15 and 30 seconds, respectively, following release of a 3-minute occlusion period.

Effects of barium on isolated frog spinal cord.

The effects of Ba2+ were studied in vitro on the isolated frog spinal cord. Ba2+ (25 microM-5 mM) caused a concentration-dependent depolarization of ventral (VR) and dorsal (DR) roots. TTX and Mg2+ substantially reduced the depolarization suggesting that interneuronal effects were involved. Ba2+ (25-500 microM) markedly increased the frequency and duration of spontaneous VR and DR potentials and substantially enhanced the duration (and frequently the amplitude) of VR and DR potentials evoked by DR stimulation. Higher concentrations of Ba2+ (1-5 mM) reduced both spontaneous and evoked potentials. Ba2+ (25-500 microM) enhanced the amount of K+ released by a DR volley and by application of L-glutamate and L-aspartate. The cation reduced VR and DR root depolarizations produced by elevated [K+]0. VR potentials induced by L-glutamate, L-aspartate, GABA and glycine and DR depolarizations caused by GABA were reduced by Ba2+. These results show that Ba2+ has complex actions on reflex transmission, interneuronal activity, the postsynaptic actions of excitatory and inhibitory amino acids and the evoked release of K+.

Potential changes of frog afferent terminals in response to dopamine.

The actions of dopamine on the membrane potential of afferent fibers of the isolated hemisected frog spinal cord were studied by sucrose gap techniques. The most prominent effect seen after addition of dopamine to the superfusing Ringer's solution was a slow reversible hyperpolarization at concentrations as low as 0.01 microM; its amplitude and duration were dependent upon concentration and length of application. Biphasic responses with an initial dominant hyperpolarization and a much smaller, later depolarization were also noted and were particularly prominent when dopamine was applied at higher concentrations. Exposure of the cord to apomorphine, a non-selective agonist, to SKF 38393A, a D-1 selective agonist, or to LY-14186, a D-2 selective agonist, hyperpolarized the dorsal root in a manner similar to that of dopamine, but only when the former compounds were applied at higher concentrations (100 microM or greater). Apomorphine also elicited a late depolarization. The non-selective dopamine antagonists, fluphenazine and haloperidol, reversibly reduced dopamine's actions. Similar effects were produced by the selective D-2 antagonists, sulpiride and metoclopramide, which had no effect on hyperpolarizations evoked by norepinephrine. Dopamine did not appear to activate adrenergic or serotonergic receptors, for its effects were not affected by yohimbine, corynanthine, propranolol, or methysergide. The effect of dopamine appeared to result from an action of the amine on both afferent fibers and interneurons. This inference was drawn because the potential changes produced by dopamine were substantially reduced, but never eliminated, by superfusion of the cord with solutions containing Mn2+ ions, tetrodotoxin or mephenesin.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine- and norepinephrine-evoked potential changes of frog primary afferent terminals: pharmacological characterization of alpha and beta components.

The effects of superfused epinephrine (E) and norepinephrine (NE) on the membrane potential of primary afferent fibers of the isolated frog spinal cord were studied by sucrose gap recordings from the dorsal root. In all preparations both E and NE, applied in concentrations ranging from 0.1 microM to 1.0 mM, produced a hyperpolarization of afferent terminals. In many instances this was followed by a slow depolarization and, in a small number of cords, a small depolarization preceded the increase in membrane potential. E- and NE-induced hyperpolarizations were blocked by the selective alpha 2-antagonists yohimbine and piperoxan, but not by the selective alpha 1-antagonists prazosin and corynanthine or by the beta-blockers propranolol and sotalol. The alpha 2-agonists clonidine, alpha-methylnorepinephrine and guanabenz also hyperpolarized terminals, causing a change in potential that was reduced by yohimbine and piperoxan. Taken together, these results suggest that alpha 2-receptors mediate the hyperpolarizing effects of E and NE. The beta-agonist isoproterenol evoked a slow depolarization similar to that produced by E and NE. The isoproterenol-depolarization was antagonized by propranolol. Sometimes, application of E and NE after superfusion with yohimbine produced only a depolarization of the dorsal root and this depolarization was sensitive to propranolol. It would appear therefore that the late depolarization seen after the application of E and NE is produced by activation of beta-receptors. In contrast, the alpha 1-agonist phenylephrine elicited a short latency, short duration depolarization similar to those seen preceding approximately 10% of the E- and NE-hyperpolarizations. Such short-latency depolarizations were blocked by prazosin and corynanthine. The major component of the response to both E and NE is indirectly mediated through a synaptic process: application of Mn2+, Mg2+, procaine or tetrodotoxin in concentrations sufficient to block synaptic transmission substantially reduced, but never eliminated, the actions of the catecholamines. Interneurons are probably involved because mephenesin, which reduces interneuronal transmission, significantly decreased the E and NE effects. Furthermore, interneurons which secrete excitatory amino acids and/or GABA may mediate the indirect effects of the catecholamines on afferent terminals because (-)baclofen and D.L-alpha-aminoadipate decrease, and picrotoxin and bicuculline increase, the dorsal root (DR) effects of E and NE.(ABSTRACT TRUNCATED AT 400 WORDS)

Benzodiazepine tolerance, physical dependence and withdrawal: electrophysiological study of spinal reflex function.

The in situ segmental spinal reflex system of the rat was used to determine changes in excitatory and inhibitory synaptic function associated with benzodiazepine tolerance, physical dependence and withdrawal. Rats were made physically dependent on chlordiazepoxide using a chronically equivalent dosing method. After spinalization, dorsal and ventral lumbar roots (L5 or L6) were isolated for extracellular stimulation and recording. Testing of spinal function was performed during peak withdrawal (8 days) and at peak effect (4 hr) after first ("acute") and last ("chronic") dose of chronically equivalent chlordiazepoxide. There were no quantitative or qualitative differences in the acute and chronic spinal actions of chlordiazepoxide. Polysynaptic discharges were markedly augmented during withdrawal (159% above control) and diminished during treatment (44% below control). Recovery of the 2 N reflex measured by twin pulse was shortened during withdrawal (23% above control) and lengthened during treatment (28% below control). Recovery of the 2 N reflex analyzed by low-frequency (10 Hz) stimulation was also elevated at peak withdrawal (40% above control) and depressed in treatment (41% below control). At peak withdrawal spinal inhibitions were reduced below control; presynaptic-dorsal root reflex (60%) and recurrent (62%). In contrast, drug treatment enhanced presynaptic (72%) and recurrent (48%) inhibitions above control. Only those synaptic parameters chronically altered by continuous chlordiazepoxide administration were oppositely affected during withdrawal. Consequently, benzodiazepine withdrawal is associated with rebound alterations of profound reductions in inhibitory synaptic transmission, increased net polysynaptic activity and shortened monosynaptic recovery times.

Spontaneous dorsal root potentials arise from interneuronal activity in the isolated frog spinal cord.

Spontaneous dorsal root potentials (sDRPs) were recorded from the dorsal roots of the isolated frog spinal cord using sucrose gap techniques. sDRPs were always negative (depolarizing) in sign and ranged in size from about 100 microV to 6.0 mV. The largest sDRPs were 25-40% of the amplitude of DRPs evoked by stimulation of adjacent dorsal roots. Hypoxia or accumulation of extracellular K+ ions did not appear responsible for the generation of this spontaneous activity since exposing the cord to unoxygenated Ringer's solution decreased sDRPs and K+-sensitive microelectrodes indicated that only small changes in extracellular K+ (approximately 0.15 mM) were produced coincidently with the largest sDRPs. Chemically-mediated synaptic transmission was found to be necessary for the production of sDRPs because the addition of Mn2+ or Mg2+ ions or tetrodotoxin to the Ringer's solution or reduction of its Na+ concentration blocked sDRPs, whereas application of 4-aminopyridine enhanced them. It did not seem that a direct action of GABA on afferent fiber terminals was responsible for the generation of spontaneous potentials since an increase in sDRPs was seen after: application of the GABA antagonists, bicuculline and picrotoxin; exposure to the glutamic acid decarboxylase inhibitor, semicarbazide (which significantly reduced the concentration of GABA in the cord); and lowering of the external Cl- concentration. Similarly taurine is probably not significant since the taurine antagonist, TAG, increased the amount of spontaneous activity. On the other hand, (--)-baclofen, which is thought to reduce excitatory amino acid release, D,L-alpha-aminoadipic acid, alpha, epsilon-diaminopimelic acid, and 2-amino-4-phosphonobutyric acid, which are believed to be selective postsynaptic excitatory amino acid antagonists, and [D-Pro2-D-Phe7-D-Trp9]-substance P, a postsynaptic blocker of the action of substance P, markedly and reversibly reduced sDRPs. Experiments were performed on isolated cords without supraspinal or afferent input; therefore sDRPs must be generated by intraspinal structures. It would seem that interneurons are responsible because addition of mephenesin or pentobarbital--compounds which inhibit polysynaptic reflex transmission involving interneurons--reduced the production of sDRPs. sDRPs may result from the action of excitatory transmitters such as L-glutamate, L-aspartate, or substance P released by interneuronal firing in the spinal cord. Moreover, because sDRPs were increased by application of yohimbine, corynanthine and propanolol and reduced by haloperidol, such interneurons may be under descending control of adrenergic and dopaminergic fibers.

Spinal seizures and excitatory amino acid-mediated synaptic transmission.

In the isolated frog spinal cord penicillin or strychnine produced spinal seizures with spontaneous slow paroxysmal ventral root depolarizations (pVRDs) and superimposed motoneuron spikes. Mn2+, tetrodotoxin, mephenesin and low [Na+]o suppressed pVRDs, an indication that paroxysmal activity requires intact excitatory synaptic transmission involving interneurons. Compounds reducing the release of amino acids [-)baclofen) or interfering with the activation of N-methyl-D-aspartic acid (NMDA) receptors (D,L-alpha-aminoadipate, D-2-amino-5-phosphonovalerate, gamma-D-glutamylglycine) eliminated pVRDs. The results suggest that synaptic release of excitatory amino acids (e.g. L-glutamate, L-aspartate) and subsequent activation of specific receptors sensitive to the action of NMDA underlie spinal convulsions.

Phenobarbital tolerance and physical dependence: chronically equivalent dosing model.

A rat model of phenobarbital tolerance and physical dependence has been developed based on the 'maximally tolerable, chronically equivalent' dosing paradigm. Sodium phenobarbital was administered orally twice daily for 35 days in individually adjusted doses to achieve mean daily peak CNS depression culminating in severe ataxia. Dose to dose continuity of CNS depression was maintained throughout treatment. At the time of dosing rats were mildly ataxic. Following abrupt termination of chronic treatment, an abstinence syndrome characterized by CNS hyperexcitability was observed, which demonstrates physical dependence. Signs, which included motor, autonomic, and behavioral manifestations, appeared from 12-24 h and animals recovered by 12 days. Although tolerance development was nearly complete on day 10 of treatment, the abstinence syndrome observed was more severe following 35 than after 10 days of chronic treatment. Characteristics of tolerance and physical dependence are similar to those described for other species including humans.

Experimental induction of benzodiazepine tolerance and physical dependence.

To initiate studies of benzodiazepine tolerance and physical dependence, a reproducible animal model has been developed utilizing chlordiazepoxide in rats. Based on the "chronically equivalent" dosing principle, a regimen has been devised to maintain rats in a state of quantifiable intoxication for 5 weeks. Chlordiazepoxide was delivered intragastrically on a b.i.d. basis in doses individually adjusted day-to-day and animal-to-animal to produce an equivalent impairment of motor function evaluated by a gross neurological screen. Quantitative analysis of central nervous system depression ratings during the time of peak effect (4 hr postdose) confirmed that the criterion of chronic equivalence was indeed met. Over the 5-week period of repeated dosing, tolerance was reflected in a 5-fold increase in maintenance dose, from 163.3 mg/kg on day 2 to 839.3 mg/kg on day 35. Tolerance developed more rapidly during the first 9 to 10 days, but continued to develop thereafter more slowly without apparent ceiling. Upon abrupt withdrawal, a syndrome of hyperexcitation developed. Signs included twitches, tremors, muscle hypertonus, arched back, piloerection, myoclonic jerks, augmented struggle and vocalization upon handling, increased startle response, tail erection, teeth chatter, blanched ears and weight loss. No spontaneous convulsions occurred. Latency to onset of withdrawal ranged from 2 to 5 days, and signs peaked in intensity in 8 days and disappeared by 14 days posttreatment. This animal model appears to provide a useful tool for the study of specific mechanisms underlying benzodiazepine tolerance and physical dependence.

Catecholamine effects on frog dorsal root terminals.

Dopamine, norepinephrine and epinephrine applied to the isolated superfused frog spinal cord had complex effects on the terminals of primary afferent fibers. The most consistent finding was a slow hyperpolarization of terminals with lower concentrations (10 microM or lower), but depolarizations either following or admixed with the hyperpolarizations were seen. These were particularly prominent when the catecholamines were applied in high concentrations or for prolonged periods of time. A part of the response of afferent terminals appears to be indirect since the potential changes were reduced following exposure of the cord to tetrodotoxin, Mn2+, or mephenesin. The hyperpolarizations were augmented by imipramine, a known inhibitor of catcholamine uptake. These observations are consistent with a role of catecholamines in the processing of sensory input in the spinal cord.

Excitatory amino acids and potassium release in the frog spinal cord.

Synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters appears necessary for the release of K+ by afferent stimulation in the isolated frog spinal cord. This conclusion is based on the findings that (-)baclofen, which is thought to reduce the presynaptic release of putative excitatory amino acid transmitters, and some amino dicarboxylic amino acids (D, L-alpha-aminoadipic acid, 2-amino-4-phosphonobutyric acid, and D, L-alpha, epsilon-diaminopimelic acid), which are believed to interfere with the activation of receptors by these same excitatory amino acids, significantly attenuate the increment in extracellular K+ evoked by tetanic dorsal root stimulation.

Role of gastrin in mucosal DNA synthesis after vagotomy and atropine in the rat.

The purpose of this study was to examine 1) the influence of the cholinergic innervation of the stomach on the rate of DNA synthesis in the fundic mucosa of the rat and 2) the possibility that hypergastrinemia might be involved in the response. Repeated injections of atropine in fasting rats increased by 40% the rate of DNA synthesis in the oxyntic gland mucosa. Two weeks after truncal vagotomy, the DNA synthesis rate in oxyntic gland mucosa was increased 64% compared to sham-operated control animals. In the rat colon, atropine administration produced a 56% increase in DNA synthesis compared to saline-injected controls. The injection of pentagastrin in fasting rats also increased the DNA synthesis rate in both stomach and colon, but pentagastrin combined with either atropine or vagotomy stimulated DNA synthesis no more than pentagastrin alone. Cholinergic interruption by atropine or vagotomy elevated endogenous serum gastrin concentrations, indicating that the observed DNA stimulation may be mediated by hypergastrinemia.

Elevated serum alkaline phosphatase level may aid in the diagnosis of pancreatitis.

Ten cases of pancreatitis with elevated serum alkaline phosphatase (SAP) levels are reported. Patients with chronic or relapsing pancreatitis may at times develop increased SAP levels, either with or without definitive biochemical evidence of pancreatic disease. SAP estimation may assist in establishing a clinical diagnosis in cases of abdominal pain in which pancreatitis is suspected.