The relationship between vascular expansion of the aorta and pulmonary artery and the genesis of the impedance cardiogram using the technique of sonomicrometry.

PRIMARY OBJECTIVE: This prospective animal study aims to evaluate the contribution of the pulmonary artery (PA) and aorta on the morphology of the impedance cardiogram using sonomicrometry. METHODS: Impedance electrodes were placed around the thorax, aorta and in the oesophagus of five dogs. Sonomicrometry crystals were mounted on the PA and aorta for tracking vascular distension while a Doppler flow probe measured aortic blood flow. RESULTS: No significant differences (p > 0.05) were recorded between the onset of aortic expansion, aortic blood flow and the start of the impedance dZ/dt signal. Significant differences (p > 0.001) were recorded between the onset of PA expansion and the dZ/dt signal. PA expansion began 41.6 +/- 6.0 ms, 60.7 +/- 7.2 ms and 42.2 +/- 4.9 ms respectively, before surface, aortic and oesophageal impedance recordings. CONCLUSION: The genesis of the impedance cardiogram is attributed to volumetric expansion of the aorta.

IL-10 regulates thrombus-induced vein wall inflammation and thrombosis.

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.

The effects of myofascial trigger point injections are naloxone reversible.

Ten patients with myofascial trigger point pain were entered into a double-blind cross-over study of the reversibility of myofascial trigger point injection (TPI) effects with naloxone versus placebo in order to test the hypothesis that the benefits of TPI are mediated, at least in part, through activation of an endogenous opioid system. Injection of trigger points with 0.25% bupivacaine decreased pain in all subjects and increased range of motion in subjects who, on initial assessment, demonstrated limitations of movement of the affected part(s). Allodynia and palpable bands preceding TPI when present also showed reduction after TPI. All improvements afforded by TPI were significantly reversed with intravenous naloxone (10 mg) compared to intravenous placebo. These results demonstrate a naloxone-reversible mechanism in TPI therapy. This suggests an endogenous opioid system as a mediator for the decreased pain and improved physical findings following injection of myofascial trigger points with local anesthetic.

Contrasting effects of clonidine and 5-hydroxytryptophan on spinal sympathetic pathways.

The effects of clonidine HCI were compared with those of 5-HTP on transmission through two spinal sympathetic pathways, segmental spinal reflex pathways and descending intraspinal excitatory pathways, in unanesthetized spinal cats. Evoked sympathetic discharges were recorded from upper thoracic preganglionic rami. Clonidine (5-50 microgram/kg) produced a parallel, dose-dependent depression of transmission through each pathway. The intraspinal pathway was five time more sensitive than the spinal reflex pathway (ED50's, 6 and 30 microgram/kg), and the spinal reflex pathway could not be depressed by more than 60% even by higher doses. In contrast, 5-HTP was more effective in depressing the spinal reflex than the intraspinal pathway (ED50's 32 and 44 mg/kg), and both pathways could be depressed completely. Small doses of tolazoline or yohimbine rapidly antagonized the effects of clonidine but not 5-HTP. Clonidine and 5-HTP appear to depress the excitability of sympathetic preganglionic neurons by activating alpha2- and 5-HT receptors, respectively. Each mechanism may contribute independently to regulation of the sympathetic outflow.

Depression of sympathetic preganglionic neurons by clonidine: evidence for stimulation of 5-HT receptors.

In unanesthetized spinal cats, clonidine HCl (5-50 microgram/kg, i.v.) rapidly and markedly depressed excitatory transmission through two spinal pathways to sympathetic preganglionic neurons. Depression through either pathway was dose-dependent and persisted for more than 3 hr but could be rapidly antagonized at any stage by tolazoline HCl in a dose-ratio of about 1:100. The two spinal pathways were also depressed transiently by L-dopa and for prolonged periods by 5-HTP; both precursors were shown to act by releasing 5-HT from bulbospinal 5-HT terminals and their depressant effects were also antagonized by tolazoline. In the absence of 5-HT-induced depression, L-dopa only enhanced transmission through both pathways by inducing release of catecholamines from bulbospinal NE terminals. These results indicate that clonidine depresses sympathetic activity by stimulating inhibitory 5-HT receptors on sympathetic preganglionic neurons, a mechanism that adequately accounts for its central vasodepressor effect.

L-dopa-induced hypotension: depression of spinal sympathetic neurons by release of 5-hydroxytryptamine.

In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.