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The purpose of this study was to quantitatively compare the difference in voluntary upper extremity movements between subjects with and without spasticity. Eight normal subjects (mean 26.7 +/- 2.8 years, four males and four females) and seven subjects with spasticity (mean 25.9 +/- 4.3 years, three males and four females) were involved in this study. The subjects sat in an adjustable chair and performed two voluntary tasks involving the elbow joint. Task A was to move the hand between two touch-plates which were mounted 28 cm apart on the surface of the table. Task B was to flex and extend the elbow joint in the sagittal plane with the forearm in neutral position. Reflective markers were attached on the shoulder, the elbow and the wrist. A Peak5 video-based motion analysis system was used to record the positions of the markers in the three-dimensional (3-D) space during the movement tasks. A set of quantitative parameters were used to document the elbow movement. The results revealed that in comparison to normal subjects, subjects with spasticity exhibited a higher average jerk, a larger standard deviation of the coordinates of the markers along the movement path, a larger standard deviation of the angle between the plane of the elbow joint and the horizontal plane, and a longer 3-D path length. The characteristics of spastic elbow movement and the usage of quantitative parameters were discussed.

Previously, studies have demonstrated that the effects of both a laboratory-produced vancomycin and a clinically available vancomycin were mediated, in part, by activation of both H(1) and H(2) receptors; however, other mechanisms may play a role in the vascular changes associated with vancomycin, since neither H(1) and H(2) receptor blockade has completely abolished the vasodilator responses to vancomycin in any model system. To study the mechanisms of vancomycin interactions in the hindlimb vascular bed of the rat, responses of two types of vancomycin preparations were studied. Vancomycin prepared for either clinical or laboratory use produced an initial short-lived period of vasoconstriction followed by a prolonged period of vasodilation in the hindlimb vascular bed. Responses to both the vancomycins and histamine on systemic arterial vasodilation were significantly decreased after administration of both the H(1)-receptor antagonist diphenhydramine and the H(2)-receptor antagonist famotidine. Verapamil, an L-type calcium channel blocker, significantly reduced the vasopressor responses to clinical vancomycin but not the vasopressor responses to laboratory vancomycin. Enalaprilat, and angiotensin-converting enzyme blocker, significantly reduced the vasodilator responses but not the vasoconstrictor responses of clinical vancomycin and significantly reduced the vasoconstrictor responses but not the vasodilator responses to laboratory vancomycin. Meclofenamate, a cyclo-oxygenase inhibitor, and N(omega)-L-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthetase inhibitor, had no significant effect on the biphasic responses with either vancomycin preparations. Atropine, an anticholinergic-antimuscarinic receptor antagonist, and propranolol, a beta adrenergic blocker, had no significant effect on vancomycin responses. Finally, ondansetron, a serotonin receptor blocker, and HOE 140, a bradykinin receptor blocker, also had no significant effect on vancomycin responses. These data suggest that both vancomycin preparations (clinically available and laboratory prepared) caused biphasic responses that differed from the dose-dependent vasodilation elicited by histamine. Both vancomycin preparations' vasodilator responses appear to be modulated, in part, by a histamine receptor--sensitive mechanism, while vancomycin-induced vasoconstrictor responses appear to be modulated, in part, by angiotensin-converting enzyme and L-type calcium channel--sensitive mechanisms in the rat hindlimb vascular bed. These data also suggest that the vascular responses of vancomycin are preparation dependent.

The effects of aprotinin on mean arterial pressure, carotid artery blood flow, pulmonary vascular resistance, and systemic vascular resistance have not been well documented. Therefore, the responses of aprotinin on the mean arterial pressure, carotid artery blood flow and the changes in pulmonary and hindlimb vascular resistances were investigated in the rat using ultrasonic flow probe analysis, and in two isolated vascular bed preparations. In studies on cardiac output using ultrasonic flow analysis, injections of aprotinin, in doses of 70-7000 KIU intravenously (iv), resulted in no changes in carotid artery ultrasonic flow, suggesting no changes in cardiac output. In isolated blood-perfused lung studies under conditions of controlled pulmonary blood flow, aprotinin, in doses of 7-7000 KIU intra-arterially (ia), caused no significant changes in pulmonary arterial perfusion pressure. Aprotinin, in doses of 7-240 KIU, was injected iv into the hindquarters perfusion circuit, and hindquarters arterial perfusion pressure did not change. Additionally, in the hindquarters perfusion preparation, aprotinin, in doses of 70-7000 KIU, ia resulted in no changes in mean arterial pressure. The present data demonstrate aprotinin has no significant response in MAP, carotid artery blood flow, pulmonary vascular resistance, or hindlimb vascular resistance in the rat.

Objective: Current evidence suggests that thromboxane plays a role in pathophysiologic processes in the lung. Efforts to find effective, specific therapy to modify these effects have led to the development of a new class of thromboxane receptor blockers. This present investigation examined the selectivity and duration of the inhibitory effects of one of these novel agents in the pulmonary vascular bed of anesthetized cats., Design: Prospective, randomized, controlled study with repeated measures., Setting: University research laboratory., Subjects: Twenty-nine adult cats obtained from the Tulane University School of Medicine vivarium., Interventions: The effects of GR32191, a thromboxane receptor antagonist, were investigated under constant-flow conditions in the intact-chest cat, using a triple-lumen, 6-Fr, balloon perfusion catheter that was placed by means of fluoroscopic guidance. Data were analyzed using a paired or unpaired t-test or analysis of variance. A p < .05 was considered statistically significant., Measurements and Main Results: Aortic, left atrial, and left lobar arterial pressures were measured. After administration of GR32191 (0.25 and 1.0 mg/kg iv), pulmonary vasoconstrictor responses to U46619, a thromboxane mimic, were significantly decreased. Blockade was overcome with higher doses of the thromboxane mimic. GR32191 was without significant effect on the responses to prostaglandin (PG) D2, PGF2 alpha, serotonin, the calcium-channel agonist BAY K8644, or norepinephrine. Additionally, GR32191 did not alter baseline vascular pressures. Responses to U46619 returned to 50% of control value 90 mins after administration of 0.25 mg/kg of U46619. Responses to GR32191 returned to 50% of control value 180 mins after administration of 1.0 mg/kg of GR32191. These data suggest that GR32191 selectively blocks thromboxane A2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed of the cat., Conclusions: These results are consistent with the hypothesis that discrete thromboxane A2 receptors, unrelated to receptors activated by PGF2 alpha or PGD2, are present in the feline pulmonary vascular bed. Specific thromboxane receptor antagonists, such as GR32191, could be useful therapeutic agents in the treatment of pulmonary hypertensive and thromboembolic disorders.

Vancomycin is known to cause vasodilation, and hypotension secondary to histamine release. We studied the actions of two forms of vancomycin, a clinically available preparation, clinical vancomycin, and a research grade preparation, laboratory vancomycin, in the presence of an H1 receptor blockade and during H2 receptor blockade with Doppler flow probe analysis of carotid artery flow rate. Clinical vancomycin, laboratory vancomycin, and histamine, increased the mean carotid artery blood flow from baseline in a dose-dependent manner. Diphenhydramine, H1 receptor antagonist, attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin and for each dose of histamine. Famotidine, H2 receptor antagonist, significantly attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin, the two higher doses of laboratory vancomycin, and with each dose of histamine. Both diphenhydramine and famotidine attenuated the increase of mean carotid artery blood flow with clinical vancomycin, laboratory vancomycin, and histamine. These data suggest that the change in carotid flow produced by vancomycin, is dependent, in part, on either H1 or H2 receptor activation.

The effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase; 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of soluble guanylate cyclase; glybenclamide, a ATP-sensitive K+ channel blocking agent; and 5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl)-[1,1']-biphenyl-4- yl]methyl]-3H-imidazo[4,5-b]pyridine (L158809), an angiotensin II type I receptor antagonist, on the response to ventilatory hypoxia were investigated in the isolated blood-perfused rat lung. Under conditions of controlled pulmonary blood flow, and constant left atrial pressure, injections of glybenclamide into the pulmonary arterial perfusion circuit significantly increased baseline pulmonary arterial perfusion pressure, whereas administration of N omega-nitro-L-arginine methyl ester produced smaller increases in baseline tone. Ventilatory hypoxia (3% O2-5% CO2-92% N2) significantly increased pulmonary arterial perfusion pressure and the response was reproducible with respect to time. Following administration of N omega-nitro-L-arginine methyl ester or LY83583, the response to hypoxia was significantly increased, whereas the response to hypoxia was not changed by glybenclamide or atropine. N omega-Nitro-L-arginine methyl ester also significantly enhanced pressor responses to angiotensin II, but had no effect on the pressor response to serotonin. When pulmonary vascular tone was increased with hypoxia, vasodilator responses to acetylcholine were inhibited by N omega-nitro-L-arginine methyl ester and vasodilator responses to levcromakalim were reduced by glybenclamide. In addition, L158809 did not alter the pressor response to hypoxia, whereas responses to angiotensin II were reduced in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogens have been postulated to play an important role in modulation of vascular responses to endogenous reactive substances. The effects of chronic in vivo treatment with 17 beta-estradiol on relaxant responses to acetylcholine were investigated in the rat aorta isolated from prepubertal female rats. The selectivity of effects of 17 beta-estradiol on acetylcholine-induced relaxation was evaluated using histamine, another endothelium-dependent relaxant in the rat aorta. 17 beta-Estradiol significantly enhanced endothelium-dependent relaxation induced by acetylcholine, but did not alter the vascular responses to acetylcholine in endothelium-denuded aortic rings isolated from prepubertal female rats. In contrast, 17 beta-estradiol did not change endothelium-dependent relaxation induced by histamine in endothelium-intact aortic rings. The results of the present study demonstrate that 17 beta-estradiol selectively enhances acetylcholine-induced endothelium-dependent relaxation in the rat aorta.

Responses to synthetic human adrenomedullin (ADM), a novel hypotensive peptide recently discovered in human pheochromocytoma cells, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled hindquarters blood flow, intraarterial injections of ADM (0.01-0.3 nmol) and of CGRP (0.03-0.3 nmol) caused dose-related decreases in hindquarters perfusion pressure and decreases in systemic arterial pressure. Following administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), hindquarters vasodilator and systemic depressor responses to ADM were significantly decreased, whereas L-NAME did not significantly decrease the vasodilator response to CGRP in either the hindquarters or systemic vascular beds. Following administration of the cyclooxygenase inhibitor, meclofenamate, vasodilator responses to ADM and to CGRP were not significantly decreased. When the relative vasodilator activity of the two peptides was compared on a nmol basis, responses to ADM were similar to responses with CGRP in the hindquarters vascular bed, whereas ADM was 30-100 fold less potent than CGRP in decreasing systemic arterial pressure. The present data demonstrate that ADM has significant vasodilator activity in the hindquarters vascular bed of the rat, that hindquarters vasodilator and systemic vasodepressor responses to ADM, but not to CGRP, are dependent upon the release of nitric oxide from the endothelium.

Desmopressin acetate (DDAVP) is a synthetic analogue of vasopressin used to promote hemostasis and reduce postoperative blood loss. Desmopressin acetate can cause hypotension in humans. Our study evaluated the hemodynamics of rapid administration of DDAVP into the isolated hindlimb in live rats and assessed this response after pretreatment with various antagonists. Thirty male Sprague-Dawley rats (350-450 g) were given intraperitoneal pentobarbital anesthesia (50 mg/kg). Perfusion was set at a rate that gave a control mean hindlimb perfusion pressure (HPP) of 100-120 mm Hg. Rats were assigned to five groups (N = 5, each group), with each rat serving as its own control. As a control, saline solution (in volumes equivalent to those used for the antagonists) was injected into the hindlimb preparation before the agonist injections. Each group received both the clinical preparation of DDAVP (i.e., with preservative) and a laboratory preparation of DDAVP in doses of 0.3-3 ng. Group 1 was tested before and after injection of saline solution control; group 2, before and after propranolol (0.5 mg/kg); group 3, before and after meclofenamate (1.5 mg/kg), a cyclooxygenase inhibitor; group 4, before and after nitroarginine (5 mg/kg) an inhibitor of nitric oxide synthesis; and group 5, before and after atropine sulfate (1 mg/kg). Chlorobutanol (25-75 micrograms), the preservative in the clinical preparation of DDAVP, was tested for changes in HPP in five rats similarly prepared. Systemic mean arterial pressure remained constant during the study. The HPP decreased with increasing doses of the clinical preparation of DDAVP, compared with saline solution controls, whereas no change occurred with the laboratory preparation of DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS)

The difference in pulmonary vascular response to hypoxia between Hilltop Sprague-Dawley (HT) rats and Wistar (W) rats was studied. Effects of inhibitor of leukotriene (LT) synthesis or prostaglandin (PG) synthesis on hypoxic pulmonary vasoconstriction (HPV) and chronic pulmonary hypertension were observed, and variations in plasma TXB2 and 6-keto-PGF1 alpha during hypoxia were determined. The results showed that in rats of both strains LTs are the major mediator of HPV, which is also mediated by vasoconstrictive PGs in HT rats, while modulated by vasodilative PGs in W rats. This might be the crucial mechanism responsible for the higher pulmonary vascular responsiveness in HT rats. Differences in the modulating effect of histamine and in the structural feature of pulmonary arteriole might be contributing factors as well.