Ventromedial medullary pathway mediating cardiac responses evoked from periaqueductal gray.

Periaqueductal gray (PAG) is a midbrain region that projects to areas controlling behavioral and autonomic outputs and is involved in the behavioral and physiological components of defense reactions. Since Raphe Pallidus (RPa) is a medial medullary region comprising sympathetic premotor neurons governing heart function, it is worth considering the PAG-RPa path. We assessed: i) whether PAG projects to RPa; ii) the amplitude of cardiac responses evoked from PAG; iii) whether cardiovascular responses evoked from PAG rely on RPa. Experiments conducted in Wistar rats (±300 g) were approved by Ethics Committee CEUA-UFG (092/18). Firstly, (n = 3), monosynaptic retrograde tracer Retrobeads was injected into RPa; PAG slices were analyzed. Other two groups (n = 6 each) were anesthetized with urethane (1.4 g/kg) and chloralose (120 mg/kg) and underwent craniotomy, tracheostomy, catheterization of femoral artery and vein and of cardiac left ventricle. In one group, we injected the GABAA receptor antagonist, bicuculline methiodide (BMI - 40 pmol/100 nL) into lateral/dorsolateral PAG. Another group was injected (100 nL) with the GABAA receptor agonist muscimol (20 mM) into RPa, 20 min before BMI into PAG. The results were: i) retrogradely labelled neurons were found in PAG; ii) PAG activation by BMI caused positive chronotropism and inotropism, which were accompanied by afterload increases; iii) RPa inhibition with Muscimol reduced heart rate, arterial and ventricular pressures; iv) the subsequent PAG activation still increased arterial pressure, cardiac chronotropy and inotropy, but these responses were significantly attenuated. In conclusion, PAG activation increases cardiac chronotropy and inotropy, and these responses seem to rely on a direct pathway reaching ventromedial medullary RPa neurons.

Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 µL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P < 0.05), blunted tachycardia in the stress trial (ΔHR: GS 115 ± 14, EL 117 ± 10, GL 74 ± 9 bpm; P<0.05) and spent more time in the open arms of elevated plus maze (EL 6 ± 2 vs. GL 18 ± 5%; P = 0.028) compared with GS and EL groups. These results indicate that liposome-entrapped GABA can be a potential tool for exploring the chronic effects of GABA in specific regions and pathways of the central nervous system.

The dorsomedial hypothalamus and the central pathways involved in the cardiovascular response to emotional stress.

Psychological stress elicits increases in sympathetic activity accompanied by a marked cardiovascular response. Revealing the relevant central mechanisms involved in this phenomenon could contribute significantly to our understanding of the pathogenesis of stress-related cardiovascular diseases, and the key to this understanding is the identification of the nuclei, pathways and neurotransmitters involved in the organization of the cardiovascular response to stress. The present review will focus specifically on the dorsomedial hypothalamus, a brain region now known to play a primary role in the synaptic integration underlying the cardiovascular response to emotional stress.

Functional asymmetry in the descending cardiovascular pathways from dorsomedial hypothalamic nucleus.

Neurons in the dorsomedial hypothalamus (DMH) play a key role in mediating tachycardia elicited by emotional stress. DMH activation by microinjections of the GABA(A) antagonist evokes tachycardia and physiological changes typically seen in experimental stress. DMH inhibition abolishes the tachycardia evoked by stress. Based on anatomic evidences for lateralization in the pathways from DMH, we investigated a possible inter-hemispheric difference in DMH-evoked cardiovascular responses. In anesthetized rats we compared changes in heart rate (HR), renal sympathetic activity (RSNA), mesenteric blood flow (MBF) and tail vascular conductance produced by activation of right (R) and left (L) sides of the DMH. We also evaluated the tachycardia produced by air jet stress after inhibition of R or L DMH. There were always greater increases in RSNA when bicuculline was injected ipsilaterally to the side where these parameters were recorded (average DeltaRSNA: L=+50% and R=+26%; P<0.05). Compared to pre-injection values, right DMH activation caused pronounced decrease (0.87+/-0.1% vs. 0.4+/-0.11%/mm Hg; P<0.05), whereas bicuculline methiodide (BMI) into left DMH produced no significant changes (0.95+/-0.09% vs. 1.04+/-0.25%/mm Hg) in tail vascular conductance. R or L DMH disinhibition produced decreases in MBF, but no differences in the range of these changes were observed. Activation of the right DMH caused greater tachycardia compared to the left DMH activation (average DeltaHR: R=+92 bpm; L=+48 bpm; P<0.05). Tachycardia evoked by air jet stress was smallest after right DMH inhibition (average DeltaHR: R=+57 bpm and L=+134 bpm; P<0.05). These results indicate that the descending cardiovascular pathways from DMH are predominantly lateralized and the right DMH might exert a prominent control on heart rate changes during emotional stress.

Cardiovascular reactivity after blockade of angiotensin AT1 receptors in the experimental model of tilting test in conscious rats.

BACKGROUND AND PURPOSE: Studies have shown that the angiotensin II AT(1) receptor antagonist, losartan, accentuates the hypotensive response in the orthostatic stress test (tilt) performed in anaesthetized rats. The same effect was not reported with other AT(1) antagonists. The aim of this study was to re-evaluate the effects of AT(1) receptor blockade on the cardiovascular response to tilt in a model developed for conscious rats. EXPERIMENTAL APPROACH: Rats (n=5-7 per group) were instrumented for infusion of drugs and recording of cardiovascular parameters and, after recovery, placed in a plastic tube positioned over the tilt board. The tilt test was conducted by raising the head side of the tilt board from horizontal position to 75 degrees head up position for 15 min. KEY RESULTS: Compared with control group (NaCl 0.9%, 1 ml kg(-1)), oral treatment with 1 mg kg(-1) per day of losartan or telmisartan did not alter the blood pressure response during tilt. With the 10 mg kg(-1) dose, both antagonists altered the blood pressure response during tilt (mean maximum changes -11+/-3 mm Hg; P<0.01). A post-tilt hypotension was observed with both doses in losartan and telmisartan groups (-13+/-1 and -9+/-2 mm Hg, respectively; P<0.01). CONCLUSIONS AND IMPLICATIONS: The present results indicate that the effect of losartan on the cardiovascular reactivity to tilt shares a similar profile to that of other AT(1) antagonists. Evidence discussed addresses the importance of using a conscious model for testing the influence of antihypertensive drugs on the cardiovascular reactivity to orthostatic challenges.

Cardiovascular effects produced by activation of GABA receptors in the rostral ventrolateral medulla of conscious rats.

The rostral ventrolateral medulla (RVLM) has been proposed as a region playing a major role in the tonic and reflex control of sympathetic vasomotor activity and blood pressure. Pharmacological activation of GABA(A) receptors with muscimol in the RVLM of anesthetized rats results in a large fall in mean arterial pressure (MAP), heart rate (HR) and sympathetic activity. In this study we evaluated the effects of activation of GABA receptors in the RVLM of conscious, freely moving rats. Bilateral microinjections of muscimol into the RVLM of conscious rats produced a large fall in MAP (-38+/-4 mm Hg, n=7) when compared with saline injections (NaCl 0.9%, 7+/-1 mm Hg, n=4). The decrease in MAP evoked by muscimol was accompanied by a significant increase in HR (muscimol 69+/-13 bpm vs. vehicle -33+/-12 bpm, P<0.05), an effect that was completely abolished by beta1 adrenergic receptor blockade. Conversely, bilateral microinjections of GABA(B) agonist, baclofen, evoked a pressor response, but in this case, the increase was not significantly different from that evoked by vehicle injections. These results 1) indicate that GABA(A) receptors have a powerful influence on the resting activity of RVLM neurons in conscious rats; 2) indicate that a compensatory sympathetic-mediated tachycardia is present after inhibition of RVLM neurons in conscious rats; 3) confirm and extend previous findings showing that RVLM neurons are critical for blood pressure maintenance even in normal non-anesthetized conditions.

Angiotensin peptides acting at rostral ventrolateral medulla contribute to hypertension of TGR(mREN2)27 rats.

We have previously demonstrated that microinjections of the selective angiotensin-(1-7) [ANG-(1-7)] antagonist, A-779, into the rostral ventrolateral medulla (RVLM) produces a significant fall in mean arterial pressure (MAP) and heart rate (HR) in both anesthetized and conscious rats. In contrast, microinjection of angiotensin II (ANG II) AT(1) receptor antagonists did not change MAP in anesthetized rats and produced dose-dependent increases in MAP when microinjected into the RVLM of conscious rats. In the present study, we evaluated whether endogenous ANG-(1-7) and ANG II acting at the RVLM contribute to the hypertension of transgenic rats harboring the mouse renin Ren-2 gene, TGR(mREN2)27. Unilateral microinjection of A-779 (0.1 nmol) produced a significant fall in MAP (-25 +/- 5 mmHg) and HR (-57 +/- 20 beats/min) of awake TGR rats. The hypotensive effect was greater than that observed in Sprague-Dawley (SD) rats (-9 +/- 2 mmHg). Microinjection of the AT(1) antagonist CV-11974 (0.2 nmol) produced a fall in MAP in TGR rats (-14 +/- 4 mmHg), contrasting with the pressor effect observed in SD rats (33 +/- 9 mmHg). These results indicate that endogenous ANG-(1-7) exerts a significant pressor action in the RVLM, contributing to the hypertension of TGR(mREN2)27 transgenic rats. The role of ANG II at the RVLM seems to be dependent on its endogenous level in this area.

The physiological role of AT1 receptors in the ventrolateral medulla.

Neurons in the rostral and caudal parts of the ventrolateral medulla (VLM) play a pivotal role in the regulation of sympathetic vasomotor activity and blood pressure. Studies in several species, including humans, have shown that these regions contain a high density of AT1 receptors specifically associated with neurons that regulate the sympathetic vasomotor outflow, or the secretion of vasopressin from the hypothalamus. It is well established that specific activation of AT1 receptors by application of exogenous angiotensin II in the rostral and caudal VLM excites sympathoexcitatory and sympathoinhibitory neurons, respectively, but the physiological role of these receptors in the normal synaptic regulation of VLM neurons is not known. In this paper we review studies which have defined the effects of specific activation or blockade of these receptors on cardiovascular function, and discuss what these findings tell us with regard to the physiological role of AT1 receptors in the VLM in the tonic and phasic regulation of sympathetic vasomotor activity and blood pressure.

Haemorrhage increases the pressor effect of angiotensin-(1-7) but not of angiotensin II at the rat rostral ventrolateral medulla.

OBJECTIVE: To evaluate the effects of angiotensins acting at the rostral ventrolateral medulla (RVLM) on the cardiovascular adjustments following haemorrhage. DESIGN: Changes in mean arterial pressure (MAP) and heart rate (HR) produced by micro-injections of angiotensin II (Ang II) and angiotensin (Ang)-(1-7) and different angiotensin antagonists into the RVLM of anaesthetized rats submitted to haemorrhage, were determined. METHODS: Experiments were performed in 79 urethane-anaesthetized male Wistar rats. Ang-(1-7) (2.5 and 25 pmol), Ang II (25 pmol), [Sar1,Thr8]-Ang II (non-selective angiotensin antagonist, 0.2 nmol), A-779 (Ang-(1-7) antagonist, 0.1 nmol), losartan (AT1 Ang II receptor antagonist, 0.2 nmol) or vehicle (200 nl) were bilaterally micro-injected into the RVLM under basal conditions or 30 min after blood withdrawal (0.6 ml/100 g bodyweight). In additional groups, [Sar1,Thr8]-Ang II, A-779, losartan or vehicle were micro-injected into the RVLM 10 min before bleeding to uncover a possible role of endogenous peptides during haemorrhage. RESULTS: The pressor effect produced by Ang II micro-injection was not altered by haemorrhage. Conversely, haemorrhage significantly increased the magnitude and duration of the pressor effect of Ang-(1-7) at the RVLM. The fall in MAP induced by haemorrhage was similar after micro-injection of vehicle or A-779. However, micro-injection of [Sar1,Thr8]-Ang II significantly reduced the fall in MAP after haemorrhage. A similar finding was obtained with micro-injection of losartan. In addition, while RVLM micro-injection of [Sar1,Thr8]-Ang II or losartan 30 min after blood withdrawn produced MAP changes that were similar to that observed in control animals, micro-injection of A-779 did not significantly alter baseline MAP. CONCLUSIONS: These results suggest that changes in the RVLM reactivity to Ang-(1-7) but not Ang II may contribute to the haemodynamic adjustments triggered by acute reductions in blood volume. The data obtained with [Sar1,Thr8]-Ang II and losartan suggest a primary inhibitory role for endogenous Ang II at the RVLM during haemorrhage.

Cardiovascular effects produced by nitric oxide-related drugs in the caudal ventrolateral medulla.

The role of nitric oxide in the central control of blood pressure was evaluated by interfering with its local formation in the caudal region of the ventrolateral medulla (CVLM). Urethane anesthetized male Wistar rats were used. Microinjection of L-arginine (L-Arg, 25-100 nmol) produced a hypertensive effect without significant changes in heart rate (HR). Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME, 7.4 nmol) produced a significant hypotensive effect. Microinjection of L-Arg (50 nmol) combined with L-NAME (7.4 nmol) did not significantly change mean arterial pressure or HR. A similar finding was obtained with microinjection of L-Arg (50 nmol) 5 min after microinjection of methylene blue (5 nmol) into the CVLM. The pressor effect of L-Arg was also abolished by prior i.v. injection of a vasopressin V1 receptor antagonist, but not by prior i.v. injection of prazosin. These results suggest an inhibitory role for local NO in the CVLM and that nitrergic pathways at the CVLM participate in the central regulation of AVP release.

Hyperhydricity in pepper plants regenerated in vitro: involvement of BiP (Binding Protein) and ultrastructural aspects.

Hyperhydricity in regenerated pepper plants was monitored by the induction of the ER-luminal resident protein, as observed by immunoblotting. Immunoblotting of total protein using an anti-soybean BiP serum indicated that the induction and accumulation of an 80-kDa protein was related to BiP (Binding protein), a 78-kDa ER-resident molecular chaperone. The anti-BiP serum cross-reacted with an 80-kDa protein which was significantly induced by hyperhydricity. Based on similar molecular weight and immunological reactivity we concluded that the 80-kDa protein induced in hyperhydric plants is a BiP homologue. The ultrastructural organisation of leaves in non-hyperhydric and hyperhydric pepper (Capsicum annuum L.) plants was investigated with the aim of identifying the subcellular changes associated with this phenomenon. In non-hyperhydric leaves the chloroplasts of the palisade cells had normally developed thylakoids and grana and a low accumulation or absence of starch grains and plastoglobules. In the hyperhydric plants, however, the chloroplasts exhibited thylakoid disorganisation, low grana number, an accumulation of large starch grains and a low accumulation or absence of plastoglobules. Although the structure of mitochondria and peroxisomes did not change in hyperhydric plants, the number of peroxisomes did increase.

Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats.

In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1-7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A. Sar1-Thr8-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5-50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT1 and AT2 ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar1-Thr8-Ang II and the selective Ang-(1-7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1-7) at the RVLM. The pressor activity of the ligands for AT1 and AT2 angiotensin receptor subtypes at the RVLM, remains to be clarified.

Pressor action of angiotensin I at the ventrolateral medulla: effect of selective angiotensin blockade.

In this study we explored the possibility that angiotensin-(1-7) (Ang-(1-7)) is involved in the control of blood pressure at the rostral ventrolateral medulla (RVLM) by determining the effect of angiotensin antagonists (DuP 753 and A-779) and the effect of the angiotensin converting enzyme inhibitor, ramiprilat on the pressor action produced by angiotensin I (Ang I). The pressor effect produced by bilateral microinjection of Ang I into the RVLM of anesthetized rats was not significantly altered by DuP 753 or by the ACE inhibitor ramiprilat. Conversely, the Ang-(1-7) antagonist, A-779, reduced significantly the pressor effect produced by Ang I. These data suggest that in our experimental condition Ang I was preferentially converted to Ang-(1-7) at RVLM, or that Ang I and/or one of its fragments acts through a receptor blocked by A-779.

Evidence that angiotensin-(1-7) plays a role in the central control of blood pressure at the ventro-lateral medulla acting through specific receptors.

In this study we determined which angiotensin receptors may mediate the cardiovascular effects elicited by angiotensin-(1-7) [Ang-(1-7)] in the rostral ventrolateral medulla (RVLM) and caudal pressor area (CPA) of the ventrolateral medulla (VLM) of anesthetized rats. Furthermore the role of endogenous angiotensins in these areas was also investigated. The pressor effect produced by unilateral microinjection of Ang-(1-7) into the RVLM or CPA was not modified by either the AT1 receptor antagonist, DuP 753 or by the AT2 receptor antagonist, CGP 42112A, but was completely blocked by the Ang-(1-7) selective antagonist, A-779. In contrast, the pressor effect produced by microinjection of angiotensin II (Ang II) was completely blocked by DuP 753 but was not changed by CGP 42112A or A-779. Bilateral microinjection of A-779 into the RVLM or CPA produced a significant fall in mean arterial pressure and heart rate. Microinjection of DuP 753 produced a pressor effect comparable to bilateral injection of vehicle. These results indicate that, although Ang II acts in the VLM through an AT1 receptor subtype, the cardiovascular effects produced by microinjection of Ang-(1-7) into the RVLM and CPA are mediated by a specific angiotensin receptor (AT5?). Furthermore, our data provide evidence that endogenous Ang-(1-7) participates at the VLM in the neural control of arterial blood pressure.

Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors.

In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. A-779 blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats and the changes in blood pressure produced by Ang-(1-7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1-7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 microM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 microM. Our results show that A-779 is a potent and selective antagonist for Ang-(1-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1-7).

Cardiovascular effects produced by micro-injection of angiotensin-(1-7) on vasopressor and vasodepressor sites of the ventrolateral medulla.

In this study, we determined the cardiovascular effects produced by micro-injection of the heptapeptide Angiotensin-(1-7) [Ang-(1-7)] into the rat ventrolateral medulla (VLM). Micro-injection of Ang-(1-7) into the rostral VLM and the caudal pressor area of the VLM produced significant increases in arterial pressure, comparable to that observed with micro-injection of Ang II. The changes in arterial pressure were associated with more variable changes in heart rate (HR) (usually tachycardia). On the other hand, micro-injection of Ang-(1-7) into the caudal depressor area induced decreases in arterial pressure and HR. The results suggest that, besides Ang II, Ang-(1-7) is involved in the mediation of the cardiovascular actions of the renin-angiotensin system in the VLM.

Modificaçäo técnica na cirurgia da estenose aórtica supravalvar / Technical modification in the supravalvular-aortic stenosis surgery

O tratamento cirúrgico convencional da estenose aórtica supravalvar caracteriza-se pela ampliaçao de um ou mais seios de Valsalva, utilizando-se retalhos de material protético, com ou sem secçao transversal da aorta. Uma possível limitaçao dos resultados deste procedimento é o fato do endurecimento ou calcificaçao do enxerto, dificultando o desenvolvimento da raiz da aorta, mormente quando a cirurgia é realizada em criaças. Para evitar essa complicaçao, desenvolvemos uma modificaçao técnica que, efetivamente, amplia o diâmetro da raíz da aorta, sem o uso de material protético, aproveitando apenas o tecido sadio da parede da aorta ascendente, para reconstruir e ampliar os seios de Vasalva. Com esta técnica foram operados 4 pacientes com diagnósticos clínico e hemodinâmico de estenose aórtica supravalvar, com os seguintes dados clínicos: idades, l ano e ll meses, 3 anos e 9 meses, 15 e 38 anos, sexo masculino três casos, peso corporal de 10, 12, 27 e 56 kg. Dois pacientes tinham dispnéia, um palpitaçoes freqüentes e outro era assintomático. Os gradientes entre a cavidade livre do ventrículo esquerdo e aorta ascendente eram de 50, 70, l00 e l00 mmHg. Os pacientes foram operados com o auxílio da circulaçao extracorpórea, de hipotermia moderada e emprego de cardioplegia cristalóide. A aorta ascendente foi dissecada em toda sua extensao, preferindo-se canular a artéria femoral para o retorno arterial, a fim de liberar a aorta ascendente para o procedimento. Após transecçao total da aorta e ressecçao do tecido fibrótico estenosante, foram feitas incisoes na borda livre até o fundo dos seios de Valsalva. Foram realizadas inclsoes longitudinais na porçao distel da aorta, nas regioes correspondentes aos postes comissurais da valva aórtica, de tal forma que, durante a reconstruçao por sutura direta, um segmento da parede aórtica ficasse ampliando um seio de Valsalva, obtendo-se, assim, uma raíz de aorta de aspecto anatômico e dimensoes normais. Todos os casos, tiveram evoluçao favorável. Atualmente, com um período de pós-operatório de até seis meses, estao assintomáticos.

Urgencia oftalmologica em crianca:estudo das condicoes do primeiro atendimento. / Ophthalmological emergency in children: study of the conditions of first aid

Os autores realizaram um estudo prospectivo de 225 criancas com trauma ocular atendidas no Servico de Emergencia do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, analisando as condicoes do primeiro socorro. Relataram que o mesmo foi realizado por medico nao especialista (pediatras e clinicos) em 65,7% sendo que nem sempre a conduta foi a mais indicada. Enfatizam necessidade de os cursos de graduacao terem como uma das prioridades o preparo para dar o primeiro atendimento das urgencias oculares