The role of the vagus nerve in the generation of cardiorespiratory interactions in a neotropical fish, the pacu, Piaractus mesopotamicus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The role of branchial and orobranchial O-2 chemoreceptors in the control of aquatic surface respiration in the neotropical fish tambaqui (Colossoma macropomum): progressive responses to prolonged hypoxia

The present study examined the role of branchial and orobranchial O-2 chemoreceptors in the cardiorespiratory responses, aquatic surface respiration (ASR), and the development of inferior lip swelling in tambaqui during prolonged (6 h) exposure to hypoxia. Intact fish (control) and three groups of denervated fish (bilateral denervation of cranial nerves IX+X (to the gills), of cranial nerves V+VII (to the orobranchial cavity) or of cranial nerves V alone), were exposed to severe hypoxia (Pw(O2) = 10 mmHg) for 360 min. Respiratory frequency (fR) and heart rate (fH) were recorded simultaneously with ASR. Intact (control) fish increased fR, ventilation amplitude (V-AMP) and developed hypoxic bradycardia in the first 60 min of hypoxia. The bradycardia, however, abated progressively and had returned to normoxic levels by the last hour of exposure to hypoxia. The changes in respiratory frequency and the hypoxic bradycardia were eliminated by denervation of cranial nerves IX and X but were not affected by denervation of cranial nerves V or V+VII. The VAMP was not abolished by the various denervation protocols. The fH in fish with denervation of cranial nerves V or V+VII, however, did not recover to control values as in intact fish. After 360 min of exposure to hypoxia only the intact and IX+X denervated fish performed ASR. Denervation of cranial nerve V abolished the ASR behavior. However, all (control and denervated (IX+X, V and V+VII) fish developed inferior lip swelling. These results indicate that ASR is triggered by O-2 chemoreceptors innervated by cranial nerve V but that other mechanisms, such as a direct effect of hypoxia on the lip tissue, trigger lip swelling.

Branchial O2 chemoreceptors in Nile tilapia Oreochromis niloticus: Control of cardiorespiratory function in response to hypoxia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Control of cardiorespiratory function in response to hypoxia in an air-breathing fish, the African sharptooth catfish, Clarias gariepinus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Serotoninergic receptors in the anteroventral preoptic region modulate the hypoxic ventilatory response

Hypothalamus is a site of integration of the hypoxic and thermal stimuli on breathing and there is evidence that serotonin (5-HT) receptors in the anteroventral preoptic region (AVPO) mediate hypoxic hypothermia. Once 5-HT is involved in the hypoxic ventilatory response (HVR), we investigated the participation of the 5-HT receptors (5-HT1, 5-HT2 and 5-HT7) in the AVPO in the HVR. To this end, pulmonary ventilation (V-E) of rats was measured before and after intra-AVPO microinjection of methysergide (a 5-HT1 and 5-HT2 receptor antagonist), WAY-100635 (a 5-HT1A receptor antagonist) and SB-269970 (a 5-HT7 receptor antagonist), followed by 60 min of hypoxia exposure (7% O-2). Intra-AVPO microinjection of vehicles or 5-HT antagonists did not change VE during normoxic conditions. Exposure of rats to 7% O-2 evoked typical hypoxia-induced hyperpnea after vehicle microinjection, which was not affected by methysergide. WAY-100635 and SB-269970 treatment caused an increased HVR, due to a higher tidal volume. Therefore, the current data provide the evidence that 5-HT acting on 5-HT1A and 5-HT7 receptors in the AVPO exert an inhibitory modulation on the HVR. (c) 2005 Elsevier B.V. All rights reserved.

Cardiovascular changes under normoxic and hypoxic conditions in the air-breathing teleost Synbranchus marmoratus: importance of the venous system

Synbranchus marmoratus is a facultative air-breathing fish, which uses its buccal cavity as well as its gills for air-breathing. S. marmoratus shows a very pronounced tachycardia when it surfaces to air-breathe. An elevation of heart rate decreases cardiac filling time and therefore may cause a decline in stroke volume (VS), but this can be compensated for by an increase in venous tone to maintain stroke volume. Thus, the study on S. marmoratus was undertaken to investigate how stroke volume and venous function are affected during air-breathing. To this end we measured cardiac output (Q), heart rate (fH), central venous blood pressure (PCV), mean circulatory filling pressure (MCFP), and dorsal aortic blood pressures (PDA) in S. marmoratus. Measurements were performed in aerated water (P-O2 > 130 mmHg), when the fish alternated between gill ventilation and prolonged periods of apnoeas, as well as during hypoxia (P-O2 <= 50 mmHg), when the fish changed from gill ventilation to air-breathing. Q increased significantly during gill ventilation compared to apnoea in aerated water through a significant increase in both fH and VS. PCV and MCFP also increased significantly. During hypoxia, when the animals surface to ventilate air, we found a marked rise in fH, PCV, MCFP, Q and VS, whereas PDA decreased significantly. Simultaneous increases in PCV and MCFP in aerated, as well as in hypoxic water, suggests that the venous system plays an important regulatory role for cardiac filling and VS in this species. In addition, we investigated adrenergic regulation of the venous system through bolus infusions of adrenergic agonists (adrenaline, phenylephrine and isoproterenol; 2 mu g kg(-1)). Adrenaline and phenylephrine caused a marked rise in PCV and MCFP, whereas isoproterenol led to a marked decrease in PCV, and tended to decrease MCFP. Thus, it is evident that stimulation of both alpha- and beta-adrenoreceptors affects venous tone in S. marmoratus.

Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain

Preconditioning-induced ischemic tolerance has been documented in the newborn brain, however, the signaling mechanisms of this preconditioning require further elucidation. The aims of this study were to develop a hypoxic-preconditioning (PC) model of ischemic tolerance in the newborn piglet, which emulates important clinical similarities to human situation of birth asphyxia, and to characterize some of the molecular mechanisms shown to be implicated in PC-induced neuroprotection in rodent models. One day old piglets were subjected to PC (8% O(2)/92% N(2)) for 3 h and 24 h later were exposed to hypoxia-ischemia (HI) produced by a combination of hypoxia (5% FiO(2)) for a period of 30 min and ischemia induced by a period of hypotension (10 min of reduced mean arterial blood pressure; 70% of baseline). Neuropathologic analysis and unbiased stereology, conducted at 24 h, 3 and 7 days of recovery following HI, indicated a substantial reduction in the severity of brain damage in PC piglets compared to non-PC piglets (P<0.05). PC significantly increased the mRNA expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and its target gene, vascular endothelial growth factor (VEGF) at 0 h, 6 h, 24 h, 3 and 7 days of recovery. Immunoblot analysis demonstrated that PC resulted in HIF-1 alpha protein stabilization and accumulation in nuclear extracts of cerebral cortex of newborn piglet brain compared to normoxic controls. Protein levels of VEGF increased in a time-dependent manner in both cortex and hippocampus following PC. Double-immunolabeling indicated that VEGF is mainly expressed in neurons, endothelial cells and astroglia. Our study demonstrates for the first time the protective efficacy of PC against hypoxic-ischemic injury in newborn piglet model, which recapitulates many pathophysiological features of asphyxiated human neonates. Furthermore, as has been shown in rodent models of preconditioning, our results suggest that PC-induced protection in neonatal piglets may involve upregulation of VEGF. (C) 2011 Elsevier B.V. All rights reserved.

Regulation of breathing and body temperature of a burrowing rodent during hypoxic-hypercapnia

Burrowing mammals usually have low respiratory sensitivity to hypoxia and hypercapnia. However, the interaction between ventilation (V), metabolism and body temperature (Tb) during hypoxic-hypercapnia has never been addressed. We tested the hypothesis that Clyomys bishopi, a burrowing rodent of the Brazilian cerrado, shows a small ventilatory response to hypoxic-hypercapnia, accompanied by a marked drop in Tb and metabolism. V, Tb and O-2 consumption (VO2) of C. bishopi were measured during exposure to air, hypoxia (10% and 7% O-2), hypercapnia (3% and 5% CO2) and hypoxic-hypercapnia (10% O-2 + 3% CO2). Hypoxia of 7% but not 10%, caused a significant increase in V, and a significant drop in Tb. Both hypoxic levels decreased VO2 and 7% O-2 significantly increased V/VO2. Hypercapnia of 5%, but not 3%, elicited a significant increase in V, although no significant change in Tb, VO2 or V/VO2 was detected. A combination of 10% O-2 and 3% CO2 had minor effects on V and Tb, while VO2 decreased and V/VO2 tended to increase. We conclude that C. bishopi has a low sensitivity not only to hypoxia and hypercapnia, but also to hypoxic-hypercapnia, manifested by a biphasic ventilatory response, a drop in metabolism and a tendency to increase V/VO2. The effect of hypoxic-hypercapnia was the summation of the hypoxia and hypercapnia effects, with respiratory responses tending to have hypercapnic patterns while metabolic responses, hypoxic patterns. (C) 2004 Elsevier B.V. All rights reserved.

Hypoxic cardiorespiratory reflexes in the facultative air-breathing fish jeju (Hoplerythrinus unitaeniatus): role of branchial O-2 chemoreceptors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

PROTECTIVE EFFECTS OF DILTIAZEM ON THE MECHANICAL PERFORMANCE OF THE HYPOXIC MYOCARDIUM

1. To determine whether diltiazem protects the hypoxic myocardium by reducing contractile work, we have compared the effects of diltiazem and quiescence on left ventricular (LV) papillary muscle subjected to hypoxia. Papillary muscles were obtained from male Charles River CD rats weighing 150-250 g.2. Four groups of muscles were studied: control (N = 6), non-stimulation (N = 10), diltiazem 10(-4) M (N = 6) and diltiazem 10(-4) M plus non-stimulation (N = 10).3. Isolated mt LV papillary muscles were studied in Krebs-Henseleit solution with a calcium concentration of 2.52 mM at 28-degrees-C while contracting isometrically at a stimulation rate of 0.2 Hz. Resting tension and active isometric tension were measured.4. Both diltiazem and quiescence significantly attenuated contracture tension during hypoxia (0.91 +/- 0.10 vs 2.26 +/- 0.49 g/mm2 for diltiazem vs control, and 0.55 +/- 0.18 vs 2.26 +/- 0.49 g/mm2 for quiescence vs control). Recovery of active tension was improved in the diltiazem groups during reoxygenation (4.16 +/- 0.42 vs 3.75 +/- 0.51, 3.53 +/- 0.15 vs 2.90 +/- 0.13, 5.84 +/- 0.33 vs 6.48 +/- 0.29 and 5.98 +/- 0.90 vs 7.67 +/- 0.68 g/mm2 for diltiazem, diltiazem non-stimulation, non-stimulation and control groups).5. The results suggest that the protective effect of diltiazem during hypoxia was due to the reduction in energy demand of the myocardium.

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures

Low O-2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Comparative study between atropine and hyoscine-N-butylbromide for reversal of detomidine induced bradycardia in horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Force patterns of hypoxic myocardium applied to oxygenated muscle preparations: Comparison with effects of regional ischemia on the contraction of non-ischemic myocardium

Objective: To examine the basis for local wall motion abnormalities commonly seen in patients with ischemic heart disease, computer-controlled isolated muscle studies were carried out. Methods: Force patterns of physiologically sequenced contractions (PSCs) from rat left ventricular muscle preparations under well-oxygenated conditions and during periods of hypoxia and reoxygenation were recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating myocardium, respectively. Results: Observed patterns of shortening and lengthening closely resemble those obtained from ischemic and non-ischemic myocardial segments using ultrasonic crystals in intact dog hearts during coronary occlusion and reperfusion, and are similar to findings reported in angiographic studies of humans with coronary artery disease. Conclusion: The current study, demonstrating motions of oxygenated isolated muscle preparations which are similar to those in perfused segments of intact hearts with regional ischemia, supports the concept that the multiple motions of both ischemic and non-ischemic segments seen in regional myocardial disease can be explained by interactions of strongly and weakly contracting muscle during the physiologic cardiac cycle.