Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.66, P less than 0.01) and pulmonary vascular resistance (PVR; r = -0.56, P less than 0.05) at 30 min of hypoxia in 14 animals; no such relationship was found during normoxia. ANF infusion after 60 min of hypoxia in seven pigs reduced the 156 +/- 20% increase in PVR to 124 +/- 18% (P less than 0.01) at 0.01 microgram.kg-1.min-1 and to 101 +/- 15% (P less than 0.001) at 0.05 microgram.kg-1.min-1. Cardiac output (CO) and systemic arterial pressure (Psa) remained unchanged, whereas mean Ppa decreased from 25.5 +/- 1.5 to 20.5 +/- 15 mmHg (P less than 0.001) and plasma irANF increased two- to nine-fold. ANF infused at 0.1 microgram.kg-1.min-1 (resulting in a 50-fold plasma irANF increase) decreased Psa (-14%) and reduced CO (-10%); systemic vascular resistance (SVR) was not changed, nor was a further decrease in PVR induced. No change in PVR or SVR occurred in normoxic animals at any ANF infusion rate. These results suggest that ANF may act as an endogenous pulmonary vasodilator that could modulate the pulmonary pressor response to hypoxia.     

Effect on breathing of abruptly loading and unloading the canine left heart

Cardiopulmonary bypass and pulmonary vein ligation were used to isolate left hearts of anesthetized open-chest dogs. After external gas exchange, blood was returned at constant flow (approximately 120 ml.min-1.kg-1) directly to the aorta or indirectly through the left heart ("left heart loading"). Loading caused breathing frequency (f) to increase approximately 5 breaths/min (approximately 20%), whereas systemic arterial pressure (Psa) fell approximately 15%. Because Psa was pulsatile during loading, we demonstrated separately the effect of pulsatile pressure and found it to lower mean Psa without changing f. Cooling cervical vagi to 7 degrees C eliminated the f response to loading and slightly decreased the Psa response. Loading was compared with graded distension of the fibrillating ventricle and beating atrium, which also increased f. As measured by an abdominal pneumograph, depth of breathing decreased significantly (approximately 4%) during left heart loading but did not change significantly on distension of the fibrillating heart. I conclude that left heart loading may induce tachypnea and a slightly reduced tidal volume by a vagal reflex most likely originating from the left heart.     

Neural and local effects of hypoxia on cardiovascular responses to obstructive apnea.

Obstructive sleep apnea (OSA) acutely increases systemic (Psa) and pulmonary (Ppa) arterial pressures and decreases ventricular stroke volume (SV). In this study, we used a canine model of OSA (n = 6) to examine the role of hypoxia and the autonomic nervous system (ANS) in mediating these cardiovascular responses. Hyperoxia (40% oxygen) completely blocked any increase in Ppa in response to obstructive apnea but only attenuated the increase in Psa. In contrast, after blockade of the ANS (20 mg/kg iv hexamethonium), obstructive apnea produced a decrease in Psa (-5.9 mmHg; P < 0.05) but no change in Ppa, and the fall in SV was abolished. Both the fall in Psa and the rise in Ppa that persisted after ANS blockade were abolished when apneas were induced during hyperoxia. We conclude that 1) hypoxia can account for all of the Ppa and the majority of the Psa response to obstructive apnea, 2) the ANS increases Psa but not Ppa in obstructive apnea, 3) the local effects of hypoxia associated with obstructive apnea cause vasodilation in the systemic vasculature and vasoconstriction in the pulmonary vasculature, and 4) a rise in Psa acts as an afterload to the heart and decreases SV over the course of the apnea.     

Hemodynamic effects of python neuropeptide gamma in the anesthetized python, Python regius

The effects of python neuropeptide gamma (NPgamma) on hemodynamic parameters have been investigated in the anesthetized ball python (Python regius). Bolus intra-arterial injections of synthetic python NPgamma (1-300 pmol kg-1) produced a dose-dependent decrease in systemic arterial blood pressure (Psys) concomitant with increases in systemic vascular conductance (Gsys), total cardiac output and stroke volume, but only minor effects on heart rate. The peptide had no significant effect on pulmonary arterial blood pressure (Ppul) and caused only a small increase in pulmonary conductance (Gpul) at the highest dose. In the systemic circulation, the potency of the NK1 receptor-selective agonist [Sar9,Met(0(2))11] substance P was >100-fold greater than the NK2 receptor-selective agonist [betaAla8] neurokinin A-(4-10)-peptide suggesting that the python cardiovascular system is associated with a receptor that resembles the mammalian NK1 receptor more closely than the NK2 receptor. Administration of the inhibitor of nitric oxide synthesis, L-nitro-arginine-methylester (L-NAME; 150 mg kg-1), resulted in a significant (P<0.05) increase in Psys as well as a decrease in Gsys, but no effect on Ppul and Gpul. Conversely, the nitric oxide donor, sodium nitroprusside (SNP; 60 microg kg-1) produced a significant (P<0.05) decrease in Psys along with an increase in Gsys and pulmonary blood flow. However, neither L-NAME nor indomethacin (10 mg kg-1) reduced the cardiovascular responses to NPgamma. Thus, nitric oxide is involved in regulation of basal vascular tone in the python, but neither nitric oxide nor prostaglandins mediate the vasodilatory action of NPgamma.     

Acute pulmonary hemodynamic effects of intravenous copper sulfate: role of alpha-adrenergic system

We investigated the acute pulmonary hemodynamic effects of intravenous copper sulfate (CuSO4) infusion and its mechanism of action in six groups of conscious sheep (total 40). After 300 mg CuSO4 alone, mean pulmonary artery pressure (Ppa) increased from 10.3 to 22.5 Torr and pulmonary artery wedge pressure (Ppaw) from 3.5 to 7.6 Torr, whereas systemic arterial pressure (Psa) increased from 95 to 102 Torr. Cardiac output (Qp) decreased from 4.7 to 3.3 l/min. Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) increased to 320 and 160% of base line, respectively. The hemodynamic changes correlated well with serum copper, which increased from a base-line value of 0.12 to 3.5 mg/dl after the CuSO4. Serum dopamine beta-hydroxylase increased from 3.2 U/l before CuSO4 injection to 5.7 after its administration, signifying activation of adrenergic nervous system. H1-histamine receptor blockade with chlorpheniramine failed to prevent the effects of CuSO4. Pretreatment with methysergide, a serotonin antagonist, partially attenuated the effects of CuSO4. Phenoxybenzamine, an alpha-adrenergic receptor blocker, and 6-hydroxydopamine, a catecholamine depleting agent, completely blocked the effects of CuSO4. beta-Adrenergic receptor blockade with propranolol enhanced the effects of CuSO4. We conclude, that, in conscious sheep, acute infusion of CuSO4 caused a marked reversible increase in PVR with a slight transient increase in SVR, and this pulmonary hypertension was produced by stimulation of the alpha-adrenergic nervous system.     

Selective pulmonary vasodilation with ATP-MgCl2 during pulmonary hypertension in lambs

We investigated the effects of infusions of ATP-MgCl2 on the circulation in 11 spontaneously breathing newborn lambs during pulmonary hypertension induced either by the infusion of U-46619, a thromboxane A2 mimetic, or by hypoxia. During pulmonary hypertension induced by U-46619, ATP-MgCl2 (0.01-1.0 mg.kg-1.min-1) caused a significant dose-dependent decrease in pulmonary arterial pressure (12.4-40.7%, P less than 0.05), while systemic arterial pressure decreased only at the highest doses (P less than 0.05). Left atrial infusions of ATP-MgCl2 caused systemic hypotension without decreasing pulmonary arterial pressure. During hypoxia-induced pulmonary hypertension, ATP-MgCl2 caused a similar significant dose-dependent decrease in pulmonary arterial pressure (12.0-41.1%, P less than 0.05), while systemic arterial pressure decreased only at high doses (P less than 0.05). Regression analysis showed selectivity of the vasodilating effects of ATP-MgCl2 for the pulmonary circulation during pulmonary hypertension induced either by U-46619 or hypoxia. ATP-MgCl2 is a potent vasodilator with a rapid metabolism that allows for selective vasodilation of the vascular bed first encountered (pulmonary or systemic). We conclude that infusions of ATP-MgCl2 may be clinically useful in the treatment of children with pulmonary hypertension.     

Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea.

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model (n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 +/- 1.7% decrease after apnea with arousal (P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 +/- 1.0 vs. 4.1 +/- 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 +/- 2.3 mmHg vs. 10.3 +/- 1.6 mmHg, REM vs. non-REM, respectively, P < 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation.     

Attenuation of pulmonary and systemic vasoconstriction with pentoxifylline and aminophylline

The effects of acute administration of therapeutic doses (1-10 mg/kg) of pentoxifylline and aminophylline on the resistance of the systemic and pulmonary circuits in anaesthetized dogs and pigs were tested. During room air breathing, neither of the two substances caused a significant change in systemic vascular resistance (SVR) or pulmonary vascular resistance (PVR). During hypoxia (10% O2 and nitrogen), however, both substances caused a significant reduction in PVR (p less than 0.05) without affecting SVR. The largest dose of pentoxifylline decreased PVR from 7.8 +/- 2.8 to 4.4 +/- 1.5 in dogs and from 9.9 +/- 1.4 to 5.8 +/- 0.6 mmHg.L-1.min in pigs. Aminophylline was equally effective and selective in lowering PVR but not SVR during hypoxia. When SVR was elevated in dogs by continuous infusion of angiotensin, pentoxifylline lowered SVR from 139 +/- 27 to 83 +/- 20 mmHg.L-1.min (p less than 0.05). The simultaneous small elevation in PVR during angiotensin infusion was also attenuated to base-line value by pentoxifylline injection. These results suggest that xanthines, in therapeutic doses, can have a profound vasodilator effect on either the systemic or on the pulmonary circuit, only wherever the vessels are constricted. The vasodilatory effect of pentoxifylline is viewed as a second beneficial effect besides the benefit derived from its action on erythrocyte deformability.     

Sildenafil is more selective pulmonary vasodilator than prostaglandin E1 in patients with pulmonary hypertension due to heart failure

In some patients, heart failure (HF) is associated with increased pulmonary vascular resistance (PVR). The magnitude and the reversibility of PVR elevation affect the HF management. Sildenafil has been recently recognized as potent PVR-lowering drug in HF. The aim of the study was to compare hemodynamic effects and pulmonary selectivity of sildenafil to prostaglandin E(1) (PGE(1)). Right-heart catheterization was performed in 13 euvolemic advanced HF patients with elevated PVR (6.3+/-2 Wood's units). Hemodynamic parameters were measured at the baseline, during i.v. infusion of PGE1 (alprostadil 200 ng · kg(-1) · min(-1)) and after 40 mg oral dose of sildenafil. Both drugs similarly reduced systemic vascular resistance (SVR), but sildenafil had higher effect on PVR (-28 % vs. -49 %, p = 0.05) and transpulmonary pressure gradient than PGE(1). The PVR/SVR ratio--an index of pulmonary selectivity, did not change after PGE(1) (p = 0.7) but it decreased by -32 % (p = 0.004) after sildenafil. Both drugs similarly reduced pulmonary artery mean and wedge pressures and increased cardiac index (+27 % and +28 %). Sildenafil led more often to transplant-acceptable PVR while causing smaller drop of mean systemic pressure than PGE(1). In conclusion, vasodilatatory effects of sildenafil in patients with heart failure are more pronounced in pulmonary than in systemic circulation.     

Pulmonary vascular response to endothelin in rats

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anesthesia alters pulmonary vasoregulation by angiotensin II and captopril.

We investigated the effects of an intravenous (pentobarbital sodium) and inhalational (halothane) general anesthetic on the pulmonary vascular responses to angiotensin II and angiotensin-converting enzyme inhibition (CEI). Multipoint pulmonary vascular pressure-flow (P/Q) plots were generated in conscious pentobarbital- (30 mg/kg iv) and halothane-anesthetized (approximately 1.2% end-tidal) dogs in the intact (no drug) condition, during angiotensin II administration (60 ng.kg-1.min-1 iv), and during CEI (captopril 1 mg/kg plus 1 mg.kg-1.h-1 iv). In conscious dogs, angiotensin II increased (P less than 0.001) the pulmonary vascular pressure gradient [pulmonary arterial pressure--pulmonary arterial wedge pressure (PAP-PAWP)] over the empirically measured range of Q; i.e., angiotensin II caused pulmonary vasoconstriction. Pulmonary vasoconstriction (P less than 0.01) in response to angiotensin II was also observed during pentobarbital sodium anesthesia. In contrast, angiotensin II had no effect on the P/Q relationship during halothane anesthesia. In conscious dogs, CEI decreased (P less than 0.001) PAP-PAWP over the empirically measured range of Q; i.e., CEI caused pulmonary vasodilation. However, CEI caused pulmonary vasoconstriction (P less than 0.02) during pentobarbital sodium and had no effect on the P/Q relationship during halothane. Thus, compared with the conscious state, the pulmonary vasoconstrictor response to angiotensin II is unchanged or abolished, and the pulmonary vasodilator response to CEI is reversed to vasoconstriction or abolished during pentobarbital sodium and halothane anesthesia, respectively.     

Immobilization of Himalayan tahr with a xylazine-ketamine mixture and reversal with atipamezole under field conditions

Twenty-nine free-ranging Himalayan tahr (Hemitragus jemlahicus) were darted in the Sagarmatha National Park (Nepal) using different combinations of xylazine and ketamine. Animals in Group 1 (n = 4) received a mean xylazine-ketamine dose of 2.77 +/- 0.99 mg/kg xylazine plus 3.32 +/- 0.19 mg/kg ketamine in males and 2.39 +/- 0.10 mg/kg xylazine plus 4.29 +/- 0.17 mg/kg ketamine in females. Animals in Group 2 (n = 25) received a mean xylazine-ketamine dose of 1.70 +/- 0.41 mg/kg xylazine plus 3.06 +/- 0.74 mg/kg ketamine in males and 1.82 +/- 0.29 mg/kg xylazine plus 3.29 +/- 0.52 mg/kg ketamine in females. No anesthetic-related mortality was recorded. Anesthesia was reversed by a standard dose of 11 mg/animal of atipamezole administered by intramuscular injection. Although all anesthetic dosages immobilized free-ranging tahr successfully, a quick and smooth recovery was obtained (11.1 +/- 5.6 min) only with the dosages of Group 2.     

Potent effects of aerosol compared with intravenous treprostinil on the pulmonary circulation.

Inhaled vasodilator therapy for pulmonary hypertension may decrease the systemic side effects commonly observed with systemic administration. Inhaled medications only reach ventilated areas of the lung, so local vasodilation may improve ventilation-perfusion matching and oxygenation. We compared the effects of intravenous vs. aerosolized treprostinil on pulmonary and systemic hemodynamics in an unanesthetized sheep model of sustained acute pulmonary hypertension. Acute, stable pulmonary hypertension was induced in instrumented unanesthetized sheep by infusing a PGH(2) analog, U-44069. The sheep were then administered identical doses of treprostinil either intravenously or by aerosol. Systemic and pulmonary hemodynamics were recorded during each administration. Both intravenous and aerosol delivery of treprostinil reduced pulmonary vascular resistance and pulmonary arterial pressure, but the effect was significantly greater with aerosol delivery (P < 0.05). Aerosol delivery of treprostinil had minimal effects on systemic hemodynamics, whereas intravenous delivery increased heart rate and cardiac output and decreased left atrial pressure and systemic blood pressure. Aerosol delivery of the prostacyclin analog treprostinil has a greater vasodilatory effect in the lung with minimal alterations in systemic hemodynamics compared with intravenous delivery of the drug. We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.     

Suppression of pulmonary and systemic vascular histamine H2-receptors in allergic sheep

We have previously demonstrated a depression of airway H2-receptor function in sheep allergic to Ascaris suum antigen. To investigate whether this is a generalized defect, we studied the H1- and H2- histamine receptor functions in the pulmonary and systemic circulations of allergic and nonallergic sheep. Pulmonary arterial pressure, and cardiac output were measured for calculation of pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) before and immediately after a rapid intrapulmonary infusion of histamine (10 micrograms/kg), with and without pretreatment with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine alone increased mean PVR to 435 and 401% of base line and decreased mean SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P less than 0.001). In the nonallergic sheep following pretreatment with chlorpheniramine (selective H2 stimulation) or metiamide (selective H1 stimulation), histamine decreased SVR by 18 and 36%, respectively, suggesting that approximately two-thirds of the vasodepressor response was mediated by H1-receptors and one-third by H2-receptors. Combined H1- and H2-antagonists completely blocked the histamine response. In allergic sheep the histamine-induced decrease in SVR was primarily mediated by H1-receptors, because the response was blocked by H1-antagonist, chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the pulmonary circulation selective H1-stimulation caused a similar increase in PVR in allergic (365%) and nonallergic sheep (424%), whereas selective H2-stimulation caused a significant decrease in PVR in the nonallergic group (14%) but not in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating vasoactive substances and hemodynamic adjustments at birth in lambs

Circulating vasoactive substances and hemodynamics were examined in chronically instrumented unanesthetized lambs before, during, and after cesarean section (spontaneous respiration). One of three infusions were started 20 min before birth: saline control (n = 10), saralasin (n = 5), or captopril (n = 6). Control lambs exhibited peak (means +/- SE) increases above fetal base line at 5 min after birth in plasma renin activity (5.0 +/- 1.1 to 11.0 +/- 3.4 ng.ml-1.h-1), angiotensin II (ANG II, 37 +/- 6 to 141 +/- 45 pg/ml) and total catecholamines (318 +/- 35 to 3,821 +/- 580 pg/ml). Mean systemic arterial pressure (Psa) and arterial O2 partial pressure (PaO2) increased more rapidly and to a greater extent by 1 h after birth in control lambs (Psa, 65 +/- 1 Torr; PaO2, 45 +/- 3 Torr) compared with the captopril group (Psa, 53 +/- 2 Torr; PaO2, 31 +/- 4 Torr) and the saralasin group (Psa, 56 +/- 2 Torr; PaO2, 27 +/- 3 Torr). Intravenous infusions of ANG II in control lambs, 2 h after birth resulted in a preferential systemic vs. pulmonary pressor response. The results demonstrate that at birth ANG II formation fosters the postnatal rise in Psa and PaO2, and high levels of circulating catecholamines may support postnatal cardiac output and Psa.     

Effects of dihydroergotamine on hemodynamic molsidomine actions in anesthetized dogs

In pentobarbital-anesthetized mongrel dogs the intravenous actions of 0.50 mg/kg molsidomine on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimensions (preload), left ventricular systolic and peripheral blood pressures, and total peripheral resistance (afterload), as well as on heart rate, dP/dt, stroke volume, and cardiac output (heart performance) were studied for 2 h. Hemodynamic molsidomine effects were influenced by increasing amounts of intravenously infused dihydroergotamine solution (DHE, 1-64 micrograms X kg-1 X min-1). Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h but decreased ventricular and peripheral pressures for 45 min. Systemic vascular resistance showed a tendency to decrease while heart rate and LV dP/dtmax were not altered. DHE infusion reversed molsidomine effects on the preload and afterload of the heart. The diminished stroke volume was elevated so that cardiac output also increased. Total peripheral resistance increased while heart rate fell in a dose-dependent fashion. The LV dP/dtmax remained unchanged until the highest dose of 64 micrograms X kg-1 X min-1 DHE elevated the isovolumic myocardial contractility. These experiments indicate that DHE can reverse the intravenous molsidomine effects on hemodynamics. Most likely, this is mediated through peripheral vasoconstriction of venous capacitance vessels, thereby affecting molsidomine's action on postcapillary beds of the circulation.     

Behavioral effects of acute manganese chloride administration in chickens

The behavioral effects of manganese chloride at 20 and 40 mg/kg, subcutaneously (sc), were examined in 1-mo-old broiler chickens using the open-field (5 min) and tonic immobility tests. In a separate experiment, chickens were subjected to a pharmacological challenge with the anesthetic combination of xylazine-ketamine following manganese chloride pretreatment at 50 mg/kg, sc. Manganese at 40 mg/kg significantly decreased jumping attempts of the chickens in the open-field test 30 min after the injection when compared with the control (saline) group. Both manganese treatments significantly increased the tonic immobility response of the chickens in a dose-dependent manner in comparison with the control group. Pretreatment with manganese chloride (50 mg/kg, sc) significantly increased the duration of sleep, decreased the latency to onset of analgesia, and increased the duration of analgesia in chickens treated with the anesthetic xylazine-ketamine mixture when compared with the saline control group. The respiratory rate of all anesthetized chickens significantly decreased from respective preanesthetic (time 0) values during the 60-min observation period after injection of the anesthetic. However, 60 min after the anesthetic injection, the respiratory rate of the manganese-treated group was significantly lower than that of the control group. The data suggest a depressant action of acute manganese chloride treatment in chickens.     

Systemic and portal hemodynamic effects of anandamide

The endogenous cannabinoid anandamide causes hypotension and mesenteric arteriolar dilation. A detailed analysis of its effects on systemic and portal venous hemodynamics had not yet been performed. We assessed the effects of anandamide (0.4-10 mg/kg) on systemic and portal hemodynamics with and without prior treatment with various antagonists. The specific antagonists used included SR-141716A, N(omega)-nitro-L-arginine methyl ester, indomethacin, and nordihydroguaiaretic acid. Anandamide produced a dose-dependent decrease in mean arterial pressure due to a drop in systemic vascular resistance (SVR) that was accompanied by a compensatory rise in cardiac output. Anandamide also elicited an increase in both portal venous flow and pressure, along with a decline in mesenteric vascular resistance (MVR). Pretreatment with 3 mg/kg SR-141716A, a CB(1) antagonist, prevented the decline of SVR and MVR from the lower dose of anandamide. Antagonism of nitric oxide synthetase, cyclooxygenase, or 5-lipoxygenase did not prevent the systemic nor the portal hemodynamic effects of anandamide. Furthermore, the use of R-methanandamide, a stable analog of anandamide, produced similar hemodynamic effects on the mesenteric vasculature, thereby implying that the effects of anandamide are not related to its breakdown products. Anandamide produced profound, dose-dependent alterations in both the systemic and portal circulations that could be at least partially blocked by pretreatment with SR-141716A.     

Ephedrine accelerates psychomotor recovery from anesthesia in macaque monkeys

Background Ephedrine is used in treatment of hypotension during anesthesia. We investigated its effects on the psychomotor recovery and its potential adverse reactions on cardiorespiratory functions in rhesus monkeys. Methods The monkeys received 50 μg/kg medetomidine, 2.0 mg/kg S‐ketamine with 150 IU hyaluronidase i.m. Pulse rate, blood pressure and saturation of haemoglobin were monitored for 20 minutes. Thereafter, 1 mg/kg of ephedrine or a placebo was administered i.m. and behavioural changes, pulse rate, blood pressure and saturation of haemoglobin were monitored every 5 minutes. Results Ephedrine shortened recovery from anaesthesia from 80.4 ± 25.8 to 14.83 ± 13.70 minutes. Ephedrine also increased oxygen saturation of haemoglobin and systolic blood pressure and caused significant decrease in pulse rate 5 minutes after its administration. Conclusions Ephedrine can be successfully used to accelerate psychomotor recovery after the use of common anesthetic protocols combining dissociative anesthetic agent and alpha 2‐adrenoceptor agonist in primates.     

Alpha-adrenergic agents have little effect during air embolism lung injury in awake sheep

Since it is not clear whether alpha-adrenergic receptors can modulate lung microvascular liquid and protein leakiness, we studied the effects of alpha-adrenergic receptor stimulation or blockade on lung filtration under base-line conditions and during the acute lung injury caused by a 4-h infusion of venous air emboli in six unanesthetized, chronically instrumented sheep with lung lymph fistulas. During the experiments we continuously infused the alpha-adrenergic receptor agonist phenylephrine hydrochloride (1.0 microgram X kg-1 X min-1 iv) or the alpha-adrenergic receptor antagonist phentolamine mesylate (1.0 mg X kg-1 X min-1 iv), and we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and the lymph-to-plasma protein concentration ratio. During air embolism, alpha-receptor stimulation increased pulmonary vascular resistance and decreased lung lymph flow by 25%; alpha-receptor blockade had the opposite effects. During recovery, neither agent significantly affected pulmonary hemodynamics or lymph flow. Our results indicate that alpha-adrenergic receptors are active during air embolism and modulate pulmonary filtration by causing arteriolar constriction, which reduces the surface area or the perfusion pressure in the pulmonary microvascular bed. They may also affect venous smooth muscle tone. We found no evidence that alpha-adrenergic receptors modulate lung microvascular liquid or protein leakiness directly.