Dose-dependent Effects of Halothane on the Phrenic Nerve Responses to Acute Hypoxia in Vagotomized Dogs

Background: Previous studies in dogs and humans suggest that the carotid body chemoreceptor response to hypoxia is selectively impaired by halothane. The present studies in an open-loop canine preparation were performed to better delineate the effects of anesthetic concentrations of halothane on the carotid body chemoreceptor-mediated phrenic nerve response to an acute hypoxic stimulus.

Methods: Three protocols were performed to study the effects of halothane anesthesia on the phrenic nerve response to 1 min of isocapnic hypoxia (partial pressure of oxygen [PaO2] at peak hypoxia, 35-38 mmHg) in unpremedicated, anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. In protocol 1, the dose-dependent effects of halothane from 0.5-2.0 minimum alveolar concentration (MAC) on the hypoxic response during moderate hypercapnia (partial pressure of carbon dioxide [PaCO2], 60-65 mmHg) were studied in 10 animals. In protocol 2, the hypoxic responses at 1 MAC halothane near normocapnia (PaCO2, 40-45 mmHg) and during moderate hypercapnia were compared in an additional four animals. In protocol 3, the hypoxic response of 4 of 10 dogs from protocol 1 was also studied under sodium thiopental (STP) anesthesia after they completed protocol 1.

Results: Protocol 1: Peak phrenic nerve activity (PPA) increased significantly during the hypoxic runs compared with the isocapnic hyperoxic controls at all halothane doses. The phrenic nerve response to the hypoxic stimulus was present even at the 2 MAC dose. Protocol 2: The net hypoxic responses for the two carbon dioxide background levels at 1 MAC were not significantly. Protocol 3: The net hypoxic response of PPA for the STP anesthetic was not significantly different from the 1 MAC halothane dose. Bilateral carotid sinus denervation abolished the PPA response to hypoxia.     

Effects of Incremental Halothane Levels on the Reflex Responses to Carotid Hypotension in the Dog

Arterial baroreceptor function was assessed in trained, chronically instrumented dogs by measuring the systemic haemodynamic responses to brachiocephalic artery occlusion (BCO). BCO was carried out in awake dogs and repeated at end-tidal halothane levels of 0.75 ± 0.01 % (H1), 0.94 ± 0.02% (H2) and 1.13±0.02% (H3). Before BCO, at H1 only the increased heart rate and decreased stroke volume were significantly different from awake controls (P<0.01). Mean arterial pressure and cardiac output at H2 and H3 were significantly lower than in the awake controls (P<0.05). The pressor response to BCO fell progressively with increasing halothane levels, the decrease being significant at the H2 and H3 levels (P<0.001). There was a good linear correlation between the pressor response to BCO as a percentage of the response in awake animals, and the end-tidal halothane levels (r= -0.816, P<0.001). This indicated a sensitive dose-dependent modification of the haemodynamic response to BCO by halothane. However, halothane levels existed between about 0.7-0.8%, at which levels the average pressor response to BCO was not significantly different from awake values.     

Effects of Propofol and Remifentanil on Phrenic Nerve Activity and Nociceptive Cardiovascular Responses in Rabbits

Background: The effects of propofol, remifentanil, and their combination on phrenic nerve activity (PNA), resting heart rate (HR), mean arterial pressure (MAP), and nociceptive cardiovascular responses were studied in rabbits.

Methods: Basal anesthesia and constant blood gas tensions were maintained with [alpha]-chloralose and mechanical ventilation. PNA, HR, MAP, and maximum changes in HR and MAP ([DELTA]HR, [DELTA]MAP) evoked by electrical nerve stimulation of tibial nerves were recorded. The comparative effects were observed for propofol at infusion rates from 0.05 to 3.2 mg [middle dot] kg-1 [middle dot] min-1 (group I) and remifentanil from 0.0125 to 12.8 [mu]g [middle dot] kg-1 [middle dot] min-1 alone (group II), and during constant infusions of propofol at rates of 0.1 and 0.8 mg [middle dot] kg-1 [middle dot] min-1 (groups III and IV, respectively). Finally, the effect of remifentanil on propofol blood levels was observed (group V).

Results: The infusion rates for 50% depression (ED50) of PNA, [DELTA]HR, and [DELTA]MAP were 0.41, 1.32, and 1.58 mg [middle dot] kg-1 [middle dot] min-1 for propofol, and 0.115, 0.125, and 1.090 [mu]g [middle dot] kg-1 [middle dot] min-1 for remifentanil, respectively. The ratios for the ED50 values of [DELTA]HR and [DELTA]MAP to PNA were 3.2 and 3.9 for propofol, and 1.1 and 9.5 for remifentanil, respectively. Analysis of the expected and observed responses and isobologrms showed that although their combined effects on PNA, resting HR, and MAP, and [DELTA]MAP were synergistic for [DELTA]HR, they were merely additive. Remifentanil had no effect on propofol blood levels.     

Effects of Mechanical Ventilation and Halothane on Pulmonary Serotonin Removal in Dogs

The type of anesthesia and anesthetic drug used may significantly change the capacity of the lungs to regulate blood concentrations of serotonin. This study was performed to examine the possible effect of mechanical ventilation and 1% halothane in ventilation air on pulmonary serotonin removal using C14-serotonin in eight dogs. Mechanical ventilation significantly increased serotonin removal when compared with spontaneous ventilation during anesthesia, the removal rates being 74.4% and 48.4%, respectively. The 1% halothane concentration in ventilation air did not significantly affect the pulmonary serotonin removal. It was concluded that mechanical ventilation protects the organism against harmful cardiovascular effects of serotonin during anesthesia.     

Effects of Halothane on Synaptic Neurotransmission to Medullary Expiratory Neurons in the Ventral Respiratory Group of Dogs

Background: The activity of canine expiratory neurons is primarily dependent on N-methyl-D-aspartic acid (NMDA)-receptor mediated excitatory chemodrive inputs and a powerful inhibitory gain modulatory mechanism mediated via [gamma]-aminobutyric acidA (GABAA) receptors. We examined whether the depressant effect of halothane on expiratory neuronal activity is primarily caused by a reduction in glutamatergic excitation or a potentiation of the inhibitory mechanism.

Methods: Experiments were performed in halothane-anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of a halothane dose increase from one minimum alveolar concentration (MAC) to 2 MAC on extracellularly recorded expiratory neuronal activity was studied before and during complete GABAA receptor blockade by localized picoejection of bicuculline close to the neuron. Complete blockade of the inhibitory mechanism allowed differentiation between the effects of halothane on overall NMDA-mediated excitation and on GABAA-mediated inhibition.

Results: The spontaneous activity of 12 expiratory neurons was significantly depressed (18.1%) by the 1-MAC halothane dose increase. Overall glutamatergic excitation was depressed 38.3 +/- 12.3% (mean +/- SD) by the 1-MAC halothane increase. The prevailing GABAAergic attenuation of neuronal output decreased significantly from 49.5 +/- 10 to 32.0 +/- 10.4%. Thus overall inhibition was reduced by halothane by 33.5 +/- 17.2%.     

Restoration of Elbow Flexion by Transfer of the Phrenic Nerve to Musculocutaneous Nerve after Brachial Plexus Injuries

Traumatic brachial plexus injuries are a devastating injury that results in partial or total denervation of the muscles of the upper extremity. Treatment options that include neurolysis, nerve grafting, or neurotization (nerve transfer) has become an important procedure in the restoration of function in patients with irreparable preganglionic lesions. Restoration of elbow flexion is the primary goal in treating patients with severe brachial plexus injuries. Nerve transfers are used when spinal roots are avulsed, and proximal stumps are not available. In the present study, we analyze the results obtained in 20 patients treated with phrenic–musculocutaneous nerve transfer to restore elbow flexion after brachial plexus injuries. A consecutive series of 25 adult patients (21 men and 4 women) with a brachial plexus traction/crush lesion were treated with phrenic–musculocutaneous nerve transfer, but only 20 patients (18 men and 2 women) were followed and evaluated for at least 2 years postoperatively. All patients had been referred from other institutions. At the initial evaluation, eight patients received a diagnosis of C5-6 brachial plexus nerve injury, and in the other 12 patients, a complete brachial plexus injury was identified. Reconstruction was undertaken if no clinical or electrical evidence of biceps muscle function was seen by 3 months post injury. Functional elbow flexion was obtained in the majority of cases by phrenic–musculocutaneous nerve transfer (14/20, 70%). At the final follow-up evaluation, elbow flexion strength was a Medical Research Council Grade 5 in two patients, Grade 4 in four patients, Grade 3 in eight patients, and Grade 2 or less in six patients. Transfer involving the phrenic nerve to restore elbow flexion seems to be an appropriate approach for the treatment of brachial plexus root avulsion. Traumatic brachial plexus injury is a devastating injury that result in partial or total denervation of the muscles of the upper extremity. Treatment options include neurolysis, nerve grafting, or neurotization (nerve transfer). Neurotization is the transfer of a functional but less important nerve to a denervated more important nerve. It has become an important procedure in the restoration of function in patients with irreparable preganglionic lesions. Restoration of elbow flexion is the primary goal in treating patients with severe brachial plexus injuries. Nerve transfers are used when spinal roots are avulsed, and proximal stumps are not available. Newer extraplexal sources include the ipsilateral phrenic nerve as reported by Gu et al. (Chin Med J 103:267–270, 1990) and contralateral C7 as reported by Gu et al. (J Hand Surg [Br] 17(B):518–521, 1992) and Songcharoen et al. (J Hand Surg [Am] 26(A):1058–1064, 2001). These nerve transfers have been introduced to expand on the limited donors. The phrenic nerve and its anatomic position directly within the surgical field makes it a tempting source for nerve transfer. Although not always, in cases of complete brachial plexus avulsion, the phrenic nerve is functioning as a result of its C3 and C4 major contributions. In the present study, we analyze the results obtained in 20 patients treated with phrenic–musculocutaneous nerve transfer to restore elbow flexion after brachial plexus injuries.     

Hepatic Effects of Halothane,Isoflurane or Sevoflurane Anaesthesia in Dogs

The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty‐one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1–4 years old, and weighed between 13.5 and 27 kg (18.4 ± 3.9). Xylazine HCI (1–2 mg/kg) i.m. was used as pre‐anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12–14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre‐medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs.     

Effects of Prolonged Anesthesia with Enflurane or Halothane on Renal Function in Dogs

Elevated serum inorganic fluoride levels (60–300 μmol/l), maintained over 6 h, influenced renal function in beagle dogs. Changes in water reabsorption were seen with an increased urine flow and free water clearance and decreased urinary concentration capacity. Possible nephrotoxicity as an effect of inorganic fluoride production during prolonged enflurane anesthesia was evaluated in a group of beagle dogs. Another group of dogs, anesthetized with halothane in equianesthetic doses, was studied for comparison. Serum inorganic fluoride levels and urinary oxalate excretion were determined and postanesthetic renal morphology was examined. Renal function was evaluated from endogenous clearances and concentration capacity before and after anesthesia. In the enflurane group, serum inorganic fluoride levels peaked at 22.5 μmol/1 at the end of anesthesia and decreased rapidly in the postanesthetic period. Urinary oxalate excretion did not increase. No changes in renal morphology were found. Renal function tests did not reveal any disturbance after enflurane anesthesia. The two anesthetized groups did not differ in any of the parameters studied, except in serum inorganic fluoride levels.     

Intravenous Infusion of Halothane Dissolved in Fat. Haemodynamic Effects in Dogs

Eight harrier dogs received an i.v. infusion of halothane dissolved 1:9 in a fat emulsion for i.v. nutrition (Intralipid, Vitrum). The rate of infusion was adjusted to maintain end-tidal halothane concentrations of 0.7% and 1.4%. At 1.4%, mean arterial pressure decreased to 76 ± 8 mmHg (10.1 ± 1.0 kPa) (mean ± s.e.mean) from a pre-infusion value of 122 ± 6 mmHg (16.2 ± 0.8 kPa) ( P <0.01). The concomitant decrease in cardiac output was 39% and left ventricular maximum dp/dt decreased by 50% ( P <0.01). Changes in systemic vascular resistance and pulmonary arterial pressure were small. The haemodynamic responses during halothane inhalation, to corresponding end-tidal concentrations, were similar. Arterial and mixed venous halothane concentration increased in proportion to end-tidal concentration. There were no changes in arterial Po2 during the halothane-in-fat infusion. Triglyceride concentrations in plasma increased 12-fold. Haemodynamic recovery after the infusion was fast. We conclude that the halothane-in-fat infusion caused a dose-dependent depression of myocardial contractility and arterial pressure, similar to that seen during inhalation, and that end-tidal concentration could be used for control of the infusion rate.     

Cerebrovascular Carbon Dioxide Reactivity in Carotid Artery Disease: Relation to Intraoperative Cerebral Monitoring Results in 100 Carotid Endarterectomies

Background: In patients with carotid artery disease, poor intracerebral collateralization is reflected by impaired cerebrovascular reactivity to carbon dioxide inhalation, which will improve after endarterectomy. The relationship between preoperative reactivity to carbon dioxide using transcranial Doppler sonography (TCD) and intraoperative changes of somatosensory evoked potentials (SEP) and TCD parameters were investigated.

Methods: In 94 patients, preoperative carbon dioxide reactivity was examined and defined impaired if mean blood flow velocity in the middle cerebral artery (Vm-MCA) increased less than 1.5%/mmHg during carbon dioxide challenge. Patients then underwent 100 carotid operations under general anesthesia with both SEP and TCD monitoring. Shunts were placed if SEP amplitude decreased to less then 50% of control or central conduction time increased by 20% after clamping (critical SEP changes). TCD changes were defined as critical in case of a postclamping/preclamping Vm-MCA ratio < 0.4. The incidence of critical SEP and TCD changes was compared to preoperative carbon dioxide testing using Fisher's exact test with P < 0.05 considered significant. Postoperatively, neurologic state and carbon dioxide responsiveness were reexamined.

Results: Twelve patients showed impaired preoperative carbon dioxide reactivity on the side of operation, which improved markedly after surgery. The incidence of critical SEP changes in these cases (8.3%) was not significantly different from that in the remaining patients (14.8%). Critical SEP changes were significantly correlated with critical TCD changes (P < 0.0001).     

Effects of Halothane and Isoflurane on Carbon Monoxide-induced Relaxations in the Rat Aorta

Background: Halothane and isoflurane previously were reported to attenuate endothelium-derived relaxing factor/nitric oxide-mediated vasodilation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic similarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxations and cGMP formation in the isolated rat aorta.

Methods: isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 micro Meter). This procedure was repeated three times, with anesthetics delivered 10 min before the second procedure. Carbon monoxide responses of rings contracted with the same concentration of norepinephrine (10-8 M and 2 x 10-8 M) used in the anesthetic-exposed preparations also were examined. The concentrations of cGMP were determined in denuded rings using radioimmunoassay. The rings were treated with carbon monoxide (176 micro Meter, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM or 0.72 mM). To determine whether the sequence of anesthetic delivery influenced results, vascular rings pretreated with halothane were compared with non-pretreated rings.

Results: Carbon monoxide (26-176 micro Meter) caused a dose-dependent reduction of norepinephrine-induced tension, with a maximal relaxation of 1.51+/-0.07 g (85+/-7% of norepinephrine-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the highest concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 micro Meter) significantly increased cGMP content (+88.1+/-7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this increase (-70.7 +/-6.8% and -108.1+/-10.6%, respectively). When aortic rings and carbon monoxide were added simultaneously to Krebs solution equilibrated with halothane (0.72 mM), no inhibition of cGMP formation occurred.     

腹腔镜CO2气腹对机体免疫功能的影响

多数研究者认为CO2气腹对机体免疫功能有不同程度的影响,其机制一般认为系CO2扩散入细胞、循环系统,引起pH值降低,从而引起一系列免疫、生化功能的变化.另外,气腹高压力状态解除后,引起内脏缺血再灌注损伤,亦是影响内脏生理功能改变的原因之一.     

Effects of Sevoflurane on Excitatory Neurotransmission to Medullary Expiratory Neurons and on Phrenic Nerve Activity in a Decerebrate Dog Model

Background: Sevoflurane is a new volatile anesthetic with a pronounced respiratory depressant effect. Synaptic neurotransmission in canine expiratory bulbospinal neurons is mainly mediated by excitatory N-methyl-d-aspartatic acid (NMDA) receptor input and modulated by inhibitory [gamma]-aminobutyric acid type A (GABAA) receptors. The authors investigated the effect of sevoflurane on these mechanisms in decerebrate dogs.

Methods: Studies were performed in decerebrate, vagotomized, paralyzed and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 minimum alveolar concentration (MAC; 2.4%) sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the glutamate agonist NMDA and the GABAA receptor blocker bicuculline in a two-part protocol. First, complete blockade of the GABAAergic mechanism by bicuculline allowed differentiation between the effects of sevoflurane on overall GABAAergic inhibition and on overall glutamatergic excitation. In a second step, the neuronal response to exogenous NMDA was used to estimate sevoflurane's effect on postsynaptic glutamatergic neurotransmission.

Results: One minimum alveolar concentration sevoflurane depressed the spontaneous activity of 16 expiratory neurons by 36.7 +/- 22.4% (mean +/- SD). Overall glutamatergic excitation was depressed 19.5 +/- 16.2%, and GABAAergic inhibition was enhanced 18.7 +/- 20.6%. However, the postsynaptic response to exogenous NMDA was not significantly altered. In addition, 1 MAC sevoflurane depressed peak phrenic nerve activity by 61.8 +/- 17.7%.     

A Comparative Study of the Effects of Carbon Dioxide and Perfusion Rewarming on Limited Circulatory Occlusion During Surface Hypothermia, Under Halothane and Ether Anesthesia

Effects of the use of 5% CO(2) and surface-rewarming or perfusion- rewarming on safe total circulatory occlusion time, blood gases and carbohydrate metabolism were studied in 25 dogs subjected to surface hypothermia (18 C) and 30 minutes of circulatory occlusion under halothane or ether anesthesia. Under halothane anesthesia, all animals with 100% 0(2) developed motor disorders while one of five surface-rewarmed dogs and none of the perfusion-rewarmed dogs developed motor disorders with 5% CO(2). Under ether anesthesia, all were normal with either 100% 0(2) or when 5% CO(2) was added. Ventricular fibrillation occurred in one dog at 21C under halothane anesthesia with 5% CO(2). Blood lactate levels remained low through hypothermic procedures when 5% CO(2) was used. Perfusion rewarming had little effect on lactate levels. The use of 100% 0(2) resulted in slightly higher lactate levels, especially in the ether anesthetized group, but these levels still remained within the upper limit of the normal range. Significant differences in lactate levels between halothane and ether anesthesia suggest different mechanisms of tissue circulation and metabolism during hypothermia. Halothane anesthesia can be useful with the use of CO(2) for surface hypothermia with 30 minutes circulatory occlusion but is still inferior to ether.     

The Effects of Halothane on Cardiovascular Responses in the Neuraxis of Cats: Influence of Background Anesthetic State

Background: This study examined the effects of halothane on arterial pressure after central nervous system (CNS) pressor site stimulation in anesthetized cats, cats rendered unconscious by midcollicular transection, and conscious cats.

Methods: Two anesthetized groups and two nonanesthetized groups were used. Cats were anesthetized with either alpha-chloralose and urethane or pentobarbital. Nonanesthetized groups were cats with midcollicular transections or conscious cats with chronically implanted electrodes. Stimulating electrodes were placed into vasomotor areas of the hypothalamus (HYP), reticular formation (RF), and medulla, and arterial pressure responses to increasing stimulus currents were examined during different halothane concentrations. Two groups of cats were also anesthetized with either pentobarbital or urethane and underwent bilateral carotid artery occlusion.

Results: Stimulation at each CNS site produced increases in arterial pressure and heart rate. Halothane attenuated pressor responses evoked by stimulation of all loci in all groups of cats. The inhibition by halothane on these cardiovascular responses was greatest at HYP and RF sites, while the medulla was more resistant to the effects of halothane in the anesthetized animals. Midcollicular transection decreased this medullary resistance. The inhibition of pressor responses by halothane was also greater in pentobarbital- than chloralose urethane-anesthetized animals. In contrast, pressor responses elicited by bilateral carotid occlusion were attenuated by halothane similarly in both anesthetic groups. Reticular formation stimulation in conscious animals resulted in "alerting responses" in addition to pressor effects, both of which were attenuated by halothane.     

Halothane and Enflurane Attenuate Pulmonary Vasodilation Mediated by Adenosine Triphosphate-sensitive Potassium Channels Compared to the Conscious State

Background: Adenosine triphosphate (ATP)-sensitive potassium (K sup +ATP) channels play an important role in pulmonary vasoregulation. However, the effects of volatile anesthetics on K sup +ATP channel-mediated pulmonary vasoregulation have not been elucidated. The purpose of the present study was to investigate the effects of halothane and enflurane anesthesia on the pulmonary vasodilator response to the selective K sup +ATP channel agonist lemakalim (BRL38227) compared with that measured in the conscious state. The authors also investigated the extent to which endogenous neurohumoral vasoconstrictor mechanisms modulate the vasodilator response to K sup +ATP channel activation.

Method: Nineteen conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. After preconstriction with the thromboxane analog, U46619 (9,11-dideoxy-11alpha, 9alpha -epoxymethano-prostaglandin F2alpha), the pulmonary vascular dose-response relationship for the K sup +ATP agonist lemakalim was assessed in the conscious and halothane-anesthetized states and also in the conscious and enflurane-anesthetized states. This protocol was repeated in conscious and halothane-anesthetized dogs after combined neurohumoral block with antagonists of sympathetic alpha1 adrenoreceptors, arginine vasopressin V1 -receptors, and angiotensin II receptors. The effect of the K sup +ATP antagonist glybenclamide on the baseline LPQ relationship and on the lemakalim dose-response relationship also was assessed in conscious dogs.

Results: Compared with the conscious state, halothane, enflurane and glybenclamide had no net effect on the baseline LPQ relationship. In contrast, halothane and enflurane attenuated (P < 0.05) the pulmonary vasodilator response to lemakalim compared with the conscious state. Glybenclamide also caused a rightward shift (P < 0.05) in the lemakalim dose-response relationship. Combined neurohumoral block did not modulate the vasodilator response to lemakalim in the conscious state. The halothane-induced attenuation of the vasodilator response to lemakalim was apparent after combined neurohumoral block.