Bupivacaine does not suppress cardiac sympathetic nerve activity during halothane anesthesia in the cat

Background: The finding that IV lidocaine suppresses cardiac sympathetic nerve activity during 1 MAC halothane, but not during 2 MAC or 3 MAC halothane, suggests that the neurally mediated circulatory effects of IV local anesthetics may vary with background autonomic activity. This study aimed to compare the effects of IV lidocaine and bupivacaine on cardiac sympathetic nerve activity (CSNA) during normal and high levels of CSNA.
Methods: Cats were anesthetized with halothane and allocated to three groups. In groups I-L and I-B, sympathetic hyperactivity was induced by electrical stimulation of the posterior hypothala-mus. CSNA, heart rate and mean arterial pressure were then measured before and after administration of lidocaine 2 mgkg BW^-l IV (Group I-L, n=7) or bupivacaine 0.5 mgkg BW^-1 IV (Group I-B, n=7) during 1% halothane anesthesia. In Group II (n=7), following administration of bupivacaine 0.5 mgkg BW^-1 IV, CSNA, sinus cycle length (SCL), and subintervals of atrio-ventricular conduction time (A-H, H-V, and H-S) at pacing were measured during O.8%, 1.6% and 2.4% halothane anesthesia without sympathetic hyperactivity.
Results: Lidocaine suppressed CSNA hyperactivity and tachycardia significantly in Group I-L, but bupivacaine did not do so in Group I-B. In Group 11, bupivacaine did not affect CSNA at any concentrations of halothane, but lengthened SCL, A-H, H-V and H-S intervals significantly at each concentration of halothane.
Conclusions: We conclude that IV bupivacaine, unlike IV lidocaine, does not suppress CSNA during either normal or high CSNA under halothane anesthesia although IV bupivacaine has stronger depressive effects on cardiac conduction than does IV lidocaine during deep halothane anesthesia.     

Effects of halothane and isoflurane anesthesia on sympathetic adrenal nerve responses to carbon dioxide challenge in rats

We studied the influence of two volatile anesthetics, halothane and isoflurane, on the circulatory and sympathetic nerve responses to carbon dioxide (9% CO₂) in rats.Systolic blood pressure was depressed throughout the CO₂ challenge and after an initial reduction, a gradual increase was observed in heart rate. Sympathetic adrenal nerve action potentials (SANA) significantly increased in contrast to negative responses in the circulatory functions. SANA responses against time were trapezoid in shape. There were no significant differences in SANA responses between 1% (1 MAC) and 1.5% (1.5 MAC) halothane groups, nor between 1.4% (1 MAC) and 2% (1.5 MAC) isoflurane groups. Halothane and isoflurane, therefore, did not produce dose-dependent effects on sympathetic response to hypercapnia within these concentrations. The maximum changes in SANA from the baseline values were 110% and 40% for the halothane and isoflurane groups, respectively.The sympathetic reflex response to hyperacapnia was retained at 1.5 MAC for both anesthetics, though isoflurane depressed these responses more markedly than halothane.Our results suggest that halothane is a more preferable anesthetic than isoflurane when viewed from the standpoint of preservation of sympathetic nerve response in such undesirable situations as severe hypercapnia occurring during anesthesia.(Amagasa S, Takahashi T, Takaoka S, et al.: Effects of halothane and isoflurane anesthesia on sympathetic adrenal nerve responses to carbon dioxide challenge in rats. J Anesth 7: 454–461, 1993)     

Effects of sevoflurane anesthesia and baroreceptor function on renal sympathetic nerve activity in rats

Effects of sevoflurane at various anesthetic levels on renal sympathetic nerve activity (RSNA), blood pressure and heart rate were studied in rats. Changes of these parameters produced reflexly by noxious cutaneous stimulation and effects of baroreceptor on them were also studied. Under the resting condition by increasing inspired sevoflurane concentration decreased blood pressure and heart rate dose-dependently, whereas, RSNA was unchanged. But, without the baroreceptor function, RSNA decreased and the change paralleled with changes of blood pressure and heart rate. When noxious stimulation was applied on a hindpaw by pinching, blood pressure, heart rate and RSNA all increased at sevoflurane 2.1%. The responses of these parameters were attenuated at 3.1% and almost disappeared at 4.2% of sevoflurane. However, without the baroreceptor function, RSNA increased even at 3.2 and 4.2% as at 2.1% of sevoflurane. It is suggested that under sevoflurane anesthesia, baroreceptor system has strong influences on RSNA even under sevoflurane 4.2% (2MAC).     

Venomotor changes caused by halothane acting on the sympathetic nerves.

Experiments were performed to determine whether depression of venomotor responses with halothane results from interference with sympathetic activation or from an effect on venous smooth muscle cells. Changes in isometric tension of isolated canine saphenous-vein strips were recorded. Adrenergic activation was achieved by transmural electrical stimulation, by addition of tyramine, and by addition of morepinephrine. Halothane (0.5 to 3 per cent) did not significantly alter basal tension. It lessened the reaction of the veins to electrical stimulation but not their response to norepinephrine; it increased the response to tyramine. Since the responses to norepinephrine and tyramine were not decreased, halothane appears to act on the nerve terminal to prevent release of neurotransmitter associated with nerve-terminal depolarization. Thus, halothane causes inhibition of electrically induced venoconstriction in cutaneous veins, probably by interfering with the release of norepinephrine from nerve terminals rather than by an inhibitory effect on the smooth muscle cells.     

Modulation of renal sympathetic nerve activity during pneumoperitoneum in rats

To examine neural control of renal function during pneumoperitoneum, renal sympathetic nerve activity (RSNA) was measured in pentobarbital-anesthetized rats that had their entire nervous system intact or that had undergone lower thoracic dorsal rhizotomy or abdominal vagotomy. During pneumoperitoneum with intraabdominal pressure (IAP) of 10 mmHg, the mean arterial pressure did not change, but central venous pressure increased by 10 mmHg in all groups. In intact rats, the RSNA increased to 285 +/- 22% during pneumoperitoneum and gradually recovered after release of the insufflation. The RSNA responses decreased during pneumoperitoneum in rats with dorsal rhizotomy or vagotomy compared to responses in intact rats. In intact rats the urine volume and Na+ excretion decreased during pneumoperitoneum and increased just after insufflation release. Dorsal rhizotomy, vagotomy, or renal denervation did not alter the antidiuretic and antinatriuretic responses during pneumoperitoneum; however, diuretic and natriuretic responses were completely abolished by either of these denervations following insufflation release. These results suggest that oliguria during pneumoperitoneum was not due to neural control of renal function but probably to a mechanical influence induced by the elevated IAP. On the other hand, diuretic and natriuretic responses after insufflation release were thought to be a neurally mediated response.     

Denervation of the cervical sympathetic nerve inhibited the splenic natural killer cell activity by modulation of the splenic sympathetic nerve activities in rats]

It is known that the splenic natural killer cell (NK) activity 4 weeks after unilateral resection of the cervical sympathetic nerve (csn) is significantly lower than that after sham operation in rats. To investigate the role of the splenic sympathetic nerve, the splenic NK activity after csn was compared in the control animals (n = 9) and the splenic sympathetic nerve denervated animals (n = 8). The splenic NK activity in control group was reduced significantly after csn, whereas that in splenic nerve denervated group did not reveal significant change after csn. The results suggest that the reduction of the splenic NK activity after csn is induced through the modulation of the splenic sympathetic nerve activities.     

A case of ventricular fibrillation during halothane anesthesia caused by eye drops

A case is described of a 22 years old, high risk female patient who underwent an ophtalmological operation. She developed a ventricular fibrillation during halothane anesthesia by an excess of adrenaline (epinephrine) administered in eye drops.     

High thoracic epidural anesthesia does not inhibit sympathetic nerve activity in the lower extremities.

BACKGROUND: Sympathetic nerve activity was recorded in the leg during high thoracic epidural anesthesia with a segmental sensory blockade of the upper thoracic dermatomes to test the hypothesis that the sympathetic blockade accompanying thoracic epidural anesthesia includes caudal parts of the sympathetic nervous system. METHODS: Experiments were performed on 10 patients scheduled for thoracotomy. An epidural catheter was inserted at the T3-T4 or T4-T5 interspace. In the main protocol (seven patients), blood pressure, heart rate, and skin temperature (big toe, thumb) were continuously monitored, and multiunit postganglionic sympathetic nerve activity was recorded with a tungsten microelectrode in a muscle-innervating fascicle of the peroneal nerve. After baseline data collection, muscle sympathetic nerve activity was recorded for an additional 45-min period after epidural injection of 4-6 ml bupivacaine, 5 mg/ml. In an additional three patients, the effects of thoracic epidural anesthesia on skin-innervating sympathetic nerve activity were qualitatively assessed. RESULTS: Activation of thoracic epidural anesthesia caused no significant changes in peroneal muscle sympathetic nerve activity (n = 7), blood pressure, or heart rate. Skin temperature increased significantly in the hand 15 min after activation of the blockade, from 32.7 +/- 2.4 degrees C to 34.4 +/- 1.5 degrees C (mean +/- SD), whereas no changes were observed in foot temperature. The sensory blockade extended from T1 (C4-T2) to T8 (T6-T11). CONCLUSIONS: A high thoracic epidural anesthesia with adequate sensory blockade of upper thoracic dermatomes may be achieved without blockade of caudal parts of the sympathetic nervous system. This finding differs from that of earlier studies that used indirect methods to evaluate changes in sympathetic nerve activity.     

Modifications by halothane of responses to acute hypoxia in systemic vascular capacitance, resistance, and sympathetic nerve activity in dogs

To examine the effects of halothane on segmental vascular responses to hypoxia, we used cardiopulmonary bypass with venous outflow divided into three compartments (splanchnic, coronary, and "other") in dogs anesthetized with pentobarbital sodium. The reservoir volume changes represented the inverted changes in systemic blood volume (SBV). In addition, sympathetic efferent nerve activity (SENA) was simultaneously recorded from the ventral ansa subclavian nerve. Experiments were done in two groups: severe hypoxia (PO2 of 19 mm Hg) and moderate hypoxia (PO2 of 50 mm Hg). Hypoxia provoked a significant decrease in SBV of 22.3 +/- 3.1 mL/kg and 10.5 +/- 1.6 mL/kg during severe and moderate hypoxia, respectively. Two percent end-tidal halothane attenuated the decrease in SBV to 10.3 +/- 1.3 mL/kg during severe hypoxia, and 1% halothane attenuated the decrease to 3.7 +/- 1.4 mL/kg during moderate hypoxia. Subsequent chemoreceptor denervation in the presence of 1% halothane completely abolished the moderate hypoxia-induced decrease in SBV. In the presence of halothane, vascular resistance during hypoxia was significantly less than that during control conditions. Sympathetic efferent nerve activity increased significantly during severe and moderate hypoxia by about 180% and 55%, respectively. During severe hypoxia, halothane did not cause any change in the response of SENA, whereas during moderate hypoxia, halothane tended to decrease SENA, but not significantly, and subsequent chemoreceptor denervation completely abolished the increase in SENA. Coronary resistance showed a hypoxia-induced reduction that was not influenced by halothane. These results suggest that acute hypoxia causes a decrease in SBV dependent on the severity of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of catecholamine depletion on increased blood pressure lability upon emergence from halothane anesthesia in rats: the role of sympathetic nervous activity in postanesthetic circulatory instability

PURPOSE: Circulatory instability is often observed upon emergence from general anesthesia. The increased blood pressure (BP) lability has been associated with poor clinical outcome. However, its underlying mechanisms are not fully understood. Thus, we investigated a possible role of the sympathetic nervous system (SNS) and cardiac baroreflex in the increased pressure lability observed upon emergence from general anesthesia. METHODS: Male rats (n = 16) were allocated to two groups, i.e., (1) a control group (n = 8) and (2) an alpha-methylparatyrosine (alpha-MPT; an inhibitor of tyrosine hydroxylase)-treated group (n = 8). In the alpha-MPT-treated group, in order to deplete catecholamines both in the central nervous system and in the SNS, alpha-MPT (300 mg x kg(-1)) was injected intraperitoneally (i.p.), administered twice, 4 and 2 h before halothane discontinuation (total dose, 600 mg x kg(-1) i.p.). In the control group, saline was administered at identical time-points. Systolic BP (SBP) lability was evaluated on a beat-by-beat basis, using the coefficient of variation of SBP, and the occurrence of slow and rapid rises in SBP and their amplitude, while the cardiac baroreflex slope was calculated using the "sequences" method. RESULTS: In the control group, heart rate, SBP, and the three indices of BP lability (i.e., the 3 indices of BP lability are: coefficient of variation of SBP, number of slow and rapid rises in pressure, amplitude of slow and rapid rises in pressure) all increased upon emergence from anesthesia (P < 0.05). Such increases were all blunted in the alpha-MPT-treated group, with the increases in the three indices of BP lability almost entirely suppressed (P < 0.05). The cardiac baroreflex slope was similarly decreased in both groups (P < 0.05). CONCLUSION: The postanesthetic increase in pressure lability seems largely a consequence of increased sympathetic activity, irrespective of any change in cardiac baroreflex sensitivity.     

The absence of antagonism by naloxone during halothane/nitrous oxide anaesthesia in man

Sixteen patients were studied to determine if naloxone could be shown to affect general anaesthesia with halothane and oxygen or nitrous oxide and oxygen with halothane. Changes in blood pressure, pulse rate, electroencephalogram and evidence of physical response were observed. The end-tidal halothane and carbon dioxide were controlled. The temperature and blood gases were held constant, as was the degree of neuromuscular blockade. Naloxone 1.2 mg was administered during general anaesthesia with either halothane in oxygen or halothane with nitrous oxide to 16 patients who were premedicated without a narcotic. No significant responses were recorded.     

Effects of epidural anesthesia on sympathetic nerve discharge to the skin

Direct intraneural recordings of skin sympathetic activity (SSA) were performed to determine the magnitude of blockade of sympathetic fibers to the lower extremities during epidural anesthesia. Lumbar epidural catheters were inserted in nine volunteers. Multiunit postganglionic sympathetic activity was recorded in a skin fascicle of the peroneal nerve before and after injection of 4 ml of mepivacaine 2% epidurally, followed by an additional 12-16 ml after 5 min. Arousal stimuli such as sudden loud noises and noxious electrical skin stimulation were used to elicit transient sympathetic activation. Epidural anesthesia with upper level of sensory blockade at T4-T8 (n = 7) completely blocked spontaneous SSA and no detectable skin sympathetic activity could be provoked by arousal stimuli later than 14 min after the test dose. Sympathetic blockade was accompanied by marked increases in foot skin blood flow and loss of skin resistance responses to arousal. Epidural anesthesia with sensory blockade up to T10-11 (n = 2) only produced a partial sympathetic blockade. The result shows that epidural anesthesia with sensory blockade at T8 or above is equally as effective as injections of local anesthetics directly at postganglionic nerve fibers or ganglionic blockade in producing a complete sympathetic blockade of intraneurally recorded SSA. This neural blockade was paralleled by skin vasodilatation and a loss of sudomotor responses in the foot.     

Effects of halothane and enflurane anesthesia on sympathetic beta-adrenoreceptor-mediated pulmonary vasodilation in chronically instrumented dogs

BACKGROUND: The authors previously reported that the pulmonary vasodilator response to the sympathetic beta-adrenoreceptor agonist isoproterenol is potentiated during isoflurane anesthesia compared with the conscious state. In the present in vivo study, the authors tested the hypothesis that halothane and enflurane anesthesia also enhance sympathetic beta adrenoreceptor-mediated pulmonary vasodilation. The authors also used the membrane-permeable analog of cyclic adenosine monophosphate (cAMP), dibutyryl cAMP, to help delineate the site in the signaling pathway for an anesthesia-induced effect on beta adrenoreceptor-mediated pulmonary vasodilation. METHODS: Mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were measured on separate days in the conscious, halothane-, and enflurane-anesthetized states at baseline, after preconstriction with the thromboxane analog U46619, and during the cumulative intravenous administration of isoproterenol. LPQ plots were also measured in conscious, halothane-, and isoflurane-anesthetized dogs after U46619 preconstriction and during the cumulative intravenous administration of dibutyryl cAMP. RESULTS: Compared with the conscious state, neither halothane nor enflurane had an effect on the baseline LPQ relationship. The magnitude of the pulmonary vasodilator response to isoproterenol was potentiated during halothane anesthesia but unchanged during enflurane anesthesia. The pulmonary vasodilator response to dibutyryl cAMP was not altered during either halothane or isoflurane anesthesia compared with the conscious state. CONCLUSIONS: These results indicate that inhalational anesthetic agents can exert differential effects on the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation. The potentiated vasodilator response observed during halothane and isoflurane anesthesia is the result of effects proximal to cAMP accumulation in the beta-adrenoreceptor signaling pathway.     

Effects of angiotensin II receptor antagonist on insulin sensitivity and sympathetic activity in spontaneously hypertensive rats

Although angiotensin AT1 receptor antagonist(AT1 A) improves insulin sensitivity in insulin resistant models, its effect on spontaneously hypertensive rats(SHR) has not been elucidated. We investigated the effects of AT1 A, candesartan on insulin sensitivity in SHR/Izm and the role of sympathetic activity in its mechanism. In 9-week-old SHR/Izm, candesartan(10 mg/kg/day) was given orally for 5 days. A control group received vehicle. On the 6th day, mean arterial pressure (MAP), heart rate(HR), plasma norepinephrine (PNE), plasma epinephrine(PE) and plasma dopaminc(PDA) were measured in both groups (n = 11 in each group). In the separate groups of rats, fasting blood glucose (FBG), serum sodium, serum potassium and insulin sensitivity by steady state blood glucose (SSBG) were assessed (n = 16 in the Candesartan group and n = 8 in the Control group). MAP and SSBG were significantly lower in the Candesartan group (117 +/- 2 mmHg and 138 +/- 5 mg/dl) than those in the Control group(155 +/- 6 mmHg and 164 +/- 10 mg/dl). Body weight, HR, FBG, PNE, PE, PDA, sodium and potassium were the same between the groups. In conclusion, since AT1 A, candesartal lowers blood pressure and improves insulin sensitivity irrespective of sympathetic activity in SHR/Izm, it is useful in treating hypertension associated with insulin resistance.