Chikuni Taneyama

In rabbits, landiolol, a new ultra-short-acting β-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol

PurposeTo compare the cardiovascular and sympathetic effects of a new ultra-short-acting, highly cardioselective β-blocker, landiolol, with esmolol, using anin vivo rabbit model.MethodsDifferent bolus doses of landiolol (0.3, 1.0, 3.0 and 10.0 mg·kg−1) or esmolol (0.5, 1.5 and 5.0 mg·kg−1) were given intravenously, and the effects on heart rate (HR) mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were compared.ResultsBoth landiolol and esmolol produced a dose-dependent decrease in HR. The maximum percent reductions of HR were similar with landiolol 3 mg·kg−1 and esmolol 5 mg·kg−1 (−14.0 ± 0.9% and −13.9 ± 1.4%, mean ± SE, respectively). HR decreased more rapidly with landiolol than with esmolol. Esmolol produced a dose-dependent decrease in MAP that was not observed with landiolol. The percent maximum reduction of MAP was-38.2 ± 3.2% with esmolol 5 mg·kg−1. RSNA increased in a dose-dependent fashion with esmolol, but no changes were noted with landiolol.ConclusionThese results suggest that, in rabbits, landiolol has slightly more potent negative chronotropic action than esmolol with significantly less effects on blood pressure.RésuméObjectifComparer les effets cardiovasculares et sympathiques d’un nouveau β-bloquant à action très brève et hautement cardiosélectif le landiolol, avec ceux de lésmolol, en utilisant un modèle in vivo chez le lapin.MéthodeOn a administré différents bolus Intraveineux de landiolol (0,3 ; 1,0 ; 3,0 et 10,0 mg·kg−1) ou désmolol (0,5 ; 1,5 et 5,0 mg·kg−1) et comparé les effets sur la fréquence cardiaque (FC), la tension artérielle moyenne (TAM) et l’activité sympathique rénale (ASR).RésultatsLe landiolol et l’esmolol ont produit une baisse de la FC proportionnelle à la dose. Les réductions maximales de FC ont été similaires avec 3 mg·kg−1 de landiolol et 5 mg·kg−1 désmolol (−14,0 ± 0,9 % et −13,9 ± 1,4 %, moyenne ± écart type, respectivement). La FC a baissé plus rapidement avec le landiolol qu’avec l’esmolol. L’esmolol, contrairement au landiolol, a produit une baisse de la TAM proportionnelle à la dose. La réduction maximale de TAM a été de −38,2 ± 3,2 % avec 5 mg·kg−1 désmolol. L’ASR a augmenté selon la dose avec l’esmolol, mais aucun changement n’a été observé avec le landiolol.ConclusionCes résultats suggèrent que, chez les lapins, le landiolol présente une action chronotropique négative plus puissante que l’esmolol et des effets significativement plus faibles sur la tension artérielle.

Effects of fentanyl, diazepam, and the combination of both on arterial baroreflex and sympathetic nerve activity in intact and baro-denervated dogs.

The combination of fentanyl and diazepam significantly decreases systemic vascular resistance and blood pressure. We attempted to elucidate the reason the combination of these drugs can reduce blood pressure. In α-chloralose-anesthetized dogs, we investigated the effects of fentanyl and diazepam on mean arterial pressure (MAP) and arterial baroreflex control of renal sympathetic nerve activity (RSNA) in both intact (Study 1) and baroreflex-denervated dogs (Study 2). Study 1 included five dogs that received fentanyl 10 μg/kg followed by diazepam 0.4 mg/kg after a 10-min interval. Five more received both drugs in reversed sequence. The arterial baroreflex depressor test was performed with sodium nitroprusside before and after administration of each drug. Sensitivity of arterial baroreflex was examined by using the ratio of maximum increase of RSNA to maximum decrease of MAP (δRSNA/δMAP). RSNA and MAP significantly decreased only after both drugs had been administered (P < 0.05). Fentanyl alone did not attenuate arterial baroreflex sensitivity. Diazepam after fentanyl and diazepam alone attenuated baroreflex sensitivity to the same extent (P < 0.05). Study 2 comprised 14 dogs that underwent further surgical preparation of bilateral carotid sinus, aortic, and vagal nerve denervations. Seven received fentanyl, 5 and 10 μ g/kg, and the other seven received diazepam, a total of 0.4 mg/kg. Fentanyl decreased both RSNA and MAP. Diazepam decreased only MAP significantly. The results indicate that fentanyl decreases mainly sympathetic outflow, whereas diazepam attenuates arterial baroreflex. We conclude that these combined effects of fentanyl and diazepam significantly decrease arterial blood pressure.

Attenuation of Arterial Baroreceptor Reflex Response to Acute Hypovolemia During Induced Hypotension

Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1 was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1 (P less than 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 +/- 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (delta RSNA/delta MAP, delta HR/delta MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 +/- 5 mmHg of MAP), delta RSNA/delta MAP and delta HR/delta MAP in response to rapid blood loss were significantly greater with PGE1 than those with SNP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of ketamine on renal sympathetic nerve activity and phrenic nerve activity in rabbits (with vagotomy) with and without afferent inputs from peripheral receptors

One reason for the reported conflicting results of the effect of ketamine on hemodynamics and respiration may be variations in afferent inputs from peripheral receptors to the central nervous system.In order to evaluate unmasked direct effects of ketamine on sympathetic nerve and phrenic nerve outflow, totally deafferented (involving vagus, sinus nerve, aortic depressor nerve) rabbits (n = 18), rabbits with vagotomy (n = 21), and neuraxis-intact rabbits (n = 6) were used in this study. The animals were anesthetized with urethane and mechanically ventilated. Ketamine 0.5, 1, or 2 mg/kg was injected intravenously and mean arterial pressure (MAP), heart rate (HR), and integrated renal sympathetic nerve and phrenic nerve activity (IRSNA, IPNA) were recorded before, and 1, 2, 3, 5, and 10 min after injection. MAP and IRSNA were significantly decreased, even by the smallest dose of ketamine, in the totally deafferented group. IPNA was decreased by the largest dose of ketamine only in the totally deafferented group. On the other hand, spontaneous respiratory frequency was decreased in the totally deafferented and vagotomy groups, but more so in the totally deafferented group. In the neuraxis-intact group, the only significant change with the largest dose of ketamine, 2 mg/kg was a slight increase in HR. We conclude that ketamine can suppress vasomotor and respiratory centers directly, and that the suppression is counterbalanced by afferent inputs from peripheral receptors. (Anesth Analg 1996;82:362-7)

Fractal Cardiovascular Dynamics and Baroreflex Sensitivity After Stellate Ganglion Block

BACKGROUND: It has been shown that stellate ganglion block can attenuate baroreflex sensitivity. Our primary purpose in this study was to determine whether fractal dynamics (dynamic change of self-similar fluctuation patterns) of not only heart rate but also systolic blood pressure variability are involved in attenuation of baroreflex sensitivity after stellate ganglion block. METHODS: Sixteen young, healthy volunteers entered the study. Spectral analysis of heart rate and systolic blood pressure variability was performed before and 30, 60, 90, and 120 min after either right or left stellate ganglion block, separated by a 1 to 1½-mo interval, with 6 mL of 1% mepivacaine. Shortly after each spectral analysis, baroreflex sensitivity was assessed with the head-up tilt test. RESULTS: Baroreflex sensitivity, assessed by the head-up tilt test, was significantly attenuated at 30 min after either right or left stellate ganglion block (1.26 ± 0.18 to 0.46 ± 0.08 bpm/mm Hg, P < 0.05 and 1.17 ± 0.35 to 0.51 ± 0.13 bpm/min, P < 0.01, respectively). Fractal slopes reflecting the degree of self-similarity of fluctuations were significantly increased at 30 min after either right or left stellate ganglion block (right stellate ganglion block—heart rate; −1.08 ± 0.30 to −1.62 ± 0.22, P < 0.01; right stellate ganglion block—systolic blood pressure; −1.30 ± 0.80 to −2.40 ± 0.80, P < 0.05; left stellate ganglion block—systolic blood pressure; −1.20 ± 0.40 to −2.13 ± 0.50, P < 0.05). Fractal slope did not change after left stellate ganglion block with heart rate variability analysis. CONCLUSIONS: Loss of complexity (status of being complex behavior) of both heart rate and systolic blood pressure variability, indicated by increased fractal slopes, is one mechanism in attenuating baroreflex sensitivity after stellate ganglion block.

Patients with complex regional pain syndrome type 1: fractal dynamics of heart rate variability and baroreflex evaluations.

Objective:Patients with complex regional pain syndrome type 1 might have disturbed autonomic function and increased heart rate fractal dynamics with a resultant impaired baroreflex sensitivity (BRS). We hypothesized that these parameters of impaired cardiovascular regulation might improve with a reduction of pain intensity. Methods:Ten patients and 10 healthy volunteers entered the study. Power spectral analysis of heart rate (HR) variability was performed by the maximum entropy method. Ratios of low-frequency domain to high-frequency domain (LF/HF) and a fractal slope, the slope of a regression line of power spectral density (1/f&bgr;), were calculated. BRS was assessed with a head-up tilt test. When the visual analogue scale scores decreased to ≦20 mm during treatments, those measurements were repeated. Results:LF/HF and steepness of fractal slope before treatments decreased significantly during treatments when visual analogue scale was ≦20 mm (2.23±0.68 to 1.30±0.45, P=0.005 and −1.90±0.35 to −1.16±0.14, P=0.00032, respectively). BRS before treatments was low (−0.28±0.27 bpm/mm Hg) as compared with BRS of volunteers but significantly improved to −0.62±0.48 bpm/mm Hg during treatments (P=0.032). Conclusions:Increased LF/HF ratios likely indicate that patients had an imbalance of the autonomic nervous system. The increased fractal slope suggests that patients developed strong self-similarity of HR variability. The highly predictable HR variability leads to impaired hemodynamic homeostasis, resulting in decreased BRS. The impaired cardiovascular regulation improved with a reduction of pain. Thus, spectral analysis of HR variability may be useful objectively to follow complex regional pain syndrome type 1 patients, not only for pain management but also for the status of cardiovascular stability.

Surgical stress attenuates reflex heart rate response to hypotension

PurposeThe baroreflex-mediated increase in heart rate (HR) in response to acute reduction of systolic blood pressure (SBP) was studied in order to assess whether the changes in arterial baroreflex sensitivity depend on the intensity of surgical stress, and location of visceral and somatic stimulation during surgery.MethodsPatients were divided into visceral stimulation groups [upper (n = 30) and lower (n = 30) abdominal surgery] and somatic stimulation groups [upper (n = 25) and lower (n = 25) limbs, and chest wall (n = 25) surgery]. Acute hypotension as a baroreflex depressor test was induced by prostaglandin E1 (PGE1) 10 min before surgical incision (control) and during surgical manipulation under isoflurane-N2O anaesthesia or isoflurane-N2O-fentanyl anaesthesia. Plasma level of ACTH was measured in an additional 40 patients who underwent upper abdominal surgery.ResultsDuring upper abdominal surgery, the heart rate baroreflex sensitivity (ΔHR/ΔSBP) was depressed from-0.47 ± 0.05 (control) to -0.01 ± 0.04 (P < 0.05). The reflex heart rate baroreflex sensitivity remained unchanged and was similar among the remaining groups of patients. The concentration of ACTH increased from 12.5 ± 1.0 (control) to 343 ± 78.6 pg·ml−1 (P < 0.05) with isoflurane-N2O anaesthesia but did not change with isoflurane-N2O-fentanyl anaesthesia during upper abdominal surgery.ConclusionUpper abdominal surgery is associated with the most stressful stimulation to attenuate heart rate baroreflex sensitivity. Integrity of the baroreflex can be preserved by adding opioids to supplement inhalation anaesthesia.RésuméObjectifLaugmentation de la fréquence cardiaque (FC) à médiation baroréflexe en réponse à une diminution soudaine de la tension artérielle systolique (TAS) a été étudiée dans le but d’évaluer si les changements de sensibilité artérielle baroréflexe dépendent de l’intensité du stress chirurgical et du siège de la stimulation viscérale et somatique pendant la chirurgie.MéthodeLes patients ont été répartis en différents groupes: selon une stimulation viscérale [chirurgie abdominale haute (n = 30) et basse (n = 30)] et selon une stimulation somatique [chirurgie des membres supérieurs (n =25) et inférieurs (n = 25) ou chirurgie de la paroi thoracique (n = 25)]. Une hypotension soudaine, sous forme de test dépresseur baroréflexe, a été induite par la prostaglandine E1 (PGE1) 10 min avant l’incision chirurgicale (groupe témoin) et pendant la manipulation chirurgicale sous anesthésie avec isoflurane N2O ou sous anesthésie avec isoflurane N2O et fentanyl. Le niveau plasmatique d’ACTH a été mesuré chez 40 patients additionnels admis pour une chirurgie abdominale haute.RésultatsPendant la chirurgie abdominale haute, la sensibilité de la fréquence cardiaque baroréflexe (ΔFC/ ΔTAS) était abaissée de -0,47 ± 0,05 (témoin) à -0,01 ± 0,04 (P < 0,05). La sensibilité réflexe de la fréquence cardiaque baroréflexe n’a pas changé et était similaire parmi les autres groupes de patients. La concentration d’ACTH a augmenté de 12,5 ± 1,0 (témoin) à 343 ± 78,6 pg·ml−1 (P < 0,05) avec l’anesthésie à l’isoflurane N2O mais n’a pas changé avec l’anesthésie à l’isoflurane N2O et au fentanyl pendant la chirurgie abdominale haute.ConclusionLa chirurgie abdominale haute est associée à la stimulation la plus stressante pour atténuer la sensibilité de la fréquence cardiaque baroréflexe. Lintégrité du baroréflexe peut être préservée en ajoutant des opioïdes pour compléter l’anesthésie par inhalation.

Vagal involvement in the action of exogenous adenosine triphosphate on reflex renal sympathetic nerve activity.

The reason why adenine compounds when used as hypotensive agents are devoid of significant reflex sympathetic activity, such as rebound hypertension and tachycardia, is not clearly understood. This study, performed on α-chloralose-anesthetized dogs, examined, first, the effects of adenosine triphosphate (ATP) and adenosine as compared with those of sodium nitroprusside on efferent renal sympathetic nerve activity (RSNA), as an indicator of general reflex sympathetic activity, and second, whether vagal involvement could be demonstrated in the action of ATP and adenosine on RSNA. Renal sympathetic nerve activity increased progressively with increasing doses of sodium nitroprusside (5, 10, and 20 μg/kg) and adenosine (0.5, 2.0, and 4.0 mg/kg), whereas ATP suppressed RSNA at 2.0 and 4.0 mg/kg. High doses of ATP and adenosine (4.0 mg/kg) were injected info intact (n = 7) and vagotomized dogs (n = 7). Both ATP and adenosine induced rapid onset of hypotension without rebound hypertension and tachycardia. After vagotomy, the attenuation of RSNA by ATP was completely abolished and rebound hypertension and tachycardia were observed. Vagotomy did not alter the effect of adenosine on RSNA. It is concluded that ATP-induced hypotension is associated with attenuation of sympathetic efferent nerve activity mediated through vagal afferent pathways. Vagal afferent impulses are thought to be one of the mechanisms that inhibit reflex sympathetic activities, such as rebound hypertension after ATP-induced hypotension. The mechanisms by which adenosine inhibits reflex sympathetic activity are not, however, secondary to vagal afferent involvement and must be multifactorial.

Mixtures of sodium nitroprusside and trimethaphan for induction of hypotension.

A mixture of sodium nitroprusside (SNP) and trimethaphan, empirical 1:10 weight ratio, has been advocated to decrease untoward side effects of SNP when used to induce hypotension during anesthesia and operation. The purpose of this study was to investigate the effects of various ratios of mixtures of SNP and trimethaphan on heart rate (HR), renal sympathetic nerve activity (RSNA), and renal artery blood flow to find the best ratio of SNP and trimethaphan for producing induced hypotension. Five mixtures with different ratios of SNP and trimethaphan, as well as each drug alone, were given intravenously to mongrel dogs in amounts adequate to achieve a stable mean arterial blood pressure of 75 ± 5 mm Hg. Sodium nitroprusside alone significantly increased HR (163% ± 14.5%) and RSNA (222% ± 24%). Trimethaphan alone significantly decreased RSNA (11.6% ± 4.5%). There were significant positive correlations between SNP-to-trimethaphan ratios and percent changes in HR (r2 = 0.301, P < 0.01) and in RSNA (r2 = 0.648, P < 0.01). Renal artery blood flow was well maintained with all ratios. Sodium nitroprusside and trimethaphan interacted synergistically to produce hypotension. However, they antagonize each other in their effects on arterial baroreflex-mediated changes in HR and RSNA. According to linear regression lines, HR changed least with a SNP-to-trimethaphan ratio of 1:5, and RSNA changed least with SNP-to-trimethaphan ratios of 1:2.5 and 1:5. Our results indicate that mixtures of SNP and trimethaphan in ratios of approximately 1:2.5 to 1:5 may produce induced hypotension with stable reflex sympathetic nerve activity.

Continuous positive airway pressure oxygenation during one-lung ventilation with 50% nitrous oxide and isoflurane in oxygen

Application of continuous positive airway pressure (CPAP) with an inspired oxygen concentration (FI02) of 1.0 to the nondependent lung has been reported to be an effective method of improving Pa02 during one-lung ventilation for elective thoracic surgery [1-5]. When nitrous oxide (N20)/oxygen/volatile anesthetics technique is employed during one-lung ventilation, the N20 decreases the inspired oxygen concentration and increases the chance of hypoxemia. However, the use of N20 allows maintenance of anesthesia with low concentrations of potent inhalational agents. We have constructed a CPAP unit from equipment readily available in our department. The purpose of this study was to determine whether the CPAP oxygenation, using this unit, can prevent hypoxemia during one-lung ventilation with N20 and isoflurane anesthesia (FI02 of 0.5).