G. K. Unruh

Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits

Purpose: To elucidate mechanisms by which remifentanil, an ultra-short-acting μ-opioid receptor agonsit, causes hypotension and bradycardia.Methods: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 µg·kg−1 of remifentanil in neuraxis intact (n=6 for each dose) and baro-denservated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 ·g·kg−1 after pretreatment with naloxone, 40 µg·kg−1.Results: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137±8% (mean±SE), 170±14% (P<0.05) and 225±29% (P<0.05) after 1, 2 and 5 µg·kg−1 remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77±3% (P<0.05) and 94±1% (P<0.05), respectively 300 sec after 5 µg·kg−1 remifentanil. At that time, increased RSNA (159±5%,P<0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes.Conclusion: Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral μ-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.RésuméObjectif: Expliquer les mécanismes par lesquels le rémifentanil, un agoniste à action ultra brève du récepteur de μ-opioïde, provoque de l’hypotension et de la bradycardie.Méthode: La tension artérielle moyenne (TAM), la fréquence cardiaque (FC) et l’activité nerveuse sympathique rénale (ANSR) ont été mesurées et notées après l’injections de bolus de 1, 2 ou 5 µg·kg−1 de rémifentanil dans le névraxe de lapins intacts (n=6 pour chaque dose) et de lapins baroénervés (n=6 pour chaque dose). La sensibilité artérielle baroréflexe a été évaluée par des tests dépresseurs. Six animaux supplémentaires, baroénervés, ont reçu 5µg·kg−1 de rémifentanil après un prétraitement avec 40µg·kg−1 de naloxone.Résultats: Toutes les valeurs sont exprimées en % de changement par rapport aux mesures de base. Chez les animaux intacts, la TAM et la FC ont brièvement baissé immédiatement après l’injection de rémifentanil. L’ANSR s’est accrue d’une mani7`ere dépendante de la dose: 137±8% (moyenne±écart type), 170±14 % (P<0,05) et 225±29 % (P<0,05)après 1, 2 et 5 µg·kg−1 de rémifentanil, respectivement. L’ANSR a augmenté même après que la TAM et la FC ont retrouvé les valeurs de base. Les tests dépresseurs ont révélé que le rémifentanil n’a pas atténué la sensibilité artérielle baroréflexe. Chez les lapins baroénervés, la TAM et la FC ont diminué graduellement jusqu’à 77±3 % (P<0,05) et 94±1 % (P<0,05), respectivement, 300 sec après l’administration de 5 µg·kg−1 de rémifentanil. À ce moment, l’augmentation de l’ANSR (159±9 %,P<0,05) était revenue aux valeurs de base. Le prétraitement avec la naloxone chez les lapins baroénervés a aboli ces changements.Conclusion: Le rémifentanil diminue la FC et la TAM par son effet vagotonique central et par la stimulation exercée sur les récepteurs périphériques de μ-opioïde. Ces effets semblent neutralisés et masqués par l’effet sympathotonique central et par le maintien de l’intégrité artérielle baroréflexe.

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)

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.

Efficacy of high-frequency jet ventilation in cardiac tamponade

To evaluate the effects of high-frequency jet ventilation (HFJV) (f = 60, 120 breaths/min) and conventional mechanical ventilation (CMV) (f = 10, 20) during equivalent conditions of cardiac tamponade, stroke index (SI), intra-pericardial pressure (IPP), airway pressure (Paw), and cardiac pressures were measured in anesthetized, paralyzed, chest-closed dogs with the same levels of Paco2 Cardiac tamponade was produced by infusing normal saline into the intrapericardial space to increase IPP to either 8 mm Hg (group 1, n = 8) or 12 mm Hg (group 2, n = 8). Stroke index in group 1 was 7.3±0.8 during CMV (f = 10), 8.1 ± 0.7 during CMV (f = 20), 10.9 ± 1.4 during HFJV (f= 60), and 10.7 ± 1.2 (mL·beat −1· m−2) during HFJV (f = 120). Stroke index in group 2 was 4.1 ± 0.7, 5.1 ± 0.5, 7.2 ± 0.5, and 6.7 ± 0.5 (mL·beat−1·m−2), respectively. In both IPP groups, stroke index values during HFJV were significantly higher than during CMV; however, there were no significant differences in mean left and right atrial transmural pressures between HFJV and CMV. Peak IPP, mean Paw, and peak Paw during HFJV were significantly lower than those during CMV. The results indicate that HFJV with lower mean and peak Paw, and with lower mean and peak IPP, can result in higher cardiac output than CMV in cardiac tamponade. Thus, HFJV may be superior to CMV in the clinical management of cardiac tamponade.