Victor Saldivia

Hemodynamic and Organ Blood Flow Responses to Halothane and Sevoflurane Anesthesia During Spontaneous Ventilation

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean ± SEM) for halothane and sevoflurane were 1.10% ± 0.05% and 2.40% ± 0.05%, respectively. The Paco2increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05). In conclusion, for comparable increases in Paco2, systemic hemodynamic and organ blood flow responses to halothane are significantly greater than the responses to sevoflurane at an equipotent concentration of 1.0 MAC in the spontaneously ventilating rat.

Effect of propofol infusion on splanchnic hemodynamics and liver oxygen consumption in the rat : a dose-response study

BackgroundPropofol has been used for the maintenance of anesthesia. The effects of propofol infusion on splanchnic hemodynamics and liver oxygen consumption, however, have not been reported. In the current investigation, the authors studied the effects of a continuous infusion of propofol on systemic and splanchnic hemodynamics using a new method to measure liver oxygen consumption in awake control and anesthetized rats. MethodsCannulas were inserted into the left ventricle, femorla artery, portal vein, and hepatic vein during ether anesthesia, and the rats were allowed to awaken and recover for 3–4 h before study. Animals were infused for 30 min with either saline (controls) or propofol at a rate of 300, 600, 900, or 1,200 μg.kg-1·min-1. Cardiac output and organ blood flows were measured using radiolabelled microspheres, and blood samples from the femoral artery, portal vein, and hepatic vein were used to determine liver oxygen consumption. ResultsMean arterial pressure decreased in a dose-dependent manner with a 25% reduction at the highest infusion rate. Systemic vascular resistance similarly decreased, whereas cardiac output remained unchanged at all the infusion rates. Hepatic arterial blood flow increased in a dose-dependent fashion over the dose range studied, to a maximum increase of 120%. Portal tributary blood flow increased by 30% at the highest infusion rate. Total liver blood flow increased in a dose-dependent manner to a maximum of 38%. Total oxygen delivery to the liver by the hepatic artery and portal vein increased in a dose-dependent fashion to a maximum increase of 51% at an infusion rate of 1,200 μg·kg-1·min-1. The percent of oxygen extracted by the liver was not altered by propofol infusion, and hepatic venous oxygen saturation did not decrease at any dose studied. Coronary and renal blood flows were not altered. Arterial Paco2 increased from 31 ± 2 mmHg in awake control rats to 41 ± 2 mmHg in spontaneously breathing rats infused with 1,200 μ·kg-1·min-1 propofol. ConclusionsThe maintenance of anesthesia using an infusion of propofol resulted in an increase in liver oxygen consumption that was fully compensated for by an increase in oxygen delivery to the liver. Splanchnic hemodynamics and liver oxygenation are not adversely affected during maintenance of anesthesia with propofol in the normal rat.

Cloning and characterization of additional members of the G protein-coupled receptor family

A search of the expressed sequence tag (EST) database retrieved a human cDNA sequence which partially encoded a novel G protein-coupled receptor (GPCR) GPR26. A human genomic DNA fragment encoding a partial open reading frame (ORF) and a rat cDNA encoding the full length ORF of GPR26 were obtained by library screening. The rat GPR26 cDNA encoded a protein of 317 amino acids, most similar (albeit distantly related) to the serotonin 5-HT(5A) and gastrin releasing hormone BB2 receptors. GPR26 mRNA expression analysis revealed signals in the striatum, pons, cerebellum and cortex. HEK293 and Rh7777 cells transfected with GPR26 cDNA displayed high basal cAMP levels, slow growth rate of clonal populations and derangements of normal cell shape. We also used a sequence reported only in the patent literature encoding GPR57 (a.k.a. HNHCI32) to PCR amplify a DNA fragment which was used to screen a human genomic library. This resulted in the cloning of a genomic fragment containing a pseudogene, psiGPR57, with a 99.6% nucleotide identity to GPR57. Based on shared sequence identities, the receptor encoded by GPR57 was predicted to belong to a novel subfamily of GPCRs together with GPR58 (a.k.a. phBL5, reported only in the patent literature), putative neurotransmitter receptor (PNR) and a 5-HT(4) pseudogene. Analysis of this subfamily revealed greatest identities (approximately 56%) between the receptors encoded by GPR57 and GPR58, each with shared identities of approximately 40% with PNR. Furthermore, psiGPR57, GPR58, PNR and the 5-HT(4) pseudogene were mapped in a cluster localized to chromosome 6q22-24. PNR and GPR58 were expressed in COS cells, however no specific binding was observed for various serotonin receptor-specific ligands.

Haemodynamic and organ blood flow responses to sevoflurane during spontaneous ventilation in the rat: a dose-response study

To determine the systemic haemodynamic and organ blood flow responses to the administration of sevoflurane during spontaneous ventilation, heart rate, cardiac index, mean arterial pressure, arterial blood gases, and blood flows to the brain, spinal cord, heart, kidneys and splanchnic organs were measured awake (control values) and after 30 min of anaesthesia with 0.5,1.0,1.2 or 1.5 MAC sevoflurane in rats. Cardiac output and organ blood flows were measured using radiolabelled microspheres. The MAC (mean ± SEM) of sevoflurane was found to be 2.30 ± 0.05%. At each concentration, haemodynamic variables were similar to awake values with the exception of a 12% reduction in mean arterial pressure at 1.5 MAC (P < 0.01). Arterial PCO2 increased in a dose-related fashion. Cerebral and spinal cord blood flows increased at 1.2 and 1.5 MAC whereas coronary and renal blood flows did not change significantly. Portal tributary blood flow and preportal vascular resistance were unaffected. Hepatic arterial flow increased by 63% at 1.5 MAC (P < 0.05) but total liver blood flow remained unchanged compared with awake values. In conclusion, the administration of sevoflurane during spontaneous ventilation produces a high degree of cardiovascular stability and maintains blood flow to major organs in the rat.RésuméAfin de déterminer les réponses de l’hémodynamique systémique et du débit sanguin aux organes face à l’administration de sévoflurane sous ventilation spontanée, la fréquence cardiaque, l’index cardiaque, la tension artérielle moyenne, les gaz sanguins artériels, et les débits sanguins au cerveau, à la moëlle épinière, au coeur, aux reins et aux organes splanchniques ont été mesurés chez les rats éveillés (valeur de contrôle) et après 30 minutes d’anesthésie avec 0,5, 1,0, 1,2 et 1,5 MAC de sévoflurane. Le débit cardiaque et les débits sanguins aux organes ont été mesurés en utilisant des microsphères marquées aux radioisotopes. Le MAC (moyenne ± SEM) du sévoflurane a été évalué à 2,30 ± 0,05%. A chaque concentration, les variables hémodynamiques étaient semblables aux variables en état d’éveil, à l’exception d’une réduction de 12% de la tension artérielle moyenne à 1,5 MAC (P < 0,01). La PCO2 artérielle augmentait proportionnellement à la dose. Les débits sanguins cérébraux et de la moëlle épinière augmentaient à 1,2 et 1,5 MAC, tandis que les débits sanguins coronariens et rénaux n ’ont pas changé de façon significative. Le débit sanguin tributaire portal et la résistance vasculaire préportale n’étaient pas affectés. Le débit sanguin hépatique augmentait de 63% à 1,5 MAC (P < 0,05) mais le débit sanguin hépatique total demeurait inchangé comparativement aux valeurs en état d’éveil. En conclusion, l’administration de sévoflurane sous ventilation spontanée produit un haut degré de stabilité cardiovasculaire et maintient le débit sanguin aux organes majeurs chez le rat.

The Effect of Adenosine-induced Hypotension on Systemic and Splanchnic Hemodynamics during Halothane or Sevoflurane Anesthesia in the Rat

Background: It has been suggested that the liver may be at risk for ischemic damage during adenosine-induced hypotension. This notion, however, is somewhat inconsistent with the understanding that adenosine is a powerful vasodilator of the splanchnic circulation. To help clarify the effect of adenosine-induced hypotension on splanchnic hemodynamics, we studied the systemic and splanchnic hemodynamic responses to adenosine, both alone and in the presence of halothane or sevoflurane. MethodsSystemic and splanchnic hemodynamics were determined during the infusion of adenosine in 36 rats allocated randomly to one of three study groups: (1) awake, (2) halothane anesthesia (1.0 MAC), or (3) sevoflurane anesthesia (1.0 MAC). Adenosine was infused at a rate sufficient to decrease the mean arterial pressure by 35–38% from awake control values. Cardiac output and organ blood flows were measured using the radiolabeled microsphere technique. ResultsAdenosine infusion produced stable hypotension of rapid onset due to a reduction in systemic vascular resistance. Stroke volume increased, but cardiac output remained unchanged in the awake and sevoflurane groups because of a decrease in heart rate. Infusion of adenosine during halothane anesthesia increased cardiac output enough to compensate for the decrease in cardiac output due to halothane alone. In the splanchnic circulation, there was an increase in portal tributary (42%, P < 0.01) and hepatic arterial (38%, P < 0.05) blood flows during adenosine infusion in awake rats. This resulted in an overall increase in total liver blood flow (42%, P < 0.01). Halothane anesthesia was associated with a decrease in portal tributary blood flow (28%, P < 0.05). In contrast, sevoflurane anesthesia was associated with an increase in hepatic arterial flow (35%, P < 0.05) but with no change in portal tributary blood flow. During halothane anesthesia, adenosine infusion increased portal tributary (90%, P < 0.01) and hepatic arterial (37%, P < 0.05) blood flows, thereby increasing total liver blood flow to values similar to those in awake adenosine infused rats. During sevoflurane anesthesia, adenosine infusion increased portal tributary blood flow (48%, P < 0.01), but hepatic arterial blood flow did not increase beyond the values observed during sevolfurane anesthesia alone. ConclusionsThese findings demonstrate that adenosine is a potent vasodilator of portal tributary and hepatic arterial vasculature in the rat and that the splanchnic hemodynamic effects of adenosine predominate over those of halothane and sevoflurane.