W. C. Seyde

Anesthetic Influences on Regional Hemodynamics in Normal and Hemorrhaged Rats

Forty-six male Sprague-Dawley rats were divided in five groups: awake animals and those receiving ketamine, halothane, enflurane, or isoflurane anesthesia. Cannulae were inserted into the left femoral artery and vein and the left ventricle. Inspired concentrations of the volatile anesthetics were adjusted to achieve the minimal alveolar concentration (MAC) of each drug. Ketamine, 125 mg·kg−1, was injected intraperitoneally and then infused at a rate of 1 mg·kg−1·min−1. All animals breathed spontaneously throughout the experiment (Flo2 = 0.3). Following a 2-h stabilization period, 30% of estimated blood volume was withdrawn gradually over 10 min. Immediately before and 20 min after hemorrhage, cardiac output and regional blood flows were measured by the microsphere method (85Sr, 141Ce-labeled 15-μm microspheres, respectively). Arterial blood samples were analyzed for Po2, Pco2, pH, lactate, and pyruvate at these times also. Prior to hemorrhage, cardiac output (CO) values were similar in awake rats and those receiving ketamine or isoflurane, but CO was reduced moderately by enflurane and to a greater extent by halothane. After hemorrhage, CO was greatest in awake animals and those receiving isoflurane, and awake rats tended to have the greatest organ blood flows. Values of lactate/pyruvate and excess lactate were least in awake animals. Overall results suggested that, in terms of cardiac output and regional blood flows, ketamine approximates the awake state most closely in normovolemic animals, whereas isoflurane anesthesia is most like the awake condition after hemorrhage.

Dose-dependent Effects of Bupivacaine on Rat Muscle Arterioles

The dose-dependent actions of bupivacaine on the microvasculature were evaluated by television microscopy in an in vivo rat cremaster muscle preparation. Animals were anesthetized with chloralose and urethane. Mean arterial pressure was measured via a carotid artery cannula; heart rate was calculated from the phasic pressure trace. The cremaster muscle was suffused with a balanced electrolyte solution that was controlled for temperature, pH, PO2, PCO2, and osmolarity to provide a physiologic environment. Internal diameters of fourth-order arterioles were measured with an electronic vernier displayed on the video monitor. Arteriolar diameters were measured every 30 s during a 10-min control period, a 10-min period of topical application of bupivacaine hydrochloride, and a 30-min recovery period. Bupivacaine 10−1, 100, 101, and 102 μg · ml−1 produced progressive vasoconstriction to 82.7 ± 2.9%, 75.0 ± 5.6%, 71.0 ± 7.0%, and 65.7 ± 9.4% of control (P ≤ 0.05 for each), respectively. Bupivacaine, 103 and 2.5 X 103 μg · ml−1, did not alter arteriolar diameters significantly, although there was a tendency for vasodilation. In a second group of animals, arteriolar diameters were measured during intravenous bupivacaine infusion that produced stable plasma concentrations of 2.3 ± 0.2 μg · ml−1. Vasoconstriction of 91.4 ± 2.2%, of control (P ≤ 0.01) was observed. These results demonstrate that dose-dependent arteriolar constriction occurs even with blood bupivacaine levels that are at the upper limits of those expected to occur during regional anesthesia.

Carotenoid Compound Crocetin Improves Cerebral Oxygenation in Hemorrhaged Rats

The carotenoid compound crocetin has been shown to increase oxygen diffusivity in vitro. In the present study the effect of crocetin on tissue oxygenation was examined in the cerebral cortex of rats subjected to hemorrhage. Twelve male Sprague–Dawley rats were anesthetized with pentobarbital and ventilation was controlled (PaCO2 = 33 mm Hg). A craniotomy was performed and the animals were hemorrhaged (20% of estimated total blood volume). Six of 12 animals then received a bolus of crocetin (2 U in 0.1 ml saline); the remaining animals received saline (0.1 ml i. v.) only. Values for mean arterial pressure. PO2, PCO2, pH, and hematocrit did not differ in rats that received either saline or crocetin. Tissue oxygen tension (PtO2) was measured at ∼170 locations in the parietal cerebral cortex of each rat by a platinum–oxygen microelectrode technique. Results were compared by PtO2 frequency histograms. Crocetin as compared with saline treatment resulted in a right shift of the PtO2 frequency distribution and a significant decrease in the frequency of occurrence of low PtO2 values. The average of individual median PtO2 values was significantly greater in crocetin-treated animals as compared with those receiving saline (7.6 ± 1.7 vs. 3.2 ± 1.2 mm Hg, respectively). The results suggest that the carotenoid compound crocetin improves tissue oxygenation in the cerebral cortex of hemorrhaged rats.

Cerebral Oxygen Tension in Rats during Deliberate Hypotension with Sodium Nitroprusside, 2-chloroadenosine, or Deep Isoflurane Anesthesia

Thirty-four male Sprague-Dawley rats were divided into four groups: control animals and those receiving sodium nitroprusside (SNP), 2-chloroadenosine, or a high, inspired concentration of isoflurane to produce deliberate hypotension to a mean arterial blood pressure of 50 mmHg. Ventilation was controlled (FIO2 = 0.3); control animals and those treated with sodium nitroprusside or 2-chloroadenosine breathed isoflurane 1.4 vol%, whereas isoflurane, 3.9 vol%, was required to produce hypotension by deep anesthesia alone. Multiple tissue oxygen tension values (PtO2) were measured at intervals of 10 μm over a distance of 2 mm by advancing an oxygen micro-electrode through the parietal cerebral cortex of all animals. The frequency of low tissue PO2 values (<10 mmHg) was increased with all forms of deliberate hypotension, but the magnitude of this change (a shift to the left in the frequency histogram) was significantly different among techniques. The shift toward lower PtO2 values during hypotension was least in animals receiving deep isoflurane anesthesia, intermediate in those receiving SNP, and greatest in those treated with 2-chloroadenosine. In rats, areas of the brain appear to be at risk for significant tissue hypoxia during hypotension produced by 2-chloroadenosine.

The Hemodynamic Response to Isoflurane is Altered in Genetically Hypertensive (SHR), as Compared With Normotensive (WKY), Rats

The authors compared the hemodynamic effects of isoflurane anesthesia in normotensive (WKY) and genetically hypertensive (SHR) rats. Eighteen male SHR and 18 WKY rats were subdivided into conscious animals and those anesthetized with isoflurane, 1.2 vol% inspired. During brief isoflurane anesthesia, cannulae were placed in the left cardiac ventricle, the femoral artery, and the femoral vein. Central and regional hemodynamics were determined with 85Sr-labeled microspheres (15 ± 1 μm) using the reference sample technique in both conscious and anesthetized animals. Isoflurane anesthesia caused similar reductions in mean arterial blood pressure (MAP) in all rats. This was due to a significant decrease in systemic vascular resistance in WKY rats, whereas MAP declined due to a significant decrease in cardiac output in SHR rats. In the anesthetized WKY rat, the decrease in total systemic vascular resistance resulted from significant decreases in vascular resistance of the brain and nonrespiratory skeletal muscles. In the anesthetized SHR rat, both decreases (cerebellum, hepatic artery) and increases (GI tract, skin, diaphragm) in regional vascular resistances occurred, resulting in no net change in total systemic vascular resistance. In both SHR and WKY rats, isoflurane redistributed blood flow in favor of the brain at the expense of blood flow to the GI tract, diaphragm, and skin. Blood flows to the liver, GI tract, and skin were significantly less in the anesthetized SHR as compared with WKY rats. It is concluded that isoflurane influences central and regional hemodynamics differently in hypertensive, as compared with normotensive, rats.

THE CAROTENOID COMPOUND CROCETIN IMPROVES CEREBRAL OXYGENATION IN HEMORRHAGED RATS

The carotenoid compound crocetin has been shown to increase oxygen diffusivity in vitro. In the present study the effect of crocetin on tissue oxygenation was examined in the cerebral cortex of rats subjected to hemorrhage. Twelve male Sprague-Dawley rats were anesthetized with pentobarbital and ventilation was controlled (PaCO2 = 33 mm Hg). A craniotomy was performed and the animals were hemorrhaged (20% of estimated total blood volume). Six of 12 animals then received a bolus of crocetin (2 U in 0.1 ml saline); the remaining animals received saline (0.1 ml i.v.) only. Values for mean arterial pressure. PO2, PCO2, pH, and hematocrit did not differ in rats that received either saline or crocetin. Tissue oxygen tension (PtO2) was measured at approximately 170 locations in the parietal cerebral cortex of each rat by a platinum-oxygen microelectrode technique. Results were compared by PtO2 frequency histograms. Crocetin as compared with saline treatment resulted in a right shift of the PtO2 frequency distribution and a significant decrease in the frequency of occurrence of low PtO2 values. The average of individual median PtO2 values was significantly greater in crocetin-treated animals as compared with those receiving saline (7.6 +/- 1.7 vs. 3.2 +/- 1.2 mm Hg, respectively). The results suggest that the carotenoid compound crocetin improves tissue oxygenation in the cerebral cortex of hemorrhaged rats.

The Addition of Nitrous Oxide to Halothane Decreases Renal and Splanchnic Flow and Increases Cerebral Blood Flow in Rats

Thirteen male Sprague-Dawley rats were anaesthetized with halothane and catheters were placed in the femoral artery and left ventricle. The animals breathed spontaneously through a tracheostomy throughout the investigation. After the surgical preparation, the inspired halothane concentration was maintained at 1.5 vol% (F/O2 = 0.3). After a 30-min stabilization period, strontium-85 radiolabelled microspheres (15 +/- 1 micron) were injected to the left ventricle for determination of cardiac output and regional blood flows. In six rats, nitrous oxide was then substituted for nitrogen in the inspired gas mixture. Ten min thereafter, 141Ce-labelled microspheres were injected and the haemodynamic measurements were repeated in all animals. The administration of the nitrous oxide to halothane-anaesthetized rats resulted in a decrease in cardiac output and decreases in blood flow to kidneys, liver, small bowel and spleen. Cerebral perfusion was increased.