Isoflurane-anesthetized Dogs Research Articles

Regional and systemic hemodynamics during hemodilution with isovolemic hydroxyethyl starch solution alone and in combination with sodium nitroprusside- or isoflurane-induced controlled hypotension in isoflurane-anesthetized dogs

ObjectiveThe aim of the present study was to assess systemic and splanchnic hemodynamics during isovolemic hemodilution and during controlled hypotension induced by sodium nitroprusside (SNP) or isoflurane (ISO) in ISO-anesthetized dogs. Methods: Hemodilution was performed by exchanging blood (20 mL/kg) with isovolemic hydroxyethyl starch solution (6% in saline, molecular weight 70 kd). Hypotension was induced for 90 minutes, with a mean arterial pressure of 70 mm Hg. ResultsHemodilution combined with SNP-induced hypotension produced an increased cardiac index (CI) and a maximal left ventricular pressure change (LV dp/dtmax) compared with prehemodilution values. ISO-induced hypotension produced a decreased CI. During the hypotensive period, CI and LV dp/dtmax in the SNP group were significantly greater than in the ISO group. In the SNP group, the changes from prehemodilution values in renal cortical and medullary blood flow (RCBF and RMBF) were not significant during conditions of hemodilution and induced hypotension, but liver and pancreatic blood flow (LBF and PBF) were significantly decreased (P< 0.05). However, blood flow through all splanchnic organs decreased significantly in the ISO group (P< 0.05). In the hypotensive state, LBF, RCBF, and RMBF were significantly greater in the SNP group than in the ISO group (P< 0.05). ConclusionsResults of the present paper suggest that with respect to splanchnic hemodynamic variables, SNP is preferable to ISO as a hypotensive agent during hemodilution.

Effects of isoflurane anesthesia on pulmonary vascular response to K+ ATP channel activation and circulatory hypotension in chronically instrumented dogs.

The objective of this study was to evaluate the effects of isoflurane anesthesia on the pulmonary vascular responses to exogenous adenosine triphosphate-sensitive potassium (K+ ATP) channel activation and circulatory hypotension compared with responses measured in the conscious state. In addition, the extent to which K+ ATP channel inhibition modulates the pulmonary vascular response to circulatory hypotension in conscious and isoflurane-anesthetized dogs was assessed. Fifteen conditioned, male mongrel dogs were fitted with instruments for long-term monitoring to measure the left pulmonary vascular pressure-flow relation. The dose-response relation to the K+ ATP channel agonist, lemakalim, and the pulmonary vascular response to circulatory hypotension were assessed in conscious and isoflurane-anesthetized (approximately 1.2 minimum alveolar concentration) dogs. The effect of the selective K+ ATP channel antagonist, glibenclamide, on the pulmonary vascular response to hypotension was also assessed in conscious and isoflurane-anesthetized dogs. Isoflurane had no effect on the baseline pulmonary circulation, but it attenuated (P<0.05) the pulmonary vasodilator response to lemakalim. Reducing the mean systemic arterial pressure to approximately 50 mm Hg resulted in pulmonary vasoconstriction (P<0.05) in the conscious state, and this response was attenuated (P<0.05) during isoflurane. Glibenclamide had no effect on the baseline pulmonary circulation, but it potentiated (P<0.05) the pulmonary vasoconstrictor response to hypotension in conscious and isoflurane-anesthetized dogs. These results indicate that K+ ATP-mediated pulmonary vasodilation and the pulmonary vasoconstrictor response to hypotension are attenuated during isoflurane anesthesia. Endogenous K+ ATP channel activation modulates the pulmonary vasoconstrictor response to hypotension in the conscious state, and this effect is preserved during isoflurane anesthesia.

Cardiovascular effects of xenon in isoflurane-anesthetized dogs with dilated cardiomyopathy.

Clinical interest in xenon has been rekindled recently by new recycling systems that have decreased its relative cost. The cardiovascular effects of xenon were examined in isoflurane-anesthetized dogs before and after the development of rapid left ventricular (LV) pacing-induced cardiomyopathy. Dogs (n = 10) were chronically instrumented to measure aortic and LV pressure, LV subendocardial segment length, and aortic blood flow. Hemodynamics were recorded, and indices of LV systolic and diastolic function and afterload were determined in the conscious state and during 1.5 minimum alveolar concentration isoflurane anesthesia alone and combined with 0.25, 0.42, and 0.55 minimum alveolar concentration xenon in dogs with and without cardiomyopathy. Administration of xenon to healthy dogs anesthetized with isoflurane decreased heart rate and increased the time constant (tau) of isovolumic relaxation but did not alter arterial and LV pressures, preload recruitable stroke work slope, and indices of LV afterload. Chronic rapid LV pacing increased the baseline heart rate and LV end-diastolic pressure, decreased arterial and LV systolic pressures, and produced LV systolic and diastolic dysfunction. Administration of xenon to isoflurane-anesthetized, cardiomyopathic dogs did not alter heart rate, arterial and LV pressures, myocardial contractility, and indices of early LV filling and regional chamber stiffness. More pronounced increases in tau were accompanied by increases in total arterial resistance during administration of xenon to isoflurane-anesthetized cardiomyopathic compared with healthy dogs. The results indicate that xenon produces minimal cardiovascular actions in the presence of isoflurane in dogs with and without experimental dilated cardiomyopathy.

Pharmacological characterization of A-131701, a novel ?1-adrenoceptor antagonist selective for ?1A- and ?1D-compared to ?1B-adrenoceptors

New compounds selective for α 1A -adrenoceptors in the prostate may offer enhanced efficacy for benign prostatic hyperplasia (BPH), with fewer side effects than current treatment. A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b,hexanydro-[1H]-benz[e]isoindol-2-yl)ethyl]pyrido[3',4':4,5]thien [3,2-d]pyrimidine-2,4(1H,3H)-dione), from a novel class of benz[e]isolindole pyridothienopyrimidines and pyridothienopyrazines, is selective for α 1a - and α 1d -adrenoceptors in radioligand binding studies (0.22 nM at α 1a -, 0.97 nM at aid-) compared to α 1b -sites (2.5 nM) and in isolated tissue bioassays (pA 2 values of 8.9-9.0 for α 1A -receptors in rat vas deferens or canine prostate strips, 9.1 at α 1D -sites (rat aorta)), compared to 7.9 at α 1B -sites (rat spleen). A-131701 also potently blocked radioligand binding to α 1 -adrenoceptors in canine and human prostatic membranes, but was considerably weaker at α 2 -adrenoceptors. In isoflurane-anesthetized dogs, A-131701 antagonized epinephrine-induced increases in intraurethral pressure (IUP) with a pseudo-pA 2 value of 8.17. In spontaneously hypertensive rats, A-131701 caused transient decreases in mean arterial blood pressure (MABP) and transient tachycardia. The area under the curve (AUC 0→60 min) for the hypotensive response was dose-related, with a log index value for A-131701 of 5.33, suggesting a selectivity of >600-fold comparing IUP to MABP effects. In pentobarbital-anesthetized dogs, A-131701 was more potent in blocking phenylephrine (PHE)-induced increases in IUP (pseudo-pA 2 = 8.0) compared to concurrently measured MABP (pseudo-pA 2 = 7.2), or sixfold selective. Doses greater than 1,000 nmol/kg i.v. of A-131701 were required to lower blood pressure by 10 mm Hg in these dogs (pED 10 = 5.57), indicating a uroselectivity ratio of >250, superior to doxazosin, terazosin, or tamsulosin. Thus, A-131701 is selective for α 1A - and α 1D - vs. α 1B -adrenoceptors in vitro, and prostatic function vs. blood pressure effects in vivo, which may provide therapeutic advantages in the treatment of BPH.

Pharmacokinetics, effects on renal function, and potentiation of atracurium-induced neuromuscular blockade after administration of a high dose of gentamicin in isoflurane-anesthetized dogs

Abstract Objective To determine pharmacokinetics, renal effects, and effect on atracurium-induced neuromuscular blockade of a high dose of gentamicin in isoflurane-anesthetized dogs. Animals 6 healthy, adult, mixed-breed dogs, anesthetized twice and receiving gentamicin (6 mg/kg of body weight, IV) or saline solution. Procedure Blood samples were collected before and at intervals after gentamicin administration. Pharmacokinetic values were evaluated by use of multivariant stepwise linear regression analysis. Gentamicin-induced renal changes were assessed by comparing pretreatment and 12- to 24-hour posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-γ-glutamyltransferase ratio, and urinalysis. Neuromuscular blockade, maintained by atracurium infusion, was assessed, using the train-of-four response. At stable 50% depression of first twitch (T1) gentamicin or saline solution was given. Before and at posttreatment intervals for 60 minutes, T1% and fourth twitch-to-T1 ratio were recorded. The infusion was discontinued and 50 to 75% T1 recovery time was recorded. At 75% T1, edrophonium (0.5 mg/kg) was administered IV. Results Mean values for volume of distribution and clearance were 0.263 L/kg and 2.0 ml/min/kg, respectively. Mean maximal serum concentration of gentamicin was 46.4 μg/ml. Pre and posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-γ-glutamyltransferase ratio, and other urine analytes were not significantly different. Mean (± SD) values for T1% and fourth twitch-to-T1 ratio decreased significantly after gentamicin (depression was maximal at 5 minutes). Recovery time (50 to 75% T1) was not different between groups. Edrophonium restored twitch to baseline. Conclusions Mean values for apparent volume of distribution and total body clearance of gentamicin were similar to values in unanesthetized dogs. Mean maximal serum concentration of gentamicin was greater than that in unanesthetized dogs. Renal function was unaffected. Gentamicin potentiated atracurium-induced neuromuscular blockade, but did not affect recovery time. (Am J Vet Res 1996;57:1623–1626)

Evaluation of analgesia and cardiorespiratory effects of epidurally administered butorphanol in isoflurane-anesthetized dogs

Abstract Objective To determine variations in minimal alveolar concentration (MAC) of isoflurane and analgesic and cardiorespiratory effects of lumbosacral epidural administration of 0.25 mg of butorphanol/kg of body weight in dogs. Animals 16 healthy male dogs. Procedure Dogs were anesthetized with isoflurane alone. Eight dogs received butorphanol (group B) and the others an equal volume of isotonic saline solution (group S) administered by a catheter inserted in the lumbosacral epidural space. Isoflurane MAC was determined before and 30 minutes after the epidural injection, along with noxious stimulation to the fore- and hind limbs. Cardiorespiratory variables were recorded prior to and until 120 minutes after epidural administration. At that time, isoflurane anesthesia was ended, and nociception (toe pinch and pin-prick responses) was evaluated for 7 hours. Dogs were observed for 3 days to determine presence of neurologic side effects. Results For group-B dogs, isoflurane MAC decreased by 31 ± 8.6% after butorphanol was administered. Cutaneous insensitivity (to pin-prick nociceptive test) persisted for 3 hours after the end of isoflurane anesthesia in group-B dogs. No response was observed to toe pinch stimulation for 80 minutes after anesthesia. Conclusions Epidural administration of 0.25 mg of butorphanol/kg in dogs was safe; minimal cardiorespiratory and no neurologic side effects were observed, and analgesia and an isoflurane-sparing effect were apparent. Clinical Relevance The short duration of action of epidurally administered butorphanol limits its value for clinical practice. (Am J Vet Res 1996;57:1478-1482)

The Hemodynamic Effects of Esmolol and Propranolol in Isoflurane-Anesthetized Dogs

The Hemodynamic Effects of Esmolol and Propranolol in Isoflurane-Anesthetized Dogs

Potency (minimum alveolar anesthetic concentration) of isoflurane is independent of peripheral anesthetic effects.

The spinal cord is an important site where inhaled anesthetics suppress movement in response to noxious stimuli. Inhaled anesthetics also act in peripheral tissues, although it is unclear whether these actions influence anesthetic requirements. In six isoflurane-anesthetized mongrel dogs, we placed Y cannulas in the lower aorta and vena cava, allowing us to divert blood to, and infuse blood from, a bubble oxygenator/roller pump system or to maintain normal blood flow. This technique permits a greatly diminished isoflurane concentration at the site of the noxious stimulus (tail), while maintaining isoflurane in the remainder of the body. After baseline minimum alveolar anesthetic concentration (MAC1) was determined, venous blood from the lower body was diverted to the bubble oxygenator and reinfused into the lower body via the aortic cannula; MAC2 was determined with isoflurane in the lower body at approximately 0.2%, and MAC3 was determined with isoflurane in the lower body matched to the end-tidal isoflurane. Bypass was terminated, the native circulation established, and MAC4 determined. MAC1, 2, 3, and 4 were (mean +/- SD) 1.3 +/- 0.3%, 1.2 +/- 0.1%, 1.2 +/- 0.2%, and 1.1 +/- 0.2%, respectively (P > 0.05). We conclude that the peripheral effects of isoflurane do not influence the response to a noxious stimulus.

Cardiovascular effects of epidurally administered morphine and a xylazine-morphine combination in isoflurane-anesthetized dogs

Abstract Cardiovascular effects of epidurally administered morphine, a morphine-xylazine combination, and saline solution (control) during isoflurane-maintained anesthesia were assessed in 6 healthy dogs. Anesthesia was induced with isoflurane in O2 and was maintained at 2.0% end-tidal isoflurane concentration. Ventilation was controlled to maintain PaCO2 at 35 to 45 mm of Hg. The dorsal pedal artery was cannulated for measurement of systolic, mean, and diastolic pressures, and for blood sample collection. Arterial blood pH and gas tensions were determined every 30 minutes. Cardiac output was determined by thermodilution. The ecg, heart rate, body temperature, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal isoflurane concentration, and CO2 tension were monitored. Systemic and pulmonary vascular resistance, arterial HCO3- concentration, base excess, and cardiac index were calculated. After baseline measurements were taken, morphine (0.1 mg/kg of body weight) in 5 ml of isotonic saline solution, morphine and xylazine (0.1 mg of morphine and 0.02 mg of xylazine/kg) in 5 ml of isotonic saline solution, or 5 ml of isotonic saline solution was injected into the lumbosacral epidural space. Data were recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Statistical analysis included anova for repeated measures. Significance was set at P &lt; 0.05. None of the measured variables was significantly different among the 3 treatments at any time. Results of the study indicated that epidural administration of morphine or morphine and xylazine is not associated with significant cardiovascular side effects during isoflurane-maintained anesthesia in dogs.

Isoflurane and the pulmonary vascular pressure-flow relation at baseline and during sympathetic alpha- and beta-adrenoreceptor activation in chronically instrumented dogs.

The extent to which isoflurane anesthesia alters systemic vascular regulation has received considerable attention. In contrast, the pulmonary vascular effects of isoflurane have not been elucidated. Our initial objective was to investigate the net effect of isoflurane on the baseline left pulmonary vascular pressure-flow (LPQ) relation compared with values measured in the conscious state. In addition, we assessed the extent to which isoflurane alters the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation. Twelve conditioned mongrel dogs were chronically instrumented to measure the LPQ relation. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure--left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. LPQ plots were generated at baseline in the conscious and isoflurane-anesthetized states (n = 12). The pulmonary vascular dose-response relation to the sympathetic alpha-adrenoreceptor agonist phenylephrine also was investigated in conscious and isoflurane-anesthetized dogs (n = 6). Finally, after preconstriction with the thromboxane analogue U46619, the dose-response relation to the sympathetic beta-adrenoreceptor agonist isoproterenol was assessed in the conscious and isoflurane-anesthetized states (n = 8). Compared with values measured in the conscious state, isoflurane anesthesia had no net effect on the baseline LPQ relation. The magnitude of the pulmonary vasoconstrictor response to phenylephrine observed in conscious dogs was not altered during isoflurane anesthesia. In contrast, the pulmonary vasodilator response to isoproterenol was markedly potentiated (P < 0.01) during isoflurane anesthesia compared with that in the conscious state. These results indicate that isoflurane does not exert a net vasodilator influence on the pulmonary circulation at baseline. In contrast to the systemic circulation, the pulmonary vasoconstrictor response to sympathetic alpha-adrenoreceptor activation is maintained during isoflurane anesthesia. Surprisingly, the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation is actually potentiated during isoflurane. Thus, isoflurane anesthesia has differential effects on the canine pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation.

Effects of medetomidine administration on intracranial pressure and cardiovascular variables of isoflurane-anesthetized dogs

SUMMARY Intracranial pressure and cardiovascular variables after iv administration of medetomidine (0.03 mg/kg of body weight) were evaluated in 6 healthy, mixed-breed dogs anesthetized with 1.3% end-tidal isoflurane concentration and mechanically ventilated to normocapnia (PaCO2, 35 to 45 mm of Hg). Baseline values were determined for intracranial pressure, heart rate, arterial blood pressure, cardiac output, mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, end-tidal CO2 tension and isoflurane concentration, arterial pH and CO2 and O2 tensions, and core body temperature. Cerebral perfusion pressure, cardiac index, systemic and pulmonary vascular resistances, plasma HCO3- concentration, and base excess were calculated. Intracranial pressure was measured, using a calibrated, fiberoptic transducer placed within the brain parenchyma and secured to the calvarium by means of a subarachnoid bolt. Cardiac output was determined by thermodilution. End-tidal CO2 tension and isoflurane concentration were determined, using an infrared gas analyzer. Administration of medetomidine did not change intracranial pressure, but was associated with significant (P &lt; 0.05) decreases in values for heart rate, cardiac index, end-tidal CO2, and HCO3- and with significant increases in systolic, mean, and diastolic pressure; pulmonary artery pressure; systemic vascular resistance; central venous pressure; and pulmonary capillary wedge pressure.

Inhibition of nitric oxide synthesis causes systemic and pulmonary vasoconstriction in isoflurane-anesthetized dogs

The postulate that the hemodynamic changes produced by isoflurane (1.5%) involve release of nitric oxide (NO) was examined. Fifteen dogs were anesthetized with thiamylal (15 mg/kg) and ventilated with isoflurane and oxygen. Catheters were inserted for measurement of aortic pressure, pulmonary artery pressures, and determination of cardiac output. Left thoracotomy was performed and complete heart block was induced by injection of 37% formaldehyde (0.3 mL) into the atrioventricular node; ventricular rate was fixed at 100 beats/min by external pacing. An apical microtransducer was inserted into the left ventricle (LV) via the apex for measurement of left ventricular pressure (LVP) and its first derivative (dP/dt). Flow probes were mounted on the left circumflex (Cx) and anterior descending (AD) coronary arteries. Measurements were obtained before (control period) and during NO inhibition using IV N G-nitro- l-arginine methyl ester ( l-NAME) by a 50 mg/kg bolus plus 1 mg/kg/min. Infusion of l-NAME caused immediate and sustained increases in mean arterial pressure to 145 ± 3% ( P < 0.001), mean pulmonary arterial pressure to 128 ± 5% ( P < 0.001), pulmonary capillary wedge pressure to 144 ± 8% ( P < 0.001), coronary perfusion pressure to 163 ± 4% ( P < 0.001), systemic vascular resistance to 209 ± 9% ( P < 0.001), pulmonary vascular resistance to 142 ± 12% ( P < 0.005), anterior descending flow to 115 ± 4% ( P < 0.005), and circumflex flow to 113 ± 3% ( P < 0.01) of control levels. Decreases in cardiac output to 73 ± 2% ( P < 0.001), anterior descending conductance to 71 ± 3% ( P < 0.001), and circumflex conductance to 70 ± 3% ( P < 0.001) of control, were also observed; LV dP/dt and end-diastolic pressure were unchanged. Inhibition of NO caused systemic and pulmonary vasoconstriction and depression of cardiac output. Responses to NO inhibition unmasked an intense background vasoconstriction during isoflurane, yet coronary blood flow increased due to an increase in perfusion pressure. It is concluded that NO plays a significant role in the systemic and pulmonary vasomotor and cardiac responses during isoflurane anesthesia. On the other hand, the coronary vasomotor effects appear to be mediated indirectly through changes in coronary perfusion pressure (ie, autoregulatory) rather than directly through withdrawal of NO activity.

Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow.

We tested the hypothesis that NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/- 4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE) ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10 micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x 100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L-NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O2 transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in isoflurane-anesthetized dogs

Summary Eight dogs (body weight, 12.5 to 21.5 kg) were assigned at random to each of 3 treatment groups (is, ix, im) that were not given glycopyrrolate and to each of 3 groups that were given glycopyrrolate (igs, igx, igm). Dogs were anesthetized with isoflurane (1.95% end-tidal concentration), and ventilation was controlled (PCO2, 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered iv and im at a dosage of 11 μg/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, im), or medetomidine (15 μg/kg, im) was administered 10 minutes after baseline ade determination. Redetermination of the ade at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0, 2.5, and 5.0 μg/kg/min. The ade was defined as the total dose of epinephrine that induced at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion, or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline and treatment ade values was performed by use of one-way anova. Mean ± sem baseline ade values for groups is, ix, and im were 1.55 ± 0.23, 161 ± 0.28, and 1.95 ± 0.65 μg/kg, respectively. Differences for groups is, ix, and im were – 0.12 ± 0.05, – O.31 ± 0.40, and – 0.17 ± 0.26, respectively. Differences for groups igs, igx, and igm could not be calculated because arrhythmias satisfying the ade criteria were not observed at the maximal infusion rate of 5.0 μg/kg/min. Differences among groups is, ix, and im were not significant. We conclude that in isoflurane-anesthetized dogs: preanesthetic dosages of xylazine (1.1 mg/kg, im) or medetomidine (15 μg/kg, im) do not enhance arrhythmogenicity, and at these dosages, there is no difference in the arrhythmogenic potential of either α2-adrenergic receptor agonist.

Effects of ephedrine on cardiovascular function and oxygen delivery in isoflurane-anesthetized dogs

Summary The hemodynamic effects of 2 dosages of ephedrine were studied in 6 dogs anesthetized with isoflurane only (end-tidal concentration equivalent to 1.5 times minimum alveolar concentration). Following instrumentation, baseline (time 0) measurements included heart rate (hr), respiratory rate, mean arterial blood pressure (map), cardiac output, and blood gas tensions. Cardiac index (ci), stroke volume (sv), systemic vascular resistance (svr), arterial oxygen content (Cao2), and oxygen delivery and consumption (Do2 and Vo2, respectively) were calculated. Three dogs were given ephedrine iv at a dosage of 0.1 mg/kg of body weight, and 3 dogs were given ephedrine iv at a dosage of 0.25 mg/kg. Measurements were recorded at 5, 10, 15, 30, and 60 minutes. Each dog then received the alternate dosage of ephedrine, and measurements were again recorded at the same intervals. Effects of ephedrine varied with dosage. Neither dosage was associated with significant changes in pH, Pao2, Paco2, Vo2, or respiratory rate. Ephedrine at a dosage of 0.1 mg/kg caused transient significant increases in map, ci, sv, Cao2, and Do2, significant decreases in hr and svr, and a late, slight decrease in Cao2. Ephedrine at a dosage of 0.25 mg/kg caused a greater and more prolonged increase in map, as well as increases in ci, sv, and svr, and a decrease in hr. The higher dosage of ephedrine also caused a pronounced increase in hemoglobin concentration and CaO2, resulting in a 20 to 35% increase in Do2 throughout the 60-minute experiment.

Right and left ventricular O2 uptake during hemodilution and beta-adrenergic stimulation.

Myocardial O2 uptake (MVO2) and related variables were compared in right and left ventricles (RV and LV, respectively) during isovolemic hemodilution (HD) alone and combined with isoproterenol (Iso) infusion in 13 isoflurane-anesthetized open-chest dogs. Measurements of myocardial blood flow (MBF) obtained with radioactive microspheres were used to calculate MVO2. Lactate extraction (Lacext) was determined. The study consisted of two experimental series: 1) graded HD (dextran) to hematocrit (Hct) of 10% and 2) Iso (0.1 microgram.kg-1.min-1 iv) during moderate HD (Hct = 18 +/- 1%). In series 1, arteriovenous O2 content difference in both ventricles decreased in parallel with reduced arterial O2 content caused by HD, i.e., percent O2 extraction was constant; MVO2 was maintained by proportional increases in MBF. In series 2, Iso during moderate HD raised MVO2 (RV, +156%; LV, +80%). Higher MVO2 was satisfied by combination of increased MBF and O2 extraction in RV and by increased MBF alone in LV. Lacext remained consistent with adequate myocardial O2 delivery throughout study. Conclusions were that 1) both RV and LV tolerated extreme HD (Hct = 10%) because blood flow reserves were sufficient to fully compensate for reduced arterial O2 content; 2) significant cardiac reserve was evident during HD, which could be recruited Iso; and 3) because increase in MVO2 in RV caused by Iso in presence of HD was partially satisfied by increased O2 extraction, the absence of augmented O2 extraction during HD alone was not due to impaired release of O2 from diluted red blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexmedetomidine Alters the Hemodynamic Effects of Desflurane and Isoflurane in Chronically Instrumented Dogs

Previous studies have shown that desflurane and isoflurane produce similar hemodynamic actions. This investigation examined the cardiovascular effects of desflurane and isoflurane in the presence or absence of dexmedetomidine, a highly selective alpha 2-adrenergic agonist that may be clinically useful as a premedicant or anesthetic adjuvant. Four groups, comprising 40 experiments, were performed using ten dogs that were chronically instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dtmax), diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded, and plasma concentrations of catecholamines were measured with or without oral dexmedetomidine pretreatment (30 micrograms/kg) in the conscious state and after 15 min of equilibration at 1.0, 1.3, and 1.6 end-tidal MAC desflurane or isoflurane in a random fashion. In conscious dogs, dexmedetomidine significantly decreased heart rate, cardiac output, percent segment shortening (%SS), left ventricular dp/dtmax, myocardial oxygen consumption (as estimated by the pressure-work index), and plasma norepinephrine concentration. Concomitant increases in systemic and diastolic coronary vascular resistance were observed. Pretreatment with dexmedetomidine decreased peak increases in heart rate during desflurane and isoflurane anesthesia. Mean arterial pressure was reduced less by desflurane than by isoflurane in the absence of dexmedetomidine. This difference was abolished in dogs pretreated with dexmedetomidine. Desflurane, but not isoflurane, decreased cardiac output in dexmedetomidine-pretreated dogs when compared with untreated dogs. Concomitantly, systemic vascular resistance was greater in desflurane- versus isoflurane-anesthetized dogs pretreated with dexmedetomidine. No differences in myocardial contractility, as assessed by left ventricular dP/dtmax and %SS, were observed between desflurane and isoflurane groups in the absence or presence of dexmedetomidine. The results indicate that the cardiovascular actions of desflurane or isoflurane are similar in the absence or presence of dexmedetomidine; however, some differences between anesthetic groups were noted. In the presence of dexmedetomidine, systemic vascular resistance during desflurane anesthesia was higher when compared with that during isoflurane anesthesia, indicating that desflurane produces less pronounced direct effects on peripheral vascular tone. The concomitant greater reductions in cardiac output are consistent with greater impedance to left ventricular outflow in desflurane-anesthetized dogs pretreated with dexmedetomidine, because no differences in contractile function were observed between volatile anesthetics. In contrast, cardiac output during isoflurane anesthesia after pretreatment with oral dexmedetomidine is better maintained secondary to the peripheral vasodilator actions of this agent.

Cardiovascular effects of intravenous bolus administration and infusion of ketamine-midazolam in isoflurane-anesthetized dogs

Summary Cardiovascular effects of iv administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) were determined in 12 healthy isoflurane-anesthetized (1.7% end-tidal concentration) dogs. Six dogs received a ketamine-midazolam combination (k-m) as a bolus over 30 seconds and 6 dogs received k-m as an infusion over 15 minutes. Ketamine-midazolam combination as a bolus and an infusion caused early significant (P &lt; 0.05) reductions in mean systemic blood pressure, cardiac index, and stroke index, which returned to baseline values near the end of the study. Heart rate decreased significantly (P &lt; 0.05) in dogs of the infusion group and returned to the baseline value near the end of the study. One dog died after k-m bolus administration. Mean maximal decreases from baseline for systemic blood pressure, cardiac index, and stroke index were significantly (P &lt; 0.05) greater in dogs of the bolus group than in dogs of the infusion group; therefore, cardiovascular effects of k-m after infusion were less severe than those after bolus. Base excess and pHa decreased significantly (P &lt; 0.05) in the infusion group, although similar changes occurred in both groups. Four dogs were maintained with 1.7% end-tidal isoflurane to determine temporal effects of isoflurane; these dogs did not receive k-m. Increases in heart rate, cardiac index, stroke index, and left and right ventricular stroke work indexes were significant (P &lt; 0.05) at various sample collection intervals, particularly during the later stages of the study. Isoflurane anesthesia effectively blocked the cardiostimulatory properties of k-m. Ketamine-midazolam combination should be used cautiously during isoflurane anesthesia, and administration by slow infusion may be safer than by rapid bolus administration.

Effects of abdominal insufflation with nitrous oxide on cardiorespiratory measurements in spontaneously breathing isoflurane-anesthetized dogs

Summary Cardiorespiratory effects of abdominal insufflation were evaluated in 8 dogs during isoflurane anesthesia. Each dog was studied 3 times, in 1 of the following orders of insufflation pressures: 10-20-30, 20-30-10, 30-20-10, 10-30-20, 20-10-30, and 30-10-20 mm of Hg. Anesthesia was induced by use of a mask, dogs were intubated, and anesthesia was maintained by isoflurane in 100% oxygen. After instrumentation, baseline values were recorded (time 0), and the abdomen was insufflated with nitrous oxide. Data were recorded at 5, 10, 15, 20, 25, and 30 minutes after insufflation. The abdomen was then desufflated, with recording of data continuing at 35 and 40 minutes. Mean arterial pressure increased at 5 minutes during 20 mm of Hg insufflation pressure, and from 20 to 30 minutes during 30 mm of Hg pressure. Tidal volume decreased from 5 to 30 minutes during 10 and 20 mm of Hg pressures, and from 5 to 40 minutes during 30 mm of Hg pressure. Minute ventilation decreased at 10 and 20 minutes during 20 mm of Hg pressure. End-tidal CO2 concentration increased from 5 to 30 minutes during 20 and 30 mm of Hg pressure. The PaCO2 decreased at 40 minutes during 10 mm of Hg pressure, at 30 minutes during 20 mm of Hg pressure, and from 10 to 40 minutes during 30 mm of Hg pressure. Values for pH decreased from 10 to 30 minutes during 20 and 30 mm of Hg pressures. The PaO2 decreased from 20 to 40 minutes during 10 mm of Hg pressure, at 30 minutes during 20 mm of Hg pressure, and from 10 to 40 minutes during 30 mm of Hg pressure. Percentage decrease in tidal volume was greater at 5 and 15 minutes with 30 mm of Hg pressure. Differences in percentage increase in end tidal CO2 concentration were observed among the 3 pressures from 5 to 30 minutes. Although significant, these changes do not preclude use of laparoscopy if insufflation pressure &gt; 20 mm of Hg is avoided.

Hemodynamic effects of atropine and glycopyrrolate in isoflurane-xylazine-anesthetized dogs.

Alterations in parasympathetic tone are partially responsible for xylazine's hemodynamic effects. The purpose of this study was to evaluate and compare the hemodynamic changes caused by the administration of intravenous (IV) atropine or glycopyrrolate after IV xylazine in isoflurane-anesthetized dogs. Six healthy beagles (8.2 to 10.7 kg) were used in two trials separated by 7 days. Anesthesia was induced and maintained with isoflurane in 100% oxygen with controlled ventilation. Once constant end-tidal isoflurane (1.8%) and arterial partial pressure of carbon dioxide (35 to 45 mm Hg) values were reached, baseline data were recorded and xylazine (0.5 mg/kg, i.v.) was given. In trial 1 atropine (0.1 mg/kg, i.v.) was given 5 minutes after xylazine, and in trial 2 glycopyrrolate (0.025, mg/kg, i.v.), was given 5 minutes after xylazine. Hemodynamic variables were recorded 3 minutes after xylazine and 3 minutes after anticholinergic administration. In trial 2, bilateral vagotomies were performed 10 minutes after glycopyrrolate, and hemodynamic variables were recorded 3 minutes later. Heart rate, cardiac index, and stroke index decreased; arterial pressure and systemic vascular resistance increased after xylazine. Heart rate, cardiac index, and rate pressure product increased after anticholinergic administration. Significant differences between atropine and glycopyrrolate were not observed in any of the hemodynamic parameters. Similarly, significant differences between glycopyrrolate and bilateral vagotomy were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)