Hemorrhage during Isoflurane-Nitrous Oxide Anesthesia: Effects of Endothelin-A or Angiotensin II Receptor Blockade or Both

Background: The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia.

Methods: Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour.

Results: Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, cardiac output had decreased less in controls than in all other protocols. Mean arterial pressure decreased more during ETAB than in controls, but most severely during AT1B and AT1B + ETAB. Angiotensin II increased further only in controls and ETAB, whereas vasopressin and catecholamines increased similarly in all protocols. Retransfusion: Mean arterial pressure remained below controls in all protocols but was lowest when the AT1 receptor was blocked. Cardiac output fully recovered in all but the ETAB protocol.     

Transesophageal echocardiographic assessment of pulmonary arterial and venous flow during high-frequency jet ventilation

STUDY OBJECTIVE: To evaluate high-frequency jet ventilation (HFJV) effects on pulmonary arterial and venous flow compared to those of intermittent positive-pressure ventilation (IPPV) by using pulsed Doppler transesophageal echocardiography. DESIGN: Prospective clinical study. SETTING: University-affiliated hospital operating room.Patients: 13 ASA physical status I and II patients undergoing lower abdominal or lower extremity surgery. INTERVENTIONS: Patients had total IV anesthesia with propofol and fentanyl. After anesthesia induction, a transesophageal echocardiography probe was inserted into the esophagus. IPPV (TV, 8-10 mL/kg; respiratory rate, 10-12 cycles/min; I/E ratio, 1:2; FIO(2), 1.0) and HFJV (driving pressure, 0.5-0.6 kgf/cm(2); frequency,3 Hz; I/E ratio, 1:1; FIO(2), 1.0) were performed under hemodynamically stable conditions. MEASUREMENTS: Pulmonary-arterial-flow velocity, pulmonary-venous-flow velocity, left ventricular short-axis view, and airway-pressure curve were recorded simultaneously. Parameters measured were: hemodynamic variables, arterial blood gases, inspiratory airway pressure; [from pulmonary-arterial-flow velocity] pre-ejection period (PEP), acceleration time (AT), right ventricular ejection time (RVET), and their ratios (PEP/AT, AT/RVET); [from pulmonary-venous-flow velocity] time-velocity integral of the first systolic wave (S1), second systolic wave (S2), and diastolic wave (D), and systolic fraction (integral S1 + S2/S1+ S2 + D); [from M-mode] left-ventricular-end systolic volume, left-ventricular-end diastolic volume (LVEDV), stroke volume, cardiac output, and ejection fraction, using Teichholz's method. MAIN RESULTS: Peak inspiratory airway pressure during HFJV was significantly lower than that during IPPV. HFJV significantly decreased PEP/AT, correlating positively with pulmonary arterial pressure, and significantly increased AT and AT/RVET, correlating negatively with pulmonary arterial pressure. Systolic fraction, correlating negatively with left atrial pressure, increased significantly during HFJV, as did LVEDV, stroke volume, cardiac output, and ejection fraction. CONCLUSIONS: Our results suggest that, in comparison to IPPV, HFJV significantly decreases pulmonary arterial pressure and left atrial pressure, resulting in significant increases in cardiac output and ejection fraction in healthy anesthetized adults.     

Hemo- and cardiodynamic action of halothane or isoflurane following peroral long-term pretreatment with nifedipine. An animal experimental study

This study investigated the influence of chronic oral nifedipine on the hemodynamic effects of halothane or isoflurane anesthesia in dogs. Under general anesthesia with fentanyl 0.3 microgram/kg/min i.v. and 3:1 N2O/O2 inhalation mixture a left thoracotomy was performed and two needle force probes were placed in the left ventricular wall to measure myocardial force of contraction. In the halothane group (n = 12) a Hall-effect sensor was placed on the anterior surface of the left ventricle, which in combination with a magnet on the posterior surface allowed measurements of left ventricular diameter. In the isoflurane group (n = 15) a Widney gauge was placed around the left ventricle to measure left ventricular circumference changes. The dogs were also monitored with left ventricular tip manometers, pulmonary arterial thermodilution catheters, and femoral arterial and venous catheters. Prior to surgery, in the halothane group 6 dogs were pretreated with nifedipine 6 mg/kg p.o. for 10 days; the other 6 served as controls. In the isoflurane group, 8 dogs were pretreated with nifedipine in the same way and 7 served as controls. Three hours after instrumentation baseline hemodynamic measurements were performed and repeated 15 min after adding 1 MAC and then 2 MAC halothane or isoflurane. Oral pretreatment with nifedipine caused vasodilation with a significant decrease in systemic vascular resistance (SVR) and mean arterial pressure (MAP); heart rate (HR) and dp/dt max were unchanged in comparison to the control group. The cardiac output (CO) increased. Halothane (1 MAC/2 MAC) had a dose-related circulatory depressant effect. This occurred to the same extent in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Losartan increases renal blood flow during isoflurane anesthesia in sheep

BACKGROUND: Inhaled anesthetics cause a transient reversible depression of renal function by direct renal effects or indirectly by changes in neurohumoral systems or cardiovascular performance. When the sympathetic nervous activity is decreased during anesthesia, other vasoactive systems like vasopressin (AVP) and particularly the renin angiotensin system (RAS) are of importance for blood pressure maintenance. Little is known about how the renal circulation is affected by angiotensin receptor blockade during isoflurane anesthesia. METHODS: The study was performed on isoflurane anesthetized sheep equipped with flow probes (placed around a femoral and a renal artery) and a pulmonary artery catheter. During stable conditions the sheep were given one or more of the following substances: isotonic saline (NaCl); losartan (LOS) 10 mg x kg(-1); prazosin (PRAZ) 0.2 mg x kg(-1) and a vasopressin V1-receptor antagonist (AVP-a) 10 microg x kg(-1). RESULTS: LOS and AVP-a did not affect mean arterial pressure (MAP), whereas PRAZ lowered MAP significantly (from 98+/-12 to 65+/-7 mmHg). Renal blood flow (RBF) increased after LOS treatment (148+/-34 to 222+/-33 ml x min(-1)). The other substances were without effect on RBF. Femoral blood flow remained unchanged after all treatments. CONCLUSION: We conclude that the sympathoadrenal system is still the major determinant for blood pressure maintenance during isoflurane anesthesia in sheep. The apparently increased activity of the renin angiotensin system in this situation causes a reduction in renal blood flow, which is counteracted by angiotensin II AT1-receptor blockade.     

Sympathetic blockade by epidural anesthesia attenuates the cardiovascular response to severe hypoxemia

Blood pressure is usually well maintained during epidural or spinal anesthesia even in the presence of extensive sympathetic blockade. The authors investigated whether hormonal systems support arterial pressure and how the circulation copes with a hypoxic challenge when activation of the sympathetic nervous system is selectively impaired by neural blockade. Accordingly, the effects of high epidural anesthesia alone and combined with hypoxia were evaluated in seven awake trained dogs. On different days, either bupivacaine 0.5% (8-12 ml) or saline (placebo) were randomly injected epidurally and the effects evaluated on cardiovascular (arterial pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, as well as on hormone plasma concentrations (vasopressin, norepinephrine, epinephrine, renin) during both normoxia and hypoxia. During epidural anesthesia alone, vasopressin increased tenfold (1.7 pg/ml +/- 1.0 SD to 16.8 +/- 13.8, P less than 0.05), norepinephrine decreased (90 pg/ml +/- 31 to 61 +/- 28, P less than 0.05) while epinephrine and renin concentrations remained unchanged. Mean arterial and pulse pressure decreased by 13 mmHg and 23 mmHg (P less than 0.05), respectively. In dogs without sympathetic blockade (saline group), hypoxemia (PaO2: 31 +/- 4 mmHg) evoked an increase in mean blood pressure by 37 mmHg +/- 8 and heart rate by 50 beats per min +/- 17. In contrast, in the presence of sympathetic blockade but with a similar degree of hypoxemia, blood pressure failed to increase (+ 1 mmHg +/- 14) and heart rate rose by only 15 beats per min +/- 11. These differences between groups were statistically significant (P less than 0.001). Hypoxemia induced a similar hypocarbia (PaCO2:25 mmHg) in both groups, indicating that the ventilatory response to hypoxemia was preserved after epidural blockade. During hypoxemia vasopressin concentrations increased 35-fold to 64 pg/ml +/- 38 (P less than 0.0001) compared to base line only during epidural anesthesia, but not after epidural saline (2 pg/ml +/- 2), while other hormones showed no significant differences. The authors conclude that high epidural anesthesia in awake unsedated dogs: 1) almost completely abolishes the normal cardiovascular response to hypoxemia while promoting vasopressin secretion; 2) preserves the ventilatory response to hypoxemia; and 3) is associated with increased vasopressin concentrations, most likely to compensate for decreased cardiac filling and/or arterial blood pressure when sympathoadrenal responses are impaired. Thus, the changes in cardiovascular vital signs in response to severe hypoxemia are markedly blunted when spinal sympathetic outflow is selectively eliminated by epidural anesthesia.     

Epidural anesthesia worsens uterine blood flow and fetal oxygenation during hemorrhage in gravid ewes.

Recent studies suggest that epidural anesthesia initiated before hemorrhage may improve survival and acid-base status in laboratory animals. However, studies of hemorrhagic shock in nonpregnant animals may not be applicable to less severe hemorrhage in pregnant animals. The purpose of this study was to determine whether epidural anesthesia alters maternal and fetal hemodynamic and acid-base responses to hemorrhage in gravid ewes. Twenty-four experiments were performed in twelve chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) T = 0 min: normal saline 500 ml intravenously; 2) T = 15 min: epidural administration of 0.5% bupivacaine (epidural group) or normal saline (control group); 3) T = 30 min: epidural administration of additional 0.5% bupivacaine (epidural group only) if the sensory level of anesthesia was below T10; 4) T = 45 min: maternal hemorrhage 20 ml/kg over 55 min; and 5) T = 110 min: transfusion of collected maternal blood over 55 min. At 45 min (i.e., 30 min after the epidural injection of bupivacaine), epidural bupivacaine resulted in a median sensory level of T9 in the epidural group. At that time, maternal mean arterial pressure was less (P less than 0.05) in the epidural group than in the control group (14 +/- 2% below baseline versus 4 +/- 1% above baseline, respectively). Maternal mean arterial pressure, heart rate, cardiac output, and uterine blood flow, and fetal PO2 and pH all were significantly less during hemorrhage (P less than 0.05) in the epidural group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction of anesthesia, beta-receptor blockade, and blood loss in dogs with induced myocardial infarction.

The cardiovascular effects of halothane-nitrous oxide anesthesia, and beta-receptor blockade with either propranolol or practolol, were studied in 15 dogs in which severe myocardial infarction had been induced ten days earlier. The hemodynamic responses to blood loss amounting to 25 per cent of estimated blood volume, and its subsequent replacement, were studied before and after induction of beta-receptor blockade. In terms of cardiac output and aortic blood flow acceleration, cardiac performance in the absence of beta-blockade was markedly impaired during steady-state anesthesia, compared with corresponding values in normal dogs. Practolol (2.0 mg/kg) administered during anesthesia induced no significant circulatory change other than a 14 per cent decrease in heart rate and a 25 per cent increase in strode volum. Propranolol (0.3 mg/kg) caused a comparable reduction of heart rate, but significantly reduced cardiac output (-27 per cent), aortic blood flow acceleration (-26 per cent), and peak LV power (-19 per cent), and increased systemic vascular resistance (+49 per cent). The two drugs caused comparable shifts of the isoproterenol dose-response curve during anesthesia. Graduated blood loss during anesthesia, to a total of 25 per cent of blood volume, caused consistent circulatory changes (decreased mean arterial pressure cardiac output, peak LV power, LV minute work) that were essentially similar before and after beta-receptor blockade with either propranolol or practolol. The positive inotropic effect of calcium gluconate during halothane anesthesia was significantly reduced following either propranolol or practolol, but the hemodynamic responses to changes of systemic vascular resistance induced with acetylcholine or phenylephrine were not modified by beta-receptor blockade.     

Cerebral autoregulation in awake versus isoflurane-anesthetized rats

We evaluated regional cerebral and spinal cord blood flow in rats during isoflurane anesthesia. Tissue blood flow was measured in cerebral cortex, subcortex, midbrain, and spinal cord using radioactive microspheres. Blood flow autoregulation was measured within the following arterial blood pressure ranges (mm Hg): 1 = less than 50, 2 = 50-90, 3 = 90-130, 4 = 130-170, 5 = greater than 170. Arterial blood pressure was increased using phenylephrine infusion and decreased with ganglionic blockade and hemorrhage. Three treatment groups were studied: 1 = awake control, 2 = 1.0 minimum alveolar anesthetic concentration (MAC) isoflurane, 3 = 2.0 MAC isoflurane. Autoregulation was seen in awake rats from 50 to 170 mm Hg in all tissues. The autoregulatory coefficient (change in blood flow/change in blood pressure) was increased in midbrain and spinal cord during 1.0 MAC isoflurane and in all tissues during 2.0 MAC isoflurane (P less than 0.05). Within the arterial blood pressure range of 90-130 mm Hg, isoflurane produced the following changes in tissue blood flow (percent of awake control): 1.0 MAC isoflurane: cortex = 87% +/- 8% (P greater than 0.30), subcortex = 124% +/- 11% (P greater than 0.05), midbrain = 263% +/- 20% (P less than 0.001), spinal cord = 278% +/- 19% (P less than 0.001); 2.0 MAC isoflurane: cortex = 137% +/- 13% (P less than 0.05), subcortex = 272% +/- 24% (P less than 0.001), midbrain = 510% +/- 53% (P less than 0.001), spinal cord = 535% +/- 50% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl

Hepatic blood flow and the oxygen supply/uptake relation were studied in 19 miniature pigs using labeled microspheres. Changes in hepatic arterial blood flow and portal blood flow, as well as total hepatic blood flow during halothane anesthesia were more closely associated with changes in mean arterial pressure (MAP) and cardiac output than during anesthesia with isoflurane or fentanyl. Halothane or isoflurane administered in concentrations that decreased MAP by approximately 30% were accompanied by decreases in hepatic oxygen delivery (DO2th) averaging 46% during halothane and 31% during isoflurane anesthesia and parallel decreases in hepatic blood flow. In concentrations that decreased MAP by 50%, halothane and isoflurane decreased DO2th 61 and 37%, respectively. DO2th was maintained (statistically insignificant, 23% increase) during both doses of fentanyl administered (20 micrograms/kg followed by 0.17 microgram . kg-1 . min-1, and 50 micrograms/kg followed by 0.42 microgram . kg-1 . min-1). Hepatic oxygen uptake increased 50% during fentanyl and was maintained at baseline levels during both doses of halothane and isoflurane anesthesia. Oxygen content in hepatic venous blood was maintained at baseline levels during fentanyl and isoflurane administration and was decreased by both concentrations of halothane anesthesia. The hepatic oxygen supply demand ratio was maintained at baseline levels after both doses of fentanyl and during isoflurane administered in a concentration that decreased blood pressure 30%; the ratio decreased during isoflurane administered in a concentration decreasing blood pressure by 50% and during both doses of halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of inhalational anesthetics on verapamil pharmacokinetics in dogs

Six dogs were chronically instrumented in order to collect aortic blood samples and record mean arterial pressure, cardiac output and heart rate. Each animal received verapamil 200 micrograms X kg-1 by 10-min intravenous infusions on four occasions in random sequence: awake, and during halothane 1.2%, enflurane 2.5%, and isoflurane 1.6% anesthesia. Rate of initial distribution of verapamil was reduced during anesthetic exposure. Verapamil intercompartmental clearance from the central compartment to the peripheral compartment was decreased during exposure to halothane and isoflurane, and tended to decrease during enflurane exposure as well. Verapamil terminal volume of distribution at steady-state was reduced by halothane, enflurane, and isoflurane exposure as compared with awake: 65 +/- 10, 80 +/- 9, and 93 +/- 191, respectively, versus 132 +/- 121 (mean +/- SEM; P less than 0.05). Verapamil total clearance was also reduced by halothane, enflurane, and isoflurane as compared with awake: 37 +/- 4, 39 +/- 2 and 41 +/- 31 X h-1, respectively, versus 64 +/- 71 X h-1 (P less than 0.05). Verapamil administered to awake animals resulted in a decrease from baseline in mean arterial pressure; 95 +/- 8 mmHg versus 108 +/- 4 mmHg (P less than 0.05): and an increase in cardiac output; 2.60 +/- 0.33 1 X min-1 versus 1.93 +/- 0.22 1 X min-1 (P less than 0.05). During halothane, enflurane, and isoflurane anesthesia, verapamil administration resulted in a similar decrease in mean arterial pressure; however cardiac output decreased, in contrast to the increase noted in awake animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of isoflurane-nitrous oxide anesthesia in peripheral and abdominal surgical interventions

The cardiovascular actions of isoflurane-nitrous oxide anesthesia were studied in 20 patients (age rage 46-76 yr) undergoing laparatomy (group A = 13 patients) or peripheral vascular surgery (group B = 7 patients). Measurements were performed in the awake state, 20 min after induction of anesthesia and during surgical stimulation. Isoflurane produced small changes in heart rate but a significant reduction in mean arterial pressure which was due to a reduction in peripheral vascular resistance and myocardial contractility. During surgical stimulation arterial pressure rose above control values in group A but remained below control in group B. Cardiac index and stroke volume index both decreased after induction of anesthesia in group A and B. During surgical stimulation cardiac index increased in group A due to an increase in heart rate but remained below control in group B, while stroke volume index was reduced in both groups throughout the whole procedure. These results suggest, that contrary to the findings in human volunteers, isoflurane produces a significant cardiovascular depression in aged surgical patient.     

Systemic, but not pulmonary, hemodynamics are depressed during combined high thoraco-cervical epidural and general anesthesia in dogs

PURPOSE: An epidural block is frequently combined with general anesthesia. Both systemic and pulmonary hemodynamics may be affected by high epidural anesthesia and the combined general anesthetic. These effects were investigated in a canine model. METHODS: Systemic and pulmonary hemodynamics during a combined high thoraco-cervical epidural and general anesthesia were studied in dogs; the animals were anesthetized with propofol, 10 mg.kg(-1).hr(-1), or 2% sevoflurane, and then 1% mepivacaine, 5 mL, was injected epidurally between T1 and T2. Cardiac output (CO), pulmonary capillary wedge pressure (PCWP), pulmonary arterial pressure (PAP), mean arterial pressure (MAP), central venous pressure (CVP), electrocardiogram, and arterial and mixed venous gases were monitored for over 90 min after epidural mepivacaine. The interval between sevoflurane and propofol studies was two hours. RESULTS: Baseline measurement of MAP with sevoflurane anesthesia was significantly lower (P < 0.05-0.01) at every time point than with propofol anesthesia. After epidural mepivacaine (C1)-T7/8 blockade), MAP (P < 0.05-0.01), CO (P < 0.05-0.01), and heart rate (P < 0.05-0.01) decreased significantly during both propofol and sevoflurane anesthesia. In the sevoflurane group, stroke volume decreased significantly (P < 0.05-0.01) but recovered; however, MAP (P < 0.01) and CO (P < 0.05) did not recover 90 min after the injection. Mean CVP and systemic vascular resistance were not altered. There were no changes in mean PAP, mean PCWP, and pulmonary vascular resistance. CONCLUSION: A combined high thoracic/general anesthesia depressed systemic hemodynamics, whereas the pulmonary circulation was not affected. The extent of the depression varied with the general anesthetics used, sevoflurane and propofol.     

Comparison of three perioperative fluid regimes for laparoscopic donor nephrectomy

Background Pneumoperitoneum (PP), as used for laparoscopic procedures, impairs stroke volume, renal blood flow, glomerular filtration rate and urine output. This study investigated whether perioperative fluid management can abolish these negative effects of PP on hemodynamics. Methods Twenty-one patients undergoing laparoscopic donor nephrectomy (LDN) were randomized into three groups: group 1 received overnight infusion and received a bolus of colloid before induction of anesthesia, followed by a bolus just before PP; group 2 received overnight infusion and a colloid bolus before anesthesia; group 3 served as controls and received only infusion during operation. All three groups received the same total amount of crystalloids and colloids until nephrectomy. Data analysis of the donor included; mean arterial pressure (MAP), stroke volume (SV), left ventricular ejection time (LVETc), perioperative urine output and renal function measured as the creatinine clearance (CrCl) until one-year post-operative. Results SV was significantly higher in group 1 compared to controls for all measurements. In the control group SV significantly decreased after changing from the supine to lateral position whereas there was no change in SV in both pre-hydrated groups. In all groups, MAP decreased after induction of anesthesia, and restored to pre-anesthetic values during PP. CrCl decreased in the control group during PP, but not in the other groups. From two days postoperative, CrCl was comparable between the three study groups. Conclusion Overnight infusion and a bolus of colloid just before PP attenuate hemodynamic compromise from PP. This study was performed at the Department of Anesthesiology, Erasmus University Medical Center Rotterdam and was financially supported by this Department     

Cardiovascular effects of acute changes in extracellular ionized calcium concentration induced by citrate and CaCl2 infusions in chronically instrumented dogs, conscious and during enflurane, halothane, and isoflurane anesthesia

To study the cardiovascular effects of low blood ionized calcium ion concentrations [Ca2+] induced by citrate infusion followed by high [Ca2+], induced by CaCl2 infusion awake and during enflurane (2.5% ET), halothane (1.2% ET), and isoflurane (1.6% ET) anesthesia, dogs were chronically instrumented to measure heart rate, aortic, left atrial, and left ventricular (LV) blood pressures, and cardiac output. In conscious dogs low [Ca2+] (decreased 0.35 mM); increased heart rate (HR) and mean aortic pressure (MAP) and decreased stroke volume (SV) and LV dP/dtmax. Low [Ca2+] increased HR during all three anesthetics and decreased LV dP/dtmax except during isoflurane anesthesia. Low [Ca2+] produced more hemodynamic depression during enflurane anesthesia than during anesthesia with halothane or isoflurane increasing left atrial pressure and decreasing MAP and SV. The differences seen were partially related to decreased systemic vascular resistance during halothane and isoflurane anesthesia. In conscious dogs following high [Ca2+] (increased 0.37 mM); only MAP and LV dP/dtmax increased. LVdP/dtmax was also increased by high [Ca2+] during all three anesthetics without a change in MAP. Cardiac output increased during halothane and isoflurane anesthesia but was unchanged during enflurane. It would appear that the hemodynamic sensitivity for the effects of changing [Ca2+] was enflurane greater than halothane greater than isoflurane greater than awake. The results suggest that the effects of changes in [Ca2+] induced by citrate and CaCl2 infusion are modified by the three volatile anesthetics.     

Does calcium chloride help restore maternal blood pressure and uterine blood flow during hemorrhagic hypotension in hypermagnesemic gravid ewes?

Magnesium sulfate worsens maternal hypotension and fetal oxygenation during hemorrhage in gravid ewes. The purpose of this study was to determine whether calcium chloride administration is a useful adjunct to blood transfusion during hemorrhagic hypotension in hypermagnesemic gravid ewes. Sixteen experiments were performed in eight chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included (a) T = 0: magnesium sulfate 4 g IV; (b) T = 5: infusion of magnesium sulfate 4 g/h IV; (c) T = 90: maternal hemorrhage 20 mL/kg over 55 min; (d) T = 147: calcium chloride 10 mg/kg or normal saline (NS-control) 0.1 mL/kg IV; (e) T = 160: transfusion of collected maternal blood over 55 min. Magnesium sulfate alone slightly decreased maternal mean arterial pressure (P = 0.002) and increased uterine blood flow (P = 0.0001) in both groups before hemorrhage. During hemorrhage, maternal mean arterial pressure, cardiac output, and uterine blood flow, and fetal PO2 and pH all decreased sharply (P = 0.0001). Cardiac output increased (P = 0.0005) modestly just after the intravenous bolus of calcium chloride. Maternal mean arterial pressure was significantly higher (P = 0.03) during transfusion in the calcium chloride group than in the NS-control group, but only after mean arterial pressure was near baseline measurements. Maternal uterine blood flow and fetal PO2 and pH responses over time were similar in the two groups. We conclude that intravenous administration of calcium chloride (10 mg/kg) transiently increased cardiac output during hemorrhagic hypotension and slightly increased mean arterial pressure during transfusion in hypermagnesemic gravid ewes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in normovolemic and hypovolemic cirrhotic rats

The effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in cirrhotic rats that were either normovolemic or hypovolemic following hemorrhage were characterized. Rats received at random either ketamine (30 mg/kg iv, 1.5 mg.kg-1.min-1 iv), halothane, enflurane, or isoflurane (1 MAC). Conscious rats were considered the control group. Four weeks before hemodynamic studies bile duct ligation was performed in all rats to induce cirrhosis. Hemodynamic measurements were performed using the radioactive microsphere method 1 h after the onset of anesthesia and 30 min after hemorrhage. Anesthetized rat lungs were mechanically ventilated with room air. Before hemorrhage cardiac index was higher in conscious rats and in rats receiving isoflurane than in the other groups (P less than 0.001). Hepatic arterial blood flow was similar in conscious rats and in those receiving isoflurane or halothane and was higher than in those receiving ketamine or enflurane. The lowest splanchnic and portal venous tributary blood flows were observed in rats receiving enflurane. After hemorrhage cardiac index was significantly less than before hemorrhage in all groups, except in rats receiving enflurane. After hemorrhage portal venous tributary blood flow decreased significantly in all groups except in enflurane group. During halothane and enflurane anesthesia hepatic arterial blood flow and hepatic arterial fraction of cardiac output decreased (P less than 0.01) and they were maintained in the other groups. After hemorrhage hepatic arterial fraction of cardiac output in conscious rats was higher than in those receiving ketamine, halothane, or enflurane (P less than 0.05) and was similar to those receiving isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)     

The cardiocirculatory and metabolic effects of endotoxin challenge after canine resuscitated hemorrhagic shock

Although adequate volume resuscitation has decreased mortality from hemorrhagic shock, recovery in many patients is complicated by sepsis. To determine whether a subject debilitated by hemorrhagic shock would exhibit greater cardiocirculatory dysfunction when challenged with sepsis, ten dogs (Group I) were hemorrhaged to a mean arterial blood pressure of 30 mm Hg. After 2 hours of hypotension, shed blood and lactated Ringer's solution (50 ml/kg) were given, and the dogs were observed for 3 to 6 days. Ten dogs were sham hemorrhage and served as controls (Group II). On the experimental day, all cardiovascular and hemodynamic parameters were measured in both groups of animals before endotoxin challenge. There was no significant difference in cardiac output, stroke volume, stroke work, +dP/dt max, myocardial blood flow, myocardial oxygen metabolism, or acid-base balance in the two groups. Compared to sham-hemorrhaged dogs, resuscitated shock dogs had a significantly lower mean arterial blood pressure (127 +/- 7 vs. 110 +/- 6 mm Hg; p less than 0.05), and heart rate was significantly higher (86 +/- 6 vs. 109 +/- 7 beats/minute; p less than 0.05). Furthermore, maximal rate of left ventricular pressure fall (-dP/dT max) was significantly lower in the animals previously hemorrhaged, suggesting a persistent defect in left ventricular relaxation. Blood glucose and insulin levels were significantly elevated in the resuscitated shocked dogs, likely due to increased circulating catecholamine concentrations and enhanced glycogenolysis. Endotoxin shock caused significant hypotension, acidosis, and impaired regional perfusion in all dogs. In addition, cardiac output, stroke volume, dP/dT, and left ventricular end-diastolic pressure fell and hyperglycemia and hyperinsulinemia occurred in all dogs after endotoxin injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Depth of halothane anesthesia potentiates citrate-induced ionized hypocalcemia and adverse cardiovascular events in dogs

The purpose of this study was to determine if depth of halothane anesthesia contributed to the adverse cardiovascular effects of citrate-induced ionized hypocalcemia. Six mongrel dogs were monitored with arterial, central venous, and pulmonary artery flow-directed catheters. Measured end-tidal halothane assured a constant depth of anesthesia, while controlled ventilation and arterial blood gas analysis provided constant acid-base status. Each dog received sodium citrate (USP Fenwal) equivalent to fresh frozen plasma, 1.0 ml.kg-1.min-1, during both deep (D) and light (L) halothane anesthesia. Three dogs received the infusion during L halothane anesthesia first; after a 1-h stabilization period (2.5 h after first infusion) they received a second equivalent infusion during D halothane anesthesia. Three other dogs were studied first with D, then with L halothane. Mean expired halothane (+/- SEM) for group D was 1.52 +/- 0.08%, for group L, 0.85 +/- 0.07%. Significantly greater adverse cardiovascular effects were seen during D halothane anesthesia; four of the six dogs that received citrate during D halothane anesthesia required cessation of the infusion or suffered cardiac arrest. All six infusions during L halothane anesthesia were tolerated. In both groups, significant reductions in ionized calcium [Ca++] (P less than 0.0001) and mean arterial pressure (MAP) (P less than 0.005) were observed; greater reductions in both parameters occurred in group D (P less than 0.0036-0.0005). In group D, but not in group L, cardiac output was depressed compared to baseline (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral hemodynamic effects of fluid resuscitation in the presence of an experimental intracranial mass

We addressed the impact on intracranial pressure (ICP) of posthemorrhage fluid resuscitation with a protocol in which additional fluid was infused to maintain a stable cardiac output after an initial bolus of fluid was infused. Anesthetized, mechanically ventilated mongrel dogs (n = 27) underwent a 30-minute interval of hemorrhagic shock (mean arterial pressure = 55 mm Hg) during which inflation of a subdural balloon maintained ICP at 15 mm Hg. After shock, animals were resuscitated with one of four randomly assigned fluids: (1) slightly hypotonic crystalloid (Na+, 125 mEq.L-1; designated Na-125); (2) hypertonic crystalloid (Na+, 250 mEq.L-1; designated Na-250); (3) slightly hypotonic crystalloid plus 10% pentastarch (Na-125P); or (4) hypertonic crystalloid plus 10% pentastarch (Na-250P). Supplemental fluid was administered as needed to maintain cardiac output comparable to baseline values. ICP increased progressively in all fluid groups during resuscitation. Cerebral blood flow, measured by the cerebral venous outflow method, increased immediately after resuscitation and then declined steadily over time in all groups. Fluids containing pentastarch maintained hemodynamic stability with minimal supplementation throughout most of the postresuscitation period, compared with crystalloid alone, which required substantial additional volume. If decreased intracranial compliance and hemorrhage are combined, ongoing resuscitation is associated with significantly increased ICP and significantly decreased cerebral blood flow, independent of the tonicity and oncotic pressure of the infused fluid.     

Limited upper thoracic epidural block and splanchnic perfusion in dogs

Epidural blockade leads to a sympathetic block in affected segments and an increase of sympathetic out-flow from various unblocked segments. A limited upper thoracic epidural block (LUTEB) is used during coronary artery surgery affecting the cardiac sympathetic fibers cephalad to the fifth thoracic segment. This block does not extend to the sympathetic fibers innervating the gastrointestinal organs. A LUTEB may lead to an increase of sympathetic activity in the unaffected splanchnic sympathetic segments and the decrease in splanchnic blood flow may contribute to gastrointestinal ischemia after cardiac surgery. We tested the hypothesis that a LUTEB decreases splanchnic perfusion in anesthetized dogs. Thirteen dogs were chronically instrumented with aortic and left atrial catheters, which were used for pressure measurement, as well as injection and withdrawal of reference samples. Thoracic epidural catheters were placed under general anesthesia the day before the experiment. Splanchnic blood flow was determined by using colored microspheres. Induction of a LUTEB did not change general hemodynamics in awake dogs. Propofol anesthesia induced an increase in heart rate that was abolished after LUTEB. LUTEB also decreased mean arterial pressure during propofol anesthesia. We conclude that thoracic epidural anesthesia had no effect on splanchnic blood flow. In propofol anesthetized animals, liver blood flow was increased compared with awake animals; however, it did not change after induction of LUTEB. IMPLICATIONS: A sympathetic block in certain segments leads to increased sympathetic output in unblocked segments. For an upper thoracic epidural block, this might lead to impaired splanchnic perfusion. In awake and propofol-anesthetized, chronically instrumented dogs, however, a limited upper thoracic epidural blockade had no compromising effect on gastrointestinal perfusion.