A new method to evaluate cardiovascular response in anesthetized rats. Hypertension after variable intensity, brief electrical stimuli.

To establish and standardize a nociceptive response in anesthetized rats, the hypertensive responses to defined electrical and mechanical stimuli were studied. Rats (n = 7) were given etomidate, 3.8 mg/kg/hr intravenously (i.v.) 2 hr following carotid artery and jugular vein cannulation. At 15 min after beginning the infusion, four types of noxious stimuli were administered sequentially at 1-min intervals (14 stimuli total): Type 1: Square electrical waves, 125 cps, 1.6 msec, 2-sec train duration, varying current from 0.4 to 12 mA (11 stimuli); Type 2: A single 10-mA electrical stimulus, 5-sec train duration; Type 3: Tail clamping; and, Type 4: Skin incision. After each stimulus, maximum change in systolic blood pressure (delta SBP) was measured. delta SBP after the most intense stimuli was as follows: Type 1 (12 mA, 2 sec), 32.1 +/- 2.14 mmHg; Type 2 (10 mA 5 sec), 42.9 +/- 2.4 mmHg; Type 3 (tail-clamping), 34.3 +/- 3.3 mmHg; Type 4 (skin incision), 14.2 +/- 2.8 mmHg. For the multiple Type-2 stimuli, a relationship between current and delta SBP was present. The authors believe that characterized graded electrical stimulation will allow a more quantitative evaluation of the hypertensive response to noxious stimuli in etomidate anesthetized rats, as compared to observing a single response to a single stimulus. The characterization of the electrical stimulation by amplitude, frequency, and wave form makes research work on nociception under anesthesia easily reproducible.

A new model to evaluate the hypertensive response to noxious stimuli in the anesthetized, spontaneously hypertensive rat.

We have developed a method to evaluate the hypertensive response after noxious stimuli in anesthetized rats. Anesthetic level, stimuli, and responses were standardized by using an etomidate infusion, a series of stimuli of increasing intensity applied to the tail, and measuring maximal changes in systolic blood pressure (delta SBP) after each stimulus. Normotensive Sprague Dawley rats (SD) (n = 7) were studied using an etomidate infusion of 4.2 mg.kg-1 x h-1. This method was then applied to spontaneously hypertensive rats (SHR) anesthetized with three rats of etomidate infusion: Group 1 (n = 8), 7.0 mg.kg-1 x h-1; Group 2 (n = 8), 5.6 mg.kg-1 x h-1; and Group 3 (n = 11), 4.2 mg.kg-1 x h-1. Under anesthesia, three types of noxious stimuli were applied to the tail at 1-min intervals (13 total): (a) Type 1:11 2-s electrical stimuli of increasing intensity (0.4-12 mA, to produce threshold to maximal responses); (b) Type 2: one intense, prolonged electrical stimulus (10 mA, 5 s); and (c) Type 3: tail-clamping. After each stimulus, delta SBP was measured. In the SHR, comparing single delta SBP responses to single noxious stimuli after each of the three most intense stimuli showed no statistically significant differences among the three anesthetic groups. In contrast, comparison of dose-response curves of multiple delta SBP responses to multiple Type 1 (2-s) stimuli demonstrated a significant difference among the three anesthetic groups of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

General anesthesia for cesarean section in a parturient with a single ventricle and pulmonary atresia.

The successful management of a cesarean section in a parturient with a single ventricle and pulmonary atresia using general anesthesia is discussed. After cyanosis at birth, the patient underwent cardiac catheterization, which showed an apparent severe tetralogy of Fallot, atresia of the main pulmonary artery (PA), and a large patent ductus arteriosus. When she was 7 months of age, a Blalock-Taussig shunt (right subclavian artery to right PA) was done. She remained stable until age 11, when cyanosis increased and exercise tolerance decreased. Recatheterization more clearly defined the lesion: closed shunt, pulmonary valvular atresia, severe ductal stenosis, reduced pulmonary flow, double-outlet right ventricle, and severe hypoplasia of the left atrium, mitral valve, and left ventricle. A Potts shunt (left descending aorta to left PA) was done. Compliance with therapy was poor and follow-up difficult. Exercise tolerance was poor, but the patient remained otherwise stable. At 28 weeks' gestation, this 23-year-old parturient presented with severe congestive heart failure (CHF). After initial therapy with oxygen, bed rest, digoxin, and diuretics, she improved and remained stable for a month. At that time (32 weeks' gestation), CHF worsened. Because the cervix was unfavorable for a vaginal delivery, a cesarean section was planned. The patient was then taken to the operating room electively, and an opioid-based general anesthetic was administered. Both mother and infant did well. This case is presented because the physiology of the patient's lesion and her unusual social history presented challenges for her anesthetic management.

Backache after extradural anaesthesia in the postpartum period: dissection of thoracic aneurysm.

We describe a case of postpartum ruptured dissecting aneurysm of the thoracic aorta, unrelated to the anaesthetic management with extradural anaesthesia. This complication is discussed in detail, as the anaesthetist may be the specialist required to respond to the common presenting symptom of severe back pain.

A rodent model for studying four well defined toxic endpoints during bupivacaine infusion.

An animal model with four well defined endpoints for studying the cardiotoxicity and neurotoxicity of bupivacaine is described. Five male Wistar rats (264-324 g) were anesthetized, tracheostomized and ventilated, and ECG and EEG leads were placed. Femoral arteries and veins were then cannulated. Twenty minutes before bupivacaine infusion, 0.1 mg/kg pancuronium was given intravenously, and anesthesia was adjusted to halothane 0.5%, 30% O2 and 70% N2O. Bupivacaine infusion was then begun at 2 mg/kg/minute. Bupivacaine doses producing the following endpoints were then determined: (1) first ventricular arrhythmia (ARR), (2) seizures (SZ), (3) isoelectric EEG (ISO EEG), and (4) asystole (ASYS). The doses of bupivacaine (in mg/kg +/- SD) precipitating AAR, SZ, ISO EEG and ASYS were 4.22 +/- 1.87, 7.08 +/- 1.55, 11.05 +/- 5.15 and 20.4 +/- 6.49 mg/kg, respectively. These endpoints were present and readily determined in all animals. The doses of bupivacaine producing ARR and SZ were not significantly different (p greater than 0.05). The doses producing SZ, ISO EEG and ASYS were significantly different from each other (p greater than 0.05, ANOVA and the Duncan test). These results indicate that it is possible to study, in the anesthetized and paralyzed rat that is intensely monitored, many of the variables associated with local anesthetic toxicity currently of clinical interest. The use of a constant local anesthetic infusion allows ready observation of the progression of toxic signs.

Peripartum colloid osmotic pressure changes: effects of controlled fluid management.

A prospective, fluid-controlled study of serially measured colloid osmotic pressure changes in the peripartum period was undertaken. Seventeen patients with uncomplicated pregnancies undergoing elective cesarean section at term were administered a predelivery bolus of 15 ml/kg of lactated Ringer's solution prior to operation. Maintenance crystalloid fluids were infused at 125 to 150 ml/hr both intraoperatively and post partum without the addition of blood or other colloid solutions. Serial colloid osmotic pressure measurements were obtained before hydration, after hydration, after delivery, and at 6 and 24 hours post partum. The results demonstrated a 15.9% decline in colloid osmotic pressure immediately following the hydration bolus (20.7 +/- 1.5 to 17.4 +/- 1.8 mm Hg) (p less than 0.01). A further decline in colloid osmotic pressure to 16.6 +/- 1.7 mm Hg occurred after delivery and represented an overall 22% decrease from the baseline value (p less than 0.05). The lowest mean colloid osmotic pressure value occurred at 6 hours post partum (16.1 +/- 1.1 mm Hg). These data support previous observations that colloid osmotic pressure is uniformly lowered in the immediate postpartum period with peak reductions identified at 6 hours following delivery. In addition, intravenous crystalloid administration during the peripartum interval can substantially influence this decline in colloid osmotic pressure. Although no clinical evidence of cardiopulmonary compromise was observed in this set of normal gravid women, these data may be useful in the management of the parturient patient with established risk factors for pulmonary edema where alterations in the pulmonary capillary wedge pressure-colloid osmotic pressure gradient have been shown to correlate with the development of this complication.

Influence of blood sampling conditions upon histamine concentrations in rat plasma: a study of a complex relationship with plasma epinephrine.

The concentrations of histamine reported vary considerably from species to species. The present studies sought to determine if blood sampling techniques were at least in part responsible for this large variability. Since plasma catecholamines are influenced by the stress associated with blood sampling, these biogenic amines also were measured. Finally, we explored the possible existence of a relationship between plasma histamine and plasma catecholamine concentrations. The present study confirms that concentrations of histamine in rat plasma are particularly large and establishes that the manner (e.g. awake, anesthetized) and site (e.g. intravenous, decapitation) of blood removal influence the concentrations obtained. The lowest histamine values were seen in samples taken from blood vessels in anesthetized rats. Blood obtained after decapitation showed increasing concentrations of plasma histamine in sequentially obtained samples. An inverse relationship appeared to exist between plasma histamine and plasma catecholamines (predominantly epinephrine). An inhibitory role of epinephrine upon decapitation-associated histamine release was suggested by the observation that both adrenalectomy and catecholamine depletion (alpha-methyl-para-tyrosine) elevated histamine concentrations. Our studies with propranolol, as well as work by other investigators, establish an inhibitory role of ?-receptor stimulation on the release of histamine. On the other hand, histamine injected into the perfused rat adrenal caused a marked release of adrenomedullary catecholamines. In summary our study suggests the presence of a complex interaction between catecholamines and histamine in the regulation of the release of the individual amines. Our findings point to the existence of a histamine-adrenal axis in which the release of histamine may facilitate the release of epinephrine which in turn may restrict further release of histamine.

Effect of lymphatic cannula outflow height on lung microvascular permeability estimations.

Estimates of the pulmonary microvascular membrane reflection coefficient (sigma) and permeability-surface area product (PS) are frequently made with the assumption that a percent change in transmicrovascular fluid flux (Jv) will be represented by an equal percent change in the lymph flow rate (QL) from a single cannulated lung lymph vessel. To test this, we measured QL in seven anesthetized dogs with the outflow end of the lymph cannula set at several heights (H) above and below the lung hilus. The left atrial pressure was then elevated to increase Jv, and QL was again measured at several H's. The percent increase in QL at elevated left atrial pressure depended on H. We used the QL data and lymph and plasma protein concentrations to estimate sigma and PS with a modified form of the Kedem and Katchalsky equations. The calculated values varied considerably with H. Our results indicate that changes in Jv are not represented by equal changes in QL. Therefore, techniques for estimating permeability that depend upon QL as an estimate of Jv may lead to erroneous estimates of sigma and PS.

Complications of the Ehlers-Danlos syndrome in pregnancy. A case report.

The Ehlers-Danlos syndrome (EDS) is a disorder of the connective tissue characterized by hyperextensible skin, loose jointedness, fragile tissues, bruising and bleeding diathesis. At least eight subtypes of EDS are recognized, each one with different clinical manifestations. On rare occasions EDS is associated with pregnancy. These patients are at risk for bleeding disorders and vascular, surgical and anesthetic complications as well as for premature labor, postpartum hemorrhage, bladder and uterine prolapse, abdominal hernias and wound dehiscence. We treated a pregnant patient for type 1 EDS and pregnancy-induced hypertension.

Mechanism of action of methyldopa in the rat. Role of 3-O-methylated metabolites.

We studied the effect of 3-O-methyl-methyldopa (OMMD), the 3-O-methylated metabolite of the antihypertensive drug methyldopa (alpha-methyldopa, AMD), on blood pressure in the spontaneously hypertensive rat. OMMD lowered blood pressure in a dose-related manner when given orally or intraperitoneally. Its action lasted longer than that of AMD, and daily oral administration produced a cumulative fall in blood pressure. Oral and intraperitoneal OMMD produced similar reductions of blood pressure and similar tissue OMMD levels. After intraperitoneal injection of different doses, levels of OMMD measured in brain, spinal cord, and plasma correlated with the magnitude of the antihypertensive effect. No AMD was detected in tissues after either route of administration, which suggests that the antihypertensive effect was not based on demethylation of OMMD to AMD. Peripheral inhibition of the enzyme, aromatic amino acid decarboxylase (AAAD), failed to suppress OMMD's effect on blood pressure; in contrast, central inhibition of AAAD did decrease OMMD's antihypertensive effect. These observations suggest that 3-O-methylated metabolites may participate in the antihypertensive effect of AMD.