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Biomedical subjects

J G Toole

Publications and source records attributed to J G Toole.

10 recordsLinked to original sources

Pentafraction for superior resuscitation of the ovine thermal burn.

OBJECTIVE: To determine if a new hydroxyethyl starch, pentafraction, will cause better capillary retention of fluid in thermally burned and nonburned tissues when compared with some currently used volume expanders. DESIGN: Randomized, controlled, experimental study. SETTING: University research laboratory. SUBJECTS: Twenty-one healthy adult range ewes. INTERVENTIONS: Sheep, surgically prepared for chronic study, were randomly assigned to one of three colloid groups for the resuscitation of thermal injuries: a) ovine fresh-frozen plasma group; b) pentastarch group; and c) pentafraction group. Twenty-one sheep were subjected to a 40% total body surface, third-degree flame burn under anesthesia (1.5% to 2% halothane). When awakened, the sheep received 15 mL/kg of one of the above colloids, and then lactated Ringer's solution (2 mL/hr/kg). All animals survived and were killed at 48 hrs after burn injury. MEASUREMENTS AND MAIN RESULTS: We found that cardiac index decreased and systemic vascular resistance increased in the pentastarch and plasma groups. However, cardiac index increased in the pentafraction group, while systemic vascular resistance increased by only half as much as in the other two groups. Cardiac index in the plasma group decreased significantly for the first 8 hrs, and did not return to the baseline value for 48 hrs. Systemic vascular resistance increased significantly for the first 8 hrs in both the plasma and pentastarch groups. Prefemoral lymph flow was significantly more increased in the pentastarch group, while the lung lymph/plasma oncotic gradient was maintained only by the pentafraction group. CONCLUSIONS: Pentafraction is as good, or even superior, for volume resuscitation in the burn patients, when compared with pentastarch and plasma. This conclusion is made most evident by the attenuated changes in systemic vascular resistance and cardiac index. Pentafraction decreases the fluid flux and potential subsequent edema significantly in burned tissues and effectively maintains the pulmonary microvascular integrity.

Animals↗

Combined use of esmolol and digoxin in the acute treatment of atrial fibrillation or flutter.

Safety and efficacy of simultaneous use of intravenous digoxin and esmolol in the control of rapid heart rate in 21 patients with atrial fibrillation or flutter was assessed. The mean age was 67 (range 40 to 90) years. Seven patients had class III congestive heart failure, with left ventricular ejection fraction between 18% and 61%. Baseline mean heart rate was 143 +/- 4. After 0.25 mg or 0.5 mg intravenous digoxin, esmolol was titrated with initial boluses from 2 mg/min to 16 mg/min in 25 minutes. A tolerated dose of esmolol infusion was adjusted for up to 48 hours. Rapid control of heart rate (29% decrease with heart rate 101 +/- 4) occurred at a mean interval of 21 minutes. Minimum heart rate was 87 +/- 4 at 90 minutes of treatment. Conversion to sinus rhythm occurred in five patients (25%), and one patient experienced mild transient congestive heart failure. No symptomatic hypotension or bronchospasm occurred. In conclusion, simultaneous use of digoxin and esmolol is effective in safely and rapidly controlling heart rate in atrial fibrillation or flutter.

Adrenergic beta-Antagonists↗

Effects of esmolol on patients with left ventricular dysfunction.

This study examined the effect of esmolol, an ultrashort-acting beta-receptor blocker, in 10 patients with severe left ventricular dysfunction. Simultaneous hemodynamic and radionuclide angiographic measurements were obtained at incremental doses of esmolol (2, 4, 8, 12 and 16 mg/min). At a dose of 4 mg/min, esmolol produced beats blockade: a decrease in heart rate from 91 +/- 4 to 83 +/- 4 beats/min (p less than 0.05) (mean +/- SEM) and a decrease in systolic aortic pressure from 133 +/- 5 to 128 +/- 5 mm Hg (p less than 0.05). At the maximal dose, the heart rate decreased to 79 +/- 3 beats/min (p less than 0.05) and biventricular function was depressed; the left ventricular ejection fraction decreased from 27 +/- 2 to 21 +/- 2% (p less than 0.05) and the right ventricular ejection fraction decreased from 38 +/- 2 to 29 +/- 2% (p less than 0.05). These changes were accompanied by increases in left ventricular end-diastolic volume (p less than 0.05), left ventricular end-systolic volume (p less than 0.05) and pulmonary artery wedge pressure (p less than 0.05), as well as a decrease in cardiac output (p less than 0.05). The hemodynamic abnormalities (which showed considerable interindividual variability) returned to near baseline levels 10 to 30 minutes after infusion was stopped. Thus, esmolol can be administered to patients with severe left ventricular dysfunction. The beneficial effect (beta-adrenergic blockade) is usually achieved with small doses without clinically important hemodynamic changes. At larger doses, however, significant changes in biventricular function may be observed.

Adrenergic beta-Antagonists↗

Pharmacokinetics and efficacy of pirmenol hydrochloride in the treatment of ventricular dysrhythmia.

Pirmenol hydrochloride (CI-845), a new antiarrhythmic agent available for both oral and intravenous administration, was given to seven patients with chronic ventricular dysrhythmia in an open-label fashion. After intravenous infusion of 150 mg over 30 min, the mean (+/- SD) peak plasma concentration achieved was 2.14 +/- 0.75 microgram/ml. The terminal elimination half-life, the volume of the central compartment, and the total body clearance averaged 6.5 h, 0.70 +/- 0.36 L/kg, and 3.0 +/- 2.6 ml/min/kg, respectively. After a single 150-mg oral dose, the peak plasma concentration of 1.3 +/- 0.55 microgram/ml was achieved 1 to 3 h after dosing. The mean apparent elimination half-life was 7.6 h. An estimated absorption lag time ranging from 14 to 37 min was observed in all but one patient. The mean absolute bioavailability for the oral dose was 87%. Dysrhythmia data were available in six patients. Complete (100%) suppression of ventricular ectopic beats occurred in four patients for 1/2 to 15 h after intravenous infusion, and in three patients for 7 to 25 h after oral dose. This suppression occurred with a plasma pirmenol level as low as 0.4 microgram/ml. No significant side effects were observed.

Administration, Oral↗