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In our continuing efforts to design nontoxic and biodegradable fuel-system icing-inhibitor (FSII) compounds with improved fuel solubility and anti-icing ability, and nontoxic deicers for aircraft and runways, we describe experimental and molecular modeling efforts that allow us to predict the relative performance of FSII candidates. A small-scale, recirculating simulator containing a mixture of jet fuel, FSII, and water was employed to measure the time needed for the water to freeze and the lowest temperature to be achieved before freezing. The molecular model is based on classical molecular dynamics (MD) simulations of a two component mixture consisting of FSII and water. We assume that anti-icing performance is proportional to the degree of hydrogen bonding between FSIIs and water and, therefore, inversely proportional to the degree of hydrogen bonding between water molecules. FSII performance should therefore increase with decreasing water-cluster size, which is calculated from the MD equilibrium trajectories and defined as the average number of water molecules hydrogen bonded to a given water molecule. A good agreement is found between the theoretical and experimental performance rankings for twelve FSIIs and FSII candidates.

IOCHEMICAL reactions of myocardial cells to infarction are of basic interest in arrhythmia research. The purpose of the present investigation was to measure in the same dogs concentrations of K, Na, Ca and Mg in coronary sinus and arterial blood before infarction, during a period of ventricular arrhythmia following coronary artery occlusion, and in infarcted and noninfarcted heart tissue. For comparative purposes, similar analyses were made in control, sham-operated animals. MethodsMyocardial infarction was produced by the method of Harris 1 which consisted of ligating the left anterior descending coronary artery in 2 stages. The resultant ventricular arrhythmia, •which begins 5 to 6 hours following occlusion with the appearance of scattered ectopic beats and then develops into a nearly complete ventricular tachycardia 10 to 15 hours postligation, has been described by Clark and Cummings.2 For controls, similar experiments were carried out on shamoperated animals in which ligatures were merely placed under the coronary artery.Blood samples for hematocrit and plasma electrolyte determinations were obtained by direct puncture of the coronary sinus and the common carotid artery. At the start of the coronary occlusion and sham-ligation experiments, 2 control plasma samples were collected 30 minutes apart. Then, beginning 8 hours after ligature placement, additional plasma samples were obtained at hourly intervals. An 8 to 11 hour postligation collection

Butaclamol is a member of a new chemical class for which antipsychotic activity in humans has been demonstrated. Butaclamol, a racemate, has been resolved into its optical isomers and a separation of activities was found to occur between the (+) and (-) enantiomers. The present experiments show that at doses ranging from 0.1 to 0.3 mg/kg the (+) enantiomer abolished amphetamine-induced (a) stereotyped behavior and (b) rotational behavior in rats with unilateral lesions in the substantia nigra. It also inhibited the lever-pressing response in the continuous (Sidman) avoidance procedure, blocked discriminated avoidance behavior, and decreased ambulation and rearing in the open field. In contrast, the (-) enantiomer was devoid of behavioral activity at 100-500 times larger doses. At considerably higher doses (+)-butaclamol antagonized epinephrine-induced mortality. Again, the (-)-butaclamol was devoid of this activity as well. The significance of absolute optical specifity manifested by a neuroleptic drug is discussed in the light of dopaminergic and adrenergic mechanisms.

testing the action of antiarrhythmic drugs on ventricular arrhythmias, the 2-stage ligation of the anterior descending coronary artery in the dog, as developed by Harris,' yields a useful test preparation with a predictable, longlasting ventricular tachycardia. This method has been used extensively in this laboratory*, 3, because: (1) the arrhythmia is etiologically similar to 1 type of ventricular arrhythmia occurring in man; (2) its persistence permits repeated tests and some estimate of duration of drug action; and (3) simultaneous evaluations may be made of both activity and toxicity in the unanesthetized animal. This paper will describe the characteristics of the coronary dog preparation, the method of evaluating antiarrhythmic activity, a comparison of drug responses in various experimental ventricular arrhythmias, and a correlation of these tests with results in man. Preparation and Characteristics of the ''Coronary Dog"The 2-stage ligation of the anterior descending coronary artery is performed under aseptic conditions with pentobarbital anesthesia. The ligatures are placed 0 to 5 mm. below the tip of the left auricular appendage, and 30 minutes are allowed between partial and complete occlusion. The chest is closed in layers, the pneumothorax is reduced, and the animal is allowed to recover from anesthesia. Immediately following complete occlusion there is usually little disturbance in rhythm, but within 5 to 7 hours premature ventricular beats appear regularly and increase in frequency until, after 10 to 15 hours, there exists a relatively high-rate ventricular tachycardia ranging between 180 to 280 beats per minute. The nearly complete ventricular ectopic rhythm usually persists for a t least 24 hours. By the second postoperative day, however, the total rate is usually lower, and sinus beats are evident. Spontaneous reversion to sinus rhythm occurs within 72 hours. The fully developed arrhythmia, as judged from the ECG, appears to be largely or entirely of ectopic ventricular origin, and it is usually multifocal. Ordinarily the P wave is absent or obscured. Occasional beats of apparent nodal origin are seen while, in certain animals, a number of beats of supraventricular origin with aberrant conduction occur. In the typical response to an antiarrhythmic drug, however, all abnormal pacemaker activity is usually suppressed with resumption of sinus rhythm.Most of the deaths were due to ventricular fibrillation occurring at the time of ligation, although a few animals died later unobserved. Only 2 animals failed to develop a significant ventricular tachycardia. The mortality in this preparation is In a series of 92 preparations the mortality was 16 per cent.