Joseph Balkon

A rapid isolation technique for drugs from tissues and fluids: use of the Du Pont Prep 1 system.

A microprocessor-controlled, automated extraction/concentration device, the Prep 1 (Du Pont Clinical Systems), was evaluated for application to the isolation of drug substances from postmortem fluids and tissue homogenates. Two classes of materials were investigated: barbiturates and the benzodiazepine, diazepam. With as little as 200 mg of tissue, barbiturate derivatives were successfully isolated and measured by gas chromatography using nitrogen-phosphorus detection with a coefficient of variation of 2 to 5%. Diazepam was measured in a similar fashion with a coefficient of variation of 4.4%. Preliminary investigation indicates that this system is applicable to a wide range of drug substances of toxicological interest.

A Paraquat Fatality—The Dilemma of Multiple Analyses

Presented is a case of suicidal paraquat poisoning. Postmortem analytical measurement of paraquat content in autopsy specimens was accomplished at two different analytical laboratories using different methodological approaches. Despite some disparate results, all findings indicated acute paraquat poisoning.

Measurement of oxygen tension in the ischemic myocardium using encased polargraphic oxygen electrodes

The ability to continuously monitor the delicate balance between blood flow and oxygen consumption would be a great asset in the study of myocardial ischemia. The present study was performed, in anesthetized dogs, to validate the use of encased polargraphic oxygen electrodes in the study of myocardial ischemia. Polargraphic oxygen electrodes were placed in the area to be rendered ischemic at fixed tissue depths of 3 mm (epicardium) and 9 mm (endocardium). Endocardial and epicardial oxygen tensions as well as the ratio of endocardial to epicardial oxygen tension and left circumflex coronary flow were monitored. Ischemia was induced by decreasing left circumflex coronary flow by 50%. Upon completion of a 20-min poststenotic period, endocardial pO2, endocardial/epicardial ratio, and coronary flow were significantly decreased (59 +/- 7, 52 +/- 7, and 55 +/- 4%, respectively) whereas epicardial pO2 was slightly decreased. Nitroglycerin (10 micrograms/kg, i.v.) markedly increased endocardial pO2 and endocardial/epicardial ratio above poststenotic control (13 +/- 5 mmHg and 64 +/- 10%, respectively) whereas epicardial pO2 was not significantly decreased. The increases in endocardial pO2 occurred at a point where coronary flow and mean arterial pressure were not significantly changed. Conversely, dipyridamole (125 micrograms/kg, i.v.) significantly increased coronary flow (26 +/- 2 ml/min/100 g) although it did not appreciably alter endocardial or epicardial pO2. It is concluded that encased polargraphic oxygen electrodes provide a quantitative method for determination of oxygen tension in the ischemic myocardium.

Effects of Nitroglycerin, Dipyridamole, Nifedipine, Verapamil and Diltiazem on Canine Coronary Arterial Rings Contracted with 5-Hydroxytryptamine and Anoxia

Anoxia has been shown to potentiate the constrictor effects of 5-hydroxytryptamine (5HT) in isolated vascular tissue. In the present study, canine coronary arterial rings were incubated with various treatments and exposed to 5HT (4 X 10(-7) M) and anoxia (95% N2 and 5% CO2). Developed tension was increased by 250 +/- 40 mg by 5HT alone and 2,000 +/- 90 mg by 5HT and anoxia. Calcium (5 mM) potentiated, while inorganic (lanthanum, 10(-2) M) and organic calcium antagonists (nifedipine, verapamil and diltiazem; IC50 = 7 X 10(-9), 7.3 X 10(-8) and 2.4 X 10(-7) M, respectively) blocked the anoxic potentiation. Anoxia alone decreased resting tension (RT). Methysergide 3 X 10(-5) M inhibited both the 5HT- and anoxia-potentiated responses. Nitroglycerin decreased RT and inhibited the anoxic response (IC50 = 7.6 X 10(-6) M), while dipyridamole decreased RT and did not affect the anoxic response. These data suggest that the potentiation of 5HT contraction by anoxia is dependent upon extracellular calcium influx and is linked to a 5HT receptor. In addition, inhibition of the anoxic response can be achieved at other sites and is not a property common to all coronary vasodilators.