Clinical cardiac electrophysiologic study of celiprolol.

The objective of the study was to evaluate the acute effect of intravenous celiprolol on the electrophysiologic properties of the cardiac conduction system in man and to assess potential problems in terms of its causing heart block or sinus bradycardia. Eight patients with controlled coronary artery disease and hypertension but without conduction system disease were studied. All cardiac drugs e.g., digoxin, sympathomimetics and other beta blockers were discontinued prior to entering the study. Surface ECG leads I, AVF, and Vi were applied to each patient, and the ECG was continuously displayed on an oscilloscope. A quadripolar stimulating electrode (7F) was inserted percutaneously and positioned in the high right atrium and a tripolar or bipolar His bundle recording catheter was positioned cross the tricuspid valve. The atrial and His bundle electrograms were recorded on a direct writing recorder. After completion of the baseline electrophysiologic (EP) measurements, in an open fashion, celiprolol (0.1 mg/kg) was administered intravenously at the rate of 1 mg/min into each of the five patients. The complete battery of the EP measurements were repeated immediately following completion of the infusion. Preliminary data in eight patients demonstrated no significant effect of celiprolol on the cardiac conduction system.

Anticonvulsant activity of delta9-tetrahydrocannabinol compared with three other drugs.

Delta9-tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using several standard laboratory procedures to determine anticonvulsant activity in mice, i.e., the maximal electroshock test (MES), and seizures induced by pentylenetetrazol, strychnine and nicotine. In the MES test, THC was the least potent and DPH the most potent blocker of hind limb tonic extensor convulsions whereas THC was the most potent and DPH the least potent in increasing the latency to this response and in preventing mortality. Seizures and mortality induced by pentylenetetrazol or by strychnine were enhanced by THC and DPH and were blocked by PB and CDP. In the test with nicotine, none of the four anticonvulsant agents prevented seizures; DPH was the only one which failed to increase latency; THC and DPH were less potent than PB and CDP in preventing mortality. THC most closely resembled DPH in the tests with chemical convulsant agents, but a sedative action of THC, resembling that of PB and CDP, was indicated by low ED5 0 for increased latency and for prevention of mortality in the MES test.

Arterial pressure-flow relations in the awake standing dog.

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.