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Biomedical subjects

D Kornhauser

Publications and source records attributed to D Kornhauser.

12 recordsLinked to original sources
PubMed1998

Pharmacodynamics and pharmacokinetics of DMP 728, a platelet GPIIb/IIIa antagonist, in healthy subjects.

DMP 728 showed a dose-dependent inhibition of platelet aggregation at doses of 0.05 to 0.9 mg per subject, with a maximal inhibition (> 90%) of platelet aggregation at doses of 0.9 mg per subject and higher. Minimal changes in bleeding time from baseline were observed at doses up to 0.6 mg per subject. At the 0.9 mg/subject dose level, bleeding time was prolonged by approximately twofold to threefold above the baseline. At higher doses (1.5 mg/subject to 3.9 mg/subject), bleeding time prolongation was > 30 minutes during the infusion. In all dose groups, bleeding times returned to the control value within 8 hours after cessation of the infusion. Maximum plasma concentration and area under the curve of DMP 728 increased linearly and proportionally to the dose. No clinical changes in vital signs, 12-lead electrocardiograms, physical examinations, coagulation tests, or stool hemoccult tests were observed at any of the doses. In conclusion, DMP 728 is a potent antiplatelet agent and well tolerated at doses ranging from 0.05 to 3.0 mg/subject.

Adult↗
PubMed1983

Effects of intraparenchymal hemorrhage on extracellular cortical potassium in experimental head trauma.

A model of intraparenchymal hemorrhage was created in 11 cats. The development of the parenchymal hemorrhage was accompanied by a massive cellular depolarization and K+ release in anatomically intact areas in the vicinity of the hematoma. The K+ clearance was rapid and in most instances total. This initial K+ release was not ischemic in origin but was the result of mechanical and chemical factors of the extravasated blood on cellular membranes. In contrast, an increased water content of the white matter did not affect the cellular function or levels of K+ in the extracellular space of the cerebral cortex in the recording area. The experimental results suggest that K+ release takes place at the onset of trauma in subcritically injured cellular areas in the vicinity of a hemorrhage. The cellular elements undergo massive depolarization which is accompanied by a number of chemical and biochemical changes that lead to cellular swelling. Cellular depolarization and K+ release appear to be the initial response of the central nervous system to trauma. The extent of this response may strongly influence the final degree of cellular damage and, thus, the neurological deficit in patients with head trauma.

Animals↗
PubMed1982

Antiarrhythmic effects of the quaternary propranolol analog that does not induce beta-adrenergic blockade.

Pranolium chloride (dimethylpropranolol chloride) is a nonbeta blocking quaternary ammonium that has structural similarities to propranolol and bretylium that exert antiarrhythmic effects in animals. In initial studies, eight patients with chronic ventricular arrhythmias were given gradually increasing intravenous doses of pranolium (up to 3 mg/kg) obtaining plasma concentrations up to 7 micrograms/ml without change in pulse, blood pressure, or arrhythmia frequency. We therefore evaluated the response to pranolium in seven similar patients at doses up to 10 mg/kg as an infusion of 100 microgram/kg/min over 40 to 100 min. At plasma concentrations of 4.7 to 12.2 micrograms/ml, there was suppressing of ventricular ectopic depolarization (greater than 90%) in three subjects and in two others there was partial suppression (49% and 82%). Arrhythmia frequency was unchanged in two. At plasma concentrations of 4.1 to 17.2 micrograms/ml four subjects developed nausea (two of these also vomited) and to experienced perioral numbness. There was no change in sinus heart rate, supine or standing blood pressure, venous reflex response (adrenergic reflex venoconstriction), or ECG intervals in any subject. Pranolium appeared to have antiarrhythmic efficacy in five of seven subjects, without evidence of beta-adrenergic blockade or interference with sympathetic neuron function known to occur with its congeners, propranolol and bretylium. There is a narrow margin between pranolium efficacy and toxicity. It may, however, be a prototype for antiarrhythmic drugs that do not exert undesirable effects on the adrenergic nervous system.

Adult↗
PubMed1982

Effect of subarachnoid hemorrhage on the extracellular microenvironment.

Local experimental subarachnoid hemorrhage (SAH) was produced over the cerebral cortex in 15 cats. The cellular response was monitored using ion-specific electrodes for extracellular potassium (K+) and calcium (Ca++) activity, DC cortical potential, and electrocorticogram. The response was characterized by a profound cellular depolarization and extracellular calcium (Ca++) depletion which accompanied extracellular potassium (K+) accumulation. The prehemorrhage baseline calcium levels measured 1.14 +/- 0.11 mM, and were lowered to 0.4 to 0.7 mM/liter in different experiments. The K+ accumulation reached levels between 16 and 31 mM from a baseline of 3.17 +/- 0.52 mM and were cleared to normal or nearly normal within 5 minutes. The Ca++ levels also returned to normal within 5 minutes, but remained depressed for the duration of the experiment in two animals. These results confirm that blood extravasated into the subarachnoid space had a direct effect on parenchymal elements. The combination of transient K+ elevations and calcium depression may play an important role in the development of vascular spasm by inducing or facilitating a contraction in the muscular layer in the wall of major intracranial vessels.

Animals↗
PubMed1980

Cortical cellular response in acute subarachnoid hemorrhage.

Acute subarachnoid hemorrhage (SAH) over the cerebral cortex causes single or multiple waves of cellular depolarization, which may occur in a self-propagating, reverberating fashion. This process is characterized by a massive K+ release and transient depression in electrocortical activity. The K+ levels in the extracellular space reach magnitudes known to substantially affect the membrane potentials of neurons and glia, and may cause a release of neurotransmitters from depolarized presynaptic terminals. The release of K+ may be the initial step in the development of cellular edema and, together with a multitude of other chemical and biochemical changes taking place at the cellular level, may underlie the loss of autoregulation. Cortical cells rather than blood vessels are the primary targets in the initial stages of SAH, and ischemia does not play a causal role in the pathogenesis of cellular dysfunction during this stage.

Animals↗
PubMed1979

Suppression of chronic ventricular arrhythmias with propranolol.

The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.

Adult↗
PubMedDate not supplied

Computer analysis of motor performance.

Employing the techniques of electrogoniometry and force measurement, the authors devised a system that provides rapid, reliable, and objective evaluation of a motor task. Utilizing a high-speed minicomputer, various parameters of a motor task were recorded, analyzed, and displayed. This system was used to monitor recovery of motor function after surgery, during a drug regimen, and during electrical stimulation of specific sites in the central nervous system.

Central Nervous System↗