Biomedical subjects

J A Vick

Publications and source records attributed to J A Vick.

At least 19 recordsLinked to original sources

PubMed2001

Cardiovascular effects of buccal exposure to dermal nicotine patches in the dog: a comparative evaluation.

OBJECTIVE: Safety concerns have been raised over the possible effects of inappropriate exposure to transdermal nicotine patches. This study was initiated to determine whether placement of these products into the mouth could affect cardiovascular function. METHODS: In a series of 10 anesthetized beagle dogs, Nicoderm, Habitrol, ProStep I (Intact), ProStep D (Damaged) transdermal nicotine products or the Skoal Bandit smokeless tobacco plug were placed in the buccal cavity for 5 minutes. Systemic arterial blood pressure and the electrocardiogram were monitored for up to 90 minutes after exposure with blood samples at intervals during the first 10 minutes for plasma nicotine concentration. RESULTS: The systolic and diastolic arterial blood pressures and heart rate increased within 2 minutes of buccal exposure to either the intact or the damaged ProStep nicotine product. Ventricular arrhythmias were observed in 6 of 10 dogs exposed to the intact patch and 7 of 10 dogs exposed to the damaged patch during the period of maximal cardiovascular response. Modest increases in systemic blood pressure and heart rate were seen with the Nicoderm and Habitrol products but not with the Skoal Bandit. The increases in systemic arterial pressure and heart rate occurring after exposure to ProStep were significantly more severe than those observed after Nicoderm and Habitrol. Mean peak nicotine levels of 9.8 microg/mL (ProStep 1), 5.4 microg/mL (ProStep D), 3.4 microg/mL (Habitrol), 2.5 microg/mL (Nicoderm), and 0.12 microg/mL (Skoal Bandit) were detected within 2 to 10 minutes after buccal placement of the product. CONCLUSIONS: Certain transdermal nicotine patches, when applied to a nondermal site such as the buccal cavity for a short period (5 minutes) can rapidly provoke significant cardiovascular alterations (hypertension, tachycardia, and ventricular arrhythmias). The magnitude of the cardiovascular responses occurring after buccal exposure to a product such as ProStep could pose a risk to susceptible individuals.

Administration, Oral↗

PubMed1999

Reversal of propranolol blockade of adrenergic receptors and related toxicity with drugs that increase cyclic AMP.

An overdose of propranolol, a widely used nonselective beta-adrenergic receptor blocking agent, can result in hypotension and bradycardia leading to irreversible shock and death. In addition, the blockade of adrenergic receptors can lead to alterations in neurotransmitter receptors resulting in the interruption of the activity of other second messengers and the ultimate cellular responses. In the present experiment, three agents, aminophylline, amrinone, and forskolin were tested in an attempt to reverse the potential lethal effects of a propranolol overdose in dogs. Twenty-two anesthetized beagle dogs were given a 10-min infusion of propranolol at a dose of 1 mg/kg/min. Six of the dogs, treated only with intravenous saline, served as controls. Within 15-30 min all six control dogs exhibited profound hypotension and severe bradycardia that led to cardiogenic shock and death. Seven dogs were treated with intravenous aminophylline 20 mg/kg 5 min after the end of the propranolol infusion. Within 10-15 min heart rate and systemic arterial blood pressure returned to near control levels, and all seven dogs survived. Intravenous amrinone (2-3 mg/kg) given to five dogs, and forskolin (1-2 mg/kg) given to four dogs, also increased heart rate and systemic arterial blood pressure but the recovery of these parameters was appreciably slower than that seen with aminophylline. All of these animals also survived with no apparent adverse effects. Histopathologic evaluation of the hearts of the dogs treated with aminophylline showed less damage (vacuolization, inflammation, hemorrhage) than the hearts from animals given propranolol alone. Results of this study showed that these three drugs, all of which increase cyclic AMP, are capable of reversing the otherwise lethal effects of a propranolol overdose in dogs.

Adenylyl Cyclases↗

PubMed1996

Reversal of acute theophylline toxicity by calcium channel blockers in dogs and rats.

Theophylline, widely used in the treatment of pulmonary diseases, has a narrow therapeutic index; the recommended plasma levels being 10-20 micrograms/ml in humans. The misuse or abuse of theophylline can cause life-threatening central nervous system and cardiovascular effects. Increased intracellular Ca2+ levels are thought to play an important role in theophylline toxicity and death. The objective of this study was to determine whether Ca2+ channel blockers, e.g. verapamil, nifedipine, or diltiazem, prevent sudden death caused by theophylline treatment in rats and dogs. Groups of Sprague-Dawley rats were treated with theophylline alone (150 mg/kg i.p.) or with theophylline pretreatment followed by administration of verapamil (0.25 to 0.5 mg/kg i.p.), nifedipine (0.25 to 1.0 mg/kg i.p.), or diltiazem (0.5 to 1.0 mg/kg i.p.), 2.5 to 15 min later. The rats were observed for toxic signs and survival over a period of 15 days. All three calcium channel blockers significantly reduced the theophylline-induced sudden death in rats. In a separate study, neither verapamil (0.5 mg/kg i.p.) nor nifedipine (1.0 mg/kg i.p.) prevented the theophylline-induced myocardial necrosis in the rat. In beagle dogs, verapamil (0.5 mg/kg i.v.) prevented theophylline (15 mg/kg/min i.v. for 10 min)-induced hypotension, arrhythmias, and sudden death. Our results support previously reported findings that calcium plays a major role in theophylline-induced toxicity and death.

Animals↗

PubMed1994

Medical studies of poisonous land and sea snakes.

The comparative toxicity and pathophysiology of thirteen (13) of poisonous snakes indigenous to the area in and around Saudi Arabia were determined. Four snakes from the Viperidae family, six from the Elapidae family, and three representative sea snakes from the family Hydrophiodae were included. Anesthetized adult Beagle dogs and anesthetized monkeys were used in the study. Vital physiologic functions were recorded continuously as were changes in the blood coagulation system and any tissue damage produced by the venom at the site of envenomation. Venom was administered intravenously or by an actual bite. Venom from the snakes of the family Viperidae produced death in an average of 3 hours. The average lethal dose was 1.13 mg/kg. Depression of 1st and 2nd stage clotting factors and a decrease in fibrinogen levels and in platelet counts were observed with these venoms. Findings suggestive of intravascular coagulation also were observed with moderate hemolysis of the formed elements. Some local hemorrhage was seen at the site of envenomation. Venom from the Elapidae family of snakes produced death at an average of 1.7 hours. The average lethal dose was 0.70 mg/kg. Death appeared to be primarily due to respiratory paralysis after blockade at the neuromuscular junction. Only moderate hemolysis was seen with these venoms. No intravascular coagulation or tissue damage was seen. The venom of the family Hydrophiodae consistently produced death in less than 30 minutes at an average dose of 0.06 mg/kg. Tissue damage was not observed, and changes were not observed in the hematologic parameters monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

1991 Sir Henry Wellcome Medal and Prize recipient. Medical studies of the poisonous land and sea snakes found in and around Saudi Arabia.

Studies were carried out to determine the comparative toxicity and pathophysiology of 13 of the more poisonous snakes indigenous to Saudi Arabia. Included were four snakes from the Viperidae family, six from the Elapidae family, and three representative sea snakes from the family Hydrophidae. Anesthetized adult beagle dogs and anesthetized monkeys were used in the study. Vital physiological functions were continuously recorded as were changes in the blood coagulation system and any tissue damage produced by the venom at the site of envenomation. For the intravenous administration of the venom, lyophilized venom was obtained by "milking" each of the live specimens used in the study. Actual envenomation was accomplished by grasping the poisonous reptile and allowing the snake to strike the shaved exposed gluteal muscle of the anesthetized animal. Venom from the snakes of the family Viperidae produced death in an average of 3 hours. The average lethal dose was 1.13 mg/kg. Depression of first and second stage clotting factors was observed with these venoms as well as a decrease in fibrinogen levels and in platelet counts. Findings suggestive of intravascular coagulation were also observed with moderate hemolysis of the formed elements. Some local hemorrhage was seen at the site of envenomation. Venom from the Elapidae family of snakes produced death at an average of 1.7 hours. The average lethal dose was 0.70 mg/kg. Death appeared to be primarily due to respiratory paralysis following blockade at the neuromuscular junction. Only moderate hemolysis was seen with these venoms. No intravascular coagulation or tissue damage was seen. The venom of the family Hydrophidae consistently produced death in less than 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Enantiomeric analysis of phenylpropanolamine in plasma via resolution of dinitrophenylurea derivatives on a high performance liquid chromatographic chiral stationary phase.

Racemic phenylpropanolamine was resolved on a high performance liquid chromatographic (HPLC) chiral stationary phase (CSP) as the 3,5-dinitrophenyl ureide derivative. The CSP was prepared by a simple in situ procedure in which (R)-(1-naphthyl)ethyl isocyanate was bound to aminopropyl silanized silica through a urea linkage. The enantiomeric ureides were prepared by a room-temperature, 60-second procedure, accomplishing simultaneous extraction and derivatization and utilizing achiral 3,5-dinitrophenyl isocyanate as reagent. Baseline resolution was readily achieved under normal phase conditions, with a separation factor (alpha) of 1.16 and a resolution factor (RS) of 2.2. Elution was complete within 10 min. A limit of detection, by UV at 235 nm, of 250 pg per isomer was established. Feasibility of the procedure for plasma determinations was demonstrated by assay of samples from a canine subject.

Animals↗

PubMed1991

Effectiveness of oral pyridostigmine pretreatment and cholinolytic-oxime therapy against soman intoxication in nonhuman primates.

Nonhuman primates which were fed Mestinon (pyridostigmine) syrup-impregnated food biscuits (40 mg per animal) exhibited a reproducible inhibition of whole blood cholinestrase activity of 40 to 50% for a period of 1 to 6 hr. Pyridostigmine pretreatment was supplemented by therapy with two doses of an antidotal combination (A,TM,B) consisting of 0.05 mg/kg atropine, 2.24 mg/kg TMB-4, and 0.4 mg/kg benactyzine which assured survival in five of six animals following three separate exposures to 10 LD50 soman. The protective period of this oral dose of pyridostigmine supported by A,TM,B therapy was between 1/2 and 8 hr. Oral pyridostigmine pretreatment in combination with atropine therapy (three doses of 0.07 or 1.00 mg/kg im) also saved monkeys exposed to 10 LD50 soman; however, the period of recovery was prolonged. Oral pyridostigmine pretreatment did not alter the lethality of soman in the absence of A,TM,B or atropine therapy.

Administration, Oral↗

PubMed1991

Treatment of cyanide poisoning.

The object of this study was to evaluate the effectiveness of five regimens in treating cyanide poisoning. A series of anesthetized adult beagle dogs were instrumented to record hemodynamic and respiratory function and given 2.5 mg/kg sodium cyanide intravenously. The 10 control animals given only cyanide died at from 5 to 7 minutes. Therapy, as described below, was given to other groups at from 2 to 3 minutes following the cyanide administration. Artificial respiration did not alter the lethal effects of cyanide nor prolong survival time in any of the 10 animals. Amyl nitrite given by inhalation or by the intravenous route allowed survival of all 15 animals. Sodium nitrite (20 mg/kg), dimethylaminophenol (DMAP) (5 mg/kg), and hydroxylamine hydrochloride (5 mg/kg) given intravenously with no artificial ventilation also allowed for 100% survival (15 animals). Amyl nitrite, sodium nitrite, and sodium thiosulfate were ineffective when given intramuscularly (I.M.) (0 of 12 dogs); however, I.M. DMAP (5 mg/kg) and I.M. hydroxylamine hydrochloride (50 mg/kg) increased heart rate and blood pressure and restored spontaneous breathing. All 15 animals treated with I.M. doses of either of these drugs survived the lethal dose of cyanide. Results of these studies indicate that intravenous sodium nitrite, DMAP, and hydroxylamine hydrochloride, and amyl nitrite by inhalation, are all effective in reversing the lethal effects of cyanide poisoning. Only DMAP and hydroxylamine hydrochloride are effective when given by the intramuscular route. These results provide data to support an approach to therapy that is more practical and applicable where expert medical care may not be available following cyanide exposure.

Animals↗

PubMed1989

Studies on the mechanism of action of 1-(2-methyl-3-hydroxy-5-hydroxy-methyl-4-pyridyl)-6,7-dihydroxy-1,2,3, 4- tetrahydroisoquinoline (PTIQ) on blood pressure in the anesthetized dog.

The mechanism of action of PTIQ in lowering the arterial blood pressure in the anesthetized dog was studied using pharmacological and physiological techniques. The hypotensive activity of PTIQ was significantly inhibited by pretreatment with bilateral vagotomy, propranolol, prazosin and mecamylamine. Pretreatment with either yohimbine or reserpine had no significant effect on PTIQ activity. PTIQ produced a significant decrease in the force of contraction of myocardial tissue and a transient increase in the aortic blood flow of the anesthetized dog. These results indicate a multiplicity of action of PTIQ in controlling arterial blood pressure.

Anesthesia↗

PubMed1987

Evidence for a central muscarinic action by 1-(2-methyl-3-hydroxy-5-hydroxymethyl-4-pyridyl)-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline in regulating blood pressure in the anesthetized dog.

Anesthetized dogs injected with 1-(2-methyl-3-hydroxy-5-hydroxymethyl-4-pyridyl)-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline (PTIQ) into the common carotid artery, showed an immediate fall in blood pressure, whereas injection into the femoral vein produced a fall in blood pressure after a lapse of approximately 8 sec. Anesthetized dogs pretreated with atropine showed a decrease in mean blood pressure of 22% of control (PTIQ alone) after PTIQ was injected. In contrast, dogs pretreated with methylatropine showed a decrease of 41% of control after PTIQ was injected. Our data suggest that PTIQ may act centrally and peripherally by activation of muscarinic receptors.

Anesthesia↗

PubMed1985

Studies of cyanide poisoning.

The use of amyl nitrite and phenoxybenzamine in the treatment of acute cyanide poisoning was evaluated. Sixty anesthetized beagle dogs were injected i.v. with sodium cyanide (2.5 mg/kg) and were followed for changes in the heart rate, electrocardiogram, respiration, blood pressure and methemoglobin concentration. Twenty control dogs died within 5 to 7 min, showing severe bradycardia, a sharp drop in arterial blood pressure, and respiratory paralysis. Pretreatment with phenoxybenzamine (0.5 mg/kg) prevented these changes in 8 of 10 dogs; however, this drug was ineffective if given after the cyanide. In contrast, amyl nitrite given after cyanide administration reversed both the cardiovascular changes and the respiratory paralysis in 24 of the 30 dogs studied. These changes occurred before the formation of significant amounts of methemoglobin and indicate that early death caused by cyanide may be due in part to cardiovascular-respiratory failure in addition to the classic poisoning of the cytochrome oxidase system. These studies indicate that phenoxybenzamine prevents and amyl nitrite reverses the otherwise lethal effects of cyanide.

Amyl Nitrite↗

PubMed1985

Effect of a specific tetrahydroisoquinoline on the blood pressure in animals.

1-(2-Methyl-3-hydroxy-5-hydroxymethyl-4-pyridyl)-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline (PTIQ) when injected into anesthetized normotensive minipigs and dogs lowers the arterial blood pressure in a dose-related manner. The blood pressure lowering effect of PTIQ is greater on minipigs than dogs at comparable dose levels. The heart rate is generally slower after PTIQ was injected than the control.

Animals↗

PubMed1983

Prevention of chronic doxorubicin cardiotoxicity in beagles by liposomal encapsulation.

Antitumor drugs such as doxorubicin have been encapsulated into liposomes as a means of enhancing activity and reducing toxicity. The present study was initiated to determine whether chronically administered liposome-encapsulated doxorubicin would be less toxic than the free drug. Doxorubicin was prepared in positively charged cardiolipin liposomes, and 1.75 mg/kg was given i.v. to each of five beagles. A second group received the free drug at 1.75 mg/kg. Additional animals received i.v. injections of either doxorubicin-free liposomes or 0.9% NaCl solution. All substances were given at 3-week intervals, and the experiment ended 1 week after the seventh injection (total dose, 12.25 mg/kg). A temporary reduction in food consumption was noted during the first few days after the administration of either form of doxorubicin. The effect was more severe in the dogs given free doxorubicin, and body weight decreased significantly only in this group of animals. Three dogs given free doxorubicin died or were killed before the end of the study because they were in poor condition. Lesions consisting mainly of vacuolization and myofibrillar loss were noted in the hearts of all five dogs given free doxorubicin. The severity of the lesions ranged from 2 to 4 (average, 3.4). In contrast, no abnormalities were found in any of the hearts from dogs given the liposomal doxorubicin. The most obvious general toxic effect caused by administration of free doxorubicin was alopecia, which was entirely prevented when doxorubicin was encapsulated into liposomes. At the dosage regimen utilized, liposomal doxorubicin and free doxorubicin exerted comparable degrees of bone marrow suppression. Thus, liposomal encapsulation of doxorubicin decreased cardiac and other toxic effects elicited by free doxorubicin. Whether this advantage can be translated into effective antineoplastic activity will need further evaluation.

Amines↗

PubMed1983

Reversal of propranolol and verapamil toxicity by calcium.

Because of the increasing use of propranolol and verapamil in combination, a study of their interaction was conducted. In rabbits, propranolol given IV at 1 mg/kg followed by an IV infusion of verapamil at 0.1 mg/kg/min for 15 min caused profound hypotension, bradycardia, A-V block, and death in less than 1 h in each of 30 animals. In rabbits treated with propranolol and verapamil as above, calcium chloride (300 mg/kg) given IV immediately after verapamil infusion restored blood pressure and cardiac conduction to normal but the heart rate remained slow; all 12 animals survived. In miniature swine under sodium pentobarbital anesthesia, propranolol (0.5 mg/kg) and verapamil (0.5 mg/kg) IV produced the same physiological changes and death within 15 min in each of eight animals. Calcium chloride given at 150 mg/kg to miniature swine after propranolol and verapamil injections prevented death of each of the five animals; blood pressure and the electrocardiogram were restored to normal, although bradycardia persisted. In mice, the IP LD50 value of propranolol HCl, which is 80 +/- 2.7 mg/kg, was decreased to 10 mg/kg when the drug was given in combination with verapamil HCl at an IP dose of 3 mg/kg, which is less than 1/10 of its LD50. Deaths occurred within minutes and were preceded by convulsions. Pretreatment of mice with calcium chloride (600 mg/kg, IV) prevented death due to the combination of propranolol and verapamil. The data indicate that verapamil enhances the toxicity of propranolol and that calcium can antagonize this effect.

Animals↗

PubMed1977