PubMed Health⌕ Search

Biomedical subjects

A Van de Water

Publications and source records attributed to A Van de Water.

6 recordsLinked to original sources
PubMed1992

Cardiac and hemodynamic effects of intravenous R80122, a new phosphodiesterase III inhibitor, in a canine model of myocardial ischemia and heart failure.

The cardiac and hemodynamic effects of R80122, a new specific phosphodiesterase III inhibitor, were studied in a closed-chest canine model of acute global left ventricular ischemia complicated by heart failure. The results obtained were compared with those obtained with milrinone. Intravenous infusion of the compounds (0.005 mg/kg/min for both) was started when stable heart failure had developed and was continued for 50 min followed by a washout period of 60 min. Both R80122 and milrinone improved the function of the acutely failing heart, as indicated by the increase in the values of the variables related to left ventricular function, but differences existed. The most striking differences were the normalization of the left ventricular external mechanical efficiency with R80122, but not with milrinone, and the maintenance of aortic blood pressure during infusion of R80122, which decreased during infusion of milrinone. Milrinone tends to induce ventricular tachycardia more frequently than R80122. It can be concluded that R80122 and milrinone improve the function of the acutely failing heart, but that the changes induced by R80122 are better balanced, i.e., enhancement of external mechanical efficiency with maintenance of aortic blood pressure.

Animals↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.

Acidosis↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the epileptoid activity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.

Acidosis↗
PubMed1975

Antihypertensive activity of erythro-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935).

Erythro-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935), provokes marked antihypertensive effects lasting several hours in conscious SHR (0.63 to 40 mg/kg i.p.) and beagles with renal hypertension (1.25 mg/kg p.o.). In SHR, this compound induces much less bradycardia, compared to equiactive hypotensive doses of clonidine, guanethidine and propranolol. Significant postural hypotension during tilting, is induced by guanethidine and mecamylamine but not by R 28935. In anaesthetized beagles with renal hypertension, the lowering of the blood pressure by R 28935, (0.02-0.64 mg/kg i.v.) is associated with a considerable decrease in the total peripheral vascular resistance, whereas the myocardial function is not affected. R 28935 is considered a potent antihypertensive drug, with attractive haemodynamic characteristics.

Animals↗
PubMedDate not supplied

Cardiac and hemodynamic effects of intravenous R 80122, a new phosphodiesterase III inhibitor, in anesthetized and awake dogs.

R 80122 is a newly synthesized, selective phosphodiesterase III inhibitor. The cardiac and hemodynamic effects of this compound following intravenous administration were studied in closed-chest anesthetized as well as in conscious chronically instrumented dogs. The findings in the closed-chest anesthetized dogs indicate that R 80122 has positive inotropic and possibly moderate vasodilating properties [maximum increase in LV dp/dtmax/pd: 61%, and maximum decrease in systemic vascular resistance: 29% (a 12.5% decrease for the solvent)]. As a result, cardiac output maximally increased to 149% of the control value. The most striking effect of R 80122 was its positive lusitropic effect (maximal decrease in the time constant of relaxation [T] of 46%). This pronounced lusitropic effect of R 80122 can be regarded as beneficial, because of the increasing evidence that lusitropic defects play an important role in disorders related to heart failure. These effects of R 80122 were associated with only slight changes in arterial blood pressure. The effects of R 80122 lasted about 75 min after stopping the infusion. No ventricular arrhythmias were noted during and after infusion of the compound. The positive inotropic effects seen in anesthetized dogs were confirmed in conscious nonsedated dogs. It may be concluded that R 80122 has a clinically favorable cardiovascular profile for acute applications in heart failure, because its combined positive inotropic and positive lusitropic effects, and moderate vasodilating properties lead to a pronounced increase in cardiac output and only minimal changes in aortic blood pressure.

Anesthesia↗