Postnatal development of heart rate (HR), mean aortic pressure and arterial flow responses to carotid baroreceptor stimulation (CS) or inhibition (BCCO), and to sciatic nerve stimulation (SNS), was studied in 60 newborn piglets under halothane-N₂O anesthesia. There was no HR change in most piglets during CS or BCCO, but tachycardia was observed during high frequency or intensity SNS and after bilateral vagotomy. In younger animals, smaller pressor effects were observed during high frequency or intensity SNS than in older ones. There were also age-dependent changes in femoral and renal flows and resistances to CS, BCCO, SNS or bilateral vagotomy. The results indicate postnatal maturation of regulatory mechanisms for HR and peripheral flow.

Regional blood flow changes in response to hypercapnia, hemorrhage, and sciatic nerve stimulation were studied in 22 newborn piglets. Femoral, renal and/or carotid arterial flows were recorded simultaneously with aortic pressure and heart rate in piglets lightly anesthetized with halothane. Observations were made while ventilation was regulated to maintain arterial pH and pCO₂ within the normal range, and when ventilation was adjusted to produce increased pCO₂ and decreased pH uncomplicated by hypoxia. The ability of the neonate to respond to low or high frequency and intensity sciatic nerve stimulation was studied during control, hypercapnia, and hypercapnia complicated by hemorrhage. The results indicate immaturity of the mechanisms normally utilized to compensate for these stresses.

We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (beta 1) and propranolol (beta 1, beta 2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.

No abstract

The low oral bioavailability of atenolol is primarily because of its poor absorption from the lower gastrointestinal tract. Gastroretentive dosage forms provide an opportunity to deliver the drug with absorption window in the proximal part of the GIT thereby increasing their bioavailability. The objective of this study was to develop a dosage form for atenolol with the objective of increasing the gastric residence and there by its oral bioavailability. Different formulations of floating tablets of atenolol (AT1-AT10) were prepared by varying the composition of hydroxypropyl methyl cellulose (HPMC) K100, lactose and citric acid. The tablets were evaluated for various parameters like friability, weight variation, content variation, floating lag time, total buoyancy and in vitro dissolution. The physicochemical properties of the prepared formulations were found to possess adequate physical integrity. Formulation AT8 showed the lowest floating lag time with 14 h buoyancy. Drug release was found to be dependent on the concentration of HPMC K100 and lactose in the formulation. Further, the increase in amount of citric acid leads to increase in atenolol release rate while reduces the floating time. The findings revealed that the formulation AT8 retarded the atenolol release (~73% in 12 h) and followed zero order kinetics. The in vitro data observed here substantiate the potential of the prepared formulation to provide adequate drug release and buoyancy to improve the bioavailability of atenolol, which necessitate further in vivo studies.