Pharmacokinetics of atenolol enantiomers in humans and rats.

Single dose pharmacokinetics of atenolol (AT) enantiomers was studied in human volunteers and in rats. After oral administration of 50 mg of racemic AT to humans, the areas under the plasma concentration-time curves (AUCs; mean +/- SD) were 1640 +/- 602 and 1860 +/- 652 (ng/mL)h for the S(-)- and R(+)-enantiomers, respectively (p less than 0.05). The small difference in the AUC was a reflection of a slight, but statistically significant (p less than 0.05) difference in the renal clearance (CLr, mL/min) of the enantiomers [129 +/- 32, S(-)-AT; 120 +/- 29, R(+)-AT]. However, the two enantiomers were not different from each other (p greater than 0.05) with respect to the volume of distribution (V lambda, L/kg) [0.879 +/- 0.342, S(-)-AT; 0.790 +/- 0.255, R(+)-AT] or the terminal elimination rate constant (lambda z, h-1) [0.113 +/- 0.038, S(-)-AT; 0.114 +/- 0.036, R(+)-AT]. After iv administration of 10 mg/kg of the racemic AT to rats, the R(+)-enantiomer achieved higher AUC values [(ng/mL)h] compared with its antipode (p less than 0.05) [3630 +/- 1040, S(-)-AT; 4020 +/- 1080, R(+)-AT]. Similar to the human results, this difference was due to a stereoselective renal clearance (mL/min/kg) in favor of S(-)-AT [14.9 +/- 5.78, S(-)-AT; 13.0 +/- 4.88, R(+)-AT; p less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Permanent left ventricular assistance for outpatients through surgical implantation of a modified intra-aortic balloon pump.

There is a large population of patients in end-stage congestive heart failure who cannot be treated by means of conventional cardiac surgery, cardiac transplantation, or chronic catecholamine infusions. In 2 such patients, we provided permanent left ventricular assistance on an outpatient basis by surgically implanting a modified intra-aortic balloon pump. A Dacron-velour graft to the common iliac artery served as a covering for the extravascular portion of the balloon's pneumatic tubing, which was stabilized by routing it through the iliac crest. The tubing was then carried ventrally to exit through a stoma just above the inguinal ligament. Before hospital discharge, each patient underwent a 5-day regimen of alternate pumping and ambulation. The patient was then permitted to go home, but returned daily as an outpatient in accordance with individual need, for approximately 6 hours of hemodynamic support. The 1st patient lived 3 months after pump insertion, and the 2nd patient for 38 days. Although the 1st patient developed a fever of unknown origin that prompted us to remove the intra-aortic balloon pump unnecessarily, there was no evidence of infection upon surgical exploration and subsequent tissue culturing; she died, rather, of intractable ventricular fibrillation, apparently consequent to her 36-hour loss of hemodynamic support. The 2nd patient also died of a cause unrelated to the presence of the pump, and on autopsy showed good evidence of healing and absence of infection. On the evidence of this pilot study, we conclude that intermittent left ventricular assistance, through periodic activation of a permanently implanted intra-aortic balloon pump during outpatient visits, warrants further study as an alternative for selected patients with end-stage heart disease, when medical and other surgical options have been exhausted.

A new left ventricular assist device: clinical experience in two patients.

A permanent parallel aortic pump (PAP), essentially a permanent intra-aortic balloon pump or modified dynamic aortic patch, has been designed to support failing left ventricles The PAP is a counterpulsation system in which an external energy source delivers a pulsatile wave into the central circulation during cardiac diastole and relaxes during cardiac systole. Clinical improvement occurred in two patients after PAP implantation. The initial regimen of continuous pumping evolved to intermittent left ventricular assistance, and the patients were able to be periodically disconnected from the pump and ambulated. The patients expired 39 and 34 days after implantation due to gastrointestinal bleeding and complications of chronic emphysema and tracheostomy. Autopsy revealed that surgery for both devices had entirely healed.

Measurement of sulfamethizole clearance rate by nonthrombogenic constant blood-withdrawal system.

A method for the measurement of the total body clearance rate (CR) of drugs is described. It involves a single intravenous injection of a known quantity of the drug (D) and automatic integration of the plasma concentration curve, using a portable, nonthrombogenic, constant blood-withdrawal system. When blood withdrawal is carried out until the concentration of the drug in the plasma approaches zero, the concentration of the drug in the collected pool, the integrated concentration (ICT) multiplied by the time of collection (T) yields the integral of the concentration curve: (see article). The method was tested by measuring the clearance rate of sulfamethizole in five dogs by the established constant infusion method. At three plasma levels (25, 75, and 200 mg/liter), the plasma concentration had no significant effect on the clearance rate. The clearance rate of sulfamethizole was subsequently measured in the same dogs by the new single-injection constant withdrawal method. Multiple blood samples were collected at 15-min intervals simultaneously with the constant withdrawal of blood. There was no significant difference between the clearance rate of sulfamethizole measured by the two methods. The initial peak mean concentration of the drug from the time of injection (t = 0) to the time of the first blood sampling (t = 15 min) was calculated from the difference between (see article) obtained by the constant withdrawal method and that obtained from the results of the multiple blood withdrawals by the trapezoidal rule. The integrated concentration IC15 was significantly higher than its estimation by the semilogarithmic linear regression method.