Splanchnic tissues are a major part of the rapid distribution spaces of inulin, urea and theophylline.

Distribution of kinetics of inulin, [14C]urea and theophylline were studied in five anesthetized dogs after splenectomy and gastrointestinal resection. Distribution was modeled with three-compartment mammillary systems in which the central compartment corresponds to intravascular space and the two peripheral compartments have different rates of transcapillary exchange. Compared with results in intact dogs, the surgical procedure removed between 41 and 55% of the rapidly equilibrating tissues and reduced the permeability coefficient-surface area products for the rapidly equilibrating inulin and urea compartments proportionately. This is consistent with the concept that splanchnic organs equilibrate rapidly with inulin and urea because they are supplied by fenestrated and discontinuous capillaries that are prominent in the splanchnic vascular bed. However, splanchnic organs probably do not contain all rapidly equilibrating tissues, and somatic tissues may contribute as much as 36 and 22%, respectively, of the rapidly equilibrating inulin and urea compartments. Cardiac output averaged 2.87 +/- 0.86 liters/min and was similar to the sum of compartmental blood flows estimated from the intercompartmental clearances of urea and inulin (2.74 +/- 0.96 liters/min) and to the sum of theophylline intercompartmental clearances (2.62 +/- 0.74 liters/min). Theophylline intercompartmental clearance to each peripheral compartment was similar to estimated compartmental blood flow.

Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method.

N-Acetylprocainamide (NAPA) absorption and disposition were profiled in five patients with ventricular arrhythmias by the simultaneous intravenous administration of NAPA-13C and oral administration of a 500 mg NAPA hydrochloride tablet. NAPA distribution was modeled with a three compartment mammillary system. The central compartment volume of 14.1 +/- 2.6 L (mean +/- SD) was similar to expected intravascular space, corrected for NAPA partitioning between erythrocytes and plasma. Other compartment volumes, intercompartmental and nonrenal clearances, and the steady-state distribution volume of 1.45 +/- 0.09 L/kg were similar to normal subject values. The least-squares estimate of 1.67 for the NAPA renal clearance/creatinine clearance ratio was similar to the value of 1.68 previously reported for functionally anephric patients and showed the expected age-associated decrease. The oral NAPA dose was 78.0% +/- 11.7% absorbed and interindividual variation in NAPA absorption was correlated with fast intercompartmental clearance (r = 0.89, p = 0.045). Because fast intercompartmental clearance partly reflects splanchnic blood flow, hemodynamic changes may affect NAPA bioavailability, as has been found for procainamide.

Demonstration of lack of persistence of effectiveness of intra-aortic balloon pumping of short duration in acute myocardial ischemia.

Experimental studies were carried out to quantitate the effectiveness of intra-aortic balloon pumping (ABP) in reducing severity and extent of myocardial ischemia and the persistence of induced changes after cessation of pumping. Ligation of the anterior descending coronary artery was followed by one hr of observation, IABP for one hr (12 dogs) or 3 hrs (12 dogs) and an additional one hr of observation. Epicardial mapping utilizing 20 electrodes was used to obtain the ST segment elevations (Sigma ST) and numbers of electrodes showing ischemic ST CHANGES (NST) in each group. Reductions of SigmaST of approximately 15% and 33% and reduction of NST of 15% and 20% was observed in the one and 3 hr groups respectively, and persisted throughout the period of pumping. Both parameters were noted to increase within 5 mins after cessation of IABP in both groups. SigmaST frequently rose to almost pre-IABP values in the group pumped for one hr. The group pumped for 3 hrs showed SigmaST increase of approximately 15% and NST increase of approximately 16%. Hemodynamic measurements showed in both groups a mean systolic unloading of approximately 10% and 10-20% mean diastolic augmentation. In conclusion, IABP of short duration (1-3 hrs) early after the onset of acute ischemis (one hr) induces a significant but transient decrease in SigmaST and NST, which reflects a reduction in myocardial ischemia. Further study is required to evaluate the effectiveness of intra-aortic balloon pumping, if intitated several hours after the onset of ischemia, to reproduce the clinical reality of a patient with an acute myocardial infarction.