Targeting needs of the underserved: current programs in Tennessee.

Health care needs of indigents are a major force driving the need for health care reform in the U.S. Governor McWherter of Tennessee and his Administration have highlighted the need for available, affordable, and accessible health care services for all Tennesseans and especially for the medically indigent. This paper describes programs developed and implemented during the McWherter administration. These programs include community health agencies, placement of health care providers in underserved areas, increasing the number of citizens served by the Medicaid program, coordination of high-risk prenatal and child care to year one, and special demonstration projects in various African-American communities. Major reform is needed at the national level. In the meantime, the McWherter Administration will continue to develop new and innovative ways to increase the availability, accessibility, and affordability of health services in Tennessee.

Indigent health care plan for Tennessee.

The author describes the development of an Indigent Health Care Program for the State of Tennessee from the campaign pledge of the Governor, through the development of an Indigent Care Cabinet Council, to the development and enactment of appropriate legislation required to implement this program. The program deals with availability of health care services, accessibility to health care services and funding mechanisms. The backbone of the program is the involvement of the local community and the coordinating and networking of the existing private, community and state health care providers.

Pharmacokinetic and pharmacodynamic interaction of N-acetyl procainamide and procainamide in humans.

Procainamide is a sodium channel blocker which prolongs QRS and QTc intervals, yet its major active metabolite, N-acetylprocainamide (NAPA), generally prolongs only QTc and has very different electrophysiologic and antiarrhythmic actions. In greater than 50% of patients receiving chronic treatment with procainamide, plasma concentrations of NAPA exceed those of procainamide. In this study, we examined the hypothesis that NAPA might alter the disposition kinetics or pharmacologic actions of procainamide. Ten patients with frequent ventricular extrasystoles received intravenous (i.v.) infusions of procainamide alone (study day 1), procainamide and NAPA (study day 2), and NAPA alone (study day 3) at least 48 h apart. On study days 1 and 2, procainamide was administered at a constant rate for 4 h. On study days 2 and 3, NAPA was administered as a loading and maintenance infusion designed to reach a target pseudo-equilibrium plasma concentration of 8 micrograms/ml. NAPA increased procainamide elimination half-life (t1/2) from 275 +/- 42 min (mean +/- SD) on day 1 to 340 +/- 74 min on day 2 (p less than 0.01). A significant correlations was noted between the change in procainamide total clearance on day 2 relative to day 1 and the initial procainamide total clearance on day 1 (r = -0.77, p = 0.009). Findings were similar when procainamide fractional urinary excretion was considered (r = -0.89, p = 0.007). NAPA did not alter procainamide-induced QRS prolongation, but potentiated procainamide-induced QTc prolongation. The antiarrhythmic response to procainamide was not significantly altered by NAPA in seven of nine patients. One patient had greater arrhythmia suppression when NAPA and procainamide were combined than when either was administered alone. In one patient, NAPA apparently antagonized procainamide-induced arrhythmia suppression, but this effect was not reproducible. We conclude that accumulation of NAPA during procainamide therapy can alter both procainamide elimination as well as its electrophysiologic actions.

Limitation of myocardial reperfusion injury by intravenous perfluorochemicals. Role of neutrophil activation.

Neutrophil activation and infiltration into the ischemic myocardium after reperfusion may limit the amount of salvageable myocardium (reperfusion injury). The effects of intravenous perfluorochemicals (Fluosol-DA) on infarct size, ventricular contractility, and neutrophil function were assessed in an occlusion-reperfusion canine model. Closed-chest dogs were subjected to 90 minutes of left anterior descending artery occlusion followed by 24 hours of reperfusion. Animals were randomized to receive either Fluosol-DA (FDA, n = 8) or Ringer's lactate (CONT, n = 10) intravenously over 30 minutes just before left anterior descending artery reperfusion. Neutrophil demargination and infiltration into the myocardium were assessed in vivo with In111. Neutrophil chemotaxis, superoxide radical production, and lysozyme degranulation were evaluated ex vivo at baseline, 1 hour after occlusion, and 1 hour after reperfusion. Perfluorochemicals significantly reduced infarct size expressed as percent of area at risk (FDA, 7 +/- 4%; CONT, 24 +/- 6%; p less than 0.01). This was associated with positive wall motion in the jeopardized zone of Fluosol-DA animals compared with dyskinesis in control animals (FDA, +4.4 +/- 2.1%; CONT, -1.1 +/- 1.5%; p less than 0.05). Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cells in the Fluosol-DA animals. Myocardial blood flow was greater in the ischemic endocardium of Fluosol-DA animals 1 hour after reperfusion (FDA, 1.23 +/- 0.21; CONT, 0.62 +/- 0.08 ml/g/min; p less than 0.01). Neutrophil demargination and infiltration into the ischemic myocardium was reduced in the animals treated with Fluosol-DA. (FDA, 2.5 +/- 0.7 x 10(3); CONT, 14.1 +/- 2.7 x 10(3) neutrophils/g; p less than 0.01). Neutrophil chemotaxis and lysozyme release were also markedly suppressed in the Fluosol-DA groups ex vivo. These results show that intravenous Fluosol-DA significantly reduces reperfusion injury with greater salvage of myocardium and improved left ventricular function. The chief mechanism of action of Fluosol-DA appears to be the suppression of neutrophil function.

Neuropeptide Y is a vasoconstrictor of human coronary arteries.

Neuropeptide Y (NPY) is a 36-amino-acid polypeptide which coexists with catecholamines in many adrenergic and noradrenergic neurons. It has been demonstrated to exert pressor effects in the perfused guinea pig heart and to constrict large cerebral and coronary blood vessels in animal studies. To determine if NPY might be a human coronary vasoconstrictor, the authors studied its effect on postmortem human coronary arteries. Proximal epicardial coronary rings were studied in a superfusion apparatus in Krebs-Ringer bicarbonate buffer (37 degrees C, pH 7.4) presaturated with 95% O2-5% CO2. Concentration-response curves were obtained using NPY in 0.1% bovine serum albumin in buffer and the responses were compared to those obtained in the presence of alpha 1, beta, and cyclooxygenase antagonists. A dose-related constrictor effect was obtained with NPY, which was significantly more potent than noradrenaline, constriction often being seen at 10(-12) M concentration. A vasorelaxant effect was seen in nonatherosclerotic vessels at higher concentrations. The vasoconstriction produced by noradrenaline was potentiated by subthreshold concentrations of NPY. The vasoconstrictor effect of NPY was not inhibited by prazosin (10(-6) M), and the vasodilatory effect was not inhibited by propranolol (10(-5) M). Indomethacin (3 X 10(-6) M) did not alter either vasoconstriction or vasorelaxation. The authors conclude that NPY is a potent constrictor of the human coronary artery at concentrations that may be achievable in vivo; it may thus be a contributor to sympathetic enhancement of coronary artery tone.

Preservation of endothelial cell structure and function by intracoronary perfluorochemical in a canine preparation of reperfusion.

To determine the effect of intracoronary perfluorochemical on endothelial cell structure and function, 16 dogs were randomized to receive either low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) or saline after 90 min of proximal occlusion of the left anterior descending coronary artery (LAD). The animals underwent reperfusion for 60 min with the introduction of perfluorochemical or saline 5 to 10 min after the onset of reperfusion. Endothelium-dependent coronary vasodilatory reserve was determined in vivo both at baseline and 1 hr after reperfusion by infusion of acetylcholine and then serotonin into the distal LAD bed in 12 animals (six in each group). Both agonists significantly increased regional flow measured by 133Xe washout in the two groups before occlusion, but at 1 hr after reperfusion only animals given perfluorochemical demonstrated a significant increase in flow. Vasodilatory reserve was assessed in vitro with cumulative dose-response curves to acetylcholine on LAD rings proximal and distal to the snare in all animals. These studies demonstrated a significant reduction in endothelial cell-mediated relaxation of epicardial arterial segments in the ischemic segment of control but not treated animals. Light microscopy revealed the presence of neutrophils within vessels in the ischemic zones in control animals only. Electron microscopy showed capillary obstruction by endothelial cell protrusions and neutrophil and red cell plugging in control animals in the ischemic region but an intact endothelium and predominantly unobstructed capillaries in treated animals. These findings suggest that the structural and functional endothelial damage after reperfusion may be prevented by the administration of intracoronary perfluorochemical after the onset of reperfusion.

Automated assay for alpha 1-antitrypsin with N-alpha-benzoyl-DL-arginine-p-nitroanilide as trypsin substrate and standardized with p-nitrophenyl-p'-guanidinobenzoate as titrant for trypsin active sites.

alpha 1-Antitrypsin is the most abundant of several serum protease inhibitors. Its deficiency is associated with an increased incidence of emphysema in adults, jaundice in newborns, and childhood cirrhosis. We describe an automated functional assay for the Instrumentation Laboratory's Multistat III Microcentrifugal Analyzer with N-alpha-benzoyl-DL-arginine-p-nitroanilide as trypsin substrate. The assay is standardized in terms of moles of trypsin active sites inhibited per liter of serum, by use of a chromogenic titrant for trypsin active sites, p-nitrophenyl-p'-guanidinobenzoate. The method is rapid, precise, and independent of trypsin supplier, and results correlate well with those by a manual chromogenic and a nephelometric assay.

Kinetic ethylene glycol assay with use of yeast alcohol dehydrogenase.

We describe a rapid, accurate, and precise two-point kinetic assay for ethylene glycol. The method involves use of a standard kit for ethanol determination with yeast alcohol dehydrogenase, and of a centrifugal analyzer. Alcohol dehydrogenase catalyzes the oxidation of ethylene glycol in a trichloroacetic acid-precipitated specimen; the resulting NADH production is monitored at 340 nm. The reaction rate is linear with concentration to 1.5 g of ethylene glycol per liter. Interference from methanol, ethanol, and isopropanol was easily recognized after a 30-min incubation at 100 degrees C. We believe that the method can be readily adaptable to any narrow-bandwidth, stable, temperature-controlled spectrophotometer and so should provide more widely for the prompt assessment of patients in whom ethylene glycol poisoning is suspected.