Beta adrenergic stimulation and blockade in cirrhosis: effects on azygos vein blood flow and portal hemodynamics.

It is unknown whether beta adrenergic stress has adverse hepatic hemodynamic effects. Therefore, the authors studied the hemodynamic effects of beta adrenergic stimulation and subsequent blockade in 10 patients with cirrhosis (6 Childs A, 3 Childs B, and 1 Childs C) with known or suspected portal hypertension. Free and wedged hepatic vein pressures, hepatic venous pressure gradient, heart rate, mean arterial pressure, cardiac output, and azygos vein blood flow were measured at rest and after isoproterenol infusion (mean dose = 7.3 micrograms/min: target heart rate = 150% to 200% of resting heart rate). Esmolol, an ultra-short-acting beta blocker, was then infused (dose titrated to return heart rate to baseline), and all measurements were repeated. Based on the results, the authors conclude that beta adrenergic stress provoked by isoproterenol infusion significantly increases azygos vein blood flow and hepatic venous pressure gradient. Beta blockade with esmolol reduces azygos vein blood flow and hepatic venous pressure gradient significantly below baseline.

Coronary sinus lysophosphatidylcholine accumulation during rapid atrial pacing.

The purpose of this study was to determine whether lysophosphatidylcholine (LPC) release from the myocardium could be detected in patients with pacing-induced ischemia. We measured LPC levels in plasma obtained from the coronary sinus in 20 patients undergoing diagnostic atrial pacing stress tests. In 14 patients with pacing-induced ischemia, coronary sinus LPC concentration rose from 69.1 +/- 5.3 microM at baseline to 101.7 +/- 9.0 microM at 4 minutes and to 178.0 +/- 18.0 microM at peak pacing (p less than 0.01). LPC did not increase significantly in 6 nonischemic patients (from 60.8 +/- 7.8 microM at baseline to 70.2 +/- 7.6 microM at peak pacing, difference not significant). LPC did not increase in mixed venous or arterial blood from ischemic patients. Thus, coronary sinus LPC accumulation may be an early marker of ischemia.

Potentiation of the depressant effects of lysophosphatidylcholine on contractile properties of cultured cardiac myocytes by acidosis and superoxide radical.

Lysophosphatidylcholine (LPC) accumulates in the heart during myocardial ischemia. This amphiphile accelerates Ca++ flux in cardiac myocytes and may mediate ischemic cell injury. In the present study, we evaluated the effects of LPC on the contractility of cultured neonatal rat heart cells. We also investigated the interactions between LPC and other prominent features of the ischemic milieu, acidosis, and superoxide radical. A photo-optical technique was used to measure the maximum velocities of shortening and relaxation (dS/dt and dR/dt) of cultured cells superfused with 0.1 to 100 mumol/L LPC. LPC, at all concentrations, initially increased dS/dt. After 1 minute, however, dS/dt decreased in a concentration-dependent manner in cells superfused with greater than 20 mumol/L LPC. The effect of LPC on relaxation was also dependent on LPC concentration. dR/dt increased at less than 40 mumol/L LPC but decreased at greater than or equal to 60 mumol/L LPC. Acidosis markedly potentiated LPC-mediated depression in dS/dt and dR/dt. In contrast, superoxide dismutase entirely prevented LPC-mediated depression of contractility. We conclude that whereas brief exposure to LPC stimulates contractility, prolonged exposure to greater than 40 mumol/L LPC depresses dS/dt and dR/dt in cultured myocytes. The depressant effects of LPC on contractility are potentiated by acidosis and superoxide radical. We postulate that LPC accumulation in the myocardium contributes to ischemia-mediated contractile dysfunction.