David A. Berman

Acute hemodynamic effect of oral nifedipine in severe chronic congestive heart failure

The temporal hemodynamic effects of oral nifedipine after a single dose of 20 to 40 mg were evaluated in 11 patients with severe chronic congestive heart failure (left ventricular ejection fraction 0.22 +/- 0.7 [mean +/- standard deviation]). Nifedipine significantly reduced systemic vascular resistance, from 1,850 +/- 493 to 1,315 +/- 398 dynes s cm-5 at 1 hour (29%), to 1,410 +/- 246 at 3 hours and to 1,523 +/- 286 at 6 hours (p less than 0.05). Cardiac index increased 21%, from 2.07 +/- 0.46 to 2.51 +/- 0.83 liters/min/m2 at 1 hour, to 2.38 +/- 0.53 liters/min/m2 at 3 hours (p less than 0.05) and to 2.24 +/- 0.41 liters/min/m2 at 6 hours. The group response of stroke volume to nifedipine was smaller. A peak increase of 17% was seen 3 hours after initiation of therapy (22.6 +/- 7.2 versus 25.5 +/- 6.1 ml/m2). This difference did not reach statistical significance. Mean blood pressure declined significantly, from 94 +/- 20 to 80 +/- 13 mm Hg at 1 hour, to 83 +/- 15 mm Hg at 3 hours and to 86 +/- 17 mm Hg at 6 hours (p less than 0.05) and was associated with no significant change in heart rate. The marked decrease in blood pressure resulted in a decrease in rate-pressure product from 12,272 +/- 4,230 to 10,500 +/- 2,074 mm Hg/min at 1 hour, to 10,374 +/- 2,735 mm Hg/min at 3 hours and to 11,047 +/- 3,813 mm Hg/min at 6 hours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Mathematical Analysis of Oscillatory and Non-oscillatory Recovery of Contractility after a Rested-State Contraction and Its Modification by Calcium

Recovery of contractility after a rested-state contraction in rat ventricle proceeded in two phases and is described by equations that are solutions of a nonhomogeneous second-order differential equation. The recovery can be characterized by a damping ratio defined in terms of the constants of the homogeneous portion of the differential equation. When calcium concentration was elevated, the usual smooth recovery curve underwent oscillatory variation and thus became less damped. There was a shift in phase between oscillation in recovery and in resting tension after a rested-state contraction. A control system is proposed to regulate relaxation and subsequent recovery of contractility. Possible mechanisms for an effect of calcium on such a control system are discussed.

Energy Sources for Contraction of the Rat Ventricle in Phosphate Media

Various substrates were tested for their ability to restore the amplitude of contraction of hypodynamic electrically-stimulated rat ventricle strips suspended in a phosphate-buffered medium. Greatest recovery of the contractile activity was obtained with pyruvate; lactate, β-hydroxybutyrate and acetate were more effective than succinate and glucose. The finding that glucose, in contrast to pyruvate, was relatively ineffective as an energy source for contraction, when a phosphate-buffered medium was employed, suggests that the defect was due to a rate-limiting step in the conversion of glucose to pyruvate, rather than to an impairment in the functioning of the Krebs cycle.

Mathematical analysis of isometric cardiac muscle contraction: The effects of stimulus interval, temperature, and calcium

Abstract The time course of oscillatory and nonoscillatory isometric rested-state contraction in rat ventricle has been described by solutions of a nonhomogeneous second-order linear differential equation. The experimental conditions constitute a definition of the initial conditions of the differential equation and thus determine the form of the transient solution. The response of the contractile system can be further characterized by a damping ratio defined in terms of the constants of the homogeneous part of the differential equation. Test contractions early in the recovery of contractility were more heavily damped than the rested-state contraction. During the first phase of recovery, their damping decreased to that of the rested-state contraction. Under conditions of oscillation both low temperature and high calcium decreased the damping, the latter by a specific effect on the angular frequency of oscillation.

Effect of glucose on potassium contracture tension in rat heart

Abstract The effect of substrates on potassium contracture tension of the isolated rat ventricle strip was investigated. The contracture tension magnitude of ventricle strips exposed to potassium rich medium was markedly greater with medium containing pyruvate or acetate than with glucose as the substrate. The effect of substrates on contracture tension was not related to their ability to maintain the ATP stores of the heart, for there was not a significant difference in the ATP levels in ventricle strips incubated in medium containing pyruvate, pyruvate + glucose, or glucose. Glucose reduced the K-contracture tension magnitude of heart strips suspended in medium containing pyruvate or acetate as substrate; 3-0-methylglucose and 2-deoxy-D-glucose did not have this action on K-contracture tension. The reduction of K-contracture tension by glucose was inhibited by iodoacetate and fluoride. Under anaerobic conditions, 50 mM glucose significantly reduced the K-contracture tension of ventricle strips suspended in pyruvate medium. The findings of this study suggest that glucose metabolism has an action on K-contracture tension in cardiac muscle that is not shared by acetate or pyruvate.

Oxidation of glucose-1-14C, glucose-6-14C and acetate-1-14C by rat ventricle strips during the inotropic action of fluoroacetate

Abstract The rate of oxidation of 14 C-labeled substrates by electrically stimulated rat ventricle strips during the positive inotropic action of fluoroacetate was investigated. The positive inotropic effect of fluoroacetate was accompanied by a marked depression of glucose oxidation. In the presence of fluoroacatate, the amount of 14 CO 2 derived from the metabolism of glucose-1- 14 C was not significantly different from that derived from glucose-6- 14 C. The data indicated that during the positive inotropic effect of fluoroacetate the Krebs cycle was inhibited. The energy for the positive inotropic effect does not appear to be derived from the oxidation of glucose via the phosphogluconate pathway.