We examined the influence of the systolic left ventricular pressure (LVP) waveform on the rate of isovolumetric LVP fall, as assessed by the time constant tau. Seven open-chest dogs were instrumented with a micromanometer in the left ventricle, with segment length gauges in the anterior and posterior midwall of the left ventricle, and with a balloon-tipped catheter in the proximal aorta. The intra-aortic balloon was inflated before the onset of ejection (early) or during midejection (late) to produce timed and graded increases in peak LVP of 2-20 mmHg. The rate of LVP fall slowed significantly more with late than with early increases in LVP (tau increased 1.5 +/- 0.5 vs. 0.5 +/- 0.3%/mmHg increase in peak LVP, respectively, P less than 0.001). For a similar increase in peak LVP, there was a progressively greater increase in tau when the timing of balloon inflation was progressively delayed from early to late ejection (in 10-ms increments). The differential effect of early vs. late pressure increases on tau was not related to regional differences in segment length behavior nor to an increase in regional nonuniformity between anterior and posterior sites. We conclude that under the experimental conditions of an intact, ejecting left ventricle, the systolic pressure profile is an important determinant of the rate of pressure fall. The rate of LVP fall slows in direct proportion to the magnitude of increase in systolic pressure. The sensitivity to systolic load increases progressively throughout the ejection period, so that the rate of LVP fall slows significantly more with late than with early pressure increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Background-Cardiac-directed expression of adenylyl cyclase type VI (AC VI ) in mice results in structurally normal hearts with normal basal heart rate and function but increased responses to catecholamine stimulation. We tested the hypothesis that increased left ventricular (LV) AC VI content would increase mortality after acute myocardial infarction (MI

Lipopolysaccharide (LPS) plays a key role in the pathogenesis of sepsis. Cardiac function and the inotropic response to beta-adrenergic stimulation are impaired in sepsis. We hypothesized that LPS, in clinically relevant levels (1 ng/mL), directly depresses contractility and beta-adrenergic responses in cardiac myocytes. Cardiac myocytes were isolated from the left ventricle of adult rabbits using digestive enzymes (collagenase and protease). We depyrogenated the enzymes (LPS contamination lowered from 100 to 300 ng/mL to < 0.7 ng/mL) to minimize development of LPS tolerance during cell isolation. After 6 hours of incubation with 1 ng/mL LPS, there was a decrease in the extent of active cell shortening with no change in Ca2+ transients (measured with indo 1 fluorescence), indicating decreased myofilament responsiveness to Ca2+. This was related to NO pathways, since cGMP (a second messenger of NO) increased in cardiac myocytes and LPS effects were completely reversed with a 1 mmol/L NG-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor). LPS did not alter the intracellular Ca2+ response to beta-adrenergic stimulation with isoproterenol but attenuated the contractile response (maximal cell shortening, 15.5 +/- 1.0% versus 23.3 +/- 1.1% in control myocytes; P < .001). LPS attenuation of the contractile response to isoproterenol was restored completely by L-NMMA and almost completely restored (to 86% of the control response) by an inhibitor of cGMP-dependent protein kinase. We conclude that LPS depresses cardiac contractility and the contractile response to beta-adrenergic stimulation by a NO-cGMP-mediated decrease in myofilament responsiveness to Ca2+. The direct effects of low levels of LPS on cardiac myocytes may contribute to cardiac depression and hemodynamic decompensation during sepsis.