Rate Of Left Ventricular Pressure Fall Research Articles

Intraventricular pressure gradients throughout the cardiac cycle: effects of ischaemia and modulation by afterload

The aim of the present study was to characterize the intraventricular pressure gradients (IVPGs) througout the cardiac cycle, to correlate them with myocardial segmental asynchrony and to evaluate the effects of ischaemia and modulation by afterload. Open-chest anaesthetized rabbits (n = 6) were instrumented with pressure-tip micromanometers placed in the apex and outflow tract of the left ventricular (LV) cavity and with sonomicrometer crystals placed in the apex and base of the LV free wall to measure IVPGs and myocardial segment length changes during basal, afterloaded (aortic cross-clamping) and ischaemic conditions (left anterior descending coronary artery ligation). During early diastole (rapid filling), we recorded an IVPG (4.6 ± 0.7 mmHg) from the cardiac base towards the apex followed by an apex-to-outflow pressure gradient (3.6 ± 0.2 mmHg). During systole, we recorded an IVPG (0.6 ± 0.1 mmHg) from apex to outflow during early rapid ejection, which inverted during late slow ejection. Interestingly, the maximal rate of LV pressure fall occurred earlier and relaxation rate was faster in the base than in the apex. While shortening of basal segments was complete at the end of ejection, apical segments always showed a significant amount of postsystolic shortening. The IVPGs were entirely lost during ischaemia and attenuated by afterload elevations. During ischaemia, systolic shortening of the apical segment decreased, while postsystolic shortening increased. The present study confirms the existence of diastolic and systolic IVPGs in the LV and demonstrates, for the first time, that this normal gradient pattern is related to physiological asynchrony between basal and apical myocardial segments. Moreover, we show that the IVPG, a marker of normal left ventricular function, can be attenuated, lost entirely or even reversed after regional acute ischaemia and afterload elevations.

Left ventricular dysfunction and associated cellular injury in rats exposed to chronic intermittent hypoxia

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Fifty-six rats were exposed either to CIH (nadir O(2) 4-5%) or sham (handled normoxic controls, HC), 8 h/day for 6 wk. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Compared with HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH 141.3 +/- 33.1 vs. HC 184.4 +/- 21.2 ml x min(-1) x kg(-1), P < 0.01), maximal rate of LV pressure rise in systole (+dP/dt), and maximal rate of LV pressure fall in diastole (-dP/dt). CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3,564 +/- 354 vs. HC 2,628 +/- 242 microm(2), P < 0.05) and cell length (CIH 148 +/- 23 vs. HC 115 +/- 16 microm, P < 0.05), elevated terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-stained positive cell number (CIH 98 +/- 45 vs. HC 15 +/- 13, P < 0.01), elevated caspase-3 activity (906 +/- 249 vs. 2,275 +/- 1,169 pmol x min(-1) x mg(-1), P < 0.05), and elevated expression of several remodeling gene markers, including c-fos, atrial natriuretic peptide, beta-myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, or in LV collagen deposition on trichrome-stained slices. In conclusion, CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level.

Reducing susceptibility to bacteremia after experimental burn injury: a role for selective decontamination of the digestive tract

We proposed that selective decontamination of the digestive tract (SDD) initiated after experimental burn injury would decrease myocardial inflammation and dysfunction after a second insult such as septic challenge. Rats were divided into eight experimental groups. Groups included sham burn plus sham sepsis, burn alone, sepsis alone, and burn plus sepsis given either water by oral gavage for 5 days after burn (or sham burn) or given oral antibiotics (polymyxin E, 15 mg; tobramycin, 6 mg; 5-flucytosin, 100 mg given by oral gavage, 2x daily for 5 days after burn or sham burn). Cardiac function and inflammation were studied 24 h after septic challenge. In the absence of SDD, burn alone, sepsis alone, or burn plus septic challenge promoted cardiac myocyte secretion of TNF-alpha (burn, 174+/-11; sepsis, 269+/-19; burn+sepsis, 453+/-14 pg/ml), IL-1beta (burn, 35+/-2; sepsis, 29+/-1; burn+sepsis, 48+/-7 pg/ml), and IL-6 (burn, 143+/-18; sepsis, 116+/-3; burn+sepsis, 248+/-12 pg/ml) compared with values measured in sham (TNF-alpha, 3+/-1; IL-1beta, 1+/-0.4; IL-6, 6+/-1.5 pg/ml) (P<0.05). Impaired ventricular contraction and relaxation responses were evident in the absence of SDD [burn+sepsis: left ventricular pressure (LVP), 65+/-4 mmHg; rate of LVP rise (+dP/dt), 1,320+/-131 mmHg/s compared with values measured in sham: LVP, 96+/-4 mmHg; +dP/dt, 2,095+/-99 mmHg/s, P<0.05]. SDD treatment of experimental burn attenuated septic challenge-related inflammatory responses and improved myocardial contractile responses, producing cardiac TNF-alpha, IL-1beta, and IL-6 levels, LVP, +dP/dt, and rate of LVP fall (-dP/dt) values that were significantly better (P<0.05) than values measured in burn plus sepsis in the absence of SDD. This work confirms that endogenous gut organisms contribute to sensitivity to subsequent infectious challenge.

Cardiovascular Effects of Chronic Intermittent Hypoxia in Mice

Obstructive sleep apnea syndrome (OSA), resulting from repetitive episodes of upper airway occlusion during sleep, increases cardiovascular mortality and morbidity. To determine suitability of mouse model for OSA, we examine the cardiovascular response to chronic intermittent hypoxia (CIH), one of major physiological changes in OSA. Methods Adult C57BL/6 mice were daily exposed to either CIH (cycles of 1-min hypoxia with nadir FIO2 5%, followed by 1-min normoxia, 10 daytime hours/day for 2 months, n=22) or similarly handled normoxic control (C, n=17). Measurements performed include body weight (BW); cardiac catheterization under 2% isoflurane anesthesia after 12 hours following the end of the last exposure; and heart wet weight after euthanasia. Results There is no significant difference between CIH and C in BW, heart rate, rate of left ventricular (LV) pressure rise (+dP/dtmax), rate of LV pressure fall (−dP/dtmax), and weight ratio of right ventricular free wall to BW. CIH increased mean arterial pressure (CIH: 92.8±11.7 vs C: 84.5±11.5 mm Hg, p=0.03), LV end-diastolic pressure (12.5±6.8 vs 5.5±5.4 mm Hg, p<0.01), heart weight to BW ratio (4.1±0.6 vs 3.6±0.3 mg/g, p<0.05), and LV free wall weight to BW ratio (2.07±0.27 vs 1.71±0.18 mg/g, p<0.01). Conclusions Mice with CIH develop higher blood pressure, LV dysfunction, and LV hypertrophy. These changes mimic cardiovascular changes in patients with OSA. We speculate that future use of genetically modified mice with CIH may be useful for investigation of the molecular mechanisms of cardiovascular change in OSA. Supported by NHLBI.

Effects of nicardipine and urapidil on length-dependent regulation of myocardial function in coronary artery surgery patients

Objective: To assess effects of a decrease in left ventricular (LV) afterload (pharmacologically induced by nicardipine and urapidil) on myocardial contraction and relaxation, with emphasis on the effects on load dependence of myocardial function. Design: Prospective, blinded study. Setting: University hospital. Participants: Coronary artery surgery patients. Interventions: Alterations of systolic load were effected by leg elevation in control conditions and after administration of either nicardipine or urapidil before and after cardiopulmonary bypass. Measurements and Main Results: High-fidelity LV pressure tracings were obtained at end-expiration while hearts were paced at a fixed rate of 90 beats/min. Hemodynamic effects of leg elevation were compared before and after nicardipine, 7 μg/kg ( n = 15), and before and after urapidil, 0.4 mg/kg ( n = 15). The effects of leg elevation on parameters of contraction and relaxation were coupled. Both nicardipine and urapidil similarly decreased systolic pressures and peripheral resistance. Nicardipine decreased rate of pressure development (dP/dt max) and slowed LV pressure fall, whereas load dependence of LV relaxation was not altered. Urapidil did not alter dP/dt max, rate of LV pressure fall, or load dependence of relaxation. Similar results were observed after cardiopulmonary bypass. Conclusions: The results of the present study indicate that a pharmacologically induced moderate reduction in LV afterload with nicardipine or urapidil did not alter the length—dependent regulation of myocardial function.

Restoring forces assessed with left atrial pressure clamps.

A negative pressure (P) in the fully relaxed left ventricle (LV) indicates the presence of restoring forces generated during contraction. To assess restoring forces in the intact LV under physiological filling conditions, a servomotor system was used in anesthetized open-chest dogs (n = 8) to produce nonfilling diastoles by left atrial pressure (LAP) clamping during systole such that LAP was less than left ventricular pressure (LVP) during the subsequent diastole. Steady-state LV end-diastolic pressure (EDP) was varied by volume infusion from 4.0 +/- 1.5 (+/-SD) to 12.8 +/- 2.1 mmHg. The corresponding fully relaxed LVPs increased from -2.1 +/- 1.9 to 1.1 +/- 3.2 mmHg, P < 0.001. LAP clamping increased the rate of LVP fall by 34 +/- 28% (P < 0.001) during 10 ms after the LVP dropped below the level of the LVP-LAP crossover of the preceding normal beat. During clamped beats, two-dimensional echo revealed substantial downward displacement of the mitral valve (MV) leaflets despite the reversed LA-LV gradient and absence of filling. Thus 1) restoring forces are present at low physiological EDP but absent at high physiological EDP; 2) filling retards the rate of fall of LVP; 3) even in the absence of filling, the process of LV relaxation facilitates MV opening.

Asynchrony and ryanodine modulate load-dependent relaxation in the canine left ventricle.

Load-dependent relaxation was studied in six anesthetized dogs by inflating an intra-aortic balloon to increase peak left ventricular (LV) pressure by 1-20 mmHg within a single cardiac cycle. A series of timed and graded pressure loads was produced by inflating the balloon either during diastole (early loads) or midsystole (midsystolic pressure loads). The rate of LV pressure fall was measured with the time constant (tau). There was a significant increase in tau with 63 midsystolic pressure load [tau increased 1.4 +/- 0.1% (SE)/mmHg increase in peak LV pressure] but not with 67 early pressure loads (-0.5 +/- 0.1%/mmHg). This difference remained with LV pacing-induced asynchrony (tau increased 1.8 +/- 0.1%/mmHg with 54 midsystolic pressure loads compared with -0.2 +/- 0.1%/mmHg with 56 early pressure loads) and after 5 micrograms/kg of intravenous ryanodine (tau increased 1.0 +/- 0.2%/mmHg with 58 midsystolic pressure loads compared with -0.7 +/- 0.1%/mmHg with 59 early pressure loads). When compared with control, asynchrony significantly augmented and ryanodine significantly attenuated the effects of midsystolic pressure loads. In conclusion, asynchrony and ryanodine modulate the extent of load-dependent relaxation in the intact left ventricle.

Nonuniform course of left ventricular pressure fall and its regulation by load and contractile state.

Effects of systolic left ventricular pressure (LVP) on rates of pressure fall remain incompletely understood. This study analyzed phase-plane dP/dt versus LVP plots to differentiate between accelerating and decelerating effects and to investigate the variability in reported load effects on rates of LVP fall. Abrupt aortic occlusions were performed by inflating a balloon positioned in the ascending aorta of anesthetized open-chest dogs (n = 17). The occlusions resulted in clamp elevations of systolic LVP. In protocol A, the elevations of systolic LVP induced by total aortic occlusions were timed at early, mid, and late ejection. The magnitude of the elevations was 36.0 +/- 3.6 mm Hg for early, 11.6 +/- 0.6 mm Hg for mid, and negligible for late occlusions. The course of LVP fall appeared to be more complex than previously appreciated. Pressure fall might be subdivided in an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. The initial phase accelerated with mid and late occlusions. The intermediate phase slowed down with early and to a lesser extent with mid occlusions. The terminal phase was never affected by aortic clamp occlusions. In protocol B, early elevations of systolic LVP were obtained with multiple graded aortic occlusions. The effects of matched LVP elevations of 12 mm Hg on rate of LVP fall were evaluated with the time constant of LVP fall (tau) and showed an interanimal variability ranging from acceleration and a 20% decrease in tau to deceleration and a 35% increase in tau. Changes in tau were moderately correlated with commonly used indexes of contractility (peak +dP/dt, r = -.78; regional fractional shortening, r = -.63). These changes in tau showed a close correlation with the systolic LVP of the test beat, expressed as a percentage of the peak isovolumetric LVP, obtained with total aortic occlusion (r = .984). This suggested that the contraction-relaxation coupling should be analyzed in terms of peak force development rather than contraction velocity or ejection fraction. LVP fall could be subdivided into an initial accelerative phase, an intermediate decelerative phase, and a terminal decelerative phase. Effects of elevations in systolic LVP on rate of LVP fall could be predicted by knowing peak isovolumetric LVP. Nonuniformity of LVP fall and adequate interpretation of load effects should be taken into account when clinical situations or pharmacological interventions are considered. In congestive heart failure, slow LVP fall could mainly reflect working conditions close to isovolumetric rather than relaxation disturbances.

Nonuniformity and volume loading independently influence isovolumic relaxation rates.

We examined the influence of loading conditions and nonuniformity of left ventricular (LV) function on the rate of LV pressure fall in seven anesthetized dogs. Loading conditions were altered with vena cavae occlusions and/or intravenous infusions of dextran. Nonuniformity was produced by injecting 8-20 ng of isoproterenol into the mild left anterior descending coronary artery to produce an asynchronous and early onset of segment lengthening in the anterior wall. Temporal and regional nonuniformity were quantified with indexes derived by comparing segment lengths in the anterior and posterior walls, measured with midwall sonomicrometers. The rate of LV pressure fall was assessed with peak -dP/dt, the time constant, tau, and the duration of isovolumic relaxation. Volume loading decreased the rate of LV pressure fall without altering the nonuniformity indexes. Intracoronary isoproterenol produced nonuniformity and decreased the rate of LV pressure fall without altering global loading conditions. The effects of isoproterenol (in a constant dose) were similar irrespective of the LV volume. We conclude that in the intact, ejecting left ventricle, loading conditions and nonuniformity are important determinants of the rate of LV pressure fall, but these two factors exert their influence by mechanisms that are largely independent.