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Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any. We performed a prospective study in 202 patients who died in the ICU with a central venous and/or arterial catheter. One minute after the heart stopped beating, intravascular pressures were recorded in the supine position after ventilator disconnection. Parameters at admission, during the ICU stay, and at the time of death were prospectively collected. One-minute Pmsf was 12.8 ± 5.6 mmHg. It did not differ according to gender, severity score, diagnosis at admission, fluid balance, need for and duration of mechanical ventilation, or length of stay. Nor was there any difference according to suspected cause of death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock, although a large variability of values was observed. The presence of norepinephrine at the time of death (102 patients) was associated with a higher 1-min Pmsf (14 ± 6 vs. 11.4 ± 4.5 mmHg), whereas the decision to forgo life-sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 ± 3.8 vs. 13.1 ± 5.3 mmHg). In a multiple-regression analysis, norepinephrine (β = 2.67, P = 0.0004) and age (β = -0.061, P = 0.022) were associated with 1-min Pmsf. One-minute Pmsf appeared highly variable without any difference according to the kind of shock and fluid balance, but was higher with norepinephrine. [ABSTRACT FROM AUTHOR]

Fibulin-4 is an extracellular matrix protein that is essential for proper assembly of arterial elastic fibers. Mutations in fibulin-4 cause cutis laxa with thoracic aortic aneurysms (TAAs). Sixty percent of TAAs occur in the ascending aorta (AA). Newborn mice lacking fibulin-4 (Fbln4-/-) have aneurysms in the AA, but narrowing in the descending aorta (DA), and are a unique model to investigate locational differences in aneurysm susceptibility. We measured mechanical behavior and gene expression of AA and DA segments in newborn Fbln4-/- and Fbln4-/- mice. Fbln4-/- AA has increased diameters compared with Fbln4-/- AA and Fbln4-/- DA at most applied pressures, confirming genotypic and locational specificity of the aneurysm phenotype. When diameter compliance and tangent modulus were calculated from the mechanical data, we found few significant differences between genotypes, suggesting that the mechanical response to incremental diameter changes is similar, despite the fragmented elastic fibers in Fbln4-/- aortas. Fbln4-/- aortas showed a trend toward increased circumferential stretch, which may be transmitted to smooth muscle cells (SMCs) in the wall. Gene expression data suggest activation of pathways for SMC proliferation and inflammation in Fbln4-/- aortas compared with Fbln4+/+. Additional genes in both pathways, as well as matrix metalloprotease-8 (Mmp8), are upregulated specifically in Fbln4-/- AA compared with Fbln4+/+ AA and Fbln4-/- DA. Mmp8 is a neutrophil collagenase that targets type 1 collagen, and upregulation may be necessary to allow diameter expansion in Fbln4-/- AA. Our results provide molecular and mechanical targets for further investigation in aneurysm pathogenesis. [ABSTRACT FROM AUTHOR]

Controversy exists about whether one-dimensional wave theory can explain the "self-canceling" waves that accompany the diastolic pressure decay and discharge of the arterial reservoir. Although it has been proposed that reservoir and wave effects be treated as separate phenomena, thus avoiding the issue of self-canceling waves, we have argued that reservoir effects are a phenomenological and mathematical subset of wave effects. However, a complete wave-based explanation of self-canceling diastolic expansion (pressure-decreasing) waves has not yet been advanced. These waves are present in the forward and backward components of arterial pressure and flow (P± and Q±, respectively), which are calculated by integrating incremental pressure and flow changes (dP± and dQ±, respectively). While the integration constants for this calculation have previously been considered arbitrary, we showed that physiologically meaningful constants can be obtained by identifying "undisturbed pressure" as mean circulatory pressure. Using a series of numeric experiments, absolute P± and Q± values were shown to represent "wave potential," gradients of which produce propagating wavefronts. With the aid of a "one-dimensional windkessel," we showed how wave theory predicts discharge of the arterial reservoir. Simulated data, along with hemodynamic recordings in seven sheep, suggested that self-canceling diastolic waves arise from repeated and diffuse reflection of the late systolic forward expansion wave throughout the arterial system and at the closed aortic valve, along with progressive leakage of wave potential from the conduit arteries. The combination of wave and wave potential concepts leads to a comprehensive one-dimensional (i.e., wave-based) explanation of arterial hemodynamics, including the diastolic pressure decay. [ABSTRACT FROM AUTHOR]

Isolated rat papillary muscles of the right ventricle were used to discover the origin of reduced myocardial efficiency in chronic heart failure. Right ventricular hypertrophy was induced by monocrotaline injection, causing pulmonary hypertension. Control (n = 7) and hypertrophied (n = 11) papillary muscles were subjected to sinusoidal length changes at 37°C and 5 Hz with a peak-to-peak amplitude of 15% of the length giving maximum force (L max) after being stretched to 92.5% of L max Isometric tension at L max was similar in control and hypertrophied muscles. Work was assessed from the area encompassed by force-length 1oops. Work per 1oop was 0.93 ± 0.11 and 0.84 ± 0.11 μJ/mm3 (means ± SE) for control and hypertrophied muscles, respectively (P = 0.591). Suprabasal O2 uptake per work loop was 5.7 ± 0.7 pmol/mm3 in control muscles and 8.7 ± 1.7 pmol/mm3 in hypertrophied muscles (P = 0.133). Net mechanical efficiency was calculated from the ratio of work output and suprabasal O2 uptake. The efficiency of hypertrophied muscles was 29.1 ± 3.7% and was smaller than in control muscles (43.7 ± 2.2%, P = 0.016). The right ventricular cardiomyocyte cross-sectional area increased from 272 ± 17 μm2 in control muscles to 396 ± 31 μm2 in hypertrophied muscles (P < 0.003). Mechanical efficiency correlated negatively with right ventricular wall thickness and cardiomyocyte cross-sectional area [Spearman rank correlation coefficients of -0.50 (P 0.039) and -0.53 (P = 0.024), respectively]. We conclude that efficiency decreases with increasing cardiomyocyte hypertrophy. Thus, the reduced efficiency of diseased whole hearts can be at least partly explained by reduced efficiency at the cardiomyocyte level. [ABSTRACT FROM AUTHOR]

The role of proton (H+) production from glucose metabolism in the recovery of myocardial function during postischemic reperfusion and its alteration by insulin and other metabolic modulators were examined. Rat hearts were perfused in vitro with Krebs-Henseleit solution containing palmitate (1.2 mmol/l) and glucose (11 mmol/l) under nonischemic conditions or during reperfusion following no-flow ischemia. Perfusate contained normal insulin (n-Ins, 50 mU/l), zero insulin (0-Ins), or supplemental insulin (s-Ins, 1,000 mU/l) or other metabolic modulators [dichloroacetate (DCA) at 3 mmol/l, oxfenicine at I mmol/1, and N6-cyclohexyladenosine (CHA) at 0.5 µmol/l. Relative to n-Ins, 0-Ins depressed rates of glycolysis and glucose oxidation in nonischemic hearts and impaired recovery of postischemic function. Relative to n-Ins, s-Ins did not affect aerobic glucose metabolism and did not improve recovery when present during reperfusion. When present during ischemia and reperfusion, s-Ins impaired recovery. Combinations of metabolic modulators with s-Ins stimulated glucose oxidation ~2.5-fold in nonischemic hearts and reduced H+ production. DCA and CHA, in combination with s-Ins, improved recovery of function, but addition of oxfenicine to this combination provided no further benefit. Although DCA and CHA were each partially protective in hearts perfused with n-Ins, optimal protection was achieved with DCA + CHA; recovery of function was inversely proportional to H+ production during reperfusion. Although supplemental insulin is not beneficial, elimination of H+ production from glucose metabolism by simultaneous inhibition of glycolysis and stimulation of glucose oxidation optimizes recovery of postischemic mechanical function. [ABSTRACT FROM AUTHOR]

Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7-10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution to LVFV increased from 18 ± 4 to 45 ± 13% (P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test the hypothesis that exchange transfusion with liposomal hemoglobin (LH) reduces the microheterogeneity of regional myocardial flows while sustaining cardiac function. Neo Red Cell mixed with albumin was used as the LH solution, in which the LH volume fraction was 17∼18% and hemoglobin density was nearly two-thirds smaller than in rat blood. Regional myocardial flows in left ventricular free walls were measured by tracer digitalradiography (100-μm resolution) in anesthetized rats with or without 50% blood-ER exchange transfusion. Within-layer flow distributions showed lower heterogeneity with (n = 8) than without (n = 8) LH transfusion. No extravasation of hemoglobin was confirmed by 3,3-diaminobenzidin staining (n = 2). Carotid flow increased by 68% due to LR transfusion, whereas arterial pressure and heart rate remained unchanged. On the other hand, cross-circulated rat hearts (n = 7) were used to evaluate the effects of 50% blood-ER exchange on coronary flow and tone preservation under 300-beats/mm pacing and l00-mmHg perfusion pressure. Blood-LR exchange caused a 71% increase of coronary flow and 10% decrease of percent flow increase during hyperemia after 30-s flow interruption. Myocardial O2 supply and consumption increased by 9% and 10%, respectively, whereas myocardial O2 extraction remained unchanged. The large increases of in vivo carotid flow and coronary flow in cross-circulated hearts due to LH coperfusion could be explained by the reduction of apparent flow viscosity. These results suggest that under LH coperfusion, the microheterogeneity of myocardial flows decreases with increased coronary flow while fairly preserving coronary tone and cardiac function. [ABSTRACT FROM AUTHOR]

Myocardial blood flow is unevenly distributed, but the cause of this heterogeneity is unknown. Heterogeneous blood flow may reflect heterogeneity of oxygen demand. The aim of the present study was to assess the relation between oxygen consumption and blood flow in small tissue regions in porcine left ventricle. In seven male, anesthetized,open-chest pigs, local oxygen consumption was quantitated by computational model analysis of the incorporation of 13C in glutamate via the tricarboxylic acid cycle during timed infusion of [13C]acetate into the left anterior descending coronary artery. Blood flow was measured with radioactive microspheres before and during acetate infusion. High-resolution nuclear magnetic esonance 13C spectra were obtained from extracts of tissue samples (159 mg mean dry wt) taken at the end of the acetate infusion. Mean regional myocardial blood flow was stable [5. ± 1.6 (SD) and 5.0 ± 1.4 ml·min-1·g dry t-1 before and after 30 min of acetate infusion, respectively]. Mean left ventricular oxygen consumption measured with the NMR method was 18.6 ± 7.7 micro;mol·min-1·g dry wt-1 and correlated well (r = 0.85, P = 0.02, n = 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 ± 4.7 µmol·min-1·g dry wt-1). Local blood flow and oxygen consumption were significantly correlated (r = 0.63 for pooled normalized data, P < 0.0001, n = 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand. [ABSTRACT FROM AUTHOR]

Myocardial stunning is a form of acute reversible cardiac dysfunction that occurs after brief periods of ischemia and reperfusion. In several animal models, stunning is associated with proteolytic truncation of troponin I (TnI). Mice expressing the same proteolytic TnI fragment [TnI-(1–193)] demonstrate cardiac depression with a decreased maximal calcium-activated tension. We therefore hypothesized preferential improvement in mice expressing TnI-(1–193) treated with the calcium-sensitizing drug EMD-57033. TnI-(1–193) and nontransgenic myofibrils exhibited significant sensitization to calcium in Mg-ATPase assays after EMD-57033 enhanced in vivo systolic function modestly in controls but had a marked effect in transgenic mice, with an almost threefold greater leftward shift of the end-systolic pressure-volume relation (P = 0.0005). These data indicate a targeted efficacy of EMD-57033 in offsetting the contractile defect in TnI-(1–193) mice, and this may have therapeutic implications in models displaying this myofilament defect. [ABSTRACT FROM AUTHOR]

Regional myocardial flow distributions in Langendorff rat hearts under Yyrode and blood perfusion were assessed by tracer digital radiography (100-μm resolution). Flow distributions during baseline and maximal hyperemia following a 60-s flow cessation were evaluated by the coefficient of variation of regional flows (CV; related to global flow heterogeneity) and the correlation between adjacent regional flows (CA; inversely related to local flow randomness). These values were obtained for the original images (642 pixels) and for coarsegrained images (322, 162, and 82 blocks of nearby pixels). At a given point in time during baseline, both CV and CA were higher in blood (n = 7) than in Tyrode perfusion (n = 7) over all pixel aggregates (P < 0.05, two-way ANOVA). During the maximal hyperemia, CV and CA were still significantly higher in blood (n = 7) than in Tyrode perfusion (n = 7); however, these values decreased substantially in blood perfusion and the CV and CA differences became smaller than those at baseline accordingly. During basal blood perfusion, the 60-s average flow distribution (n = 7) showed a smaller CV and CA than those at a given point in time (P < 0.05, two-way ANOVA). Coronary flow reserve was significantly higher in blood than in Tyrode perfusion. In conclusion, the flow heterogeneity and the local flow similarity are both higher in blood than in Tyrode perfusion, probably due to the different degree of coronary tone preservation and the presence or absence of blood corpuscles. Under blood perfusion, temporal flow fluctuations over 60-s order are largely involved in shaping microregional flow distributions. [ABSTRACT FROM AUTHOR]

Discusses results of a study evaluating flow heterogeneity and impaired reflow during reperfusion in isolated rabbit heart. Regional myocardial blood flow; Calculation of regional deposition density; Flow estimates with microspheres.

Focuses on a study which assessed whether a postischemic fatty acid preference significantly contributes to mechanoenergetic inefficiency in the stunned myocardium. Materials and methods; Results; Interpretation of findings.

Deals with a study which tested the hypothesis that the cardiac sympathetic afferent reflex is enhanced by plasma volume expansion and left ventricular distention in normal dogs. Methods; Results; Discussion.

Presents a study which investigated the relation between local myocardial flow (LMF) and local oxidative metabolism in isolated rabbit hearts. Heterogeneity of LMF in mammals; Methodology of the study; Discussion of the results.

Presents a study which examined the effect of increased oxygen cost of contractility derived from energy-wasteful myocardial calcium handling. Methods; Results; Discussion of the results.

Provides information on a study which assessed effects of altering myocardial substrate availability in an in vivo situation with undisturbed myocardial perfusion on the myocardial oxygen consumption. Methodology; Results and discussion; Conclusions.