The diastatic pressure-volume relationship is not the same as the end-diastolic pressure-volume relationship

The end-diastolic pressure-volume (P-V) relationship (EDPVR) is routinely used to determine the passive left ventricular (LV) stiffness, although the diastatic P-V relationship (D-PVR) has also been measured. Based on the physiological difference between diastasis (the LV and atrium are relaxed and static) and end diastole (LV volume increased by atrial systole and the atrium is contracted), we hypothesized that, although both D-PVR and EDPVR include LV chamber stiffness information, they are two different, distinguishable P-V relations. Cardiac catheterization determined LV pressures, and conductance volumes in 31 subjects were analyzed. Physiological, beat-to-beat variation of the diastatic and end-diastolic P-V points were fit by linear and exponential functions to generate the D-PVR and EDPVR. The extrapolated exponential D-PVR underestimated LVEDP in 82% of the heart beats (P < 0.001). The extrapolated EDPVR overestimated pressure at diastasis in 84% of the heart beats (P < 0.001). If each subject's diastatic and end-diastolic P-V data were combined to form a continuous data set to be fit by one exponential relation, the goodness of fit was always worse than if the diastatic and end-diastolic data were grouped separately and fit by two distinct exponential relations. Diastatic chamber stiffness was less than EDPVR stiffness (defined by the slope of P-V relation) for all 31 subjects (0.16 +/- 0.11 vs. 0.24 +/- 0.15 mmHg/ml, P < 0.001). We conclude that the D-PVR and EDPVR are distinguishable. Because it is not coupled to a contracted atrium, the D-PVR conveys passive LV stiffness better than the EDPVR. Additional studies that fully elucidate the physiology and biology of diastasis in health and disease are in progress.     

Effects of lung volume and alveolar surface tension on pulmonary vascular resistance

Utilizing the arterial and venous occlusion technique, the effects of lung inflation and deflation on the resistance of alveolar and extraalveolar vessels were measured in the dog in an isolated left lower lobe preparation. The lobe was inflated and deflated slowly (45 s) at constant speed. Two volumes at equal alveolar pressure (Palv = 9.9 +/- 0.6 mmHg) and two pressures (13.8 +/- 0.8 mmHg, inflation; 4.8 +/- 0.5 mmHg, deflation) at equal volumes during inflation and deflation were studied. The total vascular pressure drop was divided into three segments: arterial (delta Pa), middle (delta Pm), and venous (delta Pv). During inflation and deflation the changes in pulmonary arterial pressure were primarily due to changes in the resistance of the alveolar vessels. At equal Palv (9.9 mmHg), delta Pm was 10.3 +/- 1.2 mmHg during deflation compared with 6.8 +/- 1.1 mmHg during inflation. At equal lung volume, delta Pm was 10.2 +/- 1.5 mmHg during inflation (Palv = 13.8 mmHg) and 5.0 +/- 0.7 mmHg during deflation (Palv = 4.8 mmHg). These measurements suggest that the alveolar pressure was transmitted more effectively to the alveolar vessels during deflation due to a lower alveolar surface tension. It was estimated that at midlung volume, the perimicrovascular pressure was 3.5-3.8 mmHg greater during deflation than during inflation.     

Left ventricular wave speed.

Left ventricular (LV) wave speed (LVWS) was studied experimentally and confirmed in theory. Combining the definition of elastance (E) with the equations for the conservation of mass and momentum shows that LVWS is proportional to the square root of ELA, where L is long-axis length and A is the cross-sectional area, and the density of the blood. (We defined ELA = gamma, where gamma is compressibility.) We studied nine open chest, anesthetized dogs, three of which were studied during caval constriction when LV end-diastolic pressure was < or =0 mmHg. The hearts were paced at approximately 90 beats/min, and LV cross-sectional area was measured by using two pairs of ultrasonic crystals; E was calculated from the LV pressure-area loop. A pulse generator was connected to the LV apex, and LVWS was measured by using two pressure transducers: one near the apex and the other near the base. Their distance was measured roentgenographically and compared with the diameter of a reference ball. LVWS ranged from approximately 1 m/s during diastole to approximately 10 m/s during systole. The slope of the log c (where c is wave speed) vs. log gamma was 0.546, which is in agreement with theory (0.5). When gamma < or = 0, LVWS was approximately 1.5 m/s.     

Excessive sympathetic nervous system activity decreases myocardial contractility

The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema.     

Determinants of left ventricular preload-adjusted maximal power

Maximal left ventricular (LV) hydraulic power output (PWR(max)), corrected for preload as PWR(max)/(V(ed))(beta) (where V(ed) is the end-diastolic volume and beta is a constant coefficient), is an index of LV contractility. Whereas preload-adjusted maximal power (PAMP) is usually calculated with beta = 2, there is uncertainty about the optimal value of beta (beta = 1 for the normal LV and 2 for the dilated LV). The aim of this work is to study the determining factors of beta. The data set consisted of 245 recordings (steady state and vena cava occlusion) in 10 animals in an ischemic heart pig model. The occlusion data yielded the slope (E(es); 2.01 +/- 0.77 mmHg/ml, range 0.71-4.16 mmHg/ml) and intercept (V(0); -11.9 +/- 22.6 ml; range -76 to 39 ml) of the end-systolic pressure-volume relation, and the optimal beta-factor (assessed by fitting an exponential curve through the V(ed)-PWR(max) relation) was 1.94 +/- 0.88 (range 0.29-4.73). The relation of beta with V(ed) was weak [beta = 0.60 + 0.02(V(ed)); r(2) = 0.20]. In contrast, we found an excellent exponential relation between V(0) and beta [beta = 2.16e(0.0189(V(0))), r(2) = 0.70]. PAMP, calculated from the steady-state data, was 0.64 +/- 0.40 mW/ml(2) (range 0.14-2.83 mW/ml(2)) with a poor correlation with E(es) (r = 0.30, P < 0.001). An alternative formulation of PAMP as PWR(max)/(V(ed) - V(0))(2), incorporating V(0), yielded 0.47 +/- 0.26 mW/ml(2) (range 0.09-1.42 mW/ml(2)) and was highly correlated with E(es) (r = 0.89, P < 0.001). In conclusion, correct preload adjustment of maximal LV power requires incorporation of V(0) and thus of data measured under altered loading conditions.     

Intrathoracic pressures and left ventricular configuration with respiratory maneuvers

In 12 dogs, we examined the correspondence between esophageal (Pes) and pericardial pressures over the anterior, lateral, and inferior left ventricular (LV) surfaces. Pleural pressure was decreased by spontaneous inspiration, Mueller maneuver, and phrenic stimulation and increased by intermittent positive pressure ventilation (IPPV) and positive end-expiratory pressure (PEEP). To separate effects due to blood flow, we analyzed beating and nonbeating hearts. In beating hearts, there were no significant differences between changes in Pes and pericardial pressures. In arrested hearts, increasing LV pressure by 8 Torr increased pericardial pressures by only 3.6 Torr. With IPPV and PEEP, increases in Pes and pericardial pressures were equal in live hearts and in low-volume arrested hearts (LV pressure = 4 Torr). In high-volume arrested hearts (LV pressure = 12 Torr), the increase in pericardial pressure over the anterior LV surface was less than Pes, whereas that over the lateral and inferior LV surfaces was the same as Pes. At high LV volume, in arrested hearts pericardial pressures decreased less than Pes during negative pressure maneuvers. In another six dogs, external LV configuration and volume were measured. In beating hearts during spontaneous inspiration, Mueller maneuver, and phrenic stimulation (endotracheal tube open), septal-lateral dimension and LV volume decreased by approximately 3% (P less than 0.05). This was also true for PEEP. In arrested hearts, septal-lateral dimension and LV volume decreased only with PEEP. We conclude that 1) the relationship between Pes and pericardial pressures is complex and depends on LV volume, local pericardial compliance, and the means by which Pes is changed, 2) changes in measured pericardial pressures did not completely explain changes in LV configuration, and 3) during different respiratory maneuvers, different forces account for the same observed changes in LV volume and configuration.     

Altered hemodynamics in transgenic mice harboring mutant tropomyosin linked to hypertrophic cardiomyopathy

We used transgenic (TG) mice overexpressing mutant alpha-tropomyosin [alpha-Tm(Asp175Asn)], linked to familial hypertrophic cardiomyopathy (FHC), to test the hypothesis that this mutation impairs cardiac function by altering the sensitivity of myofilaments to Ca(2+). Left ventricular (LV) pressure was measured in anesthetized nontransgenic (NTG) and TG mice. In control conditions, LV relaxation was 6,970 +/- 297 mmHg/s in NTG and 5,624 +/- 392 mmHg/s in TG mice (P < 0.05). During beta-adrenergic stimulation, the rate of relaxation increased to 8,411 +/- 323 mmHg/s in NTG and to 6,080 +/- 413 mmHg/s in TG mice (P < 0.05). We measured the pCa-force relationship (pCa = -log [Ca(2+)]) in skinned fiber bundles from LV papillary muscles of NTG and TG hearts. In control conditions, the Ca(2+) concentration producing 50% maximal force (pCa(50)) was 5.77 +/- 0.02 in NTG and 5.84 +/- 0.01 in TG myofilament bundles (P < 0.05). After protein kinase A-dependent phosphorylation, the pCa(50) was 5.71 +/- 0.01 in NTG and 5.77 +/- 0. 02 in TG myofilament bundles (P < 0.05). Our results indicate that mutant alpha-Tm(Asp175Asn) increases myofilament Ca(2+)-sensitivity, which results in decreased relaxation rate and blunted response to beta-adrenergic stimulation.     

Left ventricular end-diastolic pressure-volume relationship in septic rats with open thorax

To estimate changes in compliance, we evaluated the effects of sepsis on the end-diastolic pressure-volume relationship (EDPVR) in the left ventricle of rats that had undergone an open thorax procedure. Sepsis was induced in male Wistar Hannover rats (n = 7; 240 to 270 g) by intraperitoneal administration of a slurry of cecal contents; control rats (n = 7) were given 5% dextrose only. On the third day after induction of sepsis, left ventricular (LV) pressure and LV dimensions were recorded simultaneously in animals of both groups. Using a micromanometer and ultrasonic crystals, measurements were obtained at baseline and during the increase of afterload. Blood samples were taken for determination of complete blood count, white blood cell differential count, and lactate concentration, and for bacteriologic examination. Septic rats lost weight, and developed changes in body temperature, ascites, and abscesses in the abdominal and thoracic cavities, gram-negative bacteremia, and increase in heart rate. On the third day after induction of sepsis, LV EDPVR decreased, compared with that in the control rats (regression coefficients: control group, 8.41 to 23.95; sepsis group, 3.94 to 7.92). Myocardial compliance in the left ventricle increased on the third day of sepsis in the open-thorax rat model, as evidenced by the downward shift of LV EDPVR in rats with sepsis, compared with controls.     

Continuous monitoring of right ventricular volume changes using a conductance catheter in the rabbit.

To assess the reliability of conductance (G) catheter for evaluating right ventricular (RV) volume changes, a miniature (3.5F) six-electrode catheter was developed and tested in 11 New Zealand rabbit hearts. In five animals the heart was excised; in six it was left in the thorax. RV conductance was recorded while the RV was filled with blood in 0.25-ml steps at different left ventricular (LV) volumes. Linear correlation of measured conductance vs. reference volumes was computed. RV conductance was highly correlated with reference volume [correlation coefficient (r) ranging from 0.991 to 0.999]. Slope of regression lines was not significantly affected by LV volume variations in 1-ml steps or by acute conductance changes of structures surrounding the heart, whereas the intercept was affected only by the 0- to 1-ml LV volume change. In four rabbits, RV conductance changes during a cardiac cycle [stroke volume- (SV) G] were compared in vivo with electromagnetic flow probe-derived estimates of SV (SVem) as stroke volume was varied by graded inferior vena caval occlusion. SV-G correlated well with SVem (r ranging from 0.92 to 0.96). This correlation persisted after the thorax was filled with saline; however, significant differences were found in individual slopes (P < 0.001). These results show that the conductance catheter has a potential to reliably monitor in vivo relative RV volume changes in small-animal hearts.     

Cardiomyocyte-restricted inhibition of G protein-coupled receptor kinase-3 attenuates cardiac dysfunction after chronic pressure overload

Transgenic mice with cardiac-specific expression of a peptide inhibitor of G protein-coupled receptor kinase (GRK)3 [transgenic COOH-terminal GRK3 (GRK3ct) mice] display myocardial hypercontractility without hypertrophy and enhanced α(1)-adrenergic receptor signaling. A role for GRK3 in the pathogenesis of heart failure (HF) has not been investigated, but inhibition of its isozyme, GRK2, has been beneficial in several HF models. Here, we tested whether inhibition of GRK3 modulated evolving cardiac hypertrophy and dysfunction after pressure overload. Weight-matched male GRK3ct transgenic and nontransgenic littermate control (NLC) mice subjected to chronic pressure overload by abdominal aortic banding (AB) were compared with sham-operated (SH) mice. At 6 wk after AB, a significant increase of cardiac mass consistent with induction of hypertrophy was found, but no differences between GRK3ct-AB and NLC-AB mice were discerned. Simultaneous left ventricular (LV) pressure-volume analysis of electrically paced, ex vivo perfused working hearts revealed substantially reduced systolic and diastolic function in NLC-AB mice (n = 7), which was completely preserved in GRK3ct-AB mice (n = 7). An additional cohort was subjected to in vivo cardiac catheterization and LV pressure-volume analysis at 12 wk after AB. NLC-AB mice (n = 11) displayed elevated end-diastolic pressure (8.5 ± 3.1 vs. 2.9 ± 1.2 mmHg, P < 0.05), reduced cardiac output (3,448 ± 323 vs. 4,488 ± 342 μl/min, P < 0.05), and reduced dP/dt(max) and dP/dt(min) (both P < 0.05) compared with GRK3ct-AB mice (n = 16), corroborating the preserved cardiac structure and function observed in GRK3ct-AB hearts assessed ex vivo. Increased cardiac mass and myocardial mRNA expression of β-myosin heavy chain confirmed the similar induction of cardiac hypertrophy in both AB groups, but only NLC-AB hearts displayed significantly elevated mRNA levels of brain natriuretic peptide and myocardial collagen contents as well as reduced β(1)-adrenergic receptor responsiveness to isoproterenol, indicating increased LV wall stress and the transition to HF. Inhibition of cardiac GRK3 in mice does not alter the hypertrophic response but attenuates cardiac dysfunction and HF after chronic pressure overload.     

Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans

Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.     

陶瓷载体固定化酵母发酵动力学研究

固定化细胞和固定化酶一样,作为固液两相的非均相催化反应系统,其反应速度无疑受到内外扩散的影响。世界各国的化学工程学者在固定化酶反应动力学方面研究得较多,固定化细胞反应动力学研究虽有些报道,但主要集中在以海藻酸钙为载体的固定化系统,且载体形状为球形颗粒。对于其他材料的不同形状颗粒载体的固定化细胞动力学研究报道较少。陶瓷作为固定化细胞载体是我们研究的一种固定化细胞的新型载体,在机械强度,孔径大小,细胞与之结合牢固度及其稳定活性,再生性能方面有其特有的优越性^[10]。为了给在生产实践中使用这种新型载体提供理论依据,本文采用球型陶瓷和拉西环陶瓷为载体固定化酵母,对它们的发酵动力学进行了比较研究。     

Heat acclimation: cardiac performance of isolated rat heart

Cardiac performance was studied in the isolated perfused hearts of rats heat acclimated at 34 degrees C (AC) and their age-matched controls (C). The pressure-volume curves during isovolumetric conditions showed a shift to the right in AC compared with C hearts. At similar left ventricular (LV) volumes end-diastolic and peak systolic pressures of AC hearts were lower, but no difference was observed in the maximal pressure developed at the highest LV volumes measured. In both C and AC hearts the developed force decreased as pacing rate increased. AC and C heart responses were the same up to 250 pulses/min. At higher frequencies the amplitude of the developed force of AC hearts was smaller than that of the controls. In accordance the tension produced by very early premature beat reduced in AC compared with C hearts. Since no hypertrophy was observed in AC hearts, it is concluded that heat acclimation results in a change in the intrinsic properties of the AC hearts exhibited by increased compliance, reduced chamber stiffness, and a decrease in the tension developed for each volume load. It is also suggested that at a high beating rate AC hearts fail to restitute its contractility as quickly as C hearts.     

Right and left ventricular pressure-volume response to respiratory maneuvers

With respiration, right ventricular end-diastolic volume fluctuates. We examined the importance of these right ventricular volume changes on left ventricular function. In six mongrel dogs, right and left ventricular volumes and pressures and esophageal pressure were simultaneously measured during normal respiration, Valsalva maneuver, and Mueller maneuver. The right and left ventricular volumes were calculated from cineradiographic positions of endocardial radiopaque markers. Increases in right ventricular volume were associated with changes in the left ventricular (LV) pressure-volume relationship. With normal respiration, right ventricular end-diastolic volume increased 2.3 +/- 0.7 ml during inspiration, LV transmural diastolic pressure was unchanged, and LV diastolic volume decreased slightly. This effect was accentuated by the Mueller maneuver; right ventricular end-diastolic volume increased 10.4 +/- 2.3 ml (P less than 0.05), while left ventricular end-diastolic pressure increased 3.6 mmHg (P less than 0.05) without a significant change in left ventricular end-diastolic volume. Conversely, with a Valsalva maneuver, right ventricular volume decreased 6.5 +/- 1.2 ml (P less than 0.05), and left ventricular end-diastolic pressure decreased 2.2 +/- 0.5 mmHg (P less than 0.05) despite an unchanged left ventricular end-diastolic volume. These changes in the left ventricular pressure-volume relationship, secondary to changes in right ventricular volumes, are probably due to ventricular interdependence. Ventricular interdependence may also be an additional factor for the decrease in left ventricular stroke volume during inspiration.     

Indexes of diastolic RV function: load dependence and changes after chronic RV pressure overload in lambs

Diastolic function is a major determinant of ventricular performance, especially when loading conditions are altered. We evaluated biventricular diastolic function in lambs and studied possible load dependence of diastolic parameters [minimum first derivative of pressure vs. time (dP/dt(min)) and time constant of isovolumic relaxation (tau)] in normal (n = 5) and chronic right ventricular (RV) pressure-overloaded (n = 5) hearts by using an adjustable band on the pulmonary artery (PAB). Pressure-volume relations were measured during preload reduction to obtain the end-diastolic pressure-volume relationship (EDPVR). In normal lambs, absolute dP/dt(min) and tau were lower in the RV than in the left ventricle whereas the chamber stiffness constant (b) was roughly the same. After PAB, RV tau and dP/dt(min) were significantly higher compared with control. The RV EDPVR indicated impaired diastolic function. During acute pressure reduction, both dP/dt(min) and tau showed a relationship with end-systolic pressure. These relationships could explain the increased dP/dt(min) but not the increased tau-value after banding. Therefore, the increased tau after banding reflects intrinsic myocardial changes. We conclude that after chronic RV pressure overload, RV early relaxation is prolonged and diastolic stiffness is increased, both indicative of impaired diastolic function.     

Biventricular cardiac dysfunction after acute massive pulmonary embolism in the rat.

Cardiac dysfunction has been documented in vivo after acute massive pulmonary embolism (AMPE). The present study tests whether intrinsic ventricular dysfunction occurs in rat hearts isolated after AMPE. AMPE was induced in spontaneously breathing ketamine-xylazine-anesthetized rats by thrombus infusion until mean arterial blood pressure (MAP) was approximately 40% of basal measurement. A hypotensive control group underwent controlled blood withdrawal to produce MAP approximately 40% of basal levels. Shams underwent identical surgical and anesthesia preparation but without pulmonary embolization. Hearts were perfused in isovolumetric mode, and simultaneous right ventricular (RV) and left ventricular (LV) pressures were measured. AMPE caused arterial hypotension with hypoxemia (PO(2) = 50 +/- 14 Torr), acidemia (pH = 7.26 +/- 0.11), and high lactate concentration (6.9 +/- 1.7 mM). Starling curves from both ventricles demonstrated that AMPE significantly reduced ex vivo systolic contractile function in the RV (P = 0.031) and LV (P = 0.008) compared with both the hypotensive control and sham hearts. AMPE did not alter coronary flow or compliance in either ventricle. Soluble tumor necrosis factor-alpha decreased in the RV (P = 0.043) and LV (P = 0.005) tissue. These data support the hypothesis that AMPE produces intrinsic biventricular dysfunction and suggest that arterial hypotension is not the principal mechanism of this dysfunction.     

Cardiac dysfunction in aging conscious rats: altered cardiac cytoskeletal proteins as a potential mechanism

The objective of this study was to test the hypothesis that the mechanism mediating left ventricular (LV) dysfunction in the aging rat heart involves, in part, changes in cardiac cytoskeletal components. Our results show that there were no significant differences in heart rate, LV pressure, or LV diameter between conscious, instrumented young [5.9 +/- 0.3 mo (n = 9)] and old rats [30.6 +/- 0.1 mo (n = 10)]. However, the first derivative of LV pressure (LV dP/dt) was reduced (8,309 +/- 790 vs. 11,106 +/- 555 mmHg/s, P < 0.05) and isovolumic relaxation time (tau) was increased (8.7 +/- 0.7 vs. 6.3 +/- 0.6 ms, P < 0.05) in old vs. young rats, respectively. The differences in baseline LV function in young and old rats, which were modest, were accentuated after beta-adrenergic receptor stimulation with dobutamine (20 mug/kg), which increased LV dP/dt by 170 +/- 9% in young rats, significantly more (P < 0.05) than observed in old rats (115 +/- 5%). Volume loading in anesthetized rats demonstrated significantly impaired LV compliance in old rats, as measured by the LV end-diastolic pressure and dimension relationship. In old rat hearts, there was a significant (P < 0.05) increase in the percentage of LV collagen (2.4 +/- 0.2 vs. 1.3 +/- 0.2%), alpha-tubulin (92%), and beta-tubulin (2.3-fold), whereas intact desmin decreased by 51%. Thus the cardiomyopathy of aging in old, conscious rats may be due not only to increases in collagen but also to alterations in cytoskeletal proteins.     

Changes in cardiac contractile function and myocardial

Cutaneous burn trauma causes cardiac contraction and relaxation defects, but the mechanism is unclear. Previous studies suggest that burn-related changes in myocyte handling of calcium may play an important role in postburn cardiac dysfunction. With the use of a high dissociation constant (K(d)) calcium indicator 1,2-bis(2-amino-5,6-difluorophenoxy)-ethane-N,N,N',N'-tetraacetic acid (TF-BAPTA) and (19)F NMR spectroscopy, this study examined the correlation between the changes in cytosolic free calcium concentration ([Ca(2+)](i)) and cardiac function after burn trauma. Sprague-Dawley rats were given scald burn (over 40% of the total body surface area) or sham burn. Twenty-four hours later, the hearts were excised and perfused by the Langendorff method with a modified phosphate-free Krebs-Henseleit bicarbonate buffer. Left ventricular (LV) developed pressure (LVDP), calculated from peak systolic LV pressure and LV end-diastolic pressure, was assessed through a catheter attached to an intraventricular balloon. At the same time, (31)P and (19)F NMR spectroscopy was performed before and after TF-BAPTA loading. LVDP measured in hearts from burned rats was <40% than that measured in hearts from sham burn rats (65 +/- 6 vs. 110 +/- 12 mmHg, P < 0.01); [Ca(2+)](i) was increased fourfold in hearts from the burned group compared with that measured in the sham burn group (0.807 +/- 0.192 vs. 3.891 +/- 0.929 microM). Loading TF-BAPTA in hearts transiently decreased LVDP by 15%. Phosphocreatine-to-P(i) ratio decreased, but ATP and intracellular pH remained unchanged by either TF-BAPTA loading or burn trauma. In conclusion, burn trauma impaired cardiac contractility, and this functional defect was paralleled by a significant rise in [Ca(2+)](i) in the heart.     

Regulation of middle cerebral artery blood velocity during recovery from dynamic exercise in humans.

We sought to examine the regulation of cerebral blood flow during 10 min of recovery from mild, moderate, and heavy cycling exercise by measuring middle cerebral artery blood velocity (MCA V). Transfer function analyses between changes in arterial blood pressure and MCA V were used to assess the frequency components of dynamic cerebral autoregulation (CA). After mild and moderate exercise, the decreases in mean arterial pressure (MAP) and mean MCA V (MCA Vm) were small. However, following heavy exercise, MAP was rapidly and markedly reduced, whereas MCA Vm decreased slowly (-23 +/- 4 mmHg and -4 +/- 1 cm/s after 1 min for MAP and MCA Vm, respectively; means +/- SE). Importantly, for each workload, the normalized low-frequency transfer function gain between MAP and MCA Vm remained unchanged from rest to exercise and during recovery, indicating a maintained dynamic CA. Similar results were found for the systolic blood pressure and systolic MCA V relationship. In contrast, the normalized low-frequency transfer function gain between diastolic blood pressure and diastolic MCA V (MCA Vd) increased from rest to exercise and remained elevated in the recovery period (P < 0.05). However, MCA Vd was quite stable on the cessation of exercise. These findings suggest that MCA V is well maintained following mild to heavy dynamic exercise. However, the increased transfer function gain between diastolic blood pressure and MCA Vd suggests that dynamic CA becomes less effective in response to rapid decreases in blood pressure during the initial 10 min of recovery from dynamic exercise.