Beneficial effects of perfluorochemical artificial blood on cardiac function following coronary occlusion

This study compares the effects of perfluorochemical artificial blood versus whole blood on the systolic and diastolic function of regionally ischemic myocardial preparations. Regional ischemia was produced by ligation of the circumflex coronary artery in isolated, blood-perfused rabbit hearts. Three minutes after occlusion, half the hearts were switched from the blood perfusate to perfluorochemical artificial blood; the other half continued to be perfused with blood. Isovolumic left ventricular (LV) developed pressure, dP/dt and resting pressure were monitored before, and for 2 hours after coronary occlusion. After 90 minutes of regional ischemia, perfluorochemical-treated hearts exhibited significantly greater developed pressure than those perfused with blood (78 +/- 6% versus 61 +/- 5% of preligation values; P less than 0.05). At the end of the experiment, LV dP/dt was 21% greater in the perfluorochemical-perfused group than in the blood-perfused group (74 +/- 8% versus 53 +/- 10%; P less than 0.01). Perfluorochemical perfusion also preserved diastolic function by preventing the 58% increase in left ventricular chamber stiffness (i.e., resting pressure; P less than 0.01) associated with circumflex ligation. Thus, in the present model of regional ischemia, perfluorochemical artificial blood is significantly better than blood at maintaining both systolic and diastolic myocardial function after a major coronary artery has been occluded.     

Myocardial fibrosis, impaired coronary hemodynamics, and biventricular dysfunction in salt-loaded SHR

Arterial pressure in most experimental and clinical hypertensions is exacerbated by salt. The effects of salt excess on right and left ventricular (RV and LV, respectively) functions and their respective coronary vasodilatory responses have been less explored. We therefore examined the effects of 8 wk of NaCl excess (8% in food) on arterial pressure, RV and LV functions (maximal rate of increase and decrease of ventricular pressure; dP/dt(max) and dP/dt(min)), coronary hemodynamics (microspheres), and collagen content (hydroxyproline assay and collagen volume fraction) in young adult normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), aged 16 wk by the end of the study. Prolonged salt excess in WKY and SHR elevated pressure only modestly, but it markedly increased LV mass, especially in SHR. Moreover, salt excess significantly impaired RV and LV diastolic function in SHR but only LV diastolic function in WKY rats. However, salt loading affected neither RV nor LV contractile function in both strains. Interstitial and perivascular collagen deposition was increased, whereas coronary vasodilatory responses to dipyridamole diminished in both ventricles in the salt-loaded SHR but not in WKY rats. Therefore, accumulation of ventricular collagen as well as altered myocardial perfusion importantly contributed to the development of salt-related RV and LV dysfunctions in this model of naturally occurring hypertension. The unique effects of salt loading on both ventricles in SHR, but not WKY rats, strongly suggest that nonhemodynamic mechanisms in hypertensive disease participate pathophysiologically with salt-loading hypertension. These findings point to the conclusion that the concept of "salt sensitivity" in hypertension is far more complex than simply its effects on arterial pressure or the LV.     

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.     

Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization

Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-microm diameter) for 24 +/- 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dt(min)) decreased by 25 +/- 2% (P < 0.05) and LV isovolumic relaxation constant and duration increased by 19 +/- 5% and 25 +/- 6%, respectively (both P < 0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be(alpha*EDV)) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient (alpha) increased by 62 +/- 10% (P < 0.05) and the stiffness constant (k) increased by 66 +/- 13% after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 +/- 25% and 63 +/- 24% (both P < 0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.     

Determinants of LV diastolic function during atrial fibrillation: beat-to-beat analysis in acute dog experiments

Left ventricular (LV) diastolic function during atrial fibrillation (AF) remains poorly understood due to the complex interaction of factors and beat-to-beat variability. The purpose of the present study was to elucidate the physiological determinants of beat-to-beat changes in LV diastolic function during AF. The RR intervals preceding a given cardiac beat were measured from the right ventricular electrogram in 12 healthy open-chest mongrel dogs during AF. Doppler echocardiography and LV pressure and volume beat-to-beat analyses were performed. The LV filling time (FT) and early diastolic mitral inflow velocity-time integral (E(vti)) were measured using the pulsed Doppler method. The LV end-diastolic volume (EDV), peak systolic LV pressure (LVP), minimum value of the first derivative of LV pressure curve (dP/dt(min)), and the time constant of LV pressure decay (tau) were evaluated with the use of a conductance catheter for 100 consecutive cardiac cycles. Beat-to-beat analysis revealed a cascade of important causal relations. LV-FT showed a significant positive linear relationship with E(vti) (r = 0.87). Importantly, there was a significant positive linear relationship between the RR interval and LV-EDV in the same cardiac beat (r = 0.53). Consequently, there was a positive linear relationship between LV-EDV and subsequent peak systolic LVP (r = 0.82). Furthermore, there were significant positive linear and negative curvilinear relationships between peak systolic LVP and dP/dt(min) (r = 0.95) and tau (r = -0.85), respectively, in the same cardiac beat. In addition, there was a significant negative curvilinear relationship between dP/dt(min) and tau (r = -0.86). We have concluded that the determinants of LV diastolic function in individual beats during AF depend strongly on the peak systolic LVP. This suggests that the major benefit of slower ventricular rate appears related to lengthening of LV filling interval, promoting subsequent higher peak systolic LVP and greater LV relaxation.     

Validation of echocardiographic methods for assessing left ventricular dysfunction in rats with myocardial infarction

The rat infarct model is widely used in heart failure research, but few echocardiographic indexes of left ventricular (LV) function are validated in this model. Accordingly, the objective of this study was to validate a 13-segment LV wall motion score index (WMSI) and the myocardial performance index (MPI) in infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery ligation or sham operation and were evaluated with two-dimensional and Doppler flow echocardiography 8 wk later. After echocardiography, invasive indexes were obtained using a high-fidelity catheter. WMSI and MPI were correlated with the invasive and noninvasive measurements of LV function. WMSI and MPI significantly correlated directly with end-diastolic pressure (r=0.72 and 0.42 for WMSI and MPI, respectively) and the time constant of isovolumic relaxation (r=0.68 and 0.48) and inversely with peak rate of rise of LV pressure (+dP/dt; r=-0.68 and -0.50), peak rate of decline in LV pressure (r=-0.57 and -0.44), LV developed pressure (r=-0.58 and -0.42), area fractional shortening (r=-0.85 and -0.53), and cardiac index (r=-0.74 and -0.74). Stepwise linear regression analyses revealed that LV end-diastolic pressure, +dP/dt, area fractional shortening, and cardiac index were independent determinants of WMSI (r=0.994) and that cardiac index and +dP/dt were independent determinants of MPI (r=0.781). We conclude that the 13-segment WMSI and MPI are reproducible and correlate strongly with established echocardiographic and invasive indexes of systolic and diastolic function. These findings support the use of WMSI and MPI as indexes of global LV function in the rat infarction model of heart failure.     

Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure

Inhibition of phosphodiesterase type 5 (PDE5) can relax systemic and coronary vessels by causing accumulation of cGMP. Both the endothelial dysfunction with decreased nitric oxide production and increased natriuretic peptide levels in congestive heart failure (CHF) have the potential to alter cGMP production, thereby influencing the response to PDE5 inhibition. Consequently, this study examined the effects of PDE5 inhibition with sildenafil in dogs with CHF produced by rapid ventricular pacing. CHF resulted in decreases of left ventricular (LV) systolic pressure, coronary blood flow, and the maximal first time derivative of LV pressure (LV dP/dt(max)) at rest and during treadmill exercise compared with normal, whereas resting LV end-diastolic pressure increased from 10 +/- 1.4 to 23 +/- 1.4 mmHg. Sildenafil (2 and 10 mg/kg per os) caused a 5- to 6-mmHg decrease of aortic pressure (P < 0.05), with no change of heart rate, LV systolic pressure, or LV dP/dt(max). Sildenafil caused no change in coronary flow or myocardial oxygen consumption in animals with CHF at rest or during exercise. In contrast to findings in normal animals, sildenafil did not augment endothelium-dependent coronary vasodilation in response to acetylcholine in animals with CHF. Furthermore, Western blotting showed decreased PDE5 protein expression in myocardium from failing hearts. These findings demonstrate that PDE5 contributes little to regulation of coronary hemodynamics in CHF.     

Effect of graduated embolization of the coronary vessels using microspheres on the pumping function and contractility of the left ventricle in rats

Left ventricle (LV) function and systemic hemodynamic changes after coronary artery embolization by 15 microns radioactive microspheres were studied in anesthetized rats. Selective coronary embolization was produced by microsphere injection during ascending aorta occlusion in closed chest animal by using "L"-shaped wire. Maximal pressure (Pmax) developed was evaluated during ascending aorta occlusion. Coronary embolization evoked dose-dependent reduction in Pmax and dP/dtmax and then decrease in basal LV systolic pressure. dP/dt/P, with parallel increase in end diastolic LV pressure. Changes of cardiac output were bidirectional: after administration of relatively small amount of microspheres cardiac output increased. This method can be used for producing quantitative myocardial ischemia and we suggest that it may be a suitable model of the chronic heart failure.     

The saponin of red ginseng protects the cardiac myocytes against ischemic injury in vitro and in vivo

Steamed root of Panax ginseng C.A. Mayer, known as "red ginseng", differs from other ginseng preparations in terms of its saponin components and content, as some partly deglycosylated saponins are produced as artifacts during the steaming process. However, whether saponins derived from red ginseng (SRG) can have a protective effect on cardiomyocytes remains unknown. The present study aimed to explore the effect of SRG on myocardial ischemia in vitro and in vivo. MTT assays revealed that SRG pretreatment significantly increased the viability of cardiomyocytes injured by Na(2)S(2)O(4) hypoxia in vitro. This effect was almost completely abolished by glibenclamide, a blocker of the ATP-sensitive potassium channel, but the cardioprotective activity of SRG was not influenced by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. SRG also significantly reduced the Na(2)S(2)O(4)-induced increase in intracellular calcium, as shown by Fluo-3/AM probes with flow cytometry. Adult rat heart ischemia, which was induced by ligation of the left anterior descending coronary artery, was employed for the in vivo analysis. SRG pretreatment reduced infarct size and resulted in a higher left ventricle (LV) developed pressure, LV (+)dP/dt(max) and LV systolic pressure and lower LV (-)dP/dt(max) and LV end diastolic pressure after 24h of ischemia. Moreover, SRG significantly reduced the level of cardiac Troponin I (cTnI) in the serum, which suggests that cTnI, a protein component of the troponin regulatory complex involved in cardiac contractility, contributes to the SRG-mediated recovery of cardiac systolic function. In conclusion, this study is the first to provide evidence and a mechanistic analysis of the cardioprotective effects of SRG. SRG significantly attenuated myocardial ischemic injury by improving cardiac systole function, partly by reducing cTnI secretion and improving cardiac diastolic function. Also, SRG attenuated the Ca(2+) overload in cardiomyocytes and modulated the K(ATP), but not PI3K, signaling pathway; taken together, these mechanisms synergistically reduced infarct size.     

Assessing left ventricular systolic dysfunction after myocardial infarction: are ejection fraction and dP/dt(max) complementary or redundant?

Among the various cardiac contractility parameters, left ventricular (LV) ejection fraction (EF) and maximum dP/dt (dP/dt(max)) are the simplest and most used. However, these parameters are often reported together, and it is not clear if they are complementary or redundant. We sought to compare the discriminative value of EF and dP/dt(max) in assessing systolic dysfunction after myocardial infarction (MI) in swine. A total of 220 measurements were obtained. All measurements included LV volumes and EF analysis by left ventriculography, invasive ventricular pressure tracings, and echocardiography. Baseline measurements were performed in 132 pigs, and 88 measurements were obtained at different time points after MI creation. Receiver operator characteristic (ROC) curves to distinguish the presence or absence of an MI revealed a good predictive value for EF [area under the curve (AUC): 0.998] but not by dP/dt(max) (AUC: 0.69, P < 0.001 vs. EF). Dividing dP/dt(max) by LV end-diastolic pressure and heart rate (HR) significantly increased the AUC to 0.87 (P < 0.001 vs. dP/dt(max) and P < 0.001 vs. EF). In na?ve pigs, the coefficient of variation of dP/dt(max) was twice than that of EF (22.5% vs. 9.5%, respectively). Furthermore, in n = 19 pigs, dP/dt(max) increased after MI. However, echocardiographic strain analysis of 23 pigs with EF ranging only from 36% to 40% after MI revealed significant correlations between dP/dt(max) and strain parameters in the noninfarcted area (circumferential strain: r = 0.42, P = 0.05; radial strain: r = 0.71, P < 0.001). In conclusion, EF is a more accurate measure of systolic dysfunction than dP/dt(max) in a swine model of MI. Despite the variability of dP/dt(max) both in na?ve pigs and after MI, it may sensitively reflect the small changes of myocardial contractility.     

Gender differences in the cardiac response to dietary conjugated linoleic acid isomers

The present study was undertaken to assess the heart function, by the in vivo catheterization technique, of healthy male and female Sprague-Dawley rats fed different conjugated linoleic acid (CLA) isomers, (cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12)) individually and in combination (50:50 mix as triglyceride or fatty acids) from 4 to 20 weeks of age. Whereas the triglyceride form of the CLA isomer mix lowered the heart rate, the rate of contraction (+dP/dt) and rate of relaxation (-dP/dt), systolic and diastolic pressures, mean arterial pressure, and the left ventricular systolic pressure were higher in male rats as compared with all the other dietary groups. In contrast, there were no significant effects in the cardiac function of the female rats in response to the CLA isomer mix in triglyceride form. Whereas the heart rate, +dP/dt, and left ventricular systolic pressure were lower in male rats fed the t10,c12 CLA isomer alone, the heart rate of the female rats was higher, but the systolic pressure, +dP/dt, and mean arterial pressure were lower compared with the control group. Also, the left ventricular end-diastolic pressure was specifically higher in the female rats in response to free fatty acids-containing CLA mix. Furthermore, an additive effect of the free fatty acids-containing CLA mix was seen in the +dP/dt and -dP/dt of female rats compared with the control group. These results indicate that CLA isomers exert differential effects on heart function and suggest the need for a complete evaluation of the benefits, interactions, and potential side effects of each isomer.     

Effects of mechanical limitation of apical rotation on left ventricular relaxation and end-diastolic pressure

Left ventricular (LV) twist is thought to play an important role in cardiac function. However, how twist affects systolic or diastolic function is not understood in detail. We acquired apical and basal short-axis images of dogs undergoing open-chest procedures (n = 15) using a GE Vivid 7 at baseline and during the use of an apical suction device (Starfish) to limit apical rotation. We measured LV pressure and stroke volume using a micromanometer-tipped catheter and an ultrasonic flow probe, respectively. Peak radial strain, peak rotation, peak twist, peak systolic twisting rate (TR), peak untwisting rate during isovolumic relaxation period (UR(IVR)), and peak early diastolic untwisting rate after mitral valve opening (UR(E)) were determined using speckle tracking echocardiography. Immobilizing the apex with gentle suction significantly decreased apical rotation (-50 ± 27%) and slightly increased basal rotation, resulting in a significant decrease in twist. The time constant of LV relaxation (τ) was prolonged, and LV end-diastolic pressure increased. TR and UR(IVR) decreased. LV systolic pressure, peak positive and negative first derivative of LV pressure (±dP/dt), stroke volume, radial strain, and UR(E) were not changed. The correlation between τ and UR(IVR) (r = 0.63, P = 0.0006) was stronger than that between peak +dP/dt and TR (r = 0.46, P = 0.01). Diastolic function was impaired with reduced apical rotation and UR(IVR) when the apex of the heart was immobilized using an apical suction device.     

Exhaustion of the Frank-Starling mechanism in conscious dogs with heart failure induced by chronic coronary microembolization

The role of the Frank-Starling mechanism in the regulation of cardiac systolic function in the ischemic failing heart was examined in conscious dogs. Left ventricular (LV) dimension, pressure and systolic function were assessed using surgically implanted instrumentations and non-invasive echocardiogram. Heart failure was induced by daily intra-coronary injections of microspheres for 3-4 weeks via implanted coronary catheters. Chronic coronary embolization resulted in a progressive dilation of the left ventricle (12+/-3%), increase in LV end-diastolic pressure (118+/-19%), depression of LV dP/dt(max) (-19+/-4%), fractional shortening (-36+/-7%), and cardiac work (-60+/-9%), and development of heart failure, while the LV contractile response to dobutamine was depressed. A brief inferior vena caval occlusion in dogs with heart failure decreased LV preload to match the levels attained in their control state and caused a further reduction of LV dP/dt(max), fractional shortening, stroke work and cardiac work. Moreover, in response to acute volume loading, the change in the LV end-diastolic dimension-pressure (DeltaLVEDD-DeltaLVEDP) curve in the failing heart became steeper and shifted significantly to the left, while the increases in LV stroke work and cardiac work were blunted. Thus, our results suggest that the Frank-Starling mechanism is exhausted in heart failure and unable to further respond to increasing volume while it plays an important compensatory role in adaptation to LV dysfunction in heart failure.     

Gender differences on the effects of aging on cardiac and peripheral adrenergic stimulation in old conscious monkeys

We examined the effects of gender and aging on cardiac and peripheral hemodynamic responses to beta-adrenergic receptor (beta-AR) stimulation in young (male = 5.9 +/- 0.4 yr old and female = 6.5 +/- 0.7 yr old) and old (male = 19.8 +/- 0.7 yr old and female = 21.2 +/- 0.2 yr old) conscious monkeys (Macaca fascicularis), chronically instrumented for measurements of left ventricular (LV) and arterial pressures as well as cardiac output. Baseline LV pressure, the first derivative of LV pressure (LV dP/dt), cardiac index, mean arterial pressure, total peripheral resistance (TPR), and heart rate in conscious monkeys were not different among the four groups. Increases in LV dP/dt in response to 0.1 microg/kg isoproterenol (Iso) were diminished (P < 0.05) in old males (+99 +/- 11%) compared with young males (+194 +/- 18%). In addition, the inotropic responses to norepinephrine (NE) and forskolin (FSK) were significantly depressed (P < 0.05) in old males. Iso-induced reductions of TPR were less (P < 0.05) in old males (-28 +/- 2%) than in young males (-49 +/- 2%). The changes of TPR in response to NE and FSK were also significantly attenuated (P < 0.05) in old males. However, the LV dP/dt responses to BAY y 5959 (15 microg. kg-1. min-1), a Ca2+ channel promotor independent of beta-AR signaling, were not significantly different between old and young males. In contrast to results in male monkeys, LV dP/dt and TPR responses to Iso, NE, and FSK in old females were similar to those observed in young females. Thus both cardiac contractile and peripheral vascular dynamic responses to beta-AR stimulation are preserved in old female but not old male monkeys. This may explain, in part, the reduced cardiovascular risk in the older female population.     

Functional alterations after cardiac sodium-calcium exchanger overexpression in heart failure

The sodium-calcium exchanger (NCX) is discussed as one of the key proteins involved in heart failure. However, the causal role and the extent to which NCX contributes to contractile dysfunction during heart failure are poorly understood. NCX overexpression was induced by infection with an adenovirus coding for NCX, which coexpressed green fluorescence protein (GFP) (AdNCX) by ex vivo gene transfer to nonfailing and failing rabbit cardiomyocytes. Myocardial gene transfer in rabbits in vivo was achieved by adenoviral delivery via aortic cross-clamping. Peak cell shortening of cardiomyocytes was determined photo-optically. Hemodynamic parameters in vivo were determined by echocardiography (fractional shortening) and tip catheter [maximal first derivative of left ventricular (LV) pressure (dP/dt(max)); maximal negative derivative of LV pressure (-dP/dt(max))]. Peak cell shortening was depressed after NCX gene delivery in isolated nonfailing and in failing cardiomyocytes. In nonfailing rabbits in vivo, basal systolic contractility (fractional shortening and dP/dt(max)) and maximum rate of LV relaxation (-dP/dt(max)) in vivo were largely unaffected after NCX overexpression. However, during heart failure, long-term NCX overexpression over 2 wk significantly improved fractional shortening and dP/dt(max) compared with AdGFP-infected rabbits, both without inotropic stimulation and after beta-adrenergic stimulation with isoproterenol. -dP/dt(max) was also improved after NCX overexpression in the failing rabbits group. These results indicate that short-term effects of NCX overexpression impair contractility of isolated failing and nonfailing rabbit cardiomyocytes. NCX overexpression over 2 wk in vivo does not seem to affect myocardial contractility in nonfailing rabbits. Interestingly, in vivo overexpression of NCX decreased the progression of systolic and diastolic contractile dysfunction and improved beta-adrenoceptor-mediated contractile reserve in heart failure in rabbits in vivo.     

Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker

It is not known how the angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) attenuate heart failure (HF) in viable ischemic hearts. To assess HF in a rat coronary stenosis (CS) model, we administered vehicle and quinapril or candesartan (or both) orally for 12 wk. Compared with the sham group, the vehicle group showed impaired myocardial perfusion, impaired coronary endothelial nitric oxide (NO) function in vitro, exhausted myocardial mitochondrial respiration, larger left ventricular (LV) dimensions and lower ejection fraction, lower LV rate of pressure development over time (dP/dt), lower slopes of LV end-systolic pressure-dimension relations (ESPDRs), and increased myocardial fibrosis. Treatment with quinapril or candesartan ameliorated these parameters without modifying the epicardial CS severity. Moreover, their combination maintained similar myocardial perfusion, despite a trend toward lower blood pressure, and showed distinctive neurohumoral modulation, normalized mitochondrial respiration, and increased ESPDR slopes. Thus improved myocardial blood flow and coronary flow reserve by quinapril or candesartan are the key to alleviate CS-induced HF, and their combination may have a therapeutic significance partly through ameliorated mitochondrial respiration and improved LV systolic function.     

Effect of flavone in a canine model of myocardial stunning

Putative cardioprotective action of flavone (10, 20 and 30 mg/kg) was investigated in a canine model of regional ischemia (20 min) followed by 60 min of reperfusion. In animals pretreated with vehicle, myocardial stunning was evidenced by significant changes in hemodynamic parameters (depressed mean arterial pressure, LV peak (+) dP/dt, LV peak (-) dP/dt and elevated LV end-diastolic pressure) and biochemical parameters (decreased myocardial ATP and rise in plasma malondialdehyde or MDA; a marker of free radical-induced injury). A reduction in plasma MDA was noted with 20 and 30 mg/kg flavone, although attenuation of myocardial dysfunction was evident with all the three doses. The results suggest that besides a significant dose-dependent antioxidant effect, flavone may also have some cardioprotective actions per se, which needs to be further investigated.     

Coronary collaterals provide a constant scaffold effect on the left ventricle and limit ischemic left ventricular dysfunction in humans

Coronary collaterals preserve left ventricular (LV) function during coronary occlusion by reducing myocardial ischemia and may directly influence LV compliance. We aimed to re-evaluate the relationship between coronary collaterals, measured quantitatively with a pressure wire, and simultaneously recorded LV contractility from conductance catheter data during percutaneous coronary intervention (PCI) in humans. Twenty-five patients with normal LV function awaiting PCI were recruited. Pressure-derived collateral flow index (CFI(p)): CFI(p) = (P(w) - P(v))/(P(a) - P(v)) was calculated from pressure distal to coronary balloon occlusion (P(w)), central venous pressure (P(v)), and aortic pressure (P(a)). CFI(p) was compared with the changes in simultaneously recorded LV end-diastolic pressure (ΔLVEDP), end-diastolic volume, maximum rate of rise in pressure (ΔLVdP/dt(max); systolic function), and time constant of isovolumic relaxation (ΔLV τ; diastolic function), measured by a LV cavity conductance catheter. Measurements were recorded at baseline and following a 1-min coronary occlusion and were duplicated after a 30-min recovery period. There was significant LV diastolic dysfunction following coronary occlusion (ΔLVEDP: +24.5%, P < 0.0001; and ΔLV τ: +20.0%, P < 0.0001), which inversely correlated with CFI(p) (ΔLVEDP vs. CFI(p): r = -0.54, P < 0.0001; ΔLV τ vs. CFI(p): r = -0.46, P = 0.0009). Subjects with fewer collaterals had lower LVEDP at baseline (r = 0.33, P = 0.02). CFI(p) was inversely related to the coronary stenosis pressure gradient at rest (r = -0.31, P = 0.03). Collaterals exert a direct hemodynamic effect on the ventricle and attenuate ischemic LV diastolic dysfunction during coronary occlusion. Vessels with lesions of greater hemodynamic significance have better collateral supply.     

Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (tau), and the first derivatives of LV pressure rise and fall (dP/dt(max) and dP/dt(min), respectively). During echocardiography, HR was lower in XK than AV mice (250 +/- 14 beats/min in XK vs. 453 +/- 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 +/- 0.08 mm in XK vs. 3.8 +/- 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 +/- 1.2% in XK vs. 40 +/- 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 +/- 24 beats/min) and XK (342 +/- 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 +/- 5 vs. 6.2 +/- 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/dt(max): 4,402 +/- 798 vs. 8,250 +/- 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (tau: 23 +/- 2 vs. 14 +/- 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.     

Acidaemia reduces cardiac output and left ventricular contractility in conscious lambs

We studied the effects of HCI-induced metabolic acidaemia on cardiac output, contractile function, myocardial blood flow, and myocardial oxygen consumption in nine unanaesthetized newborn lambs. Through a left thoracotomy, catheters were placed in the aorta, left atrium and coronary sinus. A pressure transducer was placed in the left ventricle. Three to four days after surgery, we measured cardiac output, dP/dt, left ventricular end diastolic and aortic mean blood pressures, heart rate, aortic and coronary sinus blood oxygen contents, and left ventricular myocardial blood flow during a control period, during metabolic acidaemia, and after the aortic pH was restored to normal. We calculated systemic vascular resistance, myocardial oxygen consumption and left ventricular work. Acidaemia was associated with reduction in cardiac output, maximal dP/dt, and aortic mean blood pressure. Left ventricular end diastolic pressure and systemic vascular resistance increased, and heart rate did not change significantly. The reduction in myocardial blood flow and oxygen consumption was accompanied by fall in cardiac work. Cardiac output returned to control levels after the pH had been normalized but maximal dP/dt was incompletely restored. Myocardial blood flow and oxygen consumption increased beyond control levels. This study demonstrates that HCI-induced metabolic acidaemia in conscious newborn lambs is associated with a reduction in cardiac output which could have been mediated by the reduction in contractile function and/or the increase in systemic vascular resistance. The decreases in myocardial blood flow and oxygen consumption appear to reflect diminished cardiac work. The restoration of a normal cardiac output after normalization of the pH appears to have resulted from the increases in heart rate and left ventricular filling pressures in conjunction with an incomplete restoration of contractile function.