Coronary Blood Volume Research Articles

Assessment of coronary blood volume to left ventricular mass ratio: a comparative study among endurance athletes, hypertrophic cardiomyopathy patients and healthy controls

Abstract Background Pathologic left ventricular hypertrophy (LVH) may lead to a mismatch between left ventricular mass (LVM) and blood supply, potentially reducing coronary flowreserve. Typically, assessing this involves complex or invasive methods. Objective We assessed epicardial coronary blood volume (CBV) to LVM ratio (V/M) using coronary computed tomography (CT) angiography in athletes, HCM patients, and healthy controls. Methods A total of 169 individuals without obstructive coronary artery disease were included, comprising 39 endurance athletes, 55 HCM patients, and 79 healthy controls. Automated detection of the epicardial coronary tree facilitated the calculation of CBV, enabling the assessment of LVM and subsequent comparison of the V/M ratio. Results HCM patients had the highest LVM (242g ±115), followed by athletes (145g ±33.35) and healthy controls (106g ±22.53), the corresponding CBV were: (7ml ±2.09 ml), (6.35±1.68 ml), and (4.43±0.93 ml); respectively. V/M ratios were similar in athletes (0.04 ±0.01 ml/m2), and controls (0.04 ±0.01, P= 0.298 ml/m2), but were significantly lower in HCM patients (0.03 ±0.01, P<0.001 ml/m2). CBV and LVM significantly corelated among the three group (Figure). Conclusions Contrast CT findings reveal that unlike HCM patients with pathological LVH, athletes exhibit sufficient increase in CBV relative to LVM thereby maintaining normal V/M ratio.

Coronary-aortic interaction during ventricular isovolumic contraction.

In earlier work, we suggested that the start of the isovolumic contraction period could be detected in arterial pressure waveforms as the start of a temporary pre-systolic pressure perturbation (AICstart, start of the Arterially detected Isovolumic Contraction), and proposed the retrograde coronary blood volume flow in combination with a backwards traveling pressure wave as its most likely origin. In this study, we tested this hypothesis by means of a coronary artery occlusion protocol. In six Yorkshire × Landrace swine, we simultaneously occluded the left anterior descending (LAD) and left circumflex (LCx) artery for 5 s followed by a 20-s reperfusion period and repeated this sequence at least two more times. A similar procedure was used to occlude only the right coronary artery (RCA) and finally all three main coronary arteries simultaneously. None of the occlusion protocols caused a decrease in the arterial pressure perturbation in the aorta during occlusion (P > 0.20) nor an increase during reactive hyperemia (P > 0.22), despite a higher deceleration of coronary blood volume flow (P = 0.03) or increased coronary conductance (P = 0.04) during hyperemia. These results show that the pre-systolic aortic pressure perturbation does not originate from the coronary arteries.

Agonist-induced impairment of glycocalyx exclusion properties: contribution to coronary effects of adenosine

The endothelial glycocalyx is the negatively charged, gel-like mesh residing at the luminal side of the vascular endothelium and forming the interface between the flowing blood and the vessel wall. The vast majority of glycocalyx volume resides in the microcirculation, particularly in the capillaries. Intravital microscopic observations of capillaries in striated muscle preparations illustrate that under resting conditions, the glycocalyx is not accessible for flowing red blood cells and greatly hinders plasma flow in the axial direction, causing a significant reduction in functionally perfused capillary volume. Glycocalyx exclusion properties have been shown to be reduced by adenosine and other vasoactive substances. A diminished exclusion of circulating blood by the glycocalyx may facilitate nutrient exchange since it is associated with an increase in functionally perfused blood volume and surface area in the capillaries. Our recent studies have focused on the effect of adenosine on glycocalyx exclusion in the coronary circulation and demonstrate an important role for this mechanism in the increase in circulating coronary blood volume during administration of this vasodilator. The current review elaborates on the glycocalyx as a blood-excluding intravascular layer and how it can be modulated by various agonists. Further, the potential role of adenosine-induced modulation of glycocalyx exclusion properties in coupling increases in blood flow and circulating blood volume in the coronary circulation is discussed. Finally, we consider how degradation of the glycocalyx may impact on coronary blood volume regulation, thereby providing new opportunities to diagnose glycocalyx damage in the clinical setting.

Acute attenuation of glycocalyx barrier properties increases coronary blood volume independently of coronary flow reserve

Vascular endothelium is covered with an extensive mesh of glycocalyx constituents, which acts like an effective barrier up to several micrometers thick that shields the luminal surface of the vasculature from direct exposure to flowing blood. Many studies report that various enzymatic and pharmaceutical challenges are able to increase glycocalyx porosity, resulting in farther permeation of plasma macromolecules and greater access of red blood cells into glycocalyx domain. Attenuation of glycocalyx barrier properties therefore potentially increases the amount of blood that effectively occupies available microvascular volume. We tested in the present study whether attenuation of coronary glycocalyx barrier properties actually increases coronary blood volume and whether such changes would be noticeable during measurements of coronary flow reserve using adenosine. In anesthetized goats (n = 6) with cannulated left main coronary artery that were perfused under controlled pressure, coronary blood volume was measured via the indicator-dilution technique using high-molecular-weight (2,000 kDa) dextrans as plasma tracer and labeled red blood cells as red blood cell tracer. Coronary blood volume was determined at baseline and during intracoronary infusion of adenosine causing maximal vasodilation (0.2-0.6 mg.kg(-1).h(-1)) before and after intracoronary hyaluronidase treatment (170,000 units) of the glycocalyx. With an intact glycocalyx, coronary blood volume was 18.9 +/- 1.1 ml/100 g heart tissue at baseline, which increased to 26.3 +/- 2.7 ml/100 g after hyaluronidase treatment of the coronary glycocalyx. Maximal vasodilation by administration of adenosine further increased coronary blood volume to 33.9 +/- 6.8 ml/100 g, a value not different from the maximal coronary blood volume of 33.2 +/- 5.3 ml/100 g obtained by administration of adenosine in the absence of hyaluronidase treatment. Adenosine-induced increases in coronary conductance were not affected by hyaluronidase treatment. We conclude that acute attenuation of glycocalyx barrier properties increases coronary blood volume by approximately 40%, which is of similar magnitude as additional changes in coronary blood volume during subsequent maximal vasodilation with adenosine. Furthermore, maximal coronary blood volume following administration of adenosine was similar with and without prior hyaluronidase degradation of the glycocalyx, suggesting that adenosine and hyaluronidase potentially increase glycocalyx porosity to a similar extent. Hyaluronidase-mediated changes in coronary blood volume did not affect baseline and adenosine-induced increases in coronary conductance, demonstrating that measurements of coronary flow reserve are insufficient to detect impairment of coronary blood volume recruitment in conditions of damaged glycocalyx.

Enzymatic endothelial glycocalyx degradation increases arterial‐venous oxygen exchange in the heart

A relatively thick endothelial glycocalyx forms the true interface between blood and the vascular wall, and thereby limits microvascular volume available for perfusion and exchange. In previous studies we have shown that hyaluronidase treatment increases coronary microvascular blood volume. We now hypothesize that acute functional or enzymatic reduction of glycocalyx volume increases microvascular exchange capacity. In the current study the effect of enzymatic glycocalyx degradation on myocardial oxygen exchange was assessed in goats (n=5). Blood samples were collected simultaneously from great cardiac vein and aorta, and blood flow was measured in the LAD. The measurement was done in control and after hyaluronidase treatment. Hyaluronidase treatment increased arterial‐venous oxygen difference significantly from 7.0 ± 0.2 to 8.3 ± 0.3 ml/100ml, which was associated with a reduced coronary flow from 66.5 ± 9.1 to 46.4 ± 2.9 ml/min/100gr tissue (P<0.05). Rate‐pressure product and oxygen consumption remained unaltered. In conclusion, acute enzymatic degradation of glycocalyx volume increases arterial‐venous oxygen exchange, consistent with our previous finding on the effect of hyaluronidase treatment on microvascular blood volume. Supported by NHF grants 2005T037 and 2003B181.

Remote periconditioning reduces myocardial no-reflow by the activation of K ATP channel via inhibition of Rho-kinase

Remote periconditioning is induced by brief cycles of ischemia and reperfusion of a remote organ applied during sustained myocardial ischemia. It remains unknown whether the remote periconditioning reduces myocardial no-reflow. The adenosine triphosphate-sensitive potassium (K ATP) channel opening and inhibition of Rho-kinase may be the important mechanism of protection against myocardial no-reflow. Therefore, this study was sought to assess the effect of remote periconditioning on myocardial no-reflow and explore the possible mechanism. Methods Coronary ligation area and area of no-reflow were determined with pathological means in 58 mini-swines randomized into 7 study groups: 9 controls, 8 in remote periconditioning, 8 in hydroxyfasudil (a specific inhibitor of Rho-kinase)-treated, 9 in glibenclamide (K ATP channel blocker)-treated, 8 in remote periconditioning and glibenclamide, 8 in hydroxyfasudil and glibenclamide and 8 sham-operated. The ischemia and reperfusion model was created with 3 h of left anterior descending artery occlusion followed by 2 h of reperfusion. Results Compared with the control group, remote periconditioning decreased Rho-kinase activity ( P < 0.01), increased coronary blood volume ( P < 0.05), decreased area of no-reflow (from 82.3 ± 3.9% to 45.5 ± 5.7% of ligation area, P < 0.01) and reduced necrosis size (from 98.5 ± 1.3% to 74.7 ± 6.3% of ligation area, P < 0.05). Hydroxyfasudil had the same effect on the above parameters as remote periconditioning. Glibenclamide abrogated the effect of remote periconditioning or hydroxyfasudil on area of no-reflow and necrosis area, but not Rho-kinase activity. Conclusion Remote periconditioning can reduce myocardial no-reflow after ischemia and reperfusion. This beneficial effect could be due to its activation of K ATP channel via inhibition of Rho-kinase.

Post‐infarction treatment with simvastatin reduces myocardial no‐reflow by opening of the KATP channel

Simvastatin can prevent cardiac remodelling after myocardial infarction, though the exact mechanisms are uncertain. Myocardial no-reflow is associated with progressive cardiac remodelling. However, it remains unknown whether post-infarction treatment with simvastatin can also reduce myocardial no-reflow for which suppression of adenosine triphosphate-sensitive K+ (K(ATP)) channel opening is an important mechanism. Area at risk and the area of no-reflow were determined by myocardial contrast echocardiography (MCE) and by pathology in 45 mini-swine randomised into 5 groups: 10 control, 9 simvastatin, 9 glibenclamide, 9 simvastatin plus glibenclamide and 8 sham-operated. A myocardial infarction and reperfusion model was created by 3-h occlusion of the coronary artery followed by 4 weeks of reperfusion. Compared with the control group, simvastatin significantly increased coronary blood volume (P<0.01) and decreased the area of no-reflow measured by MCE (78.5+/-4.5% to 43.7+/-4.3%) and pathological evaluation (82.3+/-1.9% to 45.2+/-3.8%) of area at risk (P<0.01). Simvastatin also increased the levels of K(ATP) channel proteins (SUR2 and Kir6.2) (P<0.05), but had no effect on necrosis area. The combination of simvastatin and glibenclamide had no significant effect on the above parameters. Post-infarction treatment with simvastatin can reduce myocardial no-reflow. This beneficial effect is due to activation of the K(ATP) channel.

Large-Scale 3-D Geometric Reconstruction of the Porcine Coronary Arterial Vasculature Based on Detailed Anatomical Data

The temporal and spatial distribution of coronary blood flow, pressure, and volume are determined by the branching pattern and three-dimensional (3-D) geometry of the coronary vasculature, and by the mechanics of heart wall and vascular tone. Consequently, a realistic simulation of coronary blood flow requires, as a first step, an accurate representation of the coronary vasculature in a 3-D model of the beating heart. In the present study, a large-scale stochastic reconstruction of the asymmetric coronary arterial trees (right coronary artery, RCA; left anterior descending, LAD; and left circumflex, LCx) of the porcine heart has been carried out to set the stage for future hemodynamic analysis. The model spans the entire coronary arterial tree down to the capillary vessels. The 3-D tree structure was reconstructed initially in rectangular slab geometry by means of global geometrical optimization using parallel simulated annealing (SA) algorithm. The SA optimization was subject to constraints prescribed by previously measured morphometric features of the coronary arterial trees. Subsequently, the reconstructed trees were mapped onto a prolate spheroid geometry of the heart. The transformed geometry was determined through least squares minimization of the related changes in both segments lengths and their angular characteristics. Vessel diameters were assigned based on a novel representation of diameter asymmetry along bifurcations. The reconstructed RCA, LAD and LCx arterial trees show qualitative resemblance to native coronary networks, and their morphological statistics are consistent with the measured data. The present model constitutes the first most extensive reconstruction of the entire coronary arterial system which will serve as a geometric foundation for future studies of flow in an anatomically accurate 3-D coronary vascular model.

Beneficial effects of Tong-xin-luo (herb) on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment of mini-swine model

To evaluate the beneficial effects of Tong-xin-luo on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion. Forty mini-swine were randomized into 5 equal groups: control group, low-dose group (pretreated with Tong-xin-luo 0.05 g.kg(-1).d(-1) for 3 days), medium-dose group (pretreated with Tong-xin-luo 0.2 g .kg(-1).d(-1) for 3 days), high-dose group (pretreated with Tong-xin-luo 0.5 g.kg(-1).d(-1) for 3 days), and sham-operation group. The swine in the former four groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Left ventricle systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), rate of maximum pressure change in left ventricle (+/- dp/dt(max)), cardiac output (CO), and heart rate (HR) were measured 5 min before AMI in all groups and 180 min after AMI and 60 min after reperfusion in the groups 1-4. Coronary blood volume (CBV) was recorded 5 min before AMI in all groups and immediately and 60 min after reperfusion in the group 1-4. Myocardial contrast echography (MCE) was used before AMI, 3 h after AMI, and 60 min after reperfusion in the group 1-4 so as to calculate the left ventricle wall area (LVWA), ligation area (LS), and %LA. Sixty minutes after reperfusion thioflavin-S was injected into the left ventricle to dye the reperfusion area, then the descending anterior branch was re-ligated at the original site and Evan's blue was injected into the left ventricle to dye the area outside the reperfusion area blue. The heart was taken out immediately to undergo pathological examination and calculation of LVWA, LS, area of no-reflow (SNR), LA, ANR. necrosis area (NS), and NA. (1) In the control group, systolic and diastolic blood pressures (SBP and DBP), LVSP, +/- dp/dt(max), and CO significantly decreased (P < 0.05 or P < 0.01), while LVEDP significantly increased (P < 0.01) 3 hour after AMI, and then LVSP was significantly recovered while +/- dp/dt(max) further significantly decreased (both P < 0.05) 60 minutes after reperfusion. In the 3 Tongxinluo groups, the changes of LVSP, +/- dp/dt(max), CO and LVEDP were the same as those in the control group 3 hours after AMI, and 60 minutes after reperfusion, +/- dp/dt(max), CO and LVEDP were recovered significantly in the high-dose group to degrees better than those in the control group (all P < 0.05). (2) In the control group, the LS values measured by MCE in vivo and by pathological evaluation were similar (P > 0.05), and the SNR was 78.5% by MCE in vivo and was 82.3% by pathological evaluation with the final NS reaching 98.5% of LS. There was no significant difference in LS by both MCE and pathological evaluation between the Tongxinluo groups and control group, though the values of SNR by both methods in the medium and high-dose groups were 41.1% and 42.4% and 24.1% and 25.0% respectively, all significantly lower than those in the control group and low-dose group (P < 0.05 or P < 0.01) with the values in the high-dose group being significantly lower than those in the median-dose group (P < 0.05 and P < 0.01). The final NS of pathological evaluation was also significantly decreased to 90.2%and 81.2% of LS (P < 0.05). In the control group, CBV was significantly decreased to 45.8% and 50.6% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.01). In the high-dose group, CBV was also significantly decreased to 76% and 73.5% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.05), however, both significantly higher than those in the control group (both P < 0.01). Tongxinluo is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion.

Beneficial effects of diltiazem on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion

To evaluate the beneficial effects of diltiazem on myocardial no-reflow. Twenty-four mini-swine were randomized into 3 equal groups: diltiazem-treated group subjected to 3 hours of coronary occlusion to cause acute myocardial infarction (AMI), followed by 60 minutes of reperfusion and injected with diltiazem into the coronary artery 1 minute before reperfusion, control group undergoing coronary occlusion followed by 60 minutes of reperfusion and injected with normal saline, and sham operation group. 5 minutes before AMI in all groups and 180 minutes after AMI and 60 minutes after re-perfusion in the diltiazem and control groups, hemodynamic data, such as heart rate (HR), left ventricular systolic pressure (LVSP). Left ventricular end diastolic pressure (LVEDP), +/- dp/dt(max), cardiac output (CO), and coronary blood volume (CBV) were measured. Myocardial contrast echography (MCE) was used to measure the left ventricle wall area (LVWA) and ligation area (LA) so as to calculate LA and to measure the area of no-reflow (ANR) so as to calculate ANR. 60 minutes after reperfusion thioflavin-S was injected into left ventricle so as to color the reperfused area and then the descending anterior branch was re-ligated and Evan's blue was injected into the left ventricle to color the area outside the ligation area. The heart was taken out to undergo histological examination. (1) In comparison with the values before AMI the LVSP, +/- dp/dt(max), and CO of the control group significantly declined (P < 0.05, 0.01), while the LVEDP significantly increased (P < 0.01) by the end of 3 hours after LAD occlusion; and the LVSP significantly increased and the +/- dp/dt(max) further significantly declined (both P < 0.05) 60 minutes after reperfusion. In the diltiazem group, the changes of LVSP, +/- dp/dt(max), CO, and LVEDP were the same as those in the control group after 3 hours of AMI, while the +/- dp/dt(max), CO, and LVEDP recovered significantly, more significantly than those in the control group, 60 minutes after reperfusion (all P < 0.05). (2) In the control group, the sizes of coronary ligation area (LA) measured by both MCE in vivo and histopathological evaluation were similar (P > 0.05), and the values of area of no-reflow (ANR) measured by MCE in vivo and histopathological evaluation were 78.5% and 82.3% respectively with the final necrosis area (NA) reaching 99% of the LA. There was no significant difference in LA measured by both MCE and histopathological evaluation between the control and diltiazem groups, while the values of ANR measured by both methods was significantly decreased to 19.9% and 20.6% that before AMI respectively in the diltiazem group (both P < 0.01). There was no significant difference in NA between the control and diltiazem groups (P > 0.05). The CBV of the control group was significantly declined to 45.8% and 50.6% of the baseline value respectively immediately and 60 minutes after reperfusion (both P < 0.01), while the CBV of the diltiazem group became 80.4% and 79.3% of the baseline value respectively immediately and 60 minutes after reperfusion (both P < 0.05), both significantly higher than those of the control group (both P < 0.01). Diltiazem is effective both in preventing myocardial no-reflow and improving left ventricular function, but not in reducing MI size during AMI and reperfusion.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Decrease in coronary blood flow reserve during hyperlipidemia is secondary to an increase in blood viscosity.

During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion. Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (r=0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (r=0.84), while hyperemic myocardial blood flow (MBF) decreased (r=-0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (r=-0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle. Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function.

Effects of dobutamine on left ventricular restoring forces.

Restoring forces, which are generated when the left ventricle contracts below its equilibrium volume (Veq), are responsible for diastolic suction. Their magnitude is inversely related to end-systolic volume (ESV). In previous studies in which the mitral valve was replaced with a prosthesis, increased contractility was shown to augment restoring forces independently of ESV. In the present study, we quantified restoring forces in the presence of an intact mitral valve in open-chest dogs (n = 6) as the fully relaxed pressure (FRP) after completion of left ventricular pressure (LVP) fall during nonfilling diastoles produced by a servomotor system that clamped left atrial pressure below LVP. A negative FRP indicated a restoring force was present. We related FRP to ESV during control, intravenous, and left anterior descending coronary artery (intracoronary) administration of dobutamine. With intravenous dobutamine, we observed an approximately parallel downward and rightward shift of the FRP-ESV relation, indicating increased restoring forces at any ESV less than Veq. The downward shift averaged -2.6 +/- 1.6 (SD) mmHg at the control Veq. A similar shift occurred with intracoronary dobutamine. In additional experiments (n = 2), we found that over a common range of ESV dobutamine slightly increased wall thickness (<10%) during nonfilling diastoles, consistent with an increase in coronary blood volume. We conclude that dobutamine increases restoring forces independently of changes in ESV in conjunction with an increase in Veq. This effect may partly be related to increased coronary blood volume.

Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion.

Ultrasound can cause microbubble destruction. If microbubbles are administered as a continuous infusion, then their destruction within the myocardium and measurement of their myocardial reappearance rate at steady state will provide a measure of mean myocardial microbubble velocity. Conversely, measurement of their myocardial concentration at steady state will provide an assessment of microvascular cross-sectional area. Myocardial blood flow (MBF) can then be calculated from the product of the two. Ex vivo and in vitro experiments were performed in which either flow was held constant and pulsing interval (interval between microbubble destruction and replenishment) was altered, or vice versa. In vivo experiments were performed in 21 dogs. In group 1 dogs (n=7), MBF was mechanically altered in a model in which coronary blood volume was constant. In group 2 dogs (n=5), MBF was altered by direct coronary infusions of vasodilators. In group 3 dogs (n=9), non-flow-limiting coronary stenoses were created, and MBF was measured before and after the venous administration of a coronary vasodilator. In all experiments, microbubbles were delivered as a constant infusion, and myocardial contrast echocardiography was performed using different pulsing intervals. The myocardial video intensity versus pulsing interval plots were fitted to an exponential function: y=A(1-e[-betat]), where A is the plateau video intensity reflecting the microvascular cross-sectional area, and beta reflects the rate of rise of video intensity and, hence, microbubble velocity. Excellent correlations were found between flow and beta, as well as flow and the product of A and beta. MBF can be quantified with myocardial contrast echocardiography during a venous infusion of microbubbles. This novel approach has potential for measuring tissue perfusion in any organ accessible to ultrasound.

Quantitative aspects in myocardial contrast echocardiography.

Myocardial tissue perfusion is not currently quantified in the clinical setting. Thus the aim of this paper is to review the quantitative information on myocardial perfusion provided by contrast echocardiography. In a circulatory model-without the capillary network interposed between injection and sampling point of contrast-the transit time of microbubbles (source of the echo contrast effect) is inversely related to absolute flow, thus providing accurate quantitation. A similar situation is represented by blood flow inside a vessel or a cardiac cavity, where, if the prerequisites for quantitation are respected, it is possible to measure blood flow by contrast echocardiography. In the coronary circulation, the transit time of contrast microbubbles varies according to their interaction with coronary microcirculation, and to the characteristics of contrast agents as flow tracers. Echo contrast agents with small microbubbles have been injected into the coronary branches of experimental animals, under both coronary autoregulation and maximal coronary dilation, providing good estimates of coronary blood flow. The accuracy of these measurements might improve when new contrast agents, with characteristics closer to those of a flow tracer, are available. If a tracer is injected before a bifurcation, and provided it mixes adequately, the amount of tracer distributed to each branch is proportional to the corresponding blood flow. A similar situation is encountered when an echo contrast agent is injected into the aortic root or into the left main coronary artery. Here, the ratio between myocardial signal intensity in the different perfusion territories reflects the corresponding ratio of blood flows. The validity of this approach has been previously demonstrated in experimental animals and validated in patients with coronary stenoses. The injection of contrast agents into the coronary circulation at baseline and under coronary hyperaemia has the potential for measuring coronary blood flow reserve. However, what is still unclear is whether contrast echo changes reflect changes in coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary recruitment) or both, and also whether they influence the different types of contrast agent. Finally, myocardial contrast echocardiography can provide information on the spatial distribution of myocardial perfusion, i.e. the presence, site and extent of perfused myocardium. Thus, in models where myocardial perfusion may be either present or absent, contrast echo can provide an accurate estimate of perfusion abnormalities.

Myocardial contrast echo effect: The dilemma of coronary blood flow and volume

Despite the useful information provided by myocardial contrast echocardiography, the meaning of myocardial contrast intensity remains elusive. This review is meant to define the contribution of physical and biologic factors in producing myocardial contrast and to elucidate the relative roles of coronary blood flow and intramyocardial blood volume in determining contrast effect. The main physical factors influencing the contrast echo effect include the properties of microbubbles as scattering elements (mainly their radius, compressibility, stability and concentration), electronic signal processing, instrument setting and contrast-induced signal attenuation. The effect of these factors can be limited by an appropriate experimental or clinical setup. Biologic factors are less easily controllable, and changes in coronary blood flow and alterations in myocardial blood volume appear to be the main determinants of myocardial contrast intensity. Moreover, these factors influence contrast intensity in opposite directions. Both the area under the time-intensity curve and the mean transit time of myocardial contrast are inversely related to coronary blood flow but directly related to myocardial vascularity and blood volume. Therefore, an increase in coronary flow not accompanied by an increase in myocardial vascularity and volume is accompanied by a decrease in the area under the curve and mean transit time of contrast. Conversely, an increase in coronary flow mediated by augmented myocardial vascularity and volume will produce an increase in the area under the curve and mean transit time. A better understanding of the physical and biologic determinants of contrast echo intensity will be fundamental in the clinical application of new agents and technologies.

Impact of acute pulmonary rejection on cardiac function.

Experiments were designed to define cardiac function in dogs with single lung allografts during acute rejection of the allografted lung. Left lungs were either autotransplanted (n = 4) or allotransplanted (n = 8) in adult male mongrel dogs. All allotransplanted animals were maintained on triple-drug immunosuppression (cyclosporine, azathioprine, and steroids) for 5 days after the operation. In 4 allotransplanted animals, treatment was discontinued, allowing the animals to reject (usually after a further 3 days; rejecting group); 4 other allotransplanted animals were maintained on immunosuppression for an additional 3 days (immunosuppressed group). Another group of dogs were not operated on but were maintained on the same immunosuppression as the rejecting group (controls). All experimental animals underwent fast computed tomographic scanning with measurement of left ventricular pressure and calculation of ventricular chamber volumes, cross-sectional areas of coronary arteries, myocardial perfusion, and intramyocardial blood volume. Neither cardiac output, left ventricular mass, left ventricular pressure, nor myocardial oxygen consumption was altered during acute rejection of lung allografts. However, left ventricular contractility (systolic elastance, Emax) and ejection fraction were depressed to approximately one half (P < .05) in acutely rejecting animals compared with other groups. The cross-sectional area of the coronary arteries was less in autotransplanted and allotransplanted treated animals than in animals that were not operated on. Cross-sectional area of the coronary arteries was decreased by an additional 30% in the rejecting group (P < .05). The results of this study indicate that acute rejection of a single lung allograft decreases cardiac performance and reduces diameter of coronary arteries in the recipient. Alterations of circulating humoral factors and activated leukocytes may contribute to these changes.

Assessment of regional myocardial perfusion with myocardial contrast echocardiography in a canine model of varying degrees of coronary stenosis

Previous studies showed that myocardial contrast echocardiography can be used to detect relative regional underperfusion in a canine model of critical coronary stenoses. The aim of this study was to determine if myocardial contrast echocardiography performed with a sterile sonicated human serum albumin preparation (Albunex, Molecular Biosystems, San Diego, Calif.) could detect the presence of coronary stenoses of variable degrees of severity. The results were compared with myocardial blood flow as assessed by radiolabeled microspheres in 16 open-chest dogs during baseline, following the creation of a coronary stenosis of variable severity and at the peak of dipyridamole-induced hyperemia. When flow ratios (that is, flow in the control area/ischemic area) were examined, a good correlation was observed between the area under the time-intensity curve and radioactive microsphere blood flow ( r = 0.94, p < 0.0001), which allowed distinction of mild from severe stenosis. However, a consistent underestimation of the dipyridamole-induced hyperemia by myocardial contrast echo was seen in the control zone. This could be partially explained by a simultaneous increase in coronary blood flow and blood volume with dipyridamole and by attentuation of the ultrasound signal because of the high concentration of microbubbles at high flows. Myocardial contrast echocardiography can quantitate the amount of jeopardized myocardium during various degrees of coronary stenoses.

130 A new approach to the evaluation of coronary blood flow velocity and volume by the Doppler technique in hypertensive patients

Magrini, Fabio; Reggiani, Paolo; Ciulla, Michelle; Bonagura, F.; Vandoni, P.; Saino, A.; Pomidossi, Guido; Rimini, A.; Perondi, R. Author Information

Continuous measurement of canine coronary blood volume change with alterations of heart rate

The aim was to examine the effects of heart rate on total coronary blood volume with pressure-type plethysmography in isolated and vasodilated canine hearts. Nine hearts were excised from anaesthetised mongrel dogs (13.1-15.2 kg) and perfused with arterial blood of other dogs (17.0-29.0 kg). The venous blood returning to the right atrium and both ventricles was drained under constant negative pressure (-10 mm Hg). A thin latex balloon filled with water was inserted into the left ventricle to keep the intraventricular volume constant. The pressure difference between the cylinder into which the heart was placed and a compensation chamber was measured as a change in coronary blood volume while heart rate was altered from 120 beats.min-1 (control heart rate) to a target level (60, 90, 150, or 180 beats.min-1). The mean coronary blood volume change compared with that at control heart rate was 1.65(SEM 0.32) ml x 100 g-1 at 60 beats.min-1 (p < 0.005) and -0.74(0.20) ml x 100 g-1 at 180 beats.min-1 (p < 0.005) under the perfusion pressure of 70 mm Hg. The mean volume decreased with the increase in heart rate. Diastolic-systolic variations in coronary blood volume also decreased with an increase in heart rate, from 0.61(0.06) ml x 100 g-1 (60 beats.min-1) (p < 0.005) to 0.12 ml.100 g-1 (180 beats.min-1). Both mean change and variation were almost linear functions of R-R interval (r = 0.88 and r = 0.83). Lowering the perfusion pressure from 70 to 40 mm Hg diminished the changes in both mean and variation of the coronary blood volume. Tachycardia reduces the mean coronary blood volume and the diastolic-systolic variations in isolated vasodilated canine hearts.