Total Coronary Blood Flow Research Articles

Personalized coronary blood flow model based on CT perfusion to non-invasively calculate fractional flow reserve

Coronary outlet resistance, influenced by quantification and distribution of total hyperemic coronary blood flow, is critical for accurately estimating the computation of fractional flow reserve from computed tomography angiography (FFRCT). However, accurate estimation of FFRCT is still a challenging task due to the impractical of non-invasively measuring coronary outlet resistance in the clinic. While traditional methods have been used to estimate outlet resistance through population-averaged physiological assumption models, individual differences between patients limit the reliability of the models. In this work, we propose a personalized coronary flow model based on dynamic stress computed tomographic perfusion (CTP), called CTPV, to achieve a noninvasive estimation of the outlet resistance and FFRCT. The CTPV model employs myocardial blood flow (MBF) obtained from CTP to quantify the total hyperemic coronary blood flow directly. Then, myocardial perfusion territories corresponding to coronary artery branches are proposed to distribute the outlet coronary blood flow. For this purpose, we use the Voronoi algorithm to segment the myocardial perfusion territory. Finally, the outlet resistance and FFRCT are estimated based on the outlet coronary blood flow. Experiment studies on a clinical dataset consisting of 138 vessels from 86 subjects show the superiority of our CTPV model against the CTPD and LVMD models, including the method of quantifying total hyperemic coronary blood flow based on left ventricular myocardial mass (LVM) and distributing the outlet coronary blood flow based on outlet diameter. The CTPV model estimates a higher AUC for FFRCT (AUC = 0.96) than the CTPD model (AUC = 0.93) and the LVMD model (AUC = 0.92). The accuracies of CTPV, CTPD, and LVMD models are 90.6%, 87.7%, and 84.1%, respectively. Additionally, we use different outlet truncation locations to evaluate the repeatability of the CTPV and CTPD models for estimating FFRCT on a random dataset of 10 vessels. The result shows that the repeatability of the CTPV model is better than the CTPD model. These compelling results evince that the proposed CTPV model can accurately estimate the coronary outlet resistance and improve the diagnostic performance and repeatability of FFRCT.

Branch flow distribution approach and its application in the calculation of fractional flow reserve in stenotic coronary artery.

To calculate fractional flow reserve (FFR) based on computed tomography angiography (i.e., FFRCT) by considering the branch flow distribution in the coronary arteries. FFR is the gold standard to diagnose myocardial ischemia caused by coronary stenosis. An accurate and noninvasive method for obtaining total coronary blood flow is needed for the calculation of FFRCT. A mathematical model for estimating the coronary blood flow rate and two approaches for setting the patient-specific flow boundary condition were proposed. Coronary branch flow distribution methods based on a volume-flow approach and a diameter-flow approach were employed for the numerical simulation of FFRCT. The values of simulated FFRCT for 16 patients were compared with their clinically measured FFR. The ratio of total coronary blood flow to cardiac output and the myocardial blood flow under the condition of hyperemia were 16.97% and 4.07 mL/min/g, respectively. The errors of FFRCT compared with clinical data under the volume-flow approach and diameter-flow approach were 10.47% and 11.76%, respectively, the diagnostic accuracies of FFRCT were 65% and 85%, and the consistencies were 95% and 90%. The mathematical model for estimating the coronary blood flow rate and the coronary branch flow distribution method can be applied to calculate the value of clinical noninvasive FFRCT.

Successful percutaneous coronary intervention significantly improves coronary sinus blood flow as assessed by transthoracic echocardiography.

Transthoracic echocardiography (TTE) has been used to assess coronary sinus blood flow (CSBF), which reflects total coronary arterial blood flow. Successful angioplasty is expected to improve coronary arterial blood flow. Changes in CSBF after percutaneous coronary intervention (PCI), as assessed by TTE, have not been systematically evaluated. TTE can be utilized to reflect increased CSBF after a successful, clinically indicated PCI. The study cohort included 31 patients (18 females, 62±11years old) referred for diagnostic cardiac catheterization for suspected coronary artery disease and possible PCI, when clinically indicated. All performed PCIs were successful, with good angiographic outcome. CSBF per cardiac cycle (mL/beat) was measured using transthoracic two-dimensional and Doppler flow imaging as the product of coronary sinus (CS) area and CS flow time-velocity integral. CSBF per minute (mL/min) was calculated as the product of heart rate and CSBF per cardiac cycle. In each patient, CSBF was assessed prospectively, before and after cardiac catheterization with and without clinically indicated PCI. Within- and between-group differences in CSBF before and after PCI were assessed using repeated measures analysis of variance. Technically adequate CSBF measurements were obtained in 24 patients (77%). In patients who did not undergo PCI, there was no significant change in CSBF (278.1±344.1 versus 342.7±248.5, p=0.36). By contrast, among patients who underwent PCI, CSBF increased significantly (254.3±194.7 versus 618.3±358.5mL/min, p<0.01, p-interaction=0.03). Other hemodynamic and echocardiographic parameters did not change significantly before and after cardiac catheterization in either treatment group. Transthoracic echocardiographic assessment can be employed to document CSBF changes after angioplasty. Future studies are needed to explore the clinical utility of this noninvasive metric.

Coronary Flow Parameters Assessed by Transesophageal Echocardiography in Patients with Coronary Artery Ectasia Baseline Measurements and the Effects of Intravenous Verapamil

Background and rationale: Coronary artery ectasia (defined as luminal dilatation 1.5 to 2 times the adjacent healthy coronary artery or the diameter of the corresponding coronary artery in the control group in case of diffuse ectasia) is an uncommon disorder, usually associated with underlying myocardial ischemia. Micro-circulatory dysfunction has been demonstrated as one possible mechanism to explain ischemia in this disorder. Calcium antagonists have been proven to relieve microvascular spasm. Aim of the study: To test the hypothesis that relieving microvascular spasm in patients with coronary artery ectasia, through intravenous administration of verapamil, may result in improvement of microvascular coronary flow as reflected by coronary flow parameters assessed by transesophageal echocardiography (TEE). Patients and methods: Thirty patients with angiographically documented coronary artery ectasia of the left anterior descending artery were prospectively enrolled in the current study. Ten patients with normal coronary arteries were included as controls. All forty patients underwent TEE using pulsed wave Doppler (PWD) to measure peak systolic and diastolic velocities (m/sec); systolic, diastolic and total velocity time integrals (cm); and the systolic, diastolic and total coronary blood flow (cm³/min) in the proximal LAD before and after intravenous injection of verapamil (0.1 mg/kg). Results: Resting systolic, diastolic, and total coronary blood flow (cm³/min) were significantly higher in patients with ectasia compared to normal subjects (60.83 ± 27.7 cm³/min versus 25.31 ± 9.01 cm³/min, p<0.001; 126.89 ± 49.22 cm³/min versus 53.15 ± 18.30 cm³/min, p<0.001; and 188.02 ± 70.36 cm³/min versus 78.46 ± 25.97 cm³/min, p<0.001). There was a trend, not reaching statistical significance, towards higher basal peak velocities in normal subjects compared to patients with ectasia. In patients with coronary artery ectasia, intravenous injection of verapamil resulted in an increase in all observed coronary flow parameters including: peak systolic velocity (m/sec) from 0.19 ± 0.05 to 0.21 ± 0.04, p=<0.05, peak diastolic velocity (m/sec) from 0.39 ± 0.11 to 0.48 ± 0.15, p=<0.001, systolic velocity time integral (cm) from 3.0 ± 1.05 to 3.38 ± 0.78, p=<0.05, diastolic velocity time integral (cm) from 6.22 ± 1.97 to 8.42 ± 2.09, p=<0.001; total velocity time integral (cm) from 9.22 ± 2.73 to 11.8 ± 2.64, p=<0.001, systolic coronary blood flow (cm³/min) from 60.83 ± 27.7 to 69.0 ± 22.7, p=<0.05, diastolic coronary blood flow (cm³/min) from 126.89 ± 49.22 to 173.01 ± 62.4 p=<0.001, and total coronary blood flow (cm³/min) from 188.02 ± 70.36 to 242.0 ± 81.82, p=<0.001. Conclusion: Intravenous administration of verapamil resulted in statistically significant improvement of coronary flow parameters in patients with coronary artery ectasia. Further studies are needed to confirm whether continued treatment with verapamil translates to symptomatic improvement in the clinical setting.

Abstract 45: Hemodynamic and Clinical Determinants of Coronary Sinus Flow in Patients Referred for Cardiac Catheterization

Background: Coronary sinus blood flow (CSBF) can be used as a measure of total coronary blood flow. Hemodynamic and clinical determinants of coronary sinus flow are not well investigated. Decreased CSBF is expected in obstructive coronary artery disease (CAD) and elevated left ventricular end-diastolic pressure (LVEDP). Material and Methods: A prospective cohort study of patients referred for cardiac catheterization was performed. CSBF (ml/min) was measured non-invasively as a product of heart rate, coronary sinus cross-sectional area (obtained in modified apical 4 chamber view), and coronary sinus time velocity integral (obtained in modified right ventricular inflow view). In patients with normal sinus rhythm and preserved atrial contraction, retrograde diastolic CSBF was subtracted from forward CSBF. Repeated measures ANOVA and chi-square analyses were used. Results: Study cohort consisted of 39 patients (19 females, 63+/-11 years old, 9 with diabetes, 30 with hypertension (HTN) and 6 with atrial fibrillation). CSBF was obtained in 24 (61%) patients. CSBF was increased in patients with normal blood pressure (1353+/-862 vs. 647+/-397 in patients with HTN, p=0.011) and in patients with right atrial (RA) pressure exceeding 5 mmHg (1228+/-654 vs. 478+/-356 in RA pressure less than 5 mmHg, p=0.002). HTN appeared to be a less important determinant of CSBF than RA pressure (RAP) in multiple ANOVA comparison (HTN p=0.643, RAP p=0.005, Figure). There was also a trend towards decreased CSBF in patients with diabetes (647 +/-507 vs. 937 +/-685 ml/min in patients without diabetes, p=0.327) and /or obstructive CAD (663+/-381 vs. 832+/-748 ml/min in non-obstructive CAD or normal coronaries, p=0.613) and females (680+/-419 vs. 1095+/-828 ml/min in males, p=0.119). There was no significant correlation between CSBF and LVEDP. Discussion and Conclusions: Coronary sinus blood flow is determined by patient morbidities and central hemodynamic parameters. CSBF tends to be lower in patients with obstructive CAD, diabetes and/or HTN. Increased RA pressure and systemic HTN are associated with augmented CSBF. We speculate that effects of RA pressure on CSBF are reflective of preload and intrathoracic pressure parameters. Increased intrathoracic pressure may augment coronary blood flow by compression of the aorta and improved coronary perfusion gradient.

Hybrid Model Analysis of Intra‐Aortic Balloon Pump Performance as a Function of Ventricular and Circulatory Parameters

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks.

Assessment of Coronary Flow Parameters by Transesophageal Echocardiography in Patients with Isolated Coronary Artery Ectasia: Effect of Intravenous Nitroglycerin

We sought to assess coronary flow parameters in patients with isolated coronary artery ectasia (CAE) as compared to subjects with normal coronaries. Consecutively, we enrolled 30 patients with ectasia of the left anterior descending (LAD) coronary artery (study group), and 10 subjects with normal coronaries (control group). All patients underwent transesophageal echocardiography to visualize the LAD. Spectral recordings of proximal LAD flow velocities were made and velocity time integrals were calculated. The diameter of the proximal LAD was measured and LAD blood flow was calculated. Nitroglycerin (0.3 mg) was administered intravenously and measurements were repeated 5 minutes later. The mean age of the whole series was 48.6 ± 8 years, 39 (97.5%) being males. A significantly higher baseline systolic, diastolic, and total coronary blood flow was found in the study group as compared to the control group (46.1 ± 34.3 vs. 23.1 ± 8.2, 123.9 ± 73.3 vs. 68.1 ± 21.6, 170.1 ± 97.9 vs. 91.1 ± 26.8 cm(3) /min, respectively, P < 0.05 for all). Within the study group, nitroglycerin administration caused a significant decrease in peak diastolic velocity; systolic, diastolic, and total velocity time integrals; and both diastolic and total coronary blood flow (P < 0.05 for all). Meanwhile, within the control group, nitroglycerin administration caused a significant increase in the total coronary blood flow (P < 0.05). Patients with CAE have higher resting coronary blood flow in comparison with subjects with normal coronaries. Intravenous nitroglycerin administration causes significant reduction of coronary blood flow in ectatic coronary arteries.

Impact of alcohol septal ablation on left anterior descending coronary artery blood flow in hypertrophic obstructive cardiomyopathy

The aim of this study was to evaluate the effects of alcohol septal ablation (ASA) on coronary blood flow in symptomatic hypertrophic obstructive cardiomyopathy (HOCM) using cardiac MR (CMR) coronary flow measurements. Background CMR flow mapping enables quantification of coronary blood flow in a noninvasive way. Both left ventricular outflow tract (LVOT) gradient reduction and myocardial scarring after ASA are expected to influence left anterior descending (LAD) coronary blood flow. Cine, contrast-enhanced (CE) imaging and breath-hold CMR phase contrast velocity mapping were performed at baseline and 1 and 6 months after ASA in seven patients. Changes of coronary blood flow were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LVOT gradient reduction, and LV rate pressure product (LVRPP). A significant mass reduction was observed both in the target septal myocardium and in the total myocardium (both P < 0.01). Mean myocardial infarct size was 23 +/- 12 g (range 7.3-41.6 g). LVRPP decreased from 13,268 +/- 2,212 to 10,685 +/- 3,918 at 1 month (P = 0.05) and 9,483 +/- 2,496 mmHg beats/min at 6 months' follow-up (P < 0.01). LAD coronary blood flow decreased from 100 +/- 37 ml/min at baseline to 84 +/- 54 ml/min (P = 0.09) at 1 month and 67 +/- 33 ml/min at 6 months follow-up (P < 0.01). A significant correlation was found between the change in LVRPP and LAD coronary flow at 1 month follow-up (r = 0.83, P = 0.02). CE-infarct size tended to modulate the blood flow changes over time (P = 0.12); no correlation was observed between enzyme release, volume of ethanol or both septal and total mass reduction and coronary blood flow. The reduction in coronary blood flow is primarily associated with diminished LV loading conditions, whereas the induction of metabolically inactive myocardial scar tissue by ASA did not significantly influence the changes in coronary blood flow.

Topical negative pressure effects on coronary blood flow in a sternal wound model

Several studies have suggested that mediastinitis is a strong predictor for poor long-term survival after coronary artery bypass surgery (CABG). In those studies, several conventional wound-healing techniques were used. Previously, we have shown no difference in long-term survival between CABG patients with topical negative pressure (TNP)-treated mediastinitis and CABG patients without mediastinitis. The present study was designed to elucidate if TNP, applied over the myocardium, resulted in an increase of the total amount of coronary blood flow. Six pigs underwent median sternotomy. The coronary blood flow was measured, before and after the application of TNP (-50 mmHg), using coronary electromagnetic flow meter probes. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium) and after 20 minutes of LAD occlusion (ischaemic myocardium). Normal myocardium: 171.3 +/- 14.5 ml/minute before to 206.3 +/- 17.6 ml/minute after TNP application, P < 0.05. Ischaemic myocardium: 133.7 +/- 18.4 ml/minute before to 183.2 +/- 18.9 ml/minute after TNP application, P < 0.05. TNP of -50 mmHg applied over the LAD region induced a significant increase in the total coronary blood flow in both normal and ischaemic myocardium.

Experimental study of new diagnostic system for coronary artery disease using coronary transit index

Objectives Noninvasive cardiac imaging techniques have had an increasing role in the diagnosis of coronary artery disease. However, these techniques are not widely available as a tool in the office setting. The purpose of this study was to provide an accurate assessment of coronary artery disease for screening purposes using Coronary Transit Index (CTI) assessment with small, high-resolution gamma cameras. Methods Total coronary blood flow was measured with ultrasonic flow probes placed around the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery in a total of 33 conditions in 5 healthy mongrel dogs. The coronary blood flow was reduced stepwise with vascular occluders placed around the coronary arteries. The procedure for obtaining CTI included 4 parts: 1) The animal was injected intravenously with a bolus of a radioactive tracer (2.5–5.0 mCi of 99mTc-DTPA); 2) Dedicated gamma sensors monitored the passage of the injected bolus; 3) Time–activity curves were measured at the left ventricle with and without its wall; 4) The ratio of the washout rates of the 2 curves determined the CTI. Results Coronary Transit Index was successfully obtained from the left ventricle. The coronary blood flows measured by flow probes were well correlated with the regional myocardial blood flow. The percentage of the baseline value of the total coronary blood flow had the highest correlation ( R = 0.807, p < 0.0001) with the Coronary Transit Index. Conclusions These data indicated that a new diagnostic system using CTI successfully identified reduced coronary blood flow.

Magnetic resonance measurement of coronary blood flow

Magnetic resonance (MR) flow measurement in the coronary artery can be achieved with either a breath-hold acquisition or a respiration-triggered acquisition. MR measurements of cardiac output are significantly depressed during breath-holding at deep inspiration, but the advantage is that the breath-hold method requires less scan time. Blood flow in the coronary sinus reflects the global myocardial blood flow because it represents approximately 96% of the total myocardial blood flow of the left ventricle (LV). If blood flow in the coronary sinus is measured with phase-contrast cine magnetic resonance imaging (MRI) and LV myocardial mass is measured with cine MRI, both the total myocardial blood flow and the average coronary blood flow per gram of myocardial mass can be quantified. Coronary flow reserve with volumetric MR flow measurement is measured to be within 4.2-5.0-fold. The noninvasive MR measurement of coronary flow reserve has been shown to be useful in identifying the functional significance of stenoses in the left anterior descending artery. The sensitivity and specificity of MR coronary flow velocity reserve for identifying stenosis of 70% or greater in the left main or left anterior descending artery were 100% and 83%, respectively. The MR quantification of total coronary blood flow and coronary blood flow per gram of myocardial mass seems to be an ideal method for evaluating coronary hemodynamics and may be useful in evaluating endothelial dysfunction of the coronary circulation.

Magnetic resonance measurement of coronary blood flow

Magnetic resonance (MR) flow measurement in the coronary artery can be achieved with either a breath-hold acquisition or a respiration-triggered acquisition. MR measurements of cardiac output are significantly depressed during breath-holding at deep inspiration, but the advantage is that the breath-hold method requires less scan time. Blood flow in the coronary sinus reflects the global myocardial blood flow because it represents approximately 96% of the total myocardial blood flow of the left ventricle (LV). If blood flow in the coronary sinus is measured with phase-contrast cine magnetic resonance imaging (MRI) and LV myocardial mass is measured with cine MRI, both the total myocardial blood flow and the average coronary blood flow per gram of myocardial mass can be quantified. Coronary flow reserve with volumetric MR flow measurement is measured to be within 4.2–5.0-fold. The noninvasive MR measurement of coronary flow reserve has been shown to be useful in identifying the functional significance of stenoses in the left anterior descending artery. The sensitivity and specificity of MR coronary flow velocity reserve for identifying stenosis of 70% or greater in the left main or left anterior descending artery were 100% and 83%, respectively. The MR quantification of total coronary blood flow and coronary blood flow per gram of myocardial mass seems to be an ideal method for evaluating coronary hemodynamics and may be useful in evaluating endothelial dysfunction of the coronary circulation. Summary Recent advances in fast MRI sequences have considerably extended the capabilities of cardiac MRI in the functional assessment of coronary blood flow and flow reserve. The MR measurement of coronary flow reserve can be used to identify restenosis of the left main and left anterior descending coronary arteries after percutaneous interventions in clinical patients. Further refinements in MR pulse sequences, including the use of phase-contrast echo-planar or spiral MR methods, may make it possible to quantify blood flow volume and flow reserve more accurately in all major branches of the coronary arteries. The MR measurement of blood flow through the coronary sinus allows a noninvasive assessment of global coronary hemodynamics. Because the coronary sinus is larger than the native coronary arteries, the errors in blood flow quantification associated with the limited spatial and temporal resolution of current phase-contrast MR sequences are substantially smaller. The MR quantification of total coronary blood flow and coronary blood flow per gram of myocardium during stress and at rest seems to be an ideal method for evaluating coronary hemodynamics in diffuse myocardial diseases of the heart, such as hypertensive heart diseases and cardiomyopathies, and may be useful in evaluating endothelial dysfunction of the coronary circulation, which develops in the earliest stages of atherosclerotic disease and may precede obstruction of the epicardial coronary arteries.

Coronary microvascular dysfunction in patients with symptomatic hypertrophic cardiomyopathy

Background: Patients with hypertrophic cardiomyopathy (HCM) have been shown to have reduced myocardial perfusion in the presence of normal epicardial arteries. The mechanism of abnormal microvascular function is not well understood. Hypothesis: A possible mechanism for the reduction in CFR may be that the microcirculation is already near maximal dilation in the basal state and is therefore limited in the ability to further dilate and compensate for the increase in myocardial demand. Methods: Eight patients with symptomatic HCM and eight age- and sex-matched controls were studied. All patients underwent coronary angiography and coronary hemodynamic assessment with an intracoronary Doppler wire to determine total coronary blood flow, coronary resistance, and coronary flow reserve (CFR). Phasic blood flow parameters were also obtained. Results: Compared with controls (n = 8), patients with HCM (n = 8) had higher coronary blood flow (52±19 versus 33±11 mL/min, P = 0.03), lower coronary resistance (2.12±0.91 versus 3.13±0.93 mm Hg/mL/min, P = 0.05), and lower CFR (2.1±0.7 versus 3.4±1.0 mm, P = 0.02). There was a direct correlation between CFR and coronary resistance (r = .5, P = .05). HCM patients also had abnormal phasic coronary flow characteristics with lower systolic velocities or reversal of flow during systole, and a more rapid deceleration of diastolic blood flow (40.7±13.2 versus 27.5±8.5 cm/sec2, P=.03). Conclusion: The reduction of CFR in HCM patients may be secondary to near maximal vasodilatation of the microcirculation in the basal state rather than narrowing of intramyocardial small arteries. Symptomatic HCM patients also have abnormal phasic coronary blood flow with a greater dependence on diastolic flow and a more rapid deceleration of diastolic blood flow.

Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation.

The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction.

Vasodilator responses of coronary conduit and resistance arteries to continuous nitroglycerin infusion in humans: a Doppler guide wire study.

To examine the responses of coronary conduit and resistance arteries to the continuous i.v. administration of nitroglycerin in 15 patients with atypical chest pain, we measured coronary blood flow velocity in the left anterior descending coronary artery using a Doppler guide wire and the lumen diameter and cross-sectional area by quantitative coronary angiography. Systolic flow, diastolic flow, total coronary flow, and coronary vascular resistance were calculated. Stepwise increases in dose of nitroglycerin resulted in significant dose-dependent decrease in mean aortic pressure (p < 0.01) and increase in lumen diameter (p < 0.05). After nitroglycerin administration of 0.5 microg/kg/min, systolic flow decreased significantly by 89.9+/-15.7% (p < 0.01), and diastolic flow increased significantly by 74.2+/-37.1% (p < 0.05). Total coronary flow did not change significantly with the various doses of nitroglycerin. However, coronary vascular resistance decreased significantly at concentrations greater than 0.5 microg/kg/min nitroglycerin. Continuous nitroglycerin infusion did not reduce either diastolic or total coronary blood flow despite a significant reduction in coronary perfusion pressure. These results indicate that subendocardial blood flow might be maintained during continuous i.v. infusion of nitroglycerin within the clinical dose range.

Thoracic Epidural Anesthesia and the Patient with Heart Disease

Thoracic Epidural Anesthesia and the Patient with Heart Disease

Bradykinin accounts for improved postischemic function and decreased glutathione release of guinea pig heart treated with the angiotensin-converting enzyme inhibitor ramiprilat.

We investigated the role of bradykinin (BK) in cardioprotection elicited by angiotensin-converting enzyme (ACE) inhibition is isolated guinea pig heart performing pressure-volume work. Cardiac output (CO), coronary blood flow (CBF), and external heart work (EHW) were determined before and after ischemia and reperfusion (15 min each). Furthermore, the glutathione (GSH) content of hearts and the release of glutathione in coronary venous effluent were measured, as was lactate production. Addition of the ACE-inhibitor ramiprilat (RT) to the perfusate throughout the experiment improved postischemic function significantly (55% recovery of EHW for 25 microM RT vs. 30% for controls). RT was cardioprotective even if only given at onset of reperfusion (50% recovery). BK (0.1 and 1 nM) was similarly beneficial (55 and 76% recovery of EHW, respectively). The BK2-receptor antagonist HOE 140 (10 nM) inhibited the RT effect and attenuated the effect of 1 nM BK. Total CBF during reperfusion, lactate production, intracellular levels of GSH, and release of oxidized GSH (GSSG) did not differ among the groups. In contrast, release of reduced GSH during the first 5 min of reperfusion was considerably influenced by pharmacologic intervention, correlating inversely with postischemic heart function. Coapplication of Hoe 140 prevented the changes in GSH release. Our results demonstrate that BK, formed endogenously in the heart, is responsible for cardioprotection by the ACE inhibitor RT in isolated guinea pig heart and decreases GSH release during reperfusion. The exact mechanisms leading to hemodynamic improvement and metabolic changes by BK remain unclear.

Treatment of hypertension with felodipine in patients with concomitant diseases.

Coexisting medical conditions often complicate the selection of antihypertensive drugs. Felodipine, a new vascular-selective calcium antagonist with demonstrated antihypertensive efficacy, has not been found to alter lipid profiles in hypertensive patients. Studies in additional patient populations have yielded insights into the effects of the drug on other diseases that may coexist with hypertension. In individuals with stable angina pectoris or congestive heart failure, acute administration of felodipine reduces systemic vascular resistance and increases cardiac output and total coronary blood flow; myocardial contractility is not depressed at doses that produce a clinically significant reduction in vascular resistance. In patients with coronary stenoses, the drug increases vessel diameter in the vicinity of obstructive lesions. Single-dose and long-term studies in patients with exertional angina have found that felodipine reduces anginal frequency and improves exercise tolerance. In patients with congestive heart failure, chronic dosing with felodipine produces a persistent reduction in vascular resistance and an increase in cardiac output, both at rest and during exercise. Symptomatic improvement and increased exercise tolerance have been noted in some studies. In patients with Raynaud's phenomenon, felodipine has been associated with a dose-dependent improvement in symptomatology. Among individuals with exercise-induced bronchospasm, the drug has no effect on resting bronchial tone and may exert some positive effects during exercise. In hypertensive patients with Type II diabetes, felodipine has not been found to raise glucose levels significantly. The data obtained thus far suggest that felodipine is safe for use in hypertensive patients with a variety of concomitant diseases.

Collateral blood flow from skeletal muscle to normal myocardium

Collateral blood vessels from skeletal muscle to myocardium might supplement intramyocardial collaterals during periods of acute myocardial ischemia. This study was conducted to verify the existence of such collaterals and to measure their contribution to collateral flow. In 12 male goats, the innate coronary collateral system to a moderate size myocardial risk area was defined with colored microspheres, and a latissimus dorsi pedicle flap was then apposed to the heart. After 3 weeks, skeletal muscle to myocardial collaterals were characterized by (a) creation of vascular casts (three animals); (b) estimation of skeletal muscle to myocardial collateral blood flow (three animals); and, (c) measurement of total collateral blood flow to the risk area (innate plus skeletal muscle to myocardial collateral flow). Under a dissecting microscope the vascular casts revealed direct communications from the skeletal muscle which penetrated deeply into the myocardium. With the coronary artery to the risk area open, the estimated myocardial collateral blood flow derived from the muscle flap was 0.01, 0.02, and 0.04 ml/min. With the coronary artery to the risk area closed, there was no significant increase in total coronary collateral blood flow. Although the quantity of blood flow delivered by skeletal muscle collaterals was small, this study demonstrates that clearly identified collateral blood vessels form between skeletal muscle and myocardium in a cardiomyoplasty model. This raises the possibility that, under conditions more favorable to their development, extramyocardial collaterals from skeletal muscle might be exploited to augment the intramyocardial collateral system.

Subendocardial coronary compression in beating dog hearts is independent of pressure in the ventricular lumen

Ventricular decompression has been shown to have little effect on either the magnitude or transmural distribution of the extravascular resistance in the small hearts of the cat or rabbit. This study tests whether that independence from ventricular pressure also occurs in the large heart of the dog, which should be more representative of the human. We measured regional myocardial flow in each in situ dog heart during three conditions: normally beating, vented beating, and arrest. Hearts were perfused at constant pressure and maximally dilated with 0.4-1.0 mg/min ic adenosine. Total coronary blood flow was measured with an electromagnetic flowmeter, and regional flow was assessed with radiolabeled microspheres. Although arrest resulted in more than a doubling of flow to the inner layer, greatly reducing ventricular pressure by venting had no significant effect on subendocardial flow. Subepicardial flow was minimally affected by either venting or arrest. We conclude that both the magnitude and the transmural distribution of extravascular resistance in the large heart of the dog is unrelated to the pressure in the ventricular lumen.