Coronary Venous System Research Articles

Images of the human coronary sinus ostium obtained from isolated working hearts

Due to increasing interest in using the coronary venous system for placement of intracardiac devices, the functional anatomy of the coronary sinus ostium is clinically important. Using Plegisol cardioplegia and stan-dard cardiac surgery procedures, six human hearts deemed not viable for transplant were explanted to an isolated heart apparatus. A modified Krebs-Henseleit buffer was used as a blood substitute to sustain the hearts, allowing for visualization of internal structures of the functioning hearts. Video footage of the coronary sinus ostia was obtained using a 6-mm diameter flexible videoscope inserted into the hearts through the superior vena cava or the right atrial appendage. A wide range of coronary sinus morphologies was observed including remnant Thebesian valves covering approximately 50% of the coronary sinus ostium and a large fenestrated Thebesian valve covering greater than 50% of the coronary sinus ostium. These images demonstrate why difficulties are sometimes encountered while cannulating the coronary sinus during surgical procedures. Figure 1 shows still images of the coronary sinus ostia of six human hearts. Each image represents a single frame captured from beta video recordings. In each image, the ostium of the coronary sinus is marked “O” and the Thebesian valve is marked “v.” Images in Figures 1A , 1B, and 1D show well-developed Thebesian valves covering large portions of the coronary sinus ostium. Images in Figures 1C, 1E, and 1F show remnant Thebesian valves. Figure 2 illustrates serial images showing the movement of Thebesian valves that cover the coronary sinus ostia in three hearts. Consecutive frames in images in Figures 2A and 2B are 0.033 seconds apart and frames in images in Figure 2C are 0.067 seconds apart. The image in Figure 2A is a different view of the Thebesian valve shown in Figure 1A. The Thebesian valves in images in Figures 2A and 2B completely cover the coronary sinus ostium during systole, except for the small fenestrations in both valves. The Thebesian valve image in Figure 2C, although large enough to cover the entire coronary sinus ostium, never actually completely covers the ostium.

Simple access to the coronary venous system for left ventricular pacing.

Implantation of the LV lead for biventricular pacing can be challenging, time consuming, and often requires extensive fluoroscopy time. A conventional diagnostic 5 Fr left Amplatz catheter was used to cannulate the coronary sinus in 15 consecutive patients undergoing implantation of a biventricular pacemaker. When the coronary sinus was cannulated, the proximal end of the Amplatz catheter was cut and the coronary sinus sheath was passed over the Amplatz catheter that was then removed. Coronary sinus cannulation was achieved in all 15 patients with a mean fluoroscopy time of 3.34 +/- 1.9 minutes. Subsequent implantation of a biventricular pacemaker was successful and free of complications in all the 15 patients.

Percutaneous transvenous cellular cardiomyoplasty: A novel nonsurgical approach for myocardial cell transplantation

ObjectivesThe study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BackgroundDirect myocardial cell repopulation has been proposed as a potential method to treat heart failure. MethodsWe harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote myocardium, and the autologous cell–hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. ResultsWe gained widespread intramyocardial access to the anterior, lateral, septal, apical, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell–biogel delivery. ConclusionsPercutaneous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty.

Resynchronisation du cœur défaillant par la stimulation

Cardiac pacing has been proposed for patients with advanced heart failure refractory to optimal drug treatment and having conduction disorders to resynchronize mechanical activity of the heart. Activation asynchronism as caused by bundle branch block results in alteration of systolic function and arrythmias. A too short or too long atrio-ventricular delay can also affect diastolic ventricular filling. Early clinical studies showed a benefit of very long atrioventricular delays shortening, not confirmed by further studies. Direct stimulation of the left ventricle was beneficial in acute hemodynamic studies. Three controlled clinical studies now completed, PATH-CHF, MUSTIC and MIRACLE have showed a functional benefit. Other studies (COMPANION, CARE-HF) are currently in process to evaluate the effect on survival and the interest to associate an automatic defibrillator. Technical aspects are also under investigation: optimal lead placement in the coronary venous system, types of leads, special pacing devices. This paper reports the experience of the first 50 patients treated with multisite pacing in Aix-en-Provence general hospital, 33 men and 17 women, 71 years of mean age, on NYHA class III or IV, and showing QRS width above 120 ms. During the follow-up (mean duration 16 months) 15 deaths (30%) happened. The benefit on NYHA class was 1,34 ; rehospitalization rate was low. Coronary sinus access was successful in 100% of cases. Sixteen per cent had a reintervention for lead displacement or threshold elevation. Left atrioventricular crosstalk, observed in six patients, supports the use of devices with three independant channels. Echocardiography is of interest for responders identification, optimal device programming and follow-up.

Contrast-echocardiography: confirmation of patency of laser channels after transmyocardial laser revascularization.

Apart from casuistic autopsy results there is no long-term evidence for channel perfusion after transmyocardial laser revascularization in humans. Fifteen consecutive patients aged 63+/-17 years were investigated 71+/-15 days after coronary artery bypass surgery and/or transmyocardial revascularization with 13-37 (20+/-5) channels (CO(2) laser, 40 J/pulse). Echocardiography was performed after injection of 6 ml echo contrast medium into left ventricular cavity and after injection of 3 ml contrast medium into the left main coronary artery. In five patients with additional bypass surgery to the same region, we also injected 3 ml contrast medium into bypass graft. We could prove in 10 of 15 patients (67%) one or two laser channels in the apical left ventricular myocardium. Channels were perfused exclusively during systole. During following heart cycles myocardium was opacified up to a mean width of 1.4+/-0.4 cm, a mean depth of 0.71+/-0.1cm, and a mean area of 1.0+/-0.6 cm(2). Contrast medium was washed out via coronary venous system in 9+/-8 systoles. This is the first clinical evidence of long-term laser-channel patency in humans showing perfused myocardium via left ventricular cavity.

Investigation of coronary venous anatomy by retrograde venography in patients with malignant ventricular tachycardia.

The coronary venous system is increasingly used for left ventricular or biventricular pacing in patients with severe heart failure. The present study investigated the structure of the coronary veins in patients presenting with structural heart disease and malignant ventricular tachyarrhythmias. The availability of veins for possible lead placement was assessed. The number, relative size, and location of coronary veins were evaluated by retrograde venography in 129 patients undergoing cardioverter-defibrillator implantation. Detailed x-ray image analysis was performed in 86 patients, for whom optimal coronary sinus occlusion and vein visualization was achieved. The anterior interventricular vein and the middle cardiac vein were visible in 85 (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these 2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86 patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were observed in 40 (46%) of 86 patients, and >2 veins were visualized in 2 (2%) of 86 patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a coronary vein in 115 (93%) of 124 patients. The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.

Catabolism of adenine nucleotides in the human heart before and after cardiac bypass surgery

Uric acid (UA) is a catabolite of the high-energy purine phosphates and of purines in DNA and RNA. Thus, cardiac net release of UA could prevail in subjects with chronic myocardial ischemia and during coronary occlusion associated with cardiac artery bypass grafting surgery (CABG). However, in acute reperfusion, reactive oxygen species could cause chemical degradation of urate, perhaps even giving rise to a negative coronary arteriovenous difference. Blood was sampled simultaneously from the arterial and coronary venous system of 24 patients undergoing elective CABG. Blood was immediately deproteinated (0.4 M HClO4) in the presence of the glutathione-scavenger N-ethylmaleimide (60 mM), and the supernatant was analysed for UA, purines, and glutathione by high performance liquid chromatography. Before the operation, CABG patients revealed a small, but significant net production of UA in the heart (+28 μmol/liter whole blood; arterial level, 223±71 μM; mean± SD). There were no coronary differences for adenosine, inosine, or hypoxanthine. UA release was not elevated in early reperfusion after cardiac arrest and tended to decrease by 20–40 min of reperfusion (coronary sinus UA 10–18 μM above arterial level, not significant). Adenosine levels were <0.2 μM at all times in all blood samples. Coronary sinus (CS) inosine levels rose approximately 10-fold during early reperfusion to 2 μM (not significant). However, CS hypoxanthine increased significantly from 8 (±3) to 35 (±14) μM at 1 min reperfusion, but after 5 min had returned to 15 μM. There was a net release of reduced glutathione from the hearts before intervention, and individual changes in coronary glutathione levels were approximately parallel to those of urate in early reperfusion. Surprisingly, urate release did not correlate to the duration of cardiac ischemia (crossclamp time). Thus, in human hearts with chronic ischemia, myocardial release of uric acid is approximately 10–30% higher than the arterial input, indicative of a pronounced catabolic state of the tissue. Metabolic recovery after CABG requires more than 1 h. Hypoxanthine (and not urate) is the better marker of acute myocardial nucleotide catabolism in early postischemic reperfusion. Adenosine underlies a tight homeostasis in the coronary system. The correlation of urate and glutathione release suggests that membrane perturbation may accompany and/or contribute to nucleotide catabolism. Drug Dev. Res. 45:159–165, 1998. © 1998 Wiley-Liss, Inc.

Angiography of the coronary venous system. Use in clinical electrophysiology

To study the angiographic anatomy of human coronary veins and the possibility of epicardial venous mapping through microelectrode catheters. We evaluated 30 patients with sustained ventricular tachycardia using a catheter which provided occlusion of the coronary sinus ostium during venous angiography. They were 25 males, 5 females, ages ranging from 24 to 76 years (mean = 52.7). The veins were studied according to their number, caliber and distribution in the anterior and posterior wall of the left ventricle. Coronary sinus was catheterized in all patients. No discomfort or complication were observed. The number of veins from posterior wall of the left ventricle was 3.1 and anterior wall, 1.9, p < 0.05. The caliber of the coronary veins were: anterior interventricular vein (distal segment = 1.19 +/- 0.22 mm, middle segment = 1.65 +/- 0.35 mm), posterior interventricular vein (distal segment = 1.83 +/- 0.47 mm, middle segment = 2.00 +/- 0.52 mm), left posterior vein (distal segment = 1.45 +/- 0.25 mm, middle segment = 2.49 +/- 0.92 mm); p < 0.05. The balloon occlusion technique for coronary venous angiography is feasible and safe. The number and the caliber (distal and middle) of the veins from the posterior wall of the left ventricle were significantly greater than those from the anterior wall. Anatomic conditions for venous epicardial mapping are more adequate in the posterior wall of the left ventricle.

Simplified retroperfusion system preserves the myocardial function during acute coronary artery occlusion.

It is known that coronary venous retroperfusion restores the blood flow to the ischemic myocardium, resulting in reduction of infarct size and improvement in left-ventricular pump function. In this study, we used an animal model to investigate the effects of a simplified coronary venous retroperfusion system on myocardial hemodynamics. Twenty dogs were entered in this study. All dogs underwent fifteen minutes occlusion of the left anterior descending artery. For the rest of the experiment the dogs were randomized into two groups: the control group (n = 10) underwent a further 2 hours left anterior descending artery occlusion, then clamps were released and the animals were observed for 6 hours. In the retroperfusion group (n = 10) a simple aortocoronary sinus connection was made and retrograde perfusion achieved with an outflow of 43 +/- 6 ml/min. Retrograde coronary sinus perfusion was maintained for three hours and then the dogs were observed for six hours. Tissue adenosine triphosphate levels were 6 +/- 3 mumol/g in the control group and 12 +/- 2 mumol/g in the retroperfusion group (p < 0.05) 6 hours after reperfusion. Creatine phosphokinase levels were 99 +/- 11 IU/L in the control group and 42 +/- 8 IU/L in the retroperfusion group 6 hours after reperfusion (p < 0.05). Cardiac index was 63 +/- 4 ml/kg/min in the control group and 79 +/- 2 ml/kg/min in the retroperfusion group 6 hours after retroperfusion (p < 0.05). Left-ventricular stroke-work index at a pulmonary capillary artery wedge pressure of 20 mmHg was 0.54 +/- 0.06 g.m/kg in the retroperfusion group and 0.29 +/- 0.03 g.m/kg in the control group 6 hours after reperfusion (p < 0.05). It is concluded that myocardial hemodynamic and biochemical function can be preserved by simplified coronary sinus retroperfusion.

Angiographic and electrophysiological substrates for ventricular tachycardia mapping through the coronary veins

ObjectiveTo study the value of epicardial mapping through the coronary venous system in patients with sustained ventricular tachycardia.Design20 consecutive patients with sustained ventricular tachycardia who were candidates for radiofrequency ablation.SettingElectrophysiological...

Longitudinal position matrix of the pig coronary vasculature and its hemodynamic implications.

Hemodynamic analysis of coronary blood flow must be based on a statistically valid geometric model of the coronary vasculature. We have previously developed a diameter-defined Strahler model for the arterial and venous trees and a network model for the capillaries. A full set of data describing the geometric properties of the porcine coronary vasculature was given. The order number, diameter, length, connectivity matrix [m,n] (CM), and parallel-series features were measured for all orders of vessels of the right coronary artery (RCA), left anterior descending artery (LAD), left circumflex artery (LCX), and coronary venous system. The purpose of the present study is to present another feature of the branching pattern of the coronary vasculature: the longitudinal position matrix [m,n] (LPM), whose component in row m and column n is the fractional longitudinal position of the branch point on vessels of order n at which vessels of order m branch off (m < or = n). The LPM of the pig RCA, LAD and LCX arterial trees, as well as the coronary sinusal and thebesian venous trees, are presented. The hemodynamic implications of the LPM are illustrated by comparing two kinds of circuits: one, the CM + LPM model, simulates the mean data on the morphology (diameters, lengths, and numbers), CM, and LPM of vessels, whereas the other, the CM model, simulates the mean data on the morphology and CM without considering the LPM. We found that the LPM affects the hemodynamics of coronary blood flow especially with regard to the nonuniformity or dispersion of flow distribution.

Differences in development of coronary arteries and veins.

The differentiation of the coronary vasculature was studied to establish in particular the formation of the coronary venous system. Antibody markers were used to demonstrate endothelial, smooth muscle, and fibroblastic cells in serial sections of embryonic quail hearts. The anti-beta myosin heavy chain and the neuronal marker HNK-1 were added to our incubation protocol. In HH32, the coronary vascular network has developed into a circulatory system with connections to the sinus venosus, the aorta and the right atrium. The connections between the aorta and the right atrium allow for direct arteriovenous shunting. Subsequently, differentiation into coronary arteries and veins occurs with an interposed capillary network. The smooth muscle cells of the coronary arterial media derive from the subepicardial layer, whereas the subepicardially located cardiac veins recrute atrial myocardium, as these cells express the beta-myosin heavy chain antigen. Ganglia are located in the subepicardium close to the vessels, while nerve fibres tend to colocalize with the formed vessel channels. A new finding is presented in which the subepicardial coronary veins have a media that consists of myocardial cells. The close positional relationship of neural tissue and coronary vessels that penetrate the heart wall is explained as inductive for vessel wall differentiation, but not for invasion into the heart.

Effects of coronary venous retroinfusion of lipo-prostaglandin E1on myocardial infarct size in pigs

The coronary venous system is an alternate route for drug delivery to the acutely ischemic myocardium when the coronary arterial blood flow is impeded. This study was designed to determine the effect of retrograde infusion of lipid microsphere containing prostaglandin E1 (lipo-PGE1), which is believed to prevent rapid destruction of PGE1, on myocardial infarct size after acute myocardial ischemia and reperfusion. Twenty-one open-chest porcine models were subjected to 45 minutes of left anterior descending coronary artery (LAD) occlusion followed by 4 hours of reperfusion. Group A (n = 7), the control group, was given, into the great cardiac vein, 4 ml of vehicle dissolved in 36 ml of saline for 5 minutes starting before the onset of reperfusion. In group B (n = 7), 20 μg/4ml of lipo-PGE1 was administered into the great cardiac vein in the same manner as in group A. Group C (n = 7) was treated the same as group B, but lipo-PGE1 was injected into the inferior vena caval vein. Infarct size, expressed as a percentage of area at risk, was significantly smaller in group B (56.1±12.6%) than groups A (79.4 ± 11.4%) and C (83.0 ± 11.1%) (p< 0.05). The results of this study indicate that retrograde infusion of lipo-PGE1 is an effective treatment for the prevention of myocardial reperfusion injury in the experimental model.

Effects of Coronary Venous Retroinfusion of Lipo-Prostaglandin E 1 on Myocardial Infarct Size in Pigs

The coronary venous system is an alternate route for drug delivery to the acutely ischemic myocardium when the coronary arterial blood flow is impeded. This study was designed to determine the effect of retrograde infusion of lipid microsphere containing prostaglandin E1 (lipo-PGE1), which is believed to prevent rapid destruction of PGE1, on myocardial infarct size after acute myocardial ischemia and reperfusion. Twenty-one open-chest porcine models were subjected to 45 minutes of left anterior descending coronary artery (LAD) occlusion followed by 4 hours of reperfusion. Group A (n = 7), the control group, was given, into the great cardiac vein, 4 ml of vehicle dissolved in 36 ml of saline for 5 minutes starting before the onset of reperfusion. In group B (n = 7), 20 μg/4ml of lipo-PGE1 was administered into the great cardiac vein in the same manner as in group A. Group C (n = 7) was treated the same as group B, but lipo-PGE1 was injected into the inferior vena caval vein. Infarct size, expressed as a percentage of area at risk, was significantly smaller in group B (56.1±12.6%) than groups A (79.4 ± 11.4%) and C (83.0 ± 11.1%) (p< 0.05). The results of this study indicate that retrograde infusion of lipo-PGE1 is an effective treatment for the prevention of myocardial reperfusion injury in the experimental model.

The relationship between cardiac contraction and intramyocardial hemodynamics.

Since coronary venous flow is squeezed out from the myocardial vascular bed by the extravascular compressive force of heart muscle, the coronary venous system provides a suitable model to investigate the relationship between cardiac contraction and intramyocardial hemodynamics. To investigate coronary venous flow velocity in more detail, we previously developed a laser Doppler velocimeter (LDV) with an optical fiber. Furthermore, we have recently developed a needle probe charge-coupled device (CCD) videomicroscope to visualize intramyocardial microvessels. In this article, we report I) blood flow velocity waveforms in the epicardial small veins of the left ventricle and 2) subendocardial venular diameter changes during a cardiac cycle.

RF ablation in the coronary venous system is associated with risk of coronary artery injury which may be prevented by use of intravascular ultrasound

RF ablation in the coronary venous system is associated with risk of coronary artery injury which may be prevented by use of intravascular ultrasound

New insights into the physiology of retrograde cardioplegia delivery

Although retrograde cardioplegia (RC) is being increasingly used in clinical practice, its physiology is unclear. Because the microvascular architecture of the coronary venous system is different from that of the arterial system, we hypothesized that myocardial perfusion would be different during RC compared with anterograde cardioplegia (AC) delivery. To better understand these differences, three groups of dogs were studied during similar RC and AC flow rates. Radiolabeled microsphere-derived microvascular flow underestimated total cardioplegia flow by 66% during RC. For the same flows, the first-pass extraction fractions of 201Tl and 99mTc were significantly less during RC compared with AC despite adjusting for microsphere loss. Myocardial contrast echocardiography (MCE), however, provided an accurate estimation of AC and RC flow rates. In addition, the rate of myocardial cooling for most of the left ventricular myocardium was similar for AC and RC at the same flow rates, as long as the flow rates were brisk. It is concluded that microvascular and nutrient flows are significantly lower at the same flow rates during RC compared with AC due to loss of RC at different microvascular sites. Unlike microspheres and diffusible radioisotopes, MCE can provide a reliable measure of myocardial flow during RC delivery. Furthermore, myocardial cooling is similar in most of the myocardium during high-flow RC and AC, which suggests that the clinical benefits of RC are probably related to myocardial cooling and that substrate replenishment may be better achieved at the same flow rates and myocardial temperatures with AC rather than RC.

Radiofrequency catheter ablation of left-sided accessory pathways: clinical and regulatory issues in the return to the coronary venous system.

Radiofrequency catheter ablation of left-sided accessory pathways: clinical and regulatory issues in the return to the coronary venous system.

901-57 Anomalies of the Coronary Venous System in Patients with and without Accessory Pathways

Anomalies of the coronary sinus (CS) were recently reported in association with accessory pathways (APs). In this prospective study, we analyzed the incidence of such anomalies in patients with and without an AP. A total of 124 consecutive pts (48 f, 76 m; 43 ± 14 yrs) were investigated; 44 had a left free wall AP, 33 a posteroseptal AP (10 right; 19 left; 4 without precise location due to failed RFC ablation) and 13 a right sided AP (7 anteroseptal; 6 right free wall). The remaining 34 pts were studied for AV nodal reentry tachycardia in 19 cases and for ventricular or atrial arrhythmias in 15 cases. Coronary artery disease was present in 7 pts. Retrograde CS angiography was performed using a 6-French catheter. A total of 11 anomalies was found, 6 of which were CS diverticula (DIV) and 5 were a persistent superior vena cava (PSVC). All were found in pts with APs. 4 DIV were in the posteroseptal (ps) and 1 in the posterior region of the CS. In 4 pts the AP could be abolished from the neck of the DIV, in 2 pts the right ps AP had no association to the ps CS DIV 4 DIV drained into the CS and 1 directly into the right atrium. 4 DIV were spherical. 1 DIV elliptical and 1 DIV cauliflower-like shaped. The size differed between 1.0 × 1.8 and 3.4 × 2.5 cm, 4 pts with the PSVC had a left lateral Ap, which could be ablated using the ventricular approach to the mitral valve annulus. 1 pt had a right anteroseptal AP, which could be ablated from the right atrium. 1. DIV of the CS are most likely present in patients with leftsided APs. 2. In most cases, an AP is associated with the neck of the DIV The association between anomalies of the venous system and those of the AV conduction system could be based on combined failures in the embryologic development.

Ischemic and Nonischemic Tissue Concentrations of Felodipine After Coronary Venous Retroinfusion During Myocardial Ischemia and Reperfusion

Summary: Tissue and plasma concentrations of felodipine, a dihydropyridine (DHP) calcium antagonist, retroinfused through the coronary venous system were studied in 27 pigs. The animals underwent 45-min myocardial ischemia followed by 4-h reperfusion. Felodipine (7 nmol/kg body weight) was administered in the coronary vein for 30 min, 5 min before reperfusion. Concentrations of felodipine in the ischemic and nonischemic myocardium and in plasma were determined by gas chromatography. In the ischemic area, felodipine concentration at start of reperfusion was 304 ± 285, 171 ± 160, and 52 ± 47 nmol/kg (mean ± SD) in the subepicardial, midmyocardial, and subendocardial layer, respectively. Corresponding concentrations in the nonischemic area were 15 ± 13, 17 ± 14, and 16 ± 15 nmol/kg (p < 0.05 vs. ischemic area). Subepicardial concentration was highest at start of reperfusion, whereas concentrations in other layers peaked at the end of retroinfusion. The transmural concentration gradient of felodipine in the ischemic area decreased progressively during the reperfusion period. The nonischemic tissue concentration increased slightly during the reperfusion period. The plasma concentration was very low throughout the study (peak = 3.2 ± 1.4 nM at 30 min). Coronary venous retroinfusion of felodipine resulted in profound accumulation of the drug, specifically in ischemic myocardium. The plasma concentration was low and did not affect systemic hemodynamics. Coronary venous retroinfusion is considered an advantageous technique for selective drug delivery.