Coronary Artery Blood Flow Velocity Research Articles

In vivo phenotypic vascular dysfunction extends beyond the aorta in a mouse model for fibrillin-1 (Fbn1) mutation

In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (Fbn1C1041G/+) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. It is well established that the MFS mouse model exhibits an accelerated-aging phenotype in elastic organs like the aorta, lung, and skin. However, the impact of Fbn1 mutations on the in vivo function and structure of various artery types with the consideration of sex and age, has not been adequately explored in real-time and a clinically relevant context. In this study, we investigate if Fbn1 mutation contributes to sex-dependent alterations in central and cerebral vascular function similar to phenotypic changes associated with normal aging in healthy control mice. In vivo ultrasound imaging of central and cerebral vasculature was performed in 6-month-old male and female MFS and C57BL/6 mice and sex-matched 12-month-old (middle-aged) healthy control mice. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters. Coronary artery blood flow velocity (BFV) in diastole was not different but left pulmonary artery BFV was decreased in MFS and 12-month-old control mice regardless of sex. At 6 months of age, MFS male mice show decreased posterior cerebral artery BFV as compared to age-matched control males, with no difference observed between female cohorts. Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex. Male MFS mice also demonstrated left ventricular hypertrophy. Overall, these results underscore the significance of biological sex in vascular function and structure in MFS mice, while highlighting a trend of pre-mature vascular aging phenotype in MFS mice that is comparable to phenotypes observed in older healthy controls. Furthermore, this research is a vital step in understanding MFS's broader implications and sets the stage for more in-depth future analyses, while providing data-driven preclinical justification for re-evaluating diagnostic approaches and therapeutic efficacy.

Cardiac rehabilitation therapy for coronary slow flow phenomenon.

To evaluate the effectiveness of cardiac rehabilitation on coronary slow flow phenomenon. Included were 30consecutive patients from June 2015 to June 2017. Athrombolysis in myocardial infarction (TIMI) frame evaluation was used to estimate coronary blood flow velocity. All coronary angiography diameters were normal, but blood flow levels did not reach the TIMI level3. All patients were treated with aspirin and rosuvastatin. Patients were randomly assigned to an experimental group (cardiac rehabilitation treatment group, n = 15) or acontrol group (normal treatment without cardiac rehabilitation, n = 15). Plasma low density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-sensitivity Creactive protein (hs-CRP), homocysteine (Hcy) and arginine (Arg) expression levels were collected after admission. These indices were reviewed again after 20-30 weeks, improved subjective symptoms were evaluated by multiple outcome criteria (MOCs), and coronary angiography was used to evaluate the velocity of coronary artery blood flow. The expression levels of LDL-C and TG in the experimental group were significantly lower than those of the control group (both P < 0.01). The plasma levels of hs-CRP, Hcy and Arg were lower than those in the control group (all P < 0.01). In the experimental group, subjective symptoms of chest pain were significantly improved and the coronary artery blood flow velocity was significantly increased compared with the control group (P < 0.01). Cardiac rehabilitation can reduce the plasma levels of LDL-C, TG, hs-CRP, Hcy and Arg, significantly improve the symptoms of coronary slow flow phenomenon and accelerate the speed of coronary artery blood flow.

Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease

Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease (IHD) by interfering with physiological regulation of coronary tone. To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting, we measured the effect of an acute oxidative stress (breathing 100% oxygen) on coronary capacitance artery diameter (quantitative angiography) and blood flow velocity through the coronary microcirculation (intracoronary Doppler ultrasonography) before and after treatment with the antioxidant vitamin C (3-g intravenous infusion) in 12 IHD patients undergoing a clinical coronary interventional procedure. Relative to room air breathing, 100% oxygen breathing promptly reduced coronary blood flow velocity by 20% and increased coronary resistance by 23%, without significantly changing the diameter of capacitance arteries. Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level, and it prevented the reinduction of coronary constriction with rechallenge with 100% oxygen. This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD, and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation. This observation may have relevance for clinical practice.

1080 Relationship between intramural coronary artery blood flow velocity and left ventricular workload in patients with aortic valve stenosis: preliminary results

1080 Relationship between intramural coronary artery blood flow velocity and left ventricular workload in patients with aortic valve stenosis: preliminary results

Systolic Wall Stress May Affect the Intramural Coronary Blood Flow Velocity in Myocardial Hypertrophy, Independently on the Left Ventricular Mass

We sought to evaluate the relationship between left ventricular systolic wall stress (LV-SWS) and coronary artery blood flow velocity in patients with LV hypertrophy (LVH). The study population comprised 38 patients, aged 66.7 +/- 12.7, who were divided into two groups based on the LV-SWS median value. Group A included 19 patients at "low-stress" (92.0 +/- 18.0 mmHg/cm2) and group B other 19 patients at "high-stress" (134.2 +/- 32.3 mmHg/cm2) (P < 0.002). Coronary blood flow velocities were measured both in the left anterior descending (LAD) and in the intramural (IM) arteries. There were no significant between-group differences in the main clinical and echocardiographic parameters. Diastolic velocity in the LAD was also comparable, while it was higher in the IM arterioles of patients from group B than from group A (peak velocity 110.9 +/- 35.2 cm/s vs 92.0 +/- 29.4 cm/s, P < 0.02; mean velocity 78.6 +/- 28.8 vs. 56.0 +/- 20.2 cm/s, P < 0.01, respectively). Overall, moderate, but significative, linear correlation was found between IM peak and mean diastolic velocity and LV-SWS (r = 0.41, P = 0.01, and r = 0.44, P = 0.007, respectively), whereas there was no correlation with wall thickening and LV mass. Main findings from the present study likely suggest that in patients with mild-to-moderate LVH, high blood flow velocity in the IM arterioles, but not in the LAD, may be related to an increase in LV-SWS, rather independent on the absolute LV mass.

Different Responses of Myocardial and Cerebral Blood Flow to Cord Occlusion in Exteriorized Fetal Sheep

Type and duration of fetal asphyxial insult affect the distribution of blood flow to the heart and brain. The purpose of this study was to describe dynamic and quantitative changes in regional myocardial and cerebral blood flow (CBF) during fetal asphyxia induced by total occlusion of the umbilical cord. Eleven exteriorized fetal sheep were subjected to total umbilical cord occlusion and five fetal sheep served as sham controls. Regional blood flow (BF) to the brain and heart was quantified using radioactive microspheres before and after 5 min of occlusion and finally when fetal mean arterial blood pressure had decreased below 25 mm Hg, 9.8 (0.8) [mean (SD)] min after occlusion. Right coronary arterial (RCA) blood flow velocity and carotid BF were registered continuously. Mean values of arterial pH and oxygen content (mL O(2)/100 mL) were 7.08 (0.11) and 4.4 (2.9) before cord occlusion and decreased to 6.83 (0.05) and 1.4 (0.9) at 5 min after occlusion (p < 0.01, respectively). Carotid BF was significantly below preocclusion values by 2.5 min (p < 0.05), whereas RCA velocity time integral per minute remained above preocclusion values for 9 min. CBF decreased from 316 (24) before cord occlusion to 156 (30) mL/min/100 g at 5 min (p < 0.01), whereas right myocardial BF was maintained at 792 (125) and 751 (183) mL/min/100 g, respectively. CBF decreased rapidly after total cord occlusion whereas myocardial BF increased and was maintained until shortly before cardiac arrest, suggesting the myocardium to be better preserved during this type of insult in already partially asphyxiated fetuses.

Coronary artery blood flow velocities in various fetal conditions.

To determine fetal coronary artery peak blood flow velocities in normal and high-risk pregnancies. Coronary artery peak systolic and diastolic blood flow velocities were measured by pulsed-wave Doppler velocimetry after identification of the coronary arteries by color Doppler imaging. Peak blood velocities obtained from normal pregnancies were related to gestational age using linear regression analysis. Blood flow velocities in normal fetuses were compared to measurements obtained in various fetal conditions. In normal fetuses coronary artery blood flow was visualized at a median gestational age of 33 + 6 weeks; median systolic and diastolic peak blood flow velocities were 0.21 and 0.43 m/s, respectively, and showed no significant change with gestational age. In growth-restricted fetuses coronary artery blood flow was visualized significantly earlier in gestation (median 28 + 2 weeks); systolic and diastolic peak blood flow velocities were higher at 0.25 and 0.48 m/s, respectively (P < 0.05). The highest coronary blood flow velocities were observed with fetal anemia. Coronary artery blood flow was also measured in fetuses with ductus arteriosus constriction due to indomethacin. Velocities did not differ from normal fetuses. Both in fetal anemia and ductus arteriosus constriction coronary artery blood flow could no longer be visualized with resolution of the underlying condition. Examination of coronary artery blood flow dynamics in the human fetus demonstrates acute increases in diastolic velocities in severe anemia and ductus arteriosus constriction based on the severity of the condition. In fetuses with growth restriction increased coronary blood flow velocities can be appreciated throughout the cardiac cycle. Clinical correlation in the interpretation of coronary blood flow dynamics in the human fetus is essential.

Magnetic resonance coronary angiography in patients with ischemic heart disease: analysis of coronary arterial blood flow velocity pattern.

Only a few reports evaluating coronary arterial blood flow velocity patterns using magnetic resonance (MR) coronary angiography have appeared to date. This study reports an evaluation of coronary arterial blood flow velocity patterns in patients with ischemic heart disease and in healthy subjects using MR coronary angiography. The subjects consisted of 20 patients with ischemic heart disease (IHD group) and 20 normal healthy subjects (N group). Using the fCARD PC method, ECG-gated MR coronary angiography was performed using an anteroposterior opposing phased array coil. Regions of interest were placed on bilateral coronary arteries to measure coronary arterial blood flow velocity patterns. The IHD group was divided into two subgroups, based on the presence (MI group) or absence (AP group) of infarcted myocardium using 99m Tc-methoxyisobutylisonitrile (MIBI) myocardial scintigraphy. Average diastolic peak velocity (ADPV) was lower in the IHD group than in the N group. In addition, the diastolic / systolic velocity ratio (DSVR) was significantly lower in the MI group. Moreover, in the AP group, both the ADPV and DSVR values were significantly increased in those who had undergone percutaneous transluminal coronary angioplasty postoperatively. Different from the Doppler guidewire method, MR coronary angiography facilitates noninvasive evaluation of coronary arterial blood flow velocity. Therefore, these results indicate that MR coronary angiography represents a potentially useful technique for diagnosing lesions of coronary arteries and evaluating their functions. This noninvasive method can be expected to replace the invasive Doppler guidewire method in the near future with development of MR coronary angiography technology.

Noninvasive assessment of the infarct-related coronary artery blood flow velocity using phase-contrast magnetic resonance imaging after coronary angioplasty

This study assesses infarct-related coronary artery blood flow velocity using phase-contrast magnetic resonance imaging (MRI) in patients with reperfused acute myocardial infarction (AMI) and compares these results with flow measurements obtained nonsimultaneously by intracoronary Doppler ultrasound. MRI examination was performed in 17 patients with AMI within 1 to 4 days (mean 2.5 days) after direct or rescue coronary angioplasty using a 0.014-in Doppler guidewire. MRI was performed on a 1.5-T clinical imager. The fast gradient echo segmented k-space phase-contrast pulse sequence was employed during breath-hold. The MRI and Doppler parameters of average peak velocity and maximum peak velocity were measured. Mean phase contrast MRI average peak velocity was 13.3 ± 10.7 cm/s, and mean phase-contrast MRI maximum peak velocity was 27 ± 16.6 cm/s. Mean Doppler average peak velocity was 17.1 ± 5.1 cm/s, and mean Doppler maximum peak velocity was 35.5 ± 10.1 cm/s. At the same anatomic levels, phase-contrast MRI average peak velocity correlated significantly to Doppler average peak velocity (r = 0.52; p <0.006) and Doppler maximum peak velocity (r = 0.42; p <0.03). Phase-contrast MRI velocity measurements were correlated with the same heterogeneity of Thrombolysis In Myocardial Infarction 3 flow velocity observed during Doppler examination. Thus, by comparing phase-contrast MRI with invasive intracoronary Doppler flow measurements, the measured MRI values showed significant correlation with Doppler data. Phase-contrast MRI has the potential to noninvasively quantify coronary flow velocity and to evaluate quality of reperfusion in patients with AMI after reperfused therapy.

Effects of pulmonary balloon valvuloplasty on right coronary artery blood flow in pulmonary valve stenosis

Pulmonary balloon valvuloplasty results in improvement in the right coronary artery blood flow velocity pattern and the volumetric flow in patients with pulmonary valve stenosis. These changes are closely related to concomitant changes in right ventricular systolic pressure.

Assessment of Coronary Artery Blood Flow Velocity Using Breath-hold Phase Contrast MR Angiography in Patients With Acute Myocardial Infarction

Assessment of Coronary Artery Blood Flow Velocity Using Breath-hold Phase Contrast MR Angiography in Patients With Acute Myocardial Infarction

Systematic review: Intra-aortic balloon counterpulsation pump therapy: a critical appraisal of the evidence for patients with acute myocardial infarction

Intra-aortic balloon counterpulsation pump (IABP) therapy has been used in several clinical situations, predominantly in critically ill patients, since 1968 [1]. In acute myocardial infarction (AMI) patients who are experiencing continued ischemia, IABP therapy may be used in an attempt to improve patency of an infarct-related coronary artery (IRA) and reduce the rates of recurrent myocardial ischemia and its sequelae. The mechanism for this benefit is thought to be a combination of reduced oxygen demand [2], increased coronary artery blood flow velocity [3], and augmentation of diastolic arterial pressure enhancing thrombolysis, leading to faster reperfusion [4]. IABP therapy may also be used in patients with ventricular septal rupture, severe mitral regurgitation, and cardiogenic shock. The technique for IABP therapy involves insertion of an 8 or 9.5 Fr helium-filled balloon via the femoral artery into the descending aorta. The device is preferably inserted through an existing vascular access site in an attempt to reduce the rate of vascular and hemorrhagic complications. It is crucial that the tip be positioned distal to the left subclavian artery, but proximal to the renal arteries. The balloon is synchronized to deflate during early systole, thus decreasing left ventricular (LV) afterload. In turn, LV ejection fraction (EF) and stroke volume (SV) are enhanced, leading to reduced myocardial oxygen consumption. The balloon inflates during early diastole, thus increasing coronary blood flow and peripheral perfusion. The IABP is usually commenced at a rate of 1 : 1. Once the benefit of IABP therapy is thought to be concluded, patients are usually gradually weaned from the pump at rates of 1 : 2 to 1 : 3 over 6-12 h. Following the procedure, one must ensure that the patient has adequate radial artery pulses, suggesting no IABP interference with the subclavian arteries. A chest roentgenogram should be inspected for the location of the IABP marker, which should be 1-2 cm below the aortic arch knuckle. The patient's serum creatinine and urine output should be followed for evidence of IABP interference with the renal arteries. When used to prevent recurrent ischemia post-AMI, all patients who receive IABP therapy should also be prescribed daily aspirin and systemic heparinization with 1000-2000 U/h infused for at least 48 h to maintain activated partial thromboplastin time (aPTT) between 50 and 84 s. Contraindications to IABP use include severe peripheral vascular disease (PVD), defined as diminished femoral pulses or absent pedal pulses; aortic valve regurgitation (AVR); aortic dissection; tortuous or aneurysmal descending thoracic or abdominal aorta; and patients unable to be systemically heparinized. IABP therapy does not prohibit the use of other medications often used in AMI patients, including aspirin, systemic heparinization, angiotensin-converting enzyme inhibitors, intravenous nitroglycerine, and beta blockers. Complications of IABP therapy may include limb ischemia and hemorrhage to the femoral access site. A recently developed technique of sheathless insertion may reduce the rate of limb ischemia [5].

Assessment of coronary artery blood flow velocity using breath-hold phase contrast MR angiography in patients with acute myocardial infarction

Assessment of coronary artery blood flow velocity using breath-hold phase contrast MR angiography in patients with acute myocardial infarction

Intracoronary Levosimendan Enhances Contractile Function of Stunned Myocardium

A decrease in myofilament sensitivity to Ca2+ has been proposed as a mechanism for reversible contractile dysfunction after ischemia and reperfusion.The direct actions of intracoronary myofilament Ca2+ sensitizers on stunned myocardium have not been examined. Barbiturate-anesthetized dogs (n = 9) were instrumented for measurement of left ventricular (LV) and aortic blood pressure, cardiac output, left anterior descending coronary artery (LAD) blood flow velocity, and subendocardial segment length (percent segment shortening [%SS]). Dogs were subjected to five 5-min LAD occlusions interspersed by 5-min reperfusions. Three hours after the final reperfusion, levosimendan (1.5,3,6, and 12 micro g/min) was administered via an intracoronary catheter. Hemodynamic effects and regional myocardial function were determined under control conditions, during each LAD occlusion and reperfusion, 3 h after final reperfusion, and after 10 min equilibration at each dose of levosimendan. Three hours after the final reperfusion, %SS and the ratio of effective to total regional work were significantly (P < 0.05) decreased, and postsystolic shortening area was increased, consistent with myocardial stunning. In stunned myocardium, intracoronary levosimendan caused dose-dependent increases in %SS (2 +/- 1 at 3 h after reperfusion to 13% +/- 2% during 12 micro g/min), abolished postsystolic shortening area, and restored the ratio of effective to total regional work while producing minimum systemic hemodynamic effects. (Anesth Analg 1997;85:23-9)

Intracoronary levosimendan enhances contractile function of stunned myocardium.

A decrease in myofilament sensitivity to Ca2+ has been proposed as a mechanism for reversible contractile dysfunction after ischemia and reperfusion. The direct actions of intracoronary myofilament Ca2+ sensitizers on stunned myocardium have not been examined. Barbiturate-anesthetized dogs (n = 9) were instrumented for measurement of left ventricular (LV) and aortic blood pressure, cardiac output, left anterior descending coronary artery (LAD) blood flow velocity, and subendocardial segment length (percent segment shortening [%SS]). Dogs were subjected to five 5-min LAD occlusions interspersed by 5-min reperfusions. Three hours after the final reperfusion, levosimendan (1.5, 3, 6, and 12 microg/min) was administered via an intracoronary catheter. Hemodynamic effects and regional myocardial function were determined under control conditions, during each LAD occlusion and reperfusion, 3 h after final reperfusion, and after 10 min equilibration at each dose of levosimendan. Three hours after the final reperfusion, %SS and the ratio of effective to total regional work were significantly (P < 0.05) decreased, and postsystolic shortening area was increased, consistent with myocardial stunning. In stunned myocardium, intracoronary levosimendan caused dose-dependent increases in %SS (2 +/- 1 at 3 h after reperfusion to 13% +/- 2% during 12 microg/min), abolished postsystolic shortening area, and restored the ratio of effective to total regional work while producing minimum systemic hemodynamic effects.

In vivo and in vitro vasoactive reactions of coronary arteriolar microvessels to nitroglycerin.

The actions of nitroglycerin on the coronary microcirculation are controversial, with some laboratories reporting that coronary arterioles dilate to the drug and others reporting that they do not. Our goal was to reconcile these disparate observations. Specifically, we hypothesized that dilation of coronary arterioles by nitroglycerin is overwhelmed by intrinsic autoregulatory escape mechanisms. Accordingly, we projected that coronary arterioles would show transient, but not sustained, dilation to nitroglycerin in vivo. Furthermore, we hypothesized that isolated coronary arterioles would show sustained dilation to the drug, because intrinsic escape mechanisms would be absent under these conditions. To test these hypotheses, we measured diameter changes of canine coronary microvessels in vivo during continuous nitroglycerin administration (intracoronary infusion or epicardial suffusion) using intravital fluorescent microscopy (n = 17 dogs) at two time points: early (1-3 min), when coronary artery blood flow velocity was increased, and late (15-20 min), after blood flow velocity returned to control. Tb study responses of coronary arterioles in the absence of autoregulatory influences, we measured the diameter of isolated canine coronary arterioles to varying doses of nitroglycerin (n = 8 vessels, maximal diameter 81 +/- 4 microns). During the early phase of nitroglycerin infusion (1,3, and 10 micrograms.kg-1.min-1), coronary arterioles dilated by 4 +/- 1, 7 +/- 2, and 13 +/- 2% (all P < 0.05), whereas small arteries dilated by 1 +/- 2, 3 +/- 1, and 4 +/- 1%, respectively (P < 0.05 for the higher doses). Coronary artery blood velocity measured increased by 45 +/- 15% (3 micrograms.kg-1.min-1, P < 0.05). Suffusion of nitroglycerin (10(-5) M) dilated coronary arterioles, but not small arteries, by 17 +/- 5% (P < 0.05) between 1 and 3 min. After 15-20 min of nitroglycerin (3 micrograms.kg-1.min-1 by intracoronary infusion), diameters of coronary arterioles and coronary artery blood velocity returned to control, whereas dilation of small arteries remained significant at 4 +/- 1%. Coronary arteriolar dilation by epicardial suffusion of nitroglycerin also waned to control values by 15-20 min, whereas dilation of small arteries was observed: 5 +/- 2% (P < 0.05). In vitro, nitroglycerin caused dose-dependent dilation of coronary arterioles to their maximal diameter, which was sustained for 20 min. Thus nitroglycerin dilates coronary arterioles and small arteries. The dilation in vivo is transient for arterioles but sustained for arteries. In vitro, the dilation is sustained. Because microvessels in vitro are capable of sustaining dilation for 20 min, we conclude that the waning of arteriolar dilation in vivo is related to autoregulatory escape from dilation by nitroglycerin.

Relation between symptoms and profiles of coronary artery blood flow velocities in patients with aortic valve stenosis: a study using transoesophageal Doppler echocardiography.

To analyse profiles of coronary artery flow velocity at rest in patients with aortic stenosis and to determine whether changes of the coronary artery flow velocities are related to symptoms in patients with aortic stenosis. A prospective study investigating the significance of aortic valve area, pressure gradient across the aortic valve, systolic left ventricular wall stress index, ejection fraction, and left ventricular mass index in the coronary flow velocity profile of aortic stenosis; and comparing flow velocity profiles between symptomatic and asymptomatic patients with aortic stenosis using transoesophageal Doppler echocardiography to obtain coronary artery flow velocities of the left anterior descending coronary artery. Tertiary referral cardiac centre. Fifty eight patients with aortic stenosis and 15 controls with normal coronary arteries. Adequate recordings of the profile of coronary artery flow velocities were obtained in 46 patients (79%). Left ventricular wall stress was the only significant haemodynamic variable for determining peak systolic velocity (r = -0.83, F = 88.5, P < 0.001). The pressure gradient across the aortic valve was the only contributor for explaining peak diastolic velocity (r = 0.56, F = 20.9, P < 0.001). Controls and asymptomatic patients with aortic stenosis (n = 12) did not differ for peak systolic velocity [32.8 (SEM 9.7) v 27.0 (8.7) cm/s, NS] and peak diastolic velocity [58.3 (18.7) v 61.9 (13.5) cm/s, NS]. In contrast, patients with angina (n = 12) or syncope (n = 8) had lower peak systolic velocities and higher peak diastolic velocities than asymptomatic patients (P < 0.01). Peak systolic and diastolic velocities were -7.7 (22.5) cm/s and 81.7 (17.6) cm/s for patients with angina, and -19.5 (22.3) cm/s and 94.0 (20.9) cm/s for patients with syncope. Asymptomatic patients and patients with dyspnoea (n = 14) did not differ. Increased pressure gradient across the aortic valve and enhanced systolic wall stress result in characteristic changes of the profile of coronary flow velocities in patients with aortic stenosis. Decreased or reversed systolic flow velocities are compensated by enhanced diastolic flow velocities, particularly in patients with angina and syncope. This characteristic pattern of the profile of coronary artery flow velocities in patients with angina or syncope may be useful for differentiating those patients from asymptomatic patients.

Effect of Chronic Dynamic Cardiomyoplasty on Coronary Arterial Blood Flow Velocity

Effect of Chronic Dynamic Cardiomyoplasty on Coronary Arterial Blood Flow Velocity

Prevention of Rethrombosis After Coronary Thrombolysis in a Chronic Canine Model. I. Adjunctive Therapy with Monoclonal Antibody 7E3 F(ab')2 Fragment

We examined the efficacy of the monoclonal antibody (MoAb) 7E3 F(ab')2 fragment, an inhibitor of the platelet glycoprotein (GP)IIb/IIIa receptor, to prevent coronary artery rethrombosis after successful thrombolysis with rt-PA. The circumflex coronary artery of anesthetized dogs was instrumented with a flow probe, an electrode, and a stenosis. After recovery from the surgical procedure, the animals were reanesthetized on post-operative day 9, and vessel wall injury was induced with current applied to the intimal surface of the circumflex coronary artery. The resulting occlusive thrombus was aged for 30 min, and recombinant tissue plasminogen activator (rt-PA) was administered. The animals were allocated to receive either placebo or a single dose of 7E3 [0.8 mg/kg intravenous (i.v.) bolus] as the sole adjunctive agent. Ex vivo platelet function and coronary artery blood flow velocity were recorded on each of 5 consecutive days. Reocclusion and mortality were reduced significantly in animals treated with 7E3 as compared with the placebo-treated group. Significant inhibition of ex vivo platelet aggregation persisted for 48 h after a single injection of 7E3. The MoAb 7E3 F(ab')2 fragment is effective as the sole adjunctive agent with rt-PA for prevention of rethrombosis. The present study is unique in that it examined the efficacy of GPIIb/IIIa inhibition in an experimental model for an extended time, demonstrating the duration of antiplatelet therapy required to prevent rethrombosis after thrombolysis.

Prevention of Rethrombosis After Coronary Thrombolysis in a Chronic Canine Model. II. Adjunctive Therapy with r-Hirudin

We examined the effectiveness of the direct-acting thrombin inhibitor, recombinant hirudin (r-hirudin), for prevention of coronary rethrombosis after thrombolysis with recombinant tissue plasminogen activator (rt-PA) in a canine model of coronary artery thrombosis. The reocclusion rate of 15-30% associated with thrombolytic therapy emphasizes the need for adjunctive therapy to prevent rethrombosis. We studied r-hirudin for its potential to prevent reocclusion in a model of coronary artery thrombosis/thrombolysis. The circumflex coronary arteries of anesthetized dogs were instrumented with a flow probe, an intraluminal electrode, and a ligature stenosis. The dogs were reanesthetized on the ninth postoperative day, and intimal injury was induced with an anodal current. After occlusive thrombus formation, tissue plasminogen activator (rt-PA) was administered. The animals were allocated to receive either placebo, r-hirudin [5 mg/kg intravenously (i.v.) bolus, 2 mg/kg/h i.v., for 3.5 h] or r-hirudin (5 mg/kg i.v., bolus, 1 mg/kg/h i.v., for 12 h). Neither aspirin nor heparin was used. Ex vivo platelet function and coronary artery blood flow velocity were recorded on each of 5 consecutive days. Infarct size and residual thrombus weight were determined at the end of the protocol. r-Hirudin infusion (3.5 and 12 h) provided little benefit over rt-PA alone. Ex vivo platelet aggregation was not affected by r-hirudin. Little improvement in the incidence of reocclusion and mortality in a model of coronary artery thrombosis/thrombolysis resulted from adjunctive treatment with r-hirudin.