Intracoronary Group Research Articles

Intracoronary Compared to Intravenous Abciximab in Patients with ST Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention Reduces Mortality, Target Vessel Revascularization and Reinfarction after 1 Year

Objectives: Administration of the glycoprotein IIb/IIIa inhibitor abciximab to patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) improves outcome. Data have suggested that an intracoronary (IC) bolus might be superior to the standard intravenous (IV) administration. We have previously reported reduced short-term mortality and need for target vessel revascularization (TVR) with the IC route. We now present long-term data from our randomized trial on IC versus IV abciximab in pPCI-treated STEMI patients. Methods: A total of 355 pPCI-treated STEMI patients were randomized to either IC or IV bolus abciximab followed by a 12-hour IV infusion. Patients were followed for 1 year to observe mortality, TVR or myocardial infarction (MI) and the combination of these. Results: The two treatment arms (IV, n = 170; IC, n = 185) were similar with regard to baseline characteristics. Mortality was reduced from 10% in the IV group to 2.7% in the IC group (p = 0.004). TVR and MI were also reduced with IC administration (TVR: 14.1 vs. 7.6%, p = 0.04; MI: 11.8 vs. 5.4%, p = 0.03). Consequently, patients in the IC treatment arm had a relative risk reduction of 55% for the combined endpoint after 1 year (p = 0.002) compared to the IV treatment arm. Conclusions: In pPCI-treated STEMI patients treated with abciximab, IC bolus administration resulted in a significant reduction in mortality, TVR and MI compared to IV bolus administration.

Abstract 16740: Intracoronary versus Intravenous Administration of GP IIb/IIIa Inhibitors During Percutaneous Coronary Intervention for Acute Coronary Syndromes: A Meta-Analysis of Randomized Controlled Trials

Background: It is unclear whether intracoronary (IC) bolus administration of glycoprotein IIb/IIIa inhibitors (GPIs) is superior to intravenous (IV) administration during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS). We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of IC and IV administration. Methods and Results: We systematically searched the Cochrane library, EMBASE, and MEDLINE databases for RCTs comparing IC and IV administration of GPIs (abciximab, eptifibatide, tirofiban) during PCI. Data were pooled using random-effects models and stratified into short (1-3 months) and mid/long-term (≥6 months) follow-up durations. Ten RCTs involving 1,590 patients met our inclusion criteria. Seven of the 10 RCTs included only patients with STEMI; in the other 3 studies, the percentage of patients presenting with STEMI ranged from 26% to 63%. Within each study, the dose and duration of GPI administration was identical in the IC and IV groups. Compared to the IV group, the IC group was more likely to have complete perfusion (TIMI 3 flow) post-PCI (relative risk [RR] 1.08, 95% confidence interval [CI] 1.02, 1.15). IC administration was associated with similar bleeding rates as IV (RR 0.91, 95% CI 0.67, 1.24), but with a significant reduction in short-term target vessel revascularization (TVR) (RR 0.55, 95% CI 0.30, 0.99). IC administration was also associated with a significant reduction in short-term mortality (RR 0.49, 95% CI 0.24, 0.99), but this reduction was no longer significant in mid/long term RCTs. Conclusions: Compared to IV, IC bolus administration of GPIs has favorable effects on post-PCI TIMI flow, TVR, and short-term mortality, with similar rates of bleeding. Data regarding mid/long term outcomes were limited and inconclusive. Large RCTs with longer follow-up are required to determine long-term safety and efficacy.

Meta-Analysis of Randomized Controlled Trials of Intracoronary Versus Intravenous Administration of Glycoprotein IIb/IIIa Inhibitors During Percutaneous Coronary Intervention for Acute Coronary Syndrome

It is unclear whether intracoronary (IC) bolus administration of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes is superior to intravenous (IV) administration. We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of IC and IV administrations of GPIs in patients with acute coronary syndromes. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for RCTs comparing IC to IV administration of GPIs (abciximab, eptifibatide, tirofiban) during PCI. Data were pooled and stratified into short (1 month to 3 months) and mid-/long-term (≥6 months) follow-up durations. Ten RCTs involving 1,590 patients met our inclusion criteria. Compared to the IV group the IC group was more likely to have complete perfusion (Thrombolysis In Myocardial Infarction grade 3 flow) after PCI (risk ratio [RR] 1.08, 95% confidence interval [CI] 1.02 to 1.15). IC administration was associated with similar bleeding rates as IV (RR 0.92, 95% CI 0.68 to 1.24) but with a significant decrease in short-term target vessel revascularization (RR 0.54, 95% CI 0.30 to 0.96). IC administration was also associated with a significant decrease in short-term mortality (RR 0.45, 95% CI 0.23 to 0.90) but this decrease was no longer significant in mid-/long-term RCTs. In conclusion, compared to IV administration IC administration of GPIs has favorable effects on Thrombolysis In Myocardial Infarction flow, target vessel revascularization, and short-term mortality after PCI, with no difference in rates of bleeding. Data regarding mid-/long-term outcomes were limited and inconclusive. Large RCTs with longer follow-up are required to determine long-term safety and efficacy.

Granulation tissue is altered after intramyocardial and intracoronary bone marrow-derived cell transfer for experimental acute myocardial infarction

Bone marrow-derived mononuclear cell (BMMC) treatment in acute myocardial infarction (AMI) has been shown to have a beneficial effect. Our objective was to study in detail the histopathological process after the cell therapy after intramyocardial (IM) or intracoronary (IC) administration of BMMCs following experimental AMI. Twenty-fours pigs were randomized to the IM group (n=8), the IC group (n=8), and the control group (n=8).After 90 min of transient occlusion of the circumflex coronary artery, BMMCs were injected either intramyocardially or by a transfemoral catheter into the circumflex coronary artery. Echocardiography was performed preoperatively, postoperatively, and after a 21-day recovery period. The heart biopsies were examined histopathologically. Volumetric ex vivo CT scan was performed to evaluate calcification of the infarcted myocardium. The ejection fraction (EF) showed significant recovery in the IM group compared to the control group at Day 21 (P=.05). Despite beneficial histological changes in the infarction site in the IC group, compared to the control group, EF failed to recover. Reduction of collagen density that depicts scar formation was seen in both cell therapy groups compared to the control (P<.001). The number of mitotic cells was higher in the control group compared to the cell therapy groups (P<.001). The IC and IM groups differed significantly from each other in muscle-specific actin staining (P<.001) and smooth muscle actin staining (P<.004). The IM therapy group showed higher density for both stainings. Additionally, macrophage density was higher in the IC group compared to the IM and control groups (P<.002). Both cell therapy regimens substantially diminished tissue calcification; due to the large variation, the effect was not statistically significant. BMMC therapy launches cellular changes that affect mostly the repair process in the granulation tissue. The cell transplantation method might have some effect on the magnitude of the effect.

Intracoronary Compared to Intravenous Bolus Abciximab during Primary Percutaneous Coronary Intervention in ST-segment Elevation Myocardial Infarction (STEMI) Patients Reduces 30-day Mortality and Target Vessel Revascularization: A Randomized Trial

Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC-bolus is superior, probably due to high local concentration. In this study, we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. In 2006-2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were bleeding complications. The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus.

Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration

Background— Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. Methods and Results— A total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P =0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P =0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group ( P =0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P =0.786). Conclusions— In ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00927615.

Aborted myocardial infarction in intracoronary compared with standard intravenous abciximab administration in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction

Backgound Abciximab reduces major adverse cardiac events (MACEs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary (IC) abciximab bolus application might be more effective than a standard intravenous (IV) bolus. So far the occurrence of aborted MI, a new therapeutic target of effective treatment in STEMI, has not been evaluated in IC versus IV abciximab administration in STEMI patients undergoing primary PCI. Methods To investigate the extent of aborted MI, 154 patients undergoing primary PCI were randomized to either IC (n = 77) or IV (n = 77) bolus abciximab administration with subsequent 12-hour intravenous infusion. For assessment of infarct size and extent of microvascular obstruction, all patients underwent late enhancement magnetic resonance imaging (MRI). Aborted MI was defined by major (≥ 50%) ST-segment resolution and a lack of subsequent cardiac enzyme rise ≥ 2 the upper normal limit. We also assessed the occurrence of true aborted MI defined as the absence of myocardial necrosis in MRI. Results The incidence of aborted MI was significantly higher in the IC group (p = 0.04); true aborted MI was only observed in the IC abciximab group (p = 0.01). At multivariable logistic regression analysis, IC abciximab application was a significant independent predictor of true aborted MI (p = 0.03). Aborted MI patients had an excellent prognosis at 6-month follow-up with no MACE as compared to 24 events in patients with non-aborted MI. Conclusions IC bolus application of abciximab in STEMI patients undergoing primary PCI results in a higher incidence of aborted MI and subsequent improved clinical outcome.

Comparison of intracoronary versus intravenous administration of tirofiban in primary percutaneous coronary intervention

The purpose of this study was to compare the intravenous bolus dose of tirofiban with intracoronary bolus dose in primary percutaneous coronary intervention (PCI) with regard to in hospital and six months clinical outcomes and peak cardiac enzyme levels. We retrospectively examined 84 ST elevation myocardial infarction (STEMI) patients who underwent primary PCI from March 2006 to February 2007. All patients received the systemic bolus dose of tirofiban 10 mcg/kg either via intracoronary (IC) or intravenous (IV) route, followed by a 36 hours of IV infusion at 0.15 mcg/kg/min. Thirty six patients in IC group were compared with 48 patients in IV group in terms of peak cardiac enzyme levels, in-hospital and six months major adverse cardiac events (MACE) rates (death, myocardial infarction and repeat revascularization). Fisher's exact test, Yates Chi-square, unpaired Student's t-test and Mann-Whitney U test were used for statistical analysis. There was no difference in cardiovascular risk profile or cardiac history between two groups. At six months the incidence of MACE was 6.25% in IV group and 11.1% in IC group (p=0.45). Peak cardiac phosphokinase (CPK) levels between IV and IC groups were also statistically non significant (2657+/-2181 U/L in IV group and 2529+/-1929 U/L in IC group) (p=0.92). Intracoronary bolus application of tirofiban was not associated with reduction in MACE rates compared to intravenous administration in patients with STEMI who underwent primary PCI. Future prospective trials with higher bolus doses of IC tirofiban should addressed to clarify this issue.

Delivery of Glycoprotein IIb/IIIa Inhibitor Therapy for Percutaneous Coronary Intervention

A major goal of any antithrombotic regimen administered during percutaneous coronary intervention (PCI) is the preservation of coronary microvascular perfusion, which is critical for myocardial survival. In addition to macrovascular thrombosis, microembolization into the downstream coronary artery bed that occurs during spontaneous plaque rupture and PCI plays a prominent role in the development of microvascular dysfunction that leads to myocardial infarction. In addition to physical obstruction of the lumen by the embolus, vasoconstriction and edema due to inflammation also impair microvascular flow.1 These events likely occur more frequently during PCI performed in the setting of unstable coronary syndromes.2 With Doppler guidewire technology, it was estimated that an average of 25 embolic events occurred during primary PCI for ST-segment elevation myocardial infarction.3 Article see p 784 Platelet aggregates are important components of coronary microemboli, along with leukocytes, erythrocytes, platelet-leukocyte aggregates, cholesterol crystals, and hyalin. Platelets and leukocytes within microemboli play a particularly important role in the pathophysiological changes of blood flow by promoting in situ microvascular thrombosis, vasoconstriction, and inflammation. Interestingly, the composition of the embolized material is similar in the settings of spontaneous and catheter-induced plaque rupture.1 In animal models, distal microembolization of inert microspheres is associated with an immediate reduction in flow due to vessel occlusion, followed by enhanced blood flow due to the effects of adenosine released from the embolized myocardium into the adjacent noninvolved myocardium.4 Microembolization results in overall reduced flow reserve and the progressive loss of contractile function, which often reverses within weeks. The degree of myocardial contractile dysfunction is disproportionate to the degree of infarction and is the result of inflammation.5 However, in the clinical condition, a more complex pathophysiology exists due to the influence of multiple components of the emboli. Platelets aggregate when fibrinogen binds to the active …

Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention—Effects on soluble CD40 ligand concentrations

Introduction CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI. Methods Patients were randomized to receive IC ( n = 25) or IV ( n = 25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60 min post bolus administration. Results Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6 ± 42.13 pg/mL vs 124.9 ± 43.04 pg/mL, P = 0.49). At 60 min post PCI, however, sCD40L levels decreased by 23% ( P < 0.001) in the IC group and by 11% ( P < 0.001) in the IV group. sCD40L levels 60 min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04 ± 12.21 pg/mL vs 99.92 ± 25.89 pg/mL, P < 0.001). Conclusion In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation.

Acute homing of bone marrow-derived mononuclear cells in intramyocardial vs. intracoronary transplantation

Objectives. Cell homing optimisation after transplantation is critical in myocardial infarction (MI) cell therapy. Design. Eight pigs were randomized to receiving autologous purified 111indium-labeled bone marrow mononuclear cells (BMMCs) (108 cells/2 ml) by intramyocardial (IM) (n=4) or by intracoronary (IC) (n=4) transplantation after 90 minutes occlusion of the CX-coronary artery. Dual isotope SPECT imaging was performed 2 and 24 hours postoperatively. Two animals were additionally analyzed on the sixth postoperative day. Tissue samples from the major organs were analyzed. Results. In SPECT imaging revealed that BMMCs administered using IM injection remained in the injured area. In contrast, minor proportion of IC transplanted cells remained in the myocardium, as most of the cells showed homing in the lungs. Analysis of the biopsies showed a seven-fold greater number of cells in the myocardium for the IM method and a 10-fold greater number of cells in the lungs in the IC group (p < 0.001). Conclusions. In producing persistently high cell homing at the infarction site, the IM transplantation is superior to the IC transplantation. However, the IC administration might be more specific in targeting injured capillaries and epithelial cells within the infarcted myocardium.

Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone

Studies of the transplantation of autologous bone marrow cells (BMCs) in patients with chronic ischemic heart disease have assessed effects on viable, peri-infarct tissue. We conducted a single-blinded, randomized, controlled study to investigate whether intramuscular or intracoronary administration of BMCs into nonviable scarred myocardium during CABG improves contractile function of scar segments compared with CABG alone. Elective CABG patients (n = 63), with established myocardial scars diagnosed as akinetic or dyskinetic segments by dobutamine stress echocardiography and confirmed at surgery, were randomly assigned CABG alone (control) or CABG with intramuscular or intracoronary administration of BMCs. The BMCs, which were obtained at the time of surgery, were injected into the mid-depth of the scar in the intramuscular group or via the graft conduit supplying the scar in the intracoronary group. Contractile function was assessed in scar segments by dobutamine stress echocardiography before and 6 months after treatment. The proportion of patients showing improved wall motion in at least one scar segment after BMC treatment was not different to that observed in the control group (P = 0.092). Quantitatively, systolic fractional thickening in scar segments did not improve with BMC administration. Furthermore, BMCs did not improve scar transmurality, infarct volume, left ventricular volume, or ejection fraction. Injection of autologous BMCs directly into the scar or into the artery supplying the scar is safe but does not improve contractility of nonviable scarred myocardium, reduce scar size, or improve left ventricular function more than CABG alone.

Effects of intracoronary compared to intravenous abciximab administration in patients undergoing transradial percutaneous coronary intervention: A sub-analysis of the EASY trial

Background In the EASY trial, we have shown the clinical equivalence between abciximab bolus-only and abciximab bolus followed by 12-h infusion in a wide spectrum of patients after percutaneous coronary intervention (PCI). Some reports have suggested better outcomes following intracoronary (IC) abciximab administration compared to intravenous (IV) delivery. We sought to compare cardiac biomarkers release and early and late clinical outcomes after IC or IV abciximab bolus delivery. Methods From 1005 patients randomized in the EASY trial and undergoing transradial coronary stent implantation, 208 received IC abciximab bolus and 797 received IV abciximab bolus. Route of administration was left to operators' discretion. Creatine Kinase-MB, and Troponin-T (Tn-T) were obtained immediately prior to angiography, 4–6 h after PCI and the next day. MACE (death, MI, TVR) rate was evaluated at 30 days, 6 months and 12 months. Results There were more patients with acute coronary syndrome (75% vs 64%, P = 0.004) and previous MI (53% vs 42%, P = 0.005) in the IC group and more patients with ≥ 3 dilated sites in the IV group (2% IC vs 7% IV, P = 0.03). After PCI, the extent of Tn-T and CK-MB release remained comparable in both groups. The MACE rate was 2% in both groups at 30 days, 9% in IC bolus vs 5% in IV bolus ( P = 0.04) at 6 months and 10% in IC bolus vs 9% in IV bolus ( P = 0.50) at 12 months. By multivariate analysis, IC abciximab bolus was not associated with better outcomes at 12 months compared to IV bolus (HR 1.07, 95% CI 0.82–1.35, P = 0.62). Conclusion Compared to IV abciximab administration, IC abciximab was not associated with less cardiac biomarkers release or better clinical outcomes after uncomplicated transradial PCI. Further studies are required in clinical scenarios including patients with higher thrombotic burden and/or occluded vessels as in primary and rescue PCI.

Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction

This study assessed safety of transendocardial (TE) electromechanical-guided delivery of bone marrow mesenchymal stem cells (MSCs) after acute myocardial infarction (AMI) and compared intracoronary (IC) delivery with TE delivery. In a canine acute myocardial ischemia model, 100×106 MSCs were delivered 7 days after AMI via IC and TE routes. Functional assessment was performed by 2D echocardiogram, and detailed histopathologic analyses were performed to assess the impact of cell therapy in vascular density and fibrosis. Patterns of cell distribution in both delivery methods were also compared. There was a statistically significant reduction in the amount of myocardial ischemia in the TE group (P=0.007). Left ventricular ejection fraction (LVEF) increased 13% (mean) in the TE group (21-day follow-up) and was significantly better than that of the controls (P=0.01), but did not improve in the IC-delivery group. Dissimilar patterns of cell distribution were noted between the IC and TE groups. This study suggests that MSC treatment is probably safe and effective after AMI. In the comparison of TE and IC delivery, the TE group showed higher cell retention (clusters even in the injury center of the infarct) with an increased vascularity and greater functional improvement than did the IC group (no clusters; cells at the border of the infarct). The higher local cell density in the TE group may be important for therapeutic effectiveness.

Transplanted bone marrow mesenchymal stem cell distribution pattern in the heart: comparison of delivery routes

Objective: To identify differences in bone marrow mesenchymal stem cell (BM-MSCs) distribution when delivered by transendocardial (TE) or intracoronary (IC) route to a canine acute myocardial ischemia model. Methods: 10 adult dogs (6 TE, 6 IC) received DAPI-labeled allogenic BM-MSCs 7 days after a 3-hour occlusion/reperfusion of the left anterior descending (LAD) and were sacrificed 14 days later. Hearts were excised, perfused and sliced into 4 transverse sections from apex to base. Each slice was separated into 9 segments. Frozen and formalin-fixed tissue was preserved. Frozen sections were immunostained for α-smooth muscle actin, α-sarcomeric actinin, or factor VIII and analyzed by epifluorescence and deconvolution fluorescence microscopy (DFM). Results: At 2 weeks post delivery, the TE group showed characteristic cluster patterns at injection sites, versus a homogeneous distribution in the IC group. The total MSC density at the infarct was 715±426 and 329±56 for the TE and IC groups, respectively. By DVM, most DAPI+ BM-MSC nuclei were localized to the interstitium, outside of cardiomyocytes. Conclusions: The TE group maintained a higher density of MSC in the infarct at 2 weeks post delivery.

Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: a comparative study

Objective Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. Methods Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 μg/kg (mid-dose, n = 6, 30 injections/animal), 6 μg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 μg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. Results In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 ± 0.04 at 1 month and 0.75 ± 0.07 at 3 months compared with 0.68 ± 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 ± 0.03 at 1 month and 0.72 ± 0.04 at 3 months compared with 0.67 ± 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 ± 0.06 at 1 month and 0.85 ± 0.05 at 3 months ( P < .001) compared with 0.67 ± 0.04 at baseline. In the high group, myocardial blood flow was 0.81 ± 0.06 at 1 month and 0.83 ± .04 at 3 months ( P = .03) compared with 0.71 ± 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. Conclusions In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 μg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.

Chlamydia pneumoniae induces neointima formation in coronary arteries of normal pigs.

We evaluated the role of intracoronary, intrapulmonary and macrophage-mediated delivery of C. pneumoniae (Cp) on coronary lesion formation. Pigs were allocated to one of three coronary protocols (intracoronary, macrophage or control groups) or to a fourth-a pulmonary group. In the intracoronary group Cp was injected into the wall of the left anterior descending (LAD) and right coronary arteries (RCA) and vehicle into the circumflex (CX). In the macrophage group autologous macrophages preincubated with Cp or not were injected into the LAD and CX wall, respectively. Animals in the control group received vehicle in LAD and CX. In the pulmonary group aerosolised Cp was given intrabronchially, after a single injection of vehicle into the LAD wall. Delivery into the coronary artery wall was performed with a balloon catheter with low-profile injector ports. Seroconversion occurred in the following proportions: 5/6 (intracoronary group), 4/5 (macrophage group), 0/6 (control group), and 1/6 (intrapulmonary group). Significantly higher maximal intimal thickness (MIT) was observed in LADs of intracoronary and pulmonary groups when compared to corresponding CXs. The presence of Cp antigen was associated with higher MIT (r=0.73; P<0.0001). Injection of macrophages into the coronary artery wall did not induce proliferation. Arteries without coronary interventions were morphologically normal. Intracoronary and intrapulmonary but not macrophage-mediated Cp inoculation were associated with moderate intimal proliferation in the absence of a lipid-rich diet. Pre-existing coronary lesions seem a prerequisite for Cp-induced proliferation.

Efficacy of intracoronary or intravenous VEGF165in a pig model of chronic myocardial ischemia

OBJECTIVESWe sought to optimize vascular endothelial growth factor (VEGF) treatment for therapeutic angiogenesis in myocardial ischemia, we explored the efficacy of five different regimens.BACKGROUNDAlthough VEGF165is one of the most potent pro-angiogenic growth factors, VEGF165treatment for myocardial ischemia has been hampered by low efficacy and dose-limiting hypotension after systemic or intracoronary delivery.METHODSThis study evaluated the effect of intravenous or intracoronary rhVEGF165in the presence or absence of nitric oxide (NO) synthase inhibition in a porcine model of chronic myocardial ischemia. Forty-two Yorkshire pigs with chronically occluded left circumflex coronary arteries were randomly assigned to receive 10 μg/kg of VEGF165: 1) rapid (40 min) intravenous VEGF1650.25 μg/kg/min, 2) slow (200 min) intravenous VEGF1650.05 μg/kg/min, 3) rapid intracoronary VEGF1650.25 μg/kg/min, 4) rapid intracoronary VEGF1650.25 μg/kg/min + nitro-L-arginine methyl ester hydrochloride (L-NAME) or 5) rapid vehicle infusion.RESULTSIntracoronary and intravenous VEGF165induced hypotension. Intracoronary VEGF-induced hypotension was blocked by L-NAME. Coronary angiography three weeks after treatment showed improvement in collateral index in both intracoronary groups but not the intravenous VEGF165groups. Likewise, myocardial blood flow and microvascular function in the ischemic territory improved in both intracoronary groups but not in the intravenous groups. Global and regional myocardial function showed no significant improvements in any groups.CONCLUSIONSIntracoronary infusion of VEGF165significantly improves blood flow to the ischemic myocardium. Concomitant administration of L-NAME inhibits VEGF-induced hypotension while most likely preserving VEGF-induced angiogenesis. Intravenous infusion of VEGF165was not effective in augmenting either myocardial flow or function in this model.

Intracoronary versus intravenous streptokinase in acute myocardial infarction

To assess the relative efficacy of coronary thrombolysis using intracoronary versus intravenous streptokinase, 32 patients with acute myocardial infarction were randomly assigned to receive intracoronary (n = 17) and intravenous streptokinase (n = 15). All patients underwent selective coronary arteriography before and after administration of streptokinase by either route within 4 hours of the onset of symptoms. Intravenous streptokinase was given as 750,000 units over 30 minutes, while a mean dose of 180,000 units was required for thrombolysis in the group having intracoronary delivery. Recanalization occurred in 71.4% (10 of 14) of patients receiving streptokinase, by the intracoronary group in contrast to only 25% of patients (3 of 12) who received the drug intravenously (P < 0.05). Spontaneous thrombolysis was seen in 17.6% and 20% of the patients in the groups having intracoronary and intravenous delivery, respectively. Bleeding complications were few in both groups. Thus, when baseline coronary arteriography is performed, recanalization with intracoronary streptokinase is more effective in the treatment of acute myocardial infarction than intravenous streptokinase.

Effects of (+)-octanoylcarnitine in intact myocardium.

Fatty acid metabolites (long-chain esters of CoA and carnitine) which collect in ischemic myocardium can form amphiphiles capable of disrupting subcellular performance. It is important to document the role of these amphiphiles in intact tissue. D-Octanoylcarnitine was chosen because of its previously described effects on inhibiting palmitoylcarnitine transferase (PCT-II) in in vitro and in vivo liver preparations. This inhibition will shift tissue levels of CoA and carnitine intermediates and thus alter amphiphile levels. The compound's actions in cardiac muscle are unknown. Dose response curves were developed in intact hearts to test the influence of D-octanoylcarnitine at pharmacological concentrations. Measurements were obtained in working, extracorporeally perfused, swine hearts. Drug was administered either systemically (IV) or via direct intracoronary (IC) infusions into the left anterior descending coronary circulation. Excess fatty acids were provided to ensure adequate fatty acid substrate for oxidation. Coronary flow was controlled at aerobic levels. Systemic administration of D-octanoylcarnitine (0.8-6.8 mM) resulted in transient peripheral hypotension which caused correlative decreases in 14CO2 production from labeled palmitate. Infusion of D-octanoylcarnitine (0.5-3.9 mM) IC did not cause appreciable hypotension and was not associated with suppression of fatty acid oxidation. No build-up of carnitine esters was noted in treated hearts but acyl CoA levels were reduced (p less than or equal to 0.002). This latter finding was modestly related to increasing dose schedule of the compound in the IC group. The lack of suppression in fatty acid oxidation argues against significant inhibition of PCT II and lessens the attractiveness of using D-octanoylcarnitine in intact myocardium to selectively block fatty acid utilization at this locus.