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Abstract Background Intracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI. Methods We searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included. Results The proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37–0.80) and heart failure (RR: 0.48, 95% CI: 0.25–0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration. Conclusions When considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considered.

Background: Intracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI. Methods: We searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included. Results: The proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37–0.80) and heart failure (RR: 0.48, 95% CI: 0.25–0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration. Conclusions: When considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considered. [ABSTRACT FROM AUTHOR]

Abstract Background Allogeneic cardiac-derived progenitor cells (CPC) without immunosuppression could provide an effective ancillary therapy to improve cardiac function in reperfused myocardial infarction. We set out to perform a comprehensive preclinical feasibility and safety evaluation of porcine CPC (pCPC) in the infarcted porcine model, analyzing biodistribution and mid-term efficacy, as well as safety in healthy non-infarcted swine. Methods The expression profile of several pCPC isolates was compared with humans using both FACS and RT-qPCR. ELISA was used to compare the functional secretome. One week after infarction, female swine received an intracoronary (IC) infusion of vehicle (CON), 25 × 106 pCPC (25 M), or 50 × 106 pCPC (50 M). Animals were followed up for 10 weeks using serial cardiac magnetic resonance imaging to assess functional and structural remodeling (left ventricular ejection fraction (LVEF), systolic and diastolic volumes, and myocardial salvage index). Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Biodistribution analysis of 18F-FDG-labeled pCPC was also performed 4 h after infarction in a different subset of animals. Results Phenotypic and functional characterization of pCPC revealed a gene expression profile comparable to their human counterparts as well as preliminary functional equivalence. Left ventricular functional and structural remodeling showed significantly increased LVEF 10 weeks after IC administration of 50 M pCPC, associated to the recovery of left ventricular volumes that returned to pre-infarction values (LVEF at 10 weeks was 42.1 ± 10.0% in CON, 46.5 ± 7.4% in 25 M, and 50.2 ± 4.9% in 50 M, p

The article presents the new possibilities of preventing the onset of irreversible myocardial damage during ischemia and effective approaches undertaken in the early reperfusion period (per - and postconditioning of the myocardium) through coronary the introduction of cardioprotective drugs. Practitioners need medicines, which have fewer complications and are universal this is by far the metabolic drugs. The author surveyed 300 patients (three groups) with acute coronary syndrome (ACS) hospitalized no later than 4 hours from the beginning of anginal attack. Patients in group I (n=109) in the prehospital phase was carried out by the system tromboliticescoy therapy (TLT) in combination with intravenous etilmetilgidroksipiridina succinate (200 mg), which the hospital performed mechanical recanalization and angioplasty of the infarct-related coronary artery (IRA) with intracoronary introduction of etilmetilgidroksipiridina succinate (200 mg). Patients in group II (n=101) etilmetilgidroksipiridina succinate (200 mg) primary intracoronary injected during the endovascular procedure. Patients III (control) group (n=90) was carried out only angioplasty of the IRA. Conclusions: the effect of restoration of coronary circulation set after conducted thrombolytic therapy with intracoronary administration of etilmetilgidroksipiridina succinate immediately after successful angioplasty of the IRA, which helped to restore adequate blood flow to prevent relapses and extension of the necrosis zone, transition to a higher angina functional classes.

Pharmaceutical treatment of coronary heart disease (CHD) should be able to solve the key task – reduction of myocardial oxygen demand, or improvement of oxygen supply via vasodilatation. Currently, metabolic therapy of CHD is of particular interest, since it can reduce myocardial oxygen demand and substantially increase the effectiveness of oxygen utilisation in myocardial ischemia settings. The study was aimed at investigating the effectiveness of pre-hospital therapy with a cytoprotector mexicor, with subsequent intracoronary mexicor administration in the first hours of acute myocardial infarction (AMI). In total, 112 AMI patients, hospitalised no later than 4 hours after AMI onset, were included in the study. Successful angioplasty of infarct-related coronary artery (IRCA) and intracoronary administration of a cardio-protector mexicor were associated with a substantial improvement in clinical effectiveness of coronary blood flow normalisation and prevention of myocardial reperfusion injury.

Background Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. Objectives To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. Results Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26–0.99; p = 0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26–1.20; p = 0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07–0.99; p = 0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n = 2574). Conclusions In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial. [ABSTRACT FROM AUTHOR]

Glycoprotein IIb-IIIa (GPIIb-IIIa) antagonists have the capacity to destabilize coronary thrombi and restore vessel patency. Antagonist concentration and residence time, which can be increased by local intracoronary (LIC) administration, and thrombus age may be key factors that influence thrombus stability. Light transmission aggregometry was used to examine the effects of exposing human platelet aggregates to extremely high local levels of GPIIb-IIIa antagonists versus conventional therapeutic levels in vitro. Freshly-formed or aged platelet aggregates were subjected to GPIIb-IIIa antagonists (abciximab, eptifibatide) or direct thrombin inhibitor bivalirudin at concentrations simulating either conventional intravenous (IV) or LIC administration. The degree of antagonist-induced disaggregation was significantly higher using elevated (LIC) doses versus conventional (IV) doses (60.1 % vs. 7.4 % for abciximab, 41.6 % or 45.3 % vs. 17.6 % for eptifibatide, p < 0.01). Bivalirudin did not promote disaggregation. Microscopy confirmed noticeably smaller, more dispersed aggregates for antagonist LIC treatments. Dosing at LIC levels also induced more disaggregation than IV levels when aggregates were aged for 30 min prior to exposure. An in vitro perfusion model was used to simulate the fluid dynamics of IV or LIC administration of abciximab using a microporous local drug delivery balloon catheter such as the Atrium ClearWay™ RX. The perfusion model resulted in more rapid thrombus clearance with LIC dosing levels compared to IV. In summary, boosting the concentration of GPIIb-IIIa antagonists enhances dispersal of human platelet aggregates in vitro. These data provide a foundation for investigating increased local concentrations of GPIIb-IIIa antagonists in patients, as with LIC administration. [ABSTRACT FROM AUTHOR]

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. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin/c-kit/GFP cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin/c-kit/GFP CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with a more homogeneous distribution of CSCs in the infarcted region and a greater increase in viable tissue in this region, suggesting greater formation of new cardiomyocytes. Intracoronary CSC delivery resulted in improved function in the infarcted region, as well as in improved global LV systolic and diastolic function, and in decreased LV dilation and LV expansion index; the magnitude of these effects was similar to that observed after intramyocardial injection. We conclude that, in the murine model of reperfused MI, intracoronary CSC infusion is at least as effective as intramyocardial injection in limiting LV remodeling and improving both regional and global LV function. The intracoronary route appears to be superior in terms of uniformity of cell distribution, myocyte regeneration, and amount of viable tissue in the risk region. To our knowledge, this is the first study to report that intracoronary infusion of stem cells in mice is feasible and effective. [ABSTRACT FROM AUTHOR]

A 57 year-old man presenting with acute inferior myocardial infarction underwent percutaneous coronary intervention. Following the placement of TAXUS Liberte 2.5 × 24 mm (Boston Sientific, USA), for 99% stenosis with delay, severe vasospasm occurred at distal portion of the stent. However, persistent vasospasm was observed despite ISDN (isosorbide dinitrate), nitroprusside, and nicorandil, were used to control the repetitive vasospasm during the course of 90 min. Then the decision was made to use intra-coronary bolus of Rho-kinase inhibitor, fasudil 100 μg/kg. Then the vasospasm resolved and no recurrence was observed during the procedure and hospital stay for 25 days. We experienced a valuable case, whose repetitive vasospasm was resolved with intracoronary administration of Rho kinase inhibitor. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the feasibility of intracoronary application of endothelial progenitor cells and the subsequent distribution within the heart. Methods: Endothelial progenitors cells (EPCs) cultured from rat bone marrow were identified by double-positive staining with Dil-Ac-LDL and BS1-lectin. Twenty-four hours before cell transplantation, EPCs were labeled with 5-bromo-2′-deoxyuridine (BrdU). Cells (5×105 in 250-μl medium) were injected into healthy rats, either as intracoronary application (n=11) or as intramyocardial injection (n=6). At 15 min or 3 days posttransplantation, hearts as well as other organs (lung, liver, kidney, and spleen) were collected and processed for subsequent BrdU immunohistochemistry. The number of BrdU-positive cells per tissue area was counted. Results: Compared to intramyocardial injection, intracoronary administration resulted in more than twice as much positive cells in the heart (P<.05), with no local differences within the heart. Whereas after 15 min, EPCs were equally distributed in all examined organs (except for the spleen), cells that were still present after 3 days, approximately 10%, were selectively restricted to the heart. Conclusions: Our data indicate that the intracoronary application provides a promising technique for EPC transplantation in the rat heart. [Copyright &y& Elsevier]

We retrospectively studied 3 patients with Kawasaki disease (KD) and acute myocardial infarction (AMI) who were treated with intracoronary administration of tissue-type plasminogen activator (t-PA). Two-dimensional echocardiogram on the next day of the treatment revealed reduction of thrombus and improvement of the cardiac function in all 3 patients. However, a 12-month-old patient treated with 200,000 U/kg of t-PA at 48 h after the onset of AMI died of recurrent myocardial infarction. The other 2 patients treated with 400,000 and 800,000 U/kg, respectively, showed clear, though not prompt, improvement in clinical symptoms and laboratory data. The intracoronary thrombolytic therapy using high-dose t-PA appears effective in treating AMI associated with KD. [ABSTRACT FROM AUTHOR]

Study objective – The aim was to evaluate the effective and safe dosage for intracoronary administration of nicorandil (2-nicotinamidoethyl nitrate) in dogs.Design – Five ml of saline with or without nicorandil (0.025, 0.25, 1.0 or 2.5 mg) was constantly infused into the left anterior descending coronary artery (LAD) in 1 min without blood flow reduction in group A (normoxic group, n = 5) and with 50% blood flow reduction of the control value in group B (ischaemic group, n = 5).Subjects – 10 mongrel dogs of either sex were used, weight 14.6–20.5 kg.Measurements and main results – The myocardial weight of the perfused area was 33.2(SD 7.9) g. In group A, LAD blood flow increased from 28.4(8.6) to 86.3(25.0) ml·min−1, p<0.05, following intracoronary infusion of 0.25 mg nicorandil. Higher doses caused no further increase. In both groups, high doses (1.0 mg or more) suppressed regional myocardial contraction, expressed as % segment shortening, from 20.0(4.7) to 10.0(9.0)%, p<0.05, in group A, and from 12.7(8.5) to 6.5(5.6)%, p<0.05, in group B. Multiple ventricular premature beats developed in both groups only at the dose of 2.5 mg: 6.8(5.5) beats·min−1 in group A and 4.5(4.2) beats·min−1 in group B. Ventricular fibrillation developed in two dogs in group B. Nicorandil did not affect the local bipolar electrocardiogram of the subendo- and subepicardium in the perfused area in either group.Conclusions – Intracoronary administration of 0.25 mg of nicorandil was effective for coronary vasodilatation without deleterious mechanical or electrical effects. Larger doses of the agent showed adverse effects depending on the dosages. [ABSTRACT FROM PUBLISHER]

Gene therapy is a promising approach in the treatment of cardiovascular diseases. The vectors available for cardiovascular gene therapy have significantly improved over time. Cardiac tropism is a primary characteristic of an ideal vector along with a long-term expression profile and a minimal risk of cellular immune response. Preclinical and clinical studies have demonstrated that adeno-associated viral (AAV) vectors are one of the most attractive vehicles for gene transfer. AAV has gained great popularity in the last years because of its biological properties and advantages over other viral vector systems. In this chapter we will describe methods for intracardiac delivery of AAV vector in rats., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Allogeneic cardiac-derived progenitor cells (CPC) without immunosuppression could provide an effective ancillary therapy to improve cardiac function in reperfused myocardial infarction. We set out to perform a comprehensive preclinical feasibility and safety evaluation of porcine CPC (pCPC) in the infarcted porcine model, analyzing biodistribution and mid-term efficacy, as well as safety in healthy non-infarcted swine. Methods: The expression profile of several pCPC isolates was compared with humans using both FACS and RT-qPCR. ELISA was used to compare the functional secretome. One week after infarction, female swine received an intracoronary (IC) infusion of vehicle (CON), 25 × 106 pCPC (25 M), or 50 × 106 pCPC (50 M). Animals were followed up for 10 weeks using serial cardiac magnetic resonance imaging to assess functional and structural remodeling (left ventricular ejection fraction (LVEF), systolic and diastolic volumes, and myocardial salvage index). Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Biodistribution analysis of 18F-FDG-labeled pCPC was also performed 4 h after infarction in a different subset of animals. Results: Phenotypic and functional characterization of pCPC revealed a gene expression profile comparable to their human counterparts as well as preliminary functional equivalence. Left ventricular functional and structural remodeling showed significantly increased LVEF 10 weeks after IC administration of 50 M pCPC, associated to the recovery of left ventricular volumes that returned to pre-infarction values (LVEF at 10 weeks was 42.1 ± 10.0% in CON, 46.5 ± 7.4% in 25 M, and 50.2 ± 4.9% in 50 M, p < 0.05). Infarct remodeling was also improved following pCPC infusion with a significantly higher myocardial salvage index in both treated groups (0.35 ± 0.20 in CON; 0.61 ± 0.20, p = 0.04, in 25 M; and 0.63 ± 0.17, p = 0.01, in 50 M). Biodistribution studies demonstrated cardiac tropism 4 h after IC administration, with substantial myocardial retention of pCPC-associated tracer activity (18% of labeled cells in the heart), and no obstruction of coronary flow, indicating their suitability as a cell therapy product. Conclusions: IC administration of allogeneic pCPC at 1 week after acute myocardial infarction is feasible, safe, and associated with marked structural and functional benefit. The robust cardiac tropism of pCPC and the paracrine effects on left ventricle post-infarction remodeling established the preclinical bases for the CAREMI clinical trial (NCT02439398). [ABSTRACT FROM AUTHOR]