Coronary Artery Reperfusion

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue

Pranolium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72226/1/j.1527-3466.1983.tb00447.x.pd

The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]

BACKGROUND: Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial. METHODS: Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge. RESULTS: There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01). CONCLUSION: Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients

Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research

Efficacy of platelet depletion in counteracting the detrimental effect of acute hypercholesterolemia on infarct size and the no-reflow phenomenon in rabbits undergoing coronary artery occlusion-reperfusion.

It has recently been demonstrated that acute hypercholesterolemia per se, independently of its atherogenic effect, increases the extent of myocardial injury in rabbits undergoing coronary artery occlusion-reperfusion. Estimation of myocardial blood flow after reperfusion indicated that this deleterious effect was due to a vascular obstruction that limited the efficacy of reperfusion. The goal of this study was to evaluate the role played by platelets in contributing to the occurrence of this deleterious effect. Accordingly, New Zealand White rabbits were fed a standard laboratory chow diet (plasma cholesterol 67 +/- 12 mg/dl) or a 2% cholesterol-enriched diet for 3 days (plasma cholesterol 329 +/- 70 mg/dl). In a first series of experiments autologous platelets were labeled with 111In-oxine. After labeling, platelets were reinjected in the same animal and 30 min later coronary artery occlusion (CAO) was induced. CAO was maintained for 30 min followed by 5.5 hr of reperfusion. The animals were then killed, their hearts were excised, and each left ventricle was divided into ischemic and normally perfused samples. Myocardial samples were then counted in a gamma counter. Platelet accumulation ratio, i.e., 111In activity in the ischemic myocardium per gram of tissue divided by 111In activity in the normal myocardium per gram of tissue, was calculated. The ratio was 2.4 +/- 0.2 (mean +/- SEM) in controls (n = 7) and 10.3 +/- 1.0 in the cholesterol-fed group (n = 6, p less than .001), indicating that a marked accumulation of platelets occurs in the ischemic myocardium of hypercholesterolemic rabbits. To evaluate the importance of this phenomenon, another series of experiments was performed.(ABSTRACT TRUNCATED AT 250 WORDS

The effect of acute hypercholesterolemia on myocardial infarct size and the no-reflow phenomenon during coronary occlusion-reperfusion.

The goal of this study was to determine the effects of acute hypercholesterolemia on the evolution of myocardial infarction in a preparation of coronary occlusion-reperfusion. New Zealand white rabbits were fed a 2% cholesterol-enriched diet for 3 days (plasma cholesterol 329 +/- 70 mg/dl), or maintained on the control diet (plasma cholesterol 67 +/- 12 mg/dl). Temporary (30 min) coronary artery occlusion was performed in open-chest rabbits with a suture snare. The snare was released to permit reperfusion. When the animals were killed 5.5 hr later, left ventricles were cut into 3 mm slices. Infarct size was determined by planimetry of tetrazolium-stained slices while the area at risk of infarction (hypoperfused zone) was determined by planimetry of the "cold spots" on autoradiograms of the slices that contained 99m Tc-labeled microspheres that had been injected 1 min after occlusion. Infarct size, expressed as percent of the hypoperfused zone, was 42.8 +/- 1.3% (n = 10) in the control group and was increased by approximately 100% in cholesterol-fed animals to 83.7 +/- 2.0% (n = 10, p less than .001). To test the hypothesis that vascular obstruction (no reflow) might account for the larger infarct size, thioflavin S was injected immediately before the animals were killed to demarcate perfused myocardium in three additional groups of animals: standard chow-fed rabbits (n = 5), cholesterol-fed rabbits (n = 5), and standard chow-fed rabbits that, in addition, received an infusion of isoproterenol (0.1 microgram/kg/min, n = 6), an intervention believed to increase infarct size through a mechanism not dependent on the no-reflow phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS