Acute Myocardial Infarction In Man Research Articles

P4027Safety and high-grade myocardial uptake of Whartons Jelly Plurioptent Stem Cells transcoronary transfer in acute myocardial infarction in man

P4027Safety and high-grade myocardial uptake of Whartons Jelly Plurioptent Stem Cells transcoronary transfer in acute myocardial infarction in man

Monocyte chemoattractant protein-1: A dichotomous role in cardiac remodeling following acute myocardial infarction in man?

Monocyte chemoattractant protein-1 (MCP-1) is elevated after acute myocardial infarction (AMI), and potentiates left ventricular (LV) remodeling in murine models of AMI. We examined the relationships between serum MCP-1, change in LV function and biomarkers related to remodeling in a cohort of AMI patients. Serum MCP-1 concentrations were measured in 100 patients (age 58.9+/-12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h), 12 and 24 weeks; cardiac magnetic resonance imaging and measurement of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9 occurred at each time-point. MCP-1 increased significantly from 697 [483, 997]pg/mL at baseline to 878 [678, 1130]pg/mL at 24 weeks (p<0.001). MMP-3 concentration increased while MMP-9 decreased significantly over time; MMP-2 concentration did not change significantly. BASELINE MCP-1 correlated with change in (Delta) LV end-systolic volume index (DeltaLVESVI; r= -0.48, p=0.01) and with DeltaLV ejection fraction (DeltaLVEF; r=0.50, p=0.02). However, DeltaMCP-1 correlated positively with DeltaLVESVI (r=0.40, p=0.006) and negatively with DeltaLVEF (r= -0.36, p=0.004). MCP-1 had no relationship with any MMP. MCP-1 may have a dichotomous role following AMI, aiding early infarct healing but potentiating later remodeling, which merits further study before any therapeutic trials of MCP-1 modulation in humans.

Cardioprotective effects of mineralocorticoid receptor antagonists at reperfusion

Pre-treatment with mineralocorticoid receptor (MR) antagonists is reported to reduce myocardial infarct size from ischaemia/reperfusion. Here, we tested whether the MR antagonists potassium canrenoate and eplerenone could protect in the more clinically relevant schedule of administration at the end of ischaemia. In all models, hearts were subjected to 30 min regional ischaemia followed by 120 min (rabbits 4 h) reperfusion. A bolus of canrenoate 5 min prior to reperfusion in open-chest mice decreased infarct size in a dose-dependent manner. Maximum protection was seen at 1 mg/kg where infarction was 18% of that in the control (P < 0.001). Ecto-5'-nucleotidase (CD73) as well as adenosine A(2b) receptor knock-out mice could no longer be protected, suggesting a role for adenosine and the A(2b) receptor in the mechanism. A 1 mg/kg bolus of canrenoate prior reperfusion also reduced infarct size in open-chest rabbits. To explore the underlying mechanisms, we studied isolated rat hearts. Eplerenone (10 microM) at the end of ischaemia was similarly protective in the rat heart and the protection was abolished by co-treatment with inhibitors of the adenosine receptor, protein kinase C, PI3-kinase, and ERK. In addition, eplerenone or canrenoate treatment increased phosphorylation of the pro-survival kinases Akt and ERK1/2 at reperfusion in the rat hearts. Taken together, MR antagonists when given at the end of ischaemia are highly effective and potent cardioprotective drugs with a signalling similar to that of ischaemic pre-conditioning and, hence, could be a very promising candidate for the treatment of acute myocardial infarction in man.

Plasma apelin concentration is depressed following acute myocardial infarction in man

Apelin, a novel peptide with a putative role in cardiovascular homeostasis, has gained interest as an endogenous inotrope, but has yet to be described following acute myocardial infarction (AMI) in man. We aimed to characterize plasma apelin concentrations following AMI and to examine its relationship with clinical and prognostic biomarkers. Plasma concentrations of apelin, N-terminal probrain natriuretic peptide (NT-proBNP), norepinephrine, and arginine vasopressin were measured in 100 patients [mean age 58.9 +/- 12 (SD) years, 77% male] admitted with AMI, with echocardiographic left ventricular (LV) ejection fraction <40%, at mean 46 h after admission and at 24 weeks. Cardiac magnetic resonance imaging was performed pre-discharge and at 24 weeks. Thirty-eight subjects with no cardiac history acted as controls. Apelin concentration was reduced early after AMI (0.54 +/- 0.25 vs. 3.22 +/- 3.01 ng/mL, P <0.001) and remained low at 24 weeks, although it did increase significantly from baseline to 0.62 +/- 0.36 ng/mL, P = 0.030. Apelin had no relationship with any parameter of LV function over time. A relationship was found between baseline apelin and norepinephrine (r = 0.26, P = 0.008). Both NT-proBNP and norepinephrine correlated with adverse ventricular function after AMI. Plasma apelin concentration is reduced early after AMI, increases significantly over time, but remains depressed at 24 weeks.

BAY 58-2667, a nitric oxide-independent guanylyl cyclase activator, pharmacologically post-conditions rabbit and rat hearts

BAY 58-2667 (BAY-58) directly activates soluble guanylyl cyclase without tolerance in a nitric oxide (NO)-independent manner, and its haemodynamic effect is similar to that of nitroglycerin. We tested whether BAY-58 could make both rabbit and rat hearts resistant to infarction when given at the end of an ischaemic insult. All hearts were exposed to 30 min regional ischaemia followed by 120-(isolated hearts) or 180-(in situ hearts) min reperfusion. BAY-58 (1-50 nM) infused for 60 min starting 5 min before reperfusion significantly reduced infarction from 33.0 +/- 3.2% in control isolated rabbit hearts to 9.5-12.7% (P < 0.05). In a more clinically relevant in situ rabbit model, infarct size was similarly reduced with a loading dose of 53.6 microg/kg followed by a 60 min infusion of 1.25 microg/kg/min (41.1 +/- 3.1% infarction in control hearts to 16.0 +/- 4.4% in treated hearts, P < 0.05). BAY-58 similarly decreased infarction in the isolated rat heart, and protection was abolished by co-treatment with a protein kinase G (PKG) antagonist, or a mitochondrial K(ATP) channel antagonist. Conversely, N(omega)-nitro-L-arginine-methyl-ester-hydrochloride, a NO-synthase inhibitor, failed to block BAY-58's ability to decrease infarction, consistent with the latter's putative NO-independent activation of PKG. Finally, BAY-58 increased myocardial cGMP content in reperfused hearts while cAMP was unchanged. When applied at reperfusion, BAY-58 is an effective cardioprotective agent with a mechanism similar to that of ischaemic pre-conditioning and, hence, should be a candidate for treatment of acute myocardial infarction in man.

Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study

To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (Echo) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man. Plasma MMP-2 and MMP-9 were assayed at intervals (0-12, 12-24, 24-48, 48-72, 72-96, and > 96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. Echo assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138-262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005-0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0-12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to < 0.001) and neutrophil count (P = 0.014 to < 0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively). Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI.

Preservation From Left Ventricular Remodeling by Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Use of Granulocyte-Colony–Stimulating Factor (FIRSTLINE-AMI)

Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man. Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control). G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.

Plasma MMP-9 and MMP-2 following acute myocardial infarction in man: correlation with echocardiographic and neurohumoral parameters of left ventricular dysfunction

Background Left ventricular dilatation and elevated plasma natriuretic peptide levels predict adverse prognosis and the development of congestive heart failure after myocardial infarction. Altered matrix metalloproteinase (MMP) activity has been implicated in the structural changes associated with development of heart failure after myocardial injury. The aims of this study were to investigate plasma MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations following acute myocardial infarction and their relationships with measures of left ventricular function. Methods and results Plasma MMP-2, MMP-9, TIMP-1, and N-terminal proBNP (N-BNP) were quantified on 5 consecutive days in 60 patients with acute myocardial infarction (39 anterior). N-BNP was measured on day 3. Echocardiographic assessment of left ventricular wall motion index and volumes was performed during admission and 6 weeks later. Plasma MMP-9 showed peaks on days 1 and 4. MMP-2 levels, similar on each day, were higher after inferior myocardial infarction. Plasma MMP-2 showed strong, inverse correlation with left ventricular volumes during and after admission. Plasma MMP-9 correlated directly with N-BNP ( P = .022) and inversely with wall motion index during admission ( P = .05). TIMP-1 levels were higher after anterior (1269, 870-1466 ng/mL) compared with inferior (1183, 856-1419 ng/mL, P = .05) acute myocardial infarction and fell from day 1 through 5 ( P < .0005). Conclusion Plasma MMP-9 concentration correlates with neurohormonal and echocardiographic measures of left ventricular dysfunction after myocardial infarction. Higher left ventricular volumes are associated with lower plasma MMP-2 concentrations. Circulating MMP concentrations may provide insights into left ventricular remodeling after acute myocardial infarction.

Keith A. Reimer, MD, PhD: 1945–2002

Keith Arnold Reimer, MD, PhD, a well-known experimental cardiologist and cardiac pathologist and a Professor of Pathology at Duke University died on March 15, 2002, at the age of 56. The cause of death was metastatic carcinoma of the kidney. His disease was advanced when it was diagnosed in September of 2001, and it essentially incapacitated him for the remainder of his life. Keith was born in Beatrice, a small town in Nebraska, on April 10, 1945. He graduated from high school in a class of 7 students. Typical of Keith is the fact that by the time he had graduated, he had taken every course offered by the school except Home Economics. After graduating from high school, he attended Bethel College in North Newton, Kansas, from which he graduated in 1967. While at Bethel, he met and married Susan Stuckey. Although this educational history seems an unlikely prelude to a career in science, he became a very successful scientist.⇓ I first met Keith on a spring day 34 years ago, when a young medical student with a red beard turned up in my laboratory at Northwestern University Medical School. At this time, he was finishing his second year in medical school and was searching for a laboratory in which to pursue graduate work. His aim was to enter the MD, PhD program at Northwestern. The goal of this program was to produce physicians trained as scientists. In Keith’s case, the science was experimental pathology. I questioned him carefully about why he wanted to follow a course of study that would lead him to become an expert in the field of cell injury, simply because research in cell injury was unpopular in 1968. Few physicians and even fewer scientists cared why cardiac muscle cells …

A Case of Acute Myocardial Infarction In Man Treated with Chemotherapy containing Doxorubicin for Non-Hodgkin Lymphoma.

Anthracyclines have been widely used in cancer therapy due to their efficacy in the treatment of various solid tumors and hematologic malignancy. Cumulative dose-related cardiotoxicity is a well-known toxicity of anthracyclines. Particularly, at total doses of more than 550 mg/m 2 , therapy with anthracyclines can produce irreversible cardiac injury. Anthracycline-induced cardiac toxicity usually manifests by congestive heart failure or arrhythmia. In contrast, acute myocardial infarction is a rare event of anthracycline-induced heart diseases. A 31-year-old man with non-Hodgkin lymphoma (NHL and a single cardiac risk factor, smoking, presented with chest pain after receiving a 2 nd round of CEOP-BLAM chemotherapy. An electrocardiogram revealed ST segment elevation in the inferior leads consistent with acute myocardial infarction. An echocardiogram revealed an ejection fraction of 60% and severe hypokinesia in the inferior wall. Three days later, coronary angiography revealed 50% of luminal stenosis of right coronary artery (RCA and near total occlusion with a large thrombi in the m-RCA. Following balloon angioplasty and stent insertion, the patient was transferred to the coronary care unit and continuous intravenous heparin infusion was started. On the 10th day, the patient was discharged in good condition. Six months later, follow-up coronary angiography showed no significant lesion in the right coronary artery. In a young man with NHL, we report an acute myocardial infarction after a 2nd course of CEOP-BLAM chemotherapy with a review of the relevant literature. (Korean Circulation J 2001;30(5 :507-511

Inhibition by beta-blockade of the ST segment elevation after acute myocardial infarction in man.

The changes in height and extent of the ST segment elevation after the administration of the β-blocking drug practolol to nine patients with acute myocardial infarction have been studied. In all the patients there was a reduction in the area of ST segment elevation recorded over the surface of the chest and in eight of the nine there was a reduction in the total height (ΣST) and mean height (ST) of the ST segment elevation. These findings are discussed in relation to (1) quantitating the extent and severity of the ischaemic lesion in man, and (2) the reduction in the extent and severity of the ischaemia by β-blockade.

The challenge of acute coronary syndromes

I n t roduc t ion Acute coronary syndromes (ACS) pose multiple challenges to physicians, cardiologists, internists, and emergency department physicians, as well as to general practitioners. General practitioners are responsible for early recognition of ACS among patients with chest discomfort and identification of patients who require hospital admission; cardiologists and other specialists prescribe initial and subsequent medical therapy and select patients for immediate, early, or elective revascularisation by percutaneous techniques (balloon angioplasty, stent) or bypass surgery. A systematic approach may guide the physicians to meet these challenges (table). The term ACS encompasses a spectrum of patients who present with chest discomfort or other symptoms caused by myocardial ischaemia. The unification of these manifestations of coronary artery disease under a single term reflects the understanding that these are caused by a similar pathophysiology, characterised by erosion, fissuring, or rupture of a pre-existing plaque, leading to intravascular thrombosis and impaired myocardial blood supply? The presence or absence of mechanical obstruction by the plaque and its contents, the amount and extent of associated thrombus formation, and the degree of collateral circulation determine the outcome of patients, particularly whether myocardial ischaemia recovers fully or results in minor or major myocardial necrosis. The common pathophysiology of different clinical presentations of ACS logically requires a similar therapeutic approach. In the 1970s, attention focused on management of lifethreatening arrhythmias. Coronary care units were introduced to detect and treat such arrhythmias by pacemakers (A-V block) or defibrillation (ventricular fibrillation). 2-~ Defibrillators were also introduced in ambulances. Antiarrhythmic drugs were also introduced to prevent ventricular fibrillation. Subsequently, attention shifted to measures to reduce myocardial oxygen consumption with [3-blockers, nitrates, and calcium antagonists. ' These agents prevented progression to myocardial infarction in patients with unstable angina, and improved outcome in selected patients with evolving infarction." In the past 10 years, reperfusion therapy has been introduced, supported by intensive antithrombotic and anticoagulant therapy. The value of reperfusion therapy with coronary occlusion (evolving infarction) by thrombolytic therapy or direct angioplasty has been well established. 9-n However, the indications for, and opt imum timing of, percutaneous or surgical coronary intervention in the spectrum of patients with unstable angina are still debated. H

Assessment of acute myocardial infarction in man with magnetic resonance imaging and the use of a new paramagnetic contrast agent gadolinium-BOPTA.

To assess the feasibility of and characterize the new paramagnetic contrast agent gadolinium-BOPTA/dimeglumine (Gd-BOPTA) to detect acute myocardial infarctions with MR imaging, 24 patients (53.3 +/- 8.3 yr) were examined 9.3 +/- 3.6 days after a first myocardial infarction. Short-axis T1-weighted and T2-weighted MR imaging was performed at three slice levels. T1-weighted images were obtained before, immediately after, 15, 30, and 45 min after injection. Patients received either 0.05 or 0.1 mmol/kg body weight Gd-BOPTA. Images were qualitatively and quantitatively analyzed. Two patients showed no signs of infarction on T2-weighted images as opposed to contrast-enhanced T1-weighted images. Contrast-to-noise ratio was not affected by the dosage level. Signal intensity (SI) of normal to infarcted myocardium was significantly improved by both dosages (p < .0005) but a dosage of 0.05 mmol/kg produced significantly higher SI inf/norm (1.42 +/- 0.07 vs. 1.34 +/- 0.06, respectively, p = .015). SI of normal and infarcted myocardium enhanced immediately after administration of 0.05 mmol/kg (29.3 +/- 5.1% and 53.8 +/- 9.6% respectively), which decreased thereafter to 5.3 +/- 4.8% and 40.2 +/- 8.5% respectively, at 45 min (p < .002 for normal myocardium). SI enhancement immediately after 0.1 mmol/kg Gd-BOPTA showed no decrease within the first 45 min. Gd-BOPTA enables the detection of myocardial infarction. Optimal infarct delineation is achieved from 15 to 45 min after administration of 0.05 mmol/kg body weight Gd-BOPTA. Gd-BOPTA at 0.05 mmol/kg does improve image quality as measured by contrast-to-noise ratio and SI enhancement as compared to 0.10 mmol/kg.

938-60 Detection of Experimental and Clinical Myocardial Infarction by High Frequency Ultrasound

To determine whether myocardial changes in acute myocardial infarction are detectable by high frequency ultrasound imaging, the left anterior descending coronary artery of 10 rats was ligated and 1 rat was sacrificed after 1 day and 3 rats were sacrificed after 2 days, 3 rats after 3 days and 3 rats after 4 days. Two rats served as sham operated controls. Unstained, 5 μm sections of rat hearts were placed on a glass slide and imaged with a 600 MHz transducer. In addition, sections of myocardium obtained at autopsy from 1 pt with acute myocardial infarction were also imaged. A serial section from each of the hearts was imaged by light microscopy. Ultrasound images of control rats and 1 day myocardial infarction showed cardiac myocytes arranged in long axis both in the anterior wall and septum. The anterior wall in the 2 day, 3 day and 4 day infarcts showed cell loss in the subendocardium and subepicardium and discrete rounded echo dense particles which corresponded to inflammatory cell infiltration on light microscopy. Between these areas were hypoechoic myocytes which corresponded to coagulation necrosis on histology. The septum (control region) showed normal myocytes. In acute myocardial infarction in man, cell necrosis and cellular infiltration was noted in the infarcted region. Thrombi in intramyocardial arterioles were seen. The changes were confirmed by light microscopy. High frequency ultrasound imaging depicted characteristic changes in acute myocardial infarction. Further development of this technique for possible IN VIVO evaluation of myocardial ischemia and differentiation of infarcted from viable myocardium appears warranted.

939-82 Efficacy of Gadolinium-BOPTA in Magnetic Resonance Imaging to Assess Acute Myocardial Infarction in Man

To assess the efficacy of the newly developed contrast agent gadolinium (Gd) benzyloxy propionic tetraacetic-acid BOPTA to detect acute myocardial infarction in patients using magnetic resonance imaging (MRI), 24 patients (age 53.3 ± 8.3) were examined 9.3 ± 3.7 days after a first myocardial infarction. Short axis Tl weighted images were obtained at 3 slice levels, before, immediately after injection of Gd-BOPTA, and after 15 min, 30 min, 45 min. Patients were divided into 2 groups according to the dose of Gd-BOPTA (0.05 mmol/kg and 0.1 mmol/kg). Contrast to noise ratio, signal intensity enhancement of normal and infarcted myocardium and signal intensity of infarcted to signal intensity of normal myocardium (SI inf/norm) was quantified. Contrast to noise ratio was not affected by the type of dosage (0.05 mmol/kg, 5.75 ± 0.85 vs. 0.1 mmol/kg, 5.32 ± 0.69). Enhancement of normal and infarcted myocardium increased immediately after administration of 0.05 mmol/kg Gd-BOPTA and gradually decreased thereafter (p &lt; 0.002 for normal myocardium) (see Figure). After 0.1 mmol/kg Gd-BOPTA administration, myocardial enhancement increased rapidly but showed no decrease within 45 minutes after administration (see Figure). Mean SI inf/norm was significantly improved after Gd-BOPTA administration (p &lt; 0.0005 for either dosage), and 0.05 mmol/kg produced significantly higher SI inf/norm than 0.1 mmol/kg (1.42 ± 0.069 vs. 1.34 ± 0.055 respectively, p = 0.015). Gd BOPTA is a useful contrast agent to assess myocardial infarction. Optimal results are obtained with a dosage of 0.05 mmol/kg body weight Gd-BOPTA. Persistent enhancement of infarcted and normal myocardium suggests an affinity of Gd-BOPTA for myocytes, making it a promising tool in MR imaging of ischemic heart disease.

988-7 Endothelin ETA/B Receptor Antagonist Reduces Infarct Size: A Novel Therapy for Acute Myocardial Infarction

We have previously shown that regional myocardial ischemia foliDwed by reperfusion (rep) significantly enhances cardiac release of the potent vasoconstrictor endothelin (ET). We now examine the association of ET production and myocardial blood flow IMBF) in rabbits (n = 14) undergoing 30 min Df circumflex occlusion and 3 hrs of rep. MBF was measured with radioactive microspheres at baseline, 15 min into occlusion, 1 min, 1 and 3 hrs into rep. Utilizing molecular biology techniques, ET 1 mRNA was measured at 3 hrs and found to be elevated in the central ischemic zone (CIZ) compared to the non ischemic zone INIZ). In a second study we investigated the effects of exogenous ET l and PD145065 (an ET A/B receptor antagonist) on infarct size of rabbits undergoing 30 min of circumflex occlusion and 48 hrs of rep. Drug infusion started with an initial bolus (PD145065 3 mg/kg; n = 10 or ET l 10 -10 m/kg; n = 9) 10 min before occlusion followed by 10 -11 m/kg/min of ET 1 or 0.6 mg/kg/min of PD145065 for 2 hrs and 40 minutes. Control animals (n = 10) received the same volumes in saline. Infarct size (AN) was measured histologically and expressed as percentage of area at risk (AR).Results as Mean ± SEM. 1. Myocardial rep after ischemia is associated with marked reactive hyperemia. This flow decreases significantly in the CIZ at 3 hrs into rep demonstrating for the first time that the “no-reflow phenomenon” exists in the rabbit model. 2. ET 1 mRNA was elevated in the CIZ at 3 hrs, suggesting a cause-effect relationship between ET 1 production and the “no-reflow phenomenon”. 3. Exogenous infusion of ET 1 fails to alter infarct size but antagonism of the ET A/B receptors significantly reduces infarct size in rabbits and this might represent a novel therapy for acute myocardial infarction in man.

Fibrin (ogen)-derived peptide Bβ 30–43 is a sensitive marker of activated neutrophils during fibrinolytic-treated acute myocardial infarction in man

Neutrophils, elastase, the specifically elastase-derived fibrin split product, Bβ 30–43, and C-reactive protein were determined in 30 consecutive patients with acute myocardial infarction. At admission to the coronary care unit 4.2 ± 0.8 hours after the onset of symptoms, all elements were increased above the reference levels, while compared with convalescent levels, only neutrophils and Bβ 30–43 were increased. After the streptokinase treatment, neutrophils, elastase, and Bβ 30–43 increased abruptly and peaked ( p < 0.0001) within 1.5 hours. Plasma creatine kinase MB and C-reactive protein reached their peak levels after about 12 and 24 hours, respectively. Peak indices of neutrophils and creatine kinase correlated ( r = 0.60, p < 0.0006). Compared with the age-matched reference range, the convalescent level of Bβ 30–43 was increased ( p < 0.0001). Of the tested elements suggestive of neutrophil activation, Bβ 30–43 showed signs of being the most sensitive. In keeping with animal studies, neutrophils are activated early during the course of acute myocardial infarction and their activation seems to become accelerated by fibrinolytic treatment. Neutrophils may remain activated in the convalescent phase.

Demonstration of the formation of hydroxyl radicals in acute myocardial infarction in man using salicylate as probe.

Dihydroxybenzoic acid (DHBA) derivatives of acetylsalicylic acid (ASA) are formed in vivo by the action of the hydroxyl radical (OH.). In order to evaluate the possible formation of OH(.) in acute myocardial infarction (AMI) in man, 9 consecutive patients with a first episode of AMI (8 males, 1 female, mean age 50.3 years), treated with rt-PA, and 8 healthy volunteers (7 males, 1 female, mean age 29.8 years) were studied. All subjects received 100 mg ASA p.o. daily; venous blood samples were taken 30 min after the first dose (time 0) and then at 3-, 6-, 12-, 24- and 48 h and 5 days. Serum was analyzed by HPLC and electrochemical detection for 2,3- and 2,5-DHBA contents. 2,3-DHBA was present in all subjects with AMI and undetectable in healthy volunteers at all time points studied. Serum levels of 2,5-DHBA did not show statistically significant differences between AMI patients and healthy volunteers. These data support the hypothesis that hydroxyl radicals are formed during AMI in man.

Formation of hydroxyl radial in acute myocardial infarction in man

Formation of hydroxyl radial in acute myocardial infarction in man

Reperfusion Arrhythmias are Rare during Acute Myocardial Infarction in Man

Reperfusion Arrhythmias are Rare during Acute Myocardial Infarction in Man