Clinico-biochemical principles of healing of myocardial infarct]

Individual glyco- and mucoproteins and collagen metabolites were determined in dynamics in 297 patients with transmural, macrofocal nontransmural, and microfocal myocardial infarction. It is shown that these laboratory findings enable one to appraise the course of myocardial infarction healing. This may serve as one of the criteria for the elaboration of individualized rehabilitation programs.     

Myocardial scintigraphy using 99m-technetium pyrophosphate in the diagnosis of acute myocardial infarct. Comparison of planar and tomographic imaging

The aim of the study was to compare the effectiveness of planar and single photon emission computed tomography (SPECT) imaging with 99mTc-pyrophosphate in the verification of acute myocardial infarction. The study was performed on 39 patients (26 males, 13 females) aged between 41-76 years (mean 61 +/- 9) admitted to CCU for acute myocardial infarction. Patients underwent planar and SPECT imaging using a double-head-camera with a 360 degrees rotation arc within 6 days of admission. Planar images were obtained in three standard projections (anterior, LAO 45 degrees, LAO 75 degrees) with acquisitions of 500000 counts each. To obtain SPECT images ninety projections, each lasting 20 seconds, were taken; subsequently images reconstruction was performed using an iterative algorithm. Positive planar images were found in 21 out of 39 patients; SPECT images were positive in 33 patients. In "Q wave" myocardial infarctions planar images were positive in 13 out of 15 patients, whereas SPECT images were positive in all subjects; in "non-Q wave" myocardial infarctions planar images were positive in 6 out of 22 patients whereas SPECT images were positive in 16 patients (p less than 0.005); in 2 patients with left bundle branch block both planar and SPECT images were positive. A bidimensional echocardiogram was carried out on 38 patients: an alteration of left ventricular regional wall motion was present in 30 subjects; in one patient diffuse hypokinesia was present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of coronary reperfusion on myocardial hemorrhage and infarct healing

Early coronary reperfusion for treatment of acute myocardial infarction is a promising mode of therapy but may result in hemorrhagic infarction. The effect of hemorrhage on healing of myocardium subjected to early reperfusion is unknown, but could be detrimental. To compare repair of reperfused infarcts and permanently ischemic infarcts, 2 coronary arteries were occluded in 14 anesthetized dogs, and after 4 hours, 1 artery was reperfused. Either 1 or 14 days later, samples from the center of the infarcts and from normal myocardium were analyzed for hemoglobin (milligrams per gram), creatine kinase (international units per milligram of protein), and hydroxyproline (micrograms per gram) content. In an additional 7 dogs killed at 3 days after coronary occlusion, the myocardium was studied histologically. Gross subendocardial hemorrhage was present in all reperfused infarcts at 1 day; hemoglobin content was 8 ± 1 in normal myocardium and 10 ± 2 in permanently ischemic infarcts, but was highest in reperfused infarcts at 38 ± 7 (p < 0.025 versus permanently ischemic infarcts). Creatine kinase content in reperfused infarcts and permanently ischemic infarcts was similarly depressed (4 ± 2 and 7 ± 1 compared with 30 ± 5 in normal myocardium, p < 0.05). At 3 days, polymorphonuclear leukocyte infiltration was less prominent in reperfused infarcts than in permanently ischemic infarcts. At 14 days, hydroxyproline levels were similar in reperfused infarcts (9.4 ± 2.7) and permanently ischemic infarcts (10.7 ± 1.9), and higher than in normal myocardium (3.3 ± 0.4). Thus, intramyocardial hemorrhage occurs early in reperfused infarcts, is more severe than in permanently ischemic infarcts, and is associated with an altered early granulocyte response, without affecting late collagen formation.     

Importance of magnetic resonance imaging in myocardial infarct

Imagery by magnetic resonance (IMR) represents a new modality of medical imagery based on the interaction between the magnetic fields produced by radio-frequency waves and living substance. IMR finds an interesting application in the study of different stages of myocardial infarction. In 30 cases of myocardial infarction IMR was compared with thallium tomoscintigraphy and echocardiography. In the acute stage, myomalacia appears in IMR as a superbrilliant zone, and in the chronic stage parietal thinning and dyskinesias are apparent. Intraventricular thromboses, but also hemostasis in aneurysmatic or akinetic sites are visualised as a high-intensity signal within these areas. IMR represents therefore a new means of evaluation of size and evolution of the necrosis. This procedure provides also functional informations about the contraction and flow anomalies.     

Time course of myocardial bloodflow changes during healing of myocardial infarct in pigs.

OBJECTIVE: To define the time course of changes in bloodflow and microsphere content at intervals between one and 28 days after surgical ligation of the circumflex coronary artery. SUBJECTS AND METHODS: After the ligation, pigs were assigned to six groups; all pigs in a group were reanesthetized at either one, three, seven, 14, 21 or 28 days post ligation to determine myocardial bloodflow distribution using radionuclide-labelled (15 +/- 2 microns) microspheres. RESULTS: Bloodflow to the infarct zone, 10 mins post ligation, was 7.3 +/- 1.4% of the normal flow. At one and three days post occlusion, infarct bloodflow was about 50% of the 'normal', declining after day 7 to between 20 and 25%. Bloodflow in the noninfarct zone was significantly elevated during the initial 14 days, declining thereafter to within the normal range. Microspheres in the infarct zone injected prior to the occlusion became concentrated and were diluted in the noninfarct zone; the ratio of infarct:noninfarct microsphere content rose progressively, reaching a 2.5-fold rise by day 28. CONCLUSIONS: The initial stages of infarct healing are associated with a marked rise in bloodflow with a subsequent fall. A more prolonged augmentation of flow is evident in the noninfarct zone. Microspheres are useful in estimating the relative magnitude of changes in the myocardium accompanying the healing (shrinkage) of the infarct and hypertrophy occurring in the noninfarct zone after a coronary occlusion.     

Leukocyte acid phosphatase activity in myocardial infarct

Leucocytic acid phosphatase (AP) activity was measured cytochemically in 21 myocardial-infarction patients aged 37 to 57. Neutrophil leucocytosis was found to result from an increase in the quantity of cells with high activity of the enzyme. Neutrophil AP activity was elevated during the first days of the infarction and dropped to the baseline level on day 14. Between days 7 and 14, the numbers of lymphocytes with cytoplasmatic AP localization were reduced, suggesting lysosome stabilization at this stage of myocardial infarction.     

Effects of early and later reperfusion on healing speed of experimental myocardial infarct

The effects of reperfusion on myocardial infarct healing in the rabbit were analyzed using two morphometric indexes: the ratio of the volume of the organized portion of infarct to the volume of the whole infarct (%O/I), and the ratio of the minimal thickness of the infarct zone to the normal zone thickness (thinning ratio). In the nonreperfused infarcts, %O/I increased from 43.8 +/- 3.1% (mean +/- SEM) at 48 h to 85.7 +/- 2.5% at seven days, which supported the validity of this index. The thinning ratio was 0.50 +/- 0.03 at 48 h and did not change during the following five days. In other groups of rabbits, the coronary artery was temporarily occluded for 30 mins (early reperfusion) or 60 mins (late reperfusion), and the hearts were analyzed at 72 h or seven days. Early reperfusion limited infarct size as a percentage of the area at risk (%I/AAR) by approximately 50%, but late reperfusion did not. In both nonreperfused and reperfused infarcts, %O/I correlated significantly with absolute infarct size. Furthermore, the regression lines of the relationship of infarct size to %O/I of early and late reperfused infarcts shifted towards higher %O/I values compared with that of nonreperfused infarcts at seven days, which suggested accelerated organization. However, such a regression line shift by reperfusion was not detected at 72 h after infarction. The thinning ratio was higher in early reperfused infarcts compared to nonreperfused or late perfused infarcts, and there was a weak inverse correlation between thinning ratio and %I/AAR when the data of reperfused and nonreperfused infarcts were pooled.(ABSTRACT TRUNCATED AT 250 WORDS)     

Structural and electrophysiological changes in the epicardial border zone of canine myocardial infarcts during infarct healing

Structural and electrophysiological properties of the epicardial muscle which survives on the surface of transmural infarcts of the canine heart (epicardial border zone) were studied at different times after occlusion of the left anterior coronary artery (LAD). Isolated preparations were superfused in vitro, transmembrane potentials recorded, and impulse propagation mapped. In preparations from subacute infarcts (1 and 5 days), resting potential, action potential amplitude, upstroke velocity, and duration were all significantly reduced. Well-defined directional differences in propagation occurred. Propagation was more rapid in the direction perpendicular to the left anterior coronary artery than in the direction perpendicular to the base of the heart, because of the uniform anisotropic structure of the surviving muscle fibers which were arranged in tightly packed bundles oriented perpendicular to the left anterior coronary artery. The only ultrastructural abnormalities found in these muscle fibers was an accumulation of large amounts of lipid droplets. As the infarcts healed, resting potential, action potential amplitude, and upstroke velocity returned to normal by 2 weeks, although action potential duration decreased further. Lipid droplets had disappeared, and connective tissue had invaded the epicardial border zone, separating the muscle bundles. By 2 months, action potentials were normal, but the muscle fibers were widely separated and disoriented by the connective tissue (parallel bundles no longer were found). In these regions with a nonuniform anisotropic structure, the well-defined directional differences in impulse propagation were lost. However, activation was very slow, perhaps because of diminished connections between cells. The persistence of slow conduction in healed infarcts may contribute to the occurrence of chronic arrhythmias.     

Stress factors in myocardial infarct patients before the appearance of myocardial infarct

Apart from somatic risk factors and the smoking of cigarettes more attention in the development of the myocardial infarction must be ascribed to the psychosocial and psychoemotional stress and its false processing. For the judgment of the stress in patients with myocardial infarction a questionnaire was constructed. It contains those questions the answer of which showed significant differences in comparison to the persons with healthy coronary vessels. The inquiries were answered by altogether 110 patients with myocardial infarction. In order to obtain references to definite characteristics concerning the structure of the personality of our patients with myocardial infarction, we used the INR-questionnaire after B?ttcher. In either sex moments of "self-stressing" dominate. Professional conflicts were mentioned more by men, familial problems more by women. Among others, definite characteristics concerning the structure of the personality (rigidity) of patients with myocardial infarction seem to be a reason for the deficient strain under stress or they increase the sensitiveness to stress. From the results of the examinations requirements to the psychic rehabilitation of patients with infarction are derived, which must be carried out parallel to the somatic rehabilitation.     

Polymorphonuclear leukocyte activity and ventricular arrhythmia in acute myocardial infarction

Polymorphonuclear leukocyte activity was compared with the incidence and severity of ventricular arrhythmia evaluated by Holter electrocardiographic monitoring in 21 patients with acute myocardial infarction. A positive correlation (r = 0.706) was seen between peripheral polymorphonuclear leukocyte count and the amount of leukotriene B4 produced by A23187 (20 microM)-stimulated polymorphonuclear leukocytes on the first hospital day (p less than 0.01). Patients were divided into 3 groups according to the severity of ventricular arrhythmia: no or mild (unifocal, maximal hourly ventricular premature complex rate less than 30, n = 6), moderate (maximal hourly ventricular premature complex rate greater than or equal to 30 or multifocal, n = 6) or severe (R on T, greater than or equal to 2 consecutive ventricular premature complexes or ventricular fibrillation, n = 9). Polymorphonuclear leukocyte count and its leukotriene B4 production were increased with the increase in severity of ventricular arrhythmia among 3 groups. Polymorphonuclear leukocyte count (13,300 +/- 900/microliter, mean +/- standard error of the mean) and its leukotriene B4 production (194 +/- 24 ng/10(7) cells) in patients exhibiting severe ventricular arrhythmia were significantly increased compared with those in patients exhibiting no or mild ventricular arrhythmia (10,300 +/- 1,000/microliter, p less than 0.05 and 120 +/- 21 ng/10(7) cells, p less than 0.05, respectively). Enzymatically estimated infarct size in the latter patient group was significantly smaller than those of the other 2 groups, between which there was no difference in infarct size. These results suggest that polymorphonuclear leukocyte activity is closely related to the incidence and severity of ventricular arrhythmia during the early phase of myocardial infarction.     

Immediate mineralocorticoid receptor blockade improves myocardial infarct healing by modulation of the inflammatory response

Mineralocorticoid receptor (MR) blockade reduces morbidity and mortality after acute myocardial infarction; however, the underlying mechanisms are still under investigation. This study examined whether MR antagonism promotes healing of the infarcted myocardium. Starting immediately after coronary ligation, male Wistar rats were treated with the selective MR antagonist eplerenone (100 mg/kg per day by gavage) or placebo for 2 to 7 days. At 7 days, eplerenone therapy versus placebo significantly reduced thinning and dilatation of the infarcted wall, improved left ventricular function, and enhanced neovessel formation in the injured myocardium. At 2 days, eplerenone-treated rats displayed lower plasma corticosterone levels, higher circulating blood monocytes, and more macrophages infiltrating the infarcted myocardium. MR blockade led to a transient upregulation (at days 2 and 3 but not at day 7) of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interleukin-4 and an increase in factor XIIIa protein expression in the healing myocardium. Prevention of macrophage accumulation into the infarct zone by treatment with liposome-encapsulated clodronate almost abrogated the protein expression of factor XIIIa and the beneficial effects of eplerenone on infarct expansion. In conclusion, selective MR blockade immediately after myocardial infarction accelerated macrophage infiltration and transiently increased the expression of healing promoting cytokines and factor XIIIa in the injured myocardium resulting in enhanced infarct neovascularization and reduced early LV dilation and dysfunction.     

Site and type of acute myocardial infarct in relation to myocardial infarct size--dynamics of global ejection fraction in acute myocardial infarct

By the ejection fraction global (EFg) statements concerning the remaining function of the myocardium in acute myocardial infarction and thus individually concerning the prognosis (classification of risk groups) become possible. For the valuation of the dynamics of the EFg in a period up to 6 months after an acute myocardial infarction the EFg was multifariously controlled. Only patients with first myocardial infarction in localization on the anterior wall and Q-wave showed a significant dynamics of the EFg between the measurements acute and third week as well as acute and 6th month (absolutely 5.2%). --In re-infarction/Q-wave this could be confirmed also for the localization of the posterior wall in the period acute till third week. For the localization on anterior and posterior wall a dynamics of the EFg could also be calculated for the period acute and 6th month. Thereby the absolute increase of the EFg was between 4.0 and 4.6%. The dynamics of the EFg in the region of the anterior wall was 5.2% for the first infarction and only 4% for the reinfarction. Thus it is below the dynamics of the EFg in an effective thrombolytic therapy.     

Effect of prednisolone on myocardial infarct healing: characteristics and comparison with indomethacin.

OBJECTIVE: To characterize retardation of myocardial infarct healing by corticosteroid administration, and to examine the role of suppression of prostaglandin production in its effect. DESIGN: The left circumflex coronary artery of the rabbit was occluded for 30 mins and reperfused for 72 h. Rabbits were divided into four groups: a control group, a low dose prednisolone group (L-PSL) that was treated with 5 mg/kg/24 h prednisolone, a high dose prednisolone group (H-PSL) that was treated with 10 mg/kg/24 h prednisolone, and an indomethacin group that received a 5 mg/kg intravenous bolus of indomethacin followed by 10 mg/kg/24 h. The status of infarct healing and infarcted wall thinning was assessed 72 h after ischemia by the percentage of infarct mass organized (%O/I) and the ratio of infarcted wall thickness to noninfarcted wall thickness (thinning ratio). MAIN RESULTS: The %O/I was 61.4 +/- 4.2% (mean +/- SEM) in the control group. The L-PSL and H-PSL groups had %O/Is of 48.3 +/- 3.7% and 29.1 +/- 2.1%, respectively, which were significantly lower than the control value. The difference in %O/I between the H-PSL and L-PSL groups was also significant. However, the %O/I of the indomethacin group (55.1 +/- 3.3%) was not significantly different from control. When the myocardial infarcts were retrospectively subgrouped into small infarcts (infarct volume less than 0.31 cm3) and large infarcts (greater than or equal to 0.31 cm3), infarct healing delay in large infarcts was evident only for H-PSL and not for L-PSL, while both L-PSL and H-PSL treatment retarded healing of small infarcts. No significant difference was observed in the thinning ratio for any group. CONCLUSION: Infarct healing delay by prednisolone is dosage dependent, and smaller infarcts may be more sensitive to its effect. Retardation of infarct healing by prednisolone is unlikely to be mediated by suppression of prostaglandins from the cyclo-oxygenase pathway.     

Dynamics of 5'-nucleotidase activity in the blood plasma in experimental myocardial infarct

The authors studied in the bloodflow the appearance of the damaged external cellular membranes of the heart during the development of experimental myocardial infarction. The appearance of the external cellular membranes was judged by the activity of their specific marked 51-nucleotidase. It was established that myocardial infarction leads to increased activity of 51-nucleotidase in the blood plasma, which is retained for about 1 month. The maximum of activity of 51-nucleotidase reflects the most intensive resorption of the damaged cardiac tissue, and is seen from 3 to 7 days after the accident. During these time limits thrombotic complications are especially dangerous.