Endocardial alterations in myocardial infarction.

Transmural infarcts of the ventrolateral wall of canine left ventricle were produced by ligation of the ventral interventricular (anterior descending) branch of the left coronary artery. Endocardium from these infarcted hearts was sampled at sites corresponding to the infarct center and periphery, and to uninfarcted (normal) area at 24 and 48 hours after ligation, and examined by correlative scanning and transmission electron microscopy and by light microscopy. Endocardial samples from sham-ligated hearts were included as a further control. Striking alterations were observed in the endocardium that lined infarcted myocardium. There was endothelial desquamation coextensive with leukocytic invasion. Leukocytes appeared to initiate sloughing by separating the endothelial cells from their basal lamina and partially from one another. The latter cells desquamated in sheets, leaving behind a denuded basal lamina. Although altered in form, the individual endothelial cells seemed to remain largely intact. Denuded subendothelial surfaces only rarely contained thrombi. In areas where the cardiac endothelium was altered, the subjacent subendocardium, myocardium, and usually the remainder of the endocardium also showed leukocytic exudate. Samples from uninfarcted regions showed an intact, leukocyte-free endocardium, as did the sham-ligated controls. The appearance of abnormal endocardium was qualitatively similar wherever found, whether in different areas of the same heart or from one heart to another, and regardless of age of infarct. In 48-hour infarcts, almost all of the central and most of the peripheral samples exhibited the changes described. The data suggested a similar pattern for hearts with 24-hour infarcts. By locating biopsy sites in frozen cardiac sections processed for histologic staining and 201-thallium autoradiography, the electron microscopy results were shown to correlate with the intramural histopathologic topography of the infarcts. The alterations described here represent the endocardial manifestation of the inflammatory stage of transmural infarcts, known to be well developed in 1- and 2-day-old lesions.     

Adipose tissue in myocardial infarction.

INTRODUCTION: The histologic evolution of myocardial infarction (MI) has been studied in some detail. However, there is little mention of the presence of adipose tissue in healed MI(HMI). Ninety-one hearts explanted during 1997-2001 were examined to determine the extent of adipose tissue within HMI. METHODS: The medical records, surgical pathology reports, and all histologic sections of the explanted heart, from patients undergoing heart transplantation for ischemic heart disease, were reviewed. Adipose tissue within the areas of HMI was quantified. The location of the HMI, the age and gender of the patient, age of HMI, and whether the patient was treated with coronary artery bypass surgery (CABG) were noted. RESULTS: Of the 91 hearts examined, 168 HMIs were identified; 141 (84%) contained some mature fat within the HMI. Adipose tissue increased with increasing age, in males, and in those patients who had CABG surgery. The amount of adipose tissue was not related to the location or age of the HMI. CONCLUSION: Adipose tissue is a prevalent histological finding in HMIs. The pathogenesis of adipose tissue is unknown, but may be influenced by current medical therapy for ischemic heart disease, thus explaining why adipose tissue in HMIs was not reported until 1997. The presence of fat supports the speculation that a regenerative cell, or multipotent stem cell, exists within the heart, and under the influence of microenvironmental or therapeutic factors can differentiate into fat, other mesenchymal tissues, and potentially even myocardium.     

Management of acute myocardial infarction with natural physiological agents

A number of natural physiological agents deserve evaluation in the treatment of acute myocardial infarction. Prostacyclin and magnesium dilate large coronary arteries and could promote collateral circulation to ischemic regions, especially if used in conjunction with alpha-agonists to prevent a drop in coronary perfusion pressure. In addition, prostacyclin has anti-aggregatory and de-aggregatory effects on platelets and a stabilizing action on hypoxic tissue, while magnesium has anti-arrhythmic, potassium-retaining, and fibrinolytic effects, all of which could improve the outcome in acute MI. Adenosine or ribose infusion could be used to promote rapid repletion of adenine nucleotides in reperfused tissue, but unfortunately arteriolar vasodilation by adenosine might reduce collateral perfusion by "coronary steal". High-dose insulin has positive-inotropic (at minimal oxygen cost) and potent anti-arrhythmic actions that have not been adequately tested in previous clinical trials of "polarizing solutions". Carnitine infusion could improve the bioenergetics of ischemic myocardium by relieving inhibition of mitochondrial adenine nucleotide translocase.     

Thrombolytic therapy and myocardial infarction.

Examination of 27 hearts from patients treated by streptokinase following myocardial infarction showed one major histopathological difference from controls, the presence of massive interstitial haemorrhage into the necrotic tissue in some cases. This change is presumably related to the re-establishment of the circulation to infarcted areas.     

The management of suspected myocardial infarction by Scottish general practitioners with access to community hospital beds.

General practitioners working in 20 community hospitals in Scotland participated in a survey of the management of myocardial infarction. During one year they suspected acute myocardial infarction in 451 patients. Of these patients, 278 (62%) were admitted to a community hospital, 125 (28%) to a district general hospital and 48 (11%) were kept at home. The main reasons given for admission to a community hospital were for monitoring and investigation, while the main reasons for admission to a district hospital rather than a community hospital were the relative youth of the patient and the severity of the illness. Acute myocardial infarction was confirmed in 323 (72%) cases, but in 26 (6%) cases the final diagnosis was other than ischaemic heart disease. Patients with acute myocardial infarction who entered a community hospital did so a median of two hours 25 minutes after the onset of symptoms. Among 18 patients admitted to a community hospital in whom resuscitation was attempted after cardiac arrest four (22%) were subsequently discharged from hospital. The mortality rate from acute myocardial infarction in the community studied was 171/418 (41%), of whom 95 died suddenly before coming under medical care. It is concluded that in rural areas of Scotland an acceptable standard of care for patients with acute myocardial infarction, including the administration of thrombolytic therapy, could be provided rapidly by general practitioners working in community hospitals.     

Collagen remodeling after myocardial infarction in the rat heart.

In this study changes in the amount and distribution of types I and III collagen mRNA and protein were investigated in the rat heart after induction of a left ventricular myocardial infarction (MI). Sham operated rats served as controls. The animals were sacrificed at different time intervals after operation. Northern blotting of cardiac RNA and hybridization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III procollagen mRNA levels were already increased at day 2 after MI, whereas type I procollagen mRNA followed this response at day 4 after MI. This increase was sustained for at least 21 days in the infarcted left ventricle for type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold increase was observed for both type I and type III procollagen mRNA levels, but only at day 4 after MI. In the non-infarcted septum a transient increase was observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sham levels thereafter. In the septum type III procollagen mRNA levels were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham operated controls. In situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells in the infarcted area around necrotic cardiomyocytes, and in the interstitial cells in the non-infarcted part of the myocardium. No labeling was detected above cardiomyocytes. Combined in situ hybridization and immunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fibroblasts in the noninfarcted septum and right ventricle. The increase in types I and III procollagen mRNA in both infarcted and non-infarcted myocardium was followed by an increased collagen deposition, measured by computerized morphometry on sirius red-stained tissue sections as well as by the hydroxyproline assay. In the non-infarcted septum and right ventricle the collagen-positive area was maximal at day 14 (3- to 5-fold increase compared with sham operated controls) and slightly declined at day 21. In the infarcted myocardium the collagen-positive area was 57 +/- 10% at day 14 after MI. Hydroxyproline contents were significantly increased in the noninfarcted septum.(ABSTRACT TRUNCATED AT 400 WORDS)     

Oral contraceptives and the risk of myocardial infarction.

BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.