Lipolytic Enzymes with Hydrolytic and Esterification Activities Produced by Filamentous Fungi Isolated from Decomposition Leaves in an Aquatic Environment.

Microbial lipases are prominent biocatalysts able to catalyze a wide variety of reactions in aqueous and nonaqueous media. In this work, filamentous fungi isolated from leaves decomposed in an aquatic environment were screened for lipase production with hydrolytic activity and esterification. Agar plates with Tween 20 and Rhodamine B were used for selection, while submerged cultures with olive oil were subsequently used to select 38 filamentous fungi. Trichoderma harzianum, Fusarium solani, Trichoderma harzianum F5, and Penicillium sp. F36 were grown in six different culture media. F. solani presented the highest lipase production (2.37 U/mL) with esterification activity of 0.07 U/mL using medium composed of (g.L-1) KH2PO4 1.00, MgSO4 H2O 1.123, and CuSO4 0.06. Supplementation of this culture medium with organic nitrogen sources increased lipase production by 461.3% using tryptone and by 419.4% using yeast extract. Among the vegetable oils from the Amazon region, degummed cotton oil induced lipase production up to 8.14 U/mL. The lipase produced by F. solani F61 has great potential to application in conventional processes and biodiesel production by transesterification of vegetable oils, as well as food industries in the production of fatty acid esters by hydrolysis and esterification.

Comparison of two angiographic systems in paediatric interventional cardiology.

The aim of this work was to analyse the radiation dose for patients and staff between X-ray systems, a new biplane with flat-panel detectors (FDs) and a conventional system equipped with image intensifier (II). Entrance surface air kerma (ESAK) and scatter doses were measured on polymethyl methacrylate (PMMA) phantoms of different thicknesses (from 4 to 16 cm). The ESAK values for the different acquisition modes and PMMA thicknesses were higher for the II in comparison with FDs. For the II, the scatter dose rates ranged from 0.67 to 12.2 mSv h(-1) at the eye position of the cardiologist during fluoroscopy and cine modes. At the lower extremities, these values were 1.11 and 24.24 mSv h(-1). In the case of the FDs, these values ranged from 0.24 to 0.67 mSv h(-1) for eye lens and from 0.73 to 2.01 mSv h(-1) for the position of cardiologist's ankle. The newly installed X-ray system showed an average reduction factor of up to 9.7 times for ESAK values. For the staff with an average reduction factor of 15.9 times at the eye position during fluoroscopy and cine modes, no protective tools are used. At the lower extremities, this value was 7.6 times.

Entrance surface air kerma in X-ray systems for paediatric interventional cardiology: a national survey.

The aims of this work were to report the results of a national survey on entrance surface air kerma (ESAK) values for different phantom thicknesses and operation modes in paediatric interventional cardiology (IC) systems and to compare them with previous values. The national survey also offers suggested investigation levels (ILs) for ESAK in paediatric cardiac procedures. ESAK was measured on phantoms of 4-16 cm thickness of polymethyl methacrylate slabs. For low fluoroscopy mode (FM), ESAK rates ranged from 0.11 to 33.1 mGy min(-1) and for high FM from 0.34 to 61.0 mGy min(-1). For cine mode, values of ESAK per frame were from 1.9 to 78.2 µGy fr(-1). The ILs were suggested as the third quartile of the values measured. This research showed lower ESAK values than in previous research, particularly for ESAK values in cine modes. This work represents a first step towards launching a national programme in paediatric dosimetry for IC procedures.

Efecto de la infección periodontal por porphyromonas gingivalis en el desarrollo de ateroesclerosis en ratones deficientes de apolipoproteína E / Effects of porphyromona gingivalis periodontal infection upon atherosclerosis development in apolipoprotein-E

Introducción: Nuestro grupo recientemente demostró una asociación significativa entre periodontitis, placas coronarias aguda y extensión de la enfermedad coronaria aterosclerótica en pacientes con síndrome coronario agudo. Objetivo: Desarrollar un modelo experimental animal para estudiar el posible efecto pro-aterogénico de la inducción de periodontitis por Porphyromona Gingivalis (PG) en ratones deficientes en la apolipoproteína E (APO-E KO). Métodos: En 12 ratones APO-E KO mantenidos con dieta hiperlipidémica se realizaron tocaciones con PG cepa ATCC 53977 en el surco gingival de los molares mandibulares a las 8 semanas de vida. Igual número de ratones APO-E KO fue intervenido con el mismo procedimiento, pero sólo con el vehículo de las tocaciones. Estos procedimientos se repitieron a las 48, 72 y 120 hrs de la infección inicial. Luego de 4 semanas post-inoculación con PG se realizaron estudios histomorfométricos en la aorta proximal para medir la severidad de las lesiones ateromatosas y en las mandíbulas, para evaluar la pérdida del hueso alveolar. Resultados: No se observó una diferencia significativa en el daño del hueso alveolar en las mandíbulas de los animales infectados versus el grupo control. En las aortas, la razón tamaño placa/pared vascular fue mayor en el grupo infectado con PG que en el grupo control (0.132 ± 0.2 versus 0.103 ± 0.15, respectivamente), pero esta diferencia no fue estadísticamente significativa. Conclusión: El diseño experimental del presente estudio no permitió establecer si la periodontitis inducida por PG es capaz o no de acelerar el proceso aterogénico de los ratones APO-E KO. Será necesario aplicar un protocolo de infección periodontal más agresivo en estos animales para evaluar más adecuadamente el efecto de PG sobre la ateroesclerosis.

Predictors of radial artery patency for coronary bypass operations.

BACKGROUND: Few data exist regarding angiographic predictors of radial artery patency for coronary bypass grafting, and the benefit of calcium antagonists is not clear. METHODS: One hundred fifteen patients were studied who had myocardial revascularization with the radial artery plus internal mammary and vein grafts with 3.5 +/- 1.1 grafts per patient. Sixty-three patients received diltiazem and 52 patients did not. Base line and follow-up angiographies were analyzed 1 year postoperatively in 50 of these patients with a quantitative computerized method. RESULTS: One hundred fourteen patients survived and were followed for 30.1 +/- 12.6 months. Patency for mammary grafts was 100%, for radial grafts it was 80%, and for saphenous vein grafts it was 68%. Patent radial artery grafts had significantly greater degree of stenosis in the native vessels than occluded grafts (73% +/- 14% vs 40% +/- 24%), (p = 0.0007; confidence interval = 95%). Radial artery patency increased to 92% when arteries with 70% or more stenosis were considered. No differences were observed for clinical and angiographic end points in the patients that received diltiazem compared with the rest who had not. CONCLUSIONS: The degree of stenosis in the native coronary artery significantly influences the patency rate of radial artery grafts, independent of diltiazem.

[The collagen of the restenosis post angioplasty with stent: Is its origin in intima or adventitia?]. / El colágeno de la reestenosis post angioplastia con stent: se origina en la íntima o en la adventicia?

BACKGROUND: Restenosis post stenting is due to the deposit of extracellular matrix, mainly collagen in the neointima. Controversy exists regarding if collagen is generated locally or by immigration from the adventitia. AIM: To study the fibrocellular response after stent implantation in rabbit iliac arteries. To observe, by immunohistochemistry and in situ hybridization, if collagen type I mRNA is expressed in the neointima, in the media or in the adventitia. MATERIAL AND METHODS: Thirty eight white rabbits (New Zealand) of 4 kg received an hypercholesterolemic diet during 1 month. After this period, in all but 6 of them, an angioplasty with stent implantation was performed via right carotid artery in both iliac arteries, using a 1:1.3 relationship regarding the reference vessel. Angiograms were performed at day 0, 4, 21, and 40, followed by paraffin fixation of the injured segments, immunohistochemistry for alpha-actin and in situ hybridization to detect procollagen type I (alpha 1R1) mRNA. RESULTS: No hybridization was observed in non injured arteries or at day 0 (n = 6). Expression of alpha 1R1 mRNA was observed in the neointima starting at day 4 after stenting (n = 8). At day 21 (n = 8) hybridization of procollagen type I was not only observed in the neointima, but also in the media, which became equally intense in both areas. At day 40 (n = 6) hybridization was observed similarly in the media and adventitia. CONCLUSIONS: In this model, hybridization of procollagen type I started in the neointima, then involved the media and finally the adventitia. This finding might be useful for designing therapies to be delivered locally at the end of an angioplasty to prevent collagen deposition in the neointima.

[Metalloproteinase activity in myocardium of rats exposed to endotoxin and its inhibition with doxycycline]. / Actividad de las metaloproteinasas en el miocardio de ratas sometidas a endotoxina y su inhibición con doxiciclina.

BACKGROUND: The ventricular dysfunction of endotoxic shock could be secondary to the activity of myocardial metalloproteinases that degrade collagenous matrix. Metalloproteinase activity can be inhibited with doxycycline in some tissues. AIM: To study if the effect of endotoxemia on myocardial metalloproteinase activity can be inhibited with doxycycline. MATERIAL AND METHODS: Left ventricular metalloproteinase activity was studied in four groups of rats. Group 1 received intraperitoneal dextrose in water, group 2 received 8 mg/kg intraperitoneal E coli endotoxin, group 3 received 60 mg/kg/day doxycycline for three days and group 4 received doxycycline and E coli endotoxin. Enzymatic activity was measured by Western Blot and zymography. RESULTS: Zymography showed a higher metalloproteinase 2 (49%) and 9 (100%) activity in rats treated with endotoxin, when compared with control rats. In group 4, doxycycline reduced the activity of metalloproteinases 2 and 9 by 71% and 63% respectively, as compared with group 3. Western blot showed a 50% increase in the expression of metalloproteinase 1 in rats treated with endotoxin, that was reduced by 64% with the use of doxycycline. CONCLUSIONS: Endotoxin administration increases myocardial metalloproteinases and doxycyclin inhibits this activation. Therefore, doxycyclin could reduce the degradation of myocardial fibrillar collagen and ventricular dysfunction of endotoxic shock.

[D/D genotype of the gene for angiotensin converting enzyme as a risk factor for post-stent coronary restenosis]. / El genotipo D/D del gen de la enzima conversiva de la angiotensina como factor de riesgo de reestenosis post-stent coronario.

INTRODUCTION: Although intracoronary stenting has decreased restenosis rate compared to percutaneous balloon angioplasty, still a high number of patients develop in-stent restenosis, which is an entity primarily due to tissue proliferation. Experimental studies have indicated that the renin-angiotensin system is involved in neointimal hyperplasia. Plasma and cellular levels of ACE are associated with an I/D polymorphism in the ACE gene. Indeed, DD subjects have the higher ACE levels. The purpose of this study was to explore the possibility that the I/D polymorphism might be related with in-stent restenosis. METHODS: We studied the ACE polymorphism in 48 consecutive patients who underwent successful implantation of an elective coronary stent in native coronary vessels and had a 6 month angiographic follow up. Restenosis (50% of the reference vessel) was observed in 23/48 patients. Patients with or without restenosis did not differ in demographic or clinical variables like diabetes, plasma cholesterol levels or in quantitative angiographic parameters such as vessel reference size or minimal lumen diameter after stent implantation. RESULTS: I/D polymorphism was distributed as follows: 22.9% of the patients were D/D; 14.5% were I/I and 62.5% of the patients were heterozygous I/D. The presence of restenosis was strongly related with the I/D polymorphism: 81.8% of the patients with D/D genotype had restenosis, compared with 40.0% of I/D patients and only 14.2% of the I/I patients (chi 2 p < 0.01). CONCLUSIONS: In this limited cohort, homocygous D/D of the ACE gene was significantly associated with in-stent restenosis, whereas restenosis was infrequent in patients with the I/I genotype.

[Chronic atrial flutter: an infrequent manifestation of sick sinus syndrome. Clinical case]. / Flutter auricular crónico: una manifestación infrecuente de enfermedad del nódulo sinusal. Caso clínico.

We report a 41 years old female, previously operated of an atrial septal defect, presenting with a persisting atrial flutter. Sinus node dysfunction became evident during an electrophysiological study at the moment of interrupting the flutter with electrical stimulation. The patient was treated with his bundle ablation and implantation of a definitive pacemaker. After one year of follow up, she is devoid of symptoms.

[Unstable angina: immediate and one-year results of transluminal coronary angioplasty treatment]. / Angina inestable: resultados inmediatos y a un año del tratamiento con angioplastía coronaria transluminal percutánea.

BACKGROUND: Unstable angina is characterized by angina at rest, angina of recent onset or accelerating angina. It is caused by a fissure or ulceration of an atheromatous plaque leading to thrombi formation and coronary spasm. AIM: To report the immediate and late results of coronary angioplasty in patients with unstable angina. PATIENTS AND METHODS: Eight hundred twenty eight patients were subjected to coronary arteriography between January 1994 and June 1996. Of these, 242 were subjected to a transluminal coronary angioplasty, 245 patients were subjected to surgical revascularization and 341 patients were treated without revascularization. RESULTS: A total of 323 stenotic lesions (1.3 lesions per patient) were subjected to angioplasty. Angiographic success was obtained in 93% of patients. Angiographic success and lack of major complications such as death, infarction of the need for surgery, was obtained in 90% of patients. Five patients (2.1%) had a non fatal infarction and five required emergency surgery. Hospital mortality was 1.2%. During the year of follow up, 15% required a new revascularization, 3.3% had a non fatal infarction and 3.3% died. CONCLUSIONS: Coronary angioplasty had a 90% immediate success and 78% of patients were free of ischemic events after one year of follow up.

[Cardiovascular effects of AV interval shortening with electrical stimulation in dilated cardiomyopathy]. / Efectos cardiovasculares del acortamiento del intervalo AV mediante estimulación eléctrica del corazón en miocardiopatía dilatada.

BACKGROUND: A temporal alteration between atrial and ventricular contraction, in which the last one would be abnormally retarded, could exist in patients with dilated cardiomyopathy. This alteration could have adverse hemodynamic effects. AIM: To study the hemodynamic modifications caused by an artificial shortening of AV interval in patients with dilated cardiomyopathy. PATIENTS AND METHODS: Nine patients with dilated cardiomyopathy were studied. Hemodynamic and tissular perfusion values, echocardiographic and radioisotopic ventricular function parameters were measured before and after six hours of AV interval shortening with electrical stimulation of the heart. RESULTS: After electrical stimulation, cardiac output increased from 3.38 +/- 0.8 to 3.87 +/- 0.79 l/min (p< 0.05). Pulmonary capillary pressure decreased from 23.8 +/- 8.9 to 19.8 +/- 9.2 mm Hg (p = NS). There were no significant changes in ventricular function parameters or in systemic and pulmonary pressures. CONCLUSIONS: Electrical shortening of AV interval in patients with dilated cardiomyopathy increases cardiac output but does not change ventricular function parameters.

[Vasodilator hormonal agents in chronic heart failure: effect of angiotensin-converting enzyme inhibitors]. / Hormonas vasodilatadoras en la insuficiencia cardíaca crónica: efecto de la inhibición de la enzima convertidora de angiotensina.

BACKGROUND: Administration of angiotensin converting enzyme (ACE) inhibitors to patients with congestive heart failure (CHF) is associated to a decrease in the abnormal vasoconstrictor neurohormonal activity. This contributes to the sustained benefits of these drugs on symptoms and survival of patients with CHF. There is little information, however, regarding the effects of ACE inhibition on vasodilator and natriuretic hormones. AIM: To evaluate the chronic effects of enalapril, in addition to digitalis and diuretics in patients with chronic cardiac failure. PATIENTS AND METHODS: Nine patients with an idiopathic dilated cardiomyopathy (8 male, aged 48 to 76 years old) under treatment with digitalis and diuretics, received enalapril 20 mg bid during eight weeks. Before and after this treatment period resting left ventricular ejection fraction, functional class, plasma levels of atrial natriuretic factor and bradykinins (BK) and urinary excretion of kalikreins (BK) and prostaglandin E2 (PGE2) were measured. RESULTS: After enalapril therapy, there was a significant increase in maximal O2 consumption (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min, p < 0.05) and radionuclide LV ejection fraction (27.4 +/- 1.1 to 31.4 +/- 0.9% p < 0.05). This was associated with a significant decrease in plasma ANP levels (559 +/- 158 to 178 +/- 54.8 pg/ml) and UK (391 +/- 112 to 243 +/- 92 Cu/24 h). CONCLUSIONS: The decrease in ANP levels, which is a well known marker of prognosis in CHF, could contribute to explain the sustained clinical benefits observed with ACE inhibitors in patients with CHF.

[Metalloproteinase activity in arteries and veins. Regulation with doxycycline]. / Actividad de metaloproteinasas de arterias y venas y su regulación mediante doxiciclina.

BACKGROUND: Alterations in the synthesis and degradation of extracellular matrix occur during atherogenesis. Metalloproteinases, whose activity may be inhibited with doxycicline in other tissues, play an important role in this process. AIMS: 1. To characterize metalloproteinase activities in internal mammary artery and saphenous vein, and 2. To assess the effect of doxycicline in the activity of metalloproteinases of these vessels and of cultured smooth muscle cells. METHODS: Segments of internal mammary arteries and saphenous veins and cultured smooth muscle cells were incubated with and without doxycicline. Metalloproteinases activity was assessed by zymography and Western Blot. RESULTS: Activity of metalloproteinase-9 in saphenous veins was 217% less than in internal mammary arteries. In these vessels doxycicline decreased metalloproteinase-9 activity by 207% and metalloproteinase-2 by 290%. Western Blot analysis showed that docycicline also inhibited metalloproteinase-1 expression. In cultured smooth muscle cells, the median inhibitory concentration of doxycicline for metalloproteinase-2 was 138 microM (r2 = 0.82). CONCLUSIONS: Internal mammary arteries and saphenous veins have different metalloproteinase activities, that are inhibited by doxycicline.

[Rotational atherectomy (Rotablator) for percutaneous transluminal coronary angioplasty]. / Aterectomía rotacional (Rotablator) en la angioplastía coronaria percutánea transluminal.

BACKGROUND: The use of Rotablator in percutaneous transluminal coronary angioplasty attempts to reduce the atheromatous plaque abrading it and fragmenting the parietal calcium of the artery. AIM: To report our experience with the use of Rotablator. PATIENTS AND METHODS: Rotational atherectomy was performed in 189 patients aged 60.8 +/- 11 years (154 men). The clinical indication for the procedure was chronic angina in 22%, unstable angina in 44%, myocardial infarction in 21%, silent angina in 7% and re-stenosis in 6%. One hundred seventy seven patients were followed for a mean of 15.9 +/- 6.3 months. RESULTS: Two hundred thirty six stenoses in 215 coronary arteries were treated with a 98.7% angiographic success rate. One patient had a Q infarction and no patient died or required emergency surgery. Fourteen patients had rises in CK MB enzymes (non Q infarction). Three patients had a pseudoaneurism and three had bleedings that required transfusion. Of the followed patients, 33 had a clinically suspected re-stenosis, that was angiographically confirmed in 23. Cardiac mortality was 2.3%. Seventy nine percent of patients had an evolution without angina or coronary events. CONCLUSIONS: Percutaneous transluminal coronary angioplasty with the use of Rotablator had a high immediate success rate and a low incidence of complications. The clinical evolution of patients has been favorable with a low incidence of mortality and ischemic events.

[Metalloproteinase in carotid endarterectomy plaques: increased activity in critical stenosis zones]. / Metaloproteinasas en placas de endarterectomía carotídea: actividad aumentada en áreas de estenosis crítica.

BACKGROUND: The presence of metalloproteinases in atherosclerotic plaques has been described but their role is not well understood. An increased secretion of these proteolytic enzymes could explain plaque instability and distal embolization. AIM: To measure metalloproteinase activity in atherosclerotic plaques obtained after carotid endarterectomy. MATERIAL AND METHODS: Plaques were divided in one segment with and one segment without stenosis, the latter being used as control. Both segments were incubated in culture media for 48 h or were fixed for histology. The conditioned medium was studied using gelatin zimography and digital densitometry. Metalloproteinases were identified by their molecular weight, inhibition with EDTA or Western Blot. Standard histologic study and immunohistochemistry were done. RESULTS: In stenotic areas, metalloproteinase 9 (92kD) secretion was 260% higher than in regular plaques (191 and 73 Kilopixels/microgram protein respectively p < 0.02). The histological study of stenotic areas showed macrophage infiltration and neoformation of blood vessels. CONCLUSIONS: The increased secretion of cellular matrix degrading enzyme metalloproteinase 9 in stenotic areas of atherosclerotic plaques, could explain plaque instability and subsequent embolization.

Extracellular matrix collagen synthesis and degradation following coronary balloon angioplasty.

Percutaneous transluminal coronary angioplasty is associated with intimal hyperplasia and extracellular matrix deposition of collagen, leading to restenosis in a significant number of cases. The purpose of the present study was to determine the effects of balloon angioplasty on extracellular matrix collagen content and collagenase activity in a porcine coronary artery restenosis model 6 weeks following balloon injury. We tested the hypothesis that in balloon-injured arteries the neointimal extracellular matrix was characterized by increased collagen content and decreased metalloproteinase activity relative to non-injured arteries. Male miniswine maintained on a high cholesterol diet underwent cardiac catheterization and double balloon injury to the right and left circumflex coronary arteries. The coronary arteries were either pressure-perfusion-fixed and prepared for histological examination, or dissected free of adventitia for further collagen and matrix metalloproteinase studies. Collagen synthesis in balloon-injured coronary arteries was compared to non-injured arteries using Northern blot analysis and histochemical stains. Comparative studies on differences between balloon-injured and non-balloon-injured arterial matrix metalloproteinase activity were done using zymography. Balloon angioplasty arterial injury resulted in a significant increase in type I collagen mRNA expression, with increased collagen deposition in the extracellular matrix. In contrast, matrix metalloproteinase activity was markedly decreased. The results suggest that the increased neointimal extracellular matrix observed late in the injury response may be due to not only increased collagen synthesis, but also reduced degradation. The failure to achieve a balance between the synthesis and degradation of extracellular matrix collagen could serve as an important mechanism responsible for restenosis.

[Non-invasive intermittent mechanical ventilation: usefulness in treatment of chronic severe heart failure]. / Ventilación mecánica no invasiva intermitente: utilidad en el tratamiento de la insuficiencia cardíaca crónica avanzada.

BACKGROUND: The higher respiratory work and less inspiratory muscle strength of patients with cardiac failure may contribute to decrease their functional capacity. AIM: To assess the effects of non invasive intermittent mechanical ventilation on clinical parameters, peripheral perfusion, cardiac and inspiratory muscle function. PATIENTS AND METHODS: Patients with chronic cardiac failure, functional capacity III-IV were subjected to 6 sessions of nasal non invasive intermittent ventilation during 4 hours or to simulated ventilation (controls). RESULTS: Fifteen ventilated patients and six controls completed the protocol. Ventilated patients improved the Mahler transition score for dyspnea by 4 +/- 1.6 points. They also improved their aerobic capacity, increasing the exercise duration from 10.9 +/- 4 to 12.7 +/- 5 min and their maximal oxygen consumption from 14.6 +/- 4 to 16.4 +/- 5.7 ml/kg/min. These patients also decreased their O2 and CO2 ventilatory equivalents. Maximal inspiratory pressure increased from 67.9 +/- 23.6 to 80.19 +/- 21.4 cm H2O, sustained maximal inspiratory pressure increased from 101.4 +/- 48 to 133 +/- 53 cm H2O and maximal endurance increased from 132 +/- 52 to 162 +/- 58 g in ventilated patients. None of these variables was modified in control patients. No changes were observed in renal function, blood volume, arterial gases, spirometry or plasma catecholamine levels in any group. CONCLUSIONS: Intermittent nasal ventilation or other measures to improve inspiratory muscle function may be beneficial for patients with severe cardiac failure.

Regulation of collagen degradation in the rat myocardium after infarction.

Fibrillar collagens, essential for maintaining the structural integrity of the myocardium, are degraded by matrix metalloproteinase (MMP-1). In other tissues collagenolysis is an important component of wound healing. Here we examined collagen degradation in the myocardium after infarction. Collagenase activity, measured by zymography, and expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of metalloproteinase (TIMP) mRNA, detected by Northern blotting and in situ hybridization, in the rat heart 6 h to 28 days after left coronary artery ligation were studied. Sham-operated rats served as controls. Infarcted left ventricle was compared to non-infarcted right ventricle and interventricular septum and to sham-operated tissues. We found a transient increase in collagenase activity in the infarcted left ventricle, which began at day 2 (4.5-fold increase compared to controls), peaked at day seven (6.5-fold increase) and declined thereafter, together with a concomitant increase and contribution in collagenolytic activity of gelatinases (MMP-2 and MMP-9). An increase in collagenase mRNA was not seen until day 7 and only in the infarcted ventricle, while changes in MMP-1 activity or mRNA expression were not observed at remote sites or in sham-operated controls. Transcription of TIMP mRNA was observed at 6 h (two-fold increase) in the infarcted ventricle, peaked on day two after MI (eight-fold increase) and slowly decreased thereafter. No change in TIMP mRNA expression was observed at remote sites or in sham-operated controls. Cells responsible for transcription of MMP-1 and TIMP mRNA were fibroblast-like cells, not inflammatory or endothelial cells. At the site of infarction post-translational activation of latent collagenase (MMP-1) plays a greater role in the wound healing response than transcription of collagenase mRNA. Collagenase mRNA is synthesized when the latent extracellular pool of MMP-1 is reduced through the activation of latent collagenases and gelatinases. TIMP mRNA synthesis is regulated by the activation of MMPs with the balance between collagenase activation and TIMP inhibition determining the amount of collagenolysis in infarcted tissue.