Prediction of isolated first diagonal branch occlusion by 12-lead electrocardiography: ST segment shift in leads I and aVL.

OBJECTIVES: This study was performed to determine electrocardiographic (ECG) features that could distinguish first diagonal branch occlusion from left anterior descending coronary artery occlusion. BACKGROUND: The ECG findings associated with first diagonal branch obstruction have not previously been compared with those of left anterior descending coronary artery obstruction. METHODS: The ECG findings in 34 patients with isolated diagonal branch occlusion (group 9) were compared with those in 20 patients with occlusion at site 6 (group 6) and 20 with occlusion at site 7 (group 7), according to American Heart Association classification. This study had a power > 80% to detect a 50% difference between groups at a probability value of 0.05. RESULTS: ST segment elevation was observed in leads I and aVL for all group 9 patients, in 80% (p < 0.05) of group 6 patients for lead I and 90% for lead aVL and in 50% (p < 0.01) of group 7 patients for lead I and 55% (p < 0.01) for lead aVL. Similarly, there was a higher incidence of abnormal Q waves and inverted T waves in leads I and aVL in group 9 than in groups 6 and 7. In contrast, group 9 showed a significantly lower incidence of ST segment elevation (3.4%), abnormal Q waves (3.0%) and inverted T waves (0%) in lead V1 than group 6 (80%, 40% and 90%, respectively) and group 7 (75%, 60% and 70%, respectively) (p < 0.01 for each). Multivariate analysis revealed that abnormalities in leads I and aVL, combined with a normal lead V1 (and V6), provided good criteria for distinguishing isolated diagonal branch occlusion from left anterior descending coronary artery occlusion. CONCLUSIONS: Isolated diagonal branch occlusion more frequently caused ECG abnormalities in leads I and aVL and less frequently caused changes in the precordial leads compared with left anterior descending coronary artery obstruction, indicating that leads I and aVL represent myocardium perfused by the diagonal branch.

Prediction of acute left main coronary artery obstruction by 12-lead electrocardiography. ST segment elevation in lead aVR with less ST segment elevation in lead V(1).

OBJECTIVES: We sought to determine the electrocardiographic (ECG) features associated with acute left main coronary artery (LMCA) obstruction. BACKGROUND: Prediction of LMCA obstruction is important with regard to selecting the appropriate treatment strategy, because acute LMCA obstruction usually causes severe hemodynamic deterioration, resulting in a less favorable prognosis. METHODS: We studied the admission 12-lead ECGs in 16 consecutive patients with acute LMCA obstruction (LMCA group), 46 patients with acute left anterior descending coronary artery (LAD) obstruction (LAD group) and 24 patients with acute right coronary artery (RCA) obstruction (RCA group). RESULTS: Lead aVR ST segment elevation (>0.05 mV) occurred with a significantly higher incidence in the LMCA group (88% [14/16]) than in the LAD (43% [20/46]) or RCA (8% [2/24]) groups. Lead aVR ST segment elevation was significantly higher in the LMCA group (0.16 +/- 0.13 mV) than in the LAD group (0.04 +/- 0.10 mV). Lead V(1) ST segment elevation was lower in the LMCA group (0.00 +/- 0.21 mV) than in the LAD group (0.14 +/- 0.11 mV). The finding of lead aVR ST segment elevation greater than or equal to lead V(1) ST segment elevation distinguished the LMCA group from the LAD group, with 81% sensitivity, 80% specificity and 81% accuracy. A ST segment shift in lead aVR and the inferior leads distinguished the LMCA group from the RCA group. In acute LMCA obstruction, death occurred more frequently in patients with higher ST segment elevation in lead aVR than in those with less severe elevation. CONCLUSIONS: Lead aVR ST segment elevation with less ST segment elevation in lead V(1) is an important predictor of acute LMCA obstruction. In acute LMCA obstruction, lead aVR ST segment elevation also contributes to predicting a patient's clinical outcome.

Reperfusion hastens appearance and extent of distribution of type I collagen in infarct zone: immunohistochemical study in rat experimental infarction.

BACKGROUND: The effects of reperfusion on time-dependent alteration of type I collagen have not been examined. OBJECTIVES: We compared the sequential changes in the appearance and distribution of type I collagen in reperfused infarct rat hearts to those in non-reperfused hearts. METHODS: Using an experimental rat model of infarction, we performed immunohistochemical staining with a polyclonal antibody to type I collagen by the avidin-biotin-peroxidase method. Reperfusion was established after 2-h coronary ligation that produced complete necrosis of myocytes. RESULTS: In reperfused hearts, type I collagen appeared in the peripheral zone of the infarct at day 2, which was 1 day earlier than in non-reperfused hearts. The extent of distribution of type I collagen in reperfused hearts was comparable to that observed approximately 1 day later in non-reperfused hearts. CONCLUSION: Reperfusion can accelerate collagen matrix formation compared with that in non-reperfused hearts after acute myocardial infarction.

Effect of adenosine deaminase inhibitors on myocardial reactive hyperaemia following brief coronary occlusions.

Effect of two agents of adenosine deaminase inhibitor, 8-azaguanine and adenine, on myocardial reactive hyperaemia was tested in the anaesthetised open-chest dog. Reactive hyperaemic flow response of the circumflex coronary artery was observed following 5, 10, 15, 20 and 30 s coronary occlusions before, during and after infusion of 8-azaguanine and adenine, which are known as adenosine deaminase inhibitors. Intracoronary infusion of 8-azaguanine and adenine caused the minimum increase in the baseline coronary flow. Both the nucleic acids shifted the dose response curve of adenosine to the left. 8-azaguanine enhanced volume response of flow at all occlusion intervals tested. The infused dose of adenine also intensified volume response of flow after 5, 15, 20 and 30 s occlusions. Fifteen minutes after termination of the nucleic acid infusions, the reactive hyperaemia returned towards control levels. The results suggest that 8-azaguanine and adenine enhance myocardial reactive hyperaemia possibly by inhibiting adenosine deaminase to degradate myocardial interstitial adenosine to inosine.

Forskolin potentiates myocardial reactive hyperaemia in the open chest dog: the contribution of adenylate cyclase.

Forskolin, a diterpene, directly stimulates adenylate cyclase and also potentiates receptor mediated stimulation of this enzyme by many stimulatory agonists. We exploited the potentiating effect of forskolin to test the hypothesis that activation of adenylate cyclase contributes to myocardial reactive hyperaemia, especially by release of adenosine at the time of brief coronary occlusions. In 10 open chest dogs, intracoronary forskolin infusions which produced plasma concentrations between 0.22 and 0.34 mumol.litre-1 slightly increased coronary blood flow and had no effect on haemodynamics or myocardial metabolism. Under these conditions, though peak reactive hyperaemic flow rates were not affected, forskolin infusions reversibly potentiated repayments of flow debt by 28, 25 and 27% following coronary occlusions of 15 s, 20 s and 30 s, respectively (p less than 0.05). In another seven dogs, after observations of the effects of forskolin (0.16-0.26 mumol), 10 mumol of 8-phenyltheophylline, a potent adenosine antagonist, was infused simultaneously with forskolin into the coronary arteries. Forskolin increased debt repayments by about 23-27% following 15 s, 20 s and 30 s occlusions, but with simultaneous 8-phenyltheophylline, forskolin induced increments in the debt repayments were reduced significantly (p less than 0.05). These results indicate that adenylate cyclase contributes to myocardial reactive hyperaemia, and adenosine has a significant role as metabolic regulator of reactive hyperaemia through activation of adenylate cyclase.

Oxygen metabolism of the hypertrophic right ventricle in open chest dogs.

STUDY OBJECTIVE: The aim was to investigate oxygen metabolism of the hypertrophic right ventricle in anaesthetised open chest dogs. DESIGN: Right ventricular hypertrophy was induced by right ventricular pressure overload with banding the pulmonary artery for six months. Coronary blood flow and myocardial oxygen metabolism of the hypertrophic right ventricle were determined during control and after increasing right ventricular oxygen consumption, and compared with those of the normal right and left ventricles. SUBJECTS: Seven mongrel dogs with right ventricular hypertrophy and 21 normal dogs were used. All were anaesthetised with pentobarbitone sodium. MEASUREMENTS AND MAIN RESULTS: Oxygen extraction [(A-V)O2] of the hypertrophic right ventricular myocardium was greater than that of normal right ventricle in controls and almost identical to the (A-V)O2 of the normal left ventricle. It showed no increase when coronary blood flow and right ventricular oxygen consumption were raised in response to a further elevation of the right ventricular pressure and isoprenaline infusion. However, the right ventricular interventions which increased right ventricular oxygen consumption produced an elevation of (A-V)O2 of the right ventricle with an increase in right coronary blood flow. CONCLUSIONS: Higher oxygen extraction during control and no response of oxygen extraction of the hypertrophied right ventricle in response to stimuli which increase right ventricular oxygen consumption indicate that oxygen supply to the hypertrophic right ventricle is different from that of the normal right ventricle, and is more like that of the left ventricle.

N6-substituted N-alkyladenosine-5'-uronamides: bifunctional ligands having recognition groups for A1 and A2 adenosine receptors.

The coronary vasoactivity of N-ethyl-1'-deoxy-1'-(6-amino-9H-purin-9-yl)-beta-D-ribofuranuronamide (NECA, 1) is over 2 orders of magnitude greater than that of adenosine, and the vasoactivity of certain N6-substituted adenosines is as much as 1 order of magnitude greater. Such results suggest that a combination of appropriate modifications at N6 and C-5' might additively augment the agonist potency of adenosine. At low temperatures 1-deoxy-1-(6-chloro-9H-purin-9-yl)-2',3'-O-isopropylidene- beta-D-ribofuranosyl chloride (5), obtained in three steps from inosine, reacts with amines to yield uronamides. The subsequent reaction of such uronamides with amines at elevated temperatures displaces the purine 6-chloro group to yield, after deblocking, N-alkyl(or aryl)-N6-alk(ar)yl-adenosine-5'-uronamides. At the coronary artery A2 receptor the potency of N6-modified analogues of 1 is similar to that of the N6-substituted adenosine, rather than equal to or greater than 1. As agonists in the A2 receptor-mediated stimulation of adenylate cyclase in plasma membranes of PC12 pheochromocytoma cells or human platelets, N6-substituted analogues of 1 are intermediate between the high potency of 1 and the lower potency of the N6-substituted adenosines. At the A1 receptor of rat brain the potency of an N6-substituted analogue of 1 is often greater than that of the corresponding N6-substituted adenosine. At all four receptors, replacing the ethyl group of N-ethyl-N6-3-pentyladenosine-5'-uronamide by larger alkyl groups reduces potency; amides of secondary amines are inactive or have only marginal activity. Analogues of 1 containing a chiral center in the N6 substituent retain the stereoselectivity characteristic of each of the four receptors. Thus, at either A1 or A2 adenosine receptors, adenosine analogues interact with both the N6 and the C-5' receptor regions. However, the effects of N6 and C-5' modifications on potency are less than additive, evidence that the interaction of a substituent with its receptor region influences the interaction of other substituents with their respective receptor regions.

Dog coronary artery adenosine receptor: structure of the N6-aryl subregion.

Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.

Dog coronary artery adenosine receptor: structure of the N6-alkyl subregion.

The moderately potent and stereoselective coronary vasoactivity of N6-[1-phenyl-2(R)-propyl]adenosine (1) is the basis for the present study that maps the N6 region of the coronary artery adenosine receptor by means of the structure-coronary vasoactivity relationships of 81 analogues of 1 in the open-thorax dog. Stereoselectivity is a general property of N6-substituted adenosines that have a chiral center adjacent to N6. The activity ratio of 1 to its S diastereomer is 10, the result of the positive interaction with the receptor of the propyl C-3 group of the R diastereomer in combination with the steric hindrance exerted by this group of the S diastereomer. Replacing the benzyl moiety of 1 by an ethyl, phenyl, phenethyl, or naphthyl group lowers potency of the R diastereomer and, accordingly, the R/S ratio. Propyl C-1 of 1 interacts with a receptor region large enough to accommodate three methylene residues and the propyl C-3 residue with a separate region large enough to accommodate two. The receptor subregion that interacts with the propyl C-1 of 1 is more tolerant of bulk and of polar substituents than the subregion that interacts with propyl C-3. Evidence bearing on the possible contribution of N6 to activity, e.g. through hydrogen bonding, is ambiguous. These results support a provisional model of the N6-alkyl subregion.

Q-wave regression unrelated to patency of infarct-related artery or left ventricular ejection fraction or volume after anterior wall acute myocardial infarction treated with or without reperfusion therapy.

We examined the relation of Q-wave regression to left ventricular (LV) indexes in acute anterior wall myocardial infarction (AMI) in relation to reperfusion therapy. A total of 94 patients with their first anterior wall AMI (segment 6 or 7 occlusion according to the American Heart Association classification) were examined. The follow-up period with 12-lead electrocardiograms ranged from 6 to 60 months (mean 24 +/- 18). An abnormal Q wave was defined as > 40 ms and > 25% of the R-wave amplitude. Q-wave regression was defined as Q-wave disappearance and r-wave regression > 0.1 mV in > or = 1 lead. Contingency tables with the chi-square test and analysis of variance were used for assessment of the relation between Q-wave regression and angiographic and clinical indexes. Q-wave regression in > or = 1 lead was found in 77% of the patients. The incidence of Q-wave regression in patients with patent infarct-related artery (81%) was not significantly different from that in those with an occluded lesion (67%). Q-wave regression appeared within 1 month in 60% of patients with a patent infarct-related artery but in 25% of those with an occluded lesion. No difference in the incidence of Q-wave regression was seen between patients with lesions at segments 6 (81%) and 7 (70%), or between those with (75%) and without (77%) collateral circulation. Q-wave regression did not correlate with LV ejection fraction, LV end-diastolic or end-systolic volumes, or regional wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure-activity relationships for N6-substituted adenosines at a brain A1-adenosine receptor with a comparison to an A2-adenosine receptor regulating coronary blood flow.

A series of 145 N6-substituted adenosines have been screened as inhibitors of the binding of [3H]cyclohexyladenosine to an A1-adenosine receptor in rat brain membranes and the results compared to the potencies of these analogs in increasing coronary blood flow via activation of an A2-adenosine receptor. The A1 receptor shows greater stereoselectivity in the N6 region of the receptor towards asymmetric aralkyl substituents, and shows greater bulk tolerance in the N6 region of the receptor such that it retains affinity for certain N6-tertiary alkyladenosines and N6-cycloalkyladenosines that are inactive at the coronary A2 receptor. At the A1 receptor, the most potent analogs have either aliphatic N6-substituents with four or more methylene residues or have an N6-halophenyl substituent. At the A2 receptor, the most potent analogs have an N6-phenethyl or similar heteroarylethyl substituent. Certain sets or series of analogs appear useful for identifying the subtypes of adenosine receptors involved in physiological functions.

Tenascin expression in endomyocardial biopsy specimens in patients with dilated cardiomyopathy: distribution along margin of fibrotic lesions.

OBJECTIVE: To examine the hypothesis that tenascin, an extracellular matrix glycoprotein, contributes to fibrotic changes in dilated cardiomyopathy. METHODS: The localisation of tenascin in biopsy specimens of the hearts obtained from eight patients with dilated cardiomyopathy was examined using staining by the avidin-biotin-peroxidase complex method. RESULTS: (1) Perimysium and endomysium. Although positive staining for tenascin was observed in the enlarged perimysium and endomysium in all patients, moderately intense staining was characteristically observed near the replacement fibrotic lesions. In the narrow perimysium and endomysium of the myocardium not containing replacement fibrotic lesions, tenascin was not present, as in the control specimens. (2) Replacement fibrotic lesions. Non-homogeneous positive staining for tenascin was detected in all replacement fibrotic lesions examined. Intense tenascin deposition was observed in the peripheral portion of the replacement fibrotic lesions. The tenascin staining observed in the small replacement fibrotic lesions was more intense than that in the large lesions. CONCLUSIONS: Tenascin contributes to the development of the fibrotic changes seen in the dilated cardiomyopathic heart. Its characteristic location, specifically the distribution along the margin of the fibrosis, suggests that fibrotic change is a continuous process in hearts with dilated cardiomyopathy.

Time dependent alterations of serum matrix metalloproteinase-1 and metalloproteinase-1 tissue inhibitor after successful reperfusion of acute myocardial infarction.

OBJECTIVE: To test the hypothesis that changes in serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) after acute myocardial infarction reflect extracellular matrix remodelling and the infarct healing process. PATIENTS: 13 consecutive patients with their first acute myocardial infarction who underwent successful reperfusion. METHODS: Blood was sampled on the day of admission, and on days 2, 3, 4, 5, 7, 14, and 28. Serum MMP-1 and TIMP-1 were measured by one step sandwich enzyme immunoassay. Left ventricular volume indices were determined by left ventriculography performed four weeks after the infarct. RESULTS: Serum concentrations of both MMP-1 and TIMP-1 changed over time. The average serum MMP-1 was more than 1 SD below the mean control values during the initial four days, increased thereafter, reaching a peak concentration around day 14, and then returned to the middle control range. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum MMP-1 on day 5, when it began to rise, and for the magnitude of rise in MMP-1 on day 5 compared to admission. Serum TIMP-1 at admission was more than 1 SD below the mean control value, and increased gradually thereafter, reaching a peak on around day 14. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum TIMP-1 on days 5 and 7, and for the magnitude of rise in TIMP-1 on days 5 and 7 compared to admission. CONCLUSIONS: Both MMP-1 and TIMP-1 showed significant time dependent alteration after acute myocardial infarction. Thus MMP-1 and TIMP-1 may provide useful information in evaluating the healing process as it affects left ventricular remodelling after acute myocardial infarction.

Sequential changes in the distribution of type I and III collagens in the infarct zone: immunohistochemical study of experimental myocardial infarction in the rat.

AIM: Ventricular remodeling following acute myocardial infarction is an important factor in prognosis. The healing process, involving changes in type I and III collagens, is one of the major factors in remodelling. We therefore examined sequential changes in type I and III collagens after experimental myocardial infarction. MATERIALS AND METHODS: Hearts were excised from 1 day to 10 weeks after permanent left coronary ligation in rats. Immunohistochemical staining with a polyclonal antibody to each collagen was performed by the avidin-biotin-peroxidase method. RESULTS: Type I collagen initially appeared in the peripheral zone of the infarct from 3 days after ligation, the extent of staining gradually increasing until it reached a maximal level on days 21-28, after which the distribution remained unchanged. Type III collagen appeared in the peripheral zone of the infarct from 3 days after ligation; the extent of staining reached the maximal level after 11-28 days, after which a slight decrease in the distribution was observed, although the staining did not entirely disappear. CONCLUSIONS: Type I collagen was a major factor in collagen matrix formation, especially in the relatively late phase. Type III collagen, however, contributed particularly to collagen matrix formation in the relatively early phase. This study improves current understanding of the time-dependent alterations in type I and III collagens involved in the healing process after coronary artery occlusion.

Effects of emergency coronary angioplasty on left ventricular volume after acute myocardial infarction compared with intracoronary thrombolysis.

BACKGROUND: The effects of emergency coronary angioplasty on left ventricular remodeling have not been fully evaluated. We compared the effects of emergency coronary angioplasty on left ventricular volume with those of intracoronary thrombolysis in patients suffering from their first acute myocardial infarction (AMI). METHODS: A total of 51 patients who had a culprit lesion at site No 6 of the American Heart Association (AHA) classification were analyzed. Patients with re-obstruction of the culprit lesion after reperfusion were excluded from the study. The coronary angioplasty and the thrombolysis groups consisted of 28 and 23 patients, respectively. Left ventricular volume was measured by left ventriculography at 4 weeks after infarction. RESULTS: Clinical and angiographic background factors showed no significant differences between these two groups. The left ventricular end-systolic volume index was significantly smaller in the angioplasty group than in the thrombolysis group (31 +/- 14 versus 45 +/- 14 ml/m2, P < 0.01). Similarly, the left ventricular end-diastolic volume index was significantly smaller in the angioplasty group (64 +/- 13 versus 82 +/- 13 ml/m2, P < 0.01). Conversely, the left ventricular ejection fraction was larger in the angioplasty group than in the thrombolysis group (54 +/- 13 versus 45 +/- 13%, P < 0.05). Multivariate analysis revealed that the selection of coronary angioplasty was one of the factors significantly associated with a decrease in left ventricular end-systolic and end-diastolic volume. CONCLUSION: These results suggest that emergency coronary angioplasty produces better left ventricular remodeling than intracoronary thrombolysis after AMI.

Reperfusion accelerates the distribution of type I and III collagen messenger RNA expression after acute myocardial infarction: in situ hybridization in experimental infarction in rats.

BACKGROUND: The effects of reperfusion on the time-dependent appearance and distribution of type I and III collagen messenger RNA (mRNA) expression had not hitherto been examined. OBJECTIVE: To compare the sequential changes in the extent of distribution of type I and III collagen mRNA expression in reperfused infarct hearts of rats with those in unreperfused infarct hearts. METHODS: Using an experimental rat model of infarction, we examined type I and III collagen mRNA expression with specific rat pro alpha 1 (I) and human pro alpha 1 (III) collagen riboprobes by in-situ hybridization. Reperfusion was established after a 2 h coronary ligation that produced complete necrosis of the myocytes. RESULTS: Positive signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA appeared in the infarct peripheral zone 12 h after coronary ligation both of the reperfused and of unreperfused hearts. The spread of signal into the infarct central zone occurred 1-2 days earlier for the reperfused hearts than it did for the unreperfused hearts. The difference between the distributions of signals for the reperfused and unreperfused hearts became obscure on day 14. No notable difference between the extents of signal distribution for alpha 1 (I) and alpha 1 (III) collagen mRNA was obtained. We observed intense signals from spindle-shaped mesenchymal cells (myofibroblasts and fibroblasts) located between surviving myocytes in the marginal zone of the infarct. No myocyte exhibited signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA. CONCLUSION: In the present study, using in-situ hybridization, we demonstrated that reperfusion accelerates the distribution of expression both of alpha 1 (I) and of alpha 1 (III) collagen mRNA in the infarct zone after acute myocardial infarction in rats.

Time-dependent increases in syndecan-1 and fibroglycan messenger RNA expression in the infarct zone after experimentally induced myocardial infarction in rats.

BACKGROUND: Syndecan-1 and fibroglycan, heparan sulphate proteoglycans, play important roles in extracellular matrix formation via their biological functions. OBJECTIVE: To examine experimentally the sequential changes in syndecan-1 and fibroglycan messenger RNA (mRNA) expression after acute myocardial infarction. MATERIALS AND METHODS: The left coronary arteries of male Sprague-Dawley rats were ligated and the hearts were excised on days 1-14, 28 and 42. Syndecan-1 and fibroglycan mRNA expression in the infarct and non-infarct zones and in sham-operated hearts was determined by reverse transcriptase-polymerase chain reaction. Amplified products were quantified by densitometry of the electrophoresed bands stained with ethidium bromide and standardized relative to the glyceraldehyde 3-phosphate dehydrogenase or beta-actin mRNA expression. Northern hybridization was also performed in the infarct and non-infarct zones on day 3. RESULTS: Expression both of syndecan-1 and of fibroglycan mRNA began to increase on day 2. The expression attained maximum levels on day 3. The maximum levels of syndecan-1 and fibroglycan expression were, respectively, sevenfold and fivefold the preligation level and the level in the sham-operated hearts. The levels remained elevated until day 14, whereupon they declined gradually, returning to the control levels by around day 42. Northern blotting also demonstrated that there was an increased expression both of syndecan-1 and of fibroglycan mRNA in the infarct compared with that in the non-infarct zone on day 3. CONCLUSION: Our results demonstrated that there are sequential increases in the expression both of syndecan-1 and of fibroglycan mRNA in the infarct zone after experimentally induced myocardial infarction in rats, suggesting that these proteoglycans play some role in the pathological course of infarction.

Greater than normal expression of the collagen-binding stress protein heat-shock protein-47 in the infarct zone in rats after experimentally-induced myocardial infarction.

BACKGROUND: The heat-shock protein with relative molecular mass 47,000 (HSP47) can bind to procollagen molecules in the endoplasmic reticulum, and acts as a molecular chaperone during the processing and secretion of procollagen. OBJECTIVE: To test our hypothesis that HSP47 is expressed in the myocardial infarct zone. METHODS: We induced myocardial infarction in male Sprague-Dawley rats by ligation of left coronary artery. The expression of HSP47 was examined by Northern blotting, in-situ hybridization, Western blotting and immunohistochemistry. The time-dependent change in the distribution of HSP47 messenger RNA (mRNA) signal was compared with the changes in expression of alpha 1(I) and alpha 1(III) collagen mRNA by in-situ hybridization. The hypoxic induction of HSP47 in cultured cardiac fibroblasts was examined by Northern-blot analysis. RESULTS: Northern blotting demonstrated that the expression of HSP47 mRNA had increased on day 2, reaching a maximum level around day 14 (induced 3.5-fold compared with the preligation hearts) and was maintained at a high level up to day 28. In-situ hybridization analysis revealed HSP47 mRNA signals in spindle-shaped mesenchymal cells located between surviving myocytes in the infarct's peripheral zone 24 h after the ligation, and in the entire infarct zone on day 14. The sequential changes in distribution of HSP47 mRNA signal were identical to those of the alpha 1(I) and alpha 1(III) collagen mRNA. Western blotting demonstrated that expression of HSP47 protein in the infarct zone had increased. Immunofluorescent staining revealed positivity for HSP47 in the infarct's peripheral zone on day 2 and in the entire infarct zone on day 14. Northern blotting revealed that the expression of HSP47 mRNA in cultured cardiac fibroblasts in hypoxic cultures was greater than that in normoxic cultures. CONCLUSION: The present data demonstrated that an increase in expression of HSP47 is produced by spindle-shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia.

BACKGROUND: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. PATIENTS AND METHODS: Thirteen patients with chronic atrial fibrillation associated with bradycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. RESULTS: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 +/- 0.8 weeks (mean +/- SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was significantly improved and the plasma atrial natriuretic polypeptide level was significantly decreased after the initiation of cilostazol treatment. CONCLUSION: Cilostazol improves the slow HR episodes associated with chronic atrial fibrillation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

Coronary to bronchial artery anastomosis in patients with noncyanotic cardiopulmonary disease: report of seven cases.

An angiographically visible coronary to bronchial artery anastomosis was found in seven (0.12%) of 6045 patients with noncyanotic cardiopulmonary disease who underwent coronary angiography between 1989 and 1995. Aortitis syndrome was associated with four patients, whereas pulmonary embolism, aortic regurgitation and vasospastic angina were the diagnoses in the others. Coronary stenotic lesions were not observed in any patients. In five of six patients who underwent pulmonary perfusion scintigraphy, perfusion defect was observed in the area supplied by the bronchial artery, which had the anastomosis to the coronary artery. In each patient this anastomosis seemed to function as collateral circulation, compensating for decreased perfusion in either the lung or the heart. When coronary to bronchial artery anastomosis is found, ischemic conditions in either the lung or the heart are likely.