Results of voluntary cardiovascular examination of elite athletes in Denmark: Proposal for Nordic collaboration.

We investigated the cardiovascular status of elite athletes in Denmark, the extent of abnormal cardiac findings--both training related and pathologic--and how participating in cardiac examination was perceived by the athletes. A standardized protocol of questionnaires, physical examination, resting electrocardiogram, and 2D echocardiography was used. In total 1347 elite athletes were invited; 516 athletes (38%) from 30 different sports participated. Results were stored in a web-based database for future research and long-term follow-up. Cardiac pathology was infrequent; eight athletes (1.6%) received a cardiac diagnosis; one athlete (0.2%) diagnosed with long QT syndrome was advised against competition level sports. In total, 60 athletes (11.6%) were referred for additional testing. The athletes presented a very low level of psychological stress before and a slight decrease immediately after the examination as measured by the REST-Q 76 Sport questionnaire. Athletes needing further examinations did not present a higher level of stress after the initial examination compared with athletes with normal test results. Overall, very few athletes were diagnosed with a cardiac condition that increased risk of sudden cardiac death. Less than half of the invited athletes volunteered, but participation was not perceived stressful by the enrolled athletes, not even when additional testing was needed.

Long-term changes in collagen formation expressed by serum carboxyterminal propeptide of type-I procollagen and relation to left ventricular function after acute myocardial infarction.

The purpose of this study was to investigate the long-term sequential changes in serum levels of the carboxyterminal propeptide of type-I procollagen (s-PICP), which is a marker of type-I collagen synthesis, and to assess its clinical value in relation to left ventricular (LV) function and prognosis following acute myocardial infarction (AMI). Forty-eight consecutive patients with their first AMI and 15 control subjects were studied. Patients with AMI were stratified according to the changes in s-PICP levels between days 1 and 90 (DeltaPICP) and divided into group I with < or =16.0 microg/l or group II with >16.0 microg/l. Patients in group II were characterized by LV dilatation, no improvement in ejection fraction and development of impaired diastolic filling from day 1 to 360, findings which were in contrast to group I. Cox regression analysis identified changes in s-PICP of >16.0 microg/l as an independent predictor of cardiac death or heart failure during follow-up. In conclusion, DeltaPICP relates to long-term changes in LV function and size, and provides prognostic information following AMI.

Relationship between serum amino-terminal propeptide of type III procollagen and changes of left ventricular function after acute myocardial infarction.

BACKGROUND: The amino-terminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen synthesis, which has previously been shown to correlate with infarct size in nonthrombolyzed myocardial infarction (MI) and to provide prognostic information after MI. METHODS AND RESULTS: The relationship between PIIINP and changes of left ventricular (LV) function was studied in 47 consecutive patients with first acute MI and 16 control subjects. Serum PIIINP analysis was measured daily during hospitalization and on days 90, 180, and 360. LV function was assessed by echocardiography on days 1, 5, 90, and 360. Patients with MI were stratified according to their serum PIIINP value at day 4 (group A, 5.0 microg/L). On arrival, LV function and size were comparable between groups A (n=31) and B (n=16). LV ejection fraction, initially depressed (day 1: group A, 47+/-7% versus group B, 47+/-8%; P=NS), increased significantly in group A (day 360: 54+/-8%, P<0.001) but was unchanged in group B (day 360: 43+/-8%, P=NS). LV volumes increased significantly in group B (P<0. 05) but not in group A. Furthermore, patients in group B developed signs of restrictive LV diastolic filling. Multivariate regression analysis identified PIIINP >5.0 microg/L and deceleration

Ischemia and reperfusion of the porcine myocardium: effect on collagen.

We studied the effect of acute myocardial infarction and late reperfusion on myocardial collagen in a closed chest porcine model, to investigate if any collagen degradation could be detected in blood samples and myocardium. Sixteen 60-80 kg pigs were used with six animals serving as controls and 10 submitted to ischemia-reperfusion. In the ischemia-reperfusion group the left anterior descending coronary artery was occluded for 6 h by inflation of a percutaneous transluminal coronary angioplasty balloon followed by reperfusion for 3 h. Blood samples were taken from the aorta and the coronary sinus and analyzed for creatine kinase and collagen degradation products, i.e. the N-terminal propeptide of procollagen type III (PIIINP) and C-terminal pyridinoline cross-linked telopeptide of collagen type I (ICTP). Myocardial tissue samples were analyzed for content of hydroxyproline, collagen volume fraction and amount of extractable PIIINP/dry weight. Transmission electron microscopy of biopsies was performed to evaluate myocytes and collagen structure outside and within the infarct zone. Creatine kinase showed a statistically significant increase during ischemia and reperfusion but we found no evidence of release of collagen degradation products either during ischemia or reperfusion compared with control. Myocardial content of hydroxyproline, collagen volume fraction and extractable PIIINP/dry weight did not differ between groups. Transmission electron microscopy of biopsies from the infarct zone showed myocyte damage but no visible evidence of collagen degradation when photos were evaluated blindly. In this porcine model of acute myocardial infarction and late reperfusion no release of collagen degradation products from the myocardium or any decrease in or damage to myocardial collagen was detected.

Serum aminoterminal propeptide of type III procollagen after cardiac transplantation and the effect of rejection.

The present study examines serum concentrations of the aminoterminal propeptide of type III procollagen (S-PIIINP), a marker of type III collagen synthesis, after heart transplantation, and assesses changes induced by rejection. Fourteen transplant patients were included with 12 coronary artery bypass patients serving as controls. Mild to moderate rejection was found in 44 biopsies, and severe rejection in 6. Two severe rejection incidents occurred before postoperative day 10, the remainder at postoperative days 23 to 57. S-PIIINP was elevated in transplant patients at postoperative days 1 to 7 (p < or = 0.01), with return to baseline at postoperative day 60 (p = 0.14, n = 6). S-PIIINP remained unchanged after mild to moderate rejection, but increased 1 to 2 weeks following severe rejection occurring after postoperative day 10. S-PIIINP was elevated in bypass patients from postoperative day 2 throughout the study period of 360 days (p < or = 0.01). Thus, type III collagen turnover after heart transplant and coronary artery bypass grafting resembles wound healing. Collagen synthesis after severe rejection is reflected by S-PIIINP approximately 2 weeks after transplant. The findings may prove to be significant concerning the prognosis of heart transplant patients.

Diffusional transport of the aminoterminal propeptide of type III procollagen in the interstitium of the globally ischaemic cat myocardium.

Local repair after acute myocardial infarction appears to be reflected by levels in serum of the aminoterminal propeptide of type III procollagen (serum-PIIINP). Furthermore, serum-PIIINP has recently been reported to provide information on prognosis after acute myocardial infarction. However, no attention has yet been paid to the resistance to diffusion offered by the myocardial interstitium. We determined the diffusion coefficient of PIIINP in the interstitium of the globally ischaemic interstitium of the cat (D'37) by means of a "true transient diffusion' method, and compared with the free diffusion in water (D37). D'37 (in cm2 s-1.10(-5) was 0.0157 +/- 0.0005 (mean +/- SEM) (n = 13), and D37 was 0.0624 +/- 0.0024 (n = 12). The mean diffusive progression during 20 min of the concentration profile of [125I]PIIINP into the tissue was calculated to be 0.19 mm. The D'37 of albumin is practically identical to the D'37 of PIIINP, and the myocardium offers a similar resistance to diffusion of PIIINP and albumin, as expressed from the ratio D37/D'37 of approximately 4 for both molecules. PIIINP has a molecular weight of 42,000 Da, is rod shaped and has an overall negative charge. These characteristics explain the similarity in diffusion coefficients of PIIINP and albumin, which has a molecular weight of 69,000 Da. Albumin is known to pass the membrane of the continuous capillaries of the heart, making it very likely that direct exchange of PIIINP between interstitium and capillary plasma can also occur. During one hour of interstitial diffusion PIIINP will have traversed a distance calculated tp correspond to 15-20 capillaries. Therefore, the results support the concept of serum-PIIINP as a direct marker of events taking place locally in the myocardium following acute myocardial infarction.

The aminoterminal propeptide of type III procollagen provides new information on prognosis after acute myocardial infarction.

The aim of the study was to examine sequential changes in serum levels of the aminoterminal propeptide of type III procollagen (S-PIIINP) after acute myocardial infarction (AMI), and to assess the value of S-PIIINP as a predictor of outcome. The study group comprised 74 patients with AMI, and 24 patients in whom AMI was suspected but disproved. S-PIIINP changed characteristically after AMI, and in patients not receiving thrombolytic therapy or having cardiogenic shock, the changes correlated to peak enzyme values (r = 0.4, p < or = 0.03). S-PIIINP was higher at days 0 to 2 in nonsurviving AMI patients than in survivors (p < 0.05). With use of either the upper quartile for S-PIIINP at day 0 for nonsurviving AMI patients or the mean value of S-PIIINP in a normal population plus 2 SDs as a cutoff, the predictive value of a negative test ranged from 0.79 to 0.87 at days 0 to 2, and the predictive value of a positive test ranged from 0.39 to 0.67. Thus, S-PIIINP on admission and for the following few days after AMI is higher in patients with poor outcome.

Glucocorticoids inhibit the synthesis rate of type III collagen, but do not affect the hepatic clearance of its aminoterminal propeptide (PIIINP).

The aminoterminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen metabolism. The serum concentration of PIIINP is increased during inflammation, probably reflecting stimulated biosynthesis of type III collagen. Serum PIIINP decreases during glucocorticoid treatment. This has been interpreted as an inhibited biosynthesis of type III collagen. However, circulating PIIINP is extracted by the liver, and the decrease in serum PIIINP may also be caused by an increased hepatic elimination. In the present study we investigated the influence of intravenous methylprednisolone on the serum PIIINP level in pigs combined with a simultaneous determination of the hepatic extraction of PIIINP. The serum level of PIIINP decreased by approximately 30% within 2 h following glucocorticoid injection (p < 0.01). The initial hepatic extraction ratio of PIIINP was 0.15 (range 0.05-0.33) and neither changed after administration of methylprednisolone nor differ from that of the controls. Injection of methylprednisolone did not influence the gel filtration profile. The results of this study confirm the previous finding of serum PIIINP being decreased following glucocorticoid administration, but disprove the hypothesis that alterations in the liver extraction of PIIINP explain the decrease.

Effect on collagen metabolism of thrombolytic therapy with tissue-plasminogen activator. A randomized, placebo-controlled study.

This paper assesses alterations in collagen metabolism following thrombolytic therapy of acute myocardial infarction with tissue-plasminogen activator. Sequential serum measurements of the amino-terminal propeptide of type III procollagen (S-PIIINP) and the carboxyterminal propeptide of type I collagen (S-PICP) in patients suspected of acute myocardial infarction randomized to tissue-plasminogen activator or placebo were used. S-PIIINP increased at 3 h in patients with acute myocardial infarction treated with tissue-plasminogen activator (P < 0.05). S-PIIINP was higher in patients treated with tissue-plasminogen activator compared with placebo-treated patients at 3 and 6 h (P < 0.05). S-PICP decreased independently of therapy and diagnosis. Tissue-plasminogen activator, therefore, induces breakdown of collagen, some of which is located in the wall of atheromatous arteries. Vascular patency following thrombolytic therapy may partly be mediated by breakdown of thrombogenic collagen in the vessel wall. The findings may suggest a role for S-PIIINP as a non-invasive indicator of the risk of reocclusion.

Thrombolytic therapy of acute myocardial infarction alters collagen metabolism.

The objective of the study was to monitor collagen metabolism after thrombolytic therapy. Sequential measurements of serum aminoterminal type-III procollagen propeptide (S-PIIINP) and carboxyterminal type-I procollagen propeptide (S-PICP) were made in 62 patients suspected of acute myocardial infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (p < or = 0.02), and decreased during the next 20 h with median values at 24 h still above the baseline (p < 0.02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p < 0.01), with values still elevated at 6 months. No similar biphasic pattern was found for S-PICP, but patients with acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p < 0.05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered for at least 6 months. Furthermore, fibrin-specific and nonspecific thrombolytic agents appear to affect collagen metabolism differently.

[Infarction expansion and ventricular remodelling after acute myocardial infarction]. / Infarktekspansion og ventrikulaer remodellering efter akut myokardieinfarkt.

Infarct expansion (IE) and ventricular remodelling (VR) are interdependent pathophysiologic processes in the heart following acute myocardial infarction (AMI), and may contribute to dilatation of the left ventricle, heart failure, left ventricular aneurysm and/or rupture, and poor prognosis. IE and VR are demonstrated by echocardiography, and are usually seen with large, transmural, anterior AMI, hypertension and persisting occlusion of the infarct-related coronary artery. All myocardial tissue components are involved in IE and VR, and local generation of growth factors, vasoactive mediators, oxygen-derived free radicals, and activation of the renin-aldosterone-angiotensin system may have pathophysiological significance. These mechanisms can provide the opportunity for therapy, and evidence suggests that treatment with angiotensin converting enzyme-inhibitors can attenuate IE and VR.

Effect of 5-aminosalicylic acid on myocardial capillary permeability following ischaemia and reperfusion.

OBJECTIVE: The aim was to evaluate the effect of 5-aminosalicylic acid on myocardial capillary permeability for small hydrophilic molecules after ischaemia and reperfusion. METHODS: Open chest anaesthetised dogs were subjected to a 20 min occlusion of the left anterior descending coronary artery followed by 1 h reperfusion. 5-Aminosalicylic acid (bolus injection 12 mg.kg-1, followed by 105 micrograms.kg-1.min-1) (n = 10) or saline (control, n = 12) was given intravenously for 1 h, starting 20 min before ischaemia. The myocardial plasma flow rate, myocardial capillary extraction fraction, and myocardial capillary permeability-surface area (PS) product for 99mTc-DTPA were determined before ischaemia, and 5 and 60 min after the start of reperfusion by employing the single injection residue detection method. Immediately after reperfusion, the reactive hyperaemic plasma flow was measured by the 133Xe washout method. RESULTS: Four dogs (two untreated and two treated with 5-aminosalicylic acid) were eliminated due to ventricular fibrillation at the time of reperfusion. In the remaining animals (10 controls and eight treated) the plasma flow rate, capillary extraction fraction and PS were similar before myocardial ischaemia. After 5 min reperfusion, the plasma flow rate and PS were significantly increased in control animals (p < 0.02 and p < 0.008, respectively), but were unchanged in dogs treated with 5-aminosalicylic acid. In addition, after 5 min reperfusion, PS was significantly higher in the control group than in treated animals (p < 0.005). Microcirculatory variables returned to preocclusive values in both groups by 60 min after reperfusion. 5-Aminosalicylic acid had no significant effect on haemodynamics or on reactive hyperaemic plasma flow. CONCLUSIONS: The results suggest that 5-aminosalicylic acid can attenuate the microvascular changes after reversible myocardial ischaemia. The effect is potentially beneficial, and may be mediated by well recognised anti-inflammatory actions of 5-aminosalicylic acid (ie, scavenging of oxygen free radicals and neutrophil inhibition).

[Traumatic rupture of a main bronchus. Clinical and peroperative presentation, physiopathological mechanisms, treatment and late sequelae]. / Traumatisk ruptur af hovedbronchus. Klinisk og peroperativ praesentation, patofysiologiske mekanismer, behandling og senfølger.

On the basis of a case report, the clinical and peroperative features of bronchial rupture caused by blunt thoracic trauma, theories concerning the pathophysiological mechanisms, the treatment and outcome are reviewed. Two distinct clinical presentations may occur: (a) with free communication between the bronchus and the pleura (as in the present case) and (b) with little or no communication. The suspected diagnosis is confirmed by bronchoscopy. Peroperatively, bronchial rupture is seen at places of reduced resistance (the junction between the cartilaginous and the membranous trachea or bronchus and the annular ligaments) and typically within 2.5 cm from the carina. The pathophysiological basis includes three mechanisms: decrease in the anteroposterior diameter of the thorax, sudden increase in intrabronchial pressure with a closed glottis and rapid deceleration. These mechanisms may occur independently or together. The initial treatment aims at maintaining the airway, reversing shock and relieving pneumothorax. Surgical repair should follow as soon as the condition of the patient permits. The optimal surgical technique is identical with that employed for vascular anastomoses. Surgical repair of bronchial rupture should only be omitted if extensive parenchymal pulmonary damage and/or suppuration are present. Even after years of delay, reconstruction will lead to partial recovery of pulmonary function.

[Reperfusion injury in the myocardium--significance of the oxygen-derived free radicals]. / Reperfusionsskade i myokardiet--betydningen af oxygenderiverede frie radikaler.

Convincing proof is now available that reperfusion of the ischaemic myocardium results in release of oxygen-derived free radicals (ODFR). Experimental data support the hypothesis that ODFR play a pathological physiological role in the development of post-ischaemic systolic dysfunction (stunning), microcirculatory disturbances and reperfusion arrhythmias. In addition, the free radicals appear to modify the energy metabolic conditions after reperfusion. The results from investigations of the effects of ODFR on the extent of myocardial infarction are difficult to interpret as, in various experimental series in which formation of ODFR is reduced to a minimum, the infarct reducing effect has not been found to be in agreement with similar durations of ischaemia. The varying results concerning the extent of the infarcts suggests that other factors e.g. collateral circulation and balance between oxygen supply and oxygen requirements play a dominating role in these problems. It has not yet been elucidated whether ODFR are of significance in man in connection with reperfusion of the ischaemic myocardium.

Arachidonic Acid-induced Platelet Aggregation ex vivo in Patients with Acute Ischaemic Heart Disease.

The threshold concentrations of arachidonic acid (AA) required to induce platelet aggregation were measured in platelet-rich plasma (PRP) from patients with acute ischaemic heart disease and healthy controls. The analytical precision of the test was very good (coefficient of variation 0-4%). Analytical accuracy was evaluated by comparing the results with threshold values for collagen-induced platelet aggregation, and a significant correlation was found (r = 0.56; p<0.01). When comparing the serum levels of thromboxane B(2) to threshold values for AA-induced platelet aggregation an inverse relationship was found (r = -0.37; p<0.01). In the clinical study significantly increased aggregability to AA was seen in patients with unstable angina pectoris (n = 13) compared to patients with stable angina pectoris (n = 14), (p<0.01), and both groups had hyperaggregating platelets compared to healthy controls (n = 27), (p<0.01). The patients with acute myocardial infarction (n = 10) had nearly normoaggregating platelets for the first 2-3 days after admission, but after a week and at day 14 their platelets showed significant hyperaggregability compared to healthy controls (p<0.01). Thus studies of AA-induced aggregation ex vivo suggest that patients with unstable angina pectoris and acute myocardial infarction, in whom coronary thrombus is frequently present, have increased platelet aggregability compared to patients with stable angina pectoris and healthy controls.

[Right-sided cardiac failure as the primary symptom of carcinoid]. / Højresidigt hjertesvigt som primaersymptom ved karcinoid.

A case is presented where endocardial fibrosis with pulmonary stenosis, incompetence of the tricuspid valve, and severe right-sided heart failure, proved to be the only signs of a carcinoid tumor in the left ovary.

[Acute myocardial infarction as the primary symptom in essential thrombocytosis in a 17-year-old male]. / Akut myokardieinfarkt som debut ved essentiel trombocytose hos 17-årig mand.

A case of acute myocardial infarction and signs of ischemic heart disease as the only manifestation of the myeloproliferative disorder essential thrombocytosis in a 17 year old male is presented.