Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population.

BACKGROUND AND PURPOSE: Trimetazidine, known as a metabolic modulator, is an anti-anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients. EXPERIMENTAL APPROACH: Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control). KEY RESULTS: There was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid. CONCLUSION AND IMPLICATIONS: Using myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism.

[THROMBOPROPHYLAXIS IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION ADMITTED IN UNIVERSITY HOSPITAL SPLIT, CROATIA, DUE TO THE ISCHAEMIC STROKE IN RELATION TO THROMBOEMBOLIC AND BLEEDING RISK].

Aim of the study was to assess the concordance of the thromboprophylactic treatment in patients with nonvalvular atrial fibrillation (nAF) at the time of admission due to ischemic stroke with clinical guidelines of the European Society of Cardiology. METHODS: In the cross-sectional study were included 327 patients [143 (44%) males] treated because of ischemic stroke associated with nAF. The index of the thromboembolic risk (TE) has been established by the CHA2DS2-VASc score, whereas the bleeding risk has been assessed by the HAS-BLED score. RESULTS: Before the ischemic stroke, 98.2% of patients belonged to the group of high TE risk. Among these patients only 179 (55%) were received thromboprophylaxis: 67.5% patients acetylsalicylic acid, 30.5% warfarin, and 4% clopidogrel. Previous ischemic stroke was independently correlated with warfarin administration (OR 2.5; 95% Cl 1.4-4.5; p=0.003), while poorly controlled arterial hypertension was independently correlated with warfarin non-administration (OR 0.47; 95% Cl 0.25-0.88; p=0.019). The 83.7% of 55 patients, who experienced ischemic stroke during anticoagulant treatment, had an INR values lower than therapeutic. CONCLUSION: Thromboprophylaxis among the patients with nAF admitted because of ischemic stroke did not correlate with their TE risk and contemporary guidelines of the European Society of Cardiology.

Peptic ulcer disease in dyspeptic patients with ischemic heart disease: search and treat?

OBJECTIVE: The aim of this study was to determine the prevalence and risk factors for peptic ulcer disease (PUD) in dyspeptic patients with ischemic heart disease (IHD), and to assess whether the healing of PUD before coronary artery bypass grafting (CABG) could reduce the need for urgent postoperative endoscopy. PATIENTS AND METHODS: A series of 894 patients referred to Dubrava University Hospital in Zagreb for elective CABG during the period from May 1998 until April 2001 was prospectively analysed. Dyspepsia was assessed by a questionnaire, PUD by upper gastrointestinal endoscopy, and H. pylori status by histology/Giemsa staining and the rapid urease test. The need for urgent postoperative endoscopy (hematemesis and/or melena, sudden onset of anemia or unexplained epigastric pain) was compared between the prospective study group of 894 patients and a series of 463 patients referred for CABG to Dubrava University Hospital during the period from January 1997 until April 1998. RESULTS: Gastroduodenal dyspepsia predominated in 184 (20.6 %) patients, 142 (77.2 %) of them with Helicobacter (H.) pylori infection and 69 (37.5 %) with verified PUD. Univariate analysis indicated the increased risk of multiple PUD to be related to a previous diagnosis of PUD (OR 3.61, 95 % CI 1.32 - 9.82), H. pylori infection (OR 18.86, 95 % CI 2.31 - 153.98), use of aspirin (OR 5.70; 95 % CI 1.80 - 18.03) and left coronary artery occlusions (3.10, 95 % CI 1.00 - 9.59). Multivariate analysis pointed to H. pylori infection (OR 16.30, 95 % CI 1.57 - 168.53) and left coronary artery occlusions (OR 4.84, 95 % CI 1.05 - 22.30) as independent risk factors for multiple PUD. The OR for urgent postoperative endoscopy due to a major gastrointestinal event was 9.9 (95 % CI 2.2 - 45.1) and the OR for active peptic ulcer with stigmata of recent bleeding was 6.9 (95 % CI 1.4 - 33.1) in the group of patients with IHD who were not submitted to evaluation for dyspepsia prior to elective heart surgery. CONCLUSIONS: In areas with a high prevalence of H. pylori infection, endoscopy and a "search and treat" strategy for IHD patients with dyspepsia before elective cardiac surgery should significantly reduce the need for urgent postoperative endoscopy due to major gastrointestinal events.

Trends in myocardial infarction in Middle Dalmatia during the war in Croatia.

The aim of this study was to determine the pattern of myocardial infarction (MI) incidence with regard to age, gender, infarction site, and the most important risk factors. All 3,454 patients hospitalized in coronary care units of Clinical Hospital Split between 1989 and 1997 were analyzed. In the 3-year period preceding the war, from 1989 to 1991, 1,024 patients were hospitalized because of MI. During the 3 years of full war activities, from 1992 to 1994, there were 1,257 patients (significantly more; p < 0.05). And in the 3-year period after the war, from 1995 to 1997, there were 1,173 patients. In the war period, there were 151 (12%) patients younger than 45 years of age (p < 0.05); of that number, 143 (95%) were men (significantly more than in the other two periods; p < 0.05) and 8 (5%) were women. In the period preceding the war, there were 66 (6.5%) patients younger than 45 years: 60 (91%) men and 6 (9%) women. In the period after the war, those numbers were 88 (7.5%), 81 (92%), and 7 (8%), respectively. The patients younger than 45 years (305) more often had MI of an inferior than an anterior site (49% vs. 28%; p < 0.001), whereas there was no difference in patients older than 45 years (36% vs. 37%; p > 0.05). The patients older than 45 years had significantly greater hospital mortality (21% vs. 4%; p < 0.001) and were more likely to have hypertension (51% vs. 15%; p < 0.001) as well as hypercholesterolemia (54% vs. 14%; p < 0.001). Smokers prevailed among those younger than 45 years (75% vs. 51%; p < 0.001). The number of hospitalized patients with MI was greatest during the war period. It included a significant increase in the incidence in men younger than 45 years (12% vs. 7%; p < 0.05), with smoking as the most important risk factor, especially for infarctions of inferior sites.

Ultrasonographic appearance of colon taeniasis.

We present the case of a 50-year-old woman with abdominal pain, nausea, loss of appetite, and frequent stools in whom the routine ultrasonographic examination demonstrated a double-reflective, ribbon-like structure in the lumen of the initial segment of the ascending colon, which suggested colon taeniasis. Because the initial parasitologic analysis yielded negative results and application of albendazol did not have any therapeutic effect, the diagnosis was confirmed by barium enema and subsequently by parasitologic examination of proglottids passed in the stool after application of niclosamide. The double-reflective, ribbon-like structure in the lumen of the intestine seems to be specific to the ultrasonographic appearance of intestinal taeniasis. Transcutaneous ultrasonography of the gastrointestinal tract, performed as a screening method before conventional radiologic or endoscopic examination, can point to the ultimate diagnosis of colon taeniasis.

Activity of serum angiotensin-converting enzyme as a tumour marker of hepatocellular carcinoma.

OBJECTIVE: Previous studies have pointed to the changes of serum angiotensin-converting enzyme (SACE) values in patients with liver disease and cancer located in different sites. The aim of this study was to determine the changes in SACE values in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. METHODS: The study comprised 30 patients with HCC (22 men and eight women) of average age 48.6 +/- 9.0 years and 30 patients with liver cirrhosis (21 men, nine women) of average age 49.1 +/- 9.5 years. The control group consisted of 30 healthy volunteers with matching anthropometric characteristics. SACE activity was determined by a spectrophotometric method using synthetic hippuryl-glycyl-glycine as substrate. RESULTS: The mean SACE value was considerably lower in patients with HCC, 22.8 U/ml (95% CI, 22.5-23.9), both those in whom HCC developed in cirrhotic liver (n = 23), 23.7 (22.9-24.5) as well as those with HCC without cirrhosis (n = 7), 21.8 (21.0-22.6), with regard to patients with liver cirrhosis, 37.2 (36.6-37.8) (P < 0.001). There was also a statistically significant difference between healthy, 29.9 (29.4-30.3), and both groups of HCC patients (P < 0.001). No significant differences could be found between the group of HCC patients with and without liver cirrhosis (P < 0.05). In patients with liver cirrhosis SACE value was increased in accordance with the severity of the disease expressed by Child's classification; however, at each stage SACE values were considerably lower in patients with HCC in cirrhotic liver (Child A, 35.8 vs 22.1; Child B, 38.7 vs 24.2; Child C, 40.0 vs 28.3) (P < 0.001). Alfa-fetoprotein (AFP) values did not correlate with the SACE activity. The SACE value was also significantly decreased in patients with HCC whose AFP were not altered. CONCLUSION: The study has shown that SACE values are low in patients with advanced HCC. It may be helpful in detecting HCC in patients with cirrhosis, where it can be difficult to differentiate between small HCC tumours and regeneration nodules.

Dermatological indicators of coronary risk: a case-control study.

OBJECTIVE: We examined the association of dermatological signs such as baldness, thoracic hairiness, hair greying and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60 years. METHODS: A hospital-based, case-control study included 842 men admitted for the first non-fatal myocardial infarction, the controls were 712 men admitted with noncardiac diagnoses, without clinical signs of coronary disease. The relative risks were estimated as odds ratios. Logistic regression was used to control for the confounding variables. RESULTS: Baldness, thoracic hairiness and earlobe crease were approximately 40% more prevalent in cases (P<10(-6) in each case). In both cases and controls, baldness and thoracic hairiness were frequently coexistent, as well as hair greying and earlobe crease (P<10(-4) in each case). After allowing for age and other established coronary risk factors, the relative risk of myocardial infarction for fronto-parietal baldness compared with no hair loss was 1.77 (95% CI 1.27-2.45) and it was 1.83 (95 CI 1.4-2.3) for men with thick, extended thoracic hairiness. The presence of a diagonal earlobe crease yielded a relative risk of 1.37 (95% CI 1.25-1.5), while hair greying was associated with myocardial infarction only in men under the age of 50 years. CONCLUSION: It appears that baldness, thoracic hairiness and diagonal earlobe crease indicate an additional risk of myocardial infarction in men under the age of 60 years, independently of age and other established coronary risk factors.

Triggers of acute myocardial infarction regarding its site.

We have studied the incidence of possible triggers of the myocardial infarction regarding its site in 750 patients with anterior and 731 patients with inferior infarction. Infarctions occurred most frequently without recalling any triggering activity, especially in patients with anterior infarction (67 vs. 44%). Physical effort as the possible precipitator was also more frequent in anterior infarctions (22 vs. 16%). However, the onset of inferior infarction was more frequent during meteorological stress (9 vs. 2%), emotional stress (10 vs. 3%), after overeating (13 vs. 3%) and nicotine abuse (6 vs. 1.5%). These triggers were independent and highly significant (P < 0.02 in each case) discriminators of the site of myocardial infarction. Bimodal circadian rhythm, with primary peak between 6 and 9 h a.m. and the secondary peak between 3 and 6 p.m. was observed in patients which did not recall any triggering activity, and this was more pronounced in patients with inferior infarction. These results support the hypothesis that the influence of the vegetative tone is most pronounced in the onset of myocardial infarction of inferior wall.

Nonspecific immunity in diabetes: hyperglycemia decreases phagocytic activity of leukocytes in diabetic patients.

Phagocytic activity of leukocytes in blood was examined in 70 patients with diabetes mellitus. 40 of them had insulin-dependent diabetes--(IDDM) or type I, while there were 30 patients with noninsulin-dependent diabetes (NIDDM) or type II. Phagocytic activity of leukocytes was determined by quantitative method of ingestion, on the principle of quantifying phagocytized fungi (Saccharomyces cerevisiae) and free phagocytes (nonphagocytizing leukocytes) by means of a phase-contrast microscope. The data have been statistically processed by the Student t-test and variance analysis test (Duncan test). The index of phagocytosis amounted to 3.2 +/- 0.77 in diabetic patients, while it was 3.47 +/- 0.29 in healthy examinees from the control group, thus yielding a statistically significant difference, p < 0.05. Out of all examined parameters (blood glucose, glycosylized hemoglobin, mean glucose value) phagocytic activity of leukocytes showed a statistically significant correlation with mean value of glucose in blood. Patients with mean glucose value higher than 12 mmol/l showed a significantly lower index of phagocytosis (2.9 +/- 0.84) than patients whose mean glucose value was lower than 12 mmol/l (3.5 +/- 0.59), p < 0.05. Neither age and sex of the patients nor chronic complications caused by diabetes affected the phagocytic activity of leukocytes in diabetic patients. There was no significant difference in the phagocytic activity of leukocytes between patients with IDDM and those with NIDDM.