PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population.

BACKGROUND: The present study evaluated the role of the PON1 L55M polymorphism independently and in conjunction with the Q192R polymorphism on the risk of coronary atherosclerosis in an Italian population. MATERIALS AND METHODS: Three hundred and ninety-one subjects with significant coronary stenosis (> 50%) (coronary artery disease-positive; CAD+), 196 subjects with normal coronary arteries (< 10% stenosis) (CAD-) and 178 healthy controls were screened using a combination of polymerase chain reaction and restriction enzyme digestion. RESULTS: In the pooled population, the frequencies of L and M alleles were 0.63 and 0.37, respectively; the most common haplotypes were QQ/LM (24.2%) and QR/LL (21.8%) and a strong linkage disequilibrium between L/55 and R/192 alleles was observed (D' = -0.91; P < 0.0001). CAD+ subjects did not show any significant differences in the distribution of PON1-55 genotypes as compared to CAD- subjects and population controls (chi2 = 1.5, P = 0.8). After controlling for other risk factors, the low-concentration M allele was not associated with a significant change of CAD risk (OR 1.02; 95% CI 0.80-1.29; P = 0.87). Moreover, the L55M polymorphism did not show any interaction with other risk factors such as smoking, diabetes, hypertension, low levels of high-density lipoprotein (HDL) or high ratios of low-density to high-density lipoproteins. The combination of L55M with the Q192R polymorphism did not show any effect on CAD risk. However, a marginal decrease in myocardial infarction risk was detected when QQ/MM carriers (OR 0.51; 95% CI 0.26-0.99; P = 0.048), but not LL/RR carriers, were compared with subjects not homozygous for an L or R allele. CONCLUSIONS: These findings did not indicate a major effect of the PON1 L55M polymorphism, either alone or in combination with the Q192R polymorphism, on CAD risk. Additional studies are needed for a better evaluation of the role of the 55/192 PON1 genotypes in combination on myocardial infarction risk.

Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning.

OBJECTIVES: Although adenosine triphosphate-dependent potassium channel openers have been shown to enhance cardioplegic protection in animal myocardium, there is a lack of data on human cardiac tissues. We aimed at determining, on human atrial muscle, whether adenosine triphosphate- dependent potassium channels are involved in protection caused by high-potassium cardioplegia and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial stunning. METHODS: Human atrial trabeculae were obtained from adult patients undergoing cardiac operations. In an organ bath at 37 degrees C, the preparations were subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control, n = 17) or in St Thomas' Hospital solution without additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 micromol/L glibenclamide (n = 7), followed by 60 minutes of reoxygenation and 15 minutes of positive inotropic stimulation with 1 micromol/L dobutamine. RESULTS: Atrial developed tension was reduced by hypoxia to 27% +/- 5% of baseline and incompletely recovered after reoxygenation to 38% +/- 7%, whereas dobutamine restored contractility to 74% +/- 7% of basal values. St Thomas' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P <.0001 vs control), whereas glibenclamide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle length) but recovered during dobutamine superfusion. CONCLUSIONS: Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial trabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to cardioplegia enhanced protection.

The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis.

The present study evaluated the role of the common lipoprotein lipase (LPL) mutations on the risk of dyslipidemia and coronary atherosclerosis in an Italian population. Cohorts of 632 patients undergoing coronary angiography, as well as 191 healthy controls, were screened by a combination of PCR and restriction enzyme digestion. In the pooled population, the frequencies of LPL D9N and N291S were 4.1%, with no homozygous carriers, whereas that of LPL S447X was 21% with 19.6% heterozygous and 1.4% homozygous carriers. Compared to non-carriers, LPL N291S carriers showed higher plasma triglycerides (TG) (p < 0.03) and increased risk of high TG phenotype (odds ratio [OR] 2.49, 95% Cl 1.06-5.81; p < 0.03). When this LPL mutation was associated with high body mass index (BMI) ( > 25 Kg/m2) or fasting, plasma insulin (> 10.6 mU ml(-1)) significantly reduced HDL-C levels were also observed. Carriers of the S447X mutation presented with higher HDL-C concentrations (p < 0.05) as compared to non-carriers; they also showed a significantly reduced risk of high TG/low HDL-C dyslipidemia (OR 0.34, 95%, Cl 0.12-0.99; p < 0.05). The favourable effect of the LPL S447X variant was even more pronounced in lean subjects and in those with low insulin levels. No significant influence on plasma lipids by the LPL D9N was observed. None of LPL variants was a significant predictor of angiographically assessed coronary atherosclerosis. At most, the risk was borderline, increased in N291S carriers and possibly decreased in S447X carriers.

A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease.

Insulin resistance is associated with increased risk of atherosclerosis. Insulin receptor substrate-1 (IRS-1) plays a key role in tissue insulin sensitivity. A common mutation (G972R) of the IRS-1 gene has been shown to impair IRS-1 function, and it has been associated with reduced insulin sensitivity and lipid abnormalities. This led us to investigate the role of the G972R mutation in predisposing individuals to coronary artery disease (CAD). The DNA of 318 subjects with angiographically documented coronary atherosclerosis (>50% stenosis) and 208 population control subjects was analyzed for the presence of the G972R mutation. This mutation was detected by nested polymerase chain reaction and BstNI restriction enzyme digestion. The frequency of the G972R mutation was significantly higher among patients with CAD than controls (18. 9% versus 6.8%, respectively; P<0.001). After controlling for other coronary risk factors, the relative risk of CAD associated with the G972R mutation was 2.93 (95% CI 1.30 to 6.60; P<0.02) in the entire cohort. This risk was found to be even higher in the subgroups of obese subjects (odds ratio [OR] 6.97, 95% CI 2.24 to 21.4; P<0.001) and subjects with clinical features of insulin resistance syndrome (OR 27.3, 95% CI 7.19 to 104.0; P<0.001). The IRS-1 gene variant was associated with a higher frequency of diabetes mellitus (14.9% among carriers versus 6.5% among noncarriers; P<0.01) and with a 60% increase of plasma total triglycerides (P<0.001). Also, plasma concentrations of total cholesterol and the ratio of total cholesterol to HDL cholesterol were significantly (P<0.001) higher among carriers than noncarriers, although to lesser a extent. These effects were independent of CAD status. The G972R mutation in the IRS-1 gene was found to be a significant independent predictor of CAD. Moreover, this mutation greatly increased the risk of CAD in obese subjects and in patients with the cluster of abnormalities of insulin resistance syndrome. Besides the increased frequency of diabetes, carriers showed a more atherogenic lipid profile, suggesting a potential role of the IRS-1 gene in the pathogenesis of lipid abnormalities associated with CAD.

Cicletanine prevents the excitation-conduction blocks induced by terfenadine in ischemic myocardium.

Terfenadine, a histamine H(1) receptor antagonist, has been associated with clinical ventricular arrhythmias and in vitro excitation-conduction blocks, whereas anti-ischemic and antiarrhythmic effects have been shown with cicletanine, a prostacyclin generation stimulator. We aimed at determining in vitro if cicletanine can protect the ischemic myocardium from excitation-conduction blocks and specifically those induced by terfenadine. In a double-chamber bath, isolated guinea pig ventricular strips were partly exposed to normoxia and partly to ischemic, then reperfused, conditions, in the presence of 10 microM terfenadine, 10 microM indomethacin (prostacyclin generation blocker) or the solvent (dimethylsulfoxide 1:100, control) randomly allocated, and thus either in the absence (n=20) or presence (n=21) of 10 microM cicletanine during the total protocol duration. The multivariate Cox's model was used to predict the excitation-conduction block events and to assess the estimated survival of preparations (excitation-conduction block-free rate). Cicletanine protected the preparations (relative risk=0.08, t=-3.28) from the ischemia-induced excitation-conduction blocks (estimated survival=0.83 versus 0.30 in control), and this effect was abolished by indomethacin (estimated survival=0.35). Terfenadine enhanced 3. 58-fold the risk of occurrence of excitation-conduction blocks during ischemia (t=2.10) and this effect was inhibited by cicletanine pretreatment (estimated survival=0.40 versus 0.10 in untreated preparations). In conclusion, these in vitro findings have provided evidence for (1) protective effects of cicletanine against ischemia-induced excitation-conduction blocks, possibly related to its stimulating activity on local prostacyclin generation, and (2) efficacy of cicletanine to prevent excitation-conduction blocks induced by terfenadine in ischemic cardiac tissue.

Enoximone coupled to very low dose dobutamine echocardiography detects myocardial viability in akinetic and dyskinetic post-myocardial infarcted areas.

Dobutamine and enoximone stimulate independently inotropic reserve by increasing intracellular cyclic adenosine monophosphate. The potential of enoximone (0.75 mg/kg body weight over 10 minutes) followed by very low dose (2.5 microg/kg/min) dobutamine echocardiography to predict recovery of ventricular function in akinetic and dyskinetic postinfarcted areas was studied. We enrolled 22 patients with previous Q-wave myocardial infarction and regional wall motion abnormalities related to left anterior descending arterial disease, left ventricular ejection fraction <40%, and all scheduled for myocardial revascularization. A 10 microg/kg/min dobutamine test was performed 48 hours before the study protocol. Test images obtained at peak of pharmacodynamic effects were compared with those obtained at 4 months after myocardial revascularization. We used a 16-segment ventricular model and a 5-grade scoring system. Resting regional myocardial dysfunction graded > or =2 was present in 267 of 352 segments evaluated. Contractile reserve (decrease in resting wall motion score > or =2 grades) at peak effect of enoximone infusion was present in 34 of 112 severely hypokinetic, 42 of 117 akinetic, and 14 of 38 dyskinetic segments. The inotropic reserve evaluated after very low dose dobutamine was observed in 34 of 112 severely hypokinetic, 49 of 117 akinetic, and 20 of 38 dyskinetic segments. After revascularization, recovery of function was observed in 31 of 112 severely hypokinetic, 49 of 117 akinetic, and 21 of 38 dyskinetic segments. Overall, there was a significant correlation between absolute score changes of segments which were abnormal at baseline (n = 267) to enoximone peak effects (r = 0.49, p <0.001) to predict absolute changes after revascularization; after dobutamine there was progress toward identity (r = 0.62, p <0.001) and the difference was significant among correlation slopes of dobutamine alone, enoximone alone, and enoximone plus very low dose dobutamine echocardiograophy (0.45+/-0.04, 0.51+/-0.04, and 0.63+/-0.04, respectively, F = 5.25, p = 0.005). Therefore, enoximone followed by very low dose dobutamine may assess myocardial viability of postinfarcted akinetic and dyskinetic areas. This test may be useful when evaluating patients with more severe cardiac failure and/or life-threatening arrhythmias.

[Left ventricular aneurysm in a patient with mildly dilated cardiomyopathy]. / Aneurisma ventricolare sinistro in un paziente con cardiomiopatia "mildly dilated".

We describe the case of a patient with mildly dilated idiopathic cardiomyopathy and left ventricular aneurysm, diagnosed in absence of a prior clinical history and anatomo-pathological features of myocardial infarction. To ascertain the diagnosis of idiopathic cardiomyopathy, the patient underwent cardiac catheterization with coronary angiography, that showed the lack of epicardial artery stenosis and a slow run-off of the contrast. An endomyocardial biopsy showed the presence of hypertrophic myocytes and interstitial fibrosis. Moreover, a thoracic high resolution computed tomography showed the features of pulmonary bilateral basal emphysema, interstitial thickening and bronchiectasis. Alfa1-anti-trypsin plasma levels were reduced. The patient, because of worsening of clinical and hemodynamic conditions, underwent at age of 36 a combined heart-lung transplantation. The pathological examination of the native organs confirmed the previous diagnosis. At the moment, this is the second report in the literature concerning the presence of left ventricular aneurysm in a patient with idiopathic cardiomyopathy without an underlying coronary artery disease or prior history of myocardial infarction.

Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling.

OBJECTIVES: The purpose of this study was to determine whether contractile recovery induced by dobutamine in dysfunctioning viable myocardium supplied by nearly occluded vessels is related to an increase in blood flow in the absence of collaterals. BACKGROUND: Dobutamine is used to improve contractility in ventricular dysfunction during acute myocardial infarction. However, it is unclear whether a significant increase in regional blood flow may be involved in dobutamine effect. METHODS: Twenty patients with 5- to 10-day old anterior infarction and > or =90% left anterior descending coronary artery stenosis underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest echocardiography and scintigraphy were repeated >1 month after revascularization. Nine patients had collaterals to the infarcted territory (group A), and 11 did not (group B). RESULTS: Baseline wall motion score was similar in both groups (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p < 0.0001). Wall motion score improved significantly (p < 0.001) in group A both at dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas at dobutamine and postrevascularization studies a significant change (F[2,30] = 65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p < 0.0001) were present. Tracer uptake increased significantly in group A both at dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/-8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization (+8.8+/-7.2%, p < 0.001). CONCLUSIONS: The increase in contractility induced by low dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase in blood flow.

[Natural harmonic echocardiography]. / Ecocardiografia in armonica naturale.

The acquisition of echocardiographic images in harmonic mode (a frequency double than the transmitted, or fundamental) improves imaging quality. We assessed whether harmonic imaging improves the detection of endocardial borders, evaluation of ventricular function and diagnostic confidence in the clinical arena. We have studied in fundamental and harmonic imaging 45 patients (age 20-89 years, mean 53 years) using a multifrequency transthoracic probe transmitting at 1.75 MHz and receiving at 3.5 MHz (Acuson Sequoia). In 34 low echogenic patients we assessed left ventricular function. The remaining 11 patients represented selected cases (i.e. atrial septal aneurysm, aortic dissection, endocarditis and atrial septal defect). The echocardiographic images were recorded on a magneto-optical disk and analyzed by two blinded observers. Endocardial definition has been semiquantitatively evaluated assigning a 0-4 score for each of the 16 segments of the left ventricle. A score of 0 was allotted to the non-visualizable segments and a score of 4 to the best detectable segments. Ejection fraction was calculated in each patient from the apical 4-chamber view. We compared endocardial border definition and ejection fraction at rest, in fundamental and harmonic mode, and assessed the interobserver agreement in the calculation of ejection fraction. Harmonic images always showed a better definition and lower noise compared to fundamental. Endocardial border definition was significantly improved in all segments (from 1.3 +/- 1.1 fundamental to 2.9 +/- 1.0 harmonic). Forty-two segments were non detectable in fundamental (score 0) compared to 5 in harmonic. Of these 42 segments, 37 were detectable in harmonic, with a score of 2.0 +/- 1.0. Conversely, none of the 5 segments non detectable in harmonic could be visualized in fundamental. The interobserver agreement in calculating ejection fraction was improved by harmonic imaging compared to fundamental (r = 0.91 and r = 0.67, respectively). In the selected clinical cases the diagnosis was easier and faster by harmonic imaging. The harmonic mode drastically improves echocardiographic imaging, it may be used routinely and reduce the need for more invasive techniques such as transesophageal echocardiography.

Benazepril causes in hypertension a greater reduction in left ventricular mass than does nitrendipine: a randomized study using magnetic resonance imaging.

To assess the comparative effects of benazepril and nitrendipine monotherapies on left ventricular mass index (LVMI) in hypertensive patients with echocardiographically determined left ventricular hypertrophy, patients with diastolic blood pressure (BP) > or = 100 mm Hg were randomized to benazepril, 10 mg, or nitrendipine, 20 mg, both given once or twice daily. After 4 weeks, only the responders (diastolic BP <90 mm Hg) entered a 5-month maintenance period. At baseline, and after 3 and 6 months, LVMI was blindly estimated by means of magnetic resonance imaging (MRI) and, for comparison, by means of echocardiography. Of the 50 randomized patients, three were excluded from the study as nonresponders after 4 weeks; moreover, two patients taking benazepril and one taking nitrendipine discontinued the treatment after 2 months for adverse effects. Both monotherapies reduced systolic and diastolic BP to a similar extent. After 3 months, MRI-estimated LVMI decreased by 21.5 g/m2 in the benazepril and 8.8 g/m2 in the nitrendipine group, with an adjusted mean difference between the two groups of 11.1 g/m2 (95% CI, 7.3-14.8 g/m2; p = 0.0001). After 6 months, it decreased by 23.6 g/m2 and 10.0 g/m2, respectively, with an adjusted mean difference of 11.3 g/m2 (95% CI, 7.5-15.5; p = 0.0001) in favor of benazepril. In conclusion, despite a similar antihypertensive effect, benazepril led to a greater reduction in MRI-measured LVMI than did nitrendipine (-16.2% vs. -7.2%) in hypertensive patients with left ventricular hypertrophy.

The gln-Arg192 polymorphism of human paraoxonase gene is not associated with coronary artery disease in italian patients.

Serum paraoxonase (PON) is an HDL-bound enzyme protecting LDL from oxidation. A common polymorphism of the paraoxonase gene (PON1) involving a Gln-to-Arg interchange at position 192 has been demonstrated to modulate PON activity toward paraoxon, a nonphysiological substrate; Arg192 (allele B) is associated with higher activity than Gln192 (allele A). This polymorphism has been proposed as a genetic marker of risk for coronary artery disease (CAD). However, the relationships between codon 192 PON1 genotypes, coronary atherosclerosis, and the occurrence of myocardial infarction (MI) are still controversial. PON1 genotypes were determined in 472 consecutive subjects (>40 years old) who underwent coronary angiography. CAD (>50% stenosis) was detected in 310 subjects (CAD+); 162 subjects with <10% stenosis served as controls (CAD-). We also evaluated 204 randomly selected individuals as population controls. PON1 genotypes were determined by PCR and AlwI restriction enzyme digestion. Frequencies of alleles A and B were 0. 70 and 0.30 in angiographically assessed subjects and 0.73 and 0.27 in population controls, respectively (chi2=2.0; P<0.3). Distribution of PON1 genotypes in CAD+ were not significantly different from those in CAD- (chi2=2.10; P<0.3). Similarly, no differences were observed in the subgroup of CAD+ with MI nor in that at higher oxidative risk (smokers and/or diabetics). After controlling for other coronary risk factors, no association was found between PON1 alleles and the presence of CAD. PON1 AA genotype was associated with reduced concentration of apolipoprotein B-containing triglyceride-rich lipoproteins. This study did not provide evidence of a significant association between codon 192 PON1 genotypes and coronary atherosclerosis in Italian patients. However, it did confirm that the PON1 low-activity allele is associated with a less atherogenic lipid profile.

Angiotensin-converting enzyme gene polymorphism is not associated with coronary atherosclerosis and myocardial infarction in a sample of Italian patients.

BACKGROUND: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been proposed as a genetic marker of the risk of ischaemic heart disease. However, the relationships between ACE genotypes, the development of coronary atherosclerosis and the occurrence of major coronary events are still controversial. METHODS: To investigate whether the ACE I/D (insertion/deletion) polymorphism predicts the risk of coronary stenosis and myocardial infarction (MI), ACE genotypes were determined in 394 consecutive patients who underwent coronary angiography. The presence determined in 394 consecutive patients who underwent coronary angiography. The presence of coronary artery disease (CAD) (defined by > 50% stenosis) was detected in 236 patients (CAD+); 85 of these individuals had a history of MI. Patients with coronary stenosis < 10% (n = 158) served as controls (CAD-). ACE genotypes were determined by agarose gel sizing after polymerase chain reaction (PCR) amplification. RESULTS: The distribution of ACE genotypes in CAD+ patients was not significantly different from that in CAD-patients (chi 2 = 2.63, P < 0.27). After controlling for other coronary risk factors, no significant increase in risk of CAD or MI was found to be associated with the D allele, regardless of whether the D allele was assumed to have a dominant, a codominant or a recessive effect. Similar results were observed in CAD+ patients at lower risk because of low body mass index and apolipoprotein B concentrations. Smoking, apolipoprotein B and history of hypertension were found to be independent predictors of CAD and MI. CONCLUSION: Our study did not provide evidence of a significant association between ACE genotypes and the development of coronary atherosclerosis. It also failed to support a role of ACE I/D polymorphism in favouring the conversion of coronary stenosis to MI.

[Visualization of native internal mammary arteries and aorto-coronary graft by means of high resolution color Doppler ultrasonography]. / Visualizzazione delle arterie mammarie interne native e del graft aortocoronarico con ecocardiografia color Doppler ad alta risoluzione.

The internal mammary artery is routinely used for coronary artery bypass grafting because of its optimal long-term patency profile. This vessel can be imaged by angiography, but only the proximal tract at the origin from the succlavian artery can be imaged by conventional echography. The aim of our study was to visualize the intrathoracic course of the native and grafted internal mammary arteries by a new ultrasound equipment which allows high-resolution transthoracic color Doppler imaging of the chest wall vessels and coronary arteries. We studied 35 patients, 16 non operated and 19 operated of coronary surgery with the internal mammary artery grafted to the left anterior descending coronary artery. We used a multifrequency 3.5-7 MHz transducer with a small insonating surface, placed at the second-fifth intercostal space at the left and right sternal border, to image the native mammary arteries. The grafted mammary artery was detected at the fourth-fifth left intercostal space 2-4 cm lateral to the sternal border. The native left internal mammary artery was visualized in all 16 non operated patients, and the right internal mammary artery in 14/16 (87%). The native left internal mammary artery peak flow velocity was 41-160 cm/s (mean 81 +/- 34 cm/s), and the mean flow velocity was 28-89 cm/s (mean 45 +/- 17 cm/s). The right internal mammary artery peak flow velocity was 35-153 cm/s (mean 82 +/- 36 cm/s), and mean flow velocity was 21-82 cm/s (mean 46 +/- 22 cm/s). The grafted left internal mammary artery was visualized in 16/19 patients (84%), evaluated at 6 days to 36 months after surgery. Peak diastolic flow velocity ranged from 24 to 80 cm/s (mean 48 +/- 17 cm/s), and mean diastolic flow velocity ranged from 13 to 57 cm/s (mean 33 +/- 11 cm/s). The left anterior descending peak flow velocity distal to the anastomosis was 22-62 cm/s (mean 37 +/- 15 cm/s) and mean flow velocity was 18-53 cm/s (mean 29 +/- 12 cm/s). We conclude that transthoracic color Doppler echocardiography allows to image the native and grafted mammary arteries, with potential clinical applications in the management of patients with coronary artery disease.

Preoperative identification of viable myocardium: effectiveness of nitroglycerine-induced changes in myocardial Sestamibi uptake.

In order to predict tissue viability in infarcted myocardial areas, changes induced by nitroglycerine infusion on Sestamibi myocardial uptake were evaluated in 37 patients with previously confirmed myocardial infarction undergoing coronary artery bypass grafting, and compared with echocardiographic and perfusional changes occurring after the operation. The improvement of Sestamibi uptake after nitroglycerine correctly classified 24/26 (92%) patients showing postoperative improvement of wall motion in the infarcted area, whereas 24/31 (77%) patients with nitroglycerine-induced increase in Sestamibi uptake had improved wall motion after operation. The presence of collateral flow to the infarcted area was associated with a significantly (P < 0.01) higher increase in Sestamibi uptake both during nitroglycerine infusion and postoperatively. An increase in wall motion score after operation was associated with a significantly higher (P < 0.05) increase in Sestamibi uptake score during nitroglycerine infusion. Thus, the results of this study suggest that Sestamibi perfusional myocardial scintigraphy during nitroglycerine infusion is capable of assessing viable but chronically hypoperfused myocardium and predicting postoperative wall motion and perfusional improvement, to yield the best results in patients with evidence of collateral circulation that supplies the infarcted area.

Handgrip increases endothelin-1 secretion in normotensive young male offspring of hypertensive parents.

OBJECTIVES: We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents. BACKGROUND: It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension. METHODS: Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery. RESULTS: Group A had higher norepinephrine levels than group B throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p < 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p < 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square=7.59, p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not. CONCLUSIONS: The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.

Acute oral trimetazidine administration increases resting technetium 99m sestamibi uptake in hibernating myocardium.

BACKGROUND: Trimetazidine is an antiischemic drug protecting the myocardium from ischemic damage through the preservation of mitochondrial oxidative metabolism, without any hemodynamic effect. 99mTc-sestamibi is accumulated by myocytes according to mitochondrial function. As mitochondrial metabolism is thought to be present in hibernating myocardium, the aim of the study was to investigate trimetazidine effects on infarcted and eventually hibernating myocardial areas by means of 99mTc-sestamibi perfusional scintigraphy, comparing them to postoperative recovery of wall motion. METHODS AND RESULTS: Twelve patients with previous myocardial infarction underwent 2 perfusion imaging tomographic studies at rest with 99mTc-sestamibi, receiving placebo or trimetazidine (60 mg orally), and subsequently underwent revascularization procedures. An echocardiographic study was carried out before and >3 months after revascularization. At polar map analysis of placebo scan, infarcted vascular territories (wall motion score index: 2.65 +/- 0.31) showed 73.7% +/- 10.4% of the territory with activity <2.5 SD from the mean of normals, for a severity (expressed as the sum of the standard deviations below average normal values in all abnormal pixels) of 833.8 +/- 345.7. Polar map analysis of the trimetazidine scan showed tracer uptake increased significantly in 11 of them, by 8.2% +/- 3.0% (p < 0.001) and by 180.3 +/- 111.0 SD (p < 0.001), respectively. Postoperative wall motion score index improved significantly in 9 of these territories (-0.9 +/- 0.4, p < 0.001). CONCLUSIONS: Trimetazidine-associated increase in 99mTc-sestamibi uptake in infarcted but viable myocardial areas is probably related to an improvement in mitochondrial oxidative metabolism that is essential to 99mTc-sestamibi retention. Additionally, coupling trimetazidine administration to 99mTc-sestamibi perfusional scintigraphy may represent a means of detecting viable myocardium.

Blood pressure circadian rhythm and variability in subjects with severe heart failure.

To explore whether a condition of severe heart failure results in alteration of the 24-h-blood pressure (BP) profile and BP circadian rhythm, 19 patients with severe heart failure (NYHA class III-IV, 17M, 2F, mean age 57+/-8 years) were considered and compared to a control group of age- and sex-matched normal subjects. All subjects were submitted to non-invasive 24-h ambulatory blood pressure monitoring using a SpaceLabs 90207 unit (recording interval 15 min). Both systolic and diastolic BP profiles were evaluated using the two-step method of analysis reported by Staessen: the existence of a BP circadian rhythm was first tested using Siegel's runs test, then a Fourier multiple harmonic analysis allowed us to obtain the BP profile parameters Acrophases (Acro, hh:mm) and Amplitudes (Ampl, mm Hg). The same methods were used for pulse rate. Our results showed the presence of a BP circadian rhythm in severe heart failure subjects, as well as in control subjects. Furthermore, no significant difference was found between the two groups when considering the BP profile parameters Acro and Ampl. In conclusion, in contrast with previous reports, our results show that both BP circadian rhythm and BP profile parameters are preserved in patients with severe heart failure.

[Univariate analysis of potential risk factors for early mortality (within 28 days) after aortocoronary bypass in Italy. OP-RISK Study Group]. / Analisi univariata su potenziali fattori di rischio della mortalità precoce (entro 28 giorni) dopo bypass aortocoronarico in Italia. Gruppo di Studio OP-RISK.

The multicenter OP-RISK study, developed during 1994-96, was aimed at: 1) investigating early (28 days) death rates following aortocoronary bypass surgery among patients recruited from four Centers representing geographical distribution in Italy; 2) defining possible risk factors for early mortality, also comparing these factors with those reported in previous studies. Average values are reported and compared of 65 variables (36 preoperative, 10 operative and 19 postoperative) out of 984 patients subdivided into alive (n = 940) or dead (n = 44, 4.47%) at 28 days (155 +/- 174 hours, interval between 12 and 576 hours) postoperatively. Causes of death were cardiac in 37 (77%), pulmonary in 3 (0.7%), vascular in 2 (0.5%) and infective in 2(0.5%) patients, respectively. During the study a total of 1126 patients were operated upon in the collaborative Centers with the diagnosis of coronary artery disease and 51 deaths were reported officially in-hospital (4.53%). Therefore, OP-RISK data represent 87% of overall patients and a superposable death rate. The potential role as risk factors of early mortality was assessed univariately for 17 preoperative, 5 operative (in 3 cases for the first time) and 5 postoperative factors. In general, it was confirmed that factors defining left ventricular function are sensitive predictors of mortality. In OP-RISK we were able to show, in addition, that tachycardia (> 130 b/min) at induction of anesthesia, and total time of anesthesia, cardiopulmonary bypass and aortic cross clamping may be significant factors among operative variables as might be among postoperative ones several arrhythmia types or a lower rate in antithrombotic therapy with aspirin at 6-12 hours postoperatively. The protective role of bypass surgery performed with at least 1 arterial segment was also ascertained. Most of these potential factors were significantly related to outcome (either directly or inversely) as were among them, as seen in a subsample (65%) of 639 patients in whom a correlation matrix was performed among 16 factors selected on the basis of the common denominator principle. Our results suggest that it is possible to collect in a multicenter experience univariate predictors of early mortality following aortocoronary bypass surgery in Italy, which are not different from those reported from previous studies performed abroad. Operative indicators may also have predictive capabilities. The effort may be worthwhile and demands further cooperative studies to be undertaken, aimed at obtaining nationwide coefficients of risk along with representative average values of factors that soon might emerge once multivariate statistics will be performed on this material.

Interleukins 6 and 8 as mediators of acute phase response in acute myocardial infarction.

The present study provides evidence that interleukin (IL)-6 and IL-8 are the main endogenous mediators of acute phase response in patients with myocardial infarction. This conclusion was supported by the observation of a strict relation between IL-6 elevation and the extent of myocardial tissue damage and rise in body temperature.