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During 1993-1994, 3590 patients who recovered from acute myocardial (undergone 1 to 6 years earlier) were examined by 139 ambulatory cardiologists. Aim of the study was to investigate blood lipid changes in 2435 (67.82%) patients in whom total-HDL-and LDL-cholesterol and triglycerides were obtained. These lipids were not abnormally elevated and actually very similar to (or slightly lower than) those of the general population examined in Italy in the context of the RIsk Factors and Life Expectancy Pooling Project (including 70,000 individuals). However, blood lipids were, in general, higher in women than in men and declined as age increased (unless HDL-cholesterol which tended to increase). Among postinfarction patients lipid-lowering drugs were taken by 19% of men and 14% of women, which contrasts with proportions observed in the general population (5 and 4%, respectively). Mean blood lipid values were higher among those who were treated with lipid-lowering drugs, either from the postinfarction series or the general population (unless HDL-cholesterol which had an opposite trend). These data may indicate why treatment was undertaken, although no conclusion may be drawn about drug-efficacy. Postinfarction patients examined after 1-2 years from illness showed lower values of mean blood lipids than those examined 3-6 years after the acute episode (however, the opposite was true for HDL-cholesterol). There are several possible explanations for these observations: high lethality in infarction-patients with high blood lipids, efficacy of lipid-lowering drugs, diet or metabolic changes following acute myocardial infarction. Nevertheless, the proportion of postinfarction patients treated with lipid-lowering drugs was lower than anticipated from (and/or recommended based on) results of recent secondary preventive trials. It seems necessary to repeat (possibly periodically) this investigation in large samples of postinfarction patients to assess whether and how, in clinical practice, indications are applied from recent large trials on secondary prevention of ischemic heart disease.

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.

The relative effects of nicotinic acid (NA) and nitroglycerin (NT) added to cold high K+ cardioplegia were studied, to represent the two moieties of the adenosine triphosphate-sensitive potassium channel (KATP) activator nicorandil (N). In addition, we made a pooled analysis of a large series of experiments performed in our Laboratory to investigate the effects of KATP activation by N, or block (by glibenclamide, G), on postcardioplegic myocardial dysfunction. In both studies, reversibility from myocardial dysfunction (stunning) was assessed by the positive inotropic agent dobutamine. Guinea pig papillary muscle preparations were immersed in Tyrode's solution (O2 content 16 ml/l, 37 degrees C), then hypoxic (O2 content 5 ml/l) superfusion with hypothermic (20 degrees C) cardioplegic Saint Thomas' Hospital solution (STHS) was performed for 120 min. We investigated: A) 5 groups based on treatments added to STHS: 1) saline (Control (C)); 2) N = 1 mmol/L; 3) G = 1 mumol/L (also given for 15 min in Tyrode's solution); 4) NA = 1 mmol/L; 5) NT = 100 mumol/L; B) 76 consecutive experiments and we defined, independent of whether just before or during STHS: 1) KATP activation (by N, in the concentration range 1 mumol/L to 1 mmol/L, n = 36); 2) KATP block (by G 1 mumol/L, either alone or just before N, n = 20); 3) controls (n = 20) (either saline, n = 12, or saline plus dimethyl sulfoxide, as vehicle, at the ratio 100 to 1, n = 8). Absolute isometric contractility variables were evaluated along with percent changes of baseline values: 1) at 30 s of STHS, 2) after 60 min of reoxygenation with Tyrode's solution and 3) following further 15 min of dobutamine 10 mumol/L. In all preparations, developed tension (DT), time to peak tension (TPT), DT/TPT and time to arrest (TTA) were measured. In study A): TTA was significantly abbreviated (intergroup F = 5.79, p < 0.001) in N (49 +/- 11 s, mean +/- SD) p < 0.01 vs C and NA). At 30 s of STHS %DT/TPT was unchanged among groups. By contrast, after 60 min of reoxygenation %DT/TPT in N (118 +/- 35%, p < 0.05 vs C, p < 0.01 vs G) was improved (intergroup F = 5.48, p < 0.002). G, NA and NT showed recovery of contractility similar to C. However, after dobutamine the poorest %DT/TPT were seen in G (p < 0.01 vs C, p < 0.05 vs N). In study B): using the multivariate logistic model, with KATP activation, the odds of normal contractile response, respectively at 60 min of reoxygenation (t = 2.81) and after dobutamine (t = 3.22), were 29.8 and 8.86 of controls, whereas TTA (t = -1.59) was inversely related. Moreover, with KATP block the odds after dobutamine was 0.204 of controls. The relative operating characteristic plots showed areas under the curve greater than 0.7, which is evidence for accurate assessment of the predictive rules adopted. This is the first report where a probabilistic approach to cardioplegia-related experiments showed high accuracy in predicting the recovery of post-hypoxic contractile function (stunning). The results indicate that on postcardioplegic stunning: 1) KATP activation by N and KATP block by G (both given prior to or contemporary with hypoxia) have opposite effects; 2) the favorable effects of nicorandil seem unrelated to its nicotinamide or nitrose moieties.

The study was aimed at comparing the effects of dobutamine (dob) and dopamine (dop) on isotonic contraction and rhythmicity of isolated guinea-pig papillary muscles (in oxygenated Tyrode at 37 degrees C), by taking into account: 1) the rate of stimulation (50% above the diastolic threshold) at 5 fixed periods: (RR: 1600, 1200, 1000, 800 and 400 ms); 2) 7 log concentrations (logC) of the index amine (from 10(-9) to 10(-3) M). To this end, a dose-relation protocol which explored the effects of all 5 RR and 7 logC was designed and 15 adult female Guinea-pigs (250 to 350 g) were randomized to either the dob (n = 8) or the dop (n = 7) arm. This enabled a total of 525 sets of data to be analyzed: in 38 sets (7.2%) premature contractions (CP) were coded. CP were sustained (freq: > 3) in 25 of these latter 38 sets (4.8%). Compared to the basal state, the amplitude (AMP%) and the log of percent amplitude (logAMP%) and time to peak (TP%) changes of the isotonic (Gould transducer) twitch were calculated along with the log of this latter variable (logTP%). AMP%, log AMP%, TP% and logTP% were linearly correlated with logC at all RR. In the range 1600-400 RR, for both amines, significant linear correlations (magnitude of 0.15 > r < magnitude of 0.70, 0.001 > p < 0.022) were seen for plots of AMP%, logAMP% and TP%:steeper correlations were observed for dop. This was confirmed in multivariate analysis (BMDP-9R) whereby AMP%, logAMP%, TP%, logTP%, CP, and freqCP were dependent variables and coded variables were included to either define the type of treatment (dop versus dob) or logC. In these analyses, logC (t > 11) and dop (t > magnitude of 3) might be used to explain (0.28 > r2 < 0.42, 0.00001 > p < 0.0025) AMP% and logAMP%, meaning that a different inotropic (isotonic) efficacy exists between these 2 amines, at all logC. On the other hand, when CP and freqCP were coded, explanatory variables were AMP% and logAMP% (4.86 > t < 6.95, 0.06 > r2 < 0.09, p < 0.00001), but not the variable used to code the type of treatment (dob versus dop).(ABSTRACT TRUNCATED AT 400 WORDS)

Nicorandil (N) increases potassium conductance in vascular smooth muscle and so induces vasodilation; N also dose-dependently reduces action potential duration (APD). However, it is unclear whether increased potassium conductance, and concomitant APD shortening, might be arrhythmogenic, particularly when myocardial ischemia (where potassium efflux is increased) concurs. Data on the anti-arrhythmic effectiveness of N have also been published: N reduced the spontaneous discharge of sino-atrial node and so reduced heart rate, both in vitro and man. On the other hand, among other vasodilators, cicletanine (C) has been reported to increase potassium conductance, an effect which was advocated to explain its antiarrhythmic potency. In the present investigation the direct myocardial effects of N were compared to those following C in 63 experiments (from 13 Guinea-pigs), using atrial strips (containing sino-atrial node) superfused in 1-compartment bath with normal Tyrode's solution. Using glass microelectrodes, standard electrophysiologic variables were recorded (APA, RMP, APD50%, Vmax) in spontaneously beating atrial tissue, either in Tyrode, dimethyl-sulfoxide (DMSO 1:100, as solvent), C 10(-5) M (in DMSO 1:100), and N 10(-3) M (in DMSO 1:100), whose respective perfusion periods (15 min) were randomized, always following 15 min of washout with Tyrode. Only N was tested in experiments of both 15 and 30 min duration.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated (multivariate Cox's model) the relative risk of stable excitation-conduction block (ECB) in right ventricular myocardial strips (2 x 5 x 1 mm) from 26 female guinea-pigs, bathed in a 2-compartment chamber (3 ml) on the anterior side of which modified Tyrode's solution (K+ 12 mM, HCO3- 9 mM, pH 7 +/- 0.05, pO2 80 +/- 10 mmHg and absence of glucose) is supraperfused (stimulation rate: 450 ms; wire in the posterior compartment), thus enabling simulation of electrophysiologic changes seen during acute myocardial ischemia. Using glass microelectrodes, action potential amplitude (APA), durations (APD50 and 90%), resting membrane potential (RMP) and upstroke velocity (Vmax) are investigated. The hypothesis was tested of prostacyclin and histamine involvement in the genesis of ischemia-induced ECB in this model. Either a weak prostacyclin stimulator (cicletanine 10(-5) M, IPSEN, Paris, F, in DMSO 1:100; n = 16) or a potent prostacyclin generation blocker (indomethacin 10(-5) M, Sigma, in DMSO 1:100; n = 10) and either DMSO alone (1:100; n = 16) or a specific histaminergic H1 receptor antagonist (terfenadine 10(-5) M, Sigma, in DMSO 1:100; n = 10) were supraperfused using a randomization scheme. Each animal was used twice and either a first or a second occlusion (supraperfusing the modified Tyrode's solution for 30 min) period was performed and the randomized substances were supraperfused, thus enabling obtention of n = 52 experiments for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

ST segment displacement sensitivity and specificity during exercise in the detection of myocardial ischemia are controversial, even when using mathematical approaches such as a linear regression analysis of ST/heart rate slope. In an attempt to see whether an exponential fit (ST = A-B*exp (-K*RR] of ST/heart rate relation during exercise could increase the diagnostic accuracy of exercise test in the detection of myocardial ischemia, we studied 165 patients (141 men and 24 women, mean age: 56 +/- 10 years) undergoing a simultaneous radionuclide assessment of regional ventricular function and myocardial perfusion at rest and at peak exercise in 4 hours by means of 2 injections of 99mTc-MIBI. Normal radionuclide findings were found in 4 subjects, whereas exercise-induced myocardial ischemia was detected in 90 patients with no evidence of previous myocardial infarction, and in 71 patients with previous myocardial infarction. ST segment depression was present at peak exercise in no normal subject, and in 52.2% and 60.4% of ischemic and infarcted patients, respectively, achieving a sensitivity of 55.9%, a specificity of 100% and a diagnostic accuracy of 57%. A, B and K coefficients of exponential analysis showed a wide variability among patients; however, the algebraic sign of K coefficient was negative in 50% of normal subjects versus 9.9% of patients (chi 2-test: p less than 0.02), thus achieving a sensitivity of 90.1%, a specificity of 50% and a diagnostic accuracy of 89.1% in the detection of exercise-induced myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim of this study was to evaluate the possible relationship among myocardial ischemia, left ventricular volume changes and QT interval changes during exercise in patients with coronary artery disease. QT interval, expressed as absolute value, corrected according to Bazett (QTc = aT/RR0.5) and Fridericia (QTf = QT/RR0.33) and calculated by adapting reciprocal changes in QT and heart rate during exercise to the exponential fit proposed by Sarma (QTs = A-B*exp (-K*RR], was compared to the scintigraphic finding of myocardial ischemia and to the changes in left ventricular volumes during exercise. We studied 151 patients (130 men and 21 women, mean age 56 +/- 11 years) with suspected or already ascertained coronary artery disease, who underwent a simultaneous evaluation of regional ventricular function and myocardial perfusion by means of first pass radionuclide angiography (multielement gamma-camera) and computerized tomography, with 2 injections of 99mTc-MIBI at rest and at peak of a computerized bicycle stress test. QT and RR intervals were measured on an averaged ECG complex through a magnifying lens, and the absolute values of left ventricular volumes were computed by radionuclide angiography. According to scintigraphic findings, patients were divided into normal subjects (n = 7) and ischemic patients with (n = 63) and without (n = 81) evidence of a previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

In 60 randomized dogs the effects of epoprostenol infusion (100 ng/kg/min) on ischemia-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), ventricular flutters and ventricular fibrillation were studied. The circumflex coronary artery occlusion canine model of sudden death was used. The results demonstrate different effects of epoprostenol on ischemia-induced ventricular arrhythmias: 1) both postischemic (7 of 30 vs 15 of 30, p = 0.0298) and postreperfusion (5 of 23 vs 8 of 15, p = 0.0492) ventricular fibrillations were prevented in epoprostenol dogs with an improvement of the global survival rate (18 of 30 vs 7 of 30, p = 0.0019) as compared to controls; 2) in epoprostenol treated dogs a significantly increased incidence of non lethal arrhythmias-including ventricular flutters that occurred in 12 of 30 dogs vs 4 of 30 in controls (p = 0.0195)--was observed; 3) a positive correlation between the percent diastolic pressure fall 10 min after the start of epoprostenol infusion and the number of non lethal arrhythmias was noted. However, hemodynamic effects of the compound, suggesting an oxygen sparing action, did not preclude the antifibrillatory effectiveness. Thus, the antifibrillatory and antiarrhythmic effects of epoprostenol after circumflex coronary artery occlusion and reperfusion in dogs seem independent from one another.

Magnetic resonance imaging (MRI) has shown low accuracy in measuring cardiac dimensions in normal subjects, when transverse tomographic sections are used in comparison with 2D-echocardiography. The rationale of this study was to compare cardiac dimensions in 19 volunteers based on angulated (30 degrees caudo-cranial) transverse tomographic sections both in MRI and 2D-echo. Since the planes investigated by both techniques are superimposable, highly significant correlated Ao, LA, IVS, LW, LV, and RV dimensions are observed. Standardized MRI tomography permits reduction of total examination time and assures repeatability. Thus, using the method reported here, cardiac dimensions in humans might be obtained accurately by MRI.