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 mu g/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 election fraction <40%, and all scheduled for myocardial revascularization. A 10 mu g/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 greater than or equal to 2 was present in 267 of 352 segments evaluated. Contractile reserve (decrease in testing wall motion score greater than or equal to 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 identify (r = 0.62, p <0.001) and the difference wets significant among correlation slopes of dobutamine alone, enoximone alone, and enoximone plus very low dose dobutamine echocardiography (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. (C) 1999 by Excerpta Medico, Inc

[Univariate analysis of potential risk factors for early mortality (within 28 days) after aortocoronary bypass in Italy. OP-RISK Study Group].

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

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

Abstract 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

Handgrip increases endothelin-1 secretion in normotensive young male off-spring of hypertensive parents

Abstract 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 &lt; 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p &lt; 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p &lt; 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p &lt; 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 &lt; 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p &lt; 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p &lt; 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p &lt; 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

[Increase of potassium conductance and spontaneous electric activity in vitro: comparison of nicorandil and cicletanine].

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

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, mmHg). 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