[Informed consent forms in medical practice: the results of a knowledge survey]. / Il consenso informato scritto nella pratica medica: i risultati di una indagine conoscitiva.

"Federico II" University of Naples Hospital Management's Staff considered 47 informed consent forms in order to evaluate quality and quantity of the information transmitted to patients. Every form, distinguished by procedure (surgical, pharmacological, anesthesiologic or related to blood transfusions) was evaluated for the accuracy and validity of information related to: diagnosis, prognosis, diagnostic and therapeutic opportunities, expected benefits, adverse-side effects, iatrogenic risks, privacy policy on personal data. The forms were judged by information completeness criteria "conformed" or "not conformed" with standards. Our analysis demonstrate that physicians often are unaware of legal and ethical topics related to constructing informed consent forms. They usually omit crucial information or would use strict technical language. So far, we conclude Hospital Management's Staff definitively has a role in improving informed consent forms by establishing guidelines and promoting ethical issues. Final result could be to deserve stronger patient confidence in medical institutions.

Influence of autonomic tone on QT interval duration.

The autonomic tone has been shown to influence the duration of the QT interval, however the independent contribution of sympathetic and parasympathetic tone is not fully elucidated. The influence of autonomic tone on QT duration was studied in 10 young healthy volunteers by evaluating the changes in QT and RR duration induced by i.v. isoproterenol infusion and by standing before and after i.v. administration of propranolol or atropine. Furthermore, the relationship between RR interval and QT duration was evaluated during nocturnal sinus arrhythmia and submaximal exercise test. Low doses of isoproterenol reduced RR (p < 0.01) but not QT interval duration, while higher doses influenced both RR (p < 0.0001) and QT (p < 0.001) duration. Propranolol did not influence standing-induced shortening of RR and QT intervals; on the contrary, atropine administration abolished standing-induced QT interval shortening, without influencing RR changes. QT duration resulted significantly related to preceding RR interval at peak exercise (r = 0.87, p < 0.001) and during nocturnal sinus arrhythmia (r = 0.73, p < 0.0005), however, the regression lines showing the correlation between QT and preceding RR interval were different. Both sympathetic and parasympathetic tone appear to contribute to heart rate-independent changes in QT duration. In the basal state parasympathetic more than sympathetic tone influences the relation QT-heart rate. Major increases of sympathetic nervous system activity may change the relation QT-heart rate. Thus, in case of abrupt autonomic changes, any proposed formula for heart rate correction of QT may result inappropriate, also in the normal range of heart rate.

Reduced left ventricular mechanical efficiency in elderly patients with coronary artery disease.

We evaluated left ventricular (LV) mechanical efficiency in 23 elderly patients (mean age 67 +/- 2) with coronary artery disease (CAD) and in 22 patients younger than 65 years (mean age 49 +/- 8) with similar severity of CAD (2.4 +/- 0.8 and 2.2 +/- 0.8 vessels per patient, respectively) and history of myocardial infarction (34% and 41%, respectively). LV mechanical efficiency was calculated as the ratio of LV work per minute and myocardial O2 consumption. LV stroke volume was calculated from left ventriculography. Coronary blood flow was measured by thermodilution. Older patients had lower values of LV stroke volume (49 +/- 16 vs 73 +/- 16 mL, p < 0.005), ejection fraction (41 +/- 17 vs 58 +/- 17%, p < 0.05), LV stroke work (93 +/- 26 vs 131 +/- 41 g.m., p < 0.02) and LV work per minute (6.7 +/- 2.6 vs 9.3 +/- 2.7 kg.m./min, p < 0.05). Since myocardial O2 consumption was similar in the two groups, LV mechanical efficiency was lower in older CAD patients (16.2 +/- 15 vs 23.8 +/- 12%, p < 0.05). Thus, elderly patients with CAD show a reduced LV mechanical pump performance and efficiency, compared with younger patients with similar disease severity and history of myocardial infarction. These observations may contribute to understanding the higher frequency of congestive heart failure in elderly patients with CAD.

Age-response effectiveness of gallopamil for the treatment of myocardial exertional ischemia. A medium-term randomized cross-over double-blind placebo-controlled trial.

We evaluated the efficacy and safety of gallopamil 150 mg daily in middle-aged and elderly patients with stable exertional ischemia, using a medium-term randomized double-blind cross-over placebo-controlled trial. Twenty middle-aged patients (52.8 +/- 6 years; range 38-61 years) and 14 elderly patients (67.4 +/- 2.8 years; range 65-73 years) with stable exertional ischemia underwent a bicycle exercise test. After a run-in period, both groups received treatment with either placebo or gallopamil 50 mg tid for 28 days. At the end of this time, each patient crossed over to the alternate regimen. Gallopamil significantly reduced heart rate, blood pressure and rate pressure product (from 15.37 +/- 2.7 to 13.65 +/- 4.16 U x 10(-3); p < 0.01) in elderly patients at submaximal exercise, but had no effect in middle-aged patients (from 14.52 +/- 4.45 to 13.49 +/- 3.77 U x 10(-3); p = NS). At peak exercise, none of the hemodynamic parameters was modified with gallopamil in either group. At peak exercise, both middle-aged and elderly patients achieved rate-pressure products similar to those reached during placebo at higher work loads. Exercise duration and maximal work load significantly increased in both groups. Electrocardiographic signs of ischemia were favorably influenced by gallopamil in both groups (from 1.39 +/- 0.5 mm to 0.76 +/- 0.73 mm; p < 0.001 in the middle-aged patients and from 1.5 +/- 0.34 mm to 1 +/- 0.76 mm; p < 0.01 in the elderly patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age and hypertension on adrenoceptor-sensitivity evaluated with CD25 and QT/QS2.

BACKGROUND: We studied the effects of age and hypertension on responses to chronotropic dose (CD25) and standing-induced changes in the ratio of electrical systole (QT) to electromechanical systole (QS2) in order to identify their role on beta adrenoceptor sensitivity and to verify the value of QT/QS2 ratio as a noninvasive parameter of beta-adrenoceptor sensitivity. METHODS: We enrolled 33 normal subjects and 37 hypertensive patients (WHO stage I and II) (age range 21-82 years). RESULTS: CD25 was significantly age-related in normotensive and hypertensive subjects, whereas standing-induced QT/QS2 changes were age-related in normotensive subjects only When we divided subjects into three age groups, beta-adrenoceptor sensitivity was found to be lower in hypertensives than normotensives in the two groups under age 60, but was not affected in those over age 60. This suggests that hypertension influences beta-adrenoceptor sensitivity in younger subjects, but not in elderly patients, whose beta-adrenoceptor sensitivity is already reduced. CONCLUSIONS: CD25 does not predict standing-induced QT/QS2 ratio changes; therefore, during autonomic stimulation, QT/QS2 ratio seems not to be significantly related to beta adrenergic sensitivity.

Effect of oral captopril (SQ 14225) on intraocular pressure in man.

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril (SQ 14225) on intraocular pressure (IOP) were studied. Four groups were analyzed: group A, ten control subjects; group B, ten hypertensive patients with normal IOP; group C, ten normotensive patients with primary open angle glaucoma (POAG); and group D, ten hypertensive patients with POAG. Systolic and diastolic blood pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1-h intervals up to 3h after an oral dose of 25 mg captopril or placebo, given in a randomized, double-blind cross-over fashion. The alternative treatment was given a week later. Captopril significantly lowered IOP in all patients, with no effects on heart rate and pupil diameter. Blood pressure changed only in patients with hypertension (groups B and D). Total outflow facility, measured by conventional tonography, increased significantly in all groups. These findings indicate that oral captopril could represent a new antiglaucomatous compound.

Regression of left ventricular hypertrophy and improvement of renal hemodynamics in hypertensive patients treated with quinapril.

Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174.7 +/- 16.7 to 131.7 +/- 7.7 mmHg (p < .0001) and diastolic pressure decreased from 101.8 +/- 9.8 to 80 +/- 4.3 mmHg (p < .0001). Left ventricular mass index decreased in the eight patients with left ventricular hypertrophy (p < .01). Basal values of GFR were lower than normal in 41% of all patients; GFR increased significantly after 20 weeks of treatment (from 96.5 +/- 32.3 to 108.6 +/- 31.12 ml/min, p < .01); it decreased in only one patient. Patients reported few adverse effects to quinapril, and no important clinical laboratory abnormality was observed. Quinapril not only lowered arterial pressure, but it had a distinct effect on regression of left ventricular hypertrophy and favorable effects on renal function.

Role of aging on electrical, mechanical, and coronary modification induced by ouabain and epinine in isolated rat heart.

OBJECTIVE: The contractile response to digitalis and beta adrenoceptor agonists is lower in the senescent than in the adult myocardium, while the development of ventricular arrhythmias is increased. The aim of this study was to examine the effects of aging on cardiac response to digitalis and an adrenergic agonist used clinically. METHODS: The electrical and mechanical responses were tested in isolated and perfused hearts from 3-24 month old rats receiving 15 min infusion of digitalis drug (ouabain, 6 x 10(-5) M) alone, and after 5 min of beta adrenoceptor agonist drug (epinine, 1.5 x 10(-7) M). RESULTS: Ouabain action was associated with a rise in left ventricular end diastolic pressure (p < 0.01) which increased progressively with aging, and with an elevation of left ventricular developed pressure (p < 0.01) which decreased progressively with aging. Epinine induced a reduction of left ventricular end diastolic pressure (p < 0.01) and a rise in left ventricular developed pressure (p < 0.01) but both effects decreased progressively with aging. Ouabain reduced coronary flow and this decrease was more pronounced with aging (p < 0.01), while epinine caused an increase (p < 0.01) that diminished in older hearts. Ouabain given after epinine resulted in a greater increase in left ventricular end diastolic pressure than epinine (p < 0.01) but lower than that caused by ouabain alone (p < 0.01), a greater increase in left ventricular developed pressure than epinine and ouabain (p < 0.01), and a smaller reduction of coronary flow rate than ouabain alone (p < 0.01). All these effects, however, diminished progressively with aging. Arrhythmia scores were higher during ouabain than in control (p < 0.01) and in epinine treated hearts (p < 0.01); pretreatment with epinine did not modify arrhythmia score during ouabain administration. The number and severity of arrhythmias, however, increased with aging in all groups. CONCLUSIONS: Aging has a negative effect on both the positive inotropic and the arrhythmogenic effects of ouabain and epinine, although these phenomena are more pronounced during ouabain administration. However, when the two drugs are given simultaneously, epinine does not modify the arrhythmogenic effect of ouabain but reduces some of its deleterious haemodynamic effects.

[Comparison of nisoldipine and diltiazem in the treatment of effort angina pectoris]. / Confronto tra nisoldipina e diltiazem nel trattamento dell'angina da sforzo.

BACKGROUND: In order to evaluate the benefits of a calcium-antagonist medium-term treatment, 20 patients with effort stable angina pectoris were treated with nisoldipine in comparison to diltiazem. METHODS: Twenty patients with stable effort angina completed a double-blind, placebo controlled trial, comparing 10 twice daily nisoldipine per os and diltiazem 120 three times daily per os for 28 days. After wash-out, placebo and drug period, ergometer stress tests were performed. Exercise tolerance, angina frequency, nitrate consumption and side effects were evaluated. RESULTS: Our results showed that both drugs significantly increased exercise tolerance. Exercise duration was 330 +/- 107 sec after placebo, 397 +/- 106 sec after nisoldipine (p < 0.05) and 378 +/- 99 sec after diltiazem (p < 0.05). Effort angina episodes decreased from 20 after placebo to 8 after nisoldipine and diltiazem. Both drugs reduced rate-pressure product at submaximal exercise in comparison to placebo. There were no differences at peak exercise between placebo or drug periods. Both drugs similarly reduced nitrate consumption and weekly effort angina attacks. No patients referred serious side-effects. CONCLUSIONS: nisoldipine, like diltiazem, is an effective drug in the treatment of stable effort angina. Moreover, the therapeutic effects of nisoldipine during medium-term treatment are probably related to decrease in oxygen consumption.

Age-related changes of antianginal effects of verapamil in patients with stable effort angina. A medium term randomized double-blind placebo controlled trial.

Our study evaluated the effects of verapamil in elderly patients with stable effort angina using a medium-term double-blind placebo-controlled protocol. Thirty-nine consecutive patients, 23 middle-age patients (50 +/- 6 years; range 38-60 years) and 16 elderly patients (66 +/- 2 years; range 65-70 years) with exertional angina were chosen. After a run-in period, both groups received treatment with either placebo or verapamil--360 mg daily--for 4 weeks. During treatment, weekly angina frequency and nitroglycerin consumption were significantly reduced in both groups. Verapamil significantly decreased the rate-pressure product at rest in elderly patients and in both groups at submaximal exercise, due to a reduction in heart rate in both groups and to a more marked decrease in arterial pressure in older patients. At peak exercise, the rate-pressure product was unchanged in both groups after verapamil, while exercise capacity showed a significant improvement in the middle-aged, and ST segment depression was reduced in both groups. After verapamil, 30% of middle-aged patients and 44% of elderly patients had to stop exercising because of angina. Side effects were rare and no drop-out was recorded. Verapamil exerted its antianginal action by means of a decrease in myocardial oxygen consumption at rest and at submaximal exercise in the elderly, while only at submaximal exercise in the middle-aged. Therefore verapamil at the dose of 360 mg daily proved an effective antianginal drug with a safe effect profile also in elderly patients.

Relationship between ventricular ectopic beat frequency and heart rate: study in patients with severe arrhythmias.

To evaluate and quantify the relationship between premature ventricular contractions (PVCs) and heart rate (HR), 57 patients (48 men and 8 women, mean age 59.8 +/- 7.9 years) with severe PVCs (Lown-Wolf grade > or = 3a) over 24 hours of Holter monitoring were studied. Twenty had no coronary artery disease (CAD), 25 had angiographically documented CAD, and 12 had acute myocardial infarction. All parameters of the 24-hour recordings from two ECG leads were measured by a Holter analyzer designed in our laboratory, based on fast microprocessors and controlled by a microcomputer. Scatter diagrams of the number of PVCs per minute as a function of HR and correlation coefficient were computed for various HR values corresponding to a total number of minutes greater than five. A positive correlation (r > or = 0.35) was found in most patients without CAD (85%); there was a complex relationship between the strength of the correlation and the presence of CAD or acute myocardial infarction because of a greater variability in the results of correlation coefficient analysis (coefficient of variation 62%, 208%, and 145% in patients without CAD, with CAD, and with acute myocardial infarction, respectively). The incidence of a positive correlation was similar in patients with Lown-Wolf grade III (63%), IVa (82%), or > or = IVb (67%) arrhythmias. The reproducibility of the correlation coefficient of the relationship between PVC frequency and HR was tested in 15 patients. The mean value of the correlation coefficient was 0.801 +/- 0.169 for the first test and 0.805 +/- 0.22 (p = NS) for the second test.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects of nifedipine, diltiazem and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study.

We evaluated the acute therapeutic effects of the oral administration of nifedipine (10 mg) and diltiazem (120 mg) alone and in combination in 16 patients with effort angina. The 16 patients (13 men and three women; mean age 59 +/- 7 years) performed a symptom-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration and time to 1 mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by the combination of drugs. Nifedipine and diltiazem alone similarly improved exercise duration as markedly as their combination. One patient stopped the test after all three treatments for angina associated with ST depression > 2 mm. The combination of drugs yielded the best symptomatic effect: only four patients complained of angina in comparison to eight and seven patients after diltiazem and nifedipine, respectively. Nifedipine and diltiazem are effective and safe antianginal drugs. Some patients respond better to one drug than to the other. Patients who remain symptomatic in spite of maximal doses of a single drug may derive some benefit from combination therapy.

Exercise induced increase in diastolic blood pressure. Is it an indicator of coronary artery disease?

It has been previously reported that an increase in diastolic blood pressure greater than 15 mmHg comparing values at rest with those on treadmill exercise, with or without ST changes, enhances the probability of coronary artery disease. To investigate whether the diastolic blood pressure variation keeps its diagnostic value during upright bicycle exercise, we evaluated the diastolic blood pressure variations in 111 patients with angiographically documented coronary artery disease without previous myocardial infarction and in 53 patients with normal coronary arteries undergoing maximal stress testing on a bicycle ergometer. The sensitivity of diastolic blood pressure (DBP) variations to detect coronary artery disease was 66%, the specificity 32%, the positive predictive value 67%, the negative predictive value 31% and the predictive accuracy 55%. The respective values for ST depression were 83% (P less than 0.001 vs DBP variations), 53% (P less than 0.05 vs DBP variations), 64% (P less than 0.05 vs DBP variations) and 75% (P less than 0.001 vs DBP variations). Forty-nine of the 75 patients with multivessel coronary artery disease and 60 of the 89 patients without coronary artery disease or with single vessel disease had abnormal DBP variations (sensitivity 65; specificity 33%). The sensitivity of ST segment depression in predicting multivessel disease was 91% (P less than 0.001 vs DBP variations), and the specificity 42%. Thus, for bicycle ergometer exercise testing, ST segment depression seems to be more accurate than DBP variations in the diagnosis of coronary artery disease.

The hypothetical role of potassium conductance on the genesis of R-wave amplitude increase during ischemia in the isolated rat heart.

The effect of increased potassium conductance on the genesis of R-wave amplitude increase during acute myocardial ischemia has been studied in the isolated perfused rat heart by simultaneously recording the R-wave amplitude of epicardial electrograms (VEE), heart rate (HR), coronary flow rate (CFR), left ventricular diastolic pressure (LVDP), and left ventricular systolic pressure (LVSP). The experiments were performed during basal and partial or total ischemic conditions at spontaneous or fixed HR. In some experiments, potassium conductance was increased by means of high-calcium (8 mM) or acetylcholine chloride (10(-6) M) perfusion. In the control experiments, partial ischemic perfusion produced an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP; total ischemic perfusion exaggerated these variations. High-calcium perfusion provoked an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP during basal conditions (p less than 0.01 vs. control experiment); these modifications increased progressively during partial ischemic perfusion (p less than 0.01 vs. control experiment) and during total ischemic perfusion (p less than 0.01 vs. control experiment). Perfusion with acetylcholine chloride produced variations similar to those observed in high-calcium solution except that LVDP under basal conditions remained unchanged from control. When the HR was maintained at a constant value by means of atrial pacing the results were similar to those observed in the unpaced hearts. In conclusion, in the isolated perfused rat heart, increasing potassium conductance may influence the genesis of R-wave amplitude increasing during acute myocardial ischemia.

Effects of intracoronary gallopamil on coronary hemodynamics and myocardial oxygen consumption in humans.

The response of coronary hemodynamics to the intracoronary (i.c.) bolus administration of gallopamil, 1.5 and 3.0 micrograms/kg, was evaluated in 14 patients with normal coronary arteries. Gallopamil, 3.0 micrograms/kg, induced a small and transient decrease in systolic and mean arterial pressure and a small increase in the preejection period. Coronary sinus blood flow increased significantly at 30 s (p less than 0.01) and returned to baseline 10 min after gallopamil administration. Coronary vascular resistance was still reduced at 10 min and returned to baseline at 15 min. Myocardial O2 consumption and extraction decreased significantly (p less than 0.01) at 30 s. While myocardial O2 consumption returned to baseline 15 min after gallopamil administration, myocardial O2 extraction was still significantly reduced at this time. Milder and more transient changes were observed after i.c. administration of the lower dose (1.5 micrograms/kg), and no significant changes were found after i.c. administration of saline. These data show that i.c. gallopamil, in patients with normal coronary arteries, induces direct, transient, and dose-related peripheral coronary vasodilation. The reduction of myocardial O2 consumption and extraction suggests a direct negative inotropic and metabolic effect of gallopamil.

[The effects of slow-release verapamil in relation to plasma concentration in aged hypertensives. A study with continuous monitoring of arterial pressure and electrocardiogram]. / Effetti del verapamil slow release negli ipertesi anziani in rapporto alle concentrazioni plasmatiche. Studio mediante monitoraggio continuo della pressione arteriosa e dell'elettrocardiogramma.

Twenty-four hour ambulatory blood pressure and electrocardiographic monitoring (Oxford method) was carried out in baseline conditions and after 15 days of therapy with a once a day administration of 240 mg verapamil slow-release in 11 elderly hypertensive patients. The 24 hour electrocardiographic monitoring (but not the blood pressure monitoring) was also carried out after 30 days of therapy. High-pressure liquid chromatography plasma concentrations of verapamil and its metabolite norverapamil were compared with the blood pressure and electrocardiographic responses. Systolic and diastolic blood pressure were significantly reduced after 15 days of therapy without circadian rhythm modification; mean heart rate was reduced after 15 and 30 days and the P-Q interval prolonged. Peak verapamil and norverapamil plasma concentrations were observed 8 hours after administration; at the 25th hour, the concentrations were respectively 60.9% and 68.3% of peak value (139.5 +/- 95.4 ng/ml and 126.4 +/- 60.9 ng/ml). Plasma levels of verapamil and norverapamil significantly correlated with heart-rate decrease. No correlation was observed between drug concentrations and systolic and diastolic blood pressure. A first-degree atrioventricular block was observed in 3 patients during therapy. Supraventricular premature contractions showed a decrease after 15 and 30 days of therapy. Thus, once a day administration of verapamil slow release is an effective anti-hypertensive medication in elderly hypertensive patients. Caution should be exercised in patients with P-Q interval prolongation and sinus bradycardia.

Differences in blood pressure profile between young and elderly hypertensive patients.

We studied 40 subjects, 20 under 60 yrs old (10 normotensive and 10 hypertensive) and 20 over 60 yrs old (10 normotensive and 10 hypertensive). Each patient underwent a 24-hour ambulatory blood pressure monitoring (8:00 a.m. to 8:00 a.m.), by a noninvasive method using an ICR 5300 apparatus. Systolic blood pressure was significantly higher on random measurement and during the daytime in the older patients. Although comparison of the other parameters did not reveal significant differences, we noted a tendency to higher systolic values among the older group, and higher diastolic values in the younger one. The variability of the values was slightly higher, although not significantly, among the older patients. In both groups random systolic measurements, and in the younger group diastolic values as well, were significantly higher than mean 24 hour values. The incidence of abnormal systolic BP values ranged from 18.8% to 100% (mean 60.2% +/- 28.9) in younger hypertensives, and from 54% to 100% (mean 76.5% +/- 14.4) in older patients. The incidence of abnormal diastolic BP values ranged from 64.5% to 100% (mean 80.4% +/- 15.6) in younger patients and from 47.2% to 96% (mean 67.8% +/- 15.8) in older patients. The correlation between mean systolic and diastolic values recorded from 8:00 to 10:00 a.m., and mean 24-hour values was significant in young hypertensives, while in the older group there was a significant correlation only for diastolic BP. The lack of significance for systolic values is probably due to a greater variability in systolic pressure in elderly subjects during the morning.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects of nisoldipine, propranolol, and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study.

We studied the short-term effects of oral administration of nisoldipine (10 mg) and propranolol (80 mg) alone and in combination in 14 patients with chronic exertional angina pectoris in a double-blind, randomized, cross-over study. The 14 patients (13 men and 1 woman, mean age 56 +/- 7 years) performed symptoms-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration, and time to 1-mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by drugs alone and in combination. Propranolol and nisoldipine alone improved exercise duration similarly and as well as the combination; however, a different response to the three pharmacologic interventions was found in patients treated with single drugs. The improvement in exercise tolerance was associated with rate-pressure product values at peak exercise, unchanged after nisoldipine and significantly reduced after both propranolol alone and in combination. After placebo, all patients had exercise-induced angina, in 9, 8, and 4 patients after nisoldipine, propranolol, and the combination of the two drugs, respectively. Nisoldipine is effective in the treatment of effort angina and its combination with propranolol may be useful and superior in patients who show poor response to monotherapy.

Arrhythmogenic age-related effects of lysophosphatidylcholine in the rat heart.

Ventricular arrhythmias are the most common cause of death among patients with coronary artery disease; this is more evident in the elderly, who tend to have more severe coronary artery disease and age-dependent modifications of cardiac electrophysiology. Lysophosphoglycerides, which accumulate in the ischemic myocardium, are responsible for oscillatory after-potentials and may contribute to the development of ventricular arrhythmias. The aim of this study was to examine the effects of lysophosphatidylcholine (5 x 10(-5) M) in the absence or presence of epinephrine (10(-6) M) in isolated, perfused hearts from adult (6-12 months old) and senescent (24 months old) rats. Rat hearts (30/group) were randomly divided into four groups each of which included hearts of 6, 12 and 24-month old rats. The groups comprised a control group, a group treated with epinephrine, a group treated with lysophosphatidylcholine and a group treated with both epinephrine and lysophosphatidylcholine. Analysis of arrhythmias indicated a linear correlation between epinephrine- and lysophosphatidylcholine-induced ventricular arrhythmias and age. The incidence of arrhythmias was higher in the hearts treated with epinephrine and lysophosphatidylcholine together than in those treated with either substance separately (p less than 0.01). The results indicate that age influences the arrhythmogenic action of lysophosphatidylcholine, and that epinephrine contributes to this effect.