Potassium channel openers and blockers in coronary artery disease. Comparison to betablockers and calcium antagonists.

Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced antiischemic effects and was found to have favorable hemodynamic, neurohumoral and antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.

Comparison of the potassium channel blocker tedisamil with the beta-adrenoceptor blocker esmolol and the calcium antagonist gallopamil in patients with coronary artery disease.

BACKGROUND: Tedisamil is a new bradycardic agent proven to exert anti-ischemic and antiarrhythmic effects by blockade of the different cardiac and vascular K+ currents. HYPOTHESIS: It was the aim of the present study to compare the favorable anti-ischemic effects of tedisamil, with two long established representatives in the treatment of coronary artery disease (CAD), namely, the beta1 blocker esmolol and the Ca2 antagonist gallopamil. METHODS: The hemodynamic and neurohumoral effects of the new potassium channel blocker tedisamil, an agent with negative chronotropic and class III antiarrhythmic properties, were compared with the ultra-short-acting beta1-selective adrenoceptor blocker esmolol and the calcium antagonist gallopamil. A total of 22 patients with angiographically proven CAD and reproducible ST-segment depression in the exercise electrocardiogram was included in two studies with an almost identical design and inclusion criteria. The investigation was carried out using right heart catheterization and bicycle ergometry. A subgroup of 8 patients receiving 0.3 mg/kg body weight tedisamil intravenously (i.v.) in an open dose-finding study was compared with a group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intraindividual comparison. RESULTS: Tedisamil and esmolol reduced heart rate at rest by 13% (p < 0.001), and 6% (p < 0.05), and at maximum working levels by 8% (p < 0.01) and 9% (p < 0.05), respectively. Gallopamil increased heart rate at rest by 7% (p < 0.05), with only slight changes occurring during exercise. Corresponding findings for each drug were observed for cardiac output both at rest and during exercise [tedisamil: at rest -10% (NS), max. exercise -8%; esmolol: at rest -14% (NS), max. exercise -18% (NS); gallopamil: no significant changes]. Compared with tedisamil, stroke volume was reduced by esmolol [at rest and max. workload: -9% (NS)] and gallopamil [rest: -6% (NS), max. exercise: -2% (NS)]. Of the indirect parameters of ventricular function, that is, mean capillary wedge pressure (PCWPm) and right ventricular ejection fraction, only PCWPm demonstrated significant differences between tedisamil and gallopamil (+18% and -6% at rest, +17% and -21% during exercise, respectively; p < 0.001). Compared with gallopamil, both tedisamil and esmolol were superior in their effects on rate-pressure product, myocardial oxygen consumption, and ST-segment depression, whereas plasma lactate concentration was more reduced by tedisamil and gallopamil. Tedisamil led to a fall in norepinephrine levels in particular. CONCLUSION: Tedisamil and esmolol showed almost equipotent anti-ischemic effects at the doses administered. Tedisamil acts mainly by reductions in heart rate, and esmolol, though to a lesser degree, also by reductions in systolic blood pressure. The mechanism of gallopamil is to reduce afterload and to improve coronary perfusion. At the doses applied, however, it has lower antianginal potency compared with tedisamil and esmolol.

Gallopamil activity on asynergic viable myocardium in acute myocardial infarction: insights on stunned and hibernating myocardium.

The influence of the calcium antagonist gallopamil on the contractility of asynergic viable myocardium after acute myocardial infarction treated with thrombolysis was investigated by two-dimensional echocardiography. Sixteen patients with > or = 1 viable segment(s), identified during the low-dose phase (up to 10 micrograms/kg/min) of a dobutamine echocardiographic test (up to 40 micrograms/kg/min) performed 4-5 days after a first acute myocardial infarction, were given a gallopamil intravenous bolus (50 micrograms/kg) 12-24 hours later. Two-dimensional echocardiography was done before and 15 minutes after the bolus. A score index of 1 (normokinesis) to 4 (dyskinesis) and a 16-segment model were used. A segment was considered viable when a resting asynergy (score > or = 2) improvement of > or = 1 grade was seen during low-dose dobutamine. Follow-up echocardiograms were done 3-5 months later. A total of 30 viable segments were found; of these, 10 showed sustained improvement in contractility (group A) during high-dose dobutamine, while 20 exhibited a biphasic response returning to their basal contractile state (group B). After the gallopamil bolus, 9 of 10 group A segments improved their contractility, in comparison with 0 of 20 group B segments (P < .001). Infarct-related vessel significant (> or = 75%) coronary stenosis was present in the tributary vessel of 0 of 10 group A and of 20 of 20 group B segments (P < .001). At follow-up, 9 of 10 group A segments showed a spontaneous contractile improvement; of the 20 group B segments, 8 of 10 that underwent revascularization (7 angioplasty, 3 bypass graft) showed contractile improvement, in comparison with 0 of 10 segments not revascularized (P = .001). We conclude that gallopamil may reverse the contractile dysfunction of postischemic stunned myocardium in patients with acute myocardial infarction, whereas no effects are apparent on ischemic/hibernating myocardium.

Vasospasm in smooth coronary arteries as a cause of asystole and syncope.

In a patient with proven myocardial infarction, coronary artery disease was excluded angiographically. Four weeks later the patient experienced recurrent syncope of unknown cause. By means of Holter monitoring, ST-segment elevation with subsequent first-degree AV block progressing to asystole and resulting in loss of consciousness were documented. Treatment with gallopamil and a VVI-pacemaker led to complete relief of all symptoms. Hence, Prinzmetal's angina may be a rare cause of syncope even in smooth coronary arteries.

Effect of gallopamil on myocardial microperfusion in patients with stable effort angina: a randomized, cross-over, double-blind, placebo-controlled trial.

We evaluated the efficacy and safety of daily administration of gallopamil 150 mg/day and its effects on myocardial perfusion in a medium-term, randomized, double-blind, cross-over, placebo-controlled trial. We studied 19 patients (17 males and 2 females; mean age 57 +/- 6.8 years) with stable effort angina, angiographically documented coronary artery disease and reversible perfusion defects during exercise thallium-201 myocardial scintigraphy of at least one segment of the left ventricle. After 2 weeks of a single-blind placebo run-in period, during which each patient underwent at least 2 exercise tests and a 48-hour Holter ECG recording, all patients were treated with either placebo or gallopamil 50 mg t.i.d. for 28 days. At the end of this period, patients crossed over to the alternate regimen. This phase was double blind. After treatment with placebo or gallopamil, patients underwent exercise tests, 24-hour Holter ECG recording and thallium-201 myocardial scintigraphy. Weekly angina frequency and trinitroglycerin (TNT) consumption and safety were also evaluated. No patients dropped out of the study because of major side effects. The number of total ischemic and symptomatic events recorded at 24-hour ECG monitoring, weekly angina frequency and TNT consumption were significantly reduced during gallopamil treatment. After gallopamil administration, exercise duration significantly increased (run-in: 419 +/- 116 s, placebo: 420 +/- 118 s, gallopamil: 511 +/- 144 s; p < 0.05), and ST segment depression was significantly reduced (run-in: -1.3 +/- 0.3 mm, placebo: -1.3 +/- 0.3 mm, gallopamil: -0.94 +/- 0.68 mm; p < 0.01), while heart rate, systolic blood pressure and rate-pressure product were unchanged at rest, at submaximal and at peak exercise. Qualitative and quantitative evaluation of myocardial perfusion and the myocardial uptake percentage of thallium-201 in ischemic zones were significantly improved by gallopamil treatment. These findings demonstrate that gallopamil can improve myocardial perfusion and reduce myocardial oxygen consumption.

Comparative study on the effect of calcium channel blockers on basal and parathyroid hormone-induced bone resorption in vitro.

A number of clinical and experimental studies suggest that the effects of calcium channel blockers are not limited to the cardiovascular system but might also involve skeletal calcium metabolism due to the presence of L-type calcium channels in osteoblastic cells. We therefore investigated the influence of calcium channel blockers of the dihydropyridine type (nifedipine, amlodipine) as well as of the phenylalkylamine type (verapamil, gallopamil) on basal and parathyroid hormone-induced bone resorption utilizing organ-cultured neonatal mouse calvaria. Only at 10(-4) M, amlodipine, verapamil and gallopamil reduced basal and parathyroid hormone-induced resorption In contrast, nifedipine, between 10(-5)-10(-4) M, exhibited a dose-dependent inhibitory effect on parathyroid hormone-related bone resorption by up to 50%. When calvariae were cultured for 48 hr in the presence of inhibitory concentrations of the calcium channel blockers and then stimulated with parathyroid hormone, only parietal bones pretreated with nifedipine remained completely responsive to the bone resorbing action of the hormone.

Systemic and regional hemodynamic effects of gallopamil in patients with essential hypertension.

Systemic and regional hemodynamics were assessed in 10 patients with uncomplicated mild to moderate essential hypertension before and during gallopamil therapy. Cardiac output was measured in triplicate with indocyanine dye. Plasma volume and renal blood flow were measured radioisotopically. Immediately following the initial dose of a slow-release (SR) formulation of gallopamil, a significant fall in arterial pressure associated with a decreased total peripheral resistance and a reflex increase in heart rate and cardiac output were seen. Then, after 8-12 weeks of treatment, arterial pressure and total peripheral resistance remained reduced, but heart rate and cardiac output returned to pretreatment levels. Gallopamil also produced significant reductions in renal and splanchnic vascular resistance. Plasma volume and total blood volume did not change. Thus, gallopamil reduced arterial pressure and vascular resistances without fluid retention or prolonged reflexive changes.

Gallopamil reduces the post-transplantation acute tubular necrosis in kidneys from aged donors.

Due to a shortage of suitable kidneys for transplantation there has been an increase in the use of kidneys taken from old and marginal donors, which has led to a high incidence of acute tubular necrosis. Several reports suggest that the administration of calcium channel blockers improves the initial function after renal transplantation. We conducted a randomized, double-blind placebo-controlled trial to study the effect of the calcium channel blocker gallopamil on the incidence and course of acute tubular necrosis following cadaveric renal transplantation. A trend developed showing a decrease in episodes of acute tubular necrosis in gallopamil versus placebo, and became statistically significant when the outcome of kidneys from donors older than 50 years was analyzed separately [gallopamil 6/14 (42%) vs. placebo 10/11 (91%), P <0.01 corrected chi2]. We conclude that pre-transplantation renal graft perfusion and post-transplantation recipient treatment with gallopamil reduces the incidence of post-transplantation acute tubular necrosis, particularly in kidney taken from older donors.

Persisting effect of Ca(2+)-channel blockers on left ventricular function in hypertrophic cardiomyopathy after 14 years' treatment.

Ca(2+)-channel blockers of the verapamil type have been reported to exert a beneficial effect on clinical symptoms and survival rates in hypertrophic cardiomyopathy. The effects of verapamil have been attributed predominantly to an improved diastolic filling. It is unknown whether an effect on diastolic filling persists in these patients after long-term treatment. Fourteen patients (12 men, 2 women, median age fifty-one [thirty-two to fifty-five] years) with hypertrophic cardiomyopathy were included in the study. Patients had been treated with verapamil 240-480 mg/d or gallopamil 150-200 mg/d for fourteen (seven to seventeen) years. The effect of a withdrawal of Ca(2+)-channel blockers on parameters of left ventricular diastolic function was evaluated at rest and during exercise in patients with hypertrophic cardiomyopathy after long-term therapy. Investigations were performed at rest and during supine ergometric exercise during ongoing Ca(2+)-channel blocking therapy and after five (four to nine) days' withdrawal (control). Pulsed Doppler echocardiography was used to record diastolic mitral flow profiles from an apical four-chamber view. Withdrawal of Ca(2+)-channel blockers of the phenylalkylamine type after long-term treatment of hypertrophic cardiomyopathy resulted in a significant reduction of early diastolic inflow velocity at rest and during exercise. In conclusion, these results indicate a persistent improvement of early diastolic filling by Ca(2+)-channel blockers even after long-term treatment.

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease.

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.

Prevention of reoxygenation-induced arrhythmias in guinea pig papillary muscles.

Effects of various agents on reoxygenation-induced arrhythmias, action potentials, and tension of guinea pig papillary muscles were recorded to investigate the site of action. Triggered activities due to delayed afterdepolarizations (DADs) and aftercontractions were elicited on reoxygenation after 60-min substrate-free hypoxia. Low extracellular Ca2+ (0.1 mM) abolished arrhythmias, and high Ca2+ (4.9 mM) increased the amplitudes of DADs and aftercontractions. D-600 at the high concentration (20 microM) decreased the incidence of arrhythmias (p < 0.05 vs. no drug) and decreased the recovery of developed tension after reoxygenation (p < 0.001). Ryanodine (1 microM) abolished aftercontractions and arrhythmias but did not affect the recovery of developed tension. Tetrodotoxin (TTX 3 microM) and nicorandil (100 microM) decreased the incidence of arrhythmias (p < 0.05), but did not affect the recovery of developed tension or the amplitudes of aftercontractions. TTX caused only a slight decrease in Ca2+ transients in a fluo-3-loaded guinea pig ventricular myocyte. The Ca2+ entry through the Ca2+ channels apparently synchronized Ca2+ release from the sarcoplasmic reticulum, and D-600 at the high concentration apparently decreased the incidence of arrhythmias. TTX and nicorandil decreased arrhythmias, probably by decreasing the Na+ current or by increasing the ATP-sensitive K+ current, respectively.

Influence of gallopamil on the gastric effects of stress in conscious rats.

The influence of the calcium-channel blocker gallopamil on cold-restraint stress (CRS)-induced gastric effects was investigated in conscious rats with gastric cannula. CRS, while leading to multiple gastric lesions, reduced gastric acid output and mast cell count, but increased the gastric emptying rate of acid solutions. Intraperitoneally injected gallopamil (1 mg/kg), given 1 h before CRS administration, prevented gastric lesion formation and partially reversed mast cell count and the emptying of acid solutions, but had no further effect on acid output. However, gallopamil in unrestrained rats did not significantly affect acid emptying or mast cell count. Regarding calcium involvement in the pathophysiology of stress-induced gastric lesions, the possible antiulcer actions of gallopamil involved in the prevention of CRS-induced lesion formation may be attributed to its putative stabilizing effect on mast cells and gastric emptying.

[The effect of gallopamil and propranolol in patients with ischemic cardiopathy and moderate depression of ventricular function]. / Efecto del gallopamil y del propranolol en pacientes con cardiopatía isquémica y depresión moderada de la función ventricular.

BACKGROUND: Calcium channel blockers have been wide and successfully used in the treatment of coronary heart disease. Gallopamil, a metoxylic derivative of verapamil, has many of its properties and so, caution is recommended when given to patients with depressed left ventricular function. Clinical studies about this effect are scarce, and we have assessed it in patients with coronary heart disease and diminished left ventricular function. METHODS: We studied 20 patients in a cross-over, randomized, double-blind study during three weeks active periods with two intercalating washout placebo periods of one week. Patients had history of previous myocardial infarction, positive exercise stress test and ejection fraction ranging from 30% to 50% by echocardiography. RESULTS: There were no significant differences between each drug and corresponding placebo on either systolic or diastolic function. When we compared both drugs, patients showed a milder increase in area under E after propranolol than after gallopamil (p < 0.008). Clinical episodes of cardiac failure were not reported, and ejection fraction did not change. CONCLUSIONS: Both gallopamil and propranolol can be used in patients with coronary heart disease and moderately depressed left ventricular ejection fraction.

Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart.

The aim of this study was to assess the effect of two different calcium channel blockers on myocardial blood flow and function in a rat model of myocardial 'stunning' by repeated short episodes of ischaemia ('repetitive ischaemia'). In an open chest rat model, the left anterior descending coronary artery was ligated for 10 min followed by 15 min reperfusion. In total, five periods of ischaemia and reperfusion were performed. Myocardial blood flow was assessed by the hydrogen clearance technique and systolic thickening fraction by pulsed Doppler. After five episodes of ischaemia, myocardial blood flow adn myocardial thickening in the ischaemic area were reduced by 60 +/- 8% and 52 +/- 7% (n=9), respectively, as compared to baseline. Continuous intravenous infusion of the calcium channel blockers nifedipine (n=6) and gallopamil (n=6), started 20 min prior to onset of ischaemia, attenuated the ischaemia-induced decrease of myocardial perfusion. Nifedipine was the most effective with only 5 +/- 2% reduction in blood flow after five ischaemic episodes, whereas reduction of myocardial blood flow was 30 +/- 4% in the presence of gallopamil. However, neither nifedipine nor gallopamil were able to prevent regional ventricular dysfunction induced by repetitive ischaemia. Despite the preservation of myocardial blood flow following repetitive ischaemia, calcium channel blockers do not prevent ischaemia-induced reduction of myocardial function in the ischaemic area.

[Analysis of heart rhythm variability in evaluation of treatment for unstable angina pectoris]. / Analiza zmiennosci rytmu serca w ocenie leczenia niestabilnej choroby wiencowej.

Unstable angina pectoris is accompanied by several unfavourable autonomic disturbances. A noninvasive assessment of the autonomic cardiac control is possible by means of heart rate variability analysis (HRV). 26 patients with unstable angina pectoris were enrolled in the study. All patients received obligatory nitroglycerin and heparin intravenously within two days, and gallopamil (G) or metoprolol (M) together with aspirin or ticlopidine orally randomly, which were continued for 3 month or shorter if coronary revascularization was earlier performed. 512 R-R intervals was registered in each patient at 7th day of hospitalization and in 14th at the time of admission. Kardioassist v.1.0 system was used for heart rate variability analysis. After analog to digital conversion, with 12 bit resolution and 1000 Hz of sampling rate, seriogram of R-R intervals was obtained, and then power spectrum density was computed with the Fast Fourier Transform. Time-domain analysis provided mean (basic) R-R interval (BCL) and its standard deviation (SD-RR). In frequency-domain the following spectral variables were analysed: power spectral density (s2/Hz) of the high frequency component (aHF, 0.15-035 Hz), low frequency component (aLF, 0.05-0.15 Hz) and very low frequency component (aVLF, 0.004-0.05 Hz), percentage power of respective components (%HF, %LF and %VLF) and autonomic balance indices: aLF:aHF and %LF:%HF. These variables were compared in patients treated with G (13 patients) against those with M (13 patients). Additionally, the effects of treatment regimen was evaluated also in 14 patients, in whom HRV analysis was performed at admission and 7 days later.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Gallopamil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in ischaemic heart disease.

Gallopamil is a methoxy derivative of verapamil. As is typical of the phenylalkylamine class of calcium antagonists, it acts on the vascular system, and on the heart and its nodal structures. In the treatment of stable angina pectoris, gallopamil is at least as effective as nifedipine and diltiazem, though apparently better tolerated than nifedipine. Typical of calcium antagonists there is little or no tolerance to the antiischaemic effects of gallopamil. Preliminary studies indicate that gallopamil, like other calcium antagonists, has cardioprotective potential. However, further investigation is required to explore the clinical relevance of the improved myocardial regional perfusion and free fatty acid utilisation in reversibly ischaemic regions, and the potential of delayed ischaemia during angioplasty that is observed during gallopamil administration. Gallopamil is well tolerated, exhibiting a low propensity for causing cardiovascular and gastrointestinal adverse effects, thus making it a suitable alternative to other calcium antagonists for the treatment of patients with ischaemic heart disease.

[Ventricular fibrillation and silent myocardial ischemia in a patient without anatomic heart disease]. / Kammerflimmern und stumme Myokardischämie bei einem Patienten ohne strukturelle Herzerkrankung.

A 44-year-old man, apparently without heart disease, suddenly collapsed with loss of consciousness. Ventricular fibrillation was documented when an external defibrillator was connected. After cardiopulmonary resuscitation and intubation he quickly regained consciousness. Clinical examination together with echocardiography, coronary angiography and electrophysiological tests discovered no abnormalities. Biochemical tests were normal except for slightly abnormal liver functions. Several long-term ECG recordings documented asymptomatic S-T elevations. During one such episode there occurred a polymorphous ventricular tachycardia of brief duration. Because the S-T elevations persisted, despite the administration of gallopamil (50 mg twice daily for one week), a defibrillator was implanted. Gallopamil was then discontinued. Long-term ECG monitoring subsequently revealed four episodes of marked S-T elevations, three of which accompanied by ventricular arrhythmias. After resuming gallopamil, now at a dose of 50 mg three times daily, further ECG monitoring showed no abnormalities.

[An ergometric cross-over evaluation of the anti-ischemic efficacy of amlodipine and gallopamil in stable angina of effort]. / Valutazione ergometrica in cross-over dell'efficacia antischemica dell'amlodipina e del gallopamil nell'angina stabile da sforzo.

In the setting of stable effort angina a single-blind, randomized, cross-over study to evaluate the effects of gallopamil (GAL) and amlodipine (AML) on exercise tolerance and ischemic ST depression was conducted. Fifteen outpatients, 12 males and 3 females, aged 40-65 years (57 +/- 9), with documented coronary atherosclerosis and reproducible ST-segment depression on 2 consecutive baseline exercise stress tests, completed the study, which consisted of 4 periods: 1 and 3 placebo, 2 and 4 at random GAL (50 mg tid) and AML (10 mg/daily). At the end of each period a multistage treadmill exercise stress test (Bruce protocol) was performed. Both drugs significantly (p = 0.0001) increased the ischemia time (IT) (0.1 mV ST depression) as compared to placebo, from 416 +/- 165 s to 635 +/- 161 s (GAL) and 607 +/- 152 s (AML) with significant difference (p = 0.2) between the 2 drugs, and reduced significantly (p = 0.001) the maximal ST depression from -0.25 +/- 0.09 mV to -0.11 +/- 0.08 mV (GAL) and -0.12 +/- 0.09 mV (AML). At the IT, the systolic blood pressure increased from 178 +/- 23 mmHg to 185 +/- 20 mmHg (GAL) and remained unchanged during AML treatment (178 +/- 15 mmHg); similarly, the heart rate increased from 126 +/- 22 b/min to 139 +/- 21 b/min (GAL) and 138 +/- 19 b/min (AML). In conclusion, both GAL and AML showed a good anti-ischemic effect (IT = +52.6% during GAL and +45.9% during AML), even if GAL proved to be significantly more effective than AML.