Search PubMed⌕ Search

Biomedical subjects

G Brevetti

Publications and source records attributed to G Brevetti.

At least 37 records · Page 2Linked to original sources
PubMed1992

Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study.

The effects of L-propionylcarnitine on walking capacity were assessed in a group of patients with peripheral vascular disease. In 12 patients, 300 mg of L-propionylcarnitine, given intravenously as a single bolus did not affect walking capacity, while 600 mg increased both initial claudication distance from the placebo value of 179 +/- 114 to 245 +/- 129 m (P less than 0.05), and maximal walking distance from 245 +/- 124 to 349 +/- 155 m (P less than 0.05). Once the efficacious dose of L-propionylcarnitine was assessed, its effect was compared to that of an equimolar dose of L-carnitine (500 mg i.v.) according to a double-blind, double-dummy, cross-over design. In 14 patients, both treatments improved walking capacity; however, the analysis of variance showed that the increase in maximal walking distance with L-propionylcarnitine was greater than that with L-carnitine (P less than 0.05). Finally, in seven additional patients, the effects of L-propionylcarnitine and L-carnitine on the haemodynamics of the affected limb were assessed by an ultrasonic duplex system. Results indicated that both drugs did not affect the blood velocity and the blood flow rate in the ischaemic leg, thus suggesting that the beneficial effect on walking capacity was dependent on a metabolic effect. In conclusion, L-propionylcarnitine improves walking capacity in patients with peripheral vascular disease, probably acting through a metabolic mechanism. On a molar basis, this beneficial effect is greater than that observed with L-carnitine and, thus, the findings of the present study may have clinical relevance in terms of treatment cost and patient compliance.

Arterial Occlusive Diseases↗
PubMed1992

Beta-adrenoceptor modulation in a case of pure autonomic failure.

In a patient with pure autonomic failure, exercise did not modify beta-adrenoceptor density, probably due to an insufficient increase in plasma catecholamines. Isoproterenol infusion increased the number of beta-adrenoceptor by only 17%. Since in control subjects an increased beta-adrenoceptor level was found, following both physical stress and isoproterenol infusion, we suggest that the lack of increased beta-adrenoceptor levels may contribute to the poor circulatory adjustments observed in autonomic dysfunction during activities involving the sympathetic nervous system.

Autonomic Nervous System Diseases↗
PubMed1992

[The reduction of beta-adrenoceptor density and the suppression of ectopic ventricular activity with low doses of amiodarone].

In 5 patients with frequent premature ventricular ectopic beats, refractory to other antiarrhythmic treatments, amiodarone, given orally at the dose of 200 mg once a day for 4 weeks, reduced beta-adrenoceptor density from 202.9 +/- 62 to 101.1 +/- 33 fmol/mg protein (p < 0.01). Similarly, kd decreased from 21.0 +/- 6 to 3.9 +/- 1 (p < 0.05). Changes in beta-adrenoceptor population were accompanied by a marked reduction in mean premature ventricular complexes (PVC) frequency from the control value of 428.9 +/- 150.3 to 13.4 +/- 10.7 PVC/h (p < 0.05) and by a decrease in heart rate, from 83.8 +/- 4 to 73.9 +/- 4 b/min (p < 0.01). On the contrary, mean arterial pressure remained unchanged. Patients did not show side effects during treatment. Therefore, low dose oral amiodarone has important pharmacologic and therapeutic effects. It significantly reduces lymphocyte beta-adrenoceptor density and is effective in treatment of ventricular arrhythmias. Additional studies were performed in vitro exposing lymphocytes to increasing concentrations of amiodarone. The analysis of variance for repeated measures showed that amiodarone-induced reduction in lymphocyte beta-adrenoceptor density is a dose-depending phenomenon. Accordingly, treatment with doses of amiodarone higher than that used in the present study may induce a major reduction in lymphocyte beta-receptor density and exert a depressant cardiac effect.

Adult↗
PubMed1991

Muscle carnitine deficiency in patients with severe peripheral vascular disease.

BACKGROUND: This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease. METHODS AND RESULTS: Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities. CONCLUSIONS: Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.

Aged↗
PubMed1990

Parkinson's disease and hypotension: 24-hour blood pressure recording in ambulant patients.

Continuous intra-arterial blood pressure was recorded in 5 ambulatory patients with Parkinson's disease and in 5 control subjects. The 24-h mean systolic blood pressure was 135 +/- 7.6 mmHg in controls and 123.8 +/- 8.1 mmHg (p less than 0.01) in the parkinsonian group. Similarly, diastolic blood pressure was 89 +/- 8.1 mmHg in the control group while in the parkinsonian patients it was lower, 69.4 +/- 5.8 (p less than 0.01). Averages were also calculated for 8-h periods, the results of which indicate that both systolic and diastolic blood pressure were significantly lower in patients than in controls in all three 8-h periods of the day. We normalized the blood pressure curve to mealtimes and arousal times and did not observe any difference between parkinsonian patients and controls. This first study reporting continuous intra-arterial blood pressure measurements in ambulant parkinsonian patients demonstrates that blood pressure in such patients is lower than the mean for their age group. This finding may be of direct relevance in the management of idiopathic parkinsonism.

Adult↗
PubMed1990

[Increase in the lymphocyte beta-adrenergic receptor population during physical exercise].

The risk of cardiac arrhythmias during exercise and the recovery period may be enhanced by sympathetic activity. Accordingly, lymphocyte beta-adrenoceptor density was measured in 5 healthy men, aged between 25 and 32 years, at rest, at peak exercise and during the recovery period. Exercise increased 3H-dihydroalprenolol binding from 125 +/- 58 to 234 +/- 70 fmol/mg protein (p less than 0.02). During recovery, beta-adrenoceptor density was still higher than at rest, being 192 +/- 36 fmol/mg protein (p less than 0.02). No significant difference was found between exercise and recovery values (Tab. I). Results did not change when binding data were standardized to lymphocyte number, thus demonstrating that increases in binding were independent of exercise-induced lymphocytosis. Kd did not change significantly during the study. Since lymphocytic beta-adrenoceptor density may parallel myocardial beta-adrenoceptor density, this study suggests the myocardium may be more sensitive to the arrhythmogenic properties of catecholamines during exercise.

Adult↗
PubMed1989

Effect of L-carnitine on the reactive hyperemia in patients affected by peripheral vascular disease: a double-blind, crossover study.

A double-blind, crossover study was designed to evaluate the effect of L-carnitine on the reactive hyperemia in patients with peripheral vascular disease. After drug washout, 18 patients were randomly assigned to receive placebo or L-carnitine, 3 g IV as a bolus, followed by continuous intravenous infusion of 2 mg/kg/min for thirty minutes. Blood flow in the affected limb was measured by impedance plethysmography, under resting conditions and every two minutes for ten minutes after a five-minute ischemia induced in the affected limb. As compared with placebo, L-carnitine did not modify blood flow at rest. On the contrary, the hyperemic response with carnitine was higher than that observed with placebo. A significant increase in blood flow was found two, four, and six minutes after the release of ischemia with placebo, whereas the blood perfusion to the affected limb rose significantly at all times of recording after carnitine administration. Moreover, the values of the blood flow at two and ten minutes with carnitine were significantly higher than those recorded after placebo at the same times of recording. After the release of ischemia, the mean maximum value of blood flow observed after carnitine was 3.1 +/- 1.4 mL/min/100 mL, a value significantly higher than that recorded after placebo, which was 2.7 +/- 1.3 mL/min/100 mL (p less than 0.05). In conclusion, this study demonstrates that L-carnitine, although not affecting blood flow and ankle/arm systolic blood pressure ratio under resting conditions, improves the functional circulatory reserve in patients with peripheral vascular disease.

Carnitine↗
PubMed1989

Beneficial effect of a new prostacyclin derivative on the walking capacity in patients with peripheral arterial insufficiency.

The efficacy, tolerance and safety of iloprost, a stable analogue of carbaprostacyclin, were evaluated in 7 patients with peripheral arterial insufficiency at stage II of Fontaine's classification. After washout, placebo was infused intravenously for seven days, then iloprost was given by a six-hour intravenous infusion of 1 ng/kg/min over the next seven days. At the end of each period, the initial (ICD) and the absolute (ACD) claudication distance were measured by treadmill. The ankle/arm systolic blood pressure ratio (WI) was also assessed, at rest and ten minutes after exercise. As compared with placebo, ICD increased from 98 +/- 60 to 137 +/- 91 meters (p less than 0.05) and ACD from 151 +/- 76 to 210 +/- 95 meters (p less than 0.05). Similarly, WI rose from 0.44 +/- 0.14 to 0.52 +/- 0.18 (p less than 0.05) at rest and from 0.40 +/- 0.13 to 0.48 +/- 0.20 (p less than 0.05) ten minutes after treadmill exercise. Owing to the spontaneous fluctuation in walking distance experienced by such patients, an increase in ACD greater than or equal to 50% was considered as clinically relevant. In 3 patients, who experienced such an improvement, iloprost continued to be infused at the same dosage as before, for an additional seven days. In the remaining 4 patients (nonresponders), the dose was increased to 2 ng/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study.

A double-blind, cross-over study was designed to evaluate the effects of L-carnitine in patients with peripheral vascular disease. After drug washout, 20 patients were randomly assigned to receive placebo or L-carnitine (2 g bid, orally) for a period of 3 weeks and were then crossed over to the other treatment for an additional 3 weeks. The effect on walking distance at the end of each treatment period was measured by treadmill test. Absolute walking distance rose from 174 +/- 63 m with placebo to 306 +/- 122 m (p less than .01) with carnitine. Biopsy of the ischemic muscle, carried out before and after 15 days of L-carnitine administration in four additional patients, showed that treatment significantly increased total carnitine levels. An additional goal of this study was to ascertain the effects of L-carnitine on the metabolic changes induced by exercise in the affected limb. In six patients under control conditions, arterial and popliteal venous lactate and pyruvate concentrations were determined at rest, when the maximal walking distance was reached, and 5 min after the walking test. Twenty-four hours later, L-carnitine was administered intravenously (3 g as a bolus followed by an infusion of 2 mg/kg/min for 30 min) and metabolic assessments were repeated. Five minutes after the walking test, popliteal venous lactate concentration increased by 107 +/- 16% before treatment and by only 54 +/- 32% (p less than .01) after carnitine. Furthermore, carnitine induced a more rapid recovery to the resting value of the lactate/pyruvate ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Carnitine↗
PubMed1985

24-hour blood pressure recording in patients with orthostatic hypotension.

Continuous intra-arterial blood pressure measurement and electrocardiograms were obtained in two ambulatory patients with orthostatic hypotension due to autonomic dysfunction. Systolic and diastolic arterial pressure presented marked variations which took place mainly during the day and were related to several physical activities; however, marked falls in blood pressure were also observed during sleep and at the moment of arousal. A peak incidence of hypotensive events was found in the afternoon, mainly in the hours following the afternoon meal. Recording was repeated after 3 weeks of treatment with propranolol, 40 mg t.i.d. In patient 1, beta blockade drastically reduced the number and severity of hypotensive episodes, while propranolol failed to control blood pressure in patient 2, who experienced a higher number of hypotensive events during treatment. Findings of this study may be relevant to the management of patients with orthostatic hypotension and should contribute to a more accurate characterization of blood pressure profile in autonomic dysfunction.

Blood Pressure↗
PubMed1984

Long-term protection of ischaemic myocardium by nitroglycerin ointment.

To assess whether the reduction in ischaemic injury during acute myocardial infarction induced by nitroglycerin (NTG) results in a decrease in tissue necrosis, 96 rats were assigned to two groups. The first group (n = 34) was sham-operated. The second group of 62 rats was randomised in a ratio of 2:1 into control (n = 43) and treated (n = 19) subgroups following coronary artery occlusion. Treated animals received an application of 2% NTG ointment every 8 h immediately post-occlusion. All rats were killed 48 h after coronary artery occlusion and total creatine kinase activity (CK) of the left ventricle (LV) was measured. Infarct size calculated by CK depletion was 65.2 +/- 14.3% (mean +/- SD) of LV in control rats, and 51.6 +/- 14.0% of LV in NTG-treated (p less than 0.02). In a further series of 46 rats with coronary occlusion, the area of infarcted myocardium 21 days post-occlusion was assessed by planimetry on histological sections. In rats with control occlusion (n = 22), the extent of infarction was 30.6 +/- 4.8% of LV, and in NTG-treated rats (n = 24) it was 16.2 +/- 5.8% of LV (p less than 0.001). The amount of scar tissue in the infarcted myocardium 21 days post-occlusion was also determined by measuring LV hydroxyproline and collagen content in an additional 32 rats randomly assigned to a control (n = 11), a NTG-treated (n = 9) and a sham-operated group (n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Dilazep-induced reduction of ischemic necrosis in rats with coronary artery occlusion.

To assess whether dilazep reduces myocardial necrosis we assigned 72 rats that survived coronary artery occlusion to 3 groups. The first control group (n = 26) received coronary occlusion and was untreated. The second group (n = 21) received coronary occlusion and was treated with dilazep (150 micrograms/kg s.c.) every 8 hours for 48 hours. The third group (n = 25) was sham-operated. Forty-eight hours later the creatine-kinase activity of the left ventricle was measured. The calculated left ventricular fraction that survived the occlusion was larger in dilazep-treated rats (44.5 +/- 4.1% of left ventricle) than in controls (31.2 +/- 3.2%; P less than 0.05). Twenty-six more rats also underwent coronary occlusion; 12 were controls and the remaining 14 were treated with dilazep at the same time and dose as before and killed 21 days after occlusion. Infarct size was evaluated on histological sections of the hearts by planimetry. The amount of left ventricle preserved from necrosis was larger in dilazep-treated rats, 82.1 +/- 0.9%, compared to controls 69.5 +/- 1.4% (P less than 0.05). Dilazep seems effective in preserving myocardial tissue from ischemic necrosis, and its beneficial effects are long-lasting, producing permanent reduction of infarct size.

Animals↗
PubMed1983

Beneficial effect of papaverine plus raubasine in peripheral arterial insufficiency.

It has been demonstrated that, in most arteriopathic patients, vasodilators induce the vascular steal phenomenon, i.e. the shunting of blood from the ischemic to the normally perfused areas. It is conceivable, therefore, that vasoconstrictors may improve in the opposite way, reducing the blood flow to the normal zones and increasing it to the ischemic. A "reverse vascular steal" caused by the simultaneous IV injection of a vasodilator and a beta-blocker has been previously shown; however, the chronic treatment of arteriopathic patients with beta-adrenoceptor blocking drugs often results in increased evidence of peripheral arterial insufficiency; therefore, the combination of a vasodilating drug with a beta-blocker is limited in the clinical practice. The aim of this study was to investigate the efficacy of the combination of the vasodilator papaverine hydrochloride with a drug having vasoconstrictive action without the undesirable side effects of beta-blockers. Accordingly, raubasine (40 mg) was given p.o. associated with papaverine (300 mg) in 10 arteriopathic patients, who presented a significant reduction of blood flow in the affected limb after the administration of 300 mg p.o. of papaverine alone. The measurements of blood flow were performed by impedance plethysmographic recordings to evaluate papaverine plasma concentrations. Data obtained by this study indicate that papaverine alone induces a significant reduction of blood flow starting from the time of its maximal plasma concentration. Raubasine alone does not induce any change in blood flow, while the combination of the 2 drugs significantly increases the blood supply to the affected limb. These favorable results, probably related to the ability of raubasine to induce a reverse vascular steal, suggest that the combination of this drug with a vasodilator such as papaverine may represent a new approach in the treatment of peripheral arterial insufficiency.

Aged↗
PubMed1982

Effects of combined alpha- and beta-blockade by labetalol in patients with coronary artery disease.

1 The effect of labetalol 100 mg orally twice daily on exercise tolerance has been compared with placebo in 19 normotensive subjects with angiographic evidence of coronary artery disease. 2 Labetalol, at the same work load as during placebo exercise, significantly reduced systolic and diastolic blood pressures, as well as heart rate and rate-pressure product. 3 Similarly, ST segment depression was reduced by labetalol from 2.0 +/- 0.4 to 1.36 +/- 0.6 mm (P less than 0.001), thus enabling an increase in exercise tolerance from a control value of 83.7 +/- 18 to 95.3 +/- 19 W (P less than 0.005). 4 In seven other patients, also with coronary artery disease, the haemodynamic effects of a single 0.6 mg/kg intravenous dose of the drug was evaluated during exercise. 5 Compared with conditions during control exercise, labetalol induced a significant reduction in rate-pressure product from 17228 +/- 2375 to 13445 +/- 2404 mmHg/min (P less than 0.005) and in peripheral vascular resistance from 612.0 +/- 61.2 to 512.7 +/- 36.2 dyn cm-5 m-2 (P less than 0.0025). These events were not accompanied by any change in cardiac index and in dP/dT left ventricular end-diastolic pressure (LVEDP) ratio. 6 These data suggest that labetalol may induce reduction in myocardial oxygen consumption, thereby increasing exercise tolerance in patients with coronary artery disease, without impairment of left ventricular performance.

Adult↗