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Biomedical subjects

L Saccà

Publications and source records attributed to L Saccà.

At least 19 recordsLinked to original sources
PubMed1997

Growth hormone and heart performance. A novel mechanism of cardiac wall stress regulation in humans.

OBJECTIVES: This study was designed to assess systolic wall stress and ventricular function in patients with deranged growth hormone secretion, in an attempt to elucidate the mechanisms of growth hormone interaction with heart performance. DESIGN: A case-control study. SUBJECTS: Thirty patients with active acromegaly, free of diabetes mellitus and coronary artery disease, and 25 subjects with congenital growth hormone deficiency were studied. Twelve growth hormone-deficient subjects were reevaluated after 12 months of recombinant human growth hormone therapy. Two groups of 30 normal subjects each were used as controls for the acromegalic and growth hormone-deficient patients, respectively. RESULTS: In the acromegalics, end-systolic wall stress was reduced (-20%; P < 0.01) due to ventricular wall thickening (+ 26%; P < 0.001), whereas cardiac output was significantly increased (+ 20%; P < 0.01). The velocity of fibre shortening was unchanged. In growth hormone-deficient subjects, end-systolic wall stress was markedly increased (+ 38%; P < 0.001) due to a significant reduction of ventricular wall thickness (- 28%; P < 0.001), whereas cardiac output was significantly decreased (-44%; P < 0.001). Replacement therapy with recombinant human growth hormone produced a partial correction of wall thickness and stress. Consequently, systolic performance and cardiac output improved significantly. CONCLUSION: This study demonstrates that growth hormone plays a role in the control of cardiac wall stress and performance through a mechanism mediated by the effect of growth hormone on myocardial tissue growth. The data may have therapeutic implications in cardiac diseases that lead to heart failure.

Acromegaly↗
PubMed1997

Increased arterial intima-media thickness in childhood-onset growth hormone deficiency.

Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 +/- 1 yr, BMI 22 +/- 0.6 Kg/m2) and in 14 age-, sex-, and BMI-matched control subjects. IMT was greater in GHD patients (0.83 +/- 0.06 and 0.81 +/- 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 +/- 0.03 and 0.64 +/- 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 +/- 0.02 mmol/L) compared with controls (0.19 +/- 0.01; P = 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load. In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

Adolescent↗
PubMed1996

A preliminary study of growth hormone in the treatment of dilated cardiomyopathy.

BACKGROUND: Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient. METHODS: Seven patients with idiopathic dilated cardiomyopathy and moderate-to-severe heart failure were studied at base line, after three months of therapy with human growth hormone, and three months after the discontinuation of growth hormone. Standard therapy for heart failure was continued throughout the study. Cardiac function was evaluated with Doppler echocardiography, right-heart catheterization, and exercise testing. RESULTS: When administered at a dose of 14 IU per week, growth hormone doubled the serum concentrations of insulin-like growth factor I. Growth hormone increased left-ventricular-wall thickness and reduced chamber size significantly. Consequently, end-systolic wall stress (a function of both wall thickness and chamber size) fell markedly (from a mean [+/-SE] of 144+/-11 to 85+/-8 dyn per square centimeter, P<0.001). Growth hormone improved cardiac output, particularly during exercise (from 7.4+/-0.7 to 9.7+/-0.9 liters per minute, P=0.003), and enhanced ventricular work, despite reductions in myocardial oxygen consumption (from 56+/-6 to 39+/-5 ml per minute, P=0.005) and energy production (from 1014+/-100 to 701+/-80 J per minute, P=0.002). Thus, ventricular mechanical efficiency rose from 9+/-2 to 21+/-5 percent (P=0.006). Growth hormone also improved clinical symptoms, exercise capacity, and the patients' quality of life. The changes in cardiac size and shape, systolic function, and exercise tolerance were partially reversed three months after growth hormone was discontinued. CONCLUSIONS: Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.

Adult↗
PubMed1996

Improved left ventricular function after growth hormone replacement in patients with hypopituitarism: assessment with radionuclide angiography.

Prolonged growth hormone deficiency (GHD) leads to marked cardiac dysfunction; however, whether reversal of this abnormality may be achieved after specific replacement therapy has not yet been completely clarified. Fourteen patients with childhood-onset GHD (nine men and five women, mean age 27+/-4 years) and 12 normal control subjects underwent equilibrium radionuclide angiography under control conditions at rest. Patients with GHD were also studied 6 months after recombinant human (rh) GH treatment (0.05 IU/kg per day). Normal control subjects and patients with GHD did not differ with respect to age, gender and heart rate. In contrast, left ventricular ejection fraction (53%+/-9% vs 66%+/-6%, P <0.001), stroke volume index (41+/-11 vs 51+/-8 ml/m2, P <0.01) and cardiac index (2.8+/-0.6 vs 3.+/-0.5 l/min/m2, P <0.001) were significantly lower in GHD patients than in normal control subjects. None of the GHD patients showed adverse or side-effects during rhGH therapy; thus none required a reduction in GH dose during the treatment period. Heart rate and arterial blood pressure were not significantly modified by rhGH treatment. After 6 months of rhGH therapy a significant improvement in left ventricular ejection fraction (from 53%+/-9% to 59%+/-9%, P <0.01), stroke volume index (from 41+/-11 to 47+/-13 ml/m2, P <0.05) and cardiac index (from 2.8+/-0.6 to 3.3+/-0.8 l/min/m2, P <0.01) was observed in GHD patients. In conclusion, prolonged lack of GH leads to impaired left ventricular function at rest. Reversal of this abnormality may be observed after 6 months of specific replacement therapy in patients with childhood-onset GHD.

Adult↗
PubMed1996

Inotropic stimulation by dobutamine increases left ventricular regional function at the expense of metabolism in hibernating myocardium.

The mechanism by which dobutamine increases the contraction of chronically dysfunctional myocardium and its effects on metabolism are still unknown. The aim of this study was to assess regional myocardial metabolism at rest and during an intracoronary dobutamine infusion in patients with hibernating myocardium. Eleven asymptomatic patients with single proximal stenosis of the left anterior descending coronary artery and persistent left ventricular dysfunction at rest (undergoing percutaneous transluminal coronary angioplasty [PTCA]) were studied prospectively. Regional left ventricular function was assessed by two-dimensional (2D) echocardiography and regional perfusion by thallium-201 single-proton-emission computed tomography. Great cardiac vein and aortic blood samples were obtained for measurements of lactate and plasma free fatty acid (FFA) concentrations. Inotropic challenge, obtained by using intracoronary dobutamine infusion, increases regional left ventricular function. However, the arteriovenous AV lactate difference was 0.206 = 0.070 mmol/L at rest, and it decreased to 0.018 = 0.069 mmol/L (p < 0.05 vs baseline) and 0.066 = 0.068 mmol/L (p < 0.05 vs baseline) at 4 and 10 minutes of dobutamine infusion, respectively. Thus the hibernating myocardium does not produce lactate at rest. However, when regional contraction is stimulated, dobutamine-induced inotropic challenge may cause a perfusion-contraction mismatch with an activation of anaerobic glycolysis.

Aged↗
PubMed1996

Impaired cardiac reserve and exercise capacity in patients receiving long-term thyrotropin suppressive therapy with levothyroxine.

To assess cardiac function and exercise tolerance in patients receiving long term TSH-suppressive therapy with levothyroxine (L-T4), we studied maximal exercise capacity with a bicycle ergometer and left ventricular function at rest and during physical exercise by radionuclide angiography. The evaluation was performed in 10 patients receiving L-T4 therapy (2.31 +/- 0.13 microgram/kg) for 5-9 yr, presenting with effort dyspnea and symptoms of adrenergic overactivity, and 10 matched control subjects. The patients were reassessed after 4 months of administration of the selective beta-adrenergic blocker bisoprolol (4.25 +/- 0.4 mg/day); L-T4 therapy remained unchanged. The results showed that at rest, left ventricular diastolic filling was impaired in the patients (P < 0.05), whereas systolic function was unaltered. During submaximal physical exercise, left ventricular ejection fraction increased in the controls from 58 +/- 2% to 65 +/- 2% (P < 0.001), whereas in the patients it fell from 63 +/- 2% to 53 +/- 2% (P < 0.01), mainly because of increased end-systolic left ventricular volume (P < 0.05). Exercise capacity was markedly reduced in the patients in terms of both peak workload (P < 0.001) and exercise duration (P < 0.001). beta-Adrenergic blockade prevented both the fall in ejection fraction and the increase in end-systolic volume during exercise, and improved exercise tolerance. In conclusion, our data show that long term TSH-suppressive therapy with L-T4 is not as harmless as believed, because it may cause marked impairment of cardiac functional reserve and physical exercise capacity. Administration of a beta-blocking drug for 4 months caused significant improvement of cardiac performance and exercise tolerance.

Adrenergic beta-Antagonists↗
PubMed1996

Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial.

In this multicentre trial tramadol and buprenorphine were compared for the treatment of neoplastic pain no longer responsive to non-steroidal antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six months. Most patients started treatment with 2-3 tablets/day in both groups, and the mean treatment period was 58 days for tramadol and 51 for buprenorphine. Almost all dose changes needed were made in the first fortnight in both treatment groups, and the largest number of patients dropped out because of inadequate pain relief or progression of the underlying disease. The results achieved in the first two weeks persisted throughout the rest of the trial, and the investigator's assessments on each patient's clinical chart corresponded closely with those that patients made in their own daily diaries. In the four hours after the first dose both drugs virtually halved the severity of pain (measured using a visual analogue scale), and this relief lasted throughout treatment. By the end of the first week the proportion of patients with strong/unbearable pain in the tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also tended to improve in the tramadol group, with the proportion of patients enjoying good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life did not change in the tramadol group; in the buprenorphine group the Karnofsky index dropped slightly after a fortnight (p < 0.05 between treatments). In the first two months of the trial the number of patients with no/moderate pain rose continuously in the tramadol group (71% and 80% after one and two months); the rise was less marked in the buprenorphine group (number of patients with mild/moderate pain, 45% and 65%). In both the short term and in the longer term, it was found that the levels of efficacy and acceptability were always significantly better in the tramadol group than in the buprenorphine group. General and biological safety in both drugs was good. The most typical side-effects were those characteristic of opioids (nausea and/or vomiting, drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%) and in 16 taking buprenorphine (26%). There were six drop-outs in the first group (9%) and seven in the second (11%). Serious symptoms arose more frequently in the buprenorphine group (19% cf. 10%). No signs of dependence or tolerance were noted.

Adult↗
PubMed1995

Forearm muscle insulin resistance during hypoglycemia: role of adrenergic mechanisms and hypoglycemia per se.

The forearm perfusion technique was used 1) to quantify the muscle metabolism of glucose and gluconeogenic precursors in response to insulin-induced hypoglycemia and 2) to assess the role of catecholamines and glucose concentration, pe se. Insulin (0.5 mU.kg-1.min-1) was infused for 4 h in three groups of healthy volunteers. In group I (n = 6), blood glucose (BG) was maintained at its basal level (4.5 +/- 0.1 mmol/l). In group II (n = 7), BG was allowed to fall to approximately 3 mmol/l. Group III (n = 6) was similar to group II except that propranolol was infused also. In addition, at 240 min, hypoglycemia was locally corrected by intrabrachial glucose infusion while maintaining the systemic milieu unperturbed. In group I, forearm glucose uptake (FGU) increased from 4.7 +/- 1.3 to a mean value of 37.8 +/- 5.0 mumol.l-1.min-1, whereas in group II it remained unchanged (8.3 +/- 2.0 mumol.l-1.min-1). In group III, propranolol partially prevented the suppression of FGU that increased to 21.6 +/- 5.2 mumol.l-1.min-1 (P < 0.05 vs. group II). Local correction of hypoglycemia normalized the FGU response (36.5 +/- 8.0 mumol.l-1.min-1). Muscle release of lactate, but not of alanine, was slightly higher during hypoglycemia (P = not significant). Forearm blood flow remained unchanged in groups I and III, whereas it increased by approximately 40% in group II (P < 0.05). It is concluded that, during mild hypoglycemia 1) extreme insulin resistance develops in the skeletal muscle, mediated by beta-adrenergic stimulation and reduced glucose mass effect and 2) mobilization of gluconeogenic precursors is only weakly activated.

Adult↗
PubMed1995

Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: beneficial effect of beta-blockade.

Thyroid-stimulating hormone (TSH) suppressive therapy with levothyroxine (L-T4) may cause adverse cardiac effects such as rhythm disturbances and ventricular hypertrophy. The latter is a predisposing condition to diastolic dysfunction. Thus, this study was designed to assess the effect of long-term TSH suppressive therapy on cardiac diastolic function. Because beta-blockade is known to reduce ventricular hypertrophy in patients on L-T4 therapy, we also tried to determine whether the addition of a beta-blocker to L-T4 improved diastolic function. Twenty-five patients (21 female and 4 male; mean age 41 +/- 10 yr) on TSH suppressive therapy for 3-9 yr (9 for differentiated carcinoma and 16 for nontoxic goiter) and 20 control subjects were studied. A subgroup of 10 patients, selected for the presence of symptoms and signs of adrenergic overactivity, was treated for 4 months with the beta-blocker bisoprolol (4.25 +/- 1.2 mg/day), and their maintaining L-T4 therapy was unchanged. In the patient group, left ventricular mass was significantly increased (P < 0.001), isovolumic relaxation time was prolonged (P < 0.001), and early diastolic filling velocity was markedly reduced (P < 0.001), whereas late diastolic filling was increased (P < 0.005). Consequently, the early-to-late diastolic flow velocity ratio was markedly decreased (P < 0.001). These alterations were more pronounced in the subgroup of patients with evidence of adrenergic overactivity. In these patients, beta-blockade induced a significant regression of cardiac hypertrophy and improved diastolic dysfunction. In particular, isovolumic relaxation time decreased (P < 0.01) and the early-to-late flow velocity ratio increased significantly (P < 0.01). Both indices reached values after beta-blockade that were no longer different from those of asymptomatic patients. It is concluded that long-term L-T4 therapy increases myocardial mass and causes relevant diastolic dysfunction, particularly in those patients with evidence of mild hyperthyroidism and adrenergic overactivity. Both myocardial hypertrophy and diastolic dysfunction are significantly improved by adrenergic beta-blockade.

Adult↗
PubMed1995

Impaired left ventricular diastolic filling in patients with acromegaly: assessment with radionuclide angiography.

UNLABELLED: Acromegaly is associated with increased cardiac morbidity and mortality, but it is not clear whether this is the result of a specific disease of heart muscle or of increased incidence of hypertension. METHODS: Twenty-six patients with acromegaly (11 male and 15 female, mean age 45 +/- 13 yr) and 15 and 12 age- and sex-matched normal controls underwent high temporal resolution radionuclide angiography and two-dimensional echocardiography at rest. RESULTS: Normal controls and patients with acromegaly did not differ with respect to heart rate, ejection fraction, time to end systole, peak ejection rate (PER) and time to PER. In contrast, peak filling rate (PFR), normalized to end diastolic volume (EDV), or stroke volume (SV), or expressed as the ratio of PFR-to-PER was reduced (p < 0.01), time to PFR (TPFR) was prolonged (p < 0.01), and echocardiographic left ventricular mass index was higher (p < 0.001) in patients with acromegaly compared to normals. Patients with acromegaly were divided in normotensives (group 1, n = 17) and hypertensives (group 2, n = 9). Although left ventricular mass index was significantly (p < 0.01) higher in group 2 compared to group 1, PFR and time to PFR were not different between the two groups of acromegalic patients. In the entire group of patients with acromegaly significant relationships between left ventricular mass index and EDV/s (r = -0.56, p < 0.01), SV/s (r = -0.73, p < 0.001), and PFR/PER (r = -0.61, p < 0.001) were observed. CONCLUSION: Patients with acromegaly have impaired left ventricular diastolic filling at rest related to greater left ventricular mass index even in the absence of systemic hypertension.

Acromegaly↗
PubMed1994

Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement.

Cardiac performance was investigated by radionuclide angiography in 11 patients with childhood-onset growth hormone (GH) deficiency and in 12 control subjects. Both at rest and during maximal physical exercise, systolic function was markedly depressed in GH-deficient patients. Ejection fraction rose from 66 +/- 6 to 76 +/- 7% during exercise in control subjects, whereas in GH-deficient patients it remained unchanged or even decreased (55 +/- 6 and 54 +/- 9% at rest and after exercise, respectively; P < 0.01 vs. controls). Cardiac index was significantly lower in GH-deficient patients than in controls, both at rest (2.7 +/- 0.6 vs. 3.7 +/- 0.5 l.min-1.m-2; P < 0.001) and during exercise (8 +/- 1.2 vs. 10 +/- 1.5 l.min-1.m-2; P < 0.01). Five GH-deficient patients were treated with recombinant human (rh) GH for 6 mo at a dose of 0.05 IU.kg-1.day-1. Cardiac index at rest improved from 2.8 +/- 0.6 to 3.3 +/- 0.8 l.min-1.m-2 (P < 0.01) after rhGH. Also, cardiac index response to exercise improved markedly and became similar to that of controls (7.5 +/- 1.2 and 10.1 +/- 1.1 l.min-1.m-2 before and after rhGH, respectively; P < 0.005). Exercise tolerance was impaired in GH-deficient patients and was restored by rhGH treatment. The data support the hypothesis that GH plays an important role in the maintenance of a normal cardiac performance in humans.

Adult↗
PubMed1994

Growth hormone and the heart.

GH exerts direct effects on myocardial growth and function. Evidence from laboratory models shows that GH (or IGF-I) induces mRNA expression for specific contractile proteins and myocyte hypertrophy. Furthermore, GH increases the force of contraction and determines myosin phenoconversion toward the low ATPase activity V3 isoform. These data provide plausible explanations for the cardiac abnormalities observed in clinical settings of excessive or defective GH production. In acromegaly, the functional consequences of GH excess initially prevail (hyperkinetic syndrome), followed by alterations of cardiac function when myocardial hypertrophy develops. This involves both ventricles and is purposeless because it occurs without increased wall stress. Hypertrophy also entails proliferation of the myocardial fibrous tissue that leads to interstitial remodeling. The functional consequence is an impaired ventricular relaxation that causes a diastolic dysfunction, followed by impairment of systolic function. In untreated disease, cardiac performance slowly but inexorably deteriorates and heart failure eventually develops. Several lines of evidence support the specificity of heart disease in acromegaly. Particularly demonstrative are the recent studies in which GH production was suppressed by octreotide, with a consequent significant regression of hypertrophy and improvement of cardiac dysfunction. It is not yet established whether full recovery of normal cardiac morphology and function is possible after correction of GH excess. The point is not a minor one since the possibility to revert, albeit partially, myocardial fibrosis is of great relevance to the control of cardiac hypertrophy in general. GHD leads to a reduced mass of both ventricles and to impaired cardiac performance with low heart rate (hypokinetic syndrome). These alterations are particularly evident during physical exercise and might provide an important contribution to the reduced exercise capacity of GHD patients, in addition to the reduced muscle mass and strength. The data also support a role of GH in the maintenance of a normal cardiac structure and performance. The hypokinetic syndrome is well documented in young patients in whom GHD began very early in their childhood. In contrast, the data in adult-onset GHD are less consistent. This suggests that the consequences of GHD are more relevant if the disorder starts during early heart development. As observed with other abnormalities associated with GHD, cardiac dysfunction is also susceptible to marked improvement by hrGH. This observation lends further support to the proposal to treat these patients with replacement therapy.

Acromegaly↗