Carlo Augusto Sorbini

Energy cost of exercise in multiple sclerosis patients with low degree of disability

In 10 patients (five females) suffering from multiple sclerosis with mild degree of disability, (EDSS ranging from 0 to 2) and in 10 age and sex matched control subjects we investigated lung function, respiratory muscles strength and cardiorespiratory response to incremental exercise in order to assess the metabolic cost of exercise. In the absence of any impairment of lung volumes and flows and in-and expiratory maximal mouth pressures, at peak of exercise oxygen consumption (VO2max=1886 ± 145 ml/min) and workload (Wmax = 137 ± 9.8 watts) were slightly diminished in patients, as compared with controls (VO2max = 2246 ± 196 ml/min and Wmax = 164 ± 14.7 watts). These findings were associated with an increased heart rate (HR) and reduced oxygen pulse (VO2/HR) at the same workloads. During the whole exercise, however, the slope of the linear relationship between VO2 and work exhibited by the patients, amounting to 9.9 ± 0.6 ml/min/watt, was similar to that of the controls (10.9 ± 0.42 ml/min/watt). Incidentally, both at rest and during exercise, the patients showed a significantly greater minute ventilation (due to a faster respiratory rate, associated with an augmented dead space (P<0.05). We conclude that an increase of metabolic cost of exercise does not occur in multiple sclerosis patients with mild disability, suggesting a lack or a low degree of spasticity and/or ataxia elicited by the effort Thus, their exertional capacity appears to be limited mainly by a poor training. The tachypnea observed in these patients at rest and during exercise was unexpected and the reason for adopting such a pattern of breathing is unclear.

Noninvasive assessment of chronotropic and inotropic response to preferential beta-1 and beta-2 adrenoceptor stimulation

The relative chronotropic and inotropic activity of preferential β1‐ and β2‐ adrenoceptor Stimulation was investigated in seven healthy male subjects in a randomized within‐subject, single‐blind study. Two doses of β1selective agonist prenalterol (1 mg/hr or 2 mg/hr) and of β2‐selective agonist salbutamol (300 µg/hr or 600 µg/hr) were infused intravenously in four separate sessions, with intervals of at least 48 hr between sessions. At each session cuff blood pressure and heart rate (HR) were measured and some hemodynamic information on the inotropic state were derived by echocardiography. Both prenalterol and salbutamol induced increases in HR, but tachycardia was greater after salbutamol, whereas the positive inotropic response to β‐stimulation was greater after prenalterol. At comparable HR rises (prenalterol, from 66.0 ± 5.5 to 72.2 ± 4 bpm; salbutamol, from 64.6 ± 6 to 70.0 ± 7 bpm), inotropic response seemed to be greater after prenalterol than after salbutamol (systolic blood pressure [SBP]: 133.5 ± 8 and 120.7 ± 8 mm Hg; mean velocity of circumferential fiber shortening [Vcf]: 1.54 ± 0.13 and 1.31 ± 0.12 c/s; ejection fraction [EF]: 72.4% ± 5% and 69.5% ± 4%; stroke index: 47.4 ± 4 and 41.7 ± 3 ml/m2). In presence of a chronotropic effect (HR from 64.6 ± 6 to 70.0 ± 7 bpm), the low salbutamol dose did not induce any changes in the indices of inotropism (SBP: from 119.2 ± 6 to 120.7 ± 8 mm Hg; mean Vcf: from 1.28 ± 0.11 to 1.31 ± 0.12 e/s; EF: from 68.1% ± 5% to 69.5% ± 4%; stroke index: from 40.2 ± 3 to 41.7 ± 3 ml/m2. On prenalterol, HR increases were accompanied by changes in all the indices of inotropism. Results would appear consistent with animal data in suggesting some heterogeneity of cardiac β‐adrenergic receptors. Inotropic response to β‐stimulation would appear to be mediated mostly by β1‐ adrenoceptors, whereas β1‐ and perhaps β2‐ adrenoceptors share a mediating action on chronotropic response to cardiac β‐adrenoceptor stimulation.

Acute effects of captopril in hypoxic pulmonary hypertension. Comparison with transient oxygen administration.

The present study was carried out to test the hypothesis of a possible effectiveness of captopril--an enzymatic inhibitor of both angiotensin II formation and bradykinin degradation--on hypoxic pulmonary hypertension. In 6 patients with this clinical condition, captopril-induced changes in pulmonary hemodynamics were observed after the acute administration of the drug with and without a short period of oxygen therapy at a flow rate sufficient to keep the PaO2 over 60 mm Hg. In our patients, captopril significantly lowered pulmonary arterial pressure and vascular resistance only when combined with oxygen, suggesting that an increase in bradykinin availability and/or a decrease in angiotensin II synthesis might be important factors in reversing pulmonary arterial hypertension only after blunting of the hypoxic stimulus on pulmonary circulation. Moreover, the authors suggest that the employment of vasodilators in the setting of hypoxic pulmonary hypertension should be considered not only as a means of relieving vasoconstriction but also as a possible tool for maintaining cardiac output and, in turn, peripheral oxygen delivery.

Metabolic and hormonal effects of preferential beta1 and beta2-adrenoceptor stimulation in man

The changes of blood glucose, serum potassium (K+), plasma non-esterified fatty acids (NEFA), plasma insulin and plasma renin activity (PRA) following the preferential stimulation of beta-1 and beta-2 adrenoceptors were studied in 7 healthy subjects during a 60-min infusion of prenalterol, a new, relatively beta-1 selective agonist and salbutamol, a well known, relatively beta-2 selective agonist. Two different high and low doses were used for both agents: 300 μg and 600 μg and 1 mg and 2 mg for salbutamol and prenalterol, respectively. The levels of PRA seemed equally increased by the two agents in proportion to the dose infused, thus suggesting an equally important role for beta-1 and beta-2 adrenoceptors in renin release. Blood glucose did not change during prenalterol infusions, while increased by 12±2 mg/100ml (mean ± SE; p< 0.01) and 25±3mg/100ml (p< 0.01) on salbutamol, at low and high dose, respectively. Similarly the decrement of serum K+ was significantly more pronounced (p< 0.01 ) after salbutamol infusion (0.6 ± 0.07 mEq/Land 1.0 < 0.09 mEq/L, at low and high dose, respectively) than after prenalterol (0.1 + 0.07 mEq/L and 0.3 ± 0.05 mEq/L). These metabolic effects should suggest a main beta-2 adrenoceptor involvement. Although both agonists determined a significant rise of plasma NEFA (p < 0.01), surprisingly the increase was significantly greater after salbutamol (441 ± 20 μEq/ L and 492 ± 25 μEq/ L, at low and high dose, respectively) than after prenalterol infusion (218 ± 25μEq/Land 269 ± 28μEq/L). Plasma insulin levels were unchanged on low dose prenalterol infusion, with a transient increment on high dose infusion, while increased significantly during both low and high dose salbutamol infusion at all observation times (12 ± 2 μU/ml and 16 ± 2 μU/ml at the end of low and high dose salbutamol infusion, respectively). This behavior might suggest a prevalent involvement of beta-2 adrenoceptors in the mechanism of the pancreatic release of insulin on sympathoadrenergic stimulation.

Reference Values for Flow-Volume Curves during Forced Vital Capacity Breathing in Male Children and Young Adults

127 non-smoking males aged 8-25 years were studied to obtain normal reference values for flow-volume (FV) curves. Analysis of variance (ANOVA) showed significant differences for all indices (PEF; MEF 25%, 50%, 75%; PIF; MIF 25%, 50%, 75%) in the first three age-groups (8-10, 11-13 and 14-16 years); the three last groups (17-19, 20-22 and 23-25 years) did not show any significant variation of FV curve data. Male subjects older than 16 years showed a negative correlation between maximal expiratory flow at 50% of forced vital capacity and standing height. Multiple regression equations relating FV curve indices to age and anthropometric data are calculated.

Breathing pattern during exercise in runners.

Summary Twelve young males, medium and long-distance runners, and five age-matched controls were studied in order to define the interrelationships between some respiratory parametres during exercise, with particular regard to the pattern of ventilation. The athletes were investigated before and immediatly after running so long a distance as they had been trained to. All subjects (athletes and controls) underwent two types of exercise: constant work rate test and one-minute incremental exercise test. Among our results we would like to emphasize that during the incremental exercise occlusion pressure (p0.1) changes appear to have the same trend as minute ventilation.