[Heart transplant. Multicenter study in Bergamo, Padua, Pavia November 1985-February 1987].
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Biomedical subjects
Publications and source records attributed to R Fiocchi.
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Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound cardiovascular adaptations. The aim of the present study was to investigate with the use of the variable neck chamber technique, the influence of the endogenous opioids on the carotid baroreflex control of blood pressure and heart rate at rest as well as during exercise. Ten normal volunteers exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg.h-1). During exercise a progressive attenuation of the carotid baroreceptor reflex control of blood pressure and heart rate was noted. However, neither at rest nor during exercise, did opioid antagonism influence the carotid baroreceptor control of blood pressure and heart rate. Intra-arterial pressure and heart rate also remained unaffected. In contrast, both at rest and during exercise, naloxone administration produced a significant increase in the plasma concentration of cortisol. The latter suggests that in vivo the opioid receptors were effectively antagonized. In conclusion the present study confirms that opioids play only a minor role in cardiovascular homeostasis at rest. In addition, this study demonstrates that they are not involved in the cardiovascular adaptation to exercise, nor in the exercise-related attenuation of the carotid baroreceptor control of pressure and heart rate.
Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.
The purpose of this study was to evaluate the sensibility of some clinical and non-invasive parameters in the early diagnosis of cardiac rejection in heart transplant patients. Eighteen patients (15 males and 3 females) aged 13-57 years (mean 44 +/- 14), with orthotopic heart transplant were followed clinically for a mean period of 15 +/- 8.7 months (range 3-27). They were all treated with cyclosporin, associated with azathioprine or prednisone, or both. During the same day of the endomyocardial biopsy, the patients were submitted to a clinical examination, 12 leads ECG and 2-dimensional and Doppler-echocardiography. The following parameters were evaluated: systolic and diastolic blood pressure, heart rate, body weight, summated QRS voltage in the 12 leads ECG, interventricular septum and left ventricular posterior wall end-diastolic thickness, left ventricular myocardial mass and fractional shortening, isovolumic relaxation time. Biopsy specimens were graded according to the Billingham criteria. Totally, 251 biopsies were performed: 130 were negative, 98 positive for mild or moderate rejection, 23 had a resolving rejection pattern; in 61 cases the patients were treated for acute rejection. Compared to negative biopsies, during acute rejection the QRS voltage and the isovolumic relaxation time significantly decreased, while left ventricular wall thickness and body weight increased. To evaluate the effects of the acute immunosuppressive therapy, the same parameters before and after treatment were compared. The QRS voltage, the wall thickness and the isovolumic relaxation time were significantly modified, returning to the pre-rejection values. In conclusion, both clinical and non-invasive information, may be useful to suspect an episode of acute rejection in heart transplant patients and to program myocardial biopsy.
A cardiac transplant recipient developed systemic aspergillosis with abscesses from aspergillus fumigatus in the brain and the right kidney. Surgical resections were performed (lobectomy for the brain abscess, partial resection for the renal abscess followed, after extension of the infection, by right nephrectomy) combined with therapy with itraconazole, a new antimycotic agent. Recovery from the infection was obtained and at 18 months of follow-up the patient feels well without signs of recurrences of the infection.
The authors report their experience between 1982 and 1986 in 16 cases of comminuted supraintercondylar fractures of the elbow treated by stable osteosynthesis using the AO method with immediate or early mobilisation. They illustrate the technical possibility of obtaining stable synthesis even in fractures with numerous fragments and analyse the long-term functional results. Because of the severity of the fracture, none of the patients recovered full flexion and extension of the elbow; nonetheless in all the patients there was recovery of at least 90 degrees of movement and, most importantly, this occurred in the most useful range of movement. These results, and the time required for healing, amply justify the use of solid synthesis in fractures where the alternative would be arthroplasty.
Cardiopulmonary receptors have been shown to modulate renin release in animals. However, their involvement in reflex control of renin in humans has never been unequivocally established. This report reviews data on the effects on plasma renin activity of maneuvers (lower body negative pressure and passive leg raising) that reduce and increase central venous pressure and cardiac diameter without affecting blood pressure and heart rate, thereby deactivating and stimulating cardiopulmonary receptors with little or no involvement of the arterial baroreceptors. In normotensive subjects, reduction in central venous pressure was accompanied by an increase in plasma renin activity that was similar to the increase observed during tilt that reduced central venous pressure to a similar extent. Conversely, an increase in central venous pressure was accompanied by a reduction in plasma renin activity. The increase in plasma renin activity that followed the reduction in central venous pressure was drastically attenuated in four patients who had undergone cardiac transplantation, along with other reflex effects (changes in forearm vascular resistance and plasma norepinephrine) of cardiopulmonary receptor manipulations. There was a modest reduction in the overall reflex changes in plasma renin activity in patients with mild to moderate essential hypertension compared with normotensive subjects. However, patients with essential hypertension and cardiac hypertrophy showed marked attenuation of all reflex influences of the cardiopulmonary receptors. In five subjects, therapeutic regression of this structural alteration was associated with a clear improvement in the cardiopulmonary reflex. Thus, in humans, cardiopulmonary receptors exert an important reflex control of renin release. This control (which is due in part to receptors located in the cardiac walls) is moderately affected by a mild to moderate blood pressure elevation but is markedly impaired when the elevation produces structural alterations in the heart. Preliminary evidence, however, suggests that the cardiopulmonary reflex may be improved by a reduction in cardiac hypertrophy.
1. Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg/h). 2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone. 3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone. 4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.
With the use of a variable pressure neck chamber, the effect of supine bicycle exercise on the carotid baroreceptor reflex was investigated in 10 normal volunteers who were studied at rest and during moderate and severe exercise, i.e., at 33% and 66% of their previously determined maximal exercise capacity. Deactivation of the carotid baroreceptors by a decrease in carotid transmural pressure produced a greater (p less than 0.001) increase in mean intra-arterial pressure at rest (+11.2 +/- 0.2 [SE] mm Hg) than during moderate (+9.0 +/- 0.2 mm Hg) and severe (+6.1 +/- 0.1 mm Hg) exercise. Heart interval decreased less (p less than 0.005) at rest (-73 +/- 3.2 msec) than during exercise (-0.7 +/- 0.7 msec and -4.6 +/- 0.2 msec, respectively). Furthermore, activation of the carotid baroreceptors by an increase in carotid transmural pressure provoked a greater (p less than 0.005) reduction in mean intra-arterial pressure at rest (-11.5 +/- 0.2 mm Hg) than during exercise (-9.8 +/- 0.1 mm Hg and -7.5 +/- 0.1 mm Hg, respectively), while the lengthening of heart interval was also more (p less than 0.005) pronounced at rest (+97 +/- 4.3 msec) than during moderate (+44 +/- 1.2 msec) and severe (+7.6 +/- 0.3 msec) exercise. Finally, carotid baroreceptor sensitivity was defined as the slope of the changes in blood pressure and heart interval that occurred with increasing (baroreceptor deactivation) and decreasing (activation) neck tissue pressure. On average, baroreceptor sensitivity was consistently smaller (p less than 0.05) during exercise, as compared to rest.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of short-term calcium antagonism with felodipine on blood pressure and on some biochemical plasma variables such as catecholamines, renin and aldosterone was studied in 10 normal volunteers at rest and during incremental bicycle exercise. At rest, diastolic blood pressure was slightly decreased during felodipine, whereas systolic pressure and heart rate were not significantly changed. The plasma noradrenaline concentration and plasma renin activity were increased during felodipine treatment; the plasma adrenaline and aldosterone concentrations on the contrary, were not significantly changed. The rises in plasma renin activity, plasma aldosterone and plasma adrenaline and noradrenaline concentrations produced by exercise were not significantly affected by felodipine. The plasma calcium concentration was significantly higher during felodipine treatment than during placebo and this was accompanied by an increased urinary calcium excretion. It is concluded that the rise in plasma renin activity during calcium antagonism with felodipine is not accompanied by a significant increase in plasma aldosterone. Furthermore, the present data suggest that, at least during exercise, calcium antagonism does not interfere with the mechanisms underlying the exercise-induced activation of renin and aldosterone release.
The chronic effect of training on intraerythrocyte cationic concentrations and on red cell Na+,K+-ATPase pump activity was studied by comparing well-trained athletes with sedentary subjects at rest. Also the acute effect of a 50-min cross-country run on these erythrocyte measurements was studied in the athletes. At rest the intraerythrocyte potassium concentration was increased (P less than 0.01) in the athletes compared to that of the control subjects. The intraerythrocyte concentrations of sodium and magnesium and red cell Na+,K+-ATPase pump activity were, however, similar in the trained and the untrained subjects. As compared with the resting condition, the intraerythrocyte potassium concentration was decreased (P less than 0.05) after exercise in the athletes, and this was accompanied by a minor increase in the intraerythrocyte sodium concentration. Red cell Na+,K+-ATPase pump activity was slightly increased (P less than 0.05) after exercise.
The effect of calcium (Ca2+) antagonism with felodipine on the intracellular concentrations and transmembrane fluxes of cations in erythrocytes, was studied in 10 normal volunteers at rest and during exercise. All subjects performed two uninterrupted incremental exercise tests on a bicycle ergometer in a randomized order either after placebo administration or after 3 days of pretreatment with felodipine 5 mg t.i.d. Felodipine did not affect the erythrocyte ouabain-sensitive 86rubidium uptake, furosemide-sensitive sodium (Na+)- and potassium (K+)-effluxes and the Na+,Li+-countertransport at rest and during exercise and recovery. Intra-erythrocyte and plasma Na+ and K+ concentrations were not different during felodipine whereas the plasma Ca2+ concentration was significantly increased. Plasma magnesium (Mg2+) concentration was reduced during felodipine treatment while the intra-erythrocyte Mg2+ concentration tended to be increased. The intra-erythrocyte to plasma concentration ratios for Na+ and K+ were not significantly affected by felodipine whereas the ratio for Mg2+ was increased. It is concluded that short-term Ca2+ antagonism with felodipine is not accompanied by major alterations in the intracellular concentrations and transmembrane fluxes of Na+ and K+ in red blood cells of normotensive subjects. The red cell transmembrane gradient for Mg2+ is however altered by felodipine.
The effect of exercise on the intraerythrocyte cationic concentrations and transmembrane fluxes such as the Na+-K+-adenosinetriphosphatase (ATPase) pump, the Na+-K+ cotransport, and the Na+-Li+ countertransport system was studied in 11 normal male volunteers. All subjects performed an uninterrupted incremental exercise test on a bicycle ergometer, starting at an initial work load of 20% of the subjects' maximal exercise capacity, as determined in a pretest. The work rate was increased with an additional 20% each 6 min up to a final work load of 80%. Blood samples were taken at rest, at 60 and 80% of maximal exercise capacity, and 1, 2, 3, 4, 5, and 30 min after cessation of exercise. At moderate exercise (60% of maximal exercise capacity) the intraerythrocyte potassium concentration was not changed, but at severe exercise (80% of maximal exercise capacity) it was decreased. After exercise the intraerythrocyte potassium concentration returned to base line within 2 min. Exercise did not affect the intraerythrocyte concentrations of sodium and magnesium. The activity of the Na+-K+-ATPase pump and the Na+-K+ cotransport in the erythrocytes during and after exercise was no different from the resting level. The activity of the Na+-Li+ countertransport system on the contrary tended to decrease during exercise. It is concluded that exercise is accompanied by a leakage of potassium out of the erythrocytes without major alterations in the active red cell cationic fluxes.
The effect of beta 1- or beta 2-antagonism on the plasma levels of glucose, lactate, triglycerides, and free fatty acids was studied in seventeen normal male volunteers. All subjects performed three graded and uninterrupted exercise tests until exhaustion. Prior to each exercise test they received in a randomized order during three consecutive days either placebo or a predominant beta 1-blocker (atenolol, 50 mg once per day) or a predominant beta 2-blocker (ICI 118,551, 20 mg t.i.d.), according to a double-blind cross-over study design. Atenolol increased the plasma level of glucose at rest but did not influence the rise in plasma glucose during exercise. ICI 118,551 did not change the resting plasma glucose level, but it prevented the exercise-induced rise in plasma glucose, observed during placebo. During beta 1-antagonism the plasma lactate concentration at rest and during or after exercise was not different from placebo. During beta 2-blockade the exercise-induced rise in plasma lactate tended to be suppressed, and during recovery the plasma lactate levels were significantly lower than during placebo. The serum triglycerides concentration at rest and exercise was not altered, either by beta 1- or by beta 2-antagonism. Atenolol and ICI 118,551 did not affect the serum level of free fatty acids at rest, but at moderate exercise the serum free fatty acids concentration was lower during beta 1-blockade than during placebo. Our results provide further evidence that beta 2-adrenergic receptors are involved in the regulation of the plasma levels of glucose and lactate during exercise.
UNLABELLED: After a run-in period on placebo, 26 patients with essential hypertension were prescribed single-blind tibalosine, 150 mg daily. On tibalosine their blood pressure decreased from 157/101 to 147/93 mm Hg (p less than 0.001) and their heart rate from 74 to 68 beats per minute (p less than 0.01), while plasma renin activity tended to fall from 0.81 to 0.65 ng/ml/hr (p = 0.06). Twelve patients, maintained on monotherapy with tibalosine for an average of 3.8 months, kept a diastolic pressure below 90 mm Hg. Ten patients, whose diastolic pressure on tibalosine alone remained equal to or higher than 90 mm Hg were continued on this drug for 6.6 months, but were additionally given in a double-blind and randomized way either placebo, or atenolol 100 mg, or chlorthalidone, 50 mg, daily. As compared to tibalosine plus placebo, blood pressure and heart rate decreased further on tibalosine plus atenolol from 148/97 to 140/90 mm Hg (p less than 0.05) and from 70 to 60 beats per minute (p less than 0.05), respectively. The additional blood pressure lowering effect of tibalosine plus chlorthalidone to a level of 143/96 mm Hg was not statistically significant. Eight of 10 patients' blood pressure responded better to tibalosine combined with atenolol than with chlorthalidone. Because of adverse reactions tibalosine was discontinued in 8 of the 26 patients (31%), namely in 4 who prematurely dropped out from the study and in another 4 patients, who remained adherent to the protocol. Somnolence, weary legs and dry mouth were reported more frequently (p less than 0.05) on tibalosine than on placebo. IN CONCLUSION: tibalosine is an effective anti-hypertensive drug, but side effects preclude its clinical use at a daily dose of 150 mg; the combination with a beta-adrenoceptor blocking drug seems therapeutically more effective than with a thiazide.
The erythrocyte concentration and fluxes of sodium and potassium were investigated in normal white male subjects during dietary sodium restriction and repletion, each period lasting for 16 weeks. During dietary sodium restriction the intra-erythrocyte sodium concentration decreased and the red cell ouabain-sensitive 86Rb-uptake increased; no significant changes were observed in the ouabain-insensitive fluxes of sodium such as the total, frusemide-resistant and frusemide-sensitive Na+-efflux and the Na+, Li+-countertransport. The decrease in the intra-erythrocyte sodium concentration could result from an increased Na+,K+-ATPase pump activity. The latter increase could be secondary to the early decrease in a digitalis-like plasma inhibitor and the late increase could be facilitated by the late rise in the intracellular ATP concentration, which is the energy supplier for this pump. During the subsequent first month of sodium repletion the intra-erythrocyte sodium concentration remained low, the red cell ouabain-sensitive 86Rb-uptake and ATP concentration remained elevated and returned to baseline only after 16 weeks. This long-term effect suggests either the involvement of a mechanism which can only be slowly reversible or a mechanism which is irreversible so that normalization takes place only when new red cells are released into the circulation.
The acute effect of exercise on the intraerythrocyte 2,3-diphosphoglycerate concentration and on various serum enzymes and some related variables was investigated in 14 male athletes before and after a 50-min cross-country run and compared at rest to 15 sedentary subjects. Compared to the sedentary subjects, the athletes had higher resting levels of serum creatine phosphokinase, plasma myoglobin, and renin substrate but had a lower plasma renin activity. The red blood cell 2,3-diphosphoglycerate concentration increased after exercise in the runners and was not different at rest between the athletes and the sedentary subjects. Our data therefore suggest that the resting plasma renin activity is reduced in athletes when compared to sedentary subjects. Training seems however not to alter the resting level of 2,3-diphosphoglycerate in the red blood cells.
Carotid baroreceptors were stimulated with neck suction in 47 healthy subjects. Pulse interval lengthening was measured and the time course of the response was evaluated. Eight intensities of neck chamber suction were applied to select a criterion for computing the "RR response" that gives a significant linear relationship with the magnitude of the stimuli in the highest number of individuals. The best criterion was the maximal RR prolongation within 5 seconds after the onset of the stimulus. The slope of this relationship was defined as baroreflex sensitivity. The effect of physical fitness on baroreceptor function was investigated in 24 cycling tourists with a wide range of peak oxygen uptake and training characteristics. Baroreflex sensitivity averaged 7.3 +/- 0.8 msec X mm Hg-1 and was not significantly related to age, weight, basal heart rate, peak oxygen uptake and ventilation and other training characteristics. The results suggest that in man the so defined sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating baroreflex sensitivity.