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Biomedical subjects

M Condorelli

Publications and source records attributed to M Condorelli.

At least 199 records · Page 11Linked to original sources

Inhibition of histamine release from human basophils in vitro by calmodulin antagonists.

Calmodulin is a ubiquitous and versatile Ca2+-binding protein that plays a pivoting role in cellular metabolism. We have investigated the possibility that calmodulin plays a role in immediate hypersensitivity reactions by evaluating the effects of two agents, trifluoperazine dihydrochloride (TFP) and the sulfonamide derivative N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) which selectively bind to calmodulin. TFP and W-7 cause a dose-dependent inhibition of histamine secretion from human basophils in vitro induced by several immunological (i.e., antigen and anti-IgE) and nonimmunological (i.e., formyl-methionine-containing peptide and the Ca2+ ionophore A23187) stimuli. These results indicating that two specific calmodulin antagonists are potent inhibitors of the secretory response of human basophils support the hypothesis that calmodulin may play a role in the control of the release of preformed mediators from human inflammatory cells.

Adult↗

Immunofluorescence localization of calmodulin in human polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes (PMNs) were purified (approximately equal to 99%) from peripheral blood of normal, adult volunteers. The indirect immunofluorescence technique was used to investigate the presence and the localization of calmodulin in human PMNs. The cellular distribution of calmodulin has been evaluated using an affinity chromatography-purified sheep IgG anti-calmodulin and fluorescein-conjugated rabbit anti-sheep IgG. The anti-calmodulin immunofluorescence pattern suggests that calmodulin is evenly distributed throughout the cytoplasm of human PMNs.

Adult↗

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↗

Protective role of collaterals in patients with coronary artery occlusion.

We reviewed the clinical, hemodynamic and angiographic data of 105 patients with right coronary artery occlusion and 82 patients with left anterior descending coronary artery occlusion, subdivided into 3 groups by the presence and quality of collaterals to the occluded coronary (absent, poor or good collaterals). We found that patients with right coronary artery occlusion and good collaterals had a lower frequency of diaphragmatic myocardial infarction (60%) than patients with absent collaterals (100%) (P less than 0.01). In addition, in patients with old diaphragmatic myocardial infarction, both poor and good collaterals were associated with a lower frequency of severe asynergy of the diaphragmatic left ventricular segments at left ventriculography (54% and 14%, respectively), compared to patients with no collaterals to the right coronary artery (92%, P less than 0.02 vs. poor collaterals, P less than 0.001 vs. good collaterals). In contrast, in patients with left anterior descending coronary artery occlusion, the presence of either poor or good collaterals to the left anterior descending coronary artery was not associated with a lower frequency of old anterior myocardial infarction, or, in patients with old anterior myocardial infarction, with a less severe asynergy of the anterior left ventricular segments. Our results suggest that collaterals are effective in protecting the diaphragmatic left ventricular wall in patients with right coronary artery occlusion, but not the anterior left ventricular wall in patients with left anterior descending coronary artery occlusion.

Collateral Circulation↗

Transesophageal pacing for prognostic evaluation of preexcitation syndrome and assessment of protective therapy.

An esophageal lead was used to perform decremental atrial pacing and elective induction of atrial fibrillation (AF) in 5 patients with the Wolff-Parkinson-White (W-P-W) syndrome before and after amiodarone therapy. In the control state, 1:1 atrioventricular (AV) conduction over the accessory pathway ranged from 220 to 260 ms (mean 232). The shortest R-R interval during AF ranged from 190 to 210 ms (mean 198). The ventricular rate ranged from 175 to 212 beats/min (mean 196). After amiodarone therapy, the shortest cycle length with 1:1 AV conduction increased in all patients, ranging from 290 to 540 ms (mean 370); during AF, no preexcited beat was present in 2 patients, whereas the minimal preexcited R-R interval in the remaining 3 was 290, 240, and 370 ms, respectively. The ventricular response during AF decreased in all patients. Thus, esophageal pacing is a useful method for identifying patients at risk with the W-P-W syndrome and for assessing appropriate management in individual patients. Amiodarone provides protection against life-threatening arrhythmias in these patients.

Adolescent↗

Predictability of antihypertensive efficacy of selective beta 1 blockers.

The possibility that hemodynamic and biohumoral factors may help predict the antihypertensive effectiveness of selective beta 1 blockers was investigated. The effects of 3 wk of treatment with two selective beta 1 blockers, metoprolol and atenolol, were observed in 54 patients with mild or moderate essential hypertension. No significant difference between the hemodynamic effects of the two drugs was found. The percent fall in systolic blood pressure induced by the two correlated strongly with the pretreatment values of the chronotropic response to isoproterenol and with the pretreatment values of cardiac output, heart rate, and plasma renin activity (PRA). There was no correlation between the decrease in systolic blood pressure induced and initial 24-hr urinary catecholamine output, total peripheral resistance, and plasma aldosterone. Percent fall in diastolic blood pressure correlated only with the pretreatment levels of PRA. Our results support the view that the hypotensive effect of beta 1 blockers are predictable on the basis of the pretreatment values of chronotropic response to isoproterenol, PRA, heart rate, and cardiac output.

Adult↗

Haemodynamic and clinical effects of long-term treatment of essential hypertension with captopril.

Captopril, an orally active inhibitor of angiotensin converting enzyme, was administered for 12 months to 20 patients with mild or moderate essential hypertension who initially responded favourably to this pharmacological treatment. Captopril induced a significant reduction in blood pressure which remained unmodified throughout the study. This fall in blood pressure was mainly due to a significant decrease in total peripheral vascular resistance, since no change in cardiac output was observed. Simultaneously, there was no significant change in left ventricular anatomy and performance evaluated by echocardiographic technique.

Adult↗

Increased cardiac output and lowered peripheral resistance during metoprolol treatment.

Echocardiography was performed at every six months in hypertensives well controlled on metoprolol, 100 mg twice a day. After six months' treatment blood pressure was reduced from 177/110 mm Hg to 147/88 (p less than 0.02). LV wall thickness (septum + posterior wall) was unchanged 2.10 cm (2.14), and a significant drop in cardiac output (CO) to 5.0 l/min (6.1, p less than 0.02) was recorded (pretreatment values in brackets). After 24 months' treatment LV wall thickness was reduced to 1.94 cm (p less than 0.02), total peripheral resistance (TPR) to 17.3 mm Hg/l/min (23.4, p less than 0.02) and CO increased to 6.7 l/min (6.1, n.s.). After six months' treatment, there was thus a drop in BP with a significant drop in CO and unchanged TPR. After 24 months' treatment, however, CO was back to the pretreatment level and the drop in BP was entirely caused by a drop in TPR which was probably secondary to a reduction in the wall thickness of the arterial resistance vessels as judged by the relationship between the reduction in wall thickness in the LV and the reduction in TPR during the treatment.

Adult↗

Valsalva maneuver in the assessment of baroreflex responsiveness in borderline hypertensives.

Baroreceptor function was assessed by (1) the reflex response during Valsalva maneuver, (2) phenylephrine injection, and (3) increase in neck tissue pressure by a neck-chamber in 15 borderline hypertensives (B) and in 15 age-matched normotensives (N). B responded to the fall in blood pressure, occurring in phase II of Valsalva maneuver, with an increase in blood pressure and a decrease in the R-R interval of comparable extent to those observed in normals. On the contrary, in phase IV B showed a depressed heart rate reflex response whether evaluated by the slope of the regression line obtained by plotting the R-R interval versus the systolic blood pressure (slope: B = 6.1 +/- 3.3; N = 35.6 +/- 7, p less than 0.005) or by the change in R-R interval (delta R-R interval: B = 67.5 +/- 37 ms; N = 319 +/- 55 ms, p less than 0.005). On the other hand, both phenylephrine injection and neck-chamber procedure showed an impaired baroreflex responsiveness in B. A linear positive correlation was found between the individual values of the slopes obtained during phase IV of Valsalva maneuver and after phenylephrine injection both in N (r = 0.944, p less than 0.001) and in B (r = 0.84, p less than 0.001). Finally, a linear positive correlation was found between the individual values of the slopes obtained by the phenylephrine technique and the corresponding maximum percent change in R-R interval during phase IV of the Valsalva maneuver both in normals and in hypertensives. In conclusion, overshoot bradycardia during Valsalva maneuver seems to show enough specificity in the evaluation of baroreflex responsiveness to be employed in epidemiological studies in this area.

Adolescent↗

Bilateral ventricular hypertrophy in rats exposed to acute or chronic hypobaric hypoxia.

Development of bilateral ventricular hypertrophy in animals exposed to sustained hypoxia is demonstrated. Female Sprague-Dawley rats (180-200 g) were subjected to acute (0.40 atm/24 h) or chronic intermittent (0.40 atm/18 h/day/7days) hypobaric hypoxia. Control animals were maintained at room pressure. The changes in ventricular mass (right ventricle and left ventricle including the septum) were evaluated on the basis of the dry weight values immediately at the end of hypoxic stimulus. Data show that both acute and chronic hypobaric hypoxia allow rate to develop a significantly degree of hypertrophy in the left as well as in the right ventricle. The factors involved in the genesis of the left ventricular hypertrophy in hypoxic conditions are presented.

Animals↗

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↗

Intropic effects of several antiarrhythmic drugs.

The effects of intravenous administration of several quinidine-like antiarrhythmic drugs (bunaftine, monochloroacetyl ajmaline, lidocaine, mexiletine, disopyramide, aprindine, diphenylhydantoin, procainamide) on left ventricular performance, evaluated by systolic time intervals (STI), were studied in 100 patients with atherosclerotic heart disease. The STI were measured: the pre-ejection period (PEP), the isometric contraction time (ICT), the left ventricular ejection time (LVET), corrected LVET (LVETc), and the PEP/LVET ratio. The degree of impairment of left ventricular performance was maximal after aprindine and disopyramide administration. This was demonstrated by significant increases in the PEP, ICT, and PEP/LVET and by significant decreases in LVET and LVETc, in patients in both III-IV and I-II NYHA classes. Bunaftine, monochloroacetyl ajmaline, and lidocaine induced a less marked impairment of myocardial performance, since the PEP, ICT, and PEP/LVET increases were not significant compared to controls in patients in NYHA class I-II, and since no variation of LVET and LVETc were observed. Mexiletine effects on myocardial performance appear to be intermediate between these groups of drugs. Diphenylhydantoin and procainamide, considered separately because of their effects on heart rate and blood pressure which are not possessed by the other drugs, induced significant increases of PEP in NYHA class III-IV patients. However, the effects of these 2 drugs on myocardial performance may have been underestimated, due to the concomitant hemodynamic effect of these drugs.

Ajmaline↗