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Biomedical subjects

L Spinelli

Publications and source records attributed to L Spinelli.

At least 19 recordsLinked to original sources

Diastolic perfusion time and exercise posture in coronary artery disease patients: correlation with ST segment changes.

The relationship between either heart rate or diastolic time and ST segment depression has been evaluated during supine and upright exercise in 16 coronary artery disease patients. Diastolic perfusion time and ST segment depression were related by a linear regression, which was independent of exercise posture. The entity of ST segment depression was greater during supine than in upright exercise for the same heart rate. The assessment of the relationship between heart rate and diastolic perfusion time during two exercises showed that at the same heart rate, diastolic perfusion time was shorter in supine posture. In conclusion, the greater entity of ST segment depression induced by supine rather than upright exercise might be explained by the effect of supine posture on diastolic perfusion time.

Coronary Disease

Method for kinetic analysis of drug-induced cell cycle perturbations.

A method is described for quantitative study of the flux of cells through the cell cycle phases in in vitro systems perturbed by chemicals, such as chemotherapeutic agents. The method utilizes cell count and the flow cytometric technique of bromodeoxyuridine (BrdUrd) labeling, according to an optimized strategy. Cells are exposed to BrdUrd during the last minutes of drug treatment and fixed for analysis at 0, 1/3Ts, 2/3Ts, Ts, and Tc + TG1 recovery times, where Ts, TG1, Tc are the mean durations of phases S and G1 and of the whole cycle of control cells. As an example of application of the proposed procedure, a kinetic study of the effect of 1-(2-chloroethyl)-1-nitrosourea (CNU) on the L1210 cell cycle is described. Simple data analysis, requiring only a pocket calculator, showed that cells in phases G1 and G2M at the end of a 1 h treatment with 1 microgram/ml CNU were fully able to leave these phases but were destined to remain blocked in the following G2M phase (G1 for a minority of them). We also found that cells initially in S phase were slightly delayed in completing their S phase and that 50% of them remained temporarily blocked in the subsequent G2M phase, irrespective of their position in the S phase.

Animals

Cis dichlorodiammine platinum induced DNA interstrand cross-links in primary cultures of human ovarian cancer.

We quantified and examined the kinetics of DNA interstrand cross links (DNA-ISC) caused by Cis dichlorodiammine platinum (DDP) using the method of alkaline elution in 58 highly purified human ovarian tumours growing in primary culture. A large heterogeneity in both the quantity and kinetics of DDP induced DNA-ISC was observed in cultures derived from neoplasms of different patients and from different lesions of the same patient. In the majority of cases. DNA-ISC lasted for prolonged time intervals after 1 h drug exposure, being significantly repaired only 48 or 72 h following drug washout. The persistence of DNA-ISC is probably due to a prolonged formation of these lesions for up to 24 h as assessed by the change in the repair kinetics that occurred after preventing new DNA-ISC formation by quenching of monoadducts with thiourea. The inefficient repair of DDP monoadducts appears therefore to be a possible reason for the permanence of DNA-ISC. These studies suggest that the long permanence of DNA-ISC in human ovarian cancer could be the basis for the high selectivity of DDP for this human malignancy.

Cisplatin

Diastolic perfusion time at ischemic threshold in patients with stress-induced ischemia.

BACKGROUND: To evaluate the relevance of diastolic perfusion time on the mechanisms underlying stress-induced ischemia, 16 patients with coronary artery disease and seven patients with syndrome X underwent five randomized stress tests (upright and supine exercise with and without therapy, transesophageal atrial pacing). METHODS AND RESULTS: Exercise duration Time to 0.1 mV ST segment depression, heart rate, rate-pressure product, and diastolic perfusion time were evaluated for each patient during stress tests. In both groups, variability coefficients of the above-mentioned parameters were not different at rest. At ischemic threshold (0.1 mV ST segment depression) in patients with coronary artery disease, the variability coefficient of exercise duration (40.1 +/- 22.2) was significantly higher (p less than 0.0001) than those of heart rate (12.8 +/- 2.9), rate-pressure product (14.8 +/- 3.3), and diastolic perfusion time (0.39 +/- 0.1). The variability coefficient of diastolic perfusion time was also significantly (p less than 0.0001) lower than those of heart rate and rate-pressure product. Similarly, the variability coefficient of diastolic perfusion time (0.44 +/- 0.1) in syndrome X patients was significantly lower (p less than 0.0001) than those of exercise duration (28.2 +/- 9.4), heart rate (12 +/- 1.4), and rate-pressure product (14.6 +/- 1.3). CONCLUSIONS: Fixed diastolic perfusion time at ischemic threshold, despite different kinds of stress tests and variability of heart rate and rate-pressure product, indicates the relevant role of diastolic perfusion time in determining myocardial ischemia.

Adult

Diastolic time at ischemic threshold in patients with syndrome X.

The patients with so-called syndrome X experience true myocardial ischaemia in spite of their anatomically normal coronary arteries. The pathogenetic mechanism of the effort-induced ischaemia in these patients should be obviously different from that of patients with atherosclerotic coronary artery lesions. An inadequate coronary dilatory capacity in response to increased oxygen demand has been proposed as mechanism responsible of ischaemic response to effort (Canon et al., 1983; Canon et al., 1985). Since diastolic duration expressed as percentage of the cardiac cycle has implications with the myocardial oxygen demand/supply ratio (Boudoulas et al., 1982; Maseri et al., 1977), the purpose of this study has been to evaluate the behaviour of this parameter at the outcome of the ischaemic electrocardiographic changes during stress testing in the patients with syndrome X.

Adult

Exercise-induced impairment of diastolic time in patients with X syndrome.

Since an abnormal shortening of diastolic duration during exercise in the patients with coronary artery disease was demonstrated, time course of diastolic period (cardiac cycle minus electromechanical systole) calculated from polycardiographic recording has been assessed in patients with X syndrome and in normal age-matched subjects during supine ergometer exercise. All patients with X syndrome had positive exercise stress response (more than 0.1 mV of ST segment depression). Duration of diastole expressed as percent of cardiac cycle was significantly shorter at the intermediate steps and at the peak of exercise in patients with X syndrome compared with normal subjects (p less than 0.05). When the relationship between heart rate and diastolic time was examined, an inverse nonlinear regression was found both in normal subjects and in patients with X syndrome. The exercise values of diastolic time observed in patients with X syndrome were significantly shorter than those predicted as normal diastolic time heart rate relation. Thus the patients with X syndrome demonstrated abnormalities in the decrement of diastolic time with exercise. We hypothesized that this disproportionate shortening, by reducing subendocardial blood flow, might induce a worsening of ischemic response to exercise.

Angina Pectoris

Alinidine in chronic stable angina: the effect on diastolic perfusion time.

The present study has been performed to assess the effects of alinidine on diastolic duration during exercise in chronic coronary artery disease. Twelve male patients with stable effort angina and without previous myocardial infarction were studied. They received alinidine or placebo in a double-blind randomized crossover trial for 3 days after a wash-out period of 4 days. Alinidine was administered at a dosage of 30 mg 3 times a day. At the end of each treatment the patients underwent upright bicycle exercise. Left ventricular time intervals were obtained by means of carotid thermistor plethysmography. Diastolic duration was calculated by subtracting the electromechanical systole from the R-R interval and expressed as a percentage of the cardiac cycle (%D). Alinidine increased both total exercise duration from 246.7 +/- 120.7 to 346.6 +/- 114.1 s (p less than 0.05) and time to 0.1-mV ST segment depression from 98.3 +/- 53 to 187.2 +/- 105 s (p less than 0.05). Similarly the drug induced a reduction of the rate-pressure product and of the extent of ischemic ST segment depression during exercise. %D was increased by alinidine both at rest and during exercise. A direct linear regression between R-R and %D was found after both alinidine and placebo treatments either at rest or during exercise. Nevertheless, no difference was observed between both slopes and intercepts. Therefore, since the relationship between R-R interval and %D was unaffected by alinidine, it was possible to hypothesize that the changes in diastolic duration were due only to the bradycardic action of the drug.

Angina Pectoris

Problems in the design of anticancer agents.

Theoretically, two predominant paths for obtaining more selective anticancer agents may be envisaged. These are: (a) to make compounds which distribute only or preferentially in cancer cells; (b) to make compounds that are able selectively to kill or to differentiate cancer cells. Although in the last two decades research into new anticancer drugs has not produced satisfactory results, there is solid ground on which novel strategies can be developed, mainly based on a much greater biological knowledge of human tumours. This article does not review all the possible approaches that may be followed, but simply discusses some ideas and problems mainly taken from the current research of our laboratory.

Animals

Non-invasive assessment of left ventricular performance in patients with coronary artery disease after chronic diltiazem therapy.

To evaluate the effects of diltiazem (240 mg/day) on the left ventricular function, we studied 13 patients with coronary artery disease (CAD). Comparison with placebo was made in a double-blind randomized crossover study. Both placebo and diltiazem were administered for 5 weeks. We assumed left ventricular systolic time intervals assessed by polycardiography as parameter of ventricular function. Diltiazem induced a significant decrease in pre-ejection period (p less than 0.01) as well as pre-ejection period/left ventricular ejection time ratio (p less than 0.01). Thus, our results suggest that diltiazem improves the contractile state of ischemic myocardium in CAD patients.

Blood Flow Velocity

Electromechanical events during spontaneous angina.

The electromechanical events occurring during acute myocardial ischemia were assessed in 10 patients who developed spontaneous angina during cardiac catheterization. Aortic pressure and electrocardiogram were recorded, and heart rate and systolic and diastolic time intervals were measured under control conditions, at the onset of angina and during the relief of chest pain. In 5 patients spontaneous angina was accompanied by an increase in heart rate and systemic arterial pressure and by ST segment changes in anterior or anterolateral precordial leads. Diastolic time, expressed as percent of cardiac cycle, shortened from 48.8 +/- 3.6% at rest to 33.6 +/- 4.8% (p less than 0.01) at the onset of angina, as a consequence of a significant increase in both electromechanical systole and heart rate, and returned to control values within 10 min after sublingual nitroglycerin. In the remaining 5 patients, spontaneous angina was accompanied by a decrease in heart rate and systemic arterial pressure and by ST segment changes in the inferior or inferolateral leads. The diastolic time increased significantly (p less than 0.05) from 39.4 +/- 6.1% at rest to 47.8 +/- 9% at the onset of angina, as a consequence of a significant decrease in heart rate and a slight decrease in electromechanical systole. Since coronary perfusion takes place mainly during diastole, our results suggest that the reflex increase in adrenergic tone may worsen myocardial ischemia by affecting diastolic perfusion time. In contrast, the increase in vagal tone may contribute to spontaneous relief of angina by prolonging diastolic perfusion time.

Adult

[Influence of posture on exercise-induced electrocardiographic and hemodynamic changes in patients with stable effort angina pectoris].

The present work was performed in order to assess the differences in electrocardiographic and hemodynamic responses to supine and upright dynamic exercise of patients with coronary artery disease. Changes in heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, rate-pressure product (RPP) and ST segment depression during supine and upright bicycle stress test were compared in twenty patients suffering from stable effort angina and without previous myocardial infarction. In the supine posture lower values of HR were observed at rest, during stress test and during three minutes of the recovery period. Conversely, in all patients both SBP and DBP were higher during the stress test in the supine position decubitus. No significant changes in RPP was observed between the two different postures. Finally, ST segment didn't show differences at rest between the upright and supine position. All the patients had a lower ischemic threshold during exercise in the supine position than in the upright one. In fact an ST segment depression greater than 1 mm was observed during stress test in the supine position at lower work-load levels and at lesser HR values. Consequently for given HR, SBP and DBP ST segment, depression was greater in the supine rather than in the upright position.

Adult