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Biomedical subjects

M Chiariello

Publications and source records attributed to M Chiariello.

At least 235 records · Page 13Linked to original sources

Paradoxical effects of cardiac arrest by multidose potassium cardioplegia on myocardial lysosome integrity and phospholipid content.

Multidose potassium cardioplegia is known to result in greater preservation of myocardial ATP content and better recovery of function as compared to cardiac arrest induced by aortic clamping. The present study was undertaken to assess the effects of this procedure on biochemical markers of tissue damage. Rat hearts undergoing either multidose cardioplegia or ischemic cardiac arrest were maintained at 18 degrees C for 1 or 2 hr and processed without reperfusion. Control hearts were processed at time zero. The activity of two lysosomal enzymes (beta-glucuronidase and acid phosphatase), as well as membrane phospholipid content, was measured in cardiac homogenates. One hour of arrest by either technique did not induce significant changes in these parameters. Two hours of arrest affected lysosomal integrity, as indicated by release of lysosomal enzymes into the cytosol. Soluble acid phosphatase activity averaged 44.7 +/- 1.3 mU/mg of protein in the hearts processed after 2 hr of cardioplegic arrest, and was significantly higher than that of control hearts (12.3 +/- 3.8 mU/mg of protein; P less than 0.01) and that of hearts subjected to 2 hr of ischemic arrest (29.2 +/- 4.5 mU/mg of protein; P less than 0.01 vs cardioplegic arrest; P less than 0.01 vs controls). Phospholipid content in hearts subjected to 2 hr of cardioplegic arrest was lower than in controls (0.49 +/- 0.06 micrograms Pi/mg of protein vs 0.76 +/- 0.03 micrograms Pi/mg of protein; P less than 0.01). In conclusion, 2 hr of hypothermic cardiac arrest was associated with biochemical indices of tissue damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

[HR/QT ratio during ergometric test: influence of ischemia and beta blocking therapy].

The aim of this study was to analyze the HR/QT relation during exercise in a group of patients with effort angina (Group B) in comparison with the same relation obtained in a group of normal subjects (Group A) comparable for age and sex. The regression analysis was carried out separately during effort in upright position and during rest in clinostatic position to avoid influences on QT by the patient's posture. During effort in patients of the Group B the regression shows a lower value of the slope and of the intercept (p less than 0.001) than those obtained in the subjects of the Group A. A similar behaviour is shown also from the regressions obtained during rest in the same groups. Thus at the highest HRs we observed a longer QT in the Group B. Moreover QT of ischemic patients in the presence of ECG signs of ischemia (ST less than or equal to 1 mm) resulted significantly longer (p less than 0.01) either during effort and at rest, respect to that obtained in Group A at comparable HRs. The analysis of the regression HR/QT after administration of atenolol 100 mg per os in a subgroup of patients of Group B clearly shows a less prolonged QT at the highest HRs where ECG ischemia frequently appears. This fact is demonstrated by the presence of a higher slope (p less than 0.05) respect to that obtained in the same group without therapy. In conclusion, myocardial transient ischemia provokes a longer QT in patients with ischemic heart disease in comparison with normal subjects. Acute therapy with atenolol per os is able to condition the regression HR/QT showing a relative shortening of QT at the highest HRs respect to that carried out in the same patients in absence of therapy.

Adrenergic beta-Antagonists↗

Cardiac effects of atrial natriuretic peptide in subjects with normal left ventricular function.

The effects of atrial natriuretic peptide (ANP) infusion were determined in 9 subjects undergoing cardiac catheterization that did not disclose heart disease. Data were obtained at rest and during the steady-state phase of alpha-human-(1-28)-atrial natriuretic peptide infusion (0.5 micrograms/kg bolus, 0.05 micrograms/kg/min intravenously for 10 minutes). Mean blood pressure decreased from 105 +/- 3 to 98 +/- 4 mm Hg (p less than 0.05); pressure measurements and left ventricular (LV) angiograms suitable for analysis were available in 7 of 9 subjects at matched heart rate. The ANP infusion reduced LV end-diastolic and end-systolic volume indexes from 93 +/- 6 to 80 +/- 6 ml/m2 (p less than 0.01) and from 25 +/- 3 to 17 +/- 1 ml/m2 (p less than 0.05), respectively. The LV ejection fraction increased insignificantly from 72 +/- 5 to 77 +/- 4%. End-systolic pressure/volume ratio showed a slight but not significant increase (from 3 +/- 0.4 to 4 +/- 0.8). Initial plasma levels of ANP (48 +/- 12 pg/ml) increased to 1,890 +/- 423 pg/ml (p less than 0.001) during the infusion and individual hemodynamic responses were not related to plasma ANP concentrations. These data suggest that the administration of ANP has no negative effects on LV function and the ANP-induced changes on cardiac performance are related to the reduced cardiac load.

Adult↗

Exercise time: a possible source of misleading results during long-term pharmacological studies by multiple stress testings in coronary artery disease.

The assessment of chronic pharmacological treatment of stable angina requires serial exercise stress testings. It is well known that exercise tolerance can be improved by the training effect of performing repeated testings. Our study investigated the values of heart rate, systolic blood pressure, rate-pressure product, and duration of exercise at 0.1 mV ST depression during exercise and the same parameters plus the maximal ST-segment depression at peak exercise, collected from three different tests. The first and second were performed at one-week intervals before, and the third (75 days after the first), was performed after a double-blind study with a drug versus placebo. We found a significant increase of exercise duration at 0.1 mV ST depression and at peak exercise, while 6 of 12 patients increased exercise duration from the second to the third test. Individual variability of exercise duration showed increasing values, ranging from 0 to 71% (first vs. third test). In contrast, the ratio of heart rate and systolic blood pressure did not differ between the tests. Our data criticized the use of mean values of exercise time for pharmacological studies; moreover, individual variability could affect results independently of drug or placebo administration. These findings should be taken into account in order to exclude misleading results.

Adrenergic beta-Antagonists↗

Paroxysmal supraventricular tachycardia: experience with propafenone.

The authors studied the efficacy of intravenous (IV) (1.5-2 mg/kg) and oral propafenone (450 to 900 mg/day) in 16 patients with paroxysmal, sustained, recurrent supraventricular tachycardia (SVT). In 5 patients IV propafenone was not given, because of intolerant SVT. Nine patients had Wolff-Parkinson-White syndrome. IV propafenone immediately stopped and prevented reinduction of SVT in 9/11 patients. Oral propafenone prevented SVT induction in 3 of 5 patients. In the 9 patients responsive to IV propafenone, oral propafenone was effective: in particular, in 6 patients SVT tachycardia was not induced by serial transesophageal pacings, and in the remaining 3 patients the arrhythmia was still induced but was slower and of brief duration (3-5 seconds). In 11/12 patients responsive to oral propafenone the minimum effective dosage in preventing the induction of the arrhythmia was 600 mg/day. In only 1 patient was the dose of 450 mg/day equally effective. Propafenone administration was not associated with major side effects. In conclusion, propafenone is very effective in the control of paroxysmal supraventricular tachycardia; intravenous propafenone can predict the efficacy of oral therapy.

Administration, Oral↗

Beneficial effect of a new prostacyclin derivative on the walking capacity in patients with peripheral arterial insufficiency.

The efficacy, tolerance and safety of iloprost, a stable analogue of carbaprostacyclin, were evaluated in 7 patients with peripheral arterial insufficiency at stage II of Fontaine's classification. After washout, placebo was infused intravenously for seven days, then iloprost was given by a six-hour intravenous infusion of 1 ng/kg/min over the next seven days. At the end of each period, the initial (ICD) and the absolute (ACD) claudication distance were measured by treadmill. The ankle/arm systolic blood pressure ratio (WI) was also assessed, at rest and ten minutes after exercise. As compared with placebo, ICD increased from 98 +/- 60 to 137 +/- 91 meters (p less than 0.05) and ACD from 151 +/- 76 to 210 +/- 95 meters (p less than 0.05). Similarly, WI rose from 0.44 +/- 0.14 to 0.52 +/- 0.18 (p less than 0.05) at rest and from 0.40 +/- 0.13 to 0.48 +/- 0.20 (p less than 0.05) ten minutes after treadmill exercise. Owing to the spontaneous fluctuation in walking distance experienced by such patients, an increase in ACD greater than or equal to 50% was considered as clinically relevant. In 3 patients, who experienced such an improvement, iloprost continued to be infused at the same dosage as before, for an additional seven days. In the remaining 4 patients (nonresponders), the dose was increased to 2 ng/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Assessment of left ventricular function using radionuclide angiography after dipyridamole infusion.

Thirty-six patients with significant coronary artery stenosis and no previous myocardial infarction and 25 subjects with normal coronary arteries underwent 99mTc RNV before and after coronary vasodilatation induced by dipyridamole, 0.75 mg/kg, given IV over 10 min. In subjects with normal coronary arteries, dipyridamole induced an increase in LVEF (from 66 +/- 8 to 76 +/- 8 percent; mean +/- SD; p less than 0.001); in patients with significant coronary artery stenosis (greater than or equal to 75 percent narrowing of at least one major vessel), dipyridamole injection did not affect LVEF (from 63 +/- 12 to 62 +/- 12 percent). In ten patients a complete, successful PTCA was performed and the RNV with the dipyridamole test repeated. The EF did not change with the dipyridamole test before PTCA (63 +/- 7 to 65 +/- 9 percent), but increased significantly after PTCA (62 +/- 11 to 70 +/- 9 percent; p less than 0.01). Sensitivity and specificity of EF changes after dipyridamole infusion were 75 and 76 percent, respectively. The test produced no major side effects or complications. Radionuclide angiography with dipyridamole helps to detect coronary artery stenosis and might be used to assess the effects of angioplasty on coronary flow reserve.

Adult↗

Effects of pharmacological treatment of acute myocardial infarction on left ventricular function.

Impairment of left ventricular function is a major consequence of acute myocardial infarction. Several interventions have been proposed to reduce the extent of myocardial tissue undergoing necrosis after cornoracy artery occlusion. Therapy for patients with acute myocardial infarction has long relied on interventions aimed at reducing oxygen consumption, such as administration of beta-blockers and nitrates. However, despite clinical evidence that these interventions can reduce mortality or prevent left ventricular dilatation, no clear benefit has been observed on left ventricular function. Over the past few years, treatment of acute myocardial infarction has radically changed. Availability of several thrombolytic agents has made reperfusion of ischemic myocardium a routine procedure. Early reperfusion has been shown to be the most powerful intervention to reduce infarct size and minimize left ventricular dysfunction in experimental preparations. Several clinical trials have also demonstrated that patients with acute myocardial infarction may greatly benefit from early thrombolysis, as this procedure is associated with improvement of global and regional left ventricular function and reduction in mortality. However, in spite of its obvious advantages, reperfusion might result in a paradoxical tissue damage that may blunt the net beneficial effect of restoring perfusion of ischemic myocardium. Reperfusion-mediated myocardial injury has been shown to occur in several experimental preparations and it has been proposed that generation of toxic oxygen metabolites at the moment of reflow is responsible for the occurrence of this phenomenon. Indeed, administration of free radical scavengers may significantly reduce the extent of reperfusion injury and improve contractile recovery in experimental preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart↗

[Effects of atrial natriuretic peptide on left ventricular function in man].

The effects of atrial natriuretic peptide (ANP) infusion were determined in 9 subjects undergoing cardiac catheterization which did not disclose heart disease. Data were obtained at rest and during the steady-state phase of alpha-human-(1-28)-atrial natriuretic peptide infusion (0.5 microgram/Kg bolus dose, 0.05 microgram Kg/min iv for 20 min). Mean blood pressure decreased from 105 +/- 3 to 98 +/- 4 mmHg (p less than 0.05); pressure measurements and left ventricular (LV) angiograms suitable for analysis were available in 7 of 9 subjects at matched heart rate. The infusion of ANP reduced LV end-diastolic and end-systolic volume indices from 93 +/- 6 to 80 +/- 6 ml/m2 (p less than 0.01) and from 25 +/- 3 to 17 +/- 1 ml/m2 (p less than 0.05), respectively. Left ventricular ejection fraction insignificantly increased from 72 +/- 5 to 77 +/- 4%. End-systolic pressure/volume ratio showed a slight but not significant rise (from 3 +/- 0.4 to 4 +/- 0.8). Initial plasma levels of ANP (48 +/- 12 pg/ml) rose to 1890 +/- 423 pg/ml (p less than 0.001) during the infusion and individual hemodynamic responses were not related to plasma concentrations of the peptide. These data suggest that the administration of ANP has no negative effects on LV function and the ANP-induced changes on cardiac performance are related to the reduced cardiac load.

Adult↗

Influence of left ventricular asynchrony on filling in coronary artery disease.

To evaluate whether the extent of left ventricular (LV) asynchrony plays a role in the impairment of LV rapid filling in patients with coronary artery disease (CAD), 48 patients underwent both radionuclide angiography and cardiac catheterization. Patients were divided into group I (n = 33), with normal LV kinesis or only mild hypokinesia, and group II (n = 15), with LV dyskinesia or akinesia. Radionuclide ejection fraction was higher in group I than in group II (62 +/- 12 vs 44 +/- 20%; p less than 0.001). Peak filling rate was significantly lower in group II (1.9 +/- 0.8 vs 2.6 +/- 0.9 end-diastolic counts/s; p less than 0.01). Time to end-systole coefficient of variation, an index of the extent of LV asynchrony, was significantly higher in group II than in group I (43 +/- 10 vs 35 +/- 6; p less than 0.0002). In group I, a highly significant inverse relation was found between this index of asynchrony and peak filling rate (r = 0.71; p less than 0.0001). This correlation was found even when time to end-systole coefficient of variation was normalized to the RR interval (r = 0.49; p less than 0.01) and when peak filling rate was expressed in stroke counts (r = 0.57; p less than 0.001). The correlation between peak filling rate and index of asynchrony was maintained up to an end-systole coefficient of variation value of approximately 35. In group II patients (most with an asynchrony value greater than or equal to 35) no relation was found between time to end-systole coefficient of variation and peak filling rate.

Adult↗

Heart rate, PR, and QT intervals in normal children: a 24-hour Holter monitoring study.

A dynamic electrocardiographic Holter monitoring study was performed in 32 healthy children (20 males and 12 females, age range 6-11 years old), without heart disease, according to clinical and noninvasive instrumental examination. We evaluated atrioventricular conduction time (PR), heart rate (HR), and QT interval patterns defining the range of normality of these electrocardiographic parameters. The PR interval ranged from 154 +/- 10 ms (mean +/- SD) for HR less than or equal to 60 to 102 +/- 12 ms for HR greater than or equal to 120 (range 85-180). The absolute mean HR was 87 +/- 10 beats/min (range 72-104), the minimum observed HR being 61 +/- 10 (range 51-79), the maximum 160 +/- 20 beats/min (range 129-186). Daytime mean HR gave a mean value of 93 +/- 10 (range 71-148), while during night hours it was 74 +/- 11 (range 54-98). The minimum QT interval averaged 261 +/- 10 ms for HR greater than 120 and the maximum 389 +/- 9 ms for HR less than or equal to 60; the corresponding mean value of QTc (i.e., QT corrected for HR) ranged from 388 +/- 8 for HR less than or equal to 60 beats/min to 403 +/- 14 ms for HR greater than 120 beats/min. The results of the present study provide data of normal children which can be readily compared against those of subjects in whom cardiac abnormalities are suspect or patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Reduction in infarct size by the prostacyclin analogue iloprost (ZK 36374) after experimental coronary artery occlusion-reperfusion.

In this study we attempted to determine whether administration of iloprost (ZK 36374), a chemically stable prostacyclin analogue, would reduce infarct size after experimental coronary artery occlusion and reperfusion. One hour of coronary artery occlusion was performed in 28 open-chest, anesthetized rabbits++, followed by 5 hours of reperfusion. Two minutes after occlusion, 99mTc-labeled albumin microspheres were injected into the left atrium for later assessment of the area at risk of infarction. Fifteen minutes after occlusion animals were randomly assigned to either the treatment group (iloprost, 1.2 micrograms/kg/min intravenously for 6 hours; n = 14) or the control group (n = 14). In vitro platelet aggregation was inhibited in rabbits receiving iloprost. In 10 rabbits (five treated and five control) regional myocardial blood flow was also measured by means of differentially labeled radioactive microspheres. Infarct size was significantly smaller in treated rabbits (53.6 +/- 4.1% of the risk zone vs 89.4 +/- 3.8% in control rabbits; p less than 0.001). Flow to the nonischemic myocardium was higher in treated animals, that is, 1.87 +/- 0.20 ml/min/gm of tissue 50 minutes after occlusion and 1.90 +/- 0.20 ml/min/gm of tissue 4 hours after reperfusion, compared with 1.54 +/- 0.20 and 1.64 +/- 0.30 ml/min/gm of tissue, respectively, in control rabbits (p less than 0.01). Collateral flow to the ischemic region was not affected by the drug. Mean arterial blood pressure, heart rate, and pressure-rate product in treated rabbits were not significantly different from values in control rabbits. In conclusion, administration of iloprost reduced myocardial infarct size in this model of myocardial ischemia and reperfusion in absence of major hemodynamic effects.

Animals↗

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↗