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Biomedical subjects

D Leosco

Publications and source records attributed to D Leosco.

At least 19 recordsLinked to original sources

Effect of beta-adrenoceptor blockade on dipyridamole-induced myocardial asynergies in coronary artery disease.

Twenty-one patients with angiographic evidence of significant coronary artery disease, and positive dipyridamole echocardiographic test results at basal condition and after 7 days of placebo treatment were prospectively studied to see whether beta blockade modifies the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to propranolol (120 mg/day) or placebo treatment in 3 divided doses for 7 days, after which each patient crossed over to the alternate regimen. Dipyridamole-echocardiographic testing was repeated at the end of each treatment. Propranolol abolished new mechanical signs of transient dipyridamole-induced ischemia (new wall motion abnormalities or an increase in degree of basal asynergies, or both) in 13 of 21 patients. The remaining 8 patients had positive results on dipyridamole echocardiographic testing after the propranolol treatment period. At basal conditions both heart rate and rate-pressure product were significantly reduced with propranolol; there was also a significant decrease in these parameters at peak dipyridamole infusion. At peak dipyridamole infusion heart rate and rate-pressure product were significantly lower in patients with negative than in those with positive echocardiographic test results after propranolol. Our data show that administration of beta blockade significantly reduces the development of transient dipyridamole-induced myocardial asynergies, the earliest markers of acute myocardial ischemia, detected with 2-dimensional echocardiography.

Adrenergic beta-Antagonists

Age-related effects of ischemia, lidocaine and verapamil on overdrive-induced suppression of ventricular pacemakers in isolated rat heart.

The effect of age on ventricular automaticity in the isolated perfused rat heart was determined under different conditions. When the ventricle is electrically stimulated at a faster rate, drive cessation is followed by a temporary suppression of ventricular automaticity (overdrive suppression). The effects of ischemia, lidocaine and verapamil on overdrive suppression were studied in isolated perfused adult and senescent rat hearts with complete atrio-ventricular block, by monitoring ventricular escape rate and escape rhythm recovery time after 1 minute of overdrive at a constant multiple (x3) of the spontaneous rate. The results demonstrated that: 1) lidocaine decreases ventricular automaticity especially in senescent hearts; 2) verapamil does not modify ventricular automaticity in basal conditions in either adult or senescent hearts; 3) myocardial ischemia causes a reduction in ventricular automaticity and more markedly in senescent hearts; and 4) lidocaine exaggerates the effect of ischemia, while verapamil seems to antagonize its depressant effect more in adult than in senescent hearts.

Aging

Age-related effects of platelet activating factor (PAF) in the isolated perfused rat heart.

Platelet Activating Factor (PAF) is a phospholipid that has been implicated as an important mediator of anaphylactic cardiac dysfunction and involved in the toxic effects of the ischaemia-reperfusion process. In the elderly, these phenomena are thought to be exaggerated by the age-related changes in response to several chemical factors and myocardial ischaemia. We evaluated the effects of PAF (acetyl-o-alkyl-l-phosphatidylcholine) on left ventricular systolic (LVSP) and diastolic (LVDP) pressure, coronary flow rate (CFR) and heart rate (HR) in adult (6 months, AH) and senescent (24 months, SH) rat hearts. The perfusion of PAF (10(-8), 10(-7) and 10(-6) M) induced a concentration-related reduction of LVSP, CFR and HR and a linear increase in LVDP. Contractile modifications were more pronounced in senescent hearts: LVSP decreased (P < 0.01) and LVDP increased with respect to younger animals (P < 0.01 vs. AH). This negative inotropic effect was also present in electrically paced hearts. PAF produced conduction arrhythmias ranging from second-degree atrio-ventricular conduction block to cardiac standstill both in adult and senescent hearts; at a higher dose (10(-6) M), cardiac standstill appeared after 96.5 +/- 15.3 s in adult hearts and after 45.5 +/- 17.6 s in senescent hearts (P < 0.01). Lyso-PAF did not modify while specific PAF antagonist compounds CV-3988 inhibited all electromechanical responses both in adult and senescent hearts. These data suggest that age influences the effect of PAF on contractile parameters, coronary flow and conduction arrhythmias by acting on receptors, whose function is unaffected by age.

Aging

Dipyridamole echocardiography as a useful and safe test in the assessment of coronary artery disease in the elderly.

We prospectively studied the sensitivity, specificity, feasibility, and safety of high-dose dipyridamole echocardiography, compared to exercise electrocardiography in 130 subjects (67 younger and 63 elderly patients) referred for angiographic evaluation of suspected or proven coronary artery disease. Sensitivity, specificity, and feasibility of dipyridamole echocardiography were respectively 75.5%, 100%, and 88.0% in younger patients and 82.9%, 100%, and 79.4% in elderly patients (P = NS). The sensitivity of exercise electrocardiography was 72.7% in young and 66.6% in elderly patients (P = NS); specificity 66.0% vs 60.0% (P = NS); feasibility 83.6 vs 63.5 (P = 0.05). Forty-nine younger and 38 elderly patients performed both tests. Sensitivity of dipyridamole echocardiography compared to exercise electrocardiography was 76.2% vs 73.8% in young patients and 83.3% vs 70% in the older group (P = NS). The feasibility of the two tests was significantly different in the elderly group only (dipyridamole echocardiography 79.4% vs exercise electrocardiography 63.5%; P less than 0.01). The incidence of side effects during dipyridamole echocardiography was similar in the two groups, except for dyspnea which was observed in 20% of older and 5% of younger patients (P less than 0.05). Our data demonstrate that the dipyridamole test combined with echocardiographic monitoring of regional myocardial contractility may be considered a valid non-invasive method for evaluating coronary artery disease in the elderly and that this test is a satisfactory alternative to the exercise stress test.

Aged

The hypothetical role of potassium conductance on the genesis of R-wave amplitude increase during ischemia in the isolated rat heart.

The effect of increased potassium conductance on the genesis of R-wave amplitude increase during acute myocardial ischemia has been studied in the isolated perfused rat heart by simultaneously recording the R-wave amplitude of epicardial electrograms (VEE), heart rate (HR), coronary flow rate (CFR), left ventricular diastolic pressure (LVDP), and left ventricular systolic pressure (LVSP). The experiments were performed during basal and partial or total ischemic conditions at spontaneous or fixed HR. In some experiments, potassium conductance was increased by means of high-calcium (8 mM) or acetylcholine chloride (10(-6) M) perfusion. In the control experiments, partial ischemic perfusion produced an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP; total ischemic perfusion exaggerated these variations. High-calcium perfusion provoked an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP during basal conditions (p less than 0.01 vs. control experiment); these modifications increased progressively during partial ischemic perfusion (p less than 0.01 vs. control experiment) and during total ischemic perfusion (p less than 0.01 vs. control experiment). Perfusion with acetylcholine chloride produced variations similar to those observed in high-calcium solution except that LVDP under basal conditions remained unchanged from control. When the HR was maintained at a constant value by means of atrial pacing the results were similar to those observed in the unpaced hearts. In conclusion, in the isolated perfused rat heart, increasing potassium conductance may influence the genesis of R-wave amplitude increasing during acute myocardial ischemia.

Acetylcholine

[Aging and left ventricular diastolic function].

Several studies have demonstrated that physiological aging significantly affects cardiovascular function. Experimental researches, conducted on cardiac muscle of senescent animals, have shown a prolongation of both contraction and relaxation times. This phenomenon was explained by a reduced Ca(++)-stimulated ATPase pump activity, responsible for the reduced sarcoplasmic reticulum Ca++ uptake rate. The myofilament response to Ca++ in the aging heart is normal as are peak contractile force production and post-extrasystolic twitch potentiation during continual paired stimulation. On the other hand, the inotropic response to cardiac glycosides and beta-adrenoceptor stimulation is diminished in senescent compared to adult myocardium. This decreased contractility could result mainly from mechanisms controlling Ca++ reuptake from sarcoplasmic reticulum and relaxation time (diastolic phase) rather than those determining force generation and contraction time (systolic phase). Age-related physiologic structural changes are not associated with significant variations in left ventricular diastolic and systolic sizes, but they seem a direct consequence of the rising systolic blood pressure observed in these age decades. Myocardial hypertrophy should not be considered a specific marker of the senescent heart, but rather an adaptive response to increased afterload conditions. As regard the relationship between age and diastole, it is important to underline that the alterations in aging cardiac muscle function primarily involve the isovolumic relaxation time and diastolic phase. With age, the early diastolic phase declines while the contribution of atrial contraction to ventricular diastolic filling increases as well as the isovolumic relaxation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Arrhythmogenic age-related effects of lysophosphatidylcholine in the rat heart.

Ventricular arrhythmias are the most common cause of death among patients with coronary artery disease; this is more evident in the elderly, who tend to have more severe coronary artery disease and age-dependent modifications of cardiac electrophysiology. Lysophosphoglycerides, which accumulate in the ischemic myocardium, are responsible for oscillatory after-potentials and may contribute to the development of ventricular arrhythmias. The aim of this study was to examine the effects of lysophosphatidylcholine (5 x 10(-5) M) in the absence or presence of epinephrine (10(-6) M) in isolated, perfused hearts from adult (6-12 months old) and senescent (24 months old) rats. Rat hearts (30/group) were randomly divided into four groups each of which included hearts of 6, 12 and 24-month old rats. The groups comprised a control group, a group treated with epinephrine, a group treated with lysophosphatidylcholine and a group treated with both epinephrine and lysophosphatidylcholine. Analysis of arrhythmias indicated a linear correlation between epinephrine- and lysophosphatidylcholine-induced ventricular arrhythmias and age. The incidence of arrhythmias was higher in the hearts treated with epinephrine and lysophosphatidylcholine together than in those treated with either substance separately (p less than 0.01). The results indicate that age influences the arrhythmogenic action of lysophosphatidylcholine, and that epinephrine contributes to this effect.

Aging

Regional left ventricular mechanical function during isometric exercise in patients with coronary artery disease: correlation with regional coronary blood flow changes.

The effects of isometric exercise on regional left ventricular mechanical function and regional coronary blood flow were evaluated in 17 patients with significant proximal stenosis of the left anterior descending coronary artery and 10 patients with normal coronary arteriograms. All patients had normal myocardial contractility in the basal condition. All performed isometric handgrip exercise at 50% of the maximal voluntary contraction for 3 min during two-dimensional echocardiographic monitoring and hemodynamic evaluation of great cardiac vein flow by thermodilution technique. During isometric exercise, 7 of the 17 patients with left anterior descending coronary stenosis developed asynergy in the anterior territory (anterior or septal segment, or both) (group I); the remaining 10 showed normal myocardial contraction during the test (group II). The 10 normal subjects manifested no regional asynergy during the test (control group). The increase in great cardiac vein flow at peak isometric exercise was significantly smaller (p less than 0.01) in group I (+15 +/- 8%) than that in group II (+98 +/- 48%) and the control group (+64 +/- 22%). Anterior coronary vascular resistance decreased in group II (-32 +/- 13%) and in the control group (-25 +/- 8%) but increased in group I (+6 +/- 8%, p less than 0.01 versus group II and control group). These data demonstrate that handgrip-induced myocardial asynergy is associated, in our study patients, with an abnormal response of the regional coronary circulation. The increase in coronary vascular resistance in group I patients with asynergy demonstrates that functional mechanisms play a dominant role in left ventricular mechanical dysfunction induced by isometric exercise.

Aged

Diagnostic value of the ratio of recovery systolic blood pressure to peak exercise systolic blood pressure for the detection of coronary artery disease.

It has been previously reported that at treadmill exercise testing an abnormal ratio of recovery systolic blood pressure (SBP) to peak exercise SBP is more sensitive than exercise-induced angina or ST segment depression for diagnosing coronary artery disease (CAD). To investigate whether the SBP ratio keeps its diagnostic value during upright bicycle exercise, we evaluated the ratio of postexercise SBP to peak SBP in 73 patients with angiographically documented CAD and in 48 patients with normal coronary arteries (OV group) undergoing maximal stress testing on a bicycle ergometer. Three minutes after exercise ended, SBP ratio was significantly higher in the CAD than in the OV group (0.79 +/- 0.1 vs 0.71 +/- 0.08; p less than .001). Setting the upper normal limits of the recovery SBP ratio at 2 SDs from the mean for the OV group (SBP ratio = 0.98 and 0.88 at 1 and 3 min after exercise, respectively), with an increase or no change in SBP ratio at between 1 and 3 min of recovery considered an abnormal response, the sensitivity of SBP ratio was 30%, the specificity was 83%, and the accuracy was 51%. The respective values for ST depression were 81% (p less than .0001 vs SBP ratio), 48% (p less than .001 vs SBP ratio), and 67% (p less than .01 vs SBP ratio). Thus, for bicycle ergometer exercise testing, ST segment depression seems to be more accurate than SBP ratio in diagnosing CAD.

Adult

[Action of magnesium salts on the toxic effects of calcium overload in the isolated and perfused rat heart].

The toxic effect of calcium overload and the action of magnesium sulfate (4 mM) and magnesium chloride (4 mM) on heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and voltage epicardial electrogram were studied in the isolated and perfused rat heart. Increasing calcium load by increasing [Ca]o from 1 to 6 mM we observed a progressive increase in heart rate coronary flow rate, left ventricular systolic pressure, dp/dt max and a decrease in voltage epicardial electrogram. During the exposure to [Ca]o 8 mM the toxic manifestations of calcium overload developed and we observed a reduction in heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and an increase in voltage epicardial electrogram. Magnesium sulfate and magnesium chloride had similar effect: in fact, in both procedures we observed a decrease in heart rate, left ventricular systolic pressure, dp/dt max, voltage epicardial electrogram and an increase in coronary flow rate at [Ca]o 2 mM. When magnesium salts were administered at the same time as the heart was exposed to [Ca]o 8 mM, we observed a reduction in the toxic effect of calcium overload. When magnesium salts were administered after the appearance of the calcium overload, they did not revert the toxic effect of calcium overload but prevented the insurgence of cardiac standstill. Thus, in the isolated perfused rat heart, the toxic manifestations of calcium overload develop at [Ca]o 8 mM and magnesium salts are able to reduce the toxic effects of calcium overload and the appearance of cardiac standstill according to their calcium-antagonism mechanism.

Animals

Role of increased cholinergic activity in reperfusion induced ventricular arrhythmias.

The effect of increased cholinergic activity on reperfusion induced ventricular arrhythmias was studied in alpha chloralose anaesthetised dogs by administering neostigmine during a 25 min occlusion of the anterior left descending coronary artery. The dogs were divided into five groups, each of 10 animals: the control group received only saline solution; group 1 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion (that is, 5 min before reperfusion); group 2 atropine 0.4 mg.kg-1 iv at 10 min of coronary occlusion and neostigmine 0.03 mg.kg-1 iv at 20 min; and group 3 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion and at the same time underwent atrial pacing at the same rate as that of the sinus node just before neostigmine administration. In group 4 heart rate was slowed (junctional rhythm) by destroying the sinus node at 20 min of coronary occlusion. The results obtained showed that ventricular tachycardia and fibrillation, which occur at the beginning of reperfusion, were significantly less frequent in group 1 (p less than 0.001) and in group 4 (p less than 0.001). The protective action of neostigmine was abolished by previous administration of atropine (group 2) and modified by preventing the decrease in the heart rate by atrial pacing (group 3). In group 3 ventricular tachycardia was more frequent but the incidence of ventricular fibrillation was reduced significantly compared with the control and atropine groups. Thus cholinergic activity has a protective role in reperfusion arrhythmias by decreasing the heart rate before release of the coronary occlusion and therefore reduces the incidence of ventricular fibrillation.

Animals