Biomedical subjects

M Chiariello

Publications and source records attributed to M Chiariello.

At least 163 records · Page 9Linked to original sources

PubMed1994

[Atrioventricular conduction before and after the radiofrequency catheter ablation of a nodal reentry tachycardia circuit].

Aim of our study was to retrospectively evaluate atrioventricular conduction 24 hours after selective radiofrequency catheter ablation of the fast pathway or after selective ablation of the slow pathway of the atrioventricular nodal reentrant tachycardia circuit. Electrophysiologic modifications were retrospectively analyzed in 47/48 patients successfully submitted to fast pathway ablation and in 90/93 patients successfully submitted to slow pathway ablation. The atrioventricular conduction intervals (P-Q and A-H), both anterograde and retrograde Wenckebach point, the effective refractory period of atrioventricular node and the atrioventricular node function curve were evaluated before and after selective radiofrequency catheter ablation of slow and fast pathway. We identified the fast pathway ablation potential as: A:V ratio > or = 2:1, His electrogram < or = 150 microV. The slow pathway potential was identified as the widest, sharpest and latest atrial electrogram recorded during sinus rhythm in the posteroseptal region of the atrioventricular junction or as the widest, sharpest and earliest observed during retrograde conduction. We observed a significant increase in the P-Q and A-H intervals in patients submitted to fast pathway ablation, while no significant modification of these parameters was appreciated in patients submitted to slow pathway ablation. No significant modification of anterograde Wenckebach point (NS) was observed in patients submitted to successfully ablation of fast pathway while a statistically significant increase in anterograde Wenckebach point (p = 0.03) was observed in patients submitted to slow pathway ablation. After selective fast pathway ablation, retrograde conduction was absent in 82.9% of patients submitted to ablation; in the remaining 17.1% a significant increase of retrograde Wenckebach point was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Myocardial damage during ischaemia and reperfusion.

Large quantities of oxygen free radicals can be generated on reperfusion of the ischemic myocardium. This phenomenon is probably responsible for a specific component of cell damage separate from ischemic injury and may blunt the beneficial effects of thrombolysis. Anti-free radical interventions may reduce the severity of this "reperfusion injury". However, reports of treatment failures indicate that reperfusion injury is a complex phenomenon, and suggest that the beneficial effects of treatment may be critically dependent on factors that are not clearly understood.

Animals↗

PubMed1994

[Ambulatory monitoring of left ventricular function in patients with ischemic heart disease: effects of coronary revascularization].

The aim of this study was to assess the efficacy of coronary artery bypass using an ambulatory radionuclide monitoring system of left ventricular function (VEST) during daily activities in patients with previous myocardial infarction and coronary artery disease. Ten patients with previous myocardial infarction, clinical evidence of residual angina and angiocardiographically proven coronary artery disease of at least two epicardial vessels were studied by VEST 8 +/- 2 days before and 15 +/- 3 days after surgical myocardial revascularization. VEST allows to monitor both left ventricular function and 2 ECG leads. During the radionuclide monitoring (at least 60 min) all patients underwent handgrip test (compression of a dynamometer for 2 min at the 75% of maximal capacity), a mental stress (arithmetic operation consisting in subtracting 17 from 17,000 for 4 min), walking (140 yards) and climbing stairs (8 flights). No significant changes in left ventricular function during mental stress and handgrip both before and after the surgical procedure were observed. In the preoperative evaluation, walking induced a significantly increase in heart rate from rest to peak exercise (73 +/- 13 versus 79 +/- 11 b/min, respectively; p < 0.01). After coronary artery bypass, heart rate (rest: 92 +/- 18 b/min, effort: 98 +/- 19 b/min; p < 0.01), ejection fraction (rest: 47 +/- 8%, effort: 53 +/- 10%; p < 0.01), cardiac output (rest: 43 +/- 8 edv/min, effort: 51 +/- 11 edv/min, p < 0.01), and stroke volume (rest: 47 +/- 9%, effort: 53 +/- 9%; p < 0.01) increased at maximal effort compared to the control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

[Protection by blockers against human low density lipoprotein peroxidation induced by oxygen free radicals].

Previous studies in other systems have shown that beta-receptor blockers may effectively inhibit oxygen radical-induced lipid peroxidation. On the other hand, it has been recently proposed that oxygen free radicals can induce peroxidation of human low density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor. This phenomenon may induce foam cells transformation in vivo. In the present study we investigated whether beta-blockers may reduce oxygen radical-mediated LDL peroxidation. Purified human LDL were oxidized by exposure to oxygen free radicals generated by xanthine (0.2 mM) and xanthine oxidase (100 mU) at 37 degrees C after a pre-incubation (30 min) in presence of different concentrations (from 1 to 30 microM) of acebutolol, metoprolol or propranolol, three agents with a different degree of lipophilicity. Peroxidation was measured from malonyldihaldehyde (MDA) production. Data have shown a significant percent inhibition of MDA formation in presence of beta-blockers (from 33 to 85%). Thus, beta-blockers reduced peroxidation of human LDL in vitro at clinically relevant concentrations. The order of potency appears to follow the degree of lipophilicity. These data suggest that, although beta-blockers are known to adversely effect lipid metabolism, these agents might on the other hand prevent atherogenesis via a mechanism of inhibition of LDL peroxidation in vivo and reduced foam cells formation.

Acebutolol↗

PubMed1994

[Heart function in chronic pressure overload caused by aortic stenosis: the role of collagen tissue].

The purpose of this study was to evaluate left ventricular (LV) structure-function interplay in aortic stenosis. LV structure was assessed from endomyocardial biopsies obtained in 27 patients with aortic stenosis. Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching) and endocardial fibrosis were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from 6 pre-transplantation donor hearts whereas other 11 patients with normal cardiac function served as hemodynamic controls. LV biplane cineangiography and high-fidelity LV pressure measurement were carried out in all patients. Systolic function was assessed by LV biplane ejection fraction, diastolic function by time constant of relaxation, peak filling rates and passive elastic properties. Total collagen volume fraction (7.3 versus 1.6%, p < 0.01) as well as the degree of cross-hatching (1.7 versus 0.8 grade, p < 0.01) were significantly increased in patients with aortic stenosis with respect to controls. Endocardial fibrosis was present in 11/27 patients with aortic stenosis and in no patients of control group. In aortic stenosis in presence of increased total collagen volume fraction there were no changes in systolic and diastolic function, whereas in presence of changes in collagen architecture ejection fraction was depressed and passive elastic properties increased. In conclusion, in aortic stenosis, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered. A prolongation of relaxation was present in aortic stenosis and appears to be mediated by muscle hypertrophy per se.

Aged↗

PubMed1994

Evaluation of left ventricular asynchrony by radionuclide angiography: comparison of phase and sector analysis.

UNLABELLED: The aim of this study was to assess the optimal method to evaluate asynchrony in equilibrium radionuclide angiography (RNA). METHODS: We studied 20 patients (14 males and 6 females, age range 25-60 yr) with RNA during atrial and sequential atrioventricular (AV) pacing, which increased left ventricular (LV) asynchrony. Both studies were performed at the same heart rate. Asynchrony was assessed either on phase images, by computing the standard deviation of the phase distribution (SD-P) and by sector analysis. Systolic and diastolic asynchrony were evaluated as the coefficient of variation of time to end systole (CV-TES) and time to peak filling rate (CV-TPFR) in four sectors. In addition, phase values were computed on time-activity curves from the same sectors, and their standard deviation (SD-Psec) was computed. RESULTS: During atrial pacing SD-P was 32.3 degrees +/- 6.7 degrees and did not change during AV pacing (32.1 degrees +/- 5.6 degrees, p = n.s.). Both CV-TES and CV-TPFR had a significant increase during AV pacing (from 7.7% +/- 3.9% to 11.5% +/- 6.4%, p < 0.01, and from 8.4 degrees +/- 5.8 degrees to 12.9 degrees +/- 6.7 degrees, p < 0.001). AV pacing led to a significant increase in SD-Psec (from 6.3 degrees +/- 4.0 degrees to 12.6 degrees +/- 9.7 degrees, p < 0.05). Moreover, reproducibility was assessed in 15 additional age-matched patients. The results of the reproducibility study indicate a better repeatability for CV-TES and CV-TPFR. CONCLUSIONS: The findings of this study suggest that sector analysis with calculation of indices of LV systolic and diastolic asynchrony is better suited for quantitation of LV temporal nonuniformity.

Cardiac Catheterization↗

PubMed1994

[The peroxidation of human glycosylated low-density lipoproteins is mediated by the superoxide radical: the protective effects of superoxide dismutase].

Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and could induce foam cell transformation. Post-translational nonenzymatic glycosylation of low density lipoprotein (LDL) occurs in vivo in diabetic patients. Glycosylated LDL (glcLDL) is degraded by macrophages in part by the classic LDL-receptor and in part by the scavenger receptor. This latter mechanism may contribute to the formation of foam cells and acceleration of atherosclerosis in diabetes mellitus. Oxygen free radicals (ORs) could induce LDL peroxidation and subsequent formation of foam cells. Glycosylation may alter protein conformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2). Thus, the aim of this study was to investigate whether glcLDL are susceptible to peroxidative modification by ORs. GlcLDL was prepared incubating LDL with 40 mM glucose in sterile phosphate-buffer-EDTA 1 mM for 10 days at 37 degrees C. Control LDL (cLDL) was similarly incubated with buffer but without glucose. After this preparation both forms of LDL were oxidized by CuSO4 (15 microM for 20 hours at 37 degrees C) or by xanthine/xanthine oxidase (X:2 mM/XO: 100 mU for 20 hours at 37 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus↗

PubMed1993

Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow.

Previous in vitro studies have shown that isolated mitochondria can generate oxygen radicals. However, whether a similar phenomenon can also occur in intact organs is unknown. In the present study, we tested the hypothesis that resumption of mitochondrial respiration upon reperfusion might be a mechanism of oxygen radical formation in postischemic hearts, and that treatment with inhibitors of mitochondrial respiration might prevent this phenomenon. Three groups of Langendorff-perfused rabbit hearts were subjected to 30 min of global ischemia at 37 degrees C, followed by reflow. Throughout ischemia and early reperfusion the hearts received, respectively: (a) 5 mM KCl (controls), (b) 5 mM sodium amobarbital (Amytal, which blocks mitochondrial respiration at Site I, at the level of NADH dehydrogenase), and (c) 5 mM potassium cyanide (to block mitochondrial respiration distally, at the level of cytochrome c oxidase). The hearts were then processed to directly evaluate oxygen radical generation by electron paramagnetic resonance spectroscopy, or to measure oxygen radical-induced membrane lipid peroxidation by malonyl dialdehyde (MDA) content of subcellular fractions. Severity of ischemia, as assessed by 31P-nuclear magnetic resonance measurements of cardiac ATP, phosphocreatine, and pH, was similar in all groups. Oxygen-centered free radical concentration averaged 3.84 +/- 0.54 microM in reperfused control hearts, and it was significantly reduced by Amytal treatment (1.98 +/- 0.26; p < 0.05), but not by KCN (2.58 +/- 0.96 microM; p = not significant (NS)), consistent with oxygen radicals being formed in the mitochondrial respiratory chain at Site I. Membrane lipid peroxidation of reperfused hearts was also reduced by treatment with Amytal, but not with KCN. MDA content of the mitochondrial fraction averaged 0.75 +/- 0.06 nM/mg protein in controls, 0.72 +/- 0.06 in KCN-treated hearts, and 0.54 +/- 0.05 in Amytal-treated hearts (p < 0.05 versus both groups). Similarly, MDA content of lysosomal membrane fraction was 0.64 +/- 0.09 nM/mg protein in controls, 0.79 +/- 0.15 in KCN-treated hearts, and 0.43 +/- 0.06 in Amytal-treated hearts (p < 0.05 versus both groups). Since the effects of Amytal are known to be reversible, in a second series of experiments we investigated whether transient mitochondrial inhibition during the initial 10 min of reperfusion was also associated with beneficial effects on subsequent recovery of cardiac function after wash-out of the drug. At the end of the experiment, recovery of left ventricular end-diastolic and of developed pressure was significantly greater in those hearts that had been treated with Amytal during ischemia and early reflow, as compared to untreated hearts.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1993

Comparison of left ventricular function in insulin- and non-insulin-dependent diabetes mellitus.

Diabetes mellitus has been reported to have controversial effects on left ventricular (LV) function in patients with no evidence of coronary artery disease. In this study, LV function at rest was evaluated in 2 groups of diabetic patients, with insulin-dependent (IDD; n = 16) and non-insulin-dependent (NIDD; n = 23) diabetes mellitus, with no evidence of coronary artery disease. All patients underwent an electrocardiographic stress test, and first-pass and equilibrium radionuclide angiography at rest and during supine exercise. Data in each group of diabetic patients were compared with those obtained from age- and sex-matched normal subjects. In both groups of diabetic patients plasma catecholamine levels were significantly greater than in control subjects. Ejection fraction at rest and during exercise did not differ between each group of diabetic patients and their respective control group. In patients with IDD, peak ejection rate (4 +/- 1 end-diastolic count/s) was significantly greater than in control subjects (2.6 +/- 0.1 end-diastolic count/s; p < 0.001); similarly, peak filling rate (4.3 +/- 1.0 end-diastolic count/s) was significantly greater than in controls (3.0 +/- 0.2 end-diastolic count/s; p < 0.001). Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects. In contrast, patients with NIDD had significantly reduced cardiac output compared with that of control subjects (5.7 +/- 0.2 vs 5.9 +/- 0.2 liter/min; p < 0.01), and increased systemic vascular resistances (1,422 +/- 137 vs 1,314 +/- 68 dynes.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Rest-injected thallium-201 redistribution and resting technetium-99m methoxyisobutylisonitrile uptake in coronary artery disease: relation to the severity of coronary artery stenosis.

To compare rest-injected thallium-201 (Tl) redistribution and resting technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) myocardial uptake in chronic coronary artery disease (CAD), 15 patients with angiographically proven CAD and left ventricular (LV) dysfunction (ejection fraction 34% +/- 9%) were studied. All patients underwent rest-redistribution Tl and resting 99mTc-MIBI cardiac imaging. Gated 99mTc-MIBI images were also acquired to assess regional LV wall motion (WM). Myocardial segments (n = 225) were divided into three groups on the basis of the degree of coronary artery stenosis: group 1 (total occlusion, n = 82), group 2 (50%-99% of stenosis, n = 84) and group 3 (< 50% of stenosis, n = 59). WM was significantly worse in groups 1 and 2 compared to group 3 (P < 0.001), but no difference was observed between groups 1 and 2. Tl and 99mTc-MIBI uptake were significantly lower in groups 1 and 2 compared to group 3 (P < 0.001), and in group 1 compared to group 2 (P < 0.001). When Tl and 99mTc-MIBI uptake were directly compared. Tl uptake was higher than 99mTc-MIBI uptake in group 1 (P < 0.001), while no significant difference was observed in groups 2 and 3. Thus, both rest-injected Tl redistribution and resting 99mTc-MIBI uptake reflected the severity of coronary artery stenosis in CAD. However, in myocardial segments with total coronary occlusion Tl uptake was significantly higher than 99mTc-MIBI uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

The effects of calcium channel antagonist treatment and oxygen radical scavenging on infarct size and the no-reflow phenomenon in reperfused hearts.

Calcium antagonists reduce ischemic injury, and anti-free-radical interventions may reduce reperfusion injury. However, the effects of treatment with both interventions have never been investigated. In the present study, anesthetized rabbits underwent 30 minutes of coronary artery ligation, which was followed by 5.5 hours of reflow. Eight animals in each group received: (1) the calcium antagonist gallopamil during ischemia, (2) the oxygen radical scavenger superoxide dismutase during reperfusion, (3) combined treatment with gallopamil and superoxide dismutase, and (4) saline solution. All groups were similar with respect to collateral flow during ischemia and extent of risk region. Infarct size averaged 60.2% +/- 5.5% of risk region in controls and was significantly smaller (p < 0.001) in rabbits that were treated with either gallopamil (28.1% +/- 3.4%) of superoxide dismutase (29.3% +/- 3.2%). Little further reduction in infarct size was observed with combination therapy (22.9% +/- 3.2% of risk region; p = NS). Superoxide dismutase had no effects on hemodynamics, whereas gallopamil significantly reduced heart rate, mean arterial pressure, and rate-pressure product. However, the reduction in infarct size that was observed in gallopamil-treated rabbits significantly exceeded the expected value in this group after corrections were made for changes in these determinants of ischemic injury. Therefore we investigated whether other factors may have contributed to the beneficial effects of gallopamil. In vitro the drug had no oxygen radical scavenging activity, nor did it exert antioxidant effects. In addition, gallopamil did not affect neutrophil function. In conclusion, in this acute model myocardial cell necrosis was significantly reduced either by administration of a calcium antagonist during ischemia or by removing oxygen radicals during reperfusion. However, superoxide dismutase administration did not further reduce infarct size when given to animals that had been treated with gallopamil. Since gallopamil has no direct effect on several mechanisms of reperfusion injury, these data suggest that calcium antagonists, by decreasing myocardial oxygen demand during ischemia, may indirectly reduce oxygen radical damage during subsequent reperfusion.

Analysis of Variance↗

PubMed1993

Effects of induced asynchrony on left ventricular diastolic function in patients with coronary artery disease.

OBJECTIVES: This study was designed to increase asynchrony with sequential atrioventricular (AV) pacing and to study its effects on left ventricular isovolumetric relaxation, rapid filling and stiffness. BACKGROUND: Left ventricular nonuniformity is a major determinant of diastolic function. METHODS: Thirteen patients with coronary artery disease were studied by simultaneous equilibrium radionuclide angiography and cardiac catheterization during atrial and AV pacing. Ejection fraction and peak filling rate were measured by radionuclide angiography. Regional analysis was obtained by analyzing time-activity curves of four left ventricular sectors; systolic and diastolic asynchrony were evaluated as the coefficient of variation of time to end-systole and, respectively, time to peak filling rate in the four sectors. Cardiac index and left ventricular pressure were measured with high fidelity catheters at cardiac catheterization. The time constant of isovolumetric relaxation was derived from left ventricular pressure. Pressure-volume loops were assembled and constants of chamber stiffness were computed. RESULTS: Atrioventricular pacing led to a decrease in cardiac index (3.7 +/- 0.9 to 3.3 +/- 0.8 liters/min per m2, p = 0.01) and peak filling rate (352 +/- 125 to 287 +/- 141 ml/s, p = 0.03; 2.4 +/- 0.8 to 2.0 +/- 0.8 end-diastolic counts/s, p = 0.02; 4 +/- 1.3 to 3.2 +/- 1.0 stroke counts/s, p = 0.008). The time constant of isovolumetric relaxation increased (57 +/- 10 to 64 +/- 12 ms, p = 0.04) and the global diastolic pressure-volume relation shifted upward. CONCLUSIONS: Atrioventricular pacing induces left ventricular asynchrony, which is associated with a slower rate of isovolumetric relaxation. The isovolumetric relaxation lasts after the filling phase has begun, thereby reducing the rate of rapid filling.

Adult↗

PubMed1993

Endogenous prostaglandin endoperoxides may alter infarct size in the presence of thromboxane synthase inhibition: studies in a rabbit model of coronary artery occlusion-reperfusion.

OBJECTIVES: The aim of this study was to assess whether prostaglandin endoperoxides, which continue to be formed in the setting of thromboxane A2 synthase inhibition, might influence the fate of ischemic myocardium in a model of coronary occlusion and reperfusion. BACKGROUND: It was recently demonstrated that thromboxane A2 synthase inhibitors reduce ischemic myocardial injury through a redirection of prostaglandin (PG) endoperoxides toward the synthesis of "cardioprotective" prostaglandins, such as PGI2, PGE2 and PGD2. However, part of these prostaglandin endoperoxides may also stimulate a receptor, shared with thromboxane A2, mediating platelet aggregation and vasoconstriction. METHODS: New Zealand White rabbits were subjected to 30 min of coronary occlusion, followed by 5.5 h of reperfusion. Fifteen minutes before reperfusion, the animals were randomized to receive 1) saline solution (control animals, n = 8); 2) SQ 29548, a potent and selective thromboxane A2/PGH2 receptor antagonist (n = 8); 3) dazoxiben, a selective thromboxane A2 synthase inhibitor (n = 8); 4) R 68070 (Ridogrel), a drug with dual thromboxane A2 synthase-inhibiting and thromboxane A2/PGH2 receptor-blocking properties (n = 8); or 5) aspirin + R 68070 (n = 8). RESULTS: Dazoxiben and R 68070, but not SQ 29548, significantly reduced thromboxane B2 formation and increased plasma levels of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha. Ex vivo platelet aggregation induced by U46619 (a thromboxane A2 mimetic) was inhibited by SQ 29548 and R 68070 but not by dazoxiben. In control animals, infarct size determined at the end of the experiment by triphenyltetrazolium chloride staining averaged 57.7 +/- 3.2% of the area at risk of infarction. The administration of SQ 29548 did not significantly reduce infarct size compared with that in control animals, whereas dazoxiben and R 68070 significantly reduced infarct size to 36.7 +/- 2.8% and 16.6 +/- 3.6% of area at risk of infarction, respectively (p < 0.001 vs. control values). In rabbits treated with R 68070, infarct size was also significantly smaller than that of dazoxiben-treated rabbits (p < 0.01). This protective effect of R 68070 was completely abolished when the drug was administered with aspirin, infarct size in this group averaging 59.7 +/- 1.6% (p = NS vs. control values). No differences in regional myocardial blood flow, systemic blood pressure, heart rate or extent of area at risk were observed among groups. CONCLUSIONS: Thus, prostaglandin endoperoxides play an important role in modulating the cardioprotective effects of thromboxane A2 synthase inhibitors. The simultaneous inhibition of thromboxane A2 synthase and blockade of thromboxane A2/PGH2 receptors by R 68070 identify a pharmacologic interaction of potential therapeutic importance.

Animals↗

PubMed1993

Evaluation of myocardial perfusion and function by technetium-99m methoxy isobutyl isonitrile before and after percutaneous transluminal coronary angioplasty. Preliminary results.

Myocardial perfusion and function were evaluated with Tc-99m MIBI myocardial scintigraphy before and after percutaneous angioplasty in six patients. In addition to conventional stress-rest images (3 projections: 45 degrees left anterior oblique, anterior, and left lateral), gated images were obtained at rest and during stress before and after angioplasty. Improvement in myocardial perfusion after angioplasty was demonstrated in all patients. The increase from rest to stress of radionuclide fractional shortening (an index of global left ventricular function computed on gated images) was greater after angioplasty than before (9% +/- 7% versus--0.5% +/- 8%, respectively, p < 0.05). Systolic wall thickening (an index of regional left ventricular function) showed a significantly greater rest-to-stress increase after angioplasty than before it in the regions supplied by treated vessels. Thus, Tc-99m MIBI myocardial scintigraphy is capable of evaluating myocardial perfusion and function.

Angioplasty, Balloon, Coronary↗

PubMed1993

Effects of calcium antagonists on left ventricular structure and function.

Effects of calcium antagonists on left ventricular hypertrophy: The goals of antihypertensive treatment are to lower systemic blood pressure and to reverse left ventricular hypertrophy. A number of different drugs can induce a decrease in left ventricular mass, some of which are calcium antagonists. In particular, verapamil, diltiazem and a number of dihydropyridines (nifedipine, isradipine, lacidipine) have proved effective in this respect. Left ventricular systolic function: Left ventricular systolic function is often normal at rest in patients with hypertension, but is quite commonly abnormal during exercise. Calcium antagonists therefore do not affect resting systolic function in this category of hypertensive patients. In contrast, in hypertensive patients with heart failure the administration of dihydropyridines improves systolic performance. Left ventricular diastolic function: Isovolumic relaxation and rapid filling are often impaired in patients with hypertension, with or without left ventricular hypertrophy. Verapamil is effective in abolishing this diastolic dysfunction when given intravenously; in contrast, medium-term therapy with calcium antagonists such as diltiazem or dihydropyridines does not improve left ventricular filling properties. However, when antihypertensive therapy achieves a reduction in left ventricular mass, a consistent improvement in diastolic properties occurs.

Antihypertensive Agents↗

PubMed1993

Platelet aggregability in patients with a VVI pacemaker.

Several studies have suggested an increased incidence of thromboembolic events in patients with VVI pacemaker (VVI patients); furthermore, other authors have demonstrated that a treatment with anticoagulants or antiplatelet drugs may be effective in reducing thromboembolic events, thus suggesting an increased formation of platelet thrombi in these patients. In this respect, platelet aggregability was investigated in ten VVI patients and ten age- and sex-matched subjects. beta-thromboglobulin (beta-Tg) and platelet factor 4 (PF4) plasma levels were determined as well as platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid. Plasma beta-Tg levels were increased in the patient group (86 +/- 24 vs 24 +/- 13 ng/mL; P < 0.001) in presence of normal PF4 values (14 +/- 11 vs 13 +/- 6 ng/mL; NS). Aggregation curves showed abnormal values of maximal amplitude, slope, and lag time. In particular, maximal amplitude was significantly higher in VVI patients as compared with controls (ADP P < 0.01, collagen P < 0.001, adrenaline P < 0.01, arachidonic acid P < 0.05). These findings strongly suggest an increase of platelet activity in VVI patients.

Adenosine Diphosphate↗

PubMed1993

Angiotensin II directly stimulates release of atrial natriuretic factor in isolated rabbit hearts.

BACKGROUND: Previous studies have shown that infusion of angiotensin II (Ang II) increases plasma concentrations of atrial natriuretic factor (ANF) in vivo. This phenomenon has been considered secondary to the effects of Ang II on cardiac and systemic hemodynamics. The present study was designed to assess whether Ang II may exert a direct stimulatory effect on ANF release from the heart independent of changes in hemodynamics. METHODS AND RESULTS: Isolated rabbit hearts were perfused in the Langendorff mode. Heart rate, coronary flow, and atrial and left ventricular (LV) volumes were kept constant. After stabilization, Ang II was infused intracoronary at increasing doses (10(-11) to 10(-8) M) in nine hearts and at a single dose of 10(-10) M in 10 hearts. Each infusion lasted for 5 minutes and was followed by a 10-minute washout period. Four hearts received vehicle alone for 80 minutes. Ang II induced a dose-dependent increase in coronary perfusion pressure and in LV developed pressure. ANF release, measured by radioimmunoassay on the extracts of the cardiac effluent, also increased during Ang II infusion and returned to the basal values during the 10-minute washout period. In the control group, coronary perfusion pressure, LV developed pressure, and LV end-diastolic pressure did not change appreciably over the observation period, whereas ANF release progressively decreased during perfusion. CONCLUSIONS: Ang II can directly stimulate cardiac release of ANF in isolated rabbit hearts independently of changes in hemodynamics.

Analysis of Variance↗

PubMed1993

Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation.

BACKGROUND: Platelet activating factor (PAF) is a phospholipid released upon stimulation by a variety of cells and has been implicated in several pathophysiological events such as asthma and inflammatory diseases. However, although the ability to aggregate platelets in vitro was the first biological activity ascribed to PAF, its role in contributing to the in vivo formation of arterial thrombi has not been thoroughly clarified. METHODS AND RESULTS: Intravascular platelet aggregation was initiated in two different animal models of arterial stenosis and endothelial injury. An external constrictor was positioned around rabbit carotid arteries and canine coronary arteries. After placement of the constrictor, a typical pattern of flow developed in the stenotic vessels. This pattern of flow, characterized by progressive reductions of carotid or coronary blood flow followed by spontaneous or induced restorations of flow (cyclic flow variations, CFVs), is related to recurrent platelet aggregation at the site of the stenosis followed by dislodgment of the thrombus. After observing CFVs for 30 minutes, BN52021 (up to 1.2 mg/kg), a potent and selective PAF antagonist, was given intravenously to rabbits (n = 12) and dogs (n = 10). BN52021 completely inhibited CFVs in 10 of 12 rabbits, whereas it was relatively ineffective in abolishing CFVs in dogs (only 2 of 10 animals inhibited). This different effect of BN52021 was not explained by too small a dose of the drug to achieve a complete blockade of PAF receptors in dogs, since ex vivo platelet aggregation was completely inhibited in both rabbits and dogs in response to exogenous PAF at concentrations up to 10(-5) mol/L. In a second group of 10 dogs, the hypothesis that PAF may become an important mediator of CFVs in dogs only several hours after endothelial injury was tested. After 30 minutes of baseline CFVs, these animals received a bolus of BN52021 up to 1.2 mg/kg. After this treatment, CFVs were completely abolished in 2 of 10 animals. The remaining 8 dogs were followed for an additional 8-hour period, at the end of which a second bolus of BN52021 was given. At this time, BN52021 was effective, as CFVs were abolished in 6 of 8 animals. These effects of BN52021 at 8 hours were not the consequence of a cumulative dose of the compound, since ex vivo platelet aggregation in response to PAF returned to baseline values immediately before administering the second dose. To identify possible sources of PAF other than aggregating platelets at the site of arterial stenosis, dogs in a third group were killed after 30 minutes (n = 7) and after 8 hours (n = 8) of CFVs. Histological sections of the stenotic coronary artery showed a marked leukocyte infiltration in these arterial segments after 8 hours of CFVs, whereas sections from dogs killed after 30 minutes showed only moderate or no infiltration. CONCLUSIONS: These data demonstrate that PAF plays an important role as a mediator of platelet aggregation in vivo in rabbits and dogs. In the canine model, PAF appears to become more important after leukocyte infiltration of the arterial wall, as it may contribute to initiating enough platelet activation to lead to cyclic flow variations at sites of arterial stenosis and endothelial injury. Data from the present study suggest that PAF antagonists may be used as antiplatelet agents.

Animals↗