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Biomedical subjects

S Chierchia

Publications and source records attributed to S Chierchia.

At least 73 records · Page 4Linked to original sources
PubMed1985

Mixed angina pectoris.

Patients who present with episodes of angina caused both by an increase in oxygen demand and by transient impairment of supply have a mixed form of angina. Distinctive clinical features allow the classification of patients in everyday practice. At one end of the spectrum are patients who have angina only and always when they exercise beyond an essentially fixed level; their angina is fairly predictable and has been termed secondary angina. At the other end of the spectrum are patients who have a normal exercise tolerance but have angina at rest or during activities usually well tolerated that must be caused by a transient impairment of coronary blood flow; their angina is typically unpredictable and has been termed primary angina. We adopted the term primary to emphasize the possible existence of multiple causes of impairment of coronary flow, which together are to be contrasted with the traditional prevailing concept of angina being secondary to excessive increase in demand. In between these ends of the spectrum are most of the patients with angina pectoris encountered in clinical practice: they have a rather predictable ceiling of exercise that they cannot exceed without developing angina, but they also have a variable proportion of unpredictable anginal attacks that occur spontaneously or at levels of activity that are usually well tolerated. We introduced the concept of mixed forms of angina when we became aware that the same patient could experience angina both as a result of an excessive increase in myocardial demand, i.e., secondary angina, and as a result of the transient impairment of coronary blood flow supply, i.e., primary angina.

Angina Pectoris↗
PubMed1985

Mechanisms of ischemic cardiac pain and silent myocardial ischemia.

The mechanisms of cardiac ischemic pain remain obscure. It is unknown whether ischemia causes cardiac pain by the release of chemical substances or by mechanical stretching. It is also unknown whether ischemia activates specific nociceptors and pain fibers or mechanoreceptors and chemoreceptors. In patients who have both painful and painless ischemic episodes, a certain minimal duration and severity of ischemia are necessary but insufficient to explain the presence of pain, since very severe ischemia of long duration can be silent. Thus, central transmission of painful stimuli and the pain perception threshold appear to play major roles in determining the presence or absence of pain. The emotional state and psychologic expectations of patients may affect their perception and threshold of pain considerably.

Angina Pectoris↗
PubMed1985

Different susceptibility to myocardial ischemia provoked by hyperventilation and cold pressor test in exertional and variant angina pectoris.

Coronary constriction at the site of atherosclerotic stenoses has been suggested to play an important role in modulating the frequency of symptoms in patients with exertional angina. To investigate whether stimuli triggering coronary constriction have similar effects in patients with exertional and variant angina, responses to hyperventilation (HV) and cold pressor test (CPT) were evaluated. Twenty patients with chronic exertional angina, positive exercise test results and coronary heart disease were compared with 14 patients with variant angina and ST-segment elevation during an ergonovine test. In patients with exertional angina, the CPT produced diagnostic ST-segment depression in 6 of 20 patients (30%) at levels of rate-pressure product much lower than those during the exercise test; all patients had low effort tolerance and severe coronary artery disease. HV produced diagnostic ST-segment depression in only 1 of 20 patients (5%) (p less than 0.05 compared to that with CPT). Conversely, in patients with variant angina, HV produced ST-segment elevation in 11 of 14 patients (78%) and CPT produced elevation in only 2 of 14 (14%) (p less than 0.01). Thus, coronary constriction can provoke myocardial ischemia not only in patients with variant angina but also in some patients with exertional angina. Furthermore, the 2 groups of patients have a different susceptibility to stimuli known to produce coronary constriction.

Adult↗
PubMed1985

Improved coronary supply: prevailing mechanism of action of nitrates in chronic stable angina.

Exercise tolerance before and after sublingual isosorbide dinitrate (ISDN), 10 mg, was assessed in 217 consecutive patients with stable angina, positive exercise test, and angiographically proved coronary artery disease. In 65 patients (30%), ISDN prevented exercise-induced ST segment depression and/or increased exercise time to 1 mm ST segment depression (greater than or equal to 3 minutes), despite the significantly higher (greater than or equal to 25 X 10(2) increment) rate-pressure product attained (increased coronary reserve). On the contrary, in 40 other patients, exercise test remained positive, and neither time to 1 mm ST segment depression nor rate-pressure product increased significantly (fixed coronary reserve). The remaining 106 patients had an intermediate response. To assess the mechanisms underlying the beneficial action of nitrates, we further investigated 13 patients with increased coronary reserve (group 1) and five with fixed coronary reserve (group 2) by the exercise response to ISDN and verapamil, the changes in left ventricular volumes after ISDN and verapamil, the ECG response to intravenous ergonovine, and the changes in coronary stenosis severity following intravenous ergonovine and intracoronary nitrates. ISDN dramatically improved exercise capacity only in group 1 patients. However, it induced a significant reduction of left ventricular volumes in both groups (p less than 0.01). Ergonovine provoked angina and ST segment depression in 62% of group 1 patients and significantly increased the severity of their coronary stenoses (p less than 0.01). In all group 2 patients, ergonovine was negative, and no significant increase in stenosis severity was observed. Intracoronary nitrates reduced stenosis severity in group 1 (p less than 0.01) but not in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Influence of the chosen model of stenosis on pressure-flow relationships in isolated perfused arteries.

Passive changes in luminal diameter caused by a fall in the intravascular distending pressure at the site of a severe coronary artery stenosis were recently proposed as a possible cause of transient myocardial ischaemia. We tested this hypothesis in 5 dog carotid arteries perfused with blood at a constant inflow (100 mm Hg) and variable outflow pressures (40-0 mm Hg). Similar degrees of stenosis were induced either with an external circumferential snare or with an intravascular fluid-filled balloon catheter. In 39 experiments outflow pressure was progressively decreased from 40 to 0 mm Hg. This was done first in the absence of stenosis, secondly with an external stenosis (snare) and finally with an internal stenosis of comparable severity (fluid-filled balloon). When stenosis was absent or intraluminal, flow increased progressively from 109.1 +/- 39 to 136 +/- 55 ml/min (P less than 0.06) and from 23 +/- 16 to 34.2 +/- 16 ml/min (P less than 0.001), respectively. Resistance also rose because flow increased proportionally less than the pressure gradient. Conversely, when stenosis was produced by a snare, flow decreased progressively, from 23.9 +/- 17 to 10.7 +/- 15 ml/min (P less than 0.001). Assuming the reduction of flow was caused by the external stenosis compressing the wall into the lumen (against the intravascular pressure) we prepared an artificial vessel with a foam rubber wall inside a silastic tubing. In this artificial vessel (but not in a glass model) a snare stenosis caused reduction in flow when outflow pressure was lowered. Passive changes in caliber due to a reduced distending pressure do not therefore appear to be a cause of flow reduction.

Animals↗
PubMed1984

Role of heart rate in pathophysiology of chronic stable angina.

11 patients with chronic, stable, effort angina, off medication apart from glyceryl trinitrate, were monitored continuously by electrocardiogram (ECG) during normal, unrestricted daily activity. Computerised ECG analysis demonstrated during 33 twenty-four hour periods of monitoring, 278 episodes of transient ischaemic ST segment depression of which 52 were associated with angina. In the 15 minutes preceding the onset of ischaemia, heart rate did not increase in 164 episodes, increased slightly (greater than or equal to 5 beats/min) in 61, and increased moderately or markedly (greater than or equal to 10 beats/min) in 53. Findings were similar when episodes with or without angina or episodes of different severity were analysed separately. In all patients, periods of sinus tachycardia exceeding the control rate by more than 30 beats/min and lasting more than 10 minutes, often occurred in the absence of angina and/or ST segment depression. Also, in 65% of the ischaemic episodes, heart rate at the beginning of the ST change was either below or less than 10 beats/min above the modal value of the twenty-four hour heart rate. This suggests that increased myocardial demand is not necessarily the only or the most common cause of acute ischaemia in patients with chronic effort angina during unrestricted daily activity. Factors which only transiently interfere with myocardial oxygen supply are probably important in this syndrome.

Aged↗
PubMed1984

Inhibition of platelet function by injectable isosorbide dinitrate.

The possibility that isosorbide dinitrate (ISDN) inhibits platelet function in humans has been explored in vitro and in vivo. Incubation of citrated platelet-rich plasma from healthy subjects with scalar concentrations (1.25, 12.5 and 125 micrograms/ml) of ISDN for 5 and 10 minutes resulted in a decrease in platelet aggregation after ADP, adrenaline, and arachidonic acid at the highest drug concentration (mean decrease: 72% [p less than 0.01], 56% [p less than 0.05] and 62% [p less than 0.05], respectively, with the 10-minute incubation). Also, a significant reduction (30%) in generated thromboxane (TX)B2 levels was observed after arachidonic acid (p less than 0.01). ISDN was then infused at rate of 4 mg/hour for 30 minutes in 11 patients with angina and at a rate of 30 mg/hour for 20 minutes in 8. The smaller dose, which caused minor changes in arterial pressure and heart rate, was accompanied by a marked, significant decrease in ADP- and adrenaline-induced aggregation, with a nadir at 60 minutes from the infusion stop (decreases of 40% and 51% respectively). Circulating platelet aggregates also decreased, with a minimum (-41%, p less than 0.05) at the end of the infusion. The higher infusion rate, causing marked hemodynamic effects, was not accompanied by the occurrence of clear antiplatelet effects. Thus, ISDN can affect platelet function both in vitro and in vivo. The in vivo effect occurs at lower concentrations than in vitro but is blunted when a marked hemodynamic response occurs.

Adenosine Diphosphate↗
PubMed1984

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation.

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF4), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGI2) (2 to 8 ng/kg/min) on PF4, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF4, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGI2 infusion resulted in a significant decrease of PF4 at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF4 levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF4 levels. The value of PF4 coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 +/- 28.9 vs 4.2 +/- 3.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Computer system for analysis of ST segment changes on 24 hour Holter monitor tapes: comparison with other available systems.

The accuracy of a computer system that was developed for the analysis of ST segment changes recorded on Holter ambulatory electrocardiographic monitoring tapes was compared with conventional visual scrutiny, beat by beat analog printouts and a commercial J point trend system. The program calculates and plots multiple electrocardiographically derived variables in a high temporal resolution trend format. Fifty tapes of good recording quality obtained from 19 patients (13 with chronic stable angina and 6 with variant angina) were assessed visually and with the computer system; of these, 20 were analyzed by all four techniques. In the 50 tapes, 629 episodes of diagnostic ST segment changes (all true positive results) were identified by using the computer system. In contrast, only 507 were identified by visual scrutiny; none of these 507 episodes was missed by computer analysis. On the 20 tapes assessed using computer, visual, beat by beat analog and J point trend system analysis, 268, 221, 230 and 178 episodes, respectively, were documented. For the four techniques, false negative and positive results were 0, 47, 38 and 90 and 0, 10, 6 and 24, respectively. The results indicate that, of the systems assessed in this study, the computer program provides the highest accuracy for detection of transient ST segment changes. This is probably accreditable to the compact presentation of multiple electrocardiographically derived variables, allowing a detailed quantitative assessment of 24 hour tapes. It is of particular value for pathophysiologic and pharmacologic studies.

Angina Pectoris↗
PubMed1984

Ouabain-induced reflex coronary vasodilatation mediated by cardiac receptors.

Experiments were performed to determine the effects of digitalis-induced stimulation of cardiac receptors on the coronary circulation. In chloralose-anesthetized dogs, left circumflex coronary artery was perfused at constant flow, and heart rate was maintained constant by electric pacing. Ouabain injection in the perfused coronary artery produced a significant decrease in coronary perfusion pressure. Epicardial application of lidocaine completely blocked the reflex response. Vagotomy also prevented this reflex response. Sympathetic blockade with intravenous guanethidine or intracoronary phentolamine partially reduced the reflex coronary vasodilatation. Intracoronary atropine also partially reduced the coronary vasodilator response to ouabain. The combined administration of guanethidine and atropine completely abolished the coronary reflex response. These data demonstrate that ouabain can evoke reflex coronary vasodilation by stimulating cardiac receptors. This reflex response is mediated by activating cholinergic vasodilator fibers and inhibiting sympathetic vasoconstrictor fibers.

Animals↗
PubMed1984

alpha-Adrenergic receptors and coronary spasm: an elusive link.

In 14 consecutive patients with variant angina we investigated the possible role of coronary alpha-adrenergic receptors in the genesis of coronary spasm. In eight patients, computerized, beat-by-beat analysis of the electrocardiogram recorded during continuous Holter monitoring failed to reveal any increase of heart rate and corrected QT interval (both indexes of cardiac sympathetic activation) in the period preceding the onset of ST segment changes in 197 episodes of ischemia caused by coronary spasm. In the same patients, analysis of the circadian distribution of ischemic episodes revealed a significantly higher incidence in the early morning hours, when sympathetic activity is at the lowest level. Twelve patients underwent serial provocative testing with cold pressor, phenylephrine, or norepinephrine infusion and administration of ergonovine maleate. Ergonovine consistently reproduced coronary spasm in all 12 patients, while results of cold pressor testing were positive in only one. Infusion of phenylephrine (eight patients) or norepinephrine after beta-blockade (four patients) failed to precipitate myocardial ischemia. In five patients infusion of phentolamine at the highest tolerated dose did not reduce significantly the number of ischemic attacks when compared with placebo. In contrast to results of previous reports, our data seem to rule out the hypothesis that an increase of sympathetic outflow to the heart plays an important role in the genesis of coronary spasm. We cannot, however, exclude the possibility of localized alpha-stimulation of epicardial arteries.

Adult↗
PubMed1984

Myocardial ischemia during ergonovine testing: different susceptibility to coronary vasoconstriction in patients with exertional and variant angina.

Coronary spasm is an accepted cause of transient myocardial ischemia in patients with variant angina; more recently it has been suggested that dynamic stenoses could also play an important role in the pathophysiology of exertional angina. To test this hypothesis we submitted 31 patients with histories typical of exertional angina to ergonovine testing and compared the electrocardiographic and clinical responses to those observed in seven patients with variant angina. All underwent bicycle ergometric exercise testing and coronary angiographic examination. For all tests, ST segment shifts of 0.1 mV or greater were considered to be diagnostic of myocardial ischemia. In patients with exertional angina, exercise testing produced diagnostic ST segment depression in 21 (68%). Ergonovine testing produced diagnostic ST segment depression in nine (29%). All nine had positive exercise test results and two- or three-vessel disease, yet the test was negative in seven other patients with positive exercise test results and similar angiographic findings. Conversely, in the seven patients with variant angina, results of exercise testing were positive in five (ST segment depression in two, ST elevation in three), while ergonovine produced ST segment elevation in all seven. Coronary angiographic examination showed normal arteries in two, one-vessel disease in four, and three-vessel disease in one. Results of all ergonovine tests were positive at values of rate pressure product much lower than those observed during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Ergonovine-induced myocardial ischemia: no role for serotonergic receptors?

Because ergonovine appears to produce coronary contractions by a serotonergic (5-HT) mechanism, we attempted to prevent ergonovine-induced ischemia in patients with vasospastic angina by pretreatment with ketanserin, a new selective 5-HT blocker. We studied seven patients with consistently positive results of ergonovine testing (ST segment elevation in three and ST segment depression in four). Ergonovine testing was performed before and after a bolus of 10 mg of ketanserin (all patients) and infusion of 2 to 4 mg/hr for 8 hr (six patients). To assess 5-HT blockade during ketanserin infusion, the constrictor response of hand veins to 5-HT was tested before and after ketanserin. Despite evidence of 5-HT blockade in hand veins, ergonovine-induced ischemia was not prevented by ketanserin in any patient, and there was no significant change in the dose of ergonovine required to provoke ischemia. In one patient, four spontaneous episodes of ST segment elevation occurred during infusion of ketanserin. The plasma concentrations of ketanserin at the time of ergonovine testing ranged from 61 to 127 ng/ml (mean 102) and were well above those that completely inhibit canine coronary 5-HT contractions in vitro. Although human coronary arteries may differ in their responsiveness to 5-HT or ketanserin, these data suggest that ischemia from ergonovine-induced coronary vasospasm is not mediated by 5-HT receptors.

Aged↗
PubMed1983

Myocardial ischaemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes.

In thirty patients with stable angina and positive exercise tests, ambulatory ST segment monitoring was used to record episodes of transient myocardial ischaemia during daily life. All patients had four consecutive days of monitoring and in 20 patients long-term variability was assessed by repeated 48 hour monitoring and exercise testing over 18 months. There were 1934 episodes of rectilinear or downsloping ST-depression (911, 1 mm; 638, 2 mm; 385, greater than 3 mm) in 446 days of recording, of which only 470 (24%) were accompanied by angina. Positron tomography showed evidence of regional myocardial ischaemia during both symptomatic and asymptomatic ST depression. On average, heart rate at the onset of both symptomatic and asymptomatic ST episodes was significantly lower than the rate at the onset of ST depression during exercise testing (98 +/- 20.5 vs 124 +/- 17 beats/minute). Heart rate rose by more than 10 beats in the minute preceding ST depression in only 23% of episodes. Over 18 months, 8 (40%) patients exhibited marked variability in the number of daily ST episodes. Variability of ST depression was consistently underestimated by symptoms and not reflected by exercise testing. Thus, patients with stable angina showed frequent, variable, and often asymptomatic electrocardiographic evidence of ischaemia. Heart rate increase was not common before myocardial ischaemia, suggesting that, in such patients, transient impairment in coronary supply may be at least as important as excessive increase in demand in the genesis of ischaemia during daily life.

Activities of Daily Living↗
PubMed1983

Variable susceptibility to dynamic coronary obstruction: an elusive link between coronary atherosclerosis and angina pectoris.

Growing evidence suggests that dynamic coronary obstructions play an important but elusive role in the genesis of ischemic events. Dynamic coronary obstructions can develop during certain phases of coronary disease as a result of a variable combination of vasoconstriction, arterial wall lesions, and increased thrombotic tendency. In a certain phase of their disease some patients develop dynamic coronary obstruction, while others with a similar degree of fixed atherosclerotic obstruction do not.

Angina Pectoris↗