Clinical course of lone atrial fibrillation since first symptomatic arrhythmic episode.
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Biomedical subjects
Publications and source records attributed to G Gensini.
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On the basis of indirect pharmacological evidence, picotamide, a methoxy derivative of 4-hydroxy-isophthalic acid (N,N'bis(3-picolyl)-4-methoxy-isophthalamide) has been postulated to inhibit platelet aggregation by competitively interfering with the thromboxane A2 (TxA2) platelet receptor. In the present study the interaction between picotamide and TxA2 receptors on human platelets was investigated by a direct radioligand assay method with [125I]PTA-OH and [3H]U46619 as labelled radioligands. The ONO11120 and U46619 inhibitory constants (Ki) for [125I]PTA-OH binding were 19 +/- 4 and 17 +/- 3 nM, respectively. Picotamide displaced [125I]PTA-OH binding with a Ki of 1472 +/- 321 nM. The Ki for ONO 11120 and U46619 on [3H]U46619 binding were 42 +/- 12 and 16 +/- 5 nM, respectively, whereas the Ki for picotamide was 1648 +/- 431 nM. These data provide evidence that picotamide can directly inhibit the TxA2 platelet receptor.
The acute hemodynamic effects of intravenously administered celiprolol and propranolol were compared in 18 patients, 12 with coronary obstruction in the presence or absence of reduced LV function and six with no significant cardiac disease. The study was performed using a single blind, randomized design with celiprolol (0.07 and 0.14 mg/kg) and propranolol (0.07 mg/kg) in six patients per treatment group. The hemodynamic parameters obtained via right and left heart catheterization were measured at baseline and at 5 and 10 min after drug infusion (1.0 mg/min). Propranolol produced a significant fall in left ventricular Vmax, left ventricular dP/dt and cardiac output. In contrast, celiprolol either caused no change or significantly increased these parameters. These results indicate that celiprolol has an acute hemodynamic profile which differs significantly from that of propranolol.
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The hemodynamic effects of indapamide were evaluated in an open clinical trial of nine patients with mild to moderate hypertension. Hemodynamic and echocardiographic measurements were made before and after six weeks of treatment with single daily doses of 2.5 mg of indapamide. Indapamide significantly reduced the mean standing systolic blood pressure (P less than 0.025), the mean standing diastolic blood pressure (P less than 0.01), the mean arterial blood pressure (P less than 0.001), and the mean total peripheral vascular resistance (P less than 0.01). Cardiac output increased 12% (P less than 0.05) during treatment. The heart rate, left ventricular end-diastolic and end-systolic volumes, systolic volume, and ejection fraction were not markedly altered after treatment with indapamide, although the systolic wall stress index fell slightly. Six weeks of indapamide administration was well tolerated with no notable adverse effects of the drug. The results suggest that indapamide reduces arterial blood pressure in hypertensive patients by decreasing total peripheral resistance.
We studied 42 subjects, each of whom demonstrated significant (greater than or equal to 50%) narrowing of a non-grafted coronary artery and a baseline cholesterol level greater than 250 mg%. All patients underwent repeat scheduled coronary arteriography after 2 years on the study. Twenty-five colestipol responders (cholesterol levels reduced at least 15% within 1 month of therapy) were compared to 17 non-responders who were given 23 months of placebo after a 1 month exposure to colestipol. Baseline risk factors and demographic characteristics were similar for the two groups. In comparison to baseline arteriography, only 3 of the 25 drug-treated patients showed progression, while 8 of 17 placebo treated patients demonstrated progression (P = 0.011). Drug-treated patients demonstrated a 20% decrease in cholesterol levels, while placebo patients did not experience a significant reduction in cholesterol levels. Our study suggests that significant reduction in serum cholesterol levels is associated with a reduced likelihood of progression of coronary atherosclerotic lesions assessed by scheduled repetitive coronary arteriography in hyperlipidemic subjects demonstrating significant coronary artery narrowing on their initial arteriograms.
The authors review the methods currently used for platelet aggregation testing, which are mainly grouped in two classes: 1. methods measuring the sensitivity of platelets to aggregating agents and to mechanical stimulation in vitro and 2. methods measuring the spontaneous tendency of platelets to aggregate in vivo. Their advantages, their pitfalls and their potential usefulness are reported. The platelet behavior as assessed by the available methods is not strictly related to the true platelet behavior in circulating blood. Therefore much criticism is requested in the interpretation of the results obtained for a given group of subjects with a given method and any unallowed extrapolation must be avoided.
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One hundred nineteen patients with coronary artery disease confirmed by coronary arteriograms were studied. Cine coronary arteriography confirmed progression of atherosclerosis in 106 (89%) patients (mean age 50.9 yr) and nonprogression in 13 (11%) patients (mean age 50.3 yr). Progression was defined as follows: any increase to 50% stenosis, 50% to 75% narrowing, 75% to 90%, 90% to 99%, 99% to total occlusion. Only one patient of the 106 who progressed (less than 1%) had ideal values for both cholesterol and triglyceride. Three of 13 patients (23%) who did not progress had ideal lipid values (P less than 0.005). Fifty four of 106 patients who progressed had cholesterol levels greater than or equal to 250 mg%; none of 13 patients who did not progress had such levels (P less than 0.005). Thirty-nine of 98 (40%) patients who progressed had hypertension; only one (8%) who did not progress had hypertension (P less than 0.025). Seventy-four of 96 patients who progressed were smokers (77%); two of 13 nonprogression patients smoked (15%) (P less than 0.005).
Twelve cases of myocardial infarction as related to strenuous exertion are presented with the pathological findings in several of these cases. Three cases with coronary arteriography are also presented. The pathology of coronary arteriosclerotic plaques and the vulnerability to acute injury is reviewed and discussed. It is concluded that strenuous exertion can cause acute injury to coronary artery plaques due to the unusual stressful whip-like action to which coronary arteries are subject. These injuries may initiate as cracks in the plaques or subintimal hemorrhages and proceed to coronary occlusion and ultimate myocardial infarction. With this concept in mind we use the term of "crack in the plaque" (Black's Crack in the Plaque) to account for the sudden appearance of clinical coronary artery disease appearing during or shortly after exertion, or other stressful situations in patients without previous existing evidence of clinical coronary artery disease. This could also account for exacerbation of symptoms or death occurring after exertion in previously quiescent asymptomatic known coronary artery disease subjects. This concept may explain some of the puzzling features of coronary disease.
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