Effects of histamine on coronary hemodynamics in humans: role of H1 and H2 receptors.

To evaluate whether histamine exerts a direct effect on coronary hemodynamics in humans, and to investigate the role played by H1 and H2 receptors in this response, intracoronary saline solution or histamine (4 micrograms) was administered in 10 patients with normal coronary arteries during diagnostic cardiac catheterization. Histamine injection was repeated after intravenous cimetidine (400 mg) and diphenhydramine (10 mg). The electrocardiogram, arterial pressure and thermodilution coronary blood flow were continuously monitored during and for 40 seconds after each injection. Immediately after histamine injection there was a significant increase in coronary blood flow (65 +/- 6%) and a decrease in coronary vascular resistance (-40 +/- 3%) (both p less than 0.001), with minor changes in the RR interval and the mean arterial pressure. H2 receptor blockade with cimetidine did not affect these changes, while H1 receptor blockade with diphenhydramine significantly reduced the histamine-induced increase in coronary blood flow and the decrease in coronary vascular resistance (26 +/- 6%, p less than 0.005 and -18 +/- 5%, p less than 0.001, respectively). Twenty to 30 seconds after histamine injection, a significant decrease in mean arterial pressure (-17 +/- 2%, p less than 0.001) and in the RR interval (-4 +/- 1%, p less than 0.01) was observed. These changes persisted after H2 receptor blockade with cimetidine, but were completely abolished after H1 receptor blockade with diphenhydramine. In each case coronary and systemic hemodynamics returned to normal within 40 seconds of the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of aging on electrical, mechanical, and coronary modification induced by ouabain and epinine in isolated rat heart.

OBJECTIVE: The contractile response to digitalis and beta adrenoceptor agonists is lower in the senescent than in the adult myocardium, while the development of ventricular arrhythmias is increased. The aim of this study was to examine the effects of aging on cardiac response to digitalis and an adrenergic agonist used clinically. METHODS: The electrical and mechanical responses were tested in isolated and perfused hearts from 3-24 month old rats receiving 15 min infusion of digitalis drug (ouabain, 6 x 10(-5) M) alone, and after 5 min of beta adrenoceptor agonist drug (epinine, 1.5 x 10(-7) M). RESULTS: Ouabain action was associated with a rise in left ventricular end diastolic pressure (p < 0.01) which increased progressively with aging, and with an elevation of left ventricular developed pressure (p < 0.01) which decreased progressively with aging. Epinine induced a reduction of left ventricular end diastolic pressure (p < 0.01) and a rise in left ventricular developed pressure (p < 0.01) but both effects decreased progressively with aging. Ouabain reduced coronary flow and this decrease was more pronounced with aging (p < 0.01), while epinine caused an increase (p < 0.01) that diminished in older hearts. Ouabain given after epinine resulted in a greater increase in left ventricular end diastolic pressure than epinine (p < 0.01) but lower than that caused by ouabain alone (p < 0.01), a greater increase in left ventricular developed pressure than epinine and ouabain (p < 0.01), and a smaller reduction of coronary flow rate than ouabain alone (p < 0.01). All these effects, however, diminished progressively with aging. Arrhythmia scores were higher during ouabain than in control (p < 0.01) and in epinine treated hearts (p < 0.01); pretreatment with epinine did not modify arrhythmia score during ouabain administration. The number and severity of arrhythmias, however, increased with aging in all groups. CONCLUSIONS: Aging has a negative effect on both the positive inotropic and the arrhythmogenic effects of ouabain and epinine, although these phenomena are more pronounced during ouabain administration. However, when the two drugs are given simultaneously, epinine does not modify the arrhythmogenic effect of ouabain but reduces some of its deleterious haemodynamic effects.

Changes of systolic time intervals in asymptomatic patients with primary hyperlipoproteinemia.

Previous studies have focused on the usefulness of systolic time intervals to assess changes of myocardial function. In a recent report, hyperlipoproteinemia (HLP) was shown to induce early signs of vascular disease in asymptomatic subjects. By means systolic time intervals (STI) we studied left ventricular functions in normal subjects and asymptomatic patients with HLP, who showed normal response to exercise on a bicycle ergometer. The results showed mean values of STI for the population in the normal range, according to standards accepted in North American reports. Different values of STI were found when we compared the data of controls with the STI of HLP patients with higher values of PEPI and PEP/LVET and lower values of LVETI in HLP patients. These results suggest that hyperlipoproteinemia affects STI in asymptomatic patients, probably as a sign of early impairment of left myocardial function.

QT/QS2 ratio as an index of autonomic tone changes.

The effects of changes in sympathetic tone on QT/QS2 ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS2 intervals in each test. In basal conditions, the QT/QS2 ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the QT/QS2 ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the QT/QS2 ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the QT/QS2 ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in QT/QS2 ratio. Therefore, the QT/QS2 ratio might represent a reliable index of sympathetic cardiac tone.

The cholinergic component in the reflex vasodilatation elicited by stimulation of the depressor nerves in the rabbit.

1 The effects of the stimulation of the cephalic endings of the depressor nerve on the resistance in the perfused hindlimb were studied in the rabbit. 2 The vasodilatation thus elicited in the perfused hindlimb was reduced either by administration of guanethidine or by sympathectomy and abolished by subsequent treatment with atropine. 3 These data confirm the existence of two components in the genesis of the reflex vasodilatation: a passive component, due to the inhibition of sympathetic discharge, and an active component which in the rabbit is cholinergic in nature.

Effects of age and hypertension on adrenoceptor-sensitivity evaluated with CD25 and QT/QS2.

BACKGROUND: We studied the effects of age and hypertension on responses to chronotropic dose (CD25) and standing-induced changes in the ratio of electrical systole (QT) to electromechanical systole (QS2) in order to identify their role on beta adrenoceptor sensitivity and to verify the value of QT/QS2 ratio as a noninvasive parameter of beta-adrenoceptor sensitivity. METHODS: We enrolled 33 normal subjects and 37 hypertensive patients (WHO stage I and II) (age range 21-82 years). RESULTS: CD25 was significantly age-related in normotensive and hypertensive subjects, whereas standing-induced QT/QS2 changes were age-related in normotensive subjects only When we divided subjects into three age groups, beta-adrenoceptor sensitivity was found to be lower in hypertensives than normotensives in the two groups under age 60, but was not affected in those over age 60. This suggests that hypertension influences beta-adrenoceptor sensitivity in younger subjects, but not in elderly patients, whose beta-adrenoceptor sensitivity is already reduced. CONCLUSIONS: CD25 does not predict standing-induced QT/QS2 ratio changes; therefore, during autonomic stimulation, QT/QS2 ratio seems not to be significantly related to beta adrenergic sensitivity.

Differences in blood pressure profile between young and elderly hypertensive patients.

We studied 40 subjects, 20 under 60 yrs old (10 normotensive and 10 hypertensive) and 20 over 60 yrs old (10 normotensive and 10 hypertensive). Each patient underwent a 24-hour ambulatory blood pressure monitoring (8:00 a.m. to 8:00 a.m.), by a noninvasive method using an ICR 5300 apparatus. Systolic blood pressure was significantly higher on random measurement and during the daytime in the older patients. Although comparison of the other parameters did not reveal significant differences, we noted a tendency to higher systolic values among the older group, and higher diastolic values in the younger one. The variability of the values was slightly higher, although not significantly, among the older patients. In both groups random systolic measurements, and in the younger group diastolic values as well, were significantly higher than mean 24 hour values. The incidence of abnormal systolic BP values ranged from 18.8% to 100% (mean 60.2% +/- 28.9) in younger hypertensives, and from 54% to 100% (mean 76.5% +/- 14.4) in older patients. The incidence of abnormal diastolic BP values ranged from 64.5% to 100% (mean 80.4% +/- 15.6) in younger patients and from 47.2% to 96% (mean 67.8% +/- 15.8) in older patients. The correlation between mean systolic and diastolic values recorded from 8:00 to 10:00 a.m., and mean 24-hour values was significant in young hypertensives, while in the older group there was a significant correlation only for diastolic BP. The lack of significance for systolic values is probably due to a greater variability in systolic pressure in elderly subjects during the morning.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive evaluation of autonomic tone changes during isometric exercise in normal subjects and in patients with coronary artery disease.

In order to evaluate the clinical implications of QT/QS2 ratio during manoeuvres of sympathetic stimulation we studied the effects of handgrip (75% of maximal voluntary contraction) in 18 middle-aged normal subjects and in 16 patients with previous myocardial infarction. We also evaluated the effects of propranolol (0.1 mg/kg i.v.) in all normal subjects and in 10 of the 16 patients with coronary artery disease. At rest the two groups had similar heart rate, blood pressure, QT, QS2 and QT/QS2 ratio values. A significant increase in heart rate and systolic blood pressure was recorded during handgrip both in normal subjects and in patients with coronary artery disease; QT/QS2 significantly increased in normal subjects but did not show significant variations in patients with coronary artery disease, with significant differences between the two groups at peak exercise. Handgrip-induced QT/QS2 changes showed a marked variability both in normal and diseased subjects. After propranolol, QT/QS2 showed no significant difference at peak exercise in the two groups. The variability of ratio changes was nullified by the administration of the drug. These findings suggest that handgrip-induced QT/QS2 changes might be an expression of beta-adrenergic discharge. The clinical value of handgrip-induced QT/QS2 changes in detecting patients with coronary artery disease is limited by the variability of the response of the ratio observed in the two groups.

Protective role of collaterals in patients with coronary artery occlusion.

We reviewed the clinical, hemodynamic and angiographic data of 105 patients with right coronary artery occlusion and 82 patients with left anterior descending coronary artery occlusion, subdivided into 3 groups by the presence and quality of collaterals to the occluded coronary (absent, poor or good collaterals). We found that patients with right coronary artery occlusion and good collaterals had a lower frequency of diaphragmatic myocardial infarction (60%) than patients with absent collaterals (100%) (P less than 0.01). In addition, in patients with old diaphragmatic myocardial infarction, both poor and good collaterals were associated with a lower frequency of severe asynergy of the diaphragmatic left ventricular segments at left ventriculography (54% and 14%, respectively), compared to patients with no collaterals to the right coronary artery (92%, P less than 0.02 vs. poor collaterals, P less than 0.001 vs. good collaterals). In contrast, in patients with left anterior descending coronary artery occlusion, the presence of either poor or good collaterals to the left anterior descending coronary artery was not associated with a lower frequency of old anterior myocardial infarction, or, in patients with old anterior myocardial infarction, with a less severe asynergy of the anterior left ventricular segments. Our results suggest that collaterals are effective in protecting the diaphragmatic left ventricular wall in patients with right coronary artery occlusion, but not the anterior left ventricular wall in patients with left anterior descending coronary artery occlusion.

Effect of oral captopril (SQ 14225) on intraocular pressure in man.

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril (SQ 14225) on intraocular pressure (IOP) were studied. Four groups were analyzed: group A, ten control subjects; group B, ten hypertensive patients with normal IOP; group C, ten normotensive patients with primary open angle glaucoma (POAG); and group D, ten hypertensive patients with POAG. Systolic and diastolic blood pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1-h intervals up to 3h after an oral dose of 25 mg captopril or placebo, given in a randomized, double-blind cross-over fashion. The alternative treatment was given a week later. Captopril significantly lowered IOP in all patients, with no effects on heart rate and pupil diameter. Blood pressure changed only in patients with hypertension (groups B and D). Total outflow facility, measured by conventional tonography, increased significantly in all groups. These findings indicate that oral captopril could represent a new antiglaucomatous compound.

Exercise tolerance as evidence of quality of life in CAD patients after coronary artery bypass by comparison with medical treatment.

The effects of coronary artery bypass (CAB) by comparison with medical treatment were evaluated on exercise tolerance in 68 patients with stable angina on effort, who underwent coronary and left ventricular cineangiography. Stress tests were performed by bicycle ergometer before medical and surgical treatment, and 6 and 12 months thereafter. Thirty-five patients (31 males and 4 females; 7 with one 70% stenosed vessel, 12 with two, 16 with three) underwent CAB; 33 (30 males and 3 females; 9 with one 70% stenosed vessel, 11 with two, 13 with three), having refused CAB, only underwent medical treatment. Both groups were given long-acting oral nitrates, none received digitalis and/or propranolol; antiarrhythmic drugs were only administered in 5% of medical and 4% of surgical patients. Both groups at 6 and 12 months follow-up showed a significant improvement in exercise tolerance. Surgical patients showed a significant increase in exercise tolerance with lower angina incidence (from the preoperative 100% to 26% and 22%, respectively), higher work load (P < .001), and a significant reduction of S-T segment depression (P < .001). Medical treatment induced an increase of exercise tolerance; angina on effort decreased (from 100% to 74% and 72%, respectively) with higher work load, and a significant reduction of S T depression (in both cases P < .001). Comparing the data of the two groups, we observed that surgical patients showed higher exercise tolerance (P < .01), lower S-T depression (P < .001) and angina incidence. Our results suggest that surgical treatment is able to improve exercise tolerance more remarkably than medical treatment.

Left ventricular function after coronary artery bypass. Non-invasive study by systolic time intervals.

Left ventricular function was evaluated with serial recording of STI intervals in 78 patients with stable angina on effort undergoing coronary and left ventricular cineangiography. On the basis of these data the patients were divided into four groups: OV) nor or mild coronary disease (n. 11); 1V) 70% stenosed vessel; 2V) two significantly affected vessels (n. 32); 3V) three significantly affected vessels (n. 18). Thirty-six patients (9 with one stenosis, 17 with 2, 10 with 3) underwent coronary artery bypass. Thirty-one 8 with one, 15 with 2, 8 with 3) refused the treatment in spite of the same clinical situation and were medically treated. Recordings were performed before medical and surgical treatment and after 6 and 12 months. Initial average values of the patients of 2V and 3V groups showed a shorter LVETI, longer PEPI and higher PEP/LVET ratio than those of 1V and 0V groups. Subjects of 2V group and abnormal left ventricular wall motion showed longer PEPI and higher PEP/LVET than patients of 2V without abnormal wall motion. On first evaluation no differences were observed between surgical and medical groups. The latter did not show any difference after 6 and 12 months. Surgical patients of 2V and 3V showed a longer LVETI, shorter PEPI and a lower PEP/LVET than the medical group. In the surgical group PEPI and PEP/LVET were significantly decreased after surgery while LVETI was prolonged. Our results suggest an improvement of left ventricular performance by coronary artery bypass in patients with coronary artery disease.

[Effects of guaiacolic ester of acetylsalicylic acid on spirometric and plethysmographic parameters in subjects with chronic obstructive bronchopneumopathy]. / Effetti dell'estere guaiacolico dell'acido acetilsalicilico su alcuni parametri spirometrici e pletismografici in soggetti affetti da broncopneumopatia cronica ostruttiva.

The effects of oral administration of guaiacolic ester of acetyl salicilic acid in 24 patients with chronic obstructive lung disease have been evaluated. 1.5 g of this drug were given daily into 3 administrations improving both objective and subjective symptomatology in 19 of the 24 patients after 1 or 3 weeks of treatment. Moreover, a statistically significant improvement of FEV 1" (p less than 0.001), Raw (p less than 0.005) and FEV 1"/VC (p less than 0.01) was observed. The remaining 5 patients discontinued the treatment failing the improvement of the subjective symptomatology.

[Informed consent forms in medical practice: the results of a knowledge survey]. / Il consenso informato scritto nella pratica medica: i risultati di una indagine conoscitiva.

"Federico II" University of Naples Hospital Management's Staff considered 47 informed consent forms in order to evaluate quality and quantity of the information transmitted to patients. Every form, distinguished by procedure (surgical, pharmacological, anesthesiologic or related to blood transfusions) was evaluated for the accuracy and validity of information related to: diagnosis, prognosis, diagnostic and therapeutic opportunities, expected benefits, adverse-side effects, iatrogenic risks, privacy policy on personal data. The forms were judged by information completeness criteria "conformed" or "not conformed" with standards. Our analysis demonstrate that physicians often are unaware of legal and ethical topics related to constructing informed consent forms. They usually omit crucial information or would use strict technical language. So far, we conclude Hospital Management's Staff definitively has a role in improving informed consent forms by establishing guidelines and promoting ethical issues. Final result could be to deserve stronger patient confidence in medical institutions.