Michel Degeorges

Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function

To elucidate the pathogenesis of bronchospasm in congestive heart failure, we studied 23 patients with chronic impairment of left ventricular function due to coronary artery disease or dilated cardiomyopathy. In 21 of them we found marked bronchial hyperresponsiveness to methacholine. The mean dose (+/- SD) of methacholine that elicited a 20 percent decrease in the forced expiratory volume in one second (FEV1) was 421 +/- 298 micrograms, nearly the same as in patients with symptomatic asthma. In contrast, there was no bronchial response to methacholine in 9 of 10 patients who had coronary artery disease but normal left ventricular function. Administration of the bronchodilator albuterol led to a partial (43 percent) reversal of the methacholine-induced bronchial obstruction. In 12 patients, pretreatment with the alpha-adrenergic agonist methoxamine (10 mg by inhalation), a potent vasoconstrictor, fully prevented the methacholine-induced decrease in FEV1. The protective effect of methoxamine was blocked by the alpha-adrenergic antagonist phentolamine in all six patients who received this agent. We conclude that bronchial hyperresponsiveness to cholinergic agonists is frequent in patients with impaired left ventricular function and may contribute to the wheezy dyspnea commonly observed in such patients. The bronchoconstriction may be mediated at least in part by dilatation of the bronchial vessels.

Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

Pre- and postoperative hemodynamic and cineangiocardiographic assessment of left ventricular function in patients with aortic regurgitation

Abstract Hemodynamic and angiocardiographic analysis was performed prior to and 14 months on the average following valve replacement in 11 patients with severe, isolated, pure, chronic aortic regurgitation. The aortic diastolic pressure, reduced prior to surgery, reverted to normal as did the cardiac index. Left ventricular filling pressure, elevated prior to surgery, returned to normal while aortic systolic pressure did not vary substantially. The markedly increased stroke volume returned to normal as did the net left ventricular stroke work. Left ventricular end-diastolic and end-systolic volumes, also markedly elevated, decreased but did not return to normal levels. The shape of the left ventricle, which was more spherical than normal during end-systole prior to surgery, as evidenced by the decrease in the systolic axis ratio, reverted to normal. The ejection fraction, severely reduced before surgery, increased moderately (46 ± 13 vs 51 ± 19 per cent) as did the extent of circumferential fiber shortening (δD) (21 ± 8 vs 27 ± 12 per cent). The mean velocity of fiber shortening ( VCF ) increased significantly (0.68 ± 0.2 vs 1.03 ± 0.47 circ./sec.), as did the mean left ventricular ejection rate (1.32 ± 0.48 vs 1.91 ± 0.76). Comparative analysis of the evolution of left ventricular function indices and of extramyocardial factors (end-diastolic fiber stretching and impedance to ejection) showed that whereas in some cases myocardial damage appeared to be irreversible, in others dramatic improvement sometimes occurred following surgery. It was not possible, however, to determine the threshold below which the damage was irreversible. It may therefore be concluded that in some patients with severe regurgitation attended by profound myocardial insufficiency, correction of the valvular defect could produce not only clinical and hemodynamic improvement, but also improvement in myocardial contractile status.

Nicardipine in the Treatment of Raynaud's Phenomenon: A Randomized Double-Blind Trial

The efficacy of the calcium-channel blocker nicardipine in the treatment of Raynauds phenomenon was assessed in a prospective, double-blind, randomized, crossover trial in 20 patients. Each patient received nicardipine 20 mg or placebo three times a day for two weeks and then was crossed over for two weeks. Nicardipine significantly decreased the frequency and severity of Raynauds phenomenon as compared with placebo. The authors conclude that nicardipine is effective in the treatment of Raynauds phenomenon.

Influence of aspirin on the hemodynamic effects of sublingual nitroglycerin.

We studied the possible interaction between aspirin and nitroglycerin (NTG) in seven healthy volunteers. Effects of NTG (0.8 mg sublingual spray) were assessed by the decrease in diastolic arterial pressure, increase in heart rate, and decrease in M-mode echocardiographic end-diastolic and end-systolic diameters of the left ventricle. Measurements were performed before and during 30 min after NTG. Plasma levels of NTG were monitored during the experimental procedure. Each of the following trials was repeated three times, in random order, in each volunteer: NTG without aspirin pretreatment, NTG 1 h after 1 g of oral aspirin, and NTG after 8 days of aspirin. 500 mg every 48 h. Aspirin at the 1-g dose level significantly increased the effects of NTG on diastolic blood pressure (p < 0.05) and left ventricular end-diastolic (p < 0.001) and end-systolic (p < 0.001) diameters. Aspirin (1 g) significantly increased (p < 0.01) mean NTG plasma levels from 0.24 ± 0.13 ng . ml−1 (control) to 0.37 ± 0.26 ng . ml−1. We conclude that pretreatment with 1 g of aspirin increases NTG plasma levels and therefore significantly enhances the pharmacodynamic effects of NTG.

Systemic alkalosis as a provocative test for coronary artery spasm in patients with infrequent resting chest pain

Systemic alkalosis was used to detect coronary spasm in 237 patients with infrequent, resting, angina-compatible chest pain. The provocative test was performed without previous coronary arteriography but only in patients with negative submaximal exercise test results. Rapid infusion of alkaline solution followed by maximal hyperventilation raised arterial pH above the 7.65 value necessary for diagnostic significance in 196 (83%) patients. In 24 (12%) of these patients the provocative test induced significant ischemic ST segment changes. In all patients with a positive response, coronary artery disease, which was predominantly vasospastic (19 patients) or atheromatous with a vasospastic contribution (five patients), was demonstrated by coronary arteriography followed, if necessary, by ergot derivative injection. Chest pain and ECG changes were always reversed within 5 minutes by intravenous nitroglycerin. Coronary arteriography was not performed in all patients with a negative response; therefore, the sensitivity of the procedure could not be assessed. However, 36 patients with a negative response to hyperventilation underwent coronary arteriography; 33 (92%) had normal arteriograms and a negative response to ergot derivatives. Hyperventilation appears to be a safe and specific diagnostic procedure in a subset of patients in whom the probability of coronary artery disease may not be judged sufficient to warrant coronary arteriography as a primary diagnostic approach.

Assessment of plexectomy in the treatment of severe coronary spasm in patients with normal coronary arteries

Abstract Surgical denervation of the heart by plexectomy was performed in 3 patients with variant angina, documented coronary spasm, and normal findings on coronary angiography. In all cases, spasm had already been responsible, preoperatively, for myocardial infarction and recurred thereafter in another territory despite medical therapy with a combination of nitrates and calcium antagonists. Plexectomy was performed using a standardized technique. The effectiveness of surgical suppression of cardiac autonomic innervation was confirmed postoperatively by pharmacologic tests. In 2 patients inferior myocardial infarction developed in the early postoperative period; in the third patient, coronary spasm recurred 3 weeks after plexectomy. Thus plexectomy, despite an adequate suppression of autonomic innervation, was ineffective in all cases and may even have been harmful in 2 patients. These data contradict the good results obtained by plexectomy associated with aortocoronary bypass in patients with variant angina and fixed stenotic coronary arteries. This discrepancy may be accounted for by a different pathophysiologic mechanism of vasospasm in normal coronary arteries and in diseased arteries at the site of the atheromatous stenosis. Thus, plexectomy should not be considered in the treatment of vasospasm involving normal coronary arteries, even if medical therapy fails to achieve satisfactory control of variant anginal attacks.

Prevention with molsidomine of coronary artery spasm caused by alkalosis

A provocative test of coronary artery spasm caused by alkalosis was used to evaluate a possible anti-coronary artery spasm effect of molsidomine. The rapid infusion of an alkaline buffer followed by maximal voluntary hyperventilation in 10 patients with angina at rest led to the appearance of anginal pain and significant, transient ischemic changes of the ST segment resulting from alkalosis-induced coronary spasm. A second provocative test was performed under the same conditions, 24 hours later, after the administration of 4 mg of molsidomine. Molsidomine prevented the development of coronary artery spasm in 8 of the 10 patients in the study group. These preliminary results justify further clinical evaluation of molsidomine in the treatment of vasospastic angina.