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NADH laser fluorimetry and mitochondrial oxigraphy were used to study myocardial oxidative energy metabolism during cardiac allograft rejection. Heterotopic cardiac transplantation was performed on Lewis rats; allografts (with Fischer rat donors) were compared with isografts (with Lewis rat donors). In vivo and in vitro assays were performed six days after transplantation. Myocardial NADH fluorescence was recorded in vivo from grafted hearts, at baseline; during brief, complete ischemia; and during reperfusion. Oxygen consumption of mitochondria isolated from both native and grafted hearts was determined. Neither baseline levels nor maximum ischemic levels of NADH fluorescence (F0 = k[NADH]) were found to be significantly different between allografts (0.45 +/- 0.05 to 0.87 +/- 0.10) and isografts (0.45 +/- 0.04 to 1.11 +/- 0.05). During recovery, the rate of fluorescence decrease was significantly lower in allografts than in isografts (0.024 +/- 0.001 vs. 0.038 +/- 0.002 delta F0.s-1, P less than 10(-3], indicating a lower rate of NADH reoxidation. In the presence of malate and glutamate substrates, mitochondrial O2 consumption was significantly lower in allografts than in isografts (30 +/- 9 vs. 100 +/- 15 nanoatoms O2. min-1.mg prot-1, P less than 10(-2]. These results indicate that mitochondrial oxidative metabolism was impaired during the rejection process. Such energy production disturbances may contribute to the dysfunction of rejecting hearts.

The bronchial circulation is a physiological left-to-left shunt; the venous return of the bronchial arteries vascularising the intra-pulmonary bronchi drains directly into the left heart chambers. In cardiac failure, increased left ventricular filling pressures affects the bronchial circulation and causes stasis and congestion. Congestion of the arterial and venous bronchial microcirculation leads to thickening of the bronchial mucosa and submucosa, resulting in a tendency to obstruct small and medium-sized airways. The bronchial circulation can be explored indirectly in cardiac failure by the spirometric response to adrenergic agonists and antagonists administered by inhalation: bronchial vasomotor phenomena explain the symptomatology of cardiac asthma and also seem to play a role in the genesis of the dyspnoea of effort in patients with cardiac failure.

Laser fluorimetry of reduced nicotinamide adenine-dinucleotide (NADH) in situ is a new technique used for real-time studies of the degree of reduction of the first link in the mitochondrial respiration chain. We present here the first results obtained in animal experiments and in clinical exploration: In rats, coronary occlusion produces a substantial rise in mitochondrial NADH, followed by a fall below basal level during reperfusion. Tetanic contraction of slow-twitch muscles in rats results in a rise in NADH level higher than that produced by contraction of fast-twitch muscles. During coronary angiography, injection of the contrast medium induces a rise in NADH in patients with a significant degree of coronary stenosis. Intravenous nitroglycerin reduces both left ventricular end-diastolic pressure and NADH fluorescence concomitantly, due to preferential distribution of the coronary blood flow to sub-endocardial layers. Exercise-induced ischaemia results in a decrease of muscular NADH concentration in Mc Ardle syndrome, due to phosphorylase deficiency.

Between January, 1975, and January, 1982, 130 patients underwent mitral valvuloplasty for pure or predominant mitral insufficiency. Mean age at operation was 30 +/- 17 years. Twenty-five patients were under 15 years of age. Mitral insufficiency was mainly (112/130) due to rheumatic disease. Fifty-nine patients (45.4%) had another diseased valve which necessitated a surgical correction (tricuspid in 36 and aortic in 23). Surgical technique for mitral valvuloplasty varied according to the lesions. Three patients died in the first month after operation (2.3%). Five patients are lost to follow-up. The mean follow-up period for the 122 remaining patients is 38 +/- 27 months. Seven patients required reoperation and three of them died. An additional patient died without reoperation. Therefore, the late mortality was 3.1% (4/122). Almost all (116/118) of the remaining patients are in Class I (105) or II (11) of the New York Heart Association. Mean cardiothoracic ratio decreased from 60.6% +/- 7.7% preoperatively to 53.7% +/- 6.2% postoperatively (p less than 0.001). Thromboembolic episodes were noted in four patients, all of them in atrial fibrillation. Actuarial curves including hospital mortality showed a 92.0% survival rate at 7 years for the overall series (1.0% +/- 0.5%/patient-year), 93.7% +/- 4.9% at 7 years for isolated mitral reconstruction and 89.9% +/- 5.6% for mitral-tricuspid valvuloplasty at 5 years. The embolism-free rate at 7 years was 91.2%, with a rate of thromboembolic episodes of 1.0 +/- 0.5%/patient-year. Eighty-eight percent were free of reoperation at 7 years, with a rate of reoperation of 1.7 +/- 0.7%/patient-year. This system of mitral repair can provide stable functional results, low surgical and late mortality, and an acceptable rate of reoperation.

Hemodynamic studies were performed in 26 patients 2-60 months after mitral valvuloplasty (average 14 months). All patients but one had an annular deformity requiring prosthetic ring annuloplasty. In addition, 25 patients had prolapsed leaflet or restricted leaflet motion requiring specific techniques of repair. All patients were asymptomatic after operation. Significant residual mitral insufficiency was present in only five patients. Roentgenograms showed a reduction in cardiothoracic ratio, from 0.62 +/- 0.07 preoperatively to 0.53 +/- 0.06 postoperatively (p less than 0.001). Mean pulmonary artery pressure decreased from 30 +/- 12 mm Hg to 18 +/- 6 mm Hg (p less than 0.001) and cardiac index returned to normal (2.7 +/- 0.7 1/min/m2 vs 3.1 +/- 0.7 1/min/m2, p less than 0.02). Angiocardiographic studies showed that end-diastolic volume index returned to normal (148 +/- 41 cm3/m2 vs 89 +/- 23 cm3/m2, p less than 0.001), with significant decreases in end-systolic volume index ( 63 +/- 27 cm3/m2 vs 43 +/- 16 cm3/m2, p less than 0.001), left ventricular mass (114 +/- 28 g/m2 vs 88 +/- 20 g/m2, p less than 0.001), ejection fraction (58 +/- 11% vs 52 +/- 11%, p less than 0.02) and mean velocity of fiber shortening (1.19 +/- 0.36 circ/sec vs 1.01 +/- 0.24 circ/sec, p less than 0.05). We conclude that mitral valvuloplasty provides good and stable midterm results and that the operation should be performed before irreversible myocardial lesions occur.

Myocardial involvement in systemic sclerosis may be caused, at least in part, by myocardial ischemia due to functional or structural abnormalities of small coronary arteries or arterioles. Coronary reserve, assessed by dipyridamole-induced coronary vasodilatation, was strikingly impaired in patients with systemic sclerosis. Thallium scans have shown numerous myocardial perfusion defects in scleroderma patients. Two studies, using oral nifedipine and intravenous dipyridamole, demonstrated that these thallium-201 myocardial perfusion defects in patients with systemic sclerosis were partially reversible. Finally, the preliminary results of long-term studies suggest that some coronary vasodilators may be beneficial in the long-term treatment of myocardial perfusion abnormalities in systemic sclerosis.

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.

Twenty patients with pure or prevalent mitral regurgitation, undergone mitral valve conservative surgery according to the Carpenter-technique from 1975 to 1979, have been studied. There are 19 women and 1 man, mean age of 25 years (range 11 to 65); 18 had a rheumatic fever; 2 had a mitral valve prolapse due to a degeneration of collagen within the central core of the cordae tendineae, which was the primarily responsible for cordae rupture in 1 case. The clinical and hemodynamic features were severe in a 50 per cent of cases (8 patients in N.Y.H.A. functional class III; 3 in class IV); there was pure mitral regurgitation in 12, combined mitral stenosis and regurgitation in 8; tricuspidalic regurgitation which needed annuloplasty in 5 patients. All the patients have been studied by hemodynamic and angiocardiographic study before and an average of 14 months after surgical treatment. Surgical conservative technique of mitral valve is described; the results are analyzed. All the patients are in N.Y.H.A. functional class I, 14 months after surgical valve therapy. In three cases, a systolic 3/6 murmur which was present immediately after surgical treatment and that not increased in time, remains. EKG left overload is still present in 2 cases; Heart-Chest ratio decreases in all the patients (range 0,61 to 0,51). Atrial fibrillation is present in 6 patients. Hemodynamic findings show: Pulmonary Systolic Pressure (PSP) decreases (45 +/- 4 to 27 +/- 1); Mean Pulmonary Capillary Wedge (PCW) pressure decreases (19 +/- 1 to 11 +/- 1); Total Peripheral Resistance (TRP) (2023 +/- 112 to 1595 +/- 70 dynes sec cm--5), Total Pulmonary Resistances (TPR) (742 +/- 89 to 351 +/- 36), Pulmonary Arterial Resistances (PArtR) (344 +/- 51 to 133 +/- 18 dynes sec cm--5), and Left Ventricle Diastolic Pressure (LVEDP) (12 +/- 1 to 8 +/- 1 mmHg) normalize. The Ejection Fraction (EF) decreases at the most operative control after surgery in 11 patients (56 +/- 3 to 50 +/- 1). Angiographic study shows no regurgitation in 4 patients, a least regurgitation in 13 cases and there is a 2/4 regurgitation in 3 cases only. The AA. have got to an excellent result in 17 patients; a 2/4 degree angiographic regurgitation persist in 3 cases, although a clear clinical improvement. The AA. consider of great utility this surgical valvular management according to a critical review of the efficacy and stability of the results.

In a fifty-three-year-old man, constrictive metastatic carcinoma of the pericardium revealed a bronchial carcinoma. The subacute course was rapidly progressive. Only partial pericardiectomy could be performed. Death occurred 16 days after the peripheral signs of compression of the heart became patent. In such cases early diagnosis, before signs of constrictive pericarditis become obvious, is very important.

Primary scleroderma myocardial disease may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. We evaluated the effect of the calcium channel blocker nicardipine on myocardial perfusion assessed by thallium-201 scanning in 16 patients with systemic sclerosis. Thallium-201 single photon emission computerized tomography was performed at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SD) number of left ventricular segments with perfusion defects significantly decreased from 6.0 +/- 2.0 at baseline to 4.1 +/- 2.3 after nicardipine (p less than 0.01). The mean global perfusion score significantly increased from 10.2 +/- 1.9 at baseline to 11.9 +/- 2.6 after nicardipine (p less than 0.02). Our study demonstrates short-term improvement in thallium-201 myocardial perfusion with nicardipine in patients with systemic sclerosis.

In this review paper, the authors summarize the studies which support the theory that a defect in production of energy by the myocardial cells is a determinant factor in the genesis and/or aggravation of dilated cardiomyopathy. Points that are common to this metabolic theory and to the other pathogenetic mechanisms usually described (notably viral or toxic mechanisms) are presented.