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The FoF1-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA–encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90 decrease in oligomycin-sensitive ATPase activity and an 86 decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory chain complex I and compensatory increase in the content of complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ATP6and ATP8genes indicates a nuclear origin of the defect.

The FoF1-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA–encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory chain complex I and compensatory increase in the content of complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ATP6 and ATP8 genes indicates a nuclear origin of the defect.

OBJECTIVES

The authors compared complications and hemodynamic and electrophysiologic effects of two formulations of diatrizoate, one with additives that bind calcium and one without, in diagnostic cardiac angiography.

Kurnik PB, Tiefenbrunn AJ, Ludbrook PA. Peripheral hemodynamic effects of intraventricular and intracoronary contrast media in man. Invest Radiol 1985;20203-211.

Previous studies suggest a role for renal vasoconstriction in the pathogenesis of radiocontrast-induced nephropathy (RCIN). A renal vasodilator such as dopamine may be protective. However, the effect of dopamine on renal blood flow (RBF) in patients with chronic renal failure (CRF) is controversial. Patients with CRF of diabetic (DM) or nondiabetic (NDM) origin were hydrated with 0.45% NaCl intravenously at 100 mL/h for 12 h and then randomized to either 0.45% NaCl IV at 100 mL/h (Group 1) or dopamine IV at 2 μg/kg/min in 0.45% NaCl at 100 mL/h for 2 h during and after cardiac catheterization. Mean arterial pressure (MAP), cardiac output (CO), and RBF were measured at baseline (t = 0), after 5 min of vehicle (Group 1) or dopamine (Group 2) but before ionic radiocontrast (t = 5 min), after ventriculogram (t = 15 min), and after coronary angiography (t = 65 min). Serum creatinine (SCr) was measured at baseline and 24 and 48 h after cardiac catheterization. RCIN was defined as a 25% increase of SCr above baseline 48 h after cardiac catheterization. Baseline characteristics demonstrated the groups to be equivalent in age, SCr, creatinine clearance, CO, MAP, RBF, and radiocontrast dose administered. The incidence of RCIN was not different between Group 1 and Group2 (Group 1, 6 of 15 patients; Group 2, 5 of 15 patients). Dopamine infusion was associated with a significant increase in RBF at 5 min (Group 1, 110 ± 13%; Group 2, 193 ± 40% at t = 5, p < .05). RBF remained elevated throughout the catheterization in Group 2. Within Group 2, RBF tended to rise only in those patients who subsequently developed RCIN (RCIN, 92 ± 40 mL/min; No RCIN, 203± 24 mL/min, p < .05 at baseline); at t = 65: RCIN 530 ± 242%; No RCIN, 184 ± 38%, p < .05. All the patients in the dopamine group who developed RCIN had diabetes mellitus. The patients with DM had lower baseline RBF than the patients with NDM, despite equivalent baseline renal function. The dopamine-stimulated increase in RBF was seen exclusively in the patients with DM. In conclusion, dopamine does not prevent RCIN in patients with CRF despite a significant renal vasodilatory effect. The renal vasodiliatory effect of low-dose dopamine in patients with CRF is heterogeneous, occurring only in patients with DM. Patients who subsequently developed RCIN had lower baseline RBF and the greatest rise in RBF with dopamine. Patients with DM and CRF have lower RBF and higher filtration fraction than NDM patients with equivalent SCr and creatinine clearance. These phenomena are functional (rather than fixed), as evidenced by the renal vasodilatory response to low-dose dopamine.

Reperfusion early during myocardial infarction improves ejection fraction and this improvement may represent myocardial salvage in the injured segment. Alternatively, reperfusion of injured myocardium may cause intramyocardial hemorrhage with resultant increased stiffness causing a dyskinetic segment to become akinetic, thus improving ejection fraction without concomitant myocardial salvage. To evaluate this possibility, diastolic stiffness was assessed in a closed chest, anesthetized, normothermic dog model immediately after a 1 or 3 h occlusion of the left anterior descending coronary artery and during the 4 weeks after occlusion.

Effects of moderate spontaneous hypothermia on left ventricular systolic and diastolic function during acute myocardial infarction were documented in 17 anesthetized dogs with micromanometric pressure and ventriculographic dimension recordings acquired at baseline and at 1 and 3 h after coronary occlusion. In Group 1 (n = 5), core temperature was allowed to decline spontaneously. In Groups 2 (n = 6) and 3 (n = 6), core temperature was maintained at normothermic levels. Hypothermia impaired isovolumic relaxation markedly despite its lack of effect on ventricular volumes or ejection fraction. At 32.3 °C, τ1/2, defined as the time needed for the left ventricular pressure at the time of peak negative rate of change of left ventricular pressure (dPdt) to fall by 50%, was increased by 129% 3 h after occlusion. In addition, at this temperature significant changes were found in heart rate, cardiac output, minute work, peak positive and peak negative dPdt, systolic ejection time, mean velocity of circumferential fiber shortening, mean aortic pressure and end-diastolic pressure.

• Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) is characterized by a variety of cutaneous, mucosal, and visceral vascular anomalies. A patient with classic hereditary hemorrhagic telangiectasia was shown to have three-vessel coronary artery ectasia without evident atherosclerosis, an association not previously demonstrated. The possibility that coronary artery ectasia may be a manifestation of hereditary hemorrhagic telangiectasia is discussed.(Arch Intern Med. 1989;149:2357-2359)

To the Editor.—Mitral stenosis is a slowly progressive disease. Activity level is often subconsciously reduced, such that symptoms are often underestimated by both the patient and the physician. While orthopnea and paroxysmal nocturnal dyspnea are usually present in severe disease, pulmonary edema may present acutely and is associated with effort, emotional stress, respiratory infection, fever, sexual intercourse, pregnancy, fluid overload, atrial fibrillation with a rapid ventricular response or other tachycardia, and any state of suddenly increased cardiac output.1I would like to describe an episode of life-threatening pulmonary edema acutely precipitated by pelvic examination in a woman whose symptoms became more impressive in retrospect.Report of a Case.—A 59-year-old woman with a diagnosis of moderate mitral stenosis with chronic atrial fibrillation led an active life and was thought to have only mild intermittent pulmonary symptoms. Admission to an outside hospital was precipitated by sudden shortness of breath