J Schaper

Myocardial structure and function in patients with aortic valve disease and their relation to postoperative results

Abstract Left ventricular angiographic studies were performed before and 6 months after aortic valve replacement with a Bjork-Shiley prosthesis in 21 patients, 5 with aortic stenosis, 8 with mixed aortic valve lesions and 8 with aortic insufficiency. The degree of myocardial fibrosis and myocardial ultrastructural changes were evaluated from transmural needle biopsy specimens obtained from the left ventricular anterior free wall at operation. Twelve patients without heart disease served as control subjects for angiographic data. Patients with aortic valve disease had a significantly higher left ventricular mass before operation than control subjects and a lower ejection fraction and mean normalized systolic ejection rate. After operation left ventricular mass decreased considerably but did not reach normal level. Ejection fraction and mean normalized systolic ejection rate became normal in all patients with aortic valve disease. The percent fibrosis determined with morphometry was significantly higher in the subendocardium than in the subepicardium of pressure-overloaded hearts (predominant stenosis) (19 versus 13 percent) but equal in both layers of volume-overloaded hearts (predominant regurgitation) (19 versus 18 percent). Electron microscopy revealed significant intracell alterations of the nucleus, sarcomeres, mitochondria and cytoplasmic reticulum. When all patients, regardless of type of aortic valve lesion, were considered, there was no significant correlation before operation between percent fibrosis and ejection fraction ( r 0.10) or mean normalized systolic ejection rate ( r 0.02) but a significant inverse relation between left ventricular mass and ejection fraction ( r 0.54) as well as mean normalized systolic ejection rate ( r 0.49). These data suggest that (1) Depressed left ventricular function in aortic valve disease is associated with ultrastructural degenerative cell changes, but complete recovery of cardiac function after aortic valve replacement is not prevented by these changes. (2) Interstitial myocardial fibrosis is not a primary determinant of depressed cardiac function in aortic valve disease.

Correlation between myocardial structure and diastolic properties of the heart in chronic aortic valve disease: Effects of corrective surgery

Abstract Left ventricular end-diastolic properties were evaluated with cineangiography and pressure measurements before and 6 months after aortic valve replacement with a Bjork-Shiley prosthesis in 10 patients with aortic stenosis, 7 patients with mixed aortic valve disease and 7 patients with aortic insufficiency. Mean left atrial pressure, left ventricular end-diastolic pressure, volume and wall thickness were measured, and the stiffness constant K A and the elastic stiffness E m were calculated. Myocardial cell diameter and the degree of myocardial fibrosis were determined with morphometric analysis of transmural needle biopsy specimens obtained from the left ventricular free wall at operation. Significant correlations were found between myocardial cell diameter and end-diastolic pressure ( r = 0.63), mean left atrial pressure ( r = 0.58), end-diastolic wall thickness ( r = 0.80), K A ( r = 0.56) and E m ( r = 0.53). However, no significant correlation existed between percent fibrosis and any of these measurements. Before operation, end-diastolic left ventricular pressure, mean left atrial pressure, K A and E m were significantly elevated in aortic stenosis and mixed aortic valve disease but not in aortic insufficiency. After valve replacement clinical improvement was seen in all patients. End-diastolic left ventricular pressure, mean left atrial pressure, enddiastolic volume and E m decreased and normalized completely in all groups. End-diastolic wall thickness and K A decreased significantly in aortic stenosis and mixed aortic valve disease (not in aortic insufficiency) but remained moderately elevated. Close correlations were found between end-diastolic wall thickness and K A ( r = 0.78) and between mean left atrial pressure and E m ( r = 0.85). These results suggest (1) myocardial cell diameter, but not myocardial fibrosis, is a major determinant of end-diastolic properties of the left ventricle in chronic aortic valve disease. (2) Corrective surgery with a Bjork-Shiley valve causes normalization of elastic stiffness of the chamber and of mean left atrial pressure, thus explaining the alleviation of congestive symptoms.

The Effects of Global Ischemia and Reperfusion on Human Myocardium: Quantitative Evaluation by Electron Microscopic Morphometry

During open-heart operation, myocardial biopsies were taken from 31 patients undergoing aortic valve replacement during total cardiopulmonary bypass. The first needle biopsy was taken before induction of cardiac arrest (Kirsch cardioplegia), the second at the end of global ischemia, and the third during the reperfusion period. Teh tissue was investigated by electron microscopy, in both a qualitative and a quantitative manner (morphometry). Ultrastructural morphometry revealed cellular and especially mitochondrial swelling that occurred during the reperfusion phase, but not after ischemia alone. On the basis of morphological measurements, this study shows the occurrence of postischemic cellular and mitochondrial edema that possibly might be avoided by the use of improved techniques of myocardial protection during operation.

Reduced volume fraction of myofibrils in myocardium of patients with decompensated pressure overload.

The relation between quantitative ultrastructural changes of the left ventricular (LV) myocardium and contractile function was studied in patients with chronic aortic stenosis (AS). The volume fractions of myofibrils, sarcoplasm and mitochondria in myocardial cells were determined by electron microscopic morphometry in small LV tissue samples of 19 patients with AS. Interstitial fibrosis was measured by light microscopic morphometry. Transmural biopsies of the LV free wall perfused by the anterior descending branch of the left anterior descending coronary artery (LAD) were obtained during aortic valve replacement. LV function was analyzed from preoperative right- and left-heart catheterization and angiography. Group 1 consisted of seven patients with ejection fractions (EFs) greater than 55% and mean left atrial pressure (LAP) less than 15 mm Hg. Group 2 consisted of 12 patients with EFs less than 55% and mean LAP greater than 15 mm Hg. Patients in group 1 had lower LV end-diastolic volume (91.9 vs 145.3 ml/m2, p < 0.05) and lower LV muscle mass (148.3 vs 199.8 g/m2, p < 0.05) than patients in group 2. The volume fraction of myofibrils was higher in group 1 than in group 2 (48.4 vs 42.1%, p < 0.05), while volume fractions of sarcoplasm (31.7 vs 36.0%) and mitochondria (20.9 vs 22.0%) were comparable (p > 0.05). Interstitial myocardial fibrosis did not differ between groups (16.3 vs 14.7%, p > 0.05). Biopsies from the area perfused by the LAD in 10 additional surgical patients who had coronary artery disease with moderate LAD stenosis and normal wall motion in the area of LV free wall perfused by the LAD were taken as controls for morphometric data. No significant difference of ultrastructural data was found between group 1 and controls. The volume fraction of myofibrils was lower in group 2 than in controls (42.1 vs 52.9%, p < 0.001), and the volume fraction of sarcoplasm was higher (36.0 vs 21.1%, p < 0.001). Mitochondria and interstitial fibrosis did not differ in group 2 and controls (p > 0.05).Thus, intracellular reduction in the volume fraction of myofibrils was the major morphologic finding in LV biopsy samples of patients with decompensated pressure overload.

Hypertrophy due to chronic volume overloading in the dog heart. A morphometric study@@@Hypertrophie nach chronischer Volumenüberlastung am Hundeherzen. Eine morphometrische Untersuchung

SummaryCardiac hypertrophy due to chronic volume overloading was produced in dogs by experimental complete AV-block. Ten weeks after operation a quantitative electron microscopic study was carried out for determination of the volume density of contractile material and mitochondria. The results were compared with a two-week group and normal dogs. The ratio of the volume density of contractile material and mitochondria is nearly constant during the course of developing hypertrophy.ZusammenfassungHerzhypertrophie, hervorgerufen durch chronische Volumenüberlastung, wurde bei Hunden durch experimentellen vollständigen AV-Block erzeugt. 10 Wochen nach Operation wurde aus elektronenmikroskopischen Aufnahmen eine quantitative Bestimmung der Volumendichten von kontraktilem Material und Mitochondrien durchgeführt. Die Ergebnisse wurden mit einer 2-Wochen-Gruppe und Normalhunden verglichen. Das Verhältnis der Volumendichten von kontraktilem Material und Mitochondrien ist während des Verlaufs der Hypertrophie näherungsweise konstant.

The ulstrastructure of sarcomeres in hypertrophied canine myocardium in spontaneous subaortic stenosis

SummaryUltrastructural alterations of sarcomeric structure were found in canine congenital subaortic stenosis leading to cardiac hypertrophy.These changes consisted of plaque-like accumulation of Z-material, widening and distortion of Z-bands resulting in disarrangement of sarcomeric units.A true lesion of the contractile apparatus seems the most likelyexplanation for our observations.ZusammenfassungBci einer kongenitalen subvalvulären Aortenstenose mit Hypertrophie des Herzens beim Hund wurden elektronenmikroskopisch Veränderungen der Sarkomerenstruktur beobachtet.Die Veränderungen bestanden aus Anhäufungen von Z-Material und Veribreiterung und Verzerrung der Z-Streifen, die schließlich zur Disorganisation der Sarkomeren fürhrten.Eine Schädigung des kontraktilen Apparates scheint die einleuchtendste Erklärung dieser Beobachtungen zu sein.

Quantitative ultrastructure of the myocardium in chronic aortic valve disease@@@Quantitative ultrastrukturelle Befunde des Myokards bei Patienten mit chronischen Aortenklappenvitien

SummaryLight and electron microscopic morphometry was carried out in tissue samples which were obtained from the left ventricular free wall in 29 patients with chronic aortic valve disease during open-heart surgery. 6 patients had aortic stenosis, 9 had aortic insufficiency and 14 had a mixed aortic valve lesson. Hemodynamics were studied before operation. Patients with mixed aortic valve disease had a higher left ventricular mass, a lower ejection fraction and mean circumferential fiber shortening rate than patients with aortic stenosis. Peak systolic wall stress was comparable between groups. The intracellular content of contractile material was lower and the sarcoplasmic volume was higher in mixed aortic valve disease than in aortic stenosis. Mitochondrial volume and interstitial fibrosis were not different between groups. Patients with aortic insufficiency showed no significant difference of parameters as compared to both other groups. We conclude that an intracellular deficiency of myofibrils causes lack of contractility in advanced hypertrophy due to mixed aortic valve disease.ZusammenfassungLicht- und elektronenoptische Morphometrie wurde an Gewebeproben des linken Ventrikels durchgeführt, die bei der Herzoperation entnommen wurden. 6 Patienten hatten eine Aortenstenose, 9 eine Aorteininsuffizienz und 14 ein kombiniertes Aortenvitium. Hämodynamische Messungen wurden vor der Operation durchgeführt. Patienten mit kombiniertem Aortenvitium hatten eine höhere linksventrikuläre Masse, eine niedrigere Ejektionsfraktion und Verkürzungsgeschwindigkeit als Patienten mit Aortenstenose. Der systolische “Wall Stress” war vergleichbar in den 3 Gruppen. Der intrazelluläre Gehalt an Myofibrillen war geringer, und der sarkoplasmatische Raum war höher bei kombinierten Aortenvitien als bei Aortenstenose. Das Mitochondrienvolumen und die interstitielle Fibrose waren nicht unterschiedlich in den Gruppen. Patienten mit Aorteninsuffizienz zeigten keinen signifikanten Unterschied zu den beiden anderen Gruppen. Wir schließen daraus, daß eine intrazelluläre Verarmung von kontraktilem Material die Ursache der eingeschränkten Myokardfunktion bei fortgeschrittener Hypertrophie infolge kombinierten Aortenvitiums ist.