No abstract

Abstract-The aim of the present study was to investigate whether and which cardiac growth factors are involved in human hypertrophy, whether growth factor synthesis is influenced by overload type and/or by the adequacy of the hypertrophy, and the relationships between cardiac growth factor formation and ventricular function. Cardiac growth factor formation was assessed by measuring aorta-coronary sinus concentration gradient in patients with isolated aortic stenosis (nϭ26) or regurgitation (nϭ15) and controls (nϭ12). Gene expression and cellular localization was investigated in ventricular biopsies using reverse transcriptase-polymerase chain reaction and in situ hybridization. Cardiac hypertrophy with end-systolic wall stress Ͻ90 kdyne/cm 2 was associated with a selective increased formation of insulin-like growth factor (IGF)-I in aortic regurgitation and of IGF-I and endothelin (ET)-1 in aortic stenosis. mRNA levels for IGF-I and preproET-1 were elevated and mainly expressed in cardiomyocytes. At stepwise analysis, IGF-I formation was correlated to the mean velocity of circumferential fiber shortening (rϭ0.86, PϽ0.001) and ET-1 formation to relative wall thickness (rϭ0.82, PϽ0.001). When end-systolic wall stress was Ͼ90 kdyne/cm 2 , IGF-I and ET-1 synthesis by cardiomyocytes was no longer detectable, and only angiotensin (Ang) II was generated, regardless of the type of overload. The mRNA level for angiotensinogen was high, and the mRNA was exclusively expressed in the interstitial cells. Ang II formation was positively correlated to end-systolic stress (rϭ0.89, PϽ0.001) and end-diastolic stress (rϭ0.84, PϽ0.001). Multivariate stepwise analysis selected end-systolic stress as the most predictive variable and left ventricular end-diastolic pressure as the independent variable for Ang II formation (rϭ0.93, PϽ0.001). In conclusion, the present results indicate that the course of human left ventricular hypertrophy is characterized by the participation of different cardiac growth factors that are selectively related both to the type of hemodynamic overload and to ventricular function. (Circ Res. 1999;85:57-67.) Key Words: myocardial hypertrophy Ⅲ aortic valve disease Ⅲ endothelin-1 Ⅲ insulin-like growth factor-I Ⅲ angiotensin II

To investigate the events that lead to acute myocardial ischemia we monitored continuously the ECG, the left ventricular (four patients) or aortic (two patients) pressure and the great cardiac vein oxygen saturation (CSO2S) by a fiberoptic catheter in six patients with frequent anginal attacks at rest. We recorded 137 transient ischemic episodes (10 with chest pain) characterized by ST-segment elevation in 28 episodes, depression in three episodes and by pseudonormalization of previously inverted or flat T waves in 106 episodes. The onset of electrocardiographic and hemodynamic changes was preceded by a large drop in CSO2S in all 135 episodes with ST-T changes in the anterior leads but not in two episodes with ST elevation on inferior leads. The fall in CSO2S, consistently followed by signs of left ventricular function impairment and never preceded by any detectable increase in the hemodynamic determinants of myocardial oxygen consumption, probably reflects a reduction in regional perfusion. Thus, a reduction in coronary flow may cause transient ischemia in patients with angina at rest. These episodes may be associated with variable, often minor electrocardiographic changes and occasionally with anginal pain.

These results provide evidence for the existence of a functional cardiac RAS independent of but related to the circulating RAS.