- Email: [email protected]
Biventricular hypertrophy in chronic ischemic heart disease suggests a humoral rather than hemodynamic etiology
DIMINISHED RESPONSIVENESS OF ADENYLATECYCLASE TO ADENOSINE AND OTHER AGENTS IN MYOCARDIAL SARCOLEMMAFROM SPONTANEOUSLYHYPERTENSIVE RATS. Madhu B.Anand-Srivastava Laboratory of Pathobiology, C l i n i c a l Research I n s t i t u t e of Montreal. Adenylate cyclase a c t i v i t y was studied in the myocardial sarcolemma from spontaneously hypertensive rats (SHR) and t h e i r respective controls (WKY). Basal adenylate cyclase a c t i v i t y was diminished in SHR as compared to WKY rats. The stimulation of adenylate cyclase by N-ethylcarboxamide adenosine (NECA) was s i g n i f i c a n t l y decreased in SHR. This decreased responsiveness of adenylate cyclase to NECA was associated with a decrease in the Vmax. In addition, epinephrine, nonepinephrine, dopamine, glucagon and prostaglandins were also able to stimulate adenylate cyclase to various degrees in both SHR and WKY but the extent of stimulation (Vagonists / Vbasal) was lower in SHR as compared to t h e i r respective controls. NaF and forskol i n which activate cyclase by receptor independent mechanism were also less responsive in SHR than in WKY. Furthermore the stimulation of adenylate cyclase by metal ions such as Mg2+ or Mn2+, and guanine nucleotides was also s i g n i f i c a n t l y reduced in SHR. The decreased enzyme a c t i v i t y and responsiveness to various hormones, NaF and f o r s k o l i n was observed at a l l ages of SHR ie from 4 weeks to 24 weeks of age. T h e s e results suggest that in SHR, not only the basal enzyme a c t i v i t y was decreased but the responsiveness to various hormones, G/F regulatory protein, and c a t a l y t i c subunit were also affected. (Supported by Grants from QHF and FRSQ).
BIVENTRICULAR HYPERTROPHY IN CHRONIC ISCHEMIC HEART DISEASE SUGGESTS A HUMORAL RATHER THAN HEMODYNAMIC ETIOLOGY P. G. Anderson, S. P. Bishop, P. Cox, J. C. Geer. Department of Pathology, Univ. of Alabama in Birmingham, Birmingham, Alabama 35294. Cardiac hypertrophy in chronic coronary artery disease (CAD) is classically considered to result from left ventricular (LV) hypertrophy compensating for loss of infarcted tissue. To characterize the cardiac hypertrophy in CAD, we studied hearts from patients (pts) in the SCOR necropsy protocol. Total heart weight (HW) and LV plus septum (LV+S) to right ventricular free wall (RV) ratio were measured in 63 pts with >75% stenosis of one or more coronary arteries. Controls were 20 pts who died of noncardiac problems. We excluded pts with only acute single vessel occlusion and those with important valvular disease or chronic pulmonary disease. Maximal stenosis was estimated from cross sections of barium gelatin perfused proximal coronary arteries. HW and HW/body weight in groups with >75% stenosis of i, 2, or 3 arteries (496• (• 6.5• 480• 7.1• 548• 7.0• respectively) were increased compared to controls (354ii02g, 4.9• p<.05). There was no correlation between increased HW and the number or severity of arteries involved. There was hypertrophy of both LV+S and RV. LV+S/RV was 2.81• 2.81• and 2.85• for hearts with 1,2, or 3 vessel disease (controls=2.99• LV+S/RV did not change with increasing HW (r=.2124, y=2.38 + .O012x). Thus, both RV and LV+S mass increased in pts with CAD. This suggests that a humoral factor may be involved in the development of cardiac hypertrophy in pts with CAD.
CELL SIZE CHANGES DURING DEVELOPMENT AND REGRESSION OF ISOPROTERENOL INDUCED CARDIAC HYPERTROPHY IN THE RAT. S. P. Bishop, P. Kirkland. Department of Pathology, University of Alabama in Birmingham, Birmingham, Alabama 35294. Removal of the stimulus responsible for the development of hypertrophy is known to cause regression of heart mass, but little is known regarding changes in cell size. To investigate cell size changes during regression of hypertrophy, we administered isoproterenol (5 mg/kg/d) to 8 week old male Sprague Dawley rats for 7d by Alzet pump and allowed 21d for regression to occur. Hearts were perfusion fixed and dissected for regional heart weights (HW) of left ventricle plus septum (LV+S) and right ventricular free wall (RV) (n=6-10 per group), or isolated myocytes were prepared by perfusion on a modified Langendorff apparatus with Ca ++ free Joklik media with 0.05% collagenase (n=lO-18/group). Cell volume (CV) was determined with a Coulter Counter system and cell length (CL) by direct observation of fixed cells. HW/BW increased at 7d by 40% compared to controls with equal distribution between RV and LV+So Cell volume increased by 23.3, 20.6 and 11.0% in LV epicardial, LV endocardial and RV respectively. CL was not different in 7d treated vs. control rats, nor after 21d cessation of treatment. CV returned to control in all regions but HW remained 10% elevated. In conclusion, isoproterenol produced an increased CV due to increase in cross sectional area, with no change in CL. CV returned to control value with regression of hypertrophy, but heart weight remained increased.
BIVENTRICULAR HYPERTROPHY IN CHRONIC ISCHEMIC HEART DISEASE SUGGESTS A HUMORAL RATHER THAN HEMODYNAMIC ETIOLOGY P. G. Anderson, S. P. Bishop, P. Cox, J. C. Geer. Department of Pathology, Univ. of Alabama in Birmingham, Birmingham, Alabama 35294. Cardiac hypertrophy in chronic coronary artery disease (CAD) is classically considered to result from left ventricular (LV) hypertrophy compensating for loss of infarcted tissue. To characterize the cardiac hypertrophy in CAD, we studied hearts from patients (pts) in the SCOR necropsy protocol. Total heart weight (HW) and LV plus septum (LV+S) to right ventricular free wall (RV) ratio were measured in 63 pts with >75% stenosis of one or more coronary arteries. Controls were 20 pts who died of noncardiac problems. We excluded pts with only acute single vessel occlusion and those with important valvular disease or chronic pulmonary disease. Maximal stenosis was estimated from cross sections of barium gelatin perfused proximal coronary arteries. HW and HW/body weight in groups with >75% stenosis of i, 2, or 3 arteries (496• (• 6.5• 480• 7.1• 548• 7.0• respectively) were increased compared to controls (354ii02g, 4.9• p<.05). There was no correlation between increased HW and the number or severity of arteries involved. There was hypertrophy of both LV+S and RV. LV+S/RV was 2.81• 2.81• and 2.85• for hearts with 1,2, or 3 vessel disease (controls=2.99• LV+S/RV did not change with increasing HW (r=.2124, y=2.38 + .O012x). Thus, both RV and LV+S mass increased in pts with CAD. This suggests that a humoral factor may be involved in the development of cardiac hypertrophy in pts with CAD.
CELL SIZE CHANGES DURING DEVELOPMENT AND REGRESSION OF ISOPROTERENOL INDUCED CARDIAC HYPERTROPHY IN THE RAT. S. P. Bishop, P. Kirkland. Department of Pathology, University of Alabama in Birmingham, Birmingham, Alabama 35294. Removal of the stimulus responsible for the development of hypertrophy is known to cause regression of heart mass, but little is known regarding changes in cell size. To investigate cell size changes during regression of hypertrophy, we administered isoproterenol (5 mg/kg/d) to 8 week old male Sprague Dawley rats for 7d by Alzet pump and allowed 21d for regression to occur. Hearts were perfusion fixed and dissected for regional heart weights (HW) of left ventricle plus septum (LV+S) and right ventricular free wall (RV) (n=6-10 per group), or isolated myocytes were prepared by perfusion on a modified Langendorff apparatus with Ca ++ free Joklik media with 0.05% collagenase (n=lO-18/group). Cell volume (CV) was determined with a Coulter Counter system and cell length (CL) by direct observation of fixed cells. HW/BW increased at 7d by 40% compared to controls with equal distribution between RV and LV+So Cell volume increased by 23.3, 20.6 and 11.0% in LV epicardial, LV endocardial and RV respectively. CL was not different in 7d treated vs. control rats, nor after 21d cessation of treatment. CV returned to control in all regions but HW remained 10% elevated. In conclusion, isoproterenol produced an increased CV due to increase in cross sectional area, with no change in CL. CV returned to control value with regression of hypertrophy, but heart weight remained increased.