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Regional myocardial blood flow in volume overload hypertrophy
REGIONAL MYOCAROIAL BLOOD FLOW IN VOLUME OVERLOAD HYPERTROPHY. F.C. White, F.R. Badke, J.W. Covell, M. LeWinter, and C.M. Bloor. Departments of Pathology and Medicine, UCSD School of Medicine, La Jolla, California. To determine whether left ventricular hypertrophy (LVH) induced by volume overload altered regional myocardial blood flow (RMBF) we constructed aortic-caval fistulae in 11 dogs (ACF) and used 6 sham operated dogs for control (C). After 12 weeks the dogs were instrumented with catheters in the left ventricle, left atrium, and aorta and trained to run on a treadmill at steady state (SS) and maximal heart rate (MHR). The dogs were infused with adenosine during SS exercise to achieve maxThe dogs had signs of failure with imal coronary vasodilitation (MCV).
elevated left
atria1
pressures and ascites.
The dogs were studied during
exercise before and after closure of the fistula. RMBF and cardiac output was determined using the tracer microsphere technique. Left ventricular weight in LVH was 51% greater than C. Resting heart rate in LVH was 138 beats/min compared to 99 in C but MHR during exercise was significantly lower in LVH (251) versus C (312). During MCV diastolic coronary resistance was similar in LVH and C before and after the fistulae were closed, but endocardial/epicardial (RMBF) ratios were lower in LVH vs. C (0.65 + 0.06 vs 0.89 f 0.07, PcO.05) when the fistula was open. Closing the Tistula changed-the endocardial/epicardial (RMBF) This suggests that a relative underperfusion ratio in LVH 0.88 + 0.12. of the endocardium-in LVH depends on the volume overload, not the presence of hypertrophy. Supported in part by NIH grant HL20190.
LYSOSOMAL ALTERATIONS IN MYOCARDIAL ISCHEMIA AND REPAIR: MODIFICATION BY CORTICOSTEROIDS. Kern Wildenthal, Robert S. Decker, and Robert M. Ridout, Univ. of Texas Health Science Center at Dallas, Dallas, Texas. Occlusion of the circumflex coronary artery induces a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases. By 30 min after ligation nonsedimentable cathepsin D activity rises significantly, and in immunohistochemical preparations cathepsin D appears to have diffused from lysosomes into the cytosol of injured cells. Methylprednisolone (50 mg/kg) delays this subcellular redistribution. Thus, in treated hearts the nonsedimentable activity of cathepsin D rises significantly only after 45-60 min of ischemia, and the appearance of immunohistochemical evidence of enzyme diffusion from lysosomes is delayed by 15-30 min. After l-2 h of ischemia, however, steroidprotected myocytes deteriorate and the biochemical activity and anatomical distribution of cathepsin D are indistinguishable from untreated ischemic hearts, indicating that the protective effect is not permanent. Recovery from sub-lethal hypoxic damage is normally characterized by extensive formation of autophagic vacuoles which subsequently decrease in size and number as damaged subcellular elements are degraded. When injured hearts are given steroids during the recovery period, however, the normal decrease in autophagic vacuoles is inhibited and digestion of damaged elements may be prevented. These results suggest that extensive lysosomal changes occur both during ischemic injury and during repair, and that corticosteroids interfere with the usual resoonses.
elevated left
atria1
pressures and ascites.
The dogs were studied during
exercise before and after closure of the fistula. RMBF and cardiac output was determined using the tracer microsphere technique. Left ventricular weight in LVH was 51% greater than C. Resting heart rate in LVH was 138 beats/min compared to 99 in C but MHR during exercise was significantly lower in LVH (251) versus C (312). During MCV diastolic coronary resistance was similar in LVH and C before and after the fistulae were closed, but endocardial/epicardial (RMBF) ratios were lower in LVH vs. C (0.65 + 0.06 vs 0.89 f 0.07, PcO.05) when the fistula was open. Closing the Tistula changed-the endocardial/epicardial (RMBF) This suggests that a relative underperfusion ratio in LVH 0.88 + 0.12. of the endocardium-in LVH depends on the volume overload, not the presence of hypertrophy. Supported in part by NIH grant HL20190.
LYSOSOMAL ALTERATIONS IN MYOCARDIAL ISCHEMIA AND REPAIR: MODIFICATION BY CORTICOSTEROIDS. Kern Wildenthal, Robert S. Decker, and Robert M. Ridout, Univ. of Texas Health Science Center at Dallas, Dallas, Texas. Occlusion of the circumflex coronary artery induces a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases. By 30 min after ligation nonsedimentable cathepsin D activity rises significantly, and in immunohistochemical preparations cathepsin D appears to have diffused from lysosomes into the cytosol of injured cells. Methylprednisolone (50 mg/kg) delays this subcellular redistribution. Thus, in treated hearts the nonsedimentable activity of cathepsin D rises significantly only after 45-60 min of ischemia, and the appearance of immunohistochemical evidence of enzyme diffusion from lysosomes is delayed by 15-30 min. After l-2 h of ischemia, however, steroidprotected myocytes deteriorate and the biochemical activity and anatomical distribution of cathepsin D are indistinguishable from untreated ischemic hearts, indicating that the protective effect is not permanent. Recovery from sub-lethal hypoxic damage is normally characterized by extensive formation of autophagic vacuoles which subsequently decrease in size and number as damaged subcellular elements are degraded. When injured hearts are given steroids during the recovery period, however, the normal decrease in autophagic vacuoles is inhibited and digestion of damaged elements may be prevented. These results suggest that extensive lysosomal changes occur both during ischemic injury and during repair, and that corticosteroids interfere with the usual resoonses.