Abnormal cardiac function in the streptozotocin-induced non-insulin-dependent diabetic rat: noninvasive assessment with doppler echocardiography and contribution of the nitric oxide pathway.

OBJECTIVES: We sought to evaluate in vivo and in vitro left ventricular (LV) geometry and function in streptozotocin-induced diabetic rats and the possible role of the nitric oxide (NO) pathway. BACKGROUND: Diabetes results in cardiac dysfunction; however, the specific abnormalities are unknown. Because decreased NO contributes to abnormal vascular function in diabetics, we hypothesized that NO pathway abnormalities may contribute to diabetic cardiomyopathy. METHODS: Control rats and those with non-insulin-dependent diabetes mellitus (NIDDM) underwent echocardiography, hemodynamic assessment, isolated heart perfusion and measurement of exhaled NO and LV endothelial constitutive nitric oxide synthase (ecNOS). RESULTS: Diabetic rats had increased LV mass (3.3 +/- 0.6 vs. 2.6 +/- 0.3 g/g body weight [BW], p < 0.001) and cavity dimensions (diastolic 2.0 +/- 0.1 vs. 1.8 +/- 0.2 cm/cm tibial length [TL], p < 0.05). Diabetic rats had prolonged isovolumic relaxation time (IVRT) (40 +/- 8 vs. 26 +/- 6 ms, p < 0.0001), increased atrial contribution to diastolic filling (0.47 +/- 0.09 vs. 0.30 +/- 0.08 m/s, p < 0.0001), and elevated in vivo LV end-diastolic pressure (7 +/- 6 vs. 2 +/- 1 mm Hg, p = 0.04). Diabetic rats had increased chamber stiffness. Shortening was similar in both groups, despite reduced meridional wall stress in diabetics, suggesting impaired systolic contractility. Exhaled NO was lower in diabetic rats (1.8 +/- 0.2 vs. 3.3 +/- 0.3 parts per billion, p < 0.01) and correlated with Doppler LV filling. The ecNOS was similar between the groups. CONCLUSIONS: Diabetic cardiomyopathy is characterized by LV systolic and diastolic dysfunction, the latter correlating with decreased exhaled NO. The NO pathway is intact, suggesting impaired availability of NO as contributor to cardiomyopathy.

Acquired dynamic left ventricular outflow tract obstruction complicating acute anterior myocardial infarction: serial echocardiographic and clinical evaluation.

We describe three cases of dynamic outflow obstruction complicating acute anterior myocardial infarction. Serial echocardiography suggests the intraventricular gradient results from basal hyperkinesis, the latter being a reciprocal response to the apical wall motion abnormality.

Cardiac tamponade in association with an atrial septal defect: echocardiographic Doppler and hemodynamic observations.

We describe a case of cardiac tamponade in association with an atrial septal defect, in which pulsus paradoxus and respiratory variations in right and left ventricular filling were absent. Doppler echocardiography of the flow across the atrial septal defect showed bidirectional shunting, explaining the absence of pulsus paradoxus and respiratory variations in chamber filling.

Mycotic aneurysm of the descending thoracic aorta: the role of transesophageal echocardiography.

Mycotic aneurysms of the aorta are prone to rupture. Thus rapid and accurate diagnosis is essential so that surgical repair can be undertaken. We report a case of mycotic aortic aneurysm caused by mitral valve endocarditis. The aneurysm situated at the junction of the thoracoabdominal aorta was readily detected by transesophageal echocardiography. Computed tomography and aortography were complementary to transesophageal echocardiography in establishing the diagnosis. The patient underwent successful repair and acute inflammation of the aneurysm was present at histologic examination.

Role of echocardiography in perioperative management of patients undergoing open heart surgery.

TEE has assumed a pivotal role in the perioperative management of patients undergoing open-heart surgery. The information obtained influences important therapeutic decisions in thoracic aortic surgery, valvular surgery, and coronary artery bypass surgery. TEE also assists in determining the reason for failure to wean from cardiopulmonary bypass and allows rapid detection of the etiology of hypotension in the patient after surgery. Advances in technology have resulted in three-dimensional images of cardiac structures, and this will further enhance the usefulness of echocardiography for the surgeon. TEE should no longer be regarded as an imaging tool available only in academic centers, but should be routinely used by qualified operators in centers performing open-heart surgery.

Cardiac sarcoidosis masquerading as a metastatic tumor: the role of transthoracic and transesophageal echocardiography.

We present an unusual case of biopsy-proven myocardial sarcoidosis in which the transthoracic and transesophageal echocardiographic findings suggested metastatic tumor involvement of the myocardium and pericardium. The pathologic, clinical, and echocardiographic features of cardiac sarcoidosis are reviewed, with emphasis on the role of echocardiography.

Effect of cyclosporin A on bone mineral metabolism in experimental diabetes mellitus in the rat.

Cyclosporin A (CsA) is widely used in diabetic transplant patients and early type I diabetes mellitus. Diabetes produces a low-turnover osteopenia, and CsA conversely induces high-turnover osteopenia in rats. We investigated whether CsA would exacerbate diabetic osteopenia. Four groups of 10-week-old male Sprague-Dawley rats (n = 11/group) were studied: On day -6, groups A and C received saline and groups B and D received intravenous streptozotocin (55 mg/kg) to induce diabetes. From day 0, groups A and B received CsA vehicle and C and D received CsA (15 mg/kg) by daily gavage. Rats were bled on days -6, 0, 11, and 22 for serum bone gla protein (BGP), 1,25-(OH)2D, PTH, blood ionized Ca, and blood glucose determinations. Double tetracycline labeling was performed on days 9 and 20 for bone histomorphometry. After sacrifice on day 22, histomorphometric analysis was performed. Serum BGP, 1,25-(OH)2D, and PTH levels were significantly decreased in the diabetic alone (B) and diabetic plus CsA (D) groups and significantly increased in the CsA alone (group C). CsA alone (group C) induced cancellous bone loss by stimulated bone resorption. Cancellous bone loss in the diabetic alone rats (group B) was caused primarily by inhibited bone formation. No differences were found in cancellous bone mass, formation, or resorption parameters between diabetic alone (group B) and CsA-treated diabetic rats (group D). Neither CsA alone (group C) nor diabetic alone (group B) nor their combination affected cortical bone mass. CsA alone (group C) stimulated periosteal bone formation and endocortical bone resorption and inhibited endocortical formation, and diabetic alone (group B) inhibited both periosteal and endocortical bone formation. No parameters of tibial diaphyses in CsA-treated diabetic rats (group D) were different from diabetic alone. Thus the addition of CSA to the diabetic treated rats (group D) could not stimulate remodeling and appeared not to worsen significantly some of the alterations in bone formation and resorption. Possible explanations for this may be that CsA in vivo requires adequate levels of PTH, 1,25-(OH)2D, insulin, and perhaps growth factors to stimulate remodeling. The use of CsA in type I diabetic patients or in organ transplant recipients who remain diabetic after transplantation may in the short term not aggravate existing osteopenia based on these findings.

Prostaglandin E2 alleviates cyclosporin A-induced bone loss in the rat.

Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.