Capillary basal laminar thichness in diabetic human myocardium.

Biopsied myocardial tissue was obtained from 24 patients electing coronary arterial bypass surgery who were divided into three groups: chemical diabetics (CD) with normal fasting blood sugar levels and incidentally encountered elevated glucose levels after sugar loading; overt diabetics (OD) requiring insulin treatment; and euglycemic, nondiabetic patients (ND) serving as a control group. Specimens from the left anterior apical segment of the heart were processed for ultrastructural examination, with special emphasis on determining capillary basal laminar thickness with the aid of morphometric techniques. Results of this study indicate that (1) a statistically significant increase in basal laminar thickness is evident in myocardial tissue of OD patients; (2) incipient alterations in laminar width are demonstrable in the CD group; (3) the predominant morphologic abnormalities, which we have examined in the parenchymal tissue of the biopsied hearts, namely myocardial hypertrophy and interstitial fibrosis, are present to a comparable degree in all three groups of patients; and (4) the average thickness of basal laminae around myocardial capillaries tends to be narrower compared with measurements reported in other tissue compartments.

Evaluation of a rat model for assessing interventions to salvage ischaemic myocardium: effects of ibuprofen and verapamil.

Coronary ligated rats were administered intraperitoneal injections of 6.24, 12.52, and 25.00 mg . kg-1 ibuprofen and 5.00 and 10.00 mg . kg-1 verapamil 1 h before ligation, 1 h after ligation, and then every 8 h for 48 h. Ibuprofen at 50.00 mg . kg-1 was administered 1 h before ligation, 1 h after ligation and 5 h after ligation. Infarct size was determined either by weighing the stained excised infarcted area or by measuring the creatine kinase activity from the excised left ventricle. Ibuprofen and verapamil treatment resulted in less myocardial damage after 48 h than placebo treatment but the differences were generally not statistically significant. The reduction in infarct size was greater in the ibuprofen treated animals compared with verapamil treated rats. In addition, there was a lower mortality with ibuprofen treatment than for either verapamil or placebo. This rat model was useful as a screening tool for the initial evolution of therapeutic interventions to reduce myocardial infarct size. It required substantially less time than large animal models and can be used to examine a variety of treatment doses. These experiments also demonstrated the importance of randomisation to treatment and control groups because of the possibility of disproportionate mortality affecting infarct size.

Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys.

A consistent group of progressive central and peripheral nervous system lesions developed in seven rhesus monkeys maintained on a vitamin E-deficient diet for 30 to 33 months. These lesions were absent from vitamin E-supplemented monkeys. The principal neuropathologic alteration was loss of sensory axons in the posterior columns, sensory roots, and peripheral nerves. Morphologic and morphometric studies indicated that the distal segments of the axons were affected most severely and large-caliber myelinated fibers are selectively involved. Swollen, dystrophic axons (spheroids) occurred infrequently. Degeneration and phagocytosis of small numbers of neuronal perikarya were observed in the dorsal root ganglia and the anterior horns. The number of affected neurons was not proportional to the number of affected axons. Accumulation of lipopigment was evident in neuronal perikarya and CNS endothelial cells. The nervous system lesion were usually accompanied by a chronic necrotizing myopathy. The neuropathologic lesions in vitamin E-deficient monkeys are compared with those in vitamin E-deficient rats and in humans with low serum vitamin E concentrations. A similar type of sensory axonopathy is associated with chronic deficiency of vitamin E in these three species.

Pathomorphologic aspects of muscular tissue in diabetes mellitus.

Biopsy specimens from the myocardium were examined in a series of 145 patients who had elected coronary arterial bypass grafting. The patients were divided into three groups; 1) overtly diabetic (OD) patients; 2) chemically diabetic (CD) patients, who demonstrated impaired glucose tolerance only when stressed with a sugar load; and 3) normoglycemic, nondiabetic (ND) patients, who served as a control group. Tissue plugs from the left anterior apical segment of the heart and from the quadriceps femoris in 71 patients, for comparative evaluation, were prepared for ultrastructural examination. Findings were as follows: 1) Myocardial hypertrophy and interstitial fibrosis were twin characteristic abnormalities, seen in all but two of the biopsy specimens; capillary endothelial changes, the third most common abnormality, were present in approximately half of these specimens, regardless of the patients' metabolic status. 2) In patients matched by sex, age, weight, blood pressure, preoperative myocardial ventricular function, and coronary arterial integrity, capillary basal laminar thickening represented a pathomorphologic hallmark, distinguishing structural alterations in the diabetic from those in the normoglycemic patient. 3) Although clear-cut and statistically significant thickening of basal laminae was noticeable in OD patients, a) in the quadriceps markedly increased laminar thickening was present in a number of ND patients, rendering interpretation of this change in skeletal muscle as pathognomonic for diabetes doubtful; and b) within cardiac muscle this increase in laminar width was less than that seen in skeletal muscle, leaving the functional implications of this alteration in doubt. 4) Early but statistically significant increases in capillary basal laminar thickening were observed in the myocardium of CD patients; these patients demonstrated impaired glucose tolerance only when stressed with a sugar load, without exhibiting overt diabetic manifestations. 5) In this group of highly selected patients with epicardial coronary arterial disease, the histopathologic profile of the diabetic myocardium did not include distinctive abnormalities sufficient to warrant the designation of "diabetic cardiomyopathy," indicating that coronary arterial bypass grafting can be recommended for the diabetic patient who requires this procedure.

Effects of dilation with a balloon catheter on the endothelium of the internal thoracic artery.

Controlled dilation of the internal thoracic artery with a balloon catheter has been reported to effectively treat intraoperative arterial spasm. It has been shown in laboratory animals that dilation of the internal thoracic artery at prescribed shear force levels will not cause intimal damage. Using scanning electron and light microscopy, we have examined the effects of calibrated balloon dilation on the endothelium of the human internal thoracic artery. In 10 patients with bilateral internal thoracic artery grafting, the artery was dilated with a Fogarty IMAG balloon catheter (Baxter Healthcare Corporation, Edwards Division, Santa Ana, Calif.) that was withdrawn at tensions of 20 or 30 gm. Arterial segments and nondilated control specimens were prepared for scanning electron microscopy. The intimal surface of each internal thoracic artery was evaluated by assigning a score (from 0 to 3) to 10 examined scanning electron microscopy fields; subsequently the arterial tissue was viewed by light microscopy with paraffin-embedded sections stained for elastic tissue. Arteries were obtained from three additional patients so that the microscopic appearance of the arteries could be observed after rough manipulation or removal of the balloon without shearing. The results of this study are as follows: (1) By scanning electron microscopy, dilated internal thoracic arteries yielded consistently higher scores than the control arteries, reflecting severe, tension-dependent alterations of the endothelium, which included marked desquamation of endothelial cells, with extensive areas of complete denudation and pronounced attachment of platelets to these areas; (2) endothelial injury occurred by inflation alone, without shearing by the inflated balloon; (3) by light microscopy, the internal thoracic arteries showed (a) fenestrations of the internal elastic lamina with occasional transmigration of smooth muscle cells through these gaps and (b) foci of intimal thickening without overt atherosclerotic lesions. We conclude that the endothelium of human internal thoracic arteries is highly vulnerable to balloon dilation, which can severely injure the intimal surface. For this reason we prefer not to include this procedure in our protocol for preparing the internal thoracic artery.

Thyrotoxic myopathy in mice: accentuation by a creatine transport inhibitor.

To demonstrate the importance of creatine and phosphocreatine in skeletal muscle during periods of metabolic stress, thyrotoxicosis was induced in mice fed the creatine transport inhibitor, beta-guanidinopropionic acid (beta-GPA). Adding 2% of beta-GPA to the diet of normal mice inhibited weight gain and caused a 75% reduction of creatine and phosphocreatine concentrations in skeletal muscle. Addition of 0.25% or 2% of thyroid powder to the diet of normal mice was associated with hyperactivity, cardiomegaly, and a high mortality rate. Superimposing thyrotoxicosis on mice already depleted of creatine and phosphocreatine resulted in degeneration of muscle fibers. These results indicate that high concentrations of creatine and phosphocreatine are essential for the maintenance of muscle integrity during periods of metabolic stress.

Ultrastructural integrity of human ventricular myocardium following cardioplegic arrest.

The appearance of the ventricular myocardium in 6 patients electing coronary bypass operation was evaluated by electron microscope before and after aortic cross-clamping. Bypassing protocol included the induction of hypothermic cardioplegia by intermittent aortic root perfusion, with potassium chloride added to cold blood serving as the cardioplegic agent. Cross-clamp intervals ranged from 66 to 125 minutes. Ultrastructural alterations following bypass manipulations, and distinct from those observed before cross-clamping, were limited to the presence of extensive myocardiocytic pooling of glycogen. Scrutiny of the intramyocardial capillary bed following perfusion with the cardioplegic solution revealed no abnormalities attributable to, or intensified by, the bypass maneuver. These findings indicate that hypothermic potassium cardioplegia, as specified, is not injurious to human myocardial ultrastructure.

Use of the inferior epigastric artery as a free graft for myocardial revascularization.

From March 1990 through January 1991, 47 patients undergoing myocardial revascularization had one (37) or both (10) inferior epigastric arteries (IEA) used as a conduit for bypass with 62 distal anastomoses. The internal thoracic artery (ITA) was used bilaterally in 41 patients and unilaterally in 6 with 100 distal anastomoses. Five patients had a single saphenous vein graft. In total, 167 anastomoses (3.55 per patient) were performed. Single IEA grafts were harvested through a paramedian incision and bilateral grafts, a midline incision. Harvest time was 36.5 minutes for IEA grafts and 29.6 minutes for ITA grafts (p less than 0.0001). Graft length was 11.9 cm for IEA grafts and 16.5 cm for ITA grafts (p less than 0.0001). Distal graft diameter was 2.0 mm for IEA grafts and 2.1 mm for ITA grafts (p less than 0.01). Graft flow was 49.7 mL/min for IEA grafts and 48.7 mL/min for ITA grafts. Microscopic assessment of segments of both the IEA and ITA from 14 patients revealed similar internal elastic laminae and an equal number of fenestrations. Combined intimal and medial thickness was comparable in both conduits. Medial elastic tissue was more prominent in ITA grafts and lacking in eight of the 14 IEA grafts. Gross plaque formation was noted in the proximal 1 to 3 cm of 50% of IEA grafts, but the lumen was not compromised and microscopic thickening was minimal. An unexpected finding was medial calcifications (Mönckeberg's disease) in two of the 14 IEAs without associated atherosclerosis. There was one hospital death, one abdominal wound infection, and one instance of fat necrosis superficial to the sternum.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of inorganic lead on heptic biochemical and ultrastructural changes produced by phenobarbital.

Lead acetate (105 mumol/kg, i.p.) decreased rat hepatic cytochrome P-450 to 57% and 63% of control values when measured 24 and 48 h after lead administration, respectively. A large increase in urinary delta-aminolevulinic acid (U-ALA) was observed after lead treatment, indicating a depression of heme synthesis. In addition, lead treatment produced dilated cisternae of the smooth endoplasmic reticulum (SER). Phenobarbital (100 mg/kg, i.p.) produced an induction of cytochrome P-450, proliferation of the SER, and did not alter U-ALA content. Simultaneous lead and phenobarbital treatment produced a delayed but robust induction of cytochrome P-450, only a moderate rise in U-ALA, and a reduced proliferation of the SER of hepatocytes. Therefore, phenobarbital, an inducer of heme synthetic enzymes, is apparently capable of reversing lead-induced inhibition of heme synthesis as measured by hepatic cytochrome P-450 induction and U-ALA content.

Quadriceps and myocardial capillary basal laminae. Their comparison in diabetic patients.

Quadriceps and myocardial biopsy specimens were obtained from 24 patients undergoing elective coronary arterial bypass grafting. Patients were divided into those with chemical diabetes (CD) (with incidentally discovered elevated glucose levels when stressed), overt diabetes (OD) (who required insulin support), and euglycemic nondiabetics (ND). Specimens from the quadriceps femoris and left anterior apical segment of the heart were examined ultrastructurally, with particular attention to the evaluation of capillary basal laminar thickness, using morphometric techniques. Results indicate (1) an increased, though statistically insignificant, thickening of capillary basal laminae in the quadriceps of CD and OD patients, in contrast with statistically significant laminar thickening in the diabetic myocardium; (2) early, mild laminar thickening in quadriceps and myocardium of the asymptomatic CD group; and (3) two characteristic patterns of basal laminar contours, homogeneous and lamellated, the latter being seen prominently in the quadriceps of diabetic patients in frequent association with pericapillary edema. These findings support the concept that basal laminar thickening in the diabetic is associated with deranged carbohydrate metabolism.