Perioperative myocardial protection with the calcium antagonist diltiazem.

The effect of the calcium channel blocker, diltiazem, on cardiac performance was examined in 90 patients who underwent isolated aortic valve replacement for aortic valve diseases with marked left ventricular hypertrophy. The patients were randomly assigned to one of five groups dependent on the treatment plan with diltiazem: group 1, 5-day preoperative treatment with oral administration of 60 mg diltiazem 3 times daily, 10 mg diltiazem intravenously as a bolus dose before the beginning of the cardiopulmonary bypass, and 5 mg diltiazem intravenously 10 min before removal of aortic clamp; group 2, 5-day preoperative treatment with oral administration of 60 mg diltiazem 3 times daily; group 3, 10 mg diltiazem intravenously as a bolus dose before the beginning of CPB and 5 mg 10 min before removal of the aortic clamp; group 4, 15 mg diltiazem in 1000 ml cardioplegic solution, given as additive; group 5, control group not receiving diltiazem. All operative procedures were performed in an identical manner with an average cross-clamping time of 57.7 min and cooling the heart down to 16 degrees-17 degrees septal temperature by perfusion of the coronary arteries with 4 degrees C cold cardioplegic solution. In each patient the heart rate (HR), cardiac output and cardiac index (CO, CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI) and systemic vascular resistance index (SVRI) were recorded and calculated before and after the ischemic period. Transmural samples were obtained three times by needle biopsy technique from the anterior free wall of the heart. Analysis of the variables revealed that: (1) complete cessation of electromechanical activity was achieved significantly more rapidly in groups 1 and 3 than in the other groups; (2) recovery of sinus rhythm and function of the conductive system required significantly longer in groups 1 and 3; (3) the time-related values of the important hemodynamic factors (CO, CI, LWSVI and SVRI) showed a significantly more effective postperfusion cardiac performance in groups 1 and 3 than in groups 2, 4 and 5. An oral dose of 180 mg diltiazem for 5 to 7 days preoperatively in combination with intravenous administration of 10 mg before the beginning of CPB and 5-10 mg during reperfusion can be recommended in patients undergoing open-heart surgery for isolated aortic valve diseases and left ventricular hypertrophy.

Incidences and surgical aspects of cardiac myxomas in Bulgaria.

63 patients with cardiac tumors underwent operative treatment between January 1970 and December 1988. Three additional patients refused the operation, despite the large left atrial myxomas and obstruction of the mitral valve, recognized by echocardiography. 62 patients had benign tumors: the only malignant neoplasm was a fibrosarcoma, originating from the right ventricle. Myxomas were found in 57 patients: 54 were located in the left and 2 in the right atrium. In one case the myxoma originated from the left ventricle. The hospital mortality of the 22 patients who underwent excision of cardiac myxomas between 1970 and 1984 was 18.18% (4 deaths), and 2.44% (1 death) of 41 patients operated on from 1984 to 1988 for cardiac tumors (35 of them with myxomas). During the follow-up time of 6 to 140 months, recurrence of myxomas occurred in only one patient, 4 years after surgery for multifocal myxoma in the left atrium. Surgical excision of the myxoma is the only acceptable therapy able to cure. Without surgical treatment, the medium and long-term prognosis is fatal. Therefore once the cardiac myxoma is identified by two-dimensional echocardiography, the tumor should be removed even in patients without symptoms. The removal of myxomas doesn't require excision of the full thickness of the interatrial septum or ventricular wall. The risk of postoperative arrhythmias after extensive excision increases. Conduction disturbances may be related to the resection of a large area of the atrial septum or wall. No recurrences have been registered after less radical procedures-- removal with excision only of the underlying endocard.

Cytomorphology of atherosclerosis: smooth muscle cells in formation and regression of atherosclerotic lesions.

Human fibrous atherosclerotic plaques from the superficial femoral artery, obtained at surgery and autopsy, were examined by transmission electron microscopy and immunofluorescence microscopy for antibodies to intermediate filament proteins (IF) vimentin, and desmin. The results showed that smooth muscle cells (SMC) of human fibrous plaques accounted for the predominant cell type, demonstrating a spectrum of phenotypes, with prevalence of cells with prominent rough endoplasmic reticulum, implying a synthetic phenotype. In regressing atherosclerotic plaques, contractile SMC were predominant and, along with them, few SMC with abundant cellular organelles were observed, displaying ultrastructural manifestation of collagen phagocytosis. SMC of both progressing and regressing atherosclerotic lesions, regardless of the morphological phenotype of the cell, contained vimentin IF and lacked desmin IF, the marker of differentiated SMC. These observations suggest the existence of a distinctive subpopulation of SMC in the human arterial intima that differs substantially from normal medial SMC by ultrastructure, biochemistry, and function.

Involvement of smooth muscle cells in collagen degradation in the postpartum uterus.

Ultrastructural study of gravid and postpartum involuting human uteri revealed a number of cells containing collagen fibrils in their cytoplasm. In gravid uteri these cells could be identified as macrophages and fibroblasts; in the postpartum uteri smooth muscle cells (SMC) were also found, containing cytoplasmic collagenous vacuoles. The morphology of intracellular collagen in SMC was similar to that observed in macrophages: fragments of banded collagen fibrils with a diameter corresponding to that of extracellular collagen were located within structures considered to be phagosomes. Limiting membranes were always smooth, most often in apposition to the fibrils that were single or packed in small groups; some cytoplasmic vacuoles contained banded elongated profiles barely discernable as collagen. The collagen fibrils within SMC of the involuting human uterus are regarded as a morphological manifestation of heterogenic enclosure of collagen fibrils and their intracellular degradation. It seems that in the postpartum uterus, where a substantial amount of collagen needs to be removed rapidly, both macrophages and SMC are involved in the process of collagen phagocytosis and degradation. These data suggest that SMC may be involved in the cellular mechanism for collagen breakdown in remodelling SMC-containing tissues like the uterus and the vascular wall.

Effects of prostaglandin E1 and 45Ca++-incorporation and spike activity in longitudinal smooth muscle of cat jejunum.

Prostaglandin E1 (0.3 muM) decreased both the 45Ca++-incorporation and the spike activity in isolated longitudinal smooth muscle preparations of the cat jejunum probably by an inhibition of the Ca++ influx.

Degradation of collagen fibers by intimal smooth muscle cells in remodelling atherosclerotic lesions in rabbits.

In electromicroscopic studies of remodelling atherosclerosis in rabbits collagen fibers within smooth muscle cells of atherosclerotic lesions were observed. Their most common appearance was in form of elongated membrane-bound profiles enclosing single banded collagen fibers with a diameter corresponding to that of extracellular collagen. The unit membranes were in apposition to the fibers, that were generally linear or slightly curved. In other instances small groups of collagen fibers lay packed together within larger compartments; still other cytoplasmic vacuoles contained structures hardly recognizable as collagen fibers. In all the cases membranes bordering collagen fibers were free of ribosomes, smooth surfaced. The presence of collagen fibers within smooth muscle cells is regarded as morphological expression of phagocytosis and decomposition of extracellular collagen in remodelling atherosclerotic lesions.

Antiatherogenic effect of pyridinolcarbamate (prodectin). Experimental study.

The experimental study was performed on Wistar rats fed on atherogenic diet for 16 months, the last 70 days of which they were given Prodectin. The study included also Chinchilla rabbits fed on cholesterol-rich diet (CRD) and Prodectin for 5 months. The data obtained showed that the continuous application of Prodectin inhibited the development of cholesterol-induced atherosclerosis both in rats and rabbits. The decrease of plasma lipids, the increased activity of the Krebs cycle enzymes as well as the lowered ADP-platelet aggregation and the decreased endothelial permeability to the pre-beta-like particles suggests a complex mechanism of Prodectin antiatherogenic action. This mechanism probably includes and activation of biological oxidation and bioenergetics, an increase of cAMP in the vascular wall, resp. a decrease of contractility of endothelial cells; an inhibition of thrombotic processes and of lipoprotein infiltration of the arterial wall.

Segmental differences in morphogenetic activity of arterial smooth muscle cells. Histochemical and radioautographic studies.

Differences in morphogenetic and metabolic activities of the arterial smooth muscle cells (s.m.c.) of the young rat's aorta and femoral artery were studied by histochemical, radiochemical and quantitative radioautographic methods. 3H-proline was found to be incorporated into the medial myocyte of both vessels and released into the extracellular connective tissue matrix during the first 6 hours. The intracellular and extracellular phases of this process were similar to those of other scleroprotein-synthesizing cells. The 3H-proline incorporation, the metachromasia (GAG) and the activities of acetyl-cholinesterase, beta-glucuronidase, aryl-sulfatase and 5'-nucleotidase were more intense in the aortic media. On the other hand, some oxido-reductases linked with cellular respiration, glycogenolysis and energy production as well as the myosin-ATPase and MAO activities are more intense in the femoral artery. These differences suggest the morpho-functional diversity of the arterial s.m.c.: greater morphogenetic activity of the aortic myocyte; earlier and higher contractile differentiation of the femoral one.

[Hypertensive arteriopathy: aortic histo-metabolic changes during postnatal ontogenesis in spontaneous hypertensive rats (Okamoto-Aoki strain) (author's transl)]. / Artériopathie hypertensive: modifications histo-métaboliques de l'aorte lors de l'ontogénèse post-natale de rat spontanément hypertendu (lignée d'Okamoto-Aoki)

27 aortic histoenzymatic activities and 6 aortic macromolecular substances were comparatively studied in spontaneous hypertensive rats (SHR) and normotensive Wistar rats (3, 5, 13 and 16 month-old). The earlier aortic changes (3rd month) were only histoenzymatic: 5 Nase and LDH were increased in the entire aorta: some oxido-reductases increase near the intima. These early minor changes might represent some of the factors of the functional disturbance of the arterial smooth muscle cell. At the stage of stable hypertension (5th-13th month) two lesion patterns were seen: 1) metabolic: increase of the histoenzymatic activities involved in lipolysis, GAG anabolism, glycolysis, cell respiration, energizing metabolism and nucleotides-esterolysis. 2) Structural: cell hypertrophy and hyperplasia, interstitial fibrosis. The stimulus of the metabolic changes seems to be dual: 1) the hypertensive factor acting upon smooth muscle cells and/or vasa vasorum. 2) The intraarterial pressure increasing endothelial crossing and stimulating myocyte contraction. The structural change is more probably the reaction to elevated pressure; it has led to diffuse medial thickening providing a balance between hypertension and arterial wall stress. On the 16th month, the cell reaction developed in two ways: 1) increase of metabolic and morphogenetic activation of some cells. 2) irreversible degeneration in some other cell groups (media necrosis, cicatricial fibrosis, decrease of oxidoreductases and lipolytic activities, increase of lysosomal enzymes). Aortic lesions during spontaneous hypertension were less dramatic and occurred later than after experimental hypertension. Some of the observed histometabolic changes might lead to maintenance and worsening of hypertension.

Dynamics of the partial restoration of slow-wave frequency of the duodenum below transection.

Transection of the proximal duodenum of dogs was followed by end-to-end anastomosis. The electrical activity of the duodenal wall of both segments was recorded. On the background of decreased slow-wave frequency below the section single slow waves were observed with duration similar to that of the slow waves above the section. In the days after surgery their number increased, small groups of such waves appearing during and after spike activity. In some of the experiments from the end of the first month of the sixth month after surgery the slow wave frequency below the section approached the slow wave rhythm above the section as evidenced by the histograms. This was a temporary phenomen, which was partly eliminated by cholinergic and alpha- and beta-adrenergic antagonists. Such a phenomenon was also observed in definitively spearated distal segments of the duodenum. Histological examination of intestinal wall taken from the area of anastomosis showed on the 3rd day the presence of single smooth-muscle cells among the granulation tissue, filling the gap between the wound edges; on the 6th day the number of these cells increased and on the 9th and 12th day they formed small groups. From the end of the first month to the sixth month small sheaves of smooth-muscle cells were observed in the cicatricial tissue. It is concluded that the intrinsic nervous system keeps the slow wave frequency below the duodenal transection at a higher level than the smooth muscle cell regeneration might ensure.

Aortic smooth muscle cells reaction in rat spontaneous hypertension.

Parallel morphometric, karyometric and ultrastructural studies of the aortic wall in Okamoto-Aoki rats with short term (3-6 months) and long-term (12-16 months) spontaneous hypertension have revealed a progressive thickening of the medial layer, which is associated with an increaase in the mean nuclear area of the arterial medial smooth muscles and reduction in their mean number per unit area. Electron microscopic studies have shown a multiplication of the intracellular components of aortic smooth muscle cells as a base for their enlargement, as well as small single foci of smooth muscle hyperplasia in the area of the innermost interlamellar space in parts of the aortic wall with intimal thickening. Results of these studies allow the conclusion, that hypertrophy is a reaction of arterial smooth muscle cells to an increased mechanical load in hypertension which, in turn, is responsible for the thickening of arterial with Hyperplasia - increase in smooth muscle cells' number in the media - played a subordinate role. The reaction of the aortic wall to elevate blood pressure is interpreted as a manifestation of the normally limited division capacity of smooth muscle cells in mammals, which does not allow an increase in its cellular components. The function of existing arterial smooth muscle smooth cells is enhanced, instead, by hyperplasia of their specific organelles and augmentation of their volume.