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Biomedical subjects

J I Fann

Publications and source records attributed to J I Fann.

46 records · Page 3Linked to original sources

Importance of the mitral subvalvular apparatus for left ventricular segmental systolic mechanics.

The relative importance of the anterolateral (ANTLAT) and posteromedial (POSTMED) papillary muscle (PM) chordae tendineae for left ventricular (LV) segmental wall function was assessed in 12 in situ ejecting canine hearts. Pairs of piezoelectric crystals were placed in the regions subtending PM insertions and the ANTLAT LV free wall to measure wall thickness. After mitral valve replacement with complete preservation of the subvalvular apparatus, chordal attachments to either the ANTLAT PM or POSTMED PM were randomly severed using exteriorized snares, followed by subsequent division of the remaining chordae tendineae. Segmental wall function in each region was determined at each stage by segmental preload recruitable stroke work (sPRSW, slope of the segmental stroke work-end-diastolic wall thickness relation). The order in which the chordae were severed was unimportant (p greater than 0.530 in all regions). When the ANTLAT PM chordae were severed first, there were significant declines in sPRSW without a change in the wall thickness intercept in both the ANTLAT (-71.0 +/- 18.3 vs. -57.7 +/- 16.8 mmHg, p less than 0.05) and POSTMED (-81.8 +/- 23.1 vs. -65.4 +/- 17.3 mmHg, p less than 0.05) PM insertion sites. No further significant reductions in sPRSW in either region were detected after severing the remaining chordal attachments to the POSTMED PM. sPRSW in the ANTLAT LV free wall decreased progressively, reaching statistical significance when both sets of chordae tendineae were divided (-88.3 +/- 14.3 vs. -74.0 +/- 15.2 mm Hg, p less than 0.05). When the POSTMED PM chordae were severed first, no significant changes in sPRSW or the wall thickness intercept in either region of PM insertion were detected. Subsequent division of the ANTLAT PM chordal attachments reduced sPRSW significantly in both the ANTLAT PM (-65.9 +/- 21.1 vs. -56.1 +/- 22.1 mm Hg, p less than 0.05) and POSTMED PM (-78.8 +/- 24.7 vs. -67.2 +/- 24.0 mm Hg, p less than 0.05) insertion sites, without a shift in the wall thickness intercept. In the ANTLAT LV free wall, sPRSW again fell progressively, achieving statistical significance only when both chordal attachments were severed (-78.6 +/- 14.8 vs. -62.2 +/- 13.7 mm Hg, p less than 0.05). In conclusion, division of the chordae tendineae resulted in a decline in segmental LV function not only in the areas subtending PM insertions but also in remote LV regions. Furthermore, the influence of the ANTLAT PM chordae predominated local LV systolic function at both PM insertion sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The reversibility of canine vein-graft arterialization.

We assessed the reversibility of functional and morphological changes of arterialized vein segments by returning them to the venous circulation. Thirteen dogs underwent right carotid and femoral veno-arterial grafting. After 12 weeks, veno-arterial grafts were removed for contractility (norepinephrine [NE] and 5-hydroxytryptamine [5-HT]), luminal prostacyclin (PGI2), and morphometric analyses; the remaining segments were used as left jugular and femoral veno-venous grafts. After another 12 weeks, the veno-venous grafts were harvested. To NE, veno-arterial grafts (ED50, 5.4 +/- 0.1 [-log M]) were less sensitive than control veins (ED50, 6.0 +/- 0.2) or veno-venous grafts (ED50, 6.4 +/- 0.2) but were more sensitive than control arteries (ED50, 4.0 +/- 0.1); the maximum tension of veno-arterial grafts (6.2 +/- 0.6 g) was greater than that of veins, less than that of arteries (9.8 +/- 1.0 g), and comparable with that of veno-venous grafts (5.1 +/- 1.1 g). To 5-HT, veno-arterial (ED50, 7.5 +/- 0.1) and veno-venous (ED50, 7.3 +/- 0.2) grafts were more sensitive than arteries (ED50, 6.0 +/- 0.3), while the vein was unresponsive; the maximum tension of veno-arterial grafts (5.0 +/- 0.7 g) was less than that of arteries (6.9 +/- 0.9 g) and greater than that of veno-venous grafts (1.4 +/- 0.3 g). PGI2 production in veins (3.6 +/- 0.8 ng/ml), veno-arterial grafts (3.9 +/- 0.8 ng/ml), and veno-venous grafts (3.3 +/- 0.9 ng/ml) was comparable and less than that of arteries (6.4 +/- 0.9 ng/ml). Veno-arterial graft intimal thickness (127 +/- 8 microns) and intimal area (15.6 +/- 1.8 x 10(3) microns 2) tended to be greater than that in the veno-venous graft (113 +/- 9 microns and 12.4 +/- 1.8 x 10(3) microns 2); also, the veno-arterial graft medial area (103.0 +/- 7.3 x 10(3) microns 2) was greater than that of the veno-venous graft (80.3 +/- 6.9 x 10(3) microns 2), thereby resulting in a similar relative intimal area (13 +/- 1%). Therefore, some changes associated with arterialization, for example, adrenergic sensitivity, maximum tension to 5-HT, medial thickening, and perhaps intimal hyperplasia, reverted toward venous values when replaced in the venous environment, possibly due to variations in pressure, flow, shear stress, and/or graft preparation techniques. Luminal PGI2 was unchanged in the grafts, implying that graft contractility was not modulated by luminal PGI2.

Animals↗

Effects of fish oil on arteriosclerosis in the Japanese quail.

The effects of fish oil on the development of arteriosclerosis were assessed using a special susceptible strain (SEA) of Japanese quail (Coturnix coturnix japonica). Sixty four quail were randomly divided into two groups and placed on isocaloric and approximately isocholesterolic (2% by weight) diets. Group A (control) was supplemented with 10% beef tallow oil, while group B received 10% Menhaden fish oil. The birds were sacrificed at 10 weeks (early) and 15-16 weeks (late). Based on semiquantitative histological grading of the arteriosclerotic lesions in the proximal aorta and brachiocephalic arteries, a score from 1 (no lesion) to 5 (severe, diffuse lesions) was assigned. A total of 57 quail were evaluated (seven died prior to scheduled sacrifice). At the early period, the mean arteriosclerosis scores for group A (n = 8) and group B (n = 8) were 3.3 (SD 1.0) and 1.9(1.0) respectively (p less than 0.017); 63% of the quail in group A and 13% of those in group B had a score greater than or equal to 3 (p less than 0.25, NS). At the late period, the scores for group A (n = 20) and group B (n = 21) were 3.8(0.6) and 2.6(0.9), respectively (p less than 0.001); 95% of the birds in group A and 43% of those in group B had a score greater than or equal to 3 (p less than 0.005). Histopathological examination of the arteriosclerotic lesions revealed disruption of the innermost elastic lamina, increased proteoglycan deposition in the medial interlamellar spaces, and the distinct involvement of macrophage like cells. Compared to human disease, arteriosclerosis in the quail is marked by distinct similarities, as well as differences. The SEA strain of Japanese quail appears to be a practical model for the study of arteriosclerosis; fish oil reduces the severity of disease in these birds when fed a high cholesterol diet.

Animals↗

Mechanisms responsible for inhibition of vein-graft arteriosclerosis by fish oil.

Favorable changes in lipoproteins, inhibition of platelet aggregation, reduction of serum thromboxane (TX), altered plasma-membrane fluidity, and reduced production of growth factors (mitogens) have all been implicated as possibly being involved in the inhibition of arteriosclerosis by fish oil (FO), which is rich in omega 3 fatty acids; however, causal relations are mostly lacking. Several putative mechanisms responsible for the salutary effects of FO were investigated in a canine model of accelerated vein-graft arteriosclerosis. Venoarterial autografts (N = 192) were implanted in 48 hypercholesterolemic dogs divided into six groups: group A, control; B, FO (as MaxEPA, 200 mg/kg/day eicosapentaenoic acid); C, aspirin (ASA, 50 mg/kg/day); D, TX synthetase inhibitor (TXSI [CGS-12970], 10 mg/kg/day); E, FO + ASA; and F, FO + TXSI. At sacrifice 3 months later, there was no significant difference in plasma lipoproteins, hepatic low density lipoprotein-receptor concentration, red blood cell fragility, bleeding time, or platelet count compared with controls; the decrease in platelet aggregation (30 +/- 5% [mean +/- SEM]) was similar in all treatment groups. Arterialized vein-graft intimal thickening was significantly inhibited by FO (with or without ASA), while ASA alone was ineffective. Conversely, serum TX was significantly lower only in the ASA and FO + ASA groups. Serum mitogenic activity was higher at 3 months in the control group versus all treatment groups. Compared with baseline values, serum mitogenic activity rose significantly over time in the control and the TXSI groups, and an increase or rising trend was present in all other treatment groups except for the FO-treated animals. Thus, the salutary biologic effect of FO in this hypercholesterolemic model of arterialized vein grafts may have been more related to in vivo inhibition of platelet-mitogen growth factor release than to changes in lipoproteins, low density lipoprotein receptors, platelet function, or eicosanoid metabolism. These observations underscore the need for further studies to clarify the interactions between FO (omega 3 fatty acids) and paracrine cellular mitogenic factors in the context of atherosclerosis prevention.

Animals↗

Global and regional left ventricular systolic performance in the in situ ejecting canine heart. Importance of the mitral apparatus.

The importance of the intact mitral apparatus in left ventricular (LV) systolic performance has been indirectly suggested by clinical studies of chordal-preserving mitral valve replacement (MVR) or reconstruction. The importance of the intact mitral apparatus has been clearly demonstrated in isovolumic experimental preparations but has not been demonstrated unequivocally in ejecting hearts. Therefore, this question was assessed independently of load in an in situ, open-chest ejecting canine heart preparation (n = 9). Three orthogonal LV dimensions were measured by sonomicrometry. During MVR with complete chordal preservation, snares were placed around the anterior and posterior papillary muscles. After the hearts were weaned from cardiopulmonary bypass, LV function was assessed by caval occlusion to alter LV preload abruptly. The slopes of the end-systolic--pressure-volume (end-systolic elastance, Ees) and stroke-work--end-diastolic volume (preload-recruitable stroke work, PRSW) relations were used to measure global LV systolic function; similarly, the slopes of the end-systolic--pressure-dimension (regional end-systolic elastance, rEes) and stroke-work--end-diastolic dimension changes in regional LV systolic performance. All chordae were then divided by pulling the snares. Immediate reassessment revealed deterioration of global LV function: Ees declined by 72% (14.1 +/- 11.2 mm Hg/ml [mean +/- SD] vs. 3.9 +/- 3.5 mm Hg/ml, p less than 0.001), and PRSW declined by 39% (129 +/- 37 vs. 79 +/- 29 mm Hg, p = 0.0001). Regional LV function was also adversely affected but somewhat selectively: rEes decreased significantly in all three LV dimensions (p less than or equal to 0.03), but rPRSW decreased significantly (-21%) only in the anteroposterior minor LV axis (89 +/- 19 vs. 70 +/- 15 mm Hg, p = 0.005) and in the septal-lateral axis (-19%, p = NS). These data demonstrate the importance of the intact mitral apparatus on LV systolic performance in ejecting hearts, particularly in the LV regions subtended by the papillary muscles.

Animals↗

Surgical management of acute aortic dissection complicated by stroke.

Although patients with acute type A aortic dissection are best managed by emergency surgical intervention, preoperative stroke is known to be an independent predictor of late mortality and is considered by some to be a contraindication to operation because of the risk of precipitating hemorrhagic cerebral infarction and poor long-term outcome. In a series of 272 consecutive, unselected patients with aortic dissection undergoing surgical treatment during a 25-year span (1963-1987), 128 (47 +/- 3% [+/- 70% confidence level (CL)]) had an acute type A dissection. A total of seven patients with acute type A dissection (2.6 +/- 1% of all patients, 5.5 +/- 2% of the acute type A cohort) developed a new stroke preoperatively. Thirteen (4.8 +/- 1%) patients had a diminished or absent carotid pulse, only four (31 +/- 13%) of whom sustained a stroke. One patient died in the immediate postoperative period due to severe brain injury, yielding an operative mortality rate of 14 +/- 14%. Two patients had persistent neurological deficits and died within 4 months of operation; the actuarial survival estimate at 1 year was 57 +/- 19% (mean +/- SEM). One patient recovered function of one upper extremity (preoperative left hemiparesis compounded by paraplegia) but died 6 years later. The remaining three long-term survivors (43 +/- 19%) had major resolution of their neurological deficits and are clinically well 2-8 years postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

"Waterseal" gastrostomy in the management of premature infants with tracheoesophageal fistula and pulmonary insufficiency.

The perioperative management of premature infants with esophageal atresia and tracheoesophageal fistula (EA/TEF) complicated by pulmonary insufficiency continues to be a challenge. Definitive repair is usually delayed or staged and a gastrostomy is initially placed to prevent reflux aspiration. In patients with decreased pulmonary compliance, gastrostomy placement results in decreased intragastric pressure leading to a loss of ventilatory pressure via the tracheoesophageal fistula. A technique using the principle of underwater seal to maintain effective ventilatory pressure after gastrostomy placement is described, and two illustrative cases are presented. After acute respiratory decompensation in these patients, the gastrostomy tube was connected to underwater seal resulting in improved respiratory status. The underwater seal is allowed to intermittently "bubble," thereby permitting partial gastric decompression. This technique maintains effective ventilatory pressure after gastrostomy placement in premature infants with EA/TEF and pulmonary insufficiency until definitive therapy can be achieved.

Esophageal Atresia↗

Endocardial activation mapping and endocardial pace-mapping using a balloon apparatus.

The relation between endocardial activation mapping and endocardial pace-mapping was evaluated in 8 dogs while they were on cardiopulmonary bypass. Pacing or recording was accomplished by using a balloon apparatus (with 32 bipolar electrodes) inserted through a left apical ventriculotomy. Ventricular tachycardia (VT) was produced by occlusion followed by reperfusion of the left anterior descending coronary artery. During each VT, activation mapping was performed and early sites determined. Pace-map correlates (sites at which endocardial pacing produced a similar QRS morphology to that of the VT) were also determined. Isochronous maps were constructed for activation mapping and pace-mapping. There was a total of 29 morphologically distinct VTs. Groups were delineated according to correlations between activation mapping and pace-mapping. In 14 episodes of VT (group 1), pace-mapping confirmed the findings of activation mapping with all early sites being pace-map correlates (total number of early sites (tES) = 19; total number of pace-map correlates (tPMC) = 88; tES same as tPMC = 19). In 9 episodes of VT (group 2), there was a partial correlation between pace-mapping and activation mapping, such that pace-mapping when used with activation mapping appeared to further delineate the region of arrhythmogenesis (tES = 31; tPMC = 59; tES same as tPMC = 14). In 6 episodes of VT (group 3), there was no correlation between pace-mapping and activation mapping (tES = 15; tPMC = 0). With the balloon apparatus, endocardial activation mapping can be performed without the need for sustained monomorphic VT, and endocardial pace-maps may be generated easily.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regional variability of prostacyclin biosynthesis.

To investigate the regional variability in arterial and venous endothelial prostacyclin (PGI2) biosynthesis, we obtained 1-cm segments of carotid arteries, external jugular veins, femoral arteries and veins, iliac arteries and veins, inferior venae cavae (IVC), and aortas from 17 dogs. Vessel luminal PGI2 production was measured in the basal state by radioimmunoassay of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). A total of 90 arterial specimens (57, 19, and 14 segments, respectively, of femoral/carotid arteries, iliac arteries, and aorta) and 41 venous specimens (15, 10, and 16 segments, respectively, of femoral/jugular veins, iliac veins, and IVC) were analyzed. Overall, arterial endothelial 6-keto-PGF1 alpha was higher than venous (8.1 +/- 0.5 ng/ml vs. 4.9 +/- 0.7 ng/ml, p less than 0.0004); 6-keto-PGF1 alpha levels were greater in the arteries than in their corresponding veins [femoral/carotid arteries (6.3 +/- 0.4 ng/ml) vs. femoral/jugular vein (2.1 +/- 0.4 ng/ml), p less than 0.0002; iliac arteries (9.3 +/- 1.0 ng/ml) vs. iliac veins (4.8 +/- 0.9 ng/ml), p less than 0.005; aorta (14.0 +/- 1.6 ng/ml) vs. IVC (7.5 +/- 1.4 ng/ml), p less than 0.006].(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Effects of fish oil on graft arteriosclerosis and MHC class II antigen expression in rat heterotopic cardiac allografts.

The effect of fish oil on accelerated graft coronary arteriosclerosis was assessed in Lewis to Brown-Norway rat heterotopic cardiac allografts. Twelve Brown-Norway rats were supplemented with 2 ml/kg/day of fish oil (68.3 mg eicosopentaenoic acid and 47.5 mg decosahexaenoic acid per milliliter). Eleven additional animals, receiving an isocaloric amount of safflower oil, served as control. All diets began 1 week before operation. Immunosuppression was obtained with low-dose cyclosporine (2 mg/kg/d). When killed (100 days), there were no significant differences in percentage weight gain, graft function, or histologic rejection score. Although lipid profiles were comparable, total cholesterol:high-density lipoprotein ratio was marginally higher in animals treated with fish oil (p = 0.069). Mean percentage luminal occlusion (before and after correcting for differences in size between coronary vessels analyzed) and average intimal thickness were similar between animals treated with fish oil and safflower oil as assessed by computer-assisted digitized, morphometric planimetry. In all allografts, donor interstitial dendritic cells were repopulated with recipient dendritic cells. The major histocompatibility complex class II cell density in the fish oil group did not differ significantly from rats supplemented with safflower oil (1.48 +/- 0.68 vs 1.48 +/- 0.65 cells per mm2, p = 0.995). In conclusion, fish oil did not exert any beneficial effect over safflower oil in terms of graft coronary arteriosclerosis, histologic rejection, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗