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Biomedical subjects

M R Moon

Publications and source records attributed to M R Moon.

At least 19 recordsLinked to original sources
PubMed2001

Rabbit antithymocyte globulin versus OKT3 induction therapy after heart-lung and lung transplantation: effect on survival, rejection, infection, and obliterative bronchiolitis.

The superiority of different induction therapies after heart-lung and lung transplantation is not clearly established; specifically, whether monoclonal (OKT3) or polyclonal antibody induction therapy provides any advantage. Between 1989 and 1991 we used induction therapy with either rabbit antithymocyte globulin (RATG) or OKT3, given at random based on the availability of RATG. RATG was used in 25 patients (RATG group 1) and OKT3 in 38 patients (OKT3 group 1). Early results suggested a survival advantage with RATG. From 1992 until 1997 we used RATG induction therapy in 108 patients (RATG group 2). This study analyzed longer-term survival, infection, rejection, and obliterative bronchiolitis (OB) rates for RATG group 1 and OKT3 group 1 and assessed outcomes for RATG group 2. The 1-, 3-, and 5-year survival for RATG group 1 was 72 %, 72 %, and 52 % and for OKT3 group 1 was 63 %, 49 %, and 34 % (P < 0.05). The 1- and 3-year survival for RATG group 2 was 84 % and 74 %. The 1-, 3-, and 5-year actuarial freedom rates from lung rejection for RATG group 1 were 38 %, 38 %, and 31 % and for OKT3 group 1 were 21 %, 0 %, and 0 % (P < 0.01). The linearized rate (events/100 patient days) of all infections at 3 months was 1.55 +/- 0.28 for RATG group 1 and 2.19 +/- 0.27 for OKT3 group 1 (P = NS). The infection rate for RATG group 2 was 1.60 +/- 0.13. The actuarial rates of freedom from OB at 1, 3, and 5 years for RATG group 1 were 84 %, 51 %, and 45 % and for OKT3 group 1 were 77 %, 61 %, and 36 % (P = NS), while for RATG group 2 the rates were 97 % and 92 % at 1 and 3 years (P < 0.01 vs RATG group 1 and OKT3 group 1). The use of RATG induction therapy from 1989 through 1991 resulted in improved actuarial survival and less rejection, without increased infection rates. The use of RATG since 1992 has continued to result in similar outcomes for survival, infection, and rejection. The time to onset of OB has improved further in recent years. This may be a result of recent improvements in cytomegalovirus (CMV) prophylaxis.

Adult↗
PubMed2001

Does the extent of proximal or distal resection influence outcome for type A dissections?

BACKGROUND: The extent of proximal and distal aortic resection that should be performed for acute type A aortic dissections remains controversial. METHODS: From 1984 to 1999, 119 patients underwent repair of an acute type A dissection. Distal resection was to the ascending aorta in 78 (66%) and hemiarch in 41 (34%) patients. Proximally, the aortic valve was preserved in 69 (58%) patients, 40 (34%) underwent composite valve grafting, and 10 (8%) underwent separate graft and valve replacement. RESULTS: Operative mortality was higher for separate graft and valve (50%+/-16%) than for valve preservation (16%+/-5%) or composite grafts (20%+/-7%) (p < 0.05). Hemiarch replacement did not increase operative risk compared to distal reconstruction to the ascending aorta (17%+/-6% versus 22%+/-5%, p > 0.71). At 10 years, freedom from reoperation was 81%+/-7% and long-term survival was 60%+/-8%, but neither was related to the proximal or distal surgical technique (p > 0.15). Risk factors for late reoperation included a nonresected primary tear and Marfan syndrome (p < 0.05). CONCLUSIONS: An aggressive surgical approach, including a full root or hemiarch replacement, is not associated with increased operative risk and should be considered when type A dissections extensively involve the valve, sinuses, or arch.

Acute Disease↗
PubMed2001

Treatment of endocarditis with valve replacement: the question of tissue versus mechanical prosthesis.

BACKGROUND: It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis. METHODS: Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients. RESULTS: Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64). CONCLUSIONS: Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

Adult↗
PubMed2000

Quality of life after aortic valve replacement at the age of >80 years.

BACKGROUND: The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival. METHODS AND RESULTS: We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84+/-3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old. CONCLUSIONS: Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.

Age Factors↗
PubMed2000

Induction of the stress response in vivo decreases nuclear factor-kappa B activity in jejunal mucosa of endotoxemic mice.

BACKGROUND: Results of previous studies suggest that the stress response protects cells and tissues by regulating proinflammatory mediators. The transcription factor nuclear factor-kappa B (NF-kappa B), normally sequestered in the cytoplasm by its inhibitory protein, I kappa B, regulates many genes involved in inflammatory responses to critical illness. Endotoxemia is associated with increased NF-kappa B activity in intestinal mucosa, but the effect of the stress response on endotoxin-induced NF-kappa B activation in intestinal mucosa is not known. HYPOTHESIS: Induction of the stress response inhibits NF-kappa B DNA binding activity in jejunal mucosa during endotoxemia. METHODS: The stress response was induced in mice by hyperthermia (42 degrees C) or injection with sodium arsenite (10 mg/kg). After 2 to 5 hours, mice were injected with endotoxin (lipopolysaccharide, 12.5 mg/kg) or a corresponding volume of sterile saline. One hour later, jejunal mucosa was harvested for preparation of nuclear and cytoplasmic extracts. RESULTS: Mucosal levels of heat shock protein-72 increased after hyperthermia or treatment with sodium arsenite, consistent with induction of the stress response. The increase in NF-kappa B DNA binding activity and decrease in I kappa B-alpha levels seen after endotoxin injection were inhibited by previous induction of the stress response. CONCLUSION: The protective effects of the stress response in vivo might, at least in part, be due to inhibited NF-kappa B activation.

Animals↗
PubMed2000

Options for repair of a bicuspid aortic valve and ascending aortic aneurysm.

BACKGROUND: Intrinsic abnormality of the aortic wall may explain the association of bicuspid aortic valves with ascending aortic aneurysms. Separate valve and graft repair of such lesions, rather than composite valve graft replacement, is more straightforward but leaves potentially abnormal sinuses behind. METHODS: Between January 1985 and January 1998, 45 patients underwent separate valve and graft (n = 27) or composite valve graft (n = 18) for an ascending aortic aneurysm and bicuspid aortic valve. Perioperative events and late results were compared. RESULTS: Patients undergoing separate valve and graft were older (mean age, 60 +/- 13 vs 42 +/- 12 years, p < 0.001) and were more likely to have purely stenotic (48% vs 6%, p = 0.003) than purely regurgitant (11% vs 72%, p < 0.001) disease. They were also more likely to require concomitant coronary artery bypass grafting (56% vs 6%, p = 0.001). There were no significant differences in operative risk and no known late complications related to recurrent aneurysms. CONCLUSIONS: Root replacement with a composite valve graft can be accomplished with low operative risk and is the first choice for repair of this lesion. Separate valve and graft repair, however, yields satisfactory early and late results and remains an acceptable option, especially when the coronary ostea are not displaced or when concomitant procedures must be performed.

Adult↗
PubMed2000

Heart-lung versus double-lung transplantation for suppurative lung disease.

OBJECTIVE: The purpose of this study was to compare outcomes after heart-lung or double-lung transplantation in patients undergoing transplantation because of end-stage suppurative lung disease. METHODS: We reviewed our experience in patients with cystic fibrosis or bronchiectasis who had heart-lung or double-lung transplantation between January 1988 and September 1997. Twenty-three patients (14 male, 21 cystic fibrosis) had heart-lung transplantation and 24 patients (8 male, 19 cystic fibrosis) had double-lung transplantation. There were no statistically significant differences between the groups in age, weight, preoperative creatinine level, cytomegalovirus status, maintenance immunosuppression, or donor demographics. Patients received induction therapy with monoclonal (OKT3) or polyclonal (rabbit anti-thymocyte globulin) antibody. RESULTS: Sixteen of 24 patients had double-lung transplantation after 1994 whereas 13 of 22 patients had heart-lung transplantation before 1991, allowing longer follow-up for the heart-lung group. Mean waiting times for transplantation were 270 +/- 245 days (heart-lung) and 361 +/- 229 days (double-lung; P =.20). The 1-, 3-, and 5-year actuarial survival figures were respectively 86%, 82%, and 65% (heart-lung) and 96%, 75%, and unavailable (double-lung; P = no significant difference). The 1-, 3-, and 5-year rates of freedom from obliterative bronchiolitis were respectively 77%, 61%, and 45% (heart-lung) and 86%, 78%, and unavailable (double-lung; P = no significant difference). Linearized overall infection rates (events/100 patient-days) were 2.05 +/- 0.33 (heart-lung) and 2.34 +/- 0.34 (double-lung; P = NS) at 3 months. Thirty-day survival was 100% (heart-lung) and 96% (double-lung). There were 7 late deaths among heart-lung recipients (3 obliterative bronchiolitis, 2 infection, 0 graft coronary artery disease, 2 other) whereas 2 late deaths related to obliterative bronchiolitis occurred in double-lung recipients. Graft coronary artery disease (all stenoses < 50%) affected 15% of heart-lung survivors, whereas 3 double-lung recipients (12.5%) required either bronchial dilatation or stenting. CONCLUSION: Heart-lung and double-lung transplantation provide similar palliation for patients with end-stage suppurative lung disease. Therefore double-lung transplantation should be the preferred operation for most patients with end-stage suppurative lung disease.

Adult↗
PubMed2000

Interleukin-1beta induces complement component C3 and IL-6 production at the basolateral and apical membranes in a human intestinal epithelial cell line.

In previous studies, stimulation of cultured enterocytes with IL-1beta resulted in production of IL-6 and complement component C3. The cellular mechanisms of these responses in the enterocyte are not fully understood. We tested the hypothesis that IL-1beta-induced C3 and IL-6 production is differentially regulated at the apical and basolateral membranes of the enterocyte. Caco-2 cells (a transformed human colonic carcinoma cell line) were grown in a 2-chamber system to full differentiation. The cells were treated with IL-1beta either at the apical or basolateral membrane, and C3 and IL-6 mRNA levels and release of C3 and IL-6 into the apical and basal chambers were determined. The release of C3 was greatest into the basal chamber regardless of whether the cells were stimulated at the apical or basolateral membrane. In contrast, the production of IL-6 was greatest at the cell membrane that was stimulated with IL-1beta. Stimulation of the Caco-2 cells with IL-1beta resulted in increased mRNA levels for C3 and IL-6 with no major differences noted when the cells were treated at the apical or basolateral membrane. The results suggest that enterocyte production and release of at least some acute phase proteins and cytokines are differentially regulated at the apical and basolateral membrane of the enterocyte after stimulation with IL-1beta.

Acute-Phase Reaction↗
PubMed2000

IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling.

IL-1beta stimulation of cultured epithelial cells induces the degradation of IkappaBalpha and the consequent nuclear translocation of NF-lambdaB, a critical proinflammatory transcription factor in the mucosal host immune response. The role of reactive oxygen intermediates, serine protease activity, and tyrosine kinase activity in the activation of NF-kappaB is weakly conserved across various cell lineages and has not been defined in human enterocytes, a major target of oxidant stress in sepsis, thermal injury, and hemorrhagic shock. We report here that in Caco-2BBe cells, a transformed human colon cancer cell line with features of small intestinal epithelial cells in culture, exposure to oxidant stress (hydrogen peroxide 1-10 mM) did not induce NF-kappaB activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL-1beta-induced IkappaBalpha degradation and NF-kappaB activation. Genistein, a nonspecific tyrosine kinase inhibitor, also had no effect on IL-1beta-mediated effects on NF-kappaB. Serine protease inhibition by tosyl-lysine-chloromethylketone and tosyl-phenylalanine-chloromethylketone inhibited IkappaBalpha degradation and NF-kappaB activation stimulated by IL-1beta. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL-1beta stimulation and NF-kappaB nuclear translocation.

Adenocarcinoma↗
PubMed2000

Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.

The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.

Animals↗
PubMed1999

Complement component C3 production in IL-1beta-stimulated human intestinal epithelial cells is blocked by NF-kappaB inhibitors and by transfection with ser 32/36 mutant IkappaBalpha.

BACKGROUND: Recent studies suggest that interleukin-1beta (IL-1beta) stimulates the production of the acute phase protein complement component C3 in human intestinal epithelial cells. The transcription factor NF-kappaB activates different genes involved in the response to cytokines. It is not known if IL-1beta-induced C3 production in the enterocyte is regulated by NF-kappaB. MATERIALS AND METHODS: Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with one of the NF-kappaB inhibitors, tosyl-lys-chloromethylketone (TLCK), genistein, or pyrrolidine dithiocarbamate (PDTC), or with N-acetyl-leu-leu-norleucinal (LLnL), a proteasome inhibitor known to block the degradation of Ikappabeta, the cytosolic inhibitor of NF-kappaB. Following this treatment, the Caco-2 cells were stimulated with IL-1beta, and C3 levels in the culture medium were measured after 24 h by ELISA. C3 mRNA levels were determined after 4 h by Northern blot analysis. In other experiments, Caco-2 cells were transfected with a mutant IkappaBalpha in which serines 32 and 36 were substituted by alanine. This mutation prevents IkBalpha phosphorylation and subsequent NF-kappaB nuclear translocation. After transfection, the cells were stimulated with IL-1beta, and C3 levels in the culture medium were measured after 24 h. Cytosolic IkappaBalpha was determined by Western blot analysis. RESULTS: TLCK, genistein, and LLnL each inhibited IL-1beta-induced C3 production in a dose-dependent fashion. These responses were associated with decreased C3 mRNA levels. In contrast, PDTC did not influence C3 production or C3 mRNA in the Caco-2 cells. Transfection of the Caco-2 cells with the Ser 32/36 mutant IkBalpha resulted in maintained IkappaBalpha levels and decreased IL-beta-induced C3 production. CONCLUSIONS: IL-1beta-stimulated C3 production in the enterocyte may be regulated by NF-kappaB.

Base Sequence↗
PubMed1999

Effects of mitral valve replacement on regional left ventricular systolic strain.

BACKGROUND: Mitral valve replacement (MVR) with chordal excision impairs left ventricular (LV) systolic function, but the responsible mechanisms remain incompletely characterized. Loss of normal annular-papillary continuity also adversely affects LV torsional deformation, possibly due to changes in myocardial fiber contraction pattern. METHODS: Twenty-seven dogs underwent insertion of LV myocardial markers and a sham procedure (cardiopulmonary bypass, no MVR, n = 6), conventional MVR with chordae tendineae excision (n = 7), or chordal-sparing MVR with reattachment of the anterior leaflet chordae to the anterior annulus (n = 7) or to the posterior annulus (n = 7). In the anterior, lateral, posterior, and septal LV regions, linear chords were constructed from each region's central marker to its surrounding markers. Percent systolic shortening (regional LV strain) was calculated for each chord, and the chords were assigned to one of four angular groups: I, left-handed oblique (subepicardial fiber direction); II, circumferential (midwall); III, right-handed oblique (subendocardial); or IV, longitudinal. Regional LV strain data were compared before and after MVR. RESULTS: Sham and anterior chordal-sparing MVR had minimal effects on regional LV strain. With posterior chordal-sparing MVR: anteriorly, left-oblique (I) strain fell (31%, p<0.05), as did circumferential (II) and right-oblique (III) strains (by 49% and 51%, respectively; p<0.01). Laterally, left-oblique (I) strain fell by 36% (p<0.05), as did longitudinal (IV) strain (54% decline, p<0.01). Conventional MVR with chordal excision disrupted regional fiber shortening diffusely, affecting oblique fibers (I and III) in the anterior and septal regions and impairing longitudinal (IV) strain in all regions (45% to 68% fall, p<0.05). CONCLUSIONS: Sham and anterior chordal-sparing MVR did not substantially alter regional LV strain; however, loss of normal anatomic valvular-ventricular integrity (conventional MVR) or posterior chordal-sparing MVR resulted in pronounced alterations in LV strain, most notably in the longitudinal and oblique fiber directions. These findings demonstrate that the deleterious effects of chordal excision are associated with perturbed internal myocardial systolic deformation, which suggests that chordal disruption distorts myofiber architecture or regional systolic loading.

Animals↗
PubMed1999

Prospective, randomized comparison of epidural versus parenteral opioid analgesia in thoracic trauma.

OBJECTIVE: To evaluate systemic versus epidural opioid administration for analgesia in patients sustaining thoracic trauma. SUMMARY BACKGROUND DATA: The authors have previously shown that epidural analgesia significantly reduces the pain associated with significant chest wall injury. Recent studies report that epidural analgesia is associated with a lower catecholamine and cytokine response in patients undergoing elective thoracotomy compared with patient-controlled analgesia (PCA). This study compares the effect of epidural analgesia and PCA on pain relief, pulmonary function, cathechol release, and immune response in patients sustaining significant thoracic trauma. METHODS: Patients (ages 18 to 60 years) sustaining thoracic injury were prospectively randomized to receive epidural analgesia or PCA during an 18-month period. Levels of serum interleukin (IL)-1beta, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured every 12 hours for 3 days by enzyme-linked immunosorbent assay. Urinary catecholamine levels were measured every 24 hours. Independent observers assessed pulmonary function using standard techniques and analgesia using a verbal rating score. RESULTS: Twenty-four patients of the 34 enrolled completed the study. Age, injury severity score, thoracic abbreviated injury score, and length of hospital stay did not differ between the two groups. There was no significant difference in plasma levels of IL-1beta, IL-2, IL-6, or TNF-alpha or urinary catecholamines between the two groups at any time point. Epidural analgesia was associated with significantly reduced plasma levels of IL-8 at days 2 and 3, verbal rating score of pain on days 1 and 3, and maximal inspiratory force and tidal volume on day 3 versus PCA. CONCLUSIONS: Epidural analgesia significantly reduced pain with chest wall excursion compared with PCA. The route of analgesia did not affect the catecholamine response. However, serum levels of IL-8, a proinflammatory chemoattractant that has been implicated in acute lung injury, were significantly reduced in patients receiving epidural analgesia on days 2 and 3. This may have important clinical implications because lower levels of IL-8 may reduce infectious or inflammatory complications in the trauma patient. Also, tidal volume and maximal inspiratory force were improved with epidural analgesia by day 3. These results demonstrate that epidural analgesia is superior to PCA in providing analgesia, improving pulmonary function, and modifying the immune response in patients with severe chest injury.

Adolescent↗
PubMed1998

Interleukin-6 production in human intestinal epithelial cells increases in association with the heat shock response.

BACKGROUND: In recent studies, IL-1beta stimulated the production of IL-6 in human enterocytes. The heat shock response influences the production of inflammatory mediators in certain cell types. We tested the hypothesis that heat shock regulates IL-1beta-induced IL-6 production in human intestinal epithelial cells. MATERIALS AND METHODS: Cultured Caco-2 cells, a human intestinal epithelial cell line, were exposed to thermal heat shock at 43 degreesC for 1 h and recovered at 37 degreesC for 1 h. Cells were harvested for analysis of heat shock protein-70 (HSP-70) production by Western blotting. In other experiments, IL-1beta (0.5 ng/ml) was added following heat shock and recovery. IL-6 protein was measured in culture medium after 24 h by enzyme-linked immunosorbent assay and IL-6 messenger RNA (mRNA) levels were measured after 4 h by competitive reverse transcriptase polymerase chain reaction. RESULTS: Heat shock resulted in the production of HSP-70 and potentiated IL-1beta-induced IL-6 production. The response to heat shock was associated with increased IL-6 mRNA levels. CONCLUSIONS: The results suggest that IL-1beta-induced IL-6 production in human enterocytes is increased in association with the heat shock response. The biological role of heat shock-potentiated IL-6 production in the enterocyte remains to be determined.

Caco-2 Cells↗
PubMed1998

Tophaceous pseudogout of the mitral valve.

This report describes a 61-year-old patient on chronic hemodialysis with multiple, left-sided, intracardiac masses causing intermittent coronary obstruction. Mitral valve replacement was performed. Massive deposition of calcium pyrophosphate crystals in and around the valve cusps led to the diagnosis of tophaceous pseudogout (tumoral calcinosis) of the mitral valve.

Calcinosis↗
PubMed1998

Estimation of regional left ventricular wall stresses in intact canine hearts.

Left ventricular (LV) wall stress is an important element in the assessment of LV systolic function; however, a reproducible technique to determine instantaneous local or regional wall stress has not been developed. Fourteen dogs underwent placement of twenty-six myocardial markers into the ventricle and septum. One week later, marker images were obtained using high-speed biplane videofluoroscopy under awake, sedated, atrially paced baseline conditions and after inotropic stimulation (calcium). With a model taking into account LV pressure, regional wall thickness, and meridional and circumferential regional radii of curvature, we computed average midwall stress for each of nine LV sites. Regional end-systolic and maximal LV wall stress were heterogeneous and dependent on latitude (increasing from apex to base, P < 0.001) and specific wall (anterior > lateral and posterior wall stresses; P = 0. 002). Multivariate ANOVA demonstrated only a trend (P = 0.056) toward increased LV stress after calcium infusion; subsequent univariate analysis isolated significant increases in end-systolic LV wall stress with increased inotropic state at all sites except the equatorial regions. The model used in this analysis incorporates local geometric factors and provides a reasonable estimate of regional LV wall stress compared with previous studies. LV wall stress is heterogeneous and dependent on the particular LV site of interest. Variation in wall stress may be caused by anatomic differences and/or extrinsic interactions between LV sites, i.e., influences of the papillary muscles and the interventricular septum.

Animals↗