Biomedical subjects

Truls Myrmel

Publications and source records attributed to Truls Myrmel.

29 records · Page 2Linked to original sources

PubMed2004

Can the principles of evidence-based medicine be applied to the treatment of aortic dissections?

Surgical treatment of patients with acute type A aortic dissections has improved early survival from 10-20 to approximately 80%. Data supporting several other treatment recommendations in patients with aortic dissection, however, are less convincing. We hypothesized that applying strict principles of evidence-based medicine would invalidate most of the recommendations in these published papers. We conducted a literature search asking three questions: (1) Is the use of routine circulatory arrest and an 'open distal' anastomosis technique better than traditional aortic cross clamping? (2) Does a persistent false lumen in the distal aorta wall have an adverse influence on long-term event-free survival? and (3) Is primary surgical or medical treatment of patients with Stanford acute type B dissections preferable in terms of long-term event-free survival? We searched Entrez Pubmed (National Library of Medicine) for all papers on these topics from 1980 to January 2003. Screening 3164 papers identified using the search terms 'aortic dissection' and 'treatment' yielded 15 papers fulfilling a set of a priori inclusion criteria. No study had a design that allowed unequivocal conclusions; moreover, the heterogeneity in study design and patient populations precluded formal meta-analysis. The difficulties inherent in conducting stringent clinical studies addressing various treatment strategies for patients with aortic dissection hamper their quality and weaken their recommendations for different treatment options. Specifically, no conclusive evidence exists favoring use of an open distal anastomosis in patients with acute type A dissections or complete elimination of flow in the distal aortic false lumen; similarly, medical therapy of patients with acute type B aortic dissections has no proven advantage over surgical treatment.

Acute Disease↗

PubMed2004

Nitric oxide synthase inhibition impairs myocardial efficiency and ventriculo-arterial matching in acute ischemic heart failure.

BACKGROUND AND AIMS: The effect of nitric oxide (NO) manipulation in acute heart failure has not been sufficiently investigated. Therefore, we assessed the impact of NO-synthase (NOS) inhibition on left ventricular (LV) function and energetics as well as overall hemodynamics, in a porcine model of acute ischemic LV failure. METHODS: Acute heart failure was induced by left coronary artery microembolization in fourteen anesthetized pigs. LV pressure-volume relationships and mechanical work (PVA) were assessed 30 min after stable heart failure, using pressure-conductance catheters. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. Microembolization led to a significant decrease in cardiac output, arterial pressure and LV systolic and diastolic performance. Animals were then randomized to a control group (n=7) or to receive 15 mg/kg N(omega)-Nitro-L-arginine-metyl ester (n=7), an inhibitor of NO synthase (NOS). RESULTS: Measurements 15 min later revealed that NOS inhibited animals had significantly reduced cardiac output (1.53+/-0.45 vs. 2.13+/-0.49 l/min, P=0.003) and stroke work (1054+/-461 vs. 1296+/-348 mmHg ml, P=0.03), and also displayed a significant increase in the slope of the MVO(2)-PVA relationship (2.57+/-0.53 vs. 1.92+/-0.15, P=0.008), i.e. an inefficient chemomechanical coupling. NOS inhibition did not alter contractility, diastolic function or arterial pressure, but afterload was significantly increased compared to controls (arterial elastance 6.03+/-1.48 vs. 2.74+/-0.34 mmHg/ml, P=0.009). CONCLUSION: Inhibition of NOS in experimental acute heart failure increased afterload without altering left ventricular systolic and diastolic function. Consequently, cardiac output was reduced. Furthermore, mechanoenergetic efficiency was severely impaired. NOS inhibition in acute heart failure and cardiogenic shock warrants further investigations.

Animals↗

PubMed2004

Increased oxygen cost of contractility in the endotoxemic porcine left ventricle.

OBJECTIVE: Myocardial oxygen consumption (MVO) in the septic myocardium is comparatively high in relation to the sepsis-induced reduction in ventricular work. Our previous studies indicate that this energetic inefficiency is due to increased energy consumption in excitation-contraction (EC) coupling, i.e. myocardial calcium handling. DESIGN: To further confirm this observation, we assessed the oxygen cost of contractility in anesthetized pigs before and 2 h after induction of endotoxemia (1 microg/kg endotoxin infusion over 1 h, Escherichia coli toxin, n=6). Baroreceptor reflexes were blocked by hexamethonium. Contractility was increased by stepwise dopamine infusions at baseline and 2 h after induction of endotoxemia. Oxygen cost of contractility was assessed as the relationship between myocardial contractility (E or elastance) and non-mechanical oxygen consumption (unloaded MVO), a measure of energy consumption in EC coupling or calcium handling. RESULTS: Non-mechanical oxygen consumption (unloaded MVO) was higher after endotoxin infusions than at baseline (0.641 +/- 0.05 vs 0.383 +/- 0.07 J/beat/100 g, p < 0.05). The relationship between unloaded MVO and E, constructed by the dopamine response, was highly linear both at baseline and endotoxemia (r2 =0.76-0.99). However, endotoxin increased oxygen cost of contractility by approximately 45% (baseline 0.06 +/- 0.03 vs endotoxin 0.09 +/- 0.04 J ml/mmHg/beat/100 g). CONCLUSION: Acute endotoxemia increases oxygen cost of contractility, a measure of energy consumed in EC coupling or myocardial calcium handling.

Animal Experimentation↗

PubMed2004

E. Coli sepsis induces profound mechanoenergetic inefficiency in the porcine left ventricle.

Myocardial dysfunction is believed to be a central part of septic multiorgan manifestations. The aim of the present study was to assess whether E. coli sepsis in an in vivo model would induce a dysfunction in the relationship between mechanical work and energy consumption in the left ventricle (LV). Accordingly, we measured hemodynamics, left ventricular pressure-volume area (PVA), and myocardial oxygen consumption (MVo2) in deeply anesthetized pigs. Eight pigs received 2.0 +/- 0.5 x 10(9) E. coli bacteria intravenously, and seven served as controls. Compared with baseline and the control group, no alternations were observed in LV diastolic function or indices of contractility in the septic group. The MVo2-PVA relationship was highly linear in both groups (all r2 = 0.96-0.99). At 5 h, the y-axis intercept of the MVo2-PVA relationship (nonmechanical MVo2) had increased in the sepsis group by 70% compared with baseline (P = 0.004) and by 60% compared with the control group (P = 0.003). Contractile efficiency (the inverse of the MVo2-PVA slope) remained unchanged over time and between groups. The study demonstrates a profound increase in nonmechanical oxygen consumption during E. coli sepsis in the LV.

Animals↗

PubMed2004

Branch vessel complications are increased in aortic dissection patients with renal insufficiency.

Morbidity and mortality from aortic dissection remain high despite advances in diagnosis and treatment. Simple markers to identify patients at high risk for non-aortic complications of dissection are lacking. We investigated the effect of renal insufficiency on the presentation, complications, and outcome of patients with acute aortic dissection. We evaluated 638 patients with type A and 365 patients with type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 2000. Chi-squared and Student's ttesting were performed to identify the effect of renal insufficiency on patient presentation, management, and outcome. Patients with renal insufficiency more often required nitroprusside for blood pressure control (type A: 40.7% vs 31.1%, p = 0.049; type B: 66.7% vs 37.3, p = 0.0001) and had a greater risk of mesenteric ischemia (type A: 10.7% vs 1.4%, p < 0.0001; type B: 17.7% vs 3.0%, p < 0.0001). In conclusion, aortic dissection patients with renal insufficiency are at increased risk for drug-resistant hypertension and aortic branch vessel compromise. Routine measurement of serum creatinine provides a readily accessible clinical marker for important complications. Upon recognition, renal impairment indicates a need for close monitoring, aggressive blood pressure control, and evaluation of aortic branch vessel circulations.

Acute Disease↗

PubMed2002

Mechanistic insights into posterior mitral leaflet inter-scallop malcoaptation during acute ischemic mitral regurgitation.

BACKGROUND: Three-dimensional dynamics of the 3 individual scallops within the posterior mitral leaflet during acute ischemic mitral regurgitations have not been previously measured. METHODS: Radiopaque markers were sutured to the mitral annulus, papillary muscle tips, and leaflet edges in 13 sheep. Immediately postoperatively, under open-chest conditions, 3-D marker coordinates were obtained using high-speed biplane videofluoroscopy before and during echocardiographically verified acute ischemic mitral regurgitation produced by occlusion of the left circumflex coronary artery. RESULTS: During acute ischemic mitral regurgitation, at end systole, the anterolateral edge of the central scallop was displaced 0.8+/-0.9 mm laterally and 0.9+/-0.6 mm apically away from the anterolateral scallop; such displacement correlated with lateral displacement of the lateral annulus (R(2)=0.7, SEE=0.7 mm, P<0.001) and movement of the right lateral annulus away from the nonischemic anterior papillary tip (R(2)=0.6, SEE=0.8 mm, P=0.002), respectively. End-systolic displacement of the posteromedial edge of the central scallop was 1.4+/-0.9 mm anteriorly and 0.9+/-0.6 mm laterally away from the posteromedial scallop, corresponding to anterior displacement of the mid-lateral annulus (R(2)=0.5, SEE=1.0 mm, P<0.001). CONCLUSIONS: Malcoaptation of the scallops within the posterior leaflet during acute left ventricular ischemia is a novel observation. The primary geometric mechanism underlying scallop malcoaptation in acute ischemic mitral regurgitation was annular dilatation, which hindered leaflet coaptation by drawing the individual scallops apart. These findings support the use of annular reduction in the repair of ischemic mitral regurgitation and also suture closure of prominent subcommissures between posterior leaflet scallops.

Acute Disease↗

PubMed2002

Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era.

OBJECTIVES: We sought to evaluate the clinical characteristics, management, and outcomes of elderly patients with acute type A aortic dissection. BACKGROUND: Few data exist on the clinical manifestations and outcomes of acute type A aortic dissection in an elderly patient cohort. METHODS: We categorized 550 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection into two age strata (<70 and >or=70 years) and compared their clinical features, management, and in-hospital events. RESULTS: Thirty-two percent of patients with type A dissection were aged >or=70 years. Marfan syndrome was exclusively associated with dissection in the young, whereas hypertension, atherosclerosis and iatrogenic dissection predominated in older patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic regurgitation murmur or pulse deficits) of dissection were less common among the elderly. Fewer elderly patients were managed surgically than younger patients (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p = 0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04) among the elderly. In-hospital mortality was higher among older patients (43% vs. 28%, p = 0.0006). Logistic regression analysis identified age >or=70 years as an independent predictor of hospital death for acute type A aortic dissection (odds ratio 1.7, 95% confidence interval 1.1-2.8; p = 0.03). CONCLUSIONS: Our study shows significant differences between older (age >or=70 years) and younger (age <70 years) patients with acute type A aortic dissection in their clinical characteristics, management, and hospital outcomes. Future research should evaluate strategies to improve outcomes in this high-risk elderly cohort.

Acute Disease↗

PubMed2002

[Long-term results with the left internal mammary artery as coronary bypass].

BACKGROUND: From 1986 we have routinely used the left internal mammary artery instead of autologous vein as bypass to the left anterior descending coronary artery. MATERIAL AND METHODS: A cohort of 52 patients has been followed up for up to 12 years. Six years postoperatively, 40 patients were evaluated by clinical examination, exercise testing and serum lipid assessment. Of these, 38 underwent angiography of the native coronary arteries and of all grafts, which represented 47 left internal mammary artery, 90 saphenous vein, and 3 right internal mammary artery bypasses. Information regarding angina recurrence and the need for repeated revascularisation was obtained from hospital records. Twelve-year mortality data were provided by public registers. RESULTS: Fifty patients were discharged alive. Two serious complications, of which one was fatal, were directly related to the use of the left internal mammary artery. After six years, all the re-examined patients had improved their exercise tolerance; 25 (63%) were angina-free. 44 (94%) left internal mammary artery and 67 (74%) saphenous vein bypasses were patent. Tobacco consumption was considerably reduced over the first six years postoperatively while mean triglyceride and cholesterol levels remained moderately elevated. After 12 years, 18 patients were deceased, half of them from coronary heart disease. INTERPRETATION: Our results are in accordance with large, international studies.

Adult↗

PubMed2002

Pressure-volume-based single-beat estimations cannot predict left ventricular contractility in vivo.

The end-systolic pressure-volume relationship is regarded as a useful index for assessing the contractile state of the heart. However, the need for preload alterations has been a serious limitation to its clinical applications, and there have been numerous attempts to develop a method for calculating contractility based on one single pressure-volume loop. We have evaluated four of these methods. Pressure-volume data were obtained by combined pressure and conductance catheters in 37 pigs. All four methods were applied to 88 steady-state pressure-volume files, including eight files sampled during dopamine infusions. Estimates of single-beat contractility (elastance) were compared with preload-varied multiple-beat elastance [E(es(MB))]. All methods had a low average bias (-0.3 to 0.5 mmHg/ml) but limits of agreement (+/-2 SD) were unacceptably high (+/-2.6 to +/-3.8 mmHg/ml). In the dopamine group, E(es(MB)) showed an increase of 1.7 +/- 0.8 mmHg/ml (mean +/- SD) compared with baseline (P < 0.001). None of the single-beat methods predicted this increase in contractility. It is therefore doubtful whether any of the methods allow for single-beat assessment of contractility.

Animals↗

PubMed2002

Vasodilation and mechanoenergetic inefficiency dominates the effect of the "Ca(2+)-sensitizer" MCI-154 in intact pigs.

OBJECTIVE: Ca(2+)-sensitizing agents hold potential as ideal cardiac inotropes, but effects in intact animals are scarcely described. We evaluated a pyridazinone derivative, MCI-154, for hemodynamic, inotropic, mechanoenergetic and oxidative metabolic effects. DESIGN: Intracavitary left ventricular (LV) pressure and conductance (volume) was assessed in open chest anesthetized pigs (n = 6). Contractile performance, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were assessed. Myocardial substrate uptake and production of (14)CO(2 )(from glucose) and (3)H(2)O (from fatty acids) were monitored. MCI-154 administration: "low range": 0.1, 0.2, 0.3, 0.5 microg/kg/min and "high range": 0.75, 1.0, 2.0, 3.0 microg/kg/min. Parameters were compared with baseline and a time reference group (n = 7). RESULTS: MCI-154 induced a progressive dose-dependent decrease in systemic vascular resistance, with a concomitant increase in heart rate and cardiac output. Contractility increased only in the high-dose range, and mechanoenergetic efficiency was significantly reduced by drug infusion in all doses. CONCLUSION: The pyridazinone derivative MCI-154 has minimal inotropic action, induces a significant "oxygen waste", and decreases vascular resistance in intact pigs. A potent phosphodiesterase inhibitory effect may explain this, which suggests further drug refinement.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Ischemia-induced malcoaptation of scallops within the posterior mitral leaflet.

BACKGROUND AND AIMS OF THE STUDY: The posterior mitral leaflet is divided into a variable number of scallops, and little is known about the role of scallopmalcoaptation in ischemic mitral regurgitation. The study aim was to assess whether acute ischemia in the posterolateral wall of the left ventricle would induce scallop separation that would contribute to mitral regurgitation. METHODS: Radio-opaque markers were surgically placed in the left ventricle, around the mitral annulus, and at three sites along the posterior mitral leaflet edge in eight sheep. Three-dimensional marker coordinates were obtained by biplane videofluoroscopy at 60 Hz and 0.1 mm resolution before and during echocardiographically verified acute ischemic mitral regurgitation produced by balloon occlusion of the circumflex coronary artery. RESULTS: During systole, the mean (+/-SD) distance between the central and anterolateral markers, both placed on the central scallop of the posterior mitral leaflet, was unaffected by ischemia (7.4+/-2.4 versus 7.4+/-2.5 mm; n = 8; p = NS). In contrast, the systolic distance between the central scallop marker and the posteromedial marker increased by 2.3+/-0.2 mm (p = 0.008) in three hearts with the posteromedial marker on the posteromedial scallop, compared with no separation (0.2+/-0.5 mm; p = NS) in five hearts with both the central and posteromedial markers on the central scallop itself. This result shows systolic separation of the central and posteromedial scallops during acute ischemic mitral regurgitation. CONCLUSION: During acute left ventricular ischemia, the central and posteromedial scallops of the posterior mitral leaflet can fail to coapt during systole, potentially contributing to the mitral regurgitation observed.

Animals↗