Publications by authors named "Stig Muller"

19 Publications

  • Page 1 of 1

Is time from diagnosis to radical prostatectomy associated with oncological outcomes?

World J Urol 2019 Aug 27;37(8):1571-1580. Epub 2018 Nov 27.

Department of Urology, Oslo University Hospital, Postboks 4950 Nydalen, 0424, Oslo, Norway.

Purpose: To study the association between time from diagnosis to radical prostatectomy (RP-interval) and prostate cancer-specific mortality (PCSM), histological findings in the RP-specimen and failure after RP (RP-failure).

Methods: Patients diagnosed with non-metastatic prostate cancer (PCa) in 2001-2010 and prostatectomized within 180 days of biopsy were identified in the Cancer Registry of Norway and the Norwegian Prostate Cancer Registry. Patients were stratified according to risk groups and RP-intervals of 0-60, 61-90, 91-120 and 121-180 days. Aalen-Johansen and Kaplan-Meier methods estimated curves for PCSM, RP-failure and overall mortality. Multivariable Cox regressions and Chi-square tests were used to evaluate the impact of RP-interval on outcomes.

Results: In 5163 eligible patients, the median time from diagnosis to RP was 93 days (range 1-180). Risk group distribution was similar in all RP-interval groups. With almost eight years of observation, no association was found between RP-interval and PCSM in the intermediate-or high-risk groups. Increasing RP-interval did not increase the rate of adverse histological outcomes or incidence of RP-failure.

Conclusions: Increasing RP-interval up to 180 days was not associated with adverse oncological outcomes at eight years follow-up. These findings should be considered when planning for prostatectomy.
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August 2019

Poor reproducibility of PIRADS score in two multiparametric MRIs before biopsy in men with elevated PSA.

World J Urol 2018 May 5;36(5):687-691. Epub 2018 Mar 5.

Department of Urology, Akershus University Hospital, Lørenskog, Norway.

Purpose: Since January 2015, all men referred to urologists in Norway due to elevated PSA or other suspicion of prostate cancer underwent multiparametric MRI (mpMRI) before prostate biopsy. At our hospital, patients and the initial MRI were assessed by an urologist and if deemed necessary, patients were referred to another institution for MR/US fusion biopsies. Before MR/US biopsy, patients underwent a second mpMRI. Since we noticed disagreement of these two mpMRIs before biopsy, we retrospectively assessed the level of agreement between the two mpMRIs from the two institutions.

Methods: During the first 6 months of 2015, 292 patients were referred to our outpatient clinic. We referred 126 patients of these to the other institution for MR/US fusion biopsy. The 2 mpMRIs were performed within 4 weeks. We analyzed MR reports and schematics for number of lesions and highest PIRADS score per side of the prostate and histological result of the biopsies. Bland-Altman's plot was used to compare the level of agreement between the two mpMRIs of the same patient before biopsy.

Results: There was a poor level of agreement between the two mpMRIs and a statistically significant difference in PIRADS scores. Regression analysis showed that there was no proportional or systematic bias.

Conclusion: In unselected patients with elevated PSA, there seems to be a significant variation of mpMRI results across institutions. The PIRADS scoring system needs to be validated with regards to MR equipment, mpMRI protocols and inter-reader variability of radiologists.
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May 2018

Pharmacological Treatment of Post-Prostatectomy Incontinence: What is the Evidence?

Drugs Aging 2016 08;33(8):535-44

Department of Urology, University Hospital North Norway, PO Box.102, N-9038, Tromsø, Norway.

Urinary incontinence is a common and debilitating problem, and post-prostatectomy incontinence (PPI) is becoming an increasing problem, with a higher risk among elderly men. Current treatment options for PPI include pelvic floor muscle exercises and surgery. Conservative treatment has disputable effects, and surgical treatment is expensive, is not always effective, and may have complications. This article describes the prevalence and causes of PPI and the current treatment methods. We conducted a search of the PUBMED database and reviewed the current literature on novel medical treatments of PPI, with special focus on the aging man. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and α-adrenergic drugs have been proposed as medical treatments for PPI. Most studies were small and used different criteria for quantifying incontinence and assessing treatment results. Thus, there is not enough evidence to recommend the use of these medications as standard treatment of PPI. To determine whether medical therapy is a viable option in the treatment of PPI, randomized, placebo-controlled studies are needed that also assess side effects in the elderly population.
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August 2016

Is robotic-assisted radical cystectomy (RARC) with intracorporeal diversion becoming the new gold standard of care?

World J Urol 2016 Jan 25;34(1):25-32. Epub 2015 Nov 25.

Department of Urology, Akershus University Hospital, Lørenskog, Norway.

Background: Totally intracorporeal robotic-assisted radical cystectomy (RARC) has perceived difficulties compared to open radical cystectomy (ORC). As the technique is increasingly adopted around the world, the benefits of RARC with intra- or extracorporeal urinary diversion or ORC for the patients are still unclear. In this article, we consider the current evidence for this issue.

Methods: We assessed two questions through using expert opinion and the medical literature: (A) Is RARC better than ORC for removing the cancer surgery and outcome? (B) Is RARC better than ORC for the urinary diversion?

Outcomes: (A) RARC is better than ORC for shorter length of stay, blood loss and complication rates. (B) Intracorporeal orthotopic neobladder may have a significant physiological and surgical benefit to the patient recovery.

Conclusions: RARC with total intracorporeal reconstruction has potential benefits to the patient. We recommend that all surgeons document patient-related outcome measures, urodynamics and enhanced recovery protocols for cystectomy patients to help us understand the real improvements within bladder cancer surgery and reconstruction.
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January 2016

Robotic and minimal access surgery: technology and surgical outcomes of radical prostatectomy for prostate cancer.

Expert Rev Anticancer Ther 2014 Nov 30;14(11):1317-21. Epub 2014 Sep 30.

Department of Urology, Akershus University Hospital, Sykehusveien 23, Lørenskog 1478, Norway.

Since the 1990s, minimal access surgery has been utilized in urology. In the past 15 years, robotic surgery has evolved and become a natural part of minimal access surgery. The dissemination has been fast and the opportunity of prospective trials has been missed. Nevertheless, robotic surgery has obvious benefits for the surgeon and patient. Even though the scientific evidence is not strong, robotic surgery is here to stay. However, there are lessons to learn from the implementation of the da Vinci system with regards to patient safety and prospective evaluation of the new technology. The future of surgery will include technologies derived from robotic surgery.
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November 2014

Quality of life and satisfaction with information after radical prostatectomy, radical external beam radiotherapy and postoperative radiotherapy: a long-term follow-up study.

J Clin Nurs 2014 Dec 3;23(23-24):3403-14. Epub 2014 Jun 3.

National Continence and Pelvic Floor Center of Norway, University Hospital of North Norway, Tromsø, Norway.

Aims And Objectives: To assess patients' symptoms, quality of life and satisfaction with information three to four years after radical prostatectomy, radical external beam radiotherapy and postoperative radiotherapy and to analyse differences between treatment groups and the relationship between disease-specific, health-related and overall quality of life and satisfaction with information.

Background: Radical prostate cancer treatments are associated with changes in quality of life. Differences between patients undergoing different treatments in symptoms and quality of life have been reported, but there are limited long-term data comparing radical prostatectomy with radical external beam radiotherapy and postoperative radiotherapy.

Design: A cross-sectional survey design was used.

Methods: The study sample included 143 men treated with radical prostatectomy and/or radical external beam radiotherapy. Quality of life was measured using the 12-item Short Form Health Survey and the 50-item Expanded Prostate Cancer Index Composite Instrument. Questions assessing overall Quality of life and satisfaction with information were included. Descriptive statistics and interference statistical methods were applied to analyse the data.

Results: Radical external beam radiotherapy was associated with less urinary incontinence and better urinary function. There were no differences between the groups for disease-specific quality of life sum scores. Sexual quality of life was reported very low in all groups. Disease-specific quality of life and health-related quality of life were associated with overall quality of life. Patients having undergone surgery were more satisfied with information, and there was a positive correlation between quality of life and patient satisfaction.

Conclusion: Pretreatment information and patient education lead to better quality of life and satisfaction. This study indicates a need for structured, pretreatment information and follow-up for all men going through radical prostate cancer treatment.

Relevance To Clinical Practice: Long-term quality of life effects should be considered when planning follow-up and information for men after radical prostate cancer treatment. Structured and organised information/education may increase preparedness for symptoms and bother after the treatment, improve symptom management strategies and result in improved quality of life.
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December 2014

Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS(®)) society recommendations.

Clin Nutr 2013 Dec 17;32(6):879-87. Epub 2013 Oct 17.

Dept of Urology, University Hospital of Lausanne, Switzerland.

Purpose: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery.

Objectives: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group.

Evidence Acquisition: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated.

Evidence Synthesis: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery.

Conclusions: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.
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December 2013

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Eur Urol 2014 Feb 22;65(2):263-6. Epub 2013 Oct 22.

Academic Urology Unit, University of Sheffield, Sheffield, UK.

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.
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February 2014

Predicting erectile function outcome in men after radical prostatectomy for prostate cancer.

BJU Int 2012 Aug 19;110(3):422-6. Epub 2011 Dec 19.

Institute of Naval Medicine, Alverstoke, UK.

Objective: • To identify the reported rates of potency after prostatectomy in the recent literature for men without preoperative erectile dysfunction (ED) and to develop a statistical model for predicting the expected potency after prostatectomy.

Materials And Methods: • A Medline search was conducted with the keywords 'potency' and 'prostatectomy' from 2003 to 2009. • In total, 33 studies in the English language reporting pre- and postoperative erectile function were identified. • Data from studies reporting outcome after open, laparoscopic and robot-assisted prostatectomy were analyzed separately. • Only data obtained from potent men before surgery were included in the analysis.

Results: • In potent men before surgery, the main predictors of post-treatment erectile function are age and time after treatment. • The cumulative range of potency rates at 48 months for all ages (45-75 years) was 49-74% for open, 58-74% for laparoscopic and 60-100% for robotic prostatectomy. • The predicted outcome differs by type of operation and patient age.

Conclusions: • Men aged <60 years have a significant likelihood of regaining erectile function after radical prostatectomy. • The reported statistical model provides a reliable estimation of erectile function outcome after prostatectomy for men with localized prostate cancer and intact erectile function.
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August 2012

Oxygen-wasting effect of inotropy: is there a need for a new evaluation? An experimental large-animal study using dobutamine and levosimendan.

Circ Heart Fail 2010 Mar 16;3(2):277-85. Epub 2009 Dec 16.

Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, and Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.

Background: We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient.

Methods And Results: Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 microg/kg loading and 0.04 microg x kg(-1) x min(-1) infusion) or an equipotent dose of dobutamine (1.25 microg x kg(-1) x min(-1)). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 microg x kg(-1) x min(-1) and 48 microg/kg loading with 0.2 microg x kg(-1) x min(-1) infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area).

Conclusions: Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.
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March 2010

Left ventricular size determines tissue Doppler-derived longitudinal strain and strain rate.

Eur J Echocardiogr 2009 Mar 30;10(2):271-7. Epub 2008 Sep 30.

Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway.

Aims: Tissue Doppler-derived indices of strain (epsilon) and strain rate (SR) have been developed to assess regional cardiac function. However, the effect of left ventricular (LV) size on epsilon and SR has not been studied in depth. The aim of this study was to assess to what extent heart size influence epsilon or SR.

Methods And Results: In 21 anaesthetized pigs ranging from 12.5 to 70.0 kg, tissue Doppler-derived epsilon and SR, and haemodynamic parameters, were assessed during controlled heart rates and different loading conditions. dP/dt did not correlate to pig weight, suggesting constant contractility during growth. Longitudinal epsilon and SR were significantly higher in smaller compared with larger hearts. The hyperbolic correlation between pigs weight and epsilon and SR was r(2)=0.621 and 0.372, respectively, both P<0.0001. Afterload elevation induced a reduction in longitudinal epsilon (from -24.2+/-3.2 to -12.1+/-5.5%, P=0.001) and SR (from -2.3+/-0.8 to -1.3+/-2.4 s(-1), P=0.034), whereas increasing preload increased epsilon (from -26.4+/-10.3 to -38.1+/-14.3%, P=0.006) and SR (from -2.3+/-0.9 to -4.22+/-1.8 s(-1), P=0.002).

Conclusion: Longitudinal epsilon and SR decrease with increasing LV dimensions in spite of an unaltered contractility. These results show and confirm that heart size influences epsilon and SR, which are highly load-dependent parameters.
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March 2009

Utilization and outcome of coronary revascularization and valve procedures in acute heart failure--an evaluation based on the classification from the European Society of Cardiology.

Interact Cardiovasc Thorac Surg 2008 Oct 4;7(5):833-8. Epub 2008 Jul 4.

Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, 9038 Tromsø, Norway.

Early invasive treatments in patients with acute heart failure (AHF) are critical components to improve outcome. We aimed to establish if such treatments were applied according to existing guidelines and also to assess the subsequent mortality in the complete AHF population. All patients with AHF admitted to the intensive care unit/coronary care unit during the years 2003-2004 (n=302) were retrospectively reviewed and classified according to the European Society of Cardiology. Invasive revascularization was applied more frequently in patients with cardiogenic shock following acute coronary syndromes (78%, n=40) than in less severe AHF (58%, n=62, P<0.05). Only 8% (n=4) of eligible patients with acute coronary syndromes and cardiogenic shock were treated non-invasively. Valvular dysfunction was a precipitating factor for AHF in 15% (n=38). Acute mitral regurgitation was treated surgically exclusively in patients with mechanical defects. In-hospital mortality rates for less severe AHF was 12%, cardiogenic shock 46% and postcardiotomy HF 32%. Invasively treated patients had lower in-hospital mortality in both cardiogenic shock (35% vs. 70%, P=0.006) and less severe AHF (6% vs.17%, P=0.042). The study revealed an appropriate use of invasive revascularization. The high mortality in patients with severe AHF indicates that more effective treatment options are needed in eligible patients.
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October 2008

How many acute heart failure patients need a ventricular assist device?

Scand Cardiovasc J 2008 Apr;42(2):118-24

Department of Cardiothoracic and Vascular Surgery, University Hospital, North Norway, Tromsø, Norway.

Objectives: The most severe forms of acute heart failure have a dismal prognosis despite modern invasive treatment. For some of these patients, improved outcome must relay on early institution of ventricular assist devices (VAD). We aimed to estimate the potential VAD need in acute heart failure.

Design: All patients admitted to the ICU or CCU for acute heart failure (AHF) in 2003/04 (n=302) were reviewed. Non-survivors with severe acute heart failure, i.e. cardiogenic shock and postcardiotomy HF, were individually reviewed to assess eligibility for VAD-treatment.

Results: Cardiogenic shock and postcardiotomy HF was present in 23% (n=69) and 19% (n=57) of the AHF patients. Overall in hospital mortality in these groups was 38% (n=48). Of these, 15 were less than 75 years of age, without serious comorbidities and thus deemed to be potential candidates for VAD-treatment.

Conclusion: This survey indicates that 12% of patients with severe acute heart failure are potential candidates for VAD-treatment. Extending these figures to a national level, indicate that approximately 70 patients per year could be candidates for short-term VAD-treatment in Norway.
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April 2008

Vasopressin impairs brain, heart and kidney perfusion: an experimental study in pigs after transient myocardial ischemia.

Crit Care 2008 21;12(1):R20. Epub 2008 Feb 21.

Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway.

Introduction: Arginine vasopressin (AVP) is increasingly used to restore mean arterial pressure (MAP) in low-pressure shock states unresponsive to conventional inotropes. This is potentially deleterious since AVP is also known to reduce cardiac output by increasing vascular resistance. The effects of AVP on blood flow to vital organs and cardiac performance in a circulation altered by cardiac ischemia are still not sufficiently clarified. We hypothesised that restoring MAP by low dose, therapeutic level AVP would reduce vital organ blood flow in a setting of experimental acute left ventricular dysfunction.

Methods: Cardiac output (CO) and arterial blood flow to the brain, heart, kidney and liver were measured in nine pigs using transit-time flow probes. Left ventricular pressure-volume catheter and central arterial and venous catheters were used for haemodynamic recordings and blood sampling. Transient left ventricular ischemia was induced by intermittent left coronary occlusions resulting in a 17% reduction in cardiac output and a drop in MAP from 87 +/- 3 to 67 +/- 4 mmHg (p < 0.001). A low-dose therapeutic level of AVP (0.005 U/kg/min) was used to restore MAP to pre-ischemic values (93 +/- 4 mmHg).

Results: AVP further impaired systemic perfusion (CO and brain, heart and kidney blood flow reduced by 29, 18, 23 and 34%, respectively) due to a 2.0-, 2.2-, 1.9- and 2.1-fold increase in systemic, brain, heart and kidney specific vascular resistances. The hypoperfusion induced by AVP was associated with an increased systemic oxygen extraction. Oxygen saturation in blood drawn from the great cardiac vein fell from 29 +/- 1 to 21 +/- 3% (p = 0.01). Finally, these effects were reversed 40 min after AVP was withdrawn.

Conclusion: Low dose AVP induced a pronounced reduction in vital organ blood flow in pigs after transient cardiac ischemia. This indicates a potentially deleterious effect of AVP in patients with heart failure or cardiogenic shock due to impaired coronary perfusion.
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June 2008

Clinical testing of nicorandil supplemented normokalemic cardioplegic solution.

Interact Cardiovasc Thorac Surg 2006 Oct 10;5(5):521-5. Epub 2006 Jul 10.

Department of Cardio-Thoracic and Vascular Surgery, University Hospital of North Norway, Breivika, P.O. Box 102/exp, N-9038 Tromsø, Norway.

Does nicorandil instead of supranormal potassium safely provide cardioplegia and cardioprotection in humans? Fifty patients eligible for coronary artery surgery were randomly divided into two groups; one group received standard St Thomas' Hospital solution (STHS) and the other group got a crystalloid solution in which supranormal potassium was replaced with 0.2 mmol/l nicorandil. We measured time to arrest, rhythm abnormalities, pre- and postoperative troponin-T, CK-MB and myoglobin release as well as hemodynamic parameters. Time to arrest was significantly shorter in the STHS group (41.0+/-16.8 s) than in the nicorandil group (120.9+/-78.8 s, P<0.001). Four patients in the nicorandil group needed additional STHS to achieve satisfactory cardiac arrest. Troponin-T was elevated in the nicorandil group at four (P=0.042) and at eight (P=0.044) hours after surgery, myoglobin levels were elevated at 0 h after surgery (P=0.014), CK-MB levels were not group different. Hemodynamic performance was similar in both groups. Potassium should probably not be replaced by nicorandil alone in the cardioplegic solution. This study of low-risk patients with short (43.2 min) aortic cross-clamp times showed similar cardioprotection as revealed by hemodynamic performance whereas early release of troponin-T and myoglobin release in the nicorandil group raised some concern.
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October 2006

Adenosine instead of supranormal potassium in cardioplegic solution improves cardioprotection.

Eur J Cardiothorac Surg 2007 Sep 5;32(3):493-500. Epub 2007 Jul 5.

Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway and Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.

Objective: To determine whether adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest and improved cardioprotection. Cold crystalloid cardioplegia with adenosine, procaine and magnesium (A) was compared with standard cold crystalloid hyperkalemic cardioplegia (K).

Methods: Sixteen pigs were randomized to receive either cold K (n=8) or A (n=8), where hyperkalemia was substituted with 1.2 mM adenosine. The cold (6 degrees C) cardioplegia was given intermittently and antegradely, with an aortic cross-clamp time of 1 h. Hemodynamic data was continuously measured and pressure-volume conductance catheters were used to determine global left ventricular systolic and diastolic function. Coronary flow and O2 content differences allowed determination of left ventricular energetics. Blood samples, and left ventricular microdialysis were used to measure parameters of ischemia. Measurements were done at 1 and 2 h after cross-clamp release.

Results: Mean arterial pressure was reduced with 55 mmHg (standard deviation, SD: 19) in the K group versus 30 mmHg (SD: 14) in the A group 2 h after cross-clamp release (p=0.030). Left ventricular contractility expressed as slope of the preload recruitable stroke work index (Mw) was reduced to 53% (SD: 14) in the K group versus 78% (SD: 23) in the A group 2h after cross-clamp release (p=0.046). Reduction of maximum of first derivate of pressure with respect to time (dP/dtmax) was 804 mmHg/s (SD: 189) in the K group versus 538 mmHg/s (SD: 184) in the A group (p=0.033). The slope of the myocardial oxygen consumption-pressure volume area was at 2 h reperfusion increased from 1.37 (SD: 0.64) to 2.86 (SD: 1.27) in the K group, whereas no shift was detected in the A group (p=0.019). Cardiac troponin T measured in the coronary sinus 1 h after cross-clamp release was 1.25 microg/l (SD: 0.64) in the K group versus 0.73 microg/l (SD: 0.31) in the A group (p=0.046).

Conclusion: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest, improves post cardioplegic left ventricular systolic function and efficiency, and attenuates myocardial cell damage.
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September 2007

Mechanical restitution curves: a possible load independent assessment of contractile function.

Eur J Cardiothorac Surg 2007 Apr 14;31(4):677-84. Epub 2007 Feb 14.

Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, N-9038 Tromsø, Norway.

Objective: The time constant of mechanical restitution (T((MRC))), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure, and might have a potential as an index of contractile function. However, in vivo studies of the effect on T((MRC)) of changing loading conditions in the normal and failing heart have not been reported. Consequently, in this study, we tested the hypothesis that the increase in T((MRC)) in vivo is independent of preload and afterload.

Methods: Left ventricular pressure-volume loops were assessed at baseline in eight open chest pigs using the combined pressure-volume conductance catheter technique during right atrial pacing at 120b/min. Mechanical restitution curves (MRC) were constructed during four different loading conditions in all eight animals: uninfluenced load, reduced preload (balloon catheter in v. cava inferior), increased afterload (balloon catheter in descending aorta), and increased preload combined with reduced afterload (aortocaval shunting). Acute LV failure was then induced by microembolization through the left main coronary artery, and the experimental protocol was repeated. Contractile response was defined as the maximal first derivative of pressure (dP/dt(max)), and T((MRC)) was calculated using a least square approximation algorithm.

Results: Hemodynamic data 30min after microembolization showed decreased mean arterial pressure (98+/-14-67+/-10mmHg, (mean+/-SD) P<0.0001) and dP/dt(max) (1482+/-193-1001+/-125mmHg/s, P=0.001). Stroke volume decreased from 30+/-5 to 20+/-5ml (P<0.0001) compared to baseline, and preload recruitable stroke work decreased from 52+/-7 to 31+/-10mmHg (P=0.002). T((MRC)) increased in all eight animals after induction of LV failure at all loading conditions. There was no difference between the different loading conditions at baseline, nor at LV heart failure, but T((MRC)) increased significantly after the induction of heart failure (ANOVA, two ways).

Conclusions: We have shown that the left ventricular T((MRC)) increases after developed heart failure. The increase in T((MRC)) was independent on loading conditions and thus have a potential for a contractility index.
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April 2007

The pressure-volume loop revisited: Is the search for a cardiac contractility index a futile cycle?

Shock 2006 Apr;25(4):370-6

Department of Surgery, Institute of Clinical Medicine, University of Tromsø, N-9038 Tromsø, Norway.

Unlabelled: Our previous studies indicate that left ventricular end-systolic pressure-volume relations (ESPVRs) or elastance (Ees) are not reduced in studies where expected reductions of contractility should be found (i.e., heart failure, stunning, and endotoxemia). The present study was done to assess whether this phenomenon is due to a particular load sensitivity of elastance, rendering this index inappropriate as a measurement of contractility in pathologic states in vivo.

Methods And Results: Analysis of previously generated data revealed an increased ESPVR in stunned hearts, in pigs made endotoxemic, and in hearts rapidly paced. After inducing acute heart failure by microembolization, the ESPVR was increased when assessed using linear relations but reduced when assessing ESPVR by a curvilinear algorithm. To further evaluate the effect of different load alterations on ESPVR, this relation was generated by (i) inferior vena caval occlusions (VCOs); (ii) gradually occluding the descending aorta (pressure interventions); and (iii) rapidly infusing blood (120 mL) into the left atrium (volume increments). The load protocol was applied in 5 pigs, before and after the left ventricle was stunned by 11 brief left main coronary artery occlusions/reperfusions (accumulated ischemia 20 min affecting 81% of the left ventricle). Correlation coefficients for left ventricular elastance ranged from 0.93 to 0.99 in all the 3 types of loading interventions. Despite significant reductions in stroke volume, stroke work, and dP/dtmax, VCO-calculated linear and curvilinear Ees increased 90 min after stunning (55% +/- 4% and 94% +/- 6%, respectively). Linear Ees during pressure interventions decreased 36% +/- 1%, whereas curvilinear Ees decreased 33% +/- 3%. During volume infusions, linear Ees decreased 27% +/- 2%. We achieved the same results after blocking the baroreceptor reflexes using hexamethonium.

Conclusions: The Ees is particularly load dependent and will reflect load interventions more than the inotropic state of the cardiac muscle. A VCO-generated Ees increase could be an unmasking of a pronounced preload sensitivity in failing myocardium.
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April 2006

Intraaortic balloon pumping improves hemodynamics and right ventricular efficiency in acute ischemic right ventricular failure.

Ann Thorac Surg 2004 Oct;78(4):1426-32

Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, Tromsø, Norway.

Background: Left ventricular unloading has a potentially deleterious effect in right ventricular failure as a result of altered septal interplay. However, a positive effect of an intraaortic balloon pump during right ventricular failure has been suggested. We investigated the impact of intraaortic balloon pumping on hemodynamics and both left and right ventricular function in an experimental model of isolated right ventricular failure.

Methods: Sixteen anesthetized pigs (25 to 34 kg) were used in an in vivo model. Pressure-conductance catheters assessed right and left ventricular pressure-volume relationships. Acute right ventricular failure was induced by right coronary microembolization, and led to severely impaired right ventricular function, reduced cardiac output and arterial pressure, and an increased pulmonary vascular resistance and pulmonary arterial elastance. Animals were then randomized to balloon pump or control groups and evaluated with respect to hemodynamics and ventricular function after 1 hour.

Results: Intraaortic balloon pumping did not alter right or left ventricular contractility. However, balloon pump-treated animals had significantly improved cardiac output (+18% +/- 18% versus -6% +/- 7%; p = 0.003) and mean arterial pressure (+36% +/- 30% versus -7% +/- 14%; p = 0.004) compared with controls. Animals in the balloon pump group had lower pulmonary vascular resistance (795 +/- 63 versus 912 +/- 259 dynes . sec . cm(-5); p < 0.01) and pulmonary arterial elastance (1.14 +/- 0.20 versus 1.69 +/- 0.65 mm Hg/mL; p < 0.01), and increased stroke volume (22.3 +/- 4.7 versus 17.9 +/- 4.7 mL; p = 0.016). Right ventricular efficiency was also improved in the balloon pump group (stroke work per pressure-volume area = 0.60 +/- 0.14 versus 0.41 +/- 0.12; p < 0.01).

Conclusions: Intraaortic balloon pump support does not alter right or left ventricular function in acute right ventricular failure. However, arterial pressure, cardiac output, and right ventricular efficiency are improved, possibly because of a balloon pump-induced reduction in pulmonary arterial resistance.
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October 2004