Cooling to Hypothermic Circulatory Arrest by Immersion vs. Cardiopulmonary Bypass (CPB): Worse Outcome After Rewarming in Immersion Cooled Pigs.

Introduction: Cooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism. Materials and Methods: Total sixteen healthy, anesthetized juvenile (2-3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMM c , n = 8), or cooling by CPB (CPB c , n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia. Results: Survival rates at 2 h after completed rewarming were 4 out of 8 in the IMM c group, and 8 out of 8 in the CPB c group. Compared with the CPB c -group, IMM c animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPB c animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMM c vs. CPB c animals. Conclusion: Our data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMM c animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.

Health-related quality of life after extracorporeal membrane oxygenation: a single centre's experience.

AIMS: The aims of this study were to evaluate health-related quality of life (HRQL) among patients treated with extracorporeal membrane oxygenation (ECMO) in northern Norway over a period of 27 years (1988-2015) and to identify variables related to HRQL. METHODS AND RESULTS: A retrospective inquiry of the ECMO registry at the University Hospital of North Norway identified 74 ECMO-treated patients (mean age 49 years, 65% males). Acute cardiac failure was the dominant indication (58%), and venoarterial ECMO was the dominant mode of treatment (87%). Mortality for discharged patients was recorded on 20 September 2016. Thirty (41%) survivors were identified. Twenty-three survivors were eligible for the survey and received a set of questionnaires at home. The main outcome measure was HRQL as measured with the 36-item Short-Form health survey (SF-36) (RAND Short Form-36 v1.2). Other questionnaires covered demographic information, problems with functioning in usual daily activities (such as hobbies, household chores, family, or work), employment status, and psychological distress. The survey was completed by 20 (87%) survivors (mean age = 49 years, 12 men). Indications for ECMO treatment (VA = 90%) had been respiratory failure (25%), cardiac failure (60%), and extracorporeal cardiopulmonary resuscitation (15%). The average time since ECMO treatment was 6.5 years. Seventy-five percent reported mental HRQL (SF-36 Mental Component Summary, mean = 43, SD = 5) or physical HRQL (SF-36 Physical Component Summary, mean = 43, SD = 4.5) within the normal range (T = 50 ± 10) in comparison with age-matched population data from national norms. Half of the responders reported problems on the SF-36 subscales general health and role physical. Seventy percent reported problems on the SF-36 subscale role emotional. All but one responder lived independently without any organized care, and 90% reported no problems related to basic self-care. Half of those in working age had returned to work after ECMO treatment. Forty percent of the responders reported some degree of restrictions in usual daily activities, problems with mobility (35%), anxiety/depression (35%), or pain/discomfort (55%). Significant univariate associations were observed for poorer HRQL and higher reports of psychological distress, pain, and experiencing restrictions in usual everyday activities. Improved HRQL was significantly related to an extended time since ECMO treatment. CONCLUSIONS: Our survey indicates an overall positive long-term HRQL outcome for our ECMO survivors. A subset reported problems with functioning and HRQL. Future research should focus on identification of the survivors at risk for poor recovery who may benefit from rehabilitation interventions.

Adrenomedullin augments the angiogenic potential of late outgrowth endothelial progenitor cells.

The therapeutic utility of endothelial progenitor cells (EPCs) in cardiovascular disease is potentially hampered by their low numbers in the circulation, impaired functional activity, and inhibitory factors in the recipient. These obstacles can possibly be circumvented by the use of proangiogenic cytokines and peptides. We sought to examine the effect of the endogenous vasoactive peptide adrenomedullin (AM) on the angiogenic potential of late outgrowth EPCs and their release of proangiogenic and proinflammatory cytokines/chemokines. Human peripheral blood mononuclear cells were cultured until the appearance of typical late outgrowth EPC colonies. The effect of AM on EPC proliferation was assessed using a colorimetric MTS proliferation assay while differentiation and formation of tubular structures in an EPC/fibroblast coculture or matrigel assay was used to assess the angiogenic potential of the cells. Finally, the release and mRNA transcripts of cytokines/chemokines were quantified in stimulated vs. nonstimulated EPCs using real-time PCR and a bead-based multiplex assay. The cultured EPCs possessed an endothelial phenotype and expressed the AM receptor (calcitonin receptor-like receptor/receptor activity modifying protein-2). AM stimulation induced proliferation of EPCs compared with controls (P < 0.05). Furthermore, AM produced a 36% and 80% increase in the formation of tubular networks in the EPC/fibroblast coculture and matrigel assay, respectively (P < 0.05). These effects seemed to be mediated through the phosphatidylinositol 3-kinase/Akt signaling pathway. AM did not seem to significantly influence the release or production of IL-6, IL-8, VEGF, stromal cell-derived factor 1, or the expression of CXCR-4 or VEGF receptor 2. In conclusion, adrenomedullin augmented the growth and angiogenic properties of late outgrowth EPCs, but did not influence their paracrine properties.

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

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.

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.

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.

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

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.

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

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.