Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

OBJECTIVES: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock. DESIGN: Prospective observational study. SETTING: Monocentric, Hopital Nord, Marseille, France. SUBJECTS: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005). CONCLUSIONS: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.

Lactate in cardiogenic shock - current understanding and clinical implications.

Adenosine triphosphate (ATP) is an essential substrate metabolite in human beings. Mitochondrial oxidative phosphorylation provides > 95% of ATP with the remainder derived from glycolysis or tricarboxylic acid cycle (TCA). In normal hearts, acetyl-CoA is synthesized from the ß-oxidation of free fatty acids (FFA) and the oxidation of pyruvate. Pyruvate is synthesized from glycolysis and can be submitted either for decarboxylation to acetyl-CoA or for dehydrogenation to lactate. Moreover, pyruvate, as well as lactate, plays a key role in aerobic glucose metabolism which is highly dependent on ubiquitous regulatory mechanisms. Many recent advances in molecular biology, genetics, and physiology have revealed new insights into the metabolic flux of lactate. The initial perception characterized by increased lactate production and accumulation in peripheral tissues in anaerobic conditions has been recently contested. The paradigm of increased lactate concentration in the anaerobic setting is discussed according to contemporary reports. Nevertheless, the clinical role of lactate as a prognostic factor in cardiovascular diseases is undisturbed, especially in the field of innovative technology of left/bi ventricular-assist devices and biochips where it reassured its diagnostic and prognostic impact on the cardiovascular system.

Percutaneous left atrial decompression in adults with refractory cardiogenic shock supported with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) distention, a recognized complication in patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock, can lead to pulmonary edema, increased myocardial oxygen consumption, and LV thrombus formation. Atrial septostomy was examined as a management strategy for LV distension. METHODS: Of 72 patients supported with VA-ECMO, seven patients underwent atrial septostomy through a trans-septal approach. The primary indication for atrial septostomy was refractory pulmonary edema. RESULTS: The mean time from ECMO initiation to LA decompression was 1.3 days (range 0-2 days). There was a 100% procedural success rate with improvement in pulmonary edema. Five patients survived to discharge with one patient exhibiting recovery of biventricular function, two patients were transplanted, one patient was decannulated, and one patient was transitioned to long-term durable ventricular assist device. Two patients died, one from multi-organ failure and one with severe anoxic brain injury. CONCLUSION: Atrial septostomy is an effective method of LV decompression that can be performed safely with a high success rate.

Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock.

INTRODUCTION: Platelet mitochondrial respiratory chain enzymes (that produce energy) are variably inhibited during human sepsis. Whether these changes occur even during other acute critical illness or are associated with impaired platelet aggregation and secretion (that consume energy) is not known. The aims of this study were firstly to compare platelet mitochondrial respiratory chain enzymes activity between patients with sepsis and those with cardiogenic shock, and secondly to study the relationship between platelet mitochondrial respiratory chain enzymes activity and platelet responsiveness to (exogenous) agonists in patients with sepsis. METHODS: This was a prospective, observational, case-control study. Platelets were isolated from venous blood of 16 patients with severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet mitochondrial respiratory chain enzymes activity was measured with spectrophotometry and expressed relative to citrate synthase activity, a marker of mitochondrial density. Platelet aggregation and secretion in response to adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating peptide were measured with lumiaggregometry only in patients with sepsis. In total, 16 healthy volunteers acted as controls for both spectrophotometry and lumiaggregometry. RESULTS: Platelets of patients with sepsis or cardiogenic shock similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and complex IV (P < 0.001) activity than those of controls. Platelets of patients with sepsis were generally hypo-responsive to exogenous agonists, both in terms of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial NADH (R (2) 0.36; P < 0.001), complex I (R (2) 0.38; P < 0.001), complex I and III (R (2) 0.27; P = 0.002) and complex IV (R (2) 0.43; P < 0.001) activity was associated with lower first wave of aggregation with ADP. CONCLUSIONS: Several platelet mitochondrial respiratory chain enzymes are similarly inhibited during human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial dysfunction is associated with general platelet hypo-responsiveness to exogenous agonists. TRIAL REGISTRATION: ClinicalTrials.gov NCT00541827 . Registered 8 October 2007.

Oxygen transport and mitochondrial function in porcine septic shock, cardiogenic shock, and hypoxaemia.

INTRODUCTION: The relevance of tissue oxygenation in the pathogenesis of organ dysfunction during sepsis is controversial. We compared oxygen transport, lactate metabolism, and mitochondrial function in pigs with septic shock, cardiogenic shock, or hypoxic hypoxia. METHODS: Thirty-two anaesthetized, ventilated pigs were randomized to faecal peritonitis (P), cardiac tamponade (CT), hypoxic hypoxia (HH) or controls. Systemic and regional blood flows, lactate, mitochondrial respiration, and tissue hypoxia-inducible factor 1 alpha (HIF-1α) were measured for 24 h. RESULTS: Mortality was 50% in each intervention group. While systemic oxygen consumption (VO(2) ) was maintained in all groups, hepatic VO(2) tended to decrease in CT [0.84 (0.5-1.3) vs. 0.42 (0.06-0.8)/ml/min/kg; P = 0.06]. In P, fractional hepatic, celiac trunk, and portal vein blood flows, and especially renal blood flow [by 46 (14-91)%; P = 0.001] decreased. In CT, renal blood flow [by 50.4 (23-81)%; P = 0.004] and in HH, superior mesenteric blood flow decreased [by 38.9 (16-100)%, P = 0.009]. Hepatic lactate influx increased > 100% in P and HH, and > 200% in CT (all P < 0.02). Hepatic lactate uptake remained unchanged in P and HH and converted to release in CT. Mitochondrial respiration remained normal. Muscle adenosine triphosphate (ATP) concentrations decreased in P (5.9 ± 1.4 µmol/g wt vs. 2.8 ± 2.7 µmol/g wt, P = 0.04). HIF-1α expression was not detectable in any group. CONCLUSION: We conclude that despite shock and renal hypoperfusion, tissue hypoxia is not a major pathophysiological issue in early and established faecal peritonitis. The reasons for reduced skeletal muscle tissue ATP levels in the presence of well-preserved in-vitro muscle mitochondrial respiration should be further investigated.

Ischaemia-induced up-regulation of Toll-like receptor 2 in circulating monocytes in cardiogenic shock.

AIMS: To investigate the role of Toll-like receptor 2 (TLR2) in uncomplicated acute myocardial infarction (AMI) and in cardiogenic shock (CS). METHODS AND RESULTS: In patients with uncomplicated AMI (n = 20), CS (n = 30) and in age-matched healthy controls (HC; n = 20), TLR2 expression on monocytes was assessed by flow cytometry. Tumour necrosis factor alpha (TNFα) and interleukin-6 (IL6) expression in monocytes was analysed by intracellular cytokine staining. TLR2 expression was increased in patients with AMI compared with HC [mean fluorescence intensity (MFI) 111.1 ± 8.2 vs. 66.9 ± 1.5, P < 0.001]. In patients with CS, TLR2 expression was further increased (132.8 ± 5.6 MFI, P = 0.009 vs. AMI). This was accompanied by an increased expression of the proinflammatory cytokines TNFα (4.3 ± 1.6% in AMI vs. 20.5 ± 5.9% in CS, P = 0.004) and IL6 (6.3 ± 1.6% in AMI vs. 20.6 ± 6.2% in CS, P = 0.032). Furthermore, in all patients with myocardial infarction (AMI + CS; n = 50), a strong correlation between the monocytic TLR2 expression and the symptom to reperfusion time (r(2)= 0.706, P < 0.001) was found, implying tissue hypoxia dependency. Symptom to reperfusion time is a main factor to influence TLR2 expression but not the presence of CS. TLR2 expression of mononuclear cells exposed in vitro to hypoxia was assessed by flow cytometry and western blot. In vitro measurements showed a hypoxia-mediated monocytic TLR2 expression up-regulation. CONCLUSION: We demonstrate TLR2 up-regulation and increased proinflammatory cytokine expression in circulating monocytes in AMI/CS depending on disease severity, implying an important role of TLR2 expression in ischaemic injury.

Parathyroid carcinoma of the mediastinum.

Parathyroid carcinoma accounts for about 4% of all diseases of the parathyroid glands. It usually presents as a tumor mass in the neck region. Mediastinal parathyroid carcinoma has been reported very rarely. The present paper reports an ectopic parathyroid carcinoma in the anterior mediastinum in a 54-year male that failed to be recognized antemortem. The markedly elevated serum calcium levels were repeatedly put down to laboratory errors, and the clinical features of primary hyperparathyroidism were misjudged and managed only symptomatically. The terminal cardiogenic shock was associated with myocardial infarction. Coronary plastic surgery was carried out and a stent was placed. The postmortem examination found a solid elastic tumor mass (4 cm) firmly encapsulated in the upper half of the anterior mediastinum having trabecular structure, mild nuclear and cellular polymorphism, single irregular mitoses and an area of necrosis. The mass invaded the capsule and the surrounding adipose tissue, there were tumor emboli found in the lymph and blood vessels. Immunohistochemical study showed diffuse expression of low molecular weight cytokeratin, chromogranin A and synaptophysin, and more than 20% of the tumor cells were Ki-67 positive. Glycogen granules were found in their cytoplasm. There were clearly seen metastatic calcifications in the intramural coronary vessels, the cardiomyocytes, the kidneys and the lungs. The present case report contributes considerably to the differential diagnosis of hypercalcemia.

Fisiopatología del shock: Nuevas perspectivas / Pathophysiology of shock: New perspectives

La actividad metabólica puede modificarse mediante la regulación de la población mitocondrial en distintas enfermedades críticas. A través de observaciones y ensayos clínicos examinamos esta adaptación metabólica en el shock cardiogénico, hemorrágico y séptico. La caída de la disponibilidad de O2 (DO2) llevaría a una reducción de la población mitocondrial y consecuentemente a una disminución del consumo de O2 (VO2). Esta secuencia permite atenuar y aun evitar la adquisición de una deuda de O2, considerada hasta hoy base fundamental de la fisiopatología del shock. El costo de esta adaptación mitocondrial es menor energía disponible y el déficit energético resultante ha sido relacionado con la falla orgánica múltiple (FOM), importante complicación de diversos procesos inflamatorios agudos y estados de shock. La FOM es mejor tolerada que el metabolismo anaeróbico y es potencialmente reversible si se revierten las causas desencadenantes y se reestablece el nivel energético por medio de la biogénesis mitocondrial.El desacople de la fosforilación oxidativa mitocondrial ocurre tanto en diversos modelos experimentales de shock como así también en el shock séptico en el hombre. Esta alteración mitocondrial puede ser detectada por un aumento desmesurado del VO2 en respuesta al incremento terapéutico de la DO2. Este aumento de la actividad metabólica puede ser equívocamente interpretado como la fase de repago de una deuda de O2.

Metabolic activity can be down-regulated throughout the reduction of mitochondrial population. Lowering O2 demand in cardiogenic, hemorrhagic and septic shock is here examined through clinical observations and trials. A decrease in the availability of O2 will be followed by reductions in mitochondrial population and, therefore, in a decrease in O2 demand. This response may lessen or prevent the acquisition of an O2 debt; until now, cornerstone in the pathophysiology of shock. The cost of this adaptation is less energy production, and the resulting energy deficit has been linked to multiple organ failure (MOF), a complication of acute inflammatory processes and shock. MOF is better tolerated than anaerobic metabolism and is potentially reversible if the triggering causes are reversed and the energy level is re-established through mitochondrial biogenesis.Decoupling of mitochondrial oxidative phosphorylation occurs in both experimental models and in clinical septic shock. In critical patients this phenomenon may be detected by an inordinate increase in VO2 in response to a therapeutically increased DO2. This hipermetabolic stage can be mistakenly interpreted as the repayment phase of an O2 debt.

Role of nitroso radicals as drug targets in circulatory shock.

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO(-))] as mediators of shock and ischaemia/reperfusion injury. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3 phosphate dehydrogenase, inhibition of membrane sodium/potassium adenosine 5'-triphosphate-ase activity, inactivation of membrane sodium channels and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock and ischaemia and reperfusion. Moreover, various studies have clearly shown that treatment with either OONO(-) decomposition catalysts, which selectively inhibit OONO(-), or with superoxide dismutase (SOD) mimetics, which selectively mimic the catalytic activity of the human SOD enzymes, have been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock and ischaemia/reperfusion injury.

sGC(alpha)1(beta)1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models.

Altered cGMP signaling has been implicated in myocardial depression, morbidity, and mortality associated with sepsis. Previous studies, using inhibitors of soluble guanylate cyclase (sGC), suggested that cGMP generated by sGC contributed to the cardiac dysfunction and mortality associated with sepsis. We used sGC(alpha)(1)-deficient (sGC(alpha)(1)(-/-)) mice to unequivocally determine the role of sGC(alpha)(1)beta(1) in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin- and TNF-induced shock. At baseline, echocardiographic assessment and invasive hemodynamic measurements of left ventricular (LV) dimensions and function did not differ between wild-type (WT) mice and sGC(alpha)(1)(-/-) mice on the C57BL/6 background (sGC(alpha)(1)(-/-B6) mice). At 14 h after endotoxin challenge, cardiac dysfunction was more pronounced in sGC(alpha)(1)(-/-B6) than WT mice, as assessed using echocardiographic and hemodynamic indexes of LV function. Similarly, Ca(2+) handling and cell shortening were impaired to a greater extent in cardiomyocytes isolated from sGC(alpha)(1)(-/-B6) than WT mice after endotoxin challenge. Importantly, morbidity and mortality associated with inflammatory shock induced by endotoxin or TNF were increased in sGC(alpha)(1)(-/-B6) compared with WT mice. Together, these findings suggest that cGMP generated by sGC(alpha)(1)beta(1) protects against cardiac dysfunction and mortality in murine inflammatory shock models.

Cardiogenic shock and status epilepticus after massive bupropion overdose.

BACKGROUND: To describe a profound cardiac dysfunction and a status epilepticus after a massive bupropion overdose. CASE REPORT: A 35-year-old man was admitted in coma following the deliberate ingestion of 12 g of bupropion. The course was marked by the rapid onset of severe and prolonged status epilepticus and cardiogenic shock. Plasma bupropion level determined four hours after the estimated time of ingestion was 1.4 mg/L. All clinical features resolved completely in response to symptomatic treatment. CONCLUSION: Several cases of bupropion overdose, with sinus tachycardia and seizures rapidly corrected by symptomatic treatment, have been reported in the literature. To our knowledge, this case of overdose with bupropion alone, at very high doses, is the first to describe clinical features comprising severe and prolonged status epilepticus and direct cardiotoxicity with the development of cardiogenic shock documented by echocardiogram.

Oxidative stress and antioxidants in patients with cardiogenic shock complicating acute myocardial infarction.

BACKGROUND: Lipid peroxidation and derived oxidized products are being intensively investigated because of their potential to cause injury and because of their pathogenic role in several diseases. The view that an excess of lipid peroxidation products is present and is relevant in the pathogenesis of cardiogenic shock-induced damage has still not received definitive support. METHODS: To evaluate the extent of lipid peroxidation, the status of enzymatic and nonenzymatic antioxidants in patients with cardiogenic shock that complicate acute myocardial infarction (AMI) and to compare with normal subjects. RESULTS: Compared with normal subjects, cardiogenic shock patients had higher malondialdehyde, conjugated dienes and reduced activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lower concentrations of reduced glutathione (GSH) in erythrocyte and in plasma GSH, vitamin C, vitamin E and in beta-carotene. CONCLUSIONS: Cardiogenic shock is associated with greater than normal lipid peroxidation and with an imbalance in antioxidants' status. These results indicate that low activities of SOD, CAT, GPx and low concentrations of GSH, vitamin C, vitamin E and beta-carotene in the circulation of patients with cardiogenic shock complicating AMI may be due to increased utilization to scavenge lipid peroxides. Decrease in plasma concentrations of GSH, vitamin E and beta-carotene seems to be responsible for the elevation of lipid peroxidation in cardiogenic shock complicating AMI compared with MI.

Reversal of glucose-insulin-potassium-induced hyperglycemia by aggressive insulin treatment in postoperative heart failure. An observational study.

Metabolic support with glucose-insulin-potassium (GIK) significantly reduces the morbidity and mortality of patients in cardiogenic shock after hypothermic ischemic arrest for aortocoronary bypass surgery. However, a small subset of these patients develops postoperative insulin resistance regardless of their preoperative diabetic status. Whether GIK directly contributes to higher mortality in these patients is unknown. We reviewed the records of 322 patients whose treatment for postoperative cardiogenic shock included GIK. Ten patients (3%) had postoperative hyperglycemia (serum glucose > or =250 mg/dl or 13.9 mmol/l) due to insulin resistance. These were compared to randomly selected GIK-treated, insulin-responsive patients (n = 10) and non-GIK-treated patients (n = 10) for comparison. The insulin-resistant patients required increasing amounts of regular insulin up to 130 U/h until blood glucose levels fell below 250 mg/dl. However, short-term outcomes (IABP support time, length of stay in ICU, 7-day mortality) for insulin- resistant patients were indistinguishable from those for insulin-responsive patients. These data indicate that postoperative iatrogenic hyperglycemia in patients after cardiopulmonary bypass may not be detrimental per se and is reversible when treated with supplemental insulin.

Roles of ischemia and hypoxia and the molecular pathogenesis of post-burn cardiac shock.

OBJECTIVE: To evaluate the roles of ischemia and hypoxia in the development of post-burn cardiac shock and its molecular pathogenesis. METHODS: One hundred and fifty healthy adult Wistar rats were divided into the control group and burn group inflicted with 30% total body surface area third degree burn. Groups were processed at 1, 3, 6, 12 and 24h post-burn. Myocardial contractile function, myocardial microvascular permeability, volume of regional myocardial blood flow, levels of myocardial myosin light chain 1 (CM-LC1), myocardial NF-kappaB (nuclear factor kappa B) activity, MPO (myeloperoxidase), TNFalpha (tumor necrosis factor alpha) mRNA expression and levels of myocardial TNFalpha were measured. MAIN RESULTS: Myocardial microvascular permeability began to rise at 1h post-burn and was still rising at 24h (2.1 times as high as that of the control group); the volume of regional myocardial blood flow fell significantly and remained at a level markedly lower than that in the control group; CM-LC1 also rose significantly and reached a level 18.6 times as high as that in the control group; myocardial NF-kappaB activity and TNFalpha mRNA expression were significantly promoted; elevation of levels of myocardial TNFalpha and MPO activity occurred; cardiac mechanic parameters including LVSP, +/-dp/dt max significantly decreased while LVEDP increased. CONCLUSION: The findings of the present study suggest severe myocardial damage due to ischemia and hypoxia following burns; promotion of myocardial NF-kappaB activity and TNFalpha mRNA expression in myocardium may be an important factor in the development of post-burn cardiac shock.

Effects of cardiogenic shock on lactate and glucose metabolism after heart surgery.

BACKGROUND: Hyperlactatemia is a prominent feature of cardiogenic shock. It can be attributed to increased tissue production of lactate related to dysoxia and to impaired utilization of lactate caused by liver and tissue underperfusion. The aim of this prospective observational study was to determine the relative importance of these mechanisms during cardiogenic shock. PATIENTS: Two groups of subjects were compared: seven cardiac surgery patients with postoperative cardiogenic shock and seven healthy volunteers. METHODS: Lactate metabolism was assessed by using two independent methods: a) a pharmacokinetic approach based on lactate plasma level decay after the infusion of 2.5 mmol x kg(-1) of sodium lactate; and b) an isotope dilution technique for which the transformation of [13C]lactate into [13C]glucose and 13CO2 was measured. Glucose turnover was determined using 6,62H2-glucose. RESULTS: All patients suffered from profound shock requiring high doses of inotropes and vasopressors. Mean arterial lactate amounted to 7.8 +/- 3.4 mmol x L(-1) and mean pH to 7.25 +/- 0.07. Lactate clearance was not different in the patients and controls (7.8 +/- 3.4 vs. 10.3 +/- 2.1 mL x kg(-1) x min(-1)). By contrast, lactate production was markedly enhanced in the patients (33.6 +/- 16.4 vs. 9.6 +/- 2.2 micromol x kg(-1) x min(-1); p < .01). Exogenous [13C]lactate oxidation was not different (107 +/- 37 vs. 103 +/- 4 mmol), and transformation of [13C]lactate into [13C]glucose was not different (20.0 +/- 13.7 vs. 15.2% +/- 6.0% of exogenous lactate). Endogenous glucose production was markedly increased in the patients (1.95 +/- 0.26 vs. 5.3 +/- 3.0 mg x kg(-1) x min(-1); p < .05 [10.8 +/- 1.4 vs. 29.4 +/- 16.7 micromol x kg(-1) x min(-1)]), whereas net carbohydrate oxidation was not different (1.7 +/- 0.5 vs. 1.3 +/- 0.3 mg x kg(-1) x min(-1) [9.4 +/- 2.8 vs. 7.2 +/- 1.7 micromol x kg(-1) x min(-1)]). CONCLUSIONS: Hyperlactatemia in early postoperative cardiogenic shock was mainly related to increased tissue lactate production, whereas alterations of lactate utilization played only a minor role. Patients had hyperglycemia and increased nonoxidative glucose disposal, suggesting that glucose-induced stimulation of tissue glucose uptake and glycolysis may contribute significantly to hyperlactatemia.

Choque cardiogênico / Shock cardiogenic

O choque cardiogênico caracteriza-se quando uma severa disfunçäo miocárdica provoca hipoperfusäo tecidual e falência orgânica. Os critérios exatos para a presença de choque cardiogênico variam muito na literatura. Além disso é extremamente importante comparar o grau da disfunçäo miocárdica quando se analisam os resultados de diferentes procedimentos. Em 1973, importante estudo multicêntrico estabeleceu os seguintes critérios para a definiçäo de choque cardiogênico: - pressäo arterial sistólica < 80 mmHg (intra-arterial); - débito urinário < 20 ml/h ou confusäo mental; - pressäo de enchimento ventricular > 12 mmHg; - pressäo venosa central > 10 cm H20. Esta definiçäo tem grande utilidade clínica pois inclui a classificaçäo de Kilip para o infarto agudo do miocárdio. Além disso, incorpora os três principais componentes do choque cardiogênico: 1) comprometimento da funçäo ventricular; 2) evidência de falência orgânica como resultado do decréscimo da perfusäo tecidual; e 3) exclusäo de hipovolemia e outras causas do choque. Uma vez que esta definiçäo já foi largamente aplicada com sucesso em estudos prospectivos, pode ser considerada padräo para estudos clínicos futuros.

Circulatory assist techniques in cardiogenic shock: metabolic aspects.

Assisted circulation in severe cardiogenic shock was evaluated using a reservoir and a single pump without an oxygenator in 88 dogs. Study groups included: no treatment, substrates only (cysteine, ribose), nitroprusside, left ventricular (LV) + right atrial (RA) bypass + substrates, LV + RA bypass, left atrial (LA) + RA bypass, LA bypass, LV bypass, LV + RA + fluosol. Metabolic studies of O2 consumption, acid and alkaline phosphatase, lactate, creatine phosphokinase (CPK), myocardial depressant factor (MDF), and tissue adenosine triphosphate (ATP) were done in the course of 4-hour treatment periods followed by 2-hour observation periods. Best survival at 4-hour and 6-hour levels were achieved in LV + RA bypass. Cysteine and ribose reduced survival when added to the pump supported (LV + RA bypass) group. Cysteine/ribose improved survival over the no treatment group. O2 consumption increased significantly in the groups with best survival but remained unchanged from control or shock levels when cysteine/ribose were added. Unusually high levels of CPK, acid and alkaline phosphatase, and MDF occurred in both groups receiving cysteine/ribose, indicating significant organ damage correlating with poor survival. Lactate levels were less predictive. Heart tissue ATP levels were higher in groups with good survival. Liver ATP levels were lower in high survival groups. Lung ATP did not differ between groups.

Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury.

The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event.