M. Farstad

Serotonin Is Associated with Coronary Artery Disease and Cardiac Events

BACKGROUNDnBlood platelets are related to coronary atherogenesis. Platelets secrete serotonin (5-hydroxytryptamine) which has several effects on the vascular wall and promotes thrombogenesis, mitogenesis, and proliferation of smooth muscle cells. Serotonin may therefore be one of the factors involved in the development of coronary artery disease (CAD). We have assessed serotonin among conventional predictors for CAD in patients undergoing coronary angiography for chest pain or clinically suspected angina pectoris.nnnMETHODS AND RESULTSnOf 121 consecutive male patients (mean age 65, range 41 to 90 years) undergoing angiography, 96 had coronary artery stenosis and 25 had normal angiograms. Serotonin, blood platelet count, and conventional biochemical risk factors for CAD were determined in the morning the day before the angiography. High serotonin (cut-point 1000 nmol/L) was significantly associated with CAD with an odds ratio (OR) of 3.4 (95% confidence interval 1.2 to 9. 8). The corresponding OR for smokers was 4.8 (1.9 to 12.2); hypercholesterolemia (>7 mmol/L), 2.9 (1.1 to 7.6); high platelet count (cut-point 325 10(9)/L), 3.0 (1.0 to 9.5); and family history of heart disease, 2.3 (1.0 to 5.2). After adjustment with conventional risk factors, the OR for CAD was 3.8 (1.1 to 13.1), comparing high and low values of serotonin. The relation between serotonin and CAD was strengthened only when patients <70 years (n=82) were included in the analysis. In this age group, the occurrence of cardiac events during a mean of 3.7 years of follow-up was significantly associated with high serotonin values.nnnCONCLUSIONSnThe study suggests that serotonin is associated with coronary artery disease and occurrence of cardiac events, particularly in younger age groups. This association seems to persist after adjustment for conventional risk factors.

Rewarming from accidental hypothermia by extracorporeal circulation. A retrospective study

OBJECTIVEnTwenty-six patients with accidental hypothermia combined with circulatory arrest or severe circulatory failure were rewarmed to normothermia by use of extracorporeal circulation (ECC). The aim of the present study was to evaluate our results.nnnPATIENTS AND METHODSnThe treatment of six female and 20 male patients (median age: 26.7 years; range 1.9--76.3 years) rewarmed in the period 1987--2000 was evaluated retrospectively. Hypothermia was related to immersion/submersion in cold water (n=17), avalanche (n=1) or prolonged exposure to cold surroundings (n=8). Prior to admission, the trachea was intubated and cardiopulmonary resuscitation (CPR) initiated in all patients with cardiorespiratory arrest (n=22), whereas in those with respiration/circulation (n=4) only oxygen therapy via a face mask was given.nnnRESULTSnNineteen of the 26 patients were weaned off ECC whereas seven died because of refractory respiratory and/or cardiac failure. Eight of the 19 successfully weaned patients were discharged from hospital after a median of 10 days. One patient died 3 days after circulatory arrest (complete atrioventricular block) resulting in severe cerebral injury. The remaining ten patients died following 1--2 days due to severe hypoxic brain injury (n=5), cerebral bleeding (n=1) or irreversible cardiopulmonary insufficiency (n=4). Based on the reports from the site of accident, two groups of patients were identified: the asphyxia group (n=15) (submersions (n=14); avalanche accident (n=1)) and the non-asphyxia group (n=11) (patients immersed or exposed to cold environment). Seven intact survivors discharged from hospital belonged to the non-asphyxia group whereas one with a severe neurological deficit was identified within the asphyxia group.nnnCONCLUSIONnPatients with non-asphyxiated deep accidental hypothermia have a reasonable prognosis and should be rewarmed before further therapeutic decisions are made. In contrast, drowned patients with secondary hypothermia have a very poor prognosis. The treatment protocol under such conditions should be the subject for further discussion.

Studies on fluid extravasation related to induced hypothermia during cardiopulmonary bypass in piglets.

Background: Hypothermia, commonly used for organ protection during cardiopulmonary bypass (CPB), has been associated with changes in plasma volume, hemoconcentration and microvascular fluid shifts. Fluid pathophysiology secondary to hypothermia and the mechanisms behind these changes are still largely unknown. In a recent study we found increased fluid needs during hypothermic compared to normothermic CPB. The aim of the present study was to characterize the distribution of the fluid given to maintain normovolemia. In addition, we wanted to investigate the quantity and quality of the fluid extravasated during hypothermic compared to normothermic CPB.

Can the use of methylprednisolone, vitamin C, or α-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?

OBJECTIVEnHypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass.nnnMETHODSnA total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated.nnnRESULTSnHemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study.nnnCONCLUSIONnPretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.

Determination of plasma volume in anaesthetized piglets using the carbon monoxide (CO) method

Based on measurements of the circulating red blood cell volume (VRBC) in seven anaesthetized piglets using carbon monoxide (CO) as a label, plasma volume (PV) was calculated for each animal. The increase in carboxyhaemoglobin (COHb) concentration following administration of a known amount of CO into a closed circuit re-breathing system was determined by diode-array spectrophotometry. Simultaneously measured haematocrit (HCT) and haemoglobin (Hb) values were used for PV calculation. The PV values were compared with simultaneously measured PVs determined using the Evans blue technique. Mean values (SD) for PV were 1708.6 (287.3)ml and 1738.7 (412.4)ml with the CO method and the Evans blue technique, respectively. Comparison of PVs determined with the two techniques demonstrated good correlation (r = 0.995). The mean difference between PV measurements was -29.9 ml and the limits of agreement (mean difference ±2SD) were -289.1 ml and 229.3 ml. In conclusion, the CO method can be applied easily under general anaesthesia and controlled ventilation with a simple administration system. The agreement between the compared methods was satisfactory. Plasma volume determined with the CO method is safe, accurate and has no signs of major side effects.

Release of cardiac troponin I after temporally graded acute coronary ischaemia with electrocardiographic ST depression

BACKGROUNDnElevation of cardiac biochemical markers and ST segment depression in the electrocardiogram have important roles in the risk stratification of unstable coronary syndromes. We assessed graded duration of acute coronary ischaemia with ST depression versus release of cardiac troponin I (cTnI) and conventional cardiac markers in 15 ischaemic pigs and 11 controls.nnnMETHODSnCoronary ischaemia was induced via percutaneous technique by semiinflating an angioplasty balloon in the left circumflex artery. Blood velocity monitored by Doppler was reduced until ST depression > or =0.1 mV was obtained. Among 26 pigs, six controls had jugular vein sheath introduced only, five controls jugular vein and bilateral femoral sheaths, and 15 pigs were divided into three equal groups (n=5) in which ischaemia was maintained for 10, 20 and 30 min, respectively.nnnRESULTSnMean blood flow velocity (cm/s) at baseline was 16.3+/-6.5 and was reduced to 4.1+/-3.2 (25% of normal, range 20-29%) during ischaemia. cTnI (microg/l) did not increase in controls but increased from 0.05 to 0.52 (P<0.05) and 0.76 (P<0.05) with 10 and 20 min of ischaemia, and to 30.77 (P<0.05) with 30 min of ischaemia. A rise of myoglobin and conventional cardiac enzymes did not distinguish controls with arterial cut-down from the ischaemia groups.nnnCONCLUSIONnRelease of cTnI depends on the duration of ST depression ischaemia. The critical time for a major release seems to be between 20 and 30 min. Thus, very early intervention in patients with prolonged ST depression ischemia should be focused on in future clinical trials.

Fluid shift is moderate and short‐lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets

Background:u2002 Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time‐course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB.

Infusion of hypertonic saline/starch during cardiopulmonary bypass reduces fluid overload and may impact cardiac function.

Objective: Peri‐operative fluid accumulation resulting in myocardial and pulmonary tissue edema is one possible mechanism behind post‐operative cardiopulmonary dysfunction. This study aimed to confirm an improvement of cardiopulmonary function by reducing fluid loading during an open‐heart surgery.

Reduced fluid gain during cardiopulmonary bypass in piglets using a continuous infusion of a hyperosmolar/hyperoncotic solution

Background:u2002 The aim of this study was to evaluate how a continuous infusion of a hyperosmolar/hyperoncotic solution influences fluid shifts and intracranial pressure during cardiopulmonary bypass in piglets.

Long-term prognostic value of cardiac troponin I and T versus creatine kinase-MB mass after cardiac surgery in low-risk patients with stable symptoms.

The long-term prognostic value of elevated cardiac biomarkers after elective cardiac surgery is not clear. The recent guidelines for diagnosing perioperative infarcts have advocated the use of similar thresholds for creatine kinase-MB (CK-MB) mass and the cardiac troponins. However, few previous data are available comparing these biomarkers after cardiac surgery, and it is not clear whether postoperative elevations of the troponins can be treated the same as elevations of CK-MB. We sought to compare the prognostic value of the cardiac troponins versus the CK-MB mass after elective cardiac surgery in low-risk patients with stable symptoms. A total of 204 consecutive patients undergoing cardiac surgery were included in the final analysis. Blood samples were drawn just before and 1 to 3 and 4 to 8 hours after the procedure, and every morning for 3 days thereafter. Patients with elevated baseline values were excluded. Using a cutoff value of 5 times the reference, patients with high and low values (controls) of CK-MB mass, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were compared. The median follow-up time was 92 months. None developed new Q-waves on the electrocardiogram. The incidence of the composite end point of all-cause mortality, readmission for acute coronary syndrome, and target vessel revascularization in the high CK-MB group was 41.2% compared to 21.8% in the controls (p = 0.004). The corresponding values for cTnT were 33.3% and 20.4% (p = 0.075) and for cTnI were 27.0% and 34.6% (p = 0.237). The p value in the isolated coronary artery bypass grafting subgroup (n = 156) was p = 0.043 for CK-MB, p = 0.137 for cTnT, and p = 0.795 for cTnI. High CK-MB (p = 0.001), ejection fraction (p = 0.002), and body mass index (p = 0.010) were the only variables independently related to reduced event-free survival. No such relation was found for high cTnT and cTnI. In conclusion, CK-MB was superior to the cardiac troponins (values > or =5 times the reference) in predicting long-term event-free survival after elective cardiac surgery in low-risk patients with stable symptoms undergoing coronary artery bypass grafting and/or valve surgery.