S. E. Rynning

Dynamic evaluation of fluid shifts during normothermic and hypothermic cardiopulmonary bypass in piglets

Background: Edema, generalized overhydration and organ dysfunction commonly occur in patients undergoing open‐heart surgery using cardiopulmonary bypass (CPB) and induced hypothermia. Activation of inflammatory reactions induced by contact between blood and foreign surfaces are commonly held responsible for the disturbances of fluid balance (“capillary leak syndrome”). We used an online technique to determine fluid shifts between the intravascular and the interstitial space during normothermic and hypothermic CPB.

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?

OBJECTIVE Hypothermic 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. METHODS A 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. RESULTS Hemodilution 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. CONCLUSION Pretreatment 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.

Carvedilol Protects Against Lethal Reperfusion Injury Through Antiadrenergic Mechanisms

We examined the effect of carvedilol as compared with that of a combination of propranolol and doxazosin on lethal reperfusion injury in 21 feline hearts subjected to 40-min regional ischemia and 180-min reperfusion. A control group (n = 7) was compared with one group given carvedilol, a nonselective beta - and alpha 1-adrenoceptor blocker and antioxidant (n = 7) and another group given nonselective beta - and alpha 1-adrenoceptor blockade with propranolol and doxazosin (n = 7) during initial reperfusion. Infarct size (IS: percent of area at risk, AAR) determined by staining the myocardium with triphenyl tetrazolium chloride (TTC), was reduced both in the carvedilol-treated group (median 1.8%, p < 0.05) and in the group given propranolol/doxazosin (median 6.5%, p < 0.05) as compared with controls (median 14.4%). Treatment with carvedilol reduced IS more than did treatment with propranolol/doxazosin (p < 0.05). Longitudinal segment shortening measured with sonomicrometry, improved in both treatment groups as compared with control (p < 0.05), but to a greater extent in the group treated with carvedilol. In circumferential segments, only carvedilol significantly improved segment shortening. The incidence of ventricular fibrillation (VF) after reperfusion was reduced in both treatment groups as compared with control. Oxidized glutathione and thiobarbituric acid-reactive substances (TBARS) measured at the end of reperfusion did not differ between groups. Carvedilol protected against lethal reperfusion injury mainly through blockade of adrenoceptors.

Carvedilol improves function and reduces infarct size in the feline myocardium by protecting against lethal reperfusion injury

This study examined the effect of carvedilol, a vasodilating beta-adrenoceptor antagonist and antioxidant, on lethal reperfusion injury in feline hearts subjected to 40 min of regional ischemia and 180 min of reperfusion. 30 open chest anaesthetized cats were randomized into three groups. A control (n = 10) was compared with a group given carvedilol before coronary artery occlusions (n = 10) and a group given carvedilol immediately before and during early reperfusion (n = 10). Regional myocardial function was measured by sonomicrometry. Infarct size was determined by staining the left ventricle with triphenyl tetrazolium chloride. Myocardial blood flow was measured by radiolabeled microspheres. Tissue levels of glutathione were measured after reperfusion. Infarct size was significantly reduced compared to control both when carvedilol was given before ischemia (0.2 +/- 0.1 vs. 17.6 +/- 3.6%, P < 0.05). and when given immediately before reperfusion (3.7 +/- 1.3 vs. 17.6 +/- 3.6%, P < 0.05). Regional shortening improved significantly and the incidence of ventricular fibrillation during early reperfusion was reduced in both groups treated with carvedilol compared to control. Oxidized glutathione did not differ between groups in the post-ischaemic myocardium. This study supports that lethal reperfusion injury is a significant phenomenon. Furthermore, carvedilol reduces infarct size and reperfusion arrhythmias, and improves post-ischaemic regional myocardial function by protecting against both ischaemic and lethal reperfusion injury. The present study does not answer whether it is the non-selective beta- or alpha 1-receptor antagonism, the antiarrhythmic or the antioxidant actions of carvedilol that is responsible for the protective effect.

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

Background:  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.

Endogenous Adenosine Attenuates Myocardial Stunning by Antiadrenergic Effects Exerted During Ischemia and Not During Reperfusion

Summary The effect of adenosine receptor blockade and adrenergic blockade on myocardial stunning [left anterior descending coronary artery (LAD) occluded for 10 min and reperfused for 180 min] was studied in 38 open-chest cats. A control group (Control) was compared with two other groups in which adenosine receptors were blocked by 8-phenyltheophylline (7.5 mg/kg) before reperfusion (8-PT-R) or before ischemia (8-PT-I). Group A, in which adrenergic receptors were blocked (doxazosin 200 μg/kg + propranolol I mg/kg), was compared with group A + 8-PT-I, in which both adenosine and adrenergic receptors were blocked before coronary artery occlusion. Regional systolic function assessed by sonomicrometry in the LAD perfused area recovered less in 8-PT-I (55 ± 5% recovery) as compared with Control (87 ± 9%) and 8-PT-R (89 ± 8%), which indicates that adenosine receptor blockade during ischemia increases stunning. Functional recovery was similar in Control, group A (96 ± 5%), and group A + 8-PT-I (87 ± 5%), which demonstrates that if adrenergic receptors are blocked, adenosine receptor blockade during ischemia does not increase stunning. These results may indicate that the cardioprotective effects of endogenous adenosine are mediated through antiadrenergic effects exerted during coronary artery occlusion.

Non-uniform recovery of segment shortening during reperfusion following regional myocardial ischaemia despite uniform recovery of ATP

OBJECTIVE This study focused on transmural postischaemic recovery of ATP and regional contractile function related to reversible and irreversible tissue injury. METHODS Fifty anaesthetised open-chest cats were randomised into two groups. Groups I: 10 min of LAD occlusion (n = 10) and 10 min of LAD occlusion followed by 180 min of reperfusion (n = 15). Group II: 40 min of LAD occlusion (n = 10) and 40 min of LAD occlusion followed by 180 min of reperfusion (n = 15). Histochemical staining (TTC) was performed in hearts from 5 additional cats subjected to 40 min of LAD occlusion and 180 min of reperfusion. Regional function was measured by sonomicrometry in the circumferential (CIRC) and longitudinal (LONG) axis of the anterior left ventricular midwall. Myocardial blood flow was measured with radiolabelled microspheres. Adenine nucleotides in the subepi- and subendocardium were measured with high-pressure liquid chromatography after LAD occlusion and after reperfusion. RESULTS Ten minutes of ischaemia induced a transmurally uniform ATP depletion. Repletion of ATP following reperfusion was transmurally uniform. Recovery of regional shortening was non-uniform with better recovery in CIRC (76 +/- 8% vs. LONG; 46 +/- 10%, P < 0.05). Forty minutes of ischaemia induced a more severe ATP depletion in the subendocardium compared to the subepicardium. A slight recovery of ATP following reperfusion was transmurally uniform. Recovery of function was present only in CIRC (48 +/- 6%). Tissue blood flow showed a transmurally homogenous flow restriction during ischaemia and uniform recovery following reperfusion. TTC staining demonstrated predominantly subendocardial infarctions following 40 min of regional ischaemia. CONCLUSIONS Postischaemic recovery of regional function is non-uniform and independent of ATP repletion and collateral blood flow during ischaemia. Absence of functional recovery in LONG is associated with development of infarction.

Mediastinitis after coronary artery bypass grafting: the effect of vacuum‐assisted closure versus traditional closed drainage on survival and re‐infection rate

Mediastinitis is treated with either vacuum‐assisted closure (VAC) or traditional closed drainage (TCD) with irrigation. The aim of the study was to determine the effect of the two treatments on mortality and re‐infection rate in a source population, using 21 314 consecutive patients undergoing isolated coronary artery bypass grafting (CABG) from January 1997 to October 2010. Median observation time was 2·9 years in the VAC group and 8·0 years in the TCD group. The epidemiological design was of an exposed (VAC, n = 64) versus non‐exposed (TCD, n = 66) cohort with two endpoints: (1) mortality and (2) failure of sternal wound healing or re‐infection. The crude effect of treatment technique versus endpoint was estimated by univariate analysis. Stratification analysis by the Mantel–Haenszel method was performed to quantify confounders and to pinpoint effect modifiers. Adjustment for confounders was performed using Cox regression analysis. Mediastinitis was diagnosed 6–105 (median 14) days after primary operation in the VAC group and 13 (5–29) days in the TCD group. There was no difference between groups in long‐term survival. Failure of sternal wound healing or re‐infection occurred less frequently in the VAC group (6%) than in the TCD group (21%; relative risk = 0·29, 95% CI = 0·06–0·88, P = 0·01). There are concerns for increase in right ventricle rupture in VAC compared with TCD. There was no difference in survival after VAC therapy and TCD therapy of post‐CABG mediastinitis. Failure of sternal wound healing or re‐infection was more common after TCD therapy.