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

BACKGROUND: 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. METHODS: Fourteen animals, randomized to the control (CT) group or the hypertonic saline/hydroxyethyl starch (HyperHaes) (HSH) group, received acetated Ringer's solution as prime and supplemental fluid. The HSH group received, in addition, HyperHaes 1 ml/kg/h. After 1 h of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (28 degrees C) was initiated and continued for 90 min. Fluid balance, plasma volume, tissue water content, acid-base parameters and intracranial pressure were recorded, and protein masses and fluid extravasation rates were calculated. RESULTS: At the start of normothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.06) to 1.57 (0.71) and 0.19 (0.09) to 0.82 (0.14) in the CT and HSH groups, respectively, with no between-group differences (P = 0.081) During hypothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.14) to 0.51 (0.10) (P < 0.01) and 0.15 (0.08) to 0.33 (0.08) (P < 0.05), respectively, with significantly lower extravasation rates in the HSH group (P < 0.01). In the HSH group, the total fluid gain during cardiopulmonary bypass decreased by about 50% (P < 0.05) and the tissue water content was significantly lower in the left and right heart as well as in the lungs. The intracranial pressure remained stable in the HSH group, but increased in the CT group. CONCLUSIONS: A continuous infusion of HSH (HyperHaes) during cardiopulmonary bypass reduced the fluid extravasation rate and the total fluid gain during bypass. No electrolyte or acid-base disturbances were present. The intracranial pressure remained stable in the HSH group.

Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with increased fluid filtration occasionally leading to post-operative organ dysfunction. One of the factors determining fluid filtration is the capillary hydrostatic pressure which depends on arterial pressure, venous pressure and pre- to post-capillary resistance ratio. The purpose of this study was to assess whether lowering of the mean arterial pressure and/or the central venous pressure could reduce fluid extravasation during normothermic and hypothermic CPB. METHODS: Seven piglets were given nitroprusside to a mean arterial pressure of 35-40 mmHg during 60 min of normothermic and 90 min of hypothermic CPB (LP group). They were compared with a control group (C group, n = 7) without blood pressure interventions. Blood chemistry, net fluid balance, plasma volume, colloid osmotic pressure in plasma and interstitial fluid, intravascular protein masses, fluid extravasation rate and total tissue water content were measured or calculated. RESULTS: Mean arterial pressure was significantly lower in the LP group than in the C group during CPB. Plasma volume tended to increase in the LP group (P > 0.05), but remained essentially unchanged in the C group. Net fluid balance in the LP group was more positive than in the C group 30 min after CPB start [1.02 (0.15) vs. 0.56 (0.13) ml/kg/min (Mean (SEM) P < 0.05)]. Fluid extravasation rate tended to be higher in the LP group and total tissue water content of the gastrointestinal tract, left myocardium and skin was significantly elevated compared with the C group. CONCLUSION: During CPB, lowering of the mean arterial pressure using nitroprusside did not reduce fluid extravasation. On the contrary, the data may implicate an increase in edema formation during low pressure CPB.

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. METHODS: Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. RESULTS: Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. CONCLUSION: Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.

Can the use of methylprednisolone, vitamin C, or alpha-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.

Fluid extravasation during cardiopulmonary bypass in piglets--effects of hypothermia and different cooling protocols.

BACKGROUND: Hypothermic cardiopulmonary bypass (CPB) is associated with capillary fluid leak and edema generation which may be secondary to hemodilution, inflammation and hypothermia. We evaluated how hypothermia and different cooling strategies influenced the fluid extravasation rate during CPB. METHODS: Fourteen piglets were given 60 min normothermic CPB, followed by randomization to two groups: 1: rapid cooling (RC-group) ( approximately 15 min to 28 degrees C); 2: slow cooling (SC-group) ( approximately 60 min to 28 degrees C). Ringer's solution was used as CPB prime and for fluid supplementation. Fluid input/losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum-proteins and total tissue water (TTW) were measured and fluid extravasation rates calculated. RESULTS: Start of normothermic CPB resulted in a 25% hemodilution. During the first 5-10 min the fluid level of the reservoir fell markedly due to an intravascular volume loss necessitating fluid supplementation. Thereafter a steady state was reached with a constant fluid need of 0.14 +/- 0.04 ml kg-1 min-1. After start of cooling the fluid needs increased in the following 30 min to 0.91 +/- 0.11 ml kg-1 min-1 in the RC group (P < 0.001) and 0.63 +/- 0.10 ml kg-1 min-1 in the SC-group (P < 0.001) with no statistical between-group differences. Fluid extravasation rates after start of hypothermic CPB increased from 0.20 +/- 0.08 ml kg-1 min-1 to 0.71 +/- 0.13 (P < 0.01) and 0.62 +/- 0.13 ml kg-1 min-1 (P < 0.05) in the RC- and SC-groups, respectively, without any changes in degree of hemodilution. TTW increased in most tissues, whereas the intravascular albumin and protein masses remained constant with no between group differences. CONCLUSION: Hypothermia increased fluid extravasation during CPB independent of cooling strategy. Intravascular albumin and protein masses remained constant. Since inflammatory fluid leakage usually results in protein rich exudates, our data with no net protein leakage may indicate that mechanisms other than inflammation could contribute to fluid extravasation during hypothermic CPB.

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

Based on measurements of the circulating red blood cell volume (V(RBC)) 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.

Temperature-related fluid extravasation during cardiopulmonary bypass: an analysis of filtration coefficients and transcapillary pressures.

BACKGROUND: Cardiopulmonary bypass (CPB) as used for cardiac surgery and for rewarming individuals suffering deep accidental hypothermia is held responsible for changes in microvascular fluid exchange often leading to edema and organ dysfunction. The purpose of this work is to improve our understanding of fluid pathophysiology and to explore the implications of the changes in determinants of transcapillary fluid exchange during CPB with and without hypothermia. This investigation might give indications on where to focus attention to reduce fluid extravasation during CPB. METHODS: Published data on "Starling variables" as well as reported changes in fluid extravasation, tissue fluid contents and lymph flow were analyzed together with assumed/estimated values for variables not measured. The analysis was based on the Starling hypothesis where the transcapillary fluid filtration rate is given by: JV=Kf [Pc-Pi-sigma(COPp-COPi)]. Here Kf is the capillary filtration coefficient, sigma the reflection coefficient, P and COP are hydrostatic and colloid osmotic pressures, and subscript 'c' refers to capillary, 'i' to the interstitium and 'p' to plasma. RESULTS AND CONCLUSION: The analysis indicates that attempts to limit fluid extravasation during normothermic CPB should address primarily changes in Kf, while changes in both Kf and Pc must be considered during 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. METHODS: Two groups of anesthetized piglets were studied during 2 h of hypothermic (28 degrees C) (n=7) or normothermic (38 degrees C) (n=7) CPB. Net fluid balance (input-output) was recorded. Changes in colloid osmotic pressures of plasma (COPp) and interstitial fluid (COPi), plasma volume (PV), hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), s-osmolality, s-albumin and s-total protein was followed throughout the experiments. Fluid extravasation rate was calculated. In addition, total tissue water content was measured and compared with a control group (n=6) (no CPB). RESULTS: During hypothermic compared with normothermic CPB, the average net positive fluid balance from 10-120 min of extracorporeal circulation was 1.35+/-0.06 ml x kg(-1) x min(-1) and 0.33+/-0.03 ml x kg(-1) x min(-1) respectively (P<0.0001). We found a marked increase in fluid extravasation during hypothermic CPB. The extravasation rate during hypothermia was 1.8+/-0.2 ml x kg(-1) x min(-1), (1st hour) and 1.1+/-0.2 ml x kg(-1) x min(-1) (2nd hour) compared with 0.8+/-0.2 ml x kg(-1) x min(-1), and 0.1+/-(0.1) ml x kg(-1) x min(-1) during normothermia, respectively (P<0.01). The total intravascular protein and albumin masses remained constant in both groups. Following hypothermic CPB, the water content increased significantly in all tissues and organs. CONCLUSION: During hypothermic CPB an increased extravasation of fluid from the intravascular to the interstitial space was found. As no leakage of proteins could be demonstrated, based on stable values for albumin and protein masses throughout the experiments, the extravasated fluid contained mainly water and small solutes.

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. METHODS: Piglets were placed on CPB (fixed pump flow) via thoracotomy in general anesthesia. In the normothermic group (n=7), the core temperature was kept at 38 degrees C prior to and during 2 h on CPB, whereas in the hypothermic group (n=7) temperature was lowered to 28 degrees C during bypass. The CPB circuit was primed with acetated Ringer's solution. The blood level in the CPB circuit reservoir was held constant during bypass. Ringer's solution was added when fluid substitution was needed (falling blood level in the reservoir). In addition to invasive hemodynamic monitoring, fluid input and losses were accurately recorded. Inflammatory mediators or markers were not measured in this study. RESULTS: Cardiac output, s-electrolytes and arterial blood gases were similar in the two groups in the pre-bypass period. At start of CPB the blood level in the machine reservoir fell markedly in both groups, necessitating fluid supplementation and leading to a markedly reduced hematocrit. This extra fluid need was transient in the normothermic group, but persisted in the hypothermic animals. After 2 h of CPB the hypothermic animals had received 7 times more fluid as compared to the normothermic pigs. CONCLUSION: We found strong indications for a greater fluid extravasation during hypothermic CPB compared with normothermic CPB. The experimental model using the CPB-circuit reservoir as a fluid gauge gives us the opportunity to study further fluid volume shifts, its causes and potential ways to optimize fluid therapy protocols.

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.

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium.

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3-8 micrograms kg-1 min-1 in group I (n = 8); left ventricular peak systolic pressure (LVSP) 84 +/- 4 mmHg (mean +/- SEM) during coronary artery occlusion. In group II (n = 7) LVSP was increased to 188 +/- 10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8 +/- 2.0% vs. 11.0 +/- 1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30 +/- 0.18 vs. 1.34 +/- 0.08 mL min-1 g-1 and 2.58 +/- 0.23 vs. 1.49 +/- 0.07 mL min-1 g-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.

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.

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.

Endogenous adenosine attenuates myocardial stunning by antiadrenergic effects exerted during ischemia and not during reperfusion.

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 micrograms/kg + propranolol 1 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.

Blockade of adenosine receptors during ischaemia increases systolic dysfunction but does not affect diastolic creep in stunned myocardium.

The impact of adenosine receptor blockade on left ventricular systolic function and diastolic creep in stunned myocardium was studied in 20 sodium pentobarbital anaesthetized cats. A control group (n = 10) was compared with a group (n = 10) where adenosine receptors were blocked by 8-phenyltheophylline (7.5 mg.kg-1 i.v.) prior to a 10 min occlusion of the left anterior descending coronary artery. Regional function was assessed by sonomicrometry of the left ventricular anterior wall. Tissue blood flow and haemodynamic measurements were obtained at pre-occlusion, during occlusion, and after 30 and 60 min of reperfusion. Tissue blood flow in the LAD region was low and homogeneous during coronary occlusion in both groups. Systolic function assessed by regional shortening and inotropic parameters was significantly more reduced in the 8-PT treated group (P < 0.05). Diastolic creep and compliance assessed by the end-diastolic pressure-length relationship did not differ between groups. Thus, endogenous adenosine protects against systolic dysfunction, but appears to have no impact on diastolic creep in stunned myocardium. Furthermore, our results show that the protective effect of endogenous adenosine is not caused by increased collateral blood flow into the ischaemic area during coronary artery occlusion or by increased blood flow in the reperfusion period.

Changes in myocardial contraction pattern during initial reperfusion.

The characteristics of hypercontraction during initial reperfusion were studied in 10 pentobarbitone-anesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 1 h of reperfusion, and regional function was assessed by two cross-oriented pairs of sonomicrometers placed in the left ventricular anterior wall. At 1 min of reperfusion (hyperfunctional phase) there was an uniform contraction pattern with 90% recovery of ejection shortening in both circumferential and longitudinal segments. During initial hypercontraction, end-diastolic segment lengths remained unchanged, whereas end-systolic segment lengths decreased transiently. Inotropic stimulation during reperfusion in four additional animals also affected end-systolic lengths more than end-diastolic lengths. This suggests that the initial hyperfunctional phase is due to an inotropic stimulation of the stunned myocardium, most probably caused by intracellular Ca2+ overload. At 5 min of reperfusion a nonuniform contraction pattern had developed with 68% recovery of shortening in circumferential segments vs. 25% in longitudinal segments. The decreased performance in longitudinal segments was paralleled by a delayed start of contraction as well as a decreased velocity of contraction. Because longitudinal segment shortening is a sensitive parameter of subendocardial performance, our results indicate a brief transmural hypercontraction followed by increasing dysfunction (stunning) in the subendocardial layer.

Non-uniform recovery of performance in stunned myocardium evaluated by two-dimensional sonomicrometry.

The objective of the present study was to assess the uniformity of contraction in reperfused myocardium. Regional function was measured by two pairs of piezo-electric crystals oriented in the circumferential and longitudinal axis of the left ventricular anterior midwall in 10 open-chest pentobarbitone-anaesthetized cats. The left anterior descending coronary artery was occluded for 10 min followed by 60 min of reperfusion. Myocardial blood flow was measured four times by radioactive labelled microspheres: at pre-occlusion, occlusion and after 30 and 60 min of reperfusion. There was a severe and transmural homogenous ischaemia during coronary occlusion. The recovery of ejection shortening was on average 76% at 30 min and 77% at 60 min of reperfusion in circumferential segments versus 25 and 44% in longitudinal segments (P < 0.05). Diastolic function was deranged in longitudinal segments; at 60 min of reperfusion the end diastolic pressure-length relation was still shifted rightwards in longitudinal segments, whereas it was normalized in circumferential segments. In conclusion, systolic and diastolic dysfunction in stunned myocardium were more severe in the longitudinal axis than in the circumferential axis of the feline heart. This indicates that stunning was more pronounced in longitudinally oriented sub-endocardial fibres which were reflected by the longitudinal segment, despite transmural homogenous ischaemia during coronary artery occlusion.

Left ventricular hypertrophy and myocardial ischaemia in hypertension: the THAMES Study.

A multicentre epidemiological study to detect the prevalence of myocardial ischaemia in hypertensive left ventricular hypertrophy (LVH) was performed in 188 asymptomatic male hypertensives (131 treated). The mean age was 55 (range 40-82) years with blood pressure (BP) > or = 160/100 mmHg or a systolic BP > or = 180 mmHg. The participants were screened with echocardiography, and left ventricular hypertrophy (LVH), defined as LV mass index (LVMI) > or = 130 g.m-2, was found in 127 (68%), of whom 95 were on antihypertensive treatment. Patients with LVH underwent a maximal bicycle ergometer exercise test and significant ST depression, indicating possible stress-induced ischaemia, was found in 29 men (23%). These subjects were subjected to exercise thallium-201 scintigraphy, which was normal in 14 but showed reversible perfusion defects in 15. Thus, a high prevalence of LVH (70%) was detected in male hypertensives selected only on age and BP. In addition, although chest pain on exertion excluded patients from entry, a substantial portion had signs of ischaemia (23% on exercise ECG alone, and in 52% confirmed by thallium scan). The prevalence of these risk factors should be considered when evaluating hypertensive patients.

Alpha-adrenergic vasoconstriction in normal and hypoperfused myocardium during sympathetic nerve stimulation.

Coronary vasoconstriction mediated by postjunctional alpha 1- and alpha 2-adrenergic receptors was studied in normally perfused (control group) and left coronary hypoperfused (stenosis group) hearts of vagotomized, beta-blocked (propranolol) cats. Cardiac sympathetic nerve stimulation was combined with alpha 1- and subsequent alpha 2-adrenergic antagonism (doxazosin and SK&F 104078). Coronary perfusion pressure and heart rate were kept constant within groups; regional myocardial blood flow and cardiac output were obtained by means of microspheres with concomitant measurement of left ventricular myocardial oxygen consumption (MVO2). alpha 1-Adrenergic antagonism alone did not significantly alter blood flow in any wall layer in either group. Subsequent alpha 2-adrenergic antagonism increased epicardial as well as composite transmural flow in the stenosis group (P < 0.025). The inverse correlation between coronary resistance and MVO2 vanished in the stenosis group following alpha 1- and alpha 2-adrenergic antagonism. Maximal first derivative of the left ventricular pressure-time relation (dP/dt) and cardiac output were reduced simultaneously (P < 0.001). Hence, the significance of alpha 1- and alpha 2-adrenergic stimulation of inotropy and cardiac performance are augmented by myocardial hypoperfusion. Furthermore, alpha 2-adrenergic receptors are responsible for epicardial vasoconstriction in hypoperfused myocardium.

[Severe hemorrhage in pancreatic pseudocyst]. / Alvorlig blødning ved pancreascyste.

Pseudocysts in the pancreas occur in 10% of patients with pancreatitis and may lead to serious complications, i.e. infection, obstruction of the bile duct, rupture, and hemorrhage. The last complication is highly lethal. Two patients are described, with differing modes of presentation and therapy. In one patient hemostasis was obtained by surgical packing followed by percutaneous embolization. In the other patient embolization failed and surgical resection was necessary.