Search PubMed⌕ Search

Biomedical subjects

R Ekroth

Publications and source records attributed to R Ekroth.

At least 55 records · Page 3Linked to original sources

Is cerebral blood flow/metabolic mismatch during rewarming a risk factor after profound hypothermic procedures in small children?

The relation between cerebral blood flow and oxygen consumption was studied in six children during cardiac operations with profound hypothermia. A combination of topical cooling and core cooling was used to reduce the nasopharyngeal temperature to 15 degrees C. The alpha-stat principle for pH management was used. Blood flow and oxygen consumption decreased significantly with temperature. At a nasopharyngeal temperature of 15 degrees C, blood flow was reduced to 25% of the awake level, corresponding to 34% of the asleep value obtained 15-30 min after intubation. Oxygen consumption decreased to 25% of the asleep value. During stable profound hypothermia, venous saturation in the jugular bulb was at the same level as 15 min after intubation (70%). Markedly lower values were observed during topical cooling, and particularly during rewarming (down to 21%), indicating a mismatch between cerebral blood flow and oxygen consumption. The speed of rewarming correlated with the fall in venous oxygen saturation (rs = 0.82, P less than 0.05). It is suggested that periods of cerebral blood flow/metabolic mismatch during topical cooling and rewarming may explain postoperative cerebral dysfunction after deep hypothermic procedures. A moderate speed of rewarming is advocated.

Blood Flow Velocity↗

Insulin as a vasodilating agent in the first hour after cardiopulmonary bypass.

To study the vasodilating effect of insulin after termination of ECC in aortocoronary bypass surgery, 21 patients were randomized to treatment with 7.5 U of fast-acting insulin/kg b.w. as a bolus injection followed by continuous infusion of 15 U/kg b.w. for 1 hour, or to serve as controls. Insulin administration was begun when the last proximal anastomosis had been completed. Cardiac output and central pressures were monitored for 1 hour after termination of ECC. Systemic vascular resistance in both groups was lower at the end of ECC than before surgery (reduction 39% in the controls, 51% in the insulin-treated group). During the following hour the peripheral resistance increased significantly in the controls (from 20 +/- 2 to 29 +/- 2 mmHg X min X m2/l), but no change was found in the insulin group. It is concluded that insulin can maintain a low vascular resistance after aortocoronary bypass surgery.

Adult↗

Glucose and lactate balances in heart and leg after coronary surgery: influence of insulin infusion.

Glucose and lactate balances in leg (representing mainly skeletal muscle) and heart were studied 1 hour after aortocoronary bypass surgery and insulin treatment. Seventeen men were randomized to receive 25 U fast-acting insulin as a bolus injection, followed by continuous infusion of 1 U/kg b.w. for 1 hour, or to serve as controls. In the leg a small glucose uptake was found while the lactate balance was negative. During the study period the lactate release increased further in the control group. In the myocardium no significant extraction of glucose or lactate could be demonstrated. Insulin treatment resulted in a fivefold increment of leg glucose uptake and in significant myocardial glucose uptake. Myocardial lactate balance was also improved by insulin treatment, with fractional extraction increased from 6 to 21%. It is concluded that myocardial carbohydrate metabolism is restricted in the early period after cardiac surgery, and that this seems to result from insulin resistance induced by the surgical trauma.

Adult↗

An evaluation of the perioperative efficacy of selective beta 1-blockade in coronary surgery. Studies with a late preoperative dose of metoprolol.

The plasma concentration of metoprolol was measured hourly following an oral dose on two consecutive days--the day before, and the day of, coronary surgery. No significant difference was found between the two sampling days, though there was a tendency to lower concentrations during and after extracorporeal circulation. After a median dose of 50 mg the peak concentration (reached on average after 1.5 h) was 545 +/- 70 nmol/l on the first day and 388 +/- 57 on the day of surgery. The respective elimination rates from plasma, expressed as half-life, were 3.4 +/- 0.21 and 3.5 +/- 0.19 hours (NS). On the day of surgery the heart rate rose during the second half of the observation period, peaking above 130 beats/min. Heart rate was inversely correlated to metoprolol concentration in plasma with coefficient -0.68 before induction of anesthesia and -0.77 two hours after termination of extracorporeal circulation. The perioperative efficacy of beta-blockade following a late preoperative oral dose of the agent thus appeared to be reduced and inadequate.

Aged↗

No flow or low flow? A study of the ischemic marker creatine kinase BB after deep hypothermic procedures.

Twenty-seven children with complex congenital heart malformations necessitating early repair were studied before and after deep hypothermic procedures. The children were allocated into two groups. One group underwent total circulatory arrest (40 +/- 6 minutes). In the other group perfusion was maintained during deep hypothermia but reduced a 25% of normal at normothermia. The temperature was reduced to 15 degrees C (nasopharynx) in both groups with a combination of topical and core cooling. To study cerebral injury, were made serial measurements of creatine kinase isoenzyme BB from arterial samples before and for 8 hours after the deep hypothermic procedure. Creatine kinase isoenzyme BB increased after both procedures from 4.3 +/- 0.9 ng/ml to 10.4 +/- 1.8 ng/ml in the circulatory arrest group and from 2.8 +/- 0.7 ng/ml to 9.9 +/- 1.9 ng/ml in the low-flow group (no significant difference). The results were analyzed in relation to age, size, study group, hemoglobin, blood glucose, and blood gases. The creatine kinase BB levels were positively related to preoperative hemoglobin and blood glucose values before the hypothermic procedures.

Blood Glucose↗

Elective deep hypothermia with total circulatory arrest: changes in plasma creatine kinase BB, blood glucose, and clinical variables.

Serial measurements of a marker of brain ischemia, creatine kinase isoenzyme BB, were performed in arterial and internal jugular venous blood from 20 infants younger than 1 year of age before and during the first 20 hours after deep hypothermic total circulatory arrest procedures. A two-site monoclonal method was used, and the results were analyzed in relation to age, size, type of cardiac lesion, hemoglobin level, blood glucose level, pH, and duration of the total circulatory arrest. The creatine kinase BB concentrations increased after the arrest, more so in venous than in arterial blood, from 3.2 +/- 0.5 ng/ml to 17.5 +/- 4.5 in arterial blood and from 3.5 +/- 0.5 ng/ml to 18.1 +/- 5.8 in venous blood. Arterial-venous concentration differences correlated with venous concentrations (r = 0.92, p less than 0.01). The duration of the arrest correlated with creatine kinase BB concentrations during reperfusion with correlation coefficients between 0.50 to 0.90 depending of what sequence of the 20-hour sampling period was analyzed. The best correlation was obtained during the first 4 hours of reperfusion. Age, size of the child, and preoperative cyanosis correlated with postoperative creatine kinase BB but were less important than the arrest time, blood glucose level (r = 0.62, p less than 0.01), pH (r = -0.78, p less than 0.01), and hemoglobin level (r = 0.76, p less than 0.01) during reperfusion. It is suggested that a different control of blood glucose level and pH during reperfusion may be of importance to reduce biochemical signs of cerebral dysfunction after deep hypothermic total circulatory arrest procedures.

Blood Glucose↗

Enzymatic activities in heart and skeletal muscle of children with cyanotic and noncyanotic congenital heart disease.

The activity of phosphofructokinase (PFK), citrate synthetase (CS), lactate dehydrogenase (LDH), 3-OH-CoA dehydrogenase (ACDH) and cytochrome-c-oxidase (cyt-ox) was measured in right atrial auricle and abdominal rectal muscle biopsies from 24 children, aged 3-12 years, with congenital heart malformations. Twelve children had cyanotic conditions (tetralogy of Fallot or truncus malformations) and 14 were noncyanotic (septal defects or vascular lesions). The cyt-ox activity was significantly higher in the cyanotic subgroup than in the noncyanotic (skeletal muscle: 55.71 +/- 10.4 vs 19.48 +/- 2.6 mmol/g protein/min, p less than 0.01; auricle: 93.1 +/- 11.8 vs 65.58 +/- 7.5, p less than 0.05). There were no significant differences between the activities of PFK, LDH, CS or ACDH in the cyanotic and noncyanotic groups. Within the normal range of hemoglobin and hematocrit, there was no correlation between these parameters and cyt-ox. On the other hand, above the normal range of hemoglobin and hematocrit a correlation coefficient of 0.89 (p less than 0.01) was observed which suggests the higher cyt-ox activity to be an adaptive phenomenon triggered by reduced availability of oxygen.

3-Hydroxyacyl CoA Dehydrogenases↗

The effect of insulin on the leg and splanchnic balance of glucose and gluconeogenic substrates after cardiac surgery.

The effect of insulin and glucose infusion on the leg and splanchnic balance of glucose and the gluconeogenic substrates lactate, pyruvate, alanine and glycerol was studied in 13 patients directly after cardiac surgery. Insulin was infused continuously at a rate of 1.0 Unit/kg/hr during 1 hour. Sixteen patients served as a control group and received no insulin and glucose infusion. A significant increase in arterial lactate concentration in both the control group (from 1.40 +/- 0.19 to 1.68 +/- 0.24 mmol/l p less than 0.01) and the insulin group (from 1.58 +/- 0.27 to 2.07 +/- 0.22 mmol/l, p less than 0.05) was observed. The arterial pyruvate concentration was significantly increased (from 0.075 +/- 0.019 to 0.105 +/- 0.021 mmol/l, p less than 0.01) and glycerol was significantly decreased (from 0.15 +/- 0.03 to 0.12 +/- 0.03 mmol/l, p less than 0.05) during the insulin and glucose infusion. The alanine concentration was unchanged in both groups. Insulin and glucose infusion was followed by an increased leg uptake of glucose (from 0.15 +/- 0.14 to 1.06 +/- 0.16 mmol/min/100 ml, p less than 0.05), and by a changed splanchnic glucose balance (from -8.2 +/- 2.8 to +4.0 +/- 1.2 mmol/kg/min, p less than 0.01). A net leg release and at the same time a net splanchnic uptake of all gluconeogenic substrates was observed. The insulin and glucose infusion did not significantly change either the splanchnic balance or the leg balance of the gluconeogenic substrates.

Aged↗

Assessment of myocardial perfusion in the empty beating porcine heart with laser Doppler flowmetry.

Laser Doppler flowmetry was applied to the empty beating heart of six pigs. Cardiopulmonary bypass was instituted and the preparation allowed continuous and simultaneous measurement of coronary sinus blood flow and local tissue perfusion. An epicardial and an intramuscular probe were used. Significant linear correlation coefficients were obtained between changes of laser Doppler signal and coronary sinus blood flow changes in all seven experiments in four animals (r from 0.71 to 0.94, p less than 0.005) and between laser Doppler signal and changes of extracorporeal bypass in five out of six experiments in four animals (r from 0.82 to 0.99, p less than 0.001). The correlation between coronary sinus flow and bypass flow of four pigs was significant (r from 0.81 to 0.98, p less than 0.001), the coronary flow being about 10% of bypass flow. Muscular activity of the heart contributed to the laser Doppler signal, the magnitude of this "noise level" varying between different experiments even in the same animal. A key question for the applicability of laser Doppler flowmetry to the beating heart is whether it will become possible to discriminate between flow and muscular contribution to the laser Doppler output.

Animals↗

Assessment of myocardial perfusion with laser Doppler flowmetry. An experimental study on porcine heart.

Laser Doppler flowmetry was applied to the arrested heart of four pigs and to the fibrillating heart of three pigs during cardiopulmonary bypass. The coronary blood flow was maintained during cardiac arrest by infusion of hyperkalemic blood into the aortic root. A significant correlation (r = 0.88, n = 52, p less than 0.001) between laser Doppler signal and coronary blood flow was found during cardiac arrest. During ventricular fibrillation after release of the aortic cross-clamp there was significant correlation (0.84, n = 38, p less than 0.01) between laser Doppler signal and extracorporeal blood flow. A residual laser Doppler signal of about 60% of the maximal value was recorded even after the bypass flow was discontinued. Laser Doppler flowmetry is concluded to permit measurement of myocardial perfusion in the arrested porcine heart. Muscular activity of the heart contributes to the output signal during ventricular fibrillation.

Animals↗

Laser Doppler flowmetry estimating myocardial perfusion after internal mammary artery grafting.

Myocardial perfusion in the anteroapical part of the left ventricle was monitored intraoperatively with laser Doppler flowmetry in ten patients after grafting of the internal mammary artery to the left anterior descending artery. The myocardial perfusion after declamping of only the mammary artery averaged 61% of the perfusion found after declamping also the aorta. Laser Doppler flowmetry is proposed to offer a means of monitoring regional myocardial perfusion in the phase immediately after internal mammary artery grafting.

Coronary Artery Disease↗

Effects of graded insulin infusions on plasma levels of free fatty acids, adrenaline and noradrenaline directly after open heart surgery.

A four-hour insulin "clamp" technique was used to study the dose-response relationship between a wide range of plasma concentrations of insulin (5.0-7000 mU/l), free fatty acids, adrenaline and noradrenaline in 28 patients directly after open heart surgery. The influence of beta-blockers is discussed. All patients had elevated levels of free fatty acids at the beginning of the study (1020 +/- 77 mumol/l). After 4 hours the decline in free fatty acids was significant in all insulin-treated patients and most pronounced in the groups with insulin concentrations of more than approximately 350 mU/l, i.e. when insulin was infused with 0.3 units/kg bw/hour or more. No significant decrease in free fatty acids was observed in the control group. Adrenaline and noradrenaline in plasma were markedly increased throughout the study and were unaffected by the insulin infusions in all groups.

Adult↗

Insulin sensitivity in patients with arterial insufficiency. Re-evaluation with the multilevel glucose clamp technique.

Previous studies have claimed that changes in insulin and glucose metabolism in patients with peripheral arterial insufficiency indicate an increased sensitivity to insulin for glucose uptake. We have re-evaluated this concept in 11 patients with intermittent claudication and 11 matched controls with a multilevel euglycaemic glucose clamp technique. The groups were matched for age, sex and body composition but not completely for smoking habits and physical fitness. Although the control group had a normal physical fitness the patients had 40% lower maximal exercising capacity. The patients' maximal walking capacity was 186 +/- 27 m evaluated on a treadmill. No patient with ischaemic ulcers or rest pain were included. The euglycaemic glucose clamp was performed at five insulin plateau levels (70, 110, 190, 590 and 1440 mU/l) of one h duration each and whole body glucose uptake during the last 20 min was calculated. No differences in maximal glucose uptake (Vmax) or insulin level for half maximal glucose uptake (Km) between the groups were observed. The concentration or the magnitude of the decrease in arterial FFA levels did not differ significantly between the groups at any physiological insulin level. This study can not confirm previously described changes in insulin sensitivity in patients with arterial insufficiency. Although the discrepancy between present and previous results remains unclear it may reflect the combined effects of different methods used, including the selection of reference patients, rather than an increased insulin sensitivity in patients with arterial insufficiency. This study suggests that previous conclusions based on glucose tolerance tests should be interpreted with caution.

Biological Transport, Active↗

Detection of cerebral injury after total circulatory arrest and profound hypothermia by estimation of specific creatine kinase isoenzyme levels using monoclonal antibody techniques.

New 2-site labeled monoclonal antibody techniques were used to measure serially plasma levels of brain-type creatine kinase (CK-BB), heart-type creatine kinase (CK-MB) and muscle-type creatine kinase (CK-MM) during a 20-hour postoperative period in 24 infants after deep hypothermia and total circulatory arrest used in pediatric cardiac surgery. A control group of 7 children undergoing cardiovascular procedures without extracorporeal circulation or circulatory arrest also were studied. There were marked increases in CK-MB and CK-BB levels in the circulatory arrest group but not in the closed group. CK-BB increased from 3.2 +/- 0.5 to 27 +/- 10 ng/ml and CK-MB from 5.9 +/- 2.1 to 137 +/- 12 ng/ml. The CK-MM concentrations increased from 299 +/- 91 and 194 +/- 49 ng/ml to 1,220 +/- 274 and 1,322 +/- 142 ng/ml in the closed and circulatory arrest groups, respectively. Peak levels of CK-MB and CK-BB occurred an average of 133 and 127 minutes, respectively, after reperfusion. The half-time of CK-BB differed significantly from that of CK-MB (149 +/- 15 vs 359 +/- 20 minutes). The arrest time had a more marked effect on CK-BB concentration than on CK-MB and CK-MM concentrations. Arteriointernal jugular venous concentration differences were consistently negative for CK-BB in the circulatory arrest group, but not for CK-MM and CK-MB.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Serial measurement of arterial and internal jugular venous creatine kinase isoenzyme BB (CK-BB) after deep hypothermic total circulatory arrest in pediatric cardiac surgery.

Profound hypothermia and circulatory arrest in infants and children undergoing cardiac surgery were followed by abnormally high plasma levels of creatine kinase isoenzyme BB (CK-BB). Differences in the levels of enzymes in the femoral arterial and jugular venous blood indicated that the origin of the additional enzyme was the brain. The extent of the rise in enzyme levels was related to the duration of circulatory arrest. These data suggest that measurements of the CK-BB enzyme in plasma provide quantitative information about cerebral damage during cardiac surgery.

Brain↗

Haemodynamic effects of insulin and beta receptor blockade during acute left ventricular failure in dogs.

Acute ischaemic heart failure was induced in 13 dogs by coronary embolisation. Severe dysfunction of the left ventricular (LV) performance was shown by a significant increase in LV end-diastolic pressure and significant decreases in maximum rate of LV pressure rise (LVdP/dtmax), stroke volume and cardiac output. 300 IU of fast-acting insulin was injected as a bolus dose in 7 dogs 90 min after the embolisation procedure. This was followed by infusion of glucose and potassium to maintain normal blood levels. After 15 min, insulin had significantly improved the performance of the failing left ventricle. Total peripheral resistance was decreased. Myocardial blood flow was significantly increased while myocardial oxygen consumption was unchanged. After beta receptor blockade with propranolol 0.5 mg kg-1 given intravenously, the improvement in cardiac performance was reduced, heart rate decreased, and a concomitant decrease in myocardial blood flow and oxygen consumption was recorded. Compared with values before treatment, the net effect of combined insulin and beta receptor blockade was unchanged LVdP/dtmax, LV end-diastolic pressure and cardiac output, significantly increased stroke volume and decreased heart rate, and moderately reduced total peripheral resistance and mean aortic blood pressure. Myocardial blood flow was unaltered, while myocardial oxygen consumption was significantly reduced. In the control group of 6 dogs propranolol was given before insulin, and similar haemodynamic alterations were found.

Acute Disease↗

Haemodynamic effects of high doses of insulin during acute left ventricular failure in dogs.

Haemodynamic effects of pharmacological doses of insulin during acute ischaemic heart failure were studied in 8 dogs. Severe depression of left ventricular function was induced by the injection of 50 micron plastic microspheres into the left main coronary artery. This was demonstrated by a significant increase in left ventricular end-diastolic pressure and a significant decrease in the maximum rate of left ventricular pressure rise (LVdP/dtmax), stroke volume and cardiac output. Eighty-five minutes after the embolization procedure, 300 IU of insulin free of glucagon and calcium was injected as a bolus. This was followed by infusion of glucose and potassium to maintain physiological levels of these factors. Five minutes after insulin administration, there was a significant improvement in left ventricular performance as shown by decreased left ventricular end-diastolic pressure (P less than 0.01) and increased LVdP/dtmax (P less than 0.01), stroke volume (P less than 0.05) and cardiac output (P less than 0.05). A significant reduction in heart rate occurred. A non-significant increase in mean aortic blood pressure and reduction in total peripheral resistance were seen. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function during acute ischaemic left ventricular failure in dogs.

Acute Disease↗

Metabolic effects of high doses of insulin during acute left ventricular failure in dogs.

Metabolic effects of pharmacological doses of insulin were studied during acute ischaemic heart failure in 7 dogs. Severe depression of left ventricular performance was induced by embolization of the left main coronary artery with 50 micron plastic microspheres. This was followed by a significant reduction in myocardial blood flow and oxygen consumption. After a period of stabilization of the haemodynamic and metabolic variables, 300 IU of insulin free of glucagon and calcium was injected as a bolus dose. Glucose and potassium were given to maintain their plasma concentrations. Insulin significantly improved performance of the failing left ventricle. Myocardial blood flow was significantly increased, whereas myocardial oxygen consumption was unchanged. Insulin significantly reduced arterial concentrations and myocardial uptake of free fatty acids, while myocardial uptake of glucose and lactate showed a non-significant increase. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function without increasing myocardial oxygen consumption during acute ischaemic left ventricular failure in dogs. This may be partly related to reduced myocardial uptake of free fatty acids relative to that of glucose.

Acute Disease↗