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Effects of phenylephrine on transmural distribution of myocardial blood flow in regions supplied by normal and collateral arteries during cardiopulmonary bypass.

Cardiopulmonary bypass is frequently accompanied by decreased peripheral vascular resistance with resultant hypotension that is unresponsive to increased flow rates. Alpha adrenergic agonists are routinely used to increase peripheral vascular resistance and augment blood pressure. In this study, the effects of the alpha adrenergic stimulant phenylephrine on blood flow distribution during cardiopulmonary bypass in myocardium supplied by normal and collateral arteries were studied in eight mongrel dogs. Microsphere determinations of blood flow were made following augmentation of perfusion pressure with phenylephrine and were compared with intraoperative normotensive and hypotensive control levels. With systemic flow rates held constant, phenylephrine was infused in doses adequate to raise perfusion pressure to normotensive levels following hypotension. In the normal region (NR), blood flow was returned to normotensive control levels with flow favoring the subendocardium. In the region supplied by collateral vessels (CR), however, phenylephrine infusion failed to return flow to the normotensive control level in the subendocardial layer, and the flow imbalance present during hypotension was not corrected. An analogue model of the calculable resistances in the CR is presented, which indicates that phenylephrine increased resistance in the collateral vessels. Associated with this inflow restriction is decreased resistance or vasodilatation of the intramyocardial vessels supplied by collateral coronary arteries.

Animals

Management of extensive lesions of the lower trachea using emergency cardiopulmonary bypass.

Rapid cardiopulmonary deterioration in patients with extensive lesions of the lower trachea presents a serious challenge in the emergency care. Conventional methods may prove inadequate to achieve airway control and to stablilize the critical condition. Severe airway obstruction and/or massive air leakage are the main causes of failure. An aggressive operative approach is mandatory. Institution of emergency cardiopulmonary bypass for resuscitative purposes and definitive surgical repair of those life-threatening uncommon tracheal lesions seems essential to us. Two cases, managed according to this concept, are presented.

Adult

High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants.

Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants.

Age Factors

Propranolol binding in plasma during cardiopulmonary bypass.

The effect of cardiopulmonary bypass on the plasma binding of propranolol was examined in seven patients. The fraction of propranolol free in plasma doubled, increasing from 6.6 to 13.5 per cent (P less than 0.001) following the administration of heparin, 400 IU/kg. Once cardiopulmonary bypass was concluded and protamine, 8 mg/kg, given, the free fraction decreased from 13.4 to 8.7 per cent (P less than 0.005). There was a further significant decrease to 6.5 per cent over the next 3.1 hours (SE +/- 0.3). Those alterations in the free fraction, which would result in more drug being available for binding to receptor sites and for exerting its pharmacologic effect, were due principally to the changes in free fatty acid levels produced by heparin and protamine, but also to the hemodilution produced by the pump prime.

Cardiopulmonary Bypass

Oxygen availability during hypothermic cardiopulmonary bypass.

Oxygen availability during cardiopulmonary bypass was assessed in 22 patients under hypothermic and relatively normothermic conditions. The patients were divided into two groups, 17 of whom received ACD blood and 5, CPD blood. The mean P50 for all patients fell from a preoperative value of 25.9 +/- 2.4 (SD) to 15.6 +/- 2.1 during hypothermia confirming a leftward shift of the oxyhemoglobin dissociation curve. Oxygen uptake, calculated from a-v oxygen content differences (avDO2) and flow, was significantly lower during hypothermic bypass (65 +/- 27 ml/min) than during rewarming (121 +/- 41 ml/min). The increase in oxygen affinity during hypothermia was influenced also by changes in acid base and 2,3-DPG concentrations, the changes being similar in both the ACD and CPD groups of patients. During rewarming, however, oxygen availability was increased in the CPD group presumably from significantly increased 2,3-DPG concentrations. A "functional" value of hemoglobin, based upon the effects of the shift of the oxyhemoglobin dissociation curve and, therefore, reflecting the true capacity of hemoglobin to unload oxygen at the tissue level, was calculated. During the hypothermic phase of bypass, this functional hemoglobin was only 4.2 g/100 ml blood, suggesting that, in spite of reduced metabolic demands, oxygenation reserves are minimal.

Adult

Cerebrospinal fluid changes in experimental cardiopulmonary bypass using hemodilution with glucose water.

Cardiopulmonary bypass using hemodilution with isotonic glucose water was performed on seven dogs. Intense systemic metabolic acidosis, hyponatremia, hypochloremia, and hyperglycemia were accompanied by only comparatively small changes in the corresponding cerebrospinal fluid values. The data suggested that in the present study, cardiopulmonary bypass was not associated with gross disruptions of the barriers for bicarbonate, sodium, chloride, and glucose between blood and cerebrospinal fluid.

Animals

Influence of alpha-adrenergic block and beta-adrenergic stimulation on distribution of cardiac output after cardiopulmonary bypass.

Organ and tissue damage restricts total cardiopulmonary bypass to a few hours in patients. The cause might be the disturbance of tissue flow in which the sympatho-adrenal hyper-activity plays a decisive role. In dogs, killed 30 min after cardiopulmonary bypass was stopped, we studied the tissue distribution of cardiac output with the method of Sapirstein. In one group the alpha-adrenergic blocker, in the other one the beta-adrenergic stimulator was continuously applied during the whole operation-period. Compared to a control group the per cent of cardiac output as well as the regional tissue flow after alpha-adrenergic block increased in the liver, ileum, adrenals, testes, kidney and in the skin and decreased in the spleen and thyroid gland. After beta-adrenergic stimulation the per cent of cardiac output increased in the heart muscle, lungs, liver, ileum, adrenals and m. soleus and decreased in the spleen and thyroid gland. The absolute values of organ tissue flow increased in ileum and decreased in the spleen, thyroid gland and in the kidney.

Adrenergic alpha-Antagonists

[Therapy of low-output syndrome in patients following cardiopulmonary bypass with sodium nitroprusside and dopamine].

In 12 patients with low output after open-heart surgery the therapeutic effect of vasodilatation with sodium nitroprusside (SNP) and dopamine was studied. All patients underwent aortocoronary bypass operations. After cardiopulmonary bypass, the cardiac index (CI) was 2.2 liters/min.m2. The pulmonary wedge pressure (PCWP) was about 20 mm Hg. Application of SNP lowered mean arterial pressure to 82 and PCWP to 13 mm Hg. Then PCWP was elevated to the control level by tranfusion of blood. This therapy increased CI by about 30% without positive inotropic intervention. Additional application of 5 micrograms dopamine/kg.min improved the CI to 3.8 liters/min.m2.

Blood Pressure

Peripheral vascular resistance and angiotensin II levels during pulsatile and non-pulsatile cardiopulmonary bypass.

The effects of pulsatile and non-pulsatile cardiopulmonary bypass (CPB) on levels of peripheral vascular resistance and plasma angiotensin II (AII) have been studied in 24 patients submitted to elective cardiac surgical procedures. Twelve patients had conventional non-pulsatile perfusion throughout the period of CPB (non-pulsatile group), while 12 had pulsatile perfusion during the central period of total CPB, using the Stockert pulsatile pump system (pulsatile group). There were no significant differences between the groups in respect of age, weight, bypass time, cross-clamp time, or in mean pump flow or mean perfusion pressure at the onset of CPB. Peripheral vascular resistance index (PVRI) and plasma AII levels were measured at the onset of total CPB and at the end of total CPB. In the non-pulsatile group PVRI rose from 19.6 units to 29.96 units during perfusion. In the pulsatile group PVRI showed little change from 20.89 units to 21.45 units during perfusion (P less than 0.001). Plasma AII levels (normal less than 35 pg/ml) rose during perfusion from 49 pg/ml to 226 pg/ml in the non-pulsatile group. The rise in the pulsatile group from 44 pg/ml to 98 pg/ml was significantly smaller than that in the non-pulsatile group (P less than 0.01). These results indicate that pulsatile cardiopulmonary bypass prevents the rise in PVRI associated with non-pulsatile perfusion, and that this effect may be achieved by preventing excessive activation of the renin-angiotensin system, thus producing significantly lower plasma concentrations of the vasoconstrictor angiotensin II.

Adult

The significance of coronary arterial stenosis during cardiopulmonary bypass.

Myocardial infarction may develop during an uneventful open-heart operation. In order to better understand this complication, we undertook an experimental study. The left circumflex coronary artery of 20 dogs was narrowed to 50 per cent of its area by a metal screw clamp to produce a localized coronary stenosis. Regional myocardial perfusion in the distribution of both the stenotic circumflex and normal left anterior descending (LAD) coronary arteries was measured by injection of a radioactive-labeled microsphere (15 +/- 5 mu). Circumflex coronary artery flow was measured with an electromagnetic flow probe. An epicardial electrogram was recorded in the distribution of the left circumflex. Measurements of regional myocardial perfusion, circumflex flow, and the epicardial electrogram were performed in each animal during the control (prebypass) state and during cardiopulmonary bypass with a beating and fibrillating ventricle. Half the animals had cardiopulmonary bypass performed at 50 mm. Hg perfusion pressure and half at 100 mm. Hg. The animals were put to death at the end of the study, and the hearts were sectioned, weighed, and counted. A cast was made of the stenotic circumflex coronary artery, the degree of stenosis is measured, and the per cent area stenosis calculated. The study showed that the effect of a 50 per cent coronary stenosis in reducing distal flow is apparent only during cardiopulmonary bypass at reduced pressure. The mechanism whereby a myocardial infarction develops during cardiopulmonary bypass could evolve from the development of a "critical" stenosis out of a mild-moderate one at a reduced perfusion pressure during cardiopulmonary bypass.

Animals

[Factor analysis fever in the early postoperative period following cardiopulmonary bypass surgery in adults. Correlation with bacteriological data. Statistical study of 518 case histories by computer].

The results of a continuous series of 518 adults undergoing cardiopulmonary bypass surgery, operated on by the same surgeon, comprising valvular replacement and aorto-coronary bypass surgery with a peroperative protocol of asepsis and a short prophylactic course of Penicillin and Streptomycin, a preoperative and postoperative bacteriological study, were treated by computer. The postoperative temperature chart showed a progressively decreasing pyrexia in the first 8 days after cardiopulmonary bypass. The nature of the operation, the bypass time, the quantity of blood used during operation and the blood loss were statistically significant factors. Patients with a clinical infection had significantly higher temperatures from the first on. 8,9% of patients had a febrile reaction which continued after the 10th day after cardiopulmonary bypass. The cause was not always apparent but the appearance of their temperature graphs was distinguishable after the first week. Analysis of the systematic bacterial specimens showed bacterial contamination of nearly 10% of drains, 10% of blood cultures, over 15% of intravenous infusion catheters and 70% of urinary catheters. The significance of these results is discussed. The normal appearance of the temperature chart after cardiopulmonary bypass surgery in the absence of clinical complications and bacterial contamination has been established.

Bacterial Infections

Temporary cardiopulmonary bypass for the treatment of endotoxic shock.

New Zealand white rabbits were employed in the laboratory to evaluate the efficacy of temporary cardiopulmonary bypass in the prevention of pulmonary injury from endotoxin. Partial cardiopulmonary bypass using peripheral cannulation was carried out for 15 minutes after intraarterial administration of E coli endotoxin of LD90 doses. A significantly better long-term (1 month) survival rate of the treated animals (60 per cent) versus the untreated animals (10 per cent) as well as less severe pulmonary changes in those that succumbed after treatment were observed. It would appear that temporary cardiopulmonary bypass by peripheral cannulation warrants further study in the treatment of patients identified early as suffering from otherwise irreversible septicemic shock.

Animals

Platelet dysfunction associated with cardiopulmonary bypass.

The clinical significance and pathogenesis of the platelet dysfunction following cardiopulmonary bypass were studied in conjunction with the degree of functional impairment associated with the use of membrane and bubble oxygenators. Forty consecutive patients had the following tests preoperatively and postoperatively: complete blood count (CBC), platelet count, prothrombin consumption time, bleeding time, prothrombin time, partial thromboplastin time, fibrinogen, euglobulin clot lysis, fibrin degradation products, and platelet aggregation tests. Six patients were given 14C-serotonin tests before and after operation, and preoperative and postoperative electron micrographs were made of the platelets of 3 patients. The amount of blood lost, the blood transfused, and plasma hemoglobin levels were also measured. Abnormal aggregation of platelets was found, with no difference between the membrane and bubble oxygenators. In vitro aggregation tests with protamine sulfate and hemoglobin solutions, as well as the 14C-serotonin studies and electron micrographs, suggest that platelets acquire storage pool deficiency and an abnormal membrane during cardiopulmonary bypass.

Blood Coagulation Tests

Ventilation in dogs on cardiopulmonary bypass with and without lungs.

In 13 anesthetized or awake dogs, on cardiopulmonary bypass, we varied PaO2 and PaCO2 while continuously monitoring ventilatory responses and mechanics, to assess the dog's ability to maintain eupneic ventilation for any chemical drive. In a second group of 13 dogs on cardiopulmonary bypass we repeated the tests after removal of both lungs, to assess the importance of pulmonary feedback and mechanics. The VE/PO2 plot formed two hyperbolas, asymptotic to 39 Torr PO2 with lungs, and to 27 without; both intercepted zero ventilation near 200 Torr. Hyperoxic apnea occurred at, or below, PCO2 30 +/- 7 Torr under barbiturate and 20 +/- 4 Torr under morphine. Steady-state low PCO2 (10 Torr) turned off hypoxic drives as low as 20 Torr PO2. Empty-chest dogs had a low respiratory frequency (18 vs. 40), and near zero dynamic elastance; ventilatory work per minute and airway resistance were the same with and without lungs. Chest wall ventilatory responses are grossly independent of the presence of absence of lungs.

Airway Resistance

Plasma vasopressin levels during cardiopulmonary bypass with and without profound haemodilution.

In cardiopulmonary bypass the effect on plasma vasopressin levels of the addition of whole blood to the pump priming solution was measured. Six patients (Group I) had blood added to the lactated Ringer's solution for the prime, and six patients (Group II) had only lactated Ringer's solution. Neither group had significant changes in plasma vasopressin levels until surgical stimulation occurred. Comparable significant elevations occurred during bypass in both groups. Greater decreases in haematocrit and urinary K+ and greater increases in urinary Na+ occurred in Group II. The degree of haemodilution does not appear to effect plasma vasopressin levels but may alter the degree of electrolyte shift.

Cardiopulmonary Bypass

Role of angiotensin II in the development of peripheral vasoconstriction during cardiopulmonary bypass.

The possible relationship between angiotensin II -- the end product of the renin-angiotensin system, and the increase in peripheral vasoconstriction associated with cardiopulmonary bypass, has been investigated in 12 patients undergoing elective open-heart surgical procedures. Plasma angiotensin II (AII) levels were measured by radio-immunoassay at the start and the end of the period of cardiopulmonary bypass. Measurements of peripheral vascular resistance index were made at the times of AII sampling. Plasma AII levels rose during CPB from 78.0 to 231.3 pg.cm-3 (normal values less than 35 pg.cm-3). Peripheral vascular resistance index also rose during perfusion from 20.87 to 27.83 units. The rise in plasma AII levels and in peripheral vascular resistance index were correlated for each of the 12 patients. A highly significant correlation was obtained (r = 0.91; P less than 0.001). These results confirm the presence of parallel rises in plasma angiotensin II levels and in peripheral vasoconstriction during conventional non-pulsatile cardiopulmonary bypass, and suggest that increased plasma AII levels may be principal causative factor in the increased vasoconstriction associated with open-heart surgical procedures.

Adult