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Biomedical subjects

J H Rousou

Publications and source records attributed to J H Rousou.

At least 19 recordsLinked to original sources
PubMed1984

Characterization of the anaphylatoxin inactivator and chemotactic factor inactivator activities during cardiopulmonary bypass.

Complement activation productive of phlogistic products has been suggested as one of the major mechanisms of the pump lung syndrome associated with cardiopulmonary bypass (CPB) surgery. Recent studies have demonstrated the presence of circulating C3a antigens in the serum of patients undergoing CPB and have suggested that the vasoactive nature of C3a may contribute directly to the interstitial edema and vascular changes seen in pump lung syndrome. In an effort to unravel the underlying mechanisms of pump lung syndrome, we undertook investigations to determine whether CPB and associated complement activation would alter the serum levels of the major regulators of both C3a and C5a complement split products. These serum regulators designated chemotactic factor inactivator (CFI) and anaphylatoxin inactivator (AI) were measured in the serum of patients undergoing CPB. In these studies, we demonstrated that during CPB a rapid and dramatic drop in the anaphylatoxin inactivator activities occurred within the first 10 minutes of CPB. These lowered AI levels were maintained throughout the CPB but AI levels returned to normal within 24 hours postsurgery. CFI levels were generally maintained throughout the CPB surgery with only minimal depressions in CFI levels during or after CPB surgery. These studies clearly demonstrate that the major regulator system of the complement-derived vasopermeability factors (C3a and C5a) is dramatically depressed during cardiopulmonary bypass and may suggest that the mechanisms of interstitial edema associated with pump lung syndrome may at least, in part, be related to the loss of the serum regulator enzyme carboxypeptidase N, also designated AI.

Anaphylatoxins↗
PubMed1983

Experimental evaluation of secondary blood cardioplegia.

Reperfusion damage after ischemia may be evidenced by myocardial cell edema, intracellular calcium accumulation, and limited utilization of oxygen. The need for cardioplegic arrest during initial reperfusion to allow oxygen to be used for reversing ischemic damage rather than for electromechanical activity has been propounded by some researchers. Reports of greater postischemic compliance and performance, low postischemic edema, and greater oxygen uptake at a perfusion pressure of 50 mm Hg or lower have been cited. The present study was conducted on 24 pigs having 2-hr cardioplegic arrest, which of 12 underwent normal reperfusion and 12 experienced secondary cardioplegia followed by normal reperfusion. The results showed that in spite of improved high-energy phosphate preservation, the secondary cardioplegia group had higher myocardial edema, less coronary flow, and poorer contractility and compliance at the end of 1 hr of reperfusion. Because of these findings and contradictory results reported by other groups, caution is urged in the clinical extrapolation of the results of such studies pending further investigations.

Animals↗
PubMed1983

High-volume crystalloid cardioplegia. An improved method of myocardial preservation.

Controlled metabolic studies were used to gauge the relative efficacy of three cardioplegic techniques in 41 patients undergoing multiple coronary artery bypass grafts. Normal-volume (1,946 +/- 155 ml) crystalloid cardioplegia (NVCC) (14 patients) was compared to high-volume (4,961 +/- 282 ml) crystalloid cardioplegia (HVCC) (14 patients) and to blood cardioplegia (BC) (1,672 +/- 127 ml) (13 patients). Measurements of coronary blood flow, coronary vascular resistance, coronary arteriovenous oxygen difference, myocardial oxygen consumption and extraction, and myocardial lactate and potassium extraction and release were all measured in the isolated, vented, paced, beating heart, before and for 20 minutes after a 1 hour arrest interval during which revascularization was completed. Additionally, during administration of the cardioplegic solution, infusion flow rate, myocardial oxygen consumption and extraction, and lactate and potassium release and uptake were noted. The results indicate that during cardioplegic administration, myocardial oxygen consumption is 1 ml O2/min with crystalloid infusion and 2.6 ml O2/min during BC infusion. The volume of crystalloid solution administered contributed to increased oxygen utilization during HVCC compared to NVCC, whereas BC promoted the highest oxygen utilization of the three groups. Potassium absorption was nearly three times greater during BC than during crystalloid administration. During myocardial reperfusion, oxygen extraction was maintained at prearrest levels only in the HVCC group. Following both NVCC and BC, oxygen extraction was depressed during the first 5 minutes of reperfusion, and the difference between the latter two groups and HVCC was significant (p less than 0.01). The rapid recovery in normal metabolic function seen with HVCC allows early discontinuation of cardiopulmonary bypass without myocardial metabolic depression.

Adult↗
PubMed1983

Mechanism of plasma catecholamine increases during coronary artery bypass and valve procedures.

Nineteen patients undergoing coronary revascularization (14 patients) or valve replacement (five patients) were studied to monitor the catecholamine levels following operation and for each of three consecutive postoperative days. A significant (p less than 0.01) elevation was observed in both the serum norepinephrine and epinephrine levels immediately following operation, with both responding in a similar fashion (r = 0.804, p = 0.016). While epinephrine returned to control levels within 3 days of operation, the norepinephrine levels remained above control. The elevation in catecholamines associated with cardiac operation is presumed to be secondary to (1) the stress of surgical trauma and (2) the influence of cardiopulmonary bypass, with its attendant hypothermia and hemodynamic alterations. A comparative analysis was performed of (1) the type of operation, (2) the sex of the patient, (3) the presence of postoperative arrhythmia, (4) the history of receiving propranolol, (5) the duration of cardiopulmonary bypass, (6) the duration of operation, and (7) the volume of fluid gradient absorbed during operation. None of these parameters except the sex of the patient was significantly related to the change in either norepinephrine or epinephrine associated with the operation. There was a significantly (p less than 0.05) higher epinephrine level at day 2 and 3 following operation in women than in men. None of the 19 patients had postoperative complications except for arrhythmias, which developed in nine patients and were not associated with the catecholamine responses. It is concluded that peak catecholamine stimulation does not reflect the ease of postoperative recovery. The duration of bypass and operation were also not directly related to the level of stimulation. It is apparent that there are multiple factors which combine to influence catecholamine secretion during cardiopulmonary bypass.

Adult↗
PubMed1983

Use of Fluosol-DA during open-heart surgery.

Cardiopulmonary bypass using a nonpulsatile pumping system and a bubble oxygenator was employed for one hour followed by one hour of recovery in nine pigs using Fluosol as the priming agent for the bypass pump. Gas exchange was found to be adequate with only a minimal decrease in arterial oxygen content and no increase in arterial CO2 content during bypass. Whole body oxygen consumption decreased slightly during bypass, which was felt to be secondary to a less than ideal blood flow of 90-100 ml/kg/min. Higher blood flows were not feasible in our animal model without significant volume expansion during perfusion. Hemodynamic data documented a significant decrease in arterial pressures and an increase in pulmonary artery pressures during the recovery phase. This was associated with a marked increase in pulmonary vascular resistance and was felt to be secondary to pulmonary congestion, the pathogenesis of which is not fully understood.

Animals↗
PubMed1982

Myocardial high-energy phosphate replenishment during ischemic arrest: aerobic versus anaerobic metabolism.

An in vivo, isolated pig heart preparation was used to study the effect of L-glutamate added to crystalloid and blood potassium cardioplegia on the myocardial high-energy phosphate compounds, adenosine triphosphate (ATP) and creatine phosphate (CP). Studies were performed during a three-hour arrest interval and during 60 minutes of reperfusion. Levels of ATP remained at or above control levels during arrest in animals receiving either unmodified blood or glutamate-enriched crystalloid cardioplegia. While glutamate significantly improved the ability of the crystalloid solution to preserve ATP during arrest, when added to blood, it contributed to a depressed ATP after a three-hour arrest. Creatine phosphate declined during arrest in all animals, but those receiving unenriched blood cardioplegia consistently had the highest levels (p less than 0.05). Addition of glutamate to crystalloid cardioplegia provided a significantly (p less than 0.05) higher level of CP at the end of three hours of arrest, which was still lower than that noted with unenriched blood. Comparable to its effect on the ATP level, when glutamate was added to blood cardioplegia, a decrease (p less than 0.05) in CP was noted after three hours of arrest. Attempts to enhance high-energy phosphate production by supplementing blood cardioplegia with L-glutamate are ineffective, while increased high-energy phosphate production results when glutamate is added to crystalloid cardioplegia. This implies that L-glutamate functions where anaerobic and not aerobic metabolism is the major component of preservation. With reperfusion, the only group of animals displaying depressed levels of ATP and CP was that receiving glutamate-enriched blood cardioplegia.

Adenosine Triphosphate↗
PubMed1982

The effect of acute coronary artery occlusion during cardioplegic arrest and reperfusion on myocardial preservation.

A study was undertaken to evaluate the effect of acute occlusion of a coronary artery during cardioplegic arrest on myocardial preservation and to elucidate the influence of reestablishment of flow versus continued occlusion during the phase of myocardial reperfusion. Coronary occlusion was simulated, and myocardial viability was determined by measuring tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in biopsies of the posterior left ventricular wall. Eighteen pigs were divided into three equal groups consisting of animals with (1) patent right coronary arteries during arrest and reperfusion, (2) occluded right coronary arteries during arrest and patent during reperfusion, and (3) occluded right coronary arteries during arrest and reperfusion. The results of ATP and CP measurements showed that while poorer protection was afforded during two-hour arrest when the coronary artery was occluded, the risk of damage was much greater during reperfusion. Failure to restore adequate blood flow by retention of occlusion caused a concurrent decrease in ATP and CP levels below prescribed limits of myocardial tolerance. When occlusion occurs in the clinical setting, impeding cardioplegia and reperfusion, the importance of revascularization is emphasized.

Adenosine Triphosphate↗
PubMed1982

The temperature dependence of recovery of metabolic function following hypothermic potassium cardioplegic arrest.

A study was performed to define the influence of reperfusate temperature on the recovery of high-energy phosphate compounds following hypothermic ischemic cardioplegic arrest. Two groups, each consisting of six pigs, were subjected to 1 hour of hypothermic potassium cardioplegic arrest (myocardial temperature 10 degrees to 15 degrees C). In one group, the arrest period was followed by a 30 minute period of normothermic reperfusion (37 degrees C) followed by a second hour of hypothermic cardioplegic arrest and a second 30 minute normothermic reperfusion period. The second group of pigs was reperfused after the first hour of arrest for 30 minutes with a cold blood (10 degrees to 14 degrees C) followed by an additional hour of hypothermic cardioplegic arrest and a second 30 minute hypothermic reperfusion period. Myocardial biopsy specimens for adenosine triphosphate (ATP) and creatine phosphate (CP) were obtained at the beginning of perfusion (control studies), at the end of each hour of the arrest interval, and at the end of each 30 minutes of reperfusion. The ATP and CP levels were significantly higher after normothermic reperfusion than after hypothermic reperfusion. After normothermic reperfusion the CP level exceeded control; following hypothermic reperfusion CP remained less than 70% of the control level. On the basis of these results, it is proposed that hypothermic reperfusion does not permit the same level of high-energy phosphorylation that is provided with normothermic reperfusion and may therefore adversely affect hemodynamic recovery of the heart after cardioplegic arrest.

Adenosine Triphosphate↗
PubMed1982

Fluosol cardioplegia--a method of optimizing aerobic metabolism during arrest.

Fluosol-DA cardioplegia was compared with crystalloid cardioplegia as a method of myocardial preservation during ischemic arrest. Two groups of 12 pigs each were studied using the in situ pig heart model. Each group was subjected to 2-hour hypothermic (temperature 10-15 degrees C), hyperkalemic (35 mEq/l potassium) cardioplegic arrest. One group received the standard crystalloid cardioplegic solution (PO2 142-164 mm Hg) and the other received an oxygenated Fluosol cardioplegic solution (PO2 420-510 mm Hg). Myocardial contractility (max Vce) compliance, coronary blood flow (six pigs), and adenosine triphosphate and creatine phosphate (six pigs) were measured before and after cardioplegic arrest; high-energy phosphate (adenosine triphosphate and creatine phosphate) levels were also measured during the 2-hour arrest interval. All pigs had 1 hour of normothermic reperfusion, with measurements performed every 15 minutes. The results documented significantly better high-energy phosphate levels in the Fluosol than in the crystalloid group during arrest. During reperfusion, high-energy phosphate levels were equal in both groups. Contractility and compliance were depressed equally during reperfusion in both groups and coronary blood flow showed no significant difference from control in either group. We conclude that Fluosol can support aerobic metabolism during ischemic cardioplegic arrest and preserve high-energy phosphates, but it has no metabolic or hemodynamic advantage during reperfusion.

Adenosine Triphosphate↗
PubMed1981

The optimal potassium concentration in cardioplegic solutions.

High-energy phosphates provide a sensitive index of myocardial preservation. This experiment was designed to use this index in order to assess the efficacy of various potassium concentrations in a crystalloid cardioplegic solution in protecting the myocardium during hypothermic ischemic arrest. The in vivo ischemic pig-heart model was used, measuring left ventricular levels of adenosine triphosphate (ATP) before, during, and after a two-hour arrest period and after 30 minutes of reperfusion. Thirty-eight animals were divided into seven groups of 5 to 6 animals each. Each group received a different potassium concentration in the cardioplegic solution, namely, 5, 10, 15, 20, 25, 30, and 35 mEq/L. The results were as follows: the ATP moiety was best preserved during ischemia and reperfusion in the 15 mEq/L group, while it remained significantly lower in the 5 mEq/L group. The 10, 20, 25, 30, and 35 mEq/L groups showed an intermediate range of ATP preservation. We conclude from these results that cardioplegic solutions containing 5 mEq/L of potassium seem to be inadequate for myocardial preservation during ischemic arrest; that solutions with 15 mEq/L of potassium may offer the best myocardial protection of all concentrations tested; and that solutions with potassium concentrations of 15 and 35 mEq/L are significantly better than normokalemic (5 mEq/L) cardioplegic solutions.

Adenosine Triphosphate↗
PubMed1981

Fluosol-DA: an artificial blood for total cardiopulmonary bypass.

The isolated, in situ pig heart model was used to determine if Fluosol could support myocardial function during cardiopulmonary bypass. Fourteen pigs were utilized; 7 underwent studies of myocardial metabolism (coronary blood flow and vascular resistance, myocardial oxygen consumption and extraction, lactate extraction, and adenosine triphosphate and creatine phosphate levels), and 7 underwent studies of myocardial contractility and compliance (intraventricular balloon measurements). Each study was carried out utilizing one hour of control hemic perfusion, followed by one hour of Fluosol perfusion, and followed by a third hour of a return of hemic perfusion. The results documented that in the vented, beating, nonischemic heart, myocardial metabolism and functional measurements are maintained during an hour of Fluosol perfusion. However, because of an increased level of ionized calcium during Fluosol perfusion, myocardial functional measurements document significantly increased contractility. The increased contractility is associated with an increase in anaerobic metabolism. The latter contributes to a decline in the high-energy phosphate level following a return of hemic perfusion as the heart recovers from the increased work load placed on it during Fluosol perfusion. It is concluded that here is sufficient oxygen-carrying capacity in Fluosol-DA to maintain cardiac function during perfusion in the large animal model. However, the carrier solution for the Fluosol must be adjusted to appropriate electrolyte content to avoid adverse effects on the myocardium.

Adenosine Triphosphate↗
PubMed1981

The effect of prolonged cardioplegic arrest on long-term ventricular function.

Twenty-five patients (15 coronary revascularizations and 10 valve replacements) having ischemic arrest times longer than 120 minutes (121 to 184 min) were studied by scintigraphy 7 to 27 months after operation. We sought to define if prolonged cardioplegic arrest could be correlated with late postoperative ventricular functional deterioration. Each patient had serial enzymes, EKG analyses, and a technetium pyrophosphate (PYP) scan immediately following operation to determine if an intraoperative infarct occurred which could predispose to functional deterioration. One coronary bypass patient (6.7%) suffered a perioperative myocardial infarct. After a follow-up period of 7 to 25 (mean 17.9) months, none of the 15 patients has developed recurrent angina, infarction or congestive heart failure. Comparing preoperative and late postoperative ventricular function, 3 patients (20%) had a greater than 10% fall in ejection fraction (EF) and 3 (20%) a greater than 10% rise. Mean EF (15 patients) prior to operation was 57.8 +/- 4.7% and at restudy 59.0 +/- 4.6%. One valve replacement patient (10%) suffered a perioperative infarction. After a follow-up period of 16 to 27 (mean 19.9) months, all patients continue to do well. Comparing preoperative to late postoperative ventricular function, 3 patients (30%), had a greater than 10% fall in EF and 2 (20%) a greater than 10% rise. Mean EF (10 patients) prior to operation was 60.5 +/- 5.0% and at restudy 60.1% +/- 5.8%. It is concluded that prolongation of cardioplegic arrest beyond 2 hours is well-tolerated in most patients. Routine early postoperative tests were not useful in prognosticating late functional deterioration in 4 of 6 patients not suffering a perioperative infarction, and in these patients depressed function may be secondary to myocardial fibrosis.

Coronary Disease↗
PubMed1981

Perfusion technology in the hypothyroid patient.

Cardiopulmonary bypass may, by necessity, have to be performed in patients who are frankly hypothyroid. In treating five such patients, all of whom required coronary revascularization, it was noted that fluid balance during perfusion was considerably different than that in the normal population. In order to attempt to evaluate this difference, ten consecutive euthyroid patients having revascularization and the five hypothyroid patients were compared to correlate all fluid absorbed and excreted with the duration of bypass, the serum sodium, and subsequent weight gain. Fluid intake, urine output, and retained fluid were significantly elevated in the hypothyroid as compared to the euthyroid group, while serum sodium following operation was not significantly different. While there are considerable data indicating that hypothyroidism is associated with abnormal salt and water excretion, there is no information concerning the alterations which occur during cardiopulmonary bypass. The present study indicates that hypothyroidism is associated with significant diuresis (without administration of exogenous diuretic agents during cardiopulmonary bypass). The proposed explanation for this diuresis rests with the assumption that with cardiopulmonary bypass and appropriate fluid administration, the contracted blood volume in hypothyroid patients expands acutely and a diuresis results.

Angina Pectoris↗
PubMed1981

The metabolic consequences of blood and crystalloid cardioplegia.

Twenty-seven patients undergoing elective coronary revascularization were evaluated by the following metabolic studies: coronary blood flow and vascular resistance, myocardial oxygen consumption and extraction, and lactate and potassium extraction, uptake and release. Patients were divided into two groups, 14 having crystalloid potassium (25 mEq/l) and 13 blood potassium (25 mEq/l) cardioplegic arrest. The groups were comparable in terms of preoperative demographic characteristics and the duration of cardioplegic arrest, which averaged 63.8 minutes in the crystalloid group and 65.6 minutes in the blood group. There were obvious differences in the effects of the two cardioplegic solutions during administration. Crystalloid cardioplegia had a significantly higher infusion rate and, accordingly, a lower vascular resistance, whereas blood cardioplegia provided increased oxygen use during administration. The amount of lactate released during cardioplegic infusion was greater in the crystalloid than in the blood group, while the amount of potassium absorbed by the heart was greater with blood. During reperfusion, coronary blood flow, vascular resistance and myocardial oxygen consumption were not significantly different in the two groups. The myocardial oxygen extraction, as manifested by a narrowed arteriovenous oxygen difference, was decreased compared with control in both groups during early reperfusion, and the extraction curves for both groups returned to control values by 20 minutes. Myocardial lactate release occurred in both groups during early reperfusion and there was no significant distinction between the two groups. Potassium release occurred during reperfusion in both groups, but significantly more potassium was released in the blood group than in the crystalloid group. We conclude that both methods of myocardial preservation provide adequate protection for 1 hour of ischemic arrest and nearly equal depression in oxygen use. Crystalloid cardioplegia allows greater lactate production during the arrest interval, whereas blood allows a greater potassium absorption by the heart during arrest but releases more potassium during reperfusion.

Adult↗