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Biomedical subjects

R M Engelman

Publications and source records attributed to R M Engelman.

At least 127 records · Page 7Linked to original sources
PubMed1988

Novel dual-wavelength monitoring approach for the improved rapid separation and estimation of adenine nucleotides and creatine phosphate by high-performance liquid chromatography.

A rapid and improved method for the simultaneous quantification of adenine nucleotides, including adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, as well as creatine phosphate by high-performance liquid chromatography is described. A programmable multi-wavelength UV detector was used to monitor the effluent initially at 210 nm for 4 min to measure creative phosphate, and then at 259 nm for 6 min to quantitate adenosine mono-, di- and triphosphate. The method is, thus, not only rapid, but also extremely sensitive because of the utilization of corresponding absorption maxima for creatine phosphate and adenine nucleotides, rather than measuring all of them at a single wavelength. In addition, computer-generated standard curves were used to estimate these compounds, thereby improving the accuracy of the measurements. Since myocardial high-energy phosphate levels are widely measured because they are reliable parameters for myocardial preservation during ischemia, these compounds were assayed in pig heart prior to and following ischemia. The results were compared with those obtained by conventional high-performance liquid chromatographic assay methods in order to examine the validity of this method. Our results indicate that this is indeed a novel method, which is more rapid as well as sensitive and accurate compared with other methods.

Adenine Nucleotides↗
PubMed1988

Perioperative morbidity in diabetics requiring coronary artery bypass surgery.

We retrospectively evaluated the operative results in 384 patients with diabetes mellitus operated on for ischemic coronary artery disease over a six-year period compared with a random group of 396 patients selected from 2,069 nondiabetic patients who underwent operation during the same study period. In our analysis of 13 preoperative and 5 intraoperative variables, diabetics revealed a significantly increased incidence of hypertension (p less than 0.05) and a smaller proportion of men (p less than 0.05). All other variables were not significantly different. The incidence of perioperative myocardial infarction, renal failure, neurological sequelae, leg infections, or thromboembolic events was similar in diabetic and nondiabetic patients. Hospital stay, however, was significantly increased in the diabetic group (p less than 0.05). The diabetic patients requiring intraaortic balloon counterpulsation had a significantly higher incidence of all postoperative complications analyzed compared with diabetics without balloon support (p less than 0.01), whereas the nondiabetic subset requiring intraaortic balloon counterpulsation exhibited only a significantly higher incidence of renal failure (p less than 0.01) and neurological complications (p less than 0.05). These results indicate that diabetes per se does not significantly increase morbidity in coronary bypass surgery.

Coronary Artery Bypass↗
PubMed1988

Improved myocardial performance induced by clofibrate during reperfusion after acute myocardial infarction.

The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.

Animals↗
PubMed1988

Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart.

In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.

Animals↗
PubMed1988

Effect of ischemia and reperfusion of the myocardium on in vitro beta-oxidation of fatty acids.

The in vivo oxidation of perfused [14C]-labeled fatty acids has been shown to decrease dramatically in hypoxic hearts. This study addresses the influence of ischemia and reperfusion on the enzymic activities of beta-oxidation of fatty acids in mitochondria and of peroxisomal origin. The rate of beta-oxidation of fatty acids in the isolated mitochondria from myocardium of swine fed control diet declined about 20% by the ischemic insult induced by hypothermic cardioplegic arrest. Upon reperfusion, the rate of mitochondrial beta-oxidation returned to a normal level. In clofibrate-fed animals, the rate of mitochondrial beta-oxidation did not vary significantly between control, ischemic, and perfused tissues. Furthermore, neither in control nor in clofibrate-fed animals did the rates of peroxisomal beta-oxidation of fatty acids vary significantly in the ischemic or reperfused tissues as compared to that of preischemic controls. These results suggest that ischemia does not contribute to any loss of enzymic activity in beta-oxidation of fatty acid cycles either in mitochondria or peroxisomes. Furthermore, the feeding of 0.5% (w/w) clofibrate to pigs increased the rate of mitochondrial beta-oxidation of fatty acids only by 50% while that of peroxisomes increased threefold. A similar threefold increase in catalase activity was also produced by clofibrate feeding. These results suggest that the heart plays a role in the hypolipidemic action of clofibrate.

Animals↗
PubMed1988

The effect of temperature and hematocrit level of oxygenated cardioplegic solutions on myocardial preservation.

The ideal temperature and hematocrit level of blood cardioplegia has not been clearly established. This study was undertaken (a) to determine the optimal temperature of blood cardioplegia and (b) to study the effect of hematocrit levels in blood cardioplegia. A comparison of myocardial preservation was done among seven groups of animals on the basis of variations in hematocrit levels and temperature of oxygenated cardioplegic solution. The experimental protocol consisted of a 2-hour hypothermic cardioplegic arrest followed by 1 hour of normothermic reperfusion. Group 1 received oxygenated crystalloid cardioplegic solution at 10 degrees C. Groups 2 through 7 received oxygenated blood cardioplegic solution with the following hematocrit values and temperatures: (2) 10%, 10 degrees C; (3) 10%, 20 degrees C; (4) 10%, 30 degrees C; (5) 20%, 10 degrees C; (6) 20%, 20 degrees C; and (7) 20%, 30 degrees C. Parameters studied include coronary blood flow, myocardial oxygen extraction, myocardial oxygen consumption, and myocardial high-energy phosphate levels of adenosine triphosphate and creatine phosphate during control (prearrest), arrest, and reperfusion. Myocardial oxygen consumption at 30 degrees C during arrest was significantly higher than at 10 degrees C and 20 degrees C, which indicates continued aerobic metabolic activity at higher temperature. Myocardial oxygen consumption and the levels of adenosine triphosphate and creatine phosphate during reperfusion were similar in all seven groups. Myocardial oxygen extraction (a measure of metabolic function after ischemia) during initial reperfusion was significantly lower in the 30 degrees C blood group than in the 10 degrees C blood group at either hematocrit level and in the oxygenated crystalloid group, which suggests inferior preservation. The hematocrit level of blood cardioplegia did not affect adenosine triphosphate or myocardial oxygen consumption or extraction. It appears from this study that blood cardioplegia at 10 degrees C and oxygenated crystalloid cardioplegia at 10 degrees C are equally effective. Elevating blood cardioplegia temperature to 30 degrees C, however, reduces the ability of the solution to preserve metabolic function regardless of hematocrit level. Therefore, the level of hypothermia is important in blood cardioplegia, whereas hematocrit level has no detectable impact, and cold oxygenated crystalloid cardioplegia is as effective as hypothermic blood cardioplegia.

Adenosine Triphosphate↗
PubMed1988

Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound. Improved cardiac performance after hypothermic cardioplegic arrest.

The effect of nicotinic acid, an antilipolytic drug, on myocardial preservation was studied on the basis of cardiac performance after 2 hours of cardioplegic arrest. Isolated in situ pig hearts were subjected to 120 minutes of hypothermic potassium (35 mEq) crystalloid cardioplegic arrest followed by 60 minutes of reperfusion. The experimental group received nicotinic acid 0.08 mmol/L 15 minutes before cardioplegic arrest, whereas the control group received 15 minutes of unmodified perfusion. There was a marked decline in myocardial creatine phosphate levels during cardioplegic arrest in both groups that returned to the baseline level during reperfusion without a significant intergroup difference, and adenosine triphosphate levels remained stable throughout the experiment in both groups. Myocardial oxygen consumption during reperfusion was significantly higher in hearts treated with nicotinic acid, which was consistent with a significantly greater cardiac contractile force as evaluated by isovolumetric left ventricular pressure measurements. There appeared to be less cardiac membrane damage as measured by creatine kinase release during reperfusion, which was significantly inhibited by treatment with nicotinic acid. The present study supports the conclusion that nicotinic acid improves cardiac performance after hypothermic cardioplegic arrest.

Adenosine Triphosphate↗
PubMed1987

Role of xanthine oxidase inhibitor as free radical scavenger: a novel mechanism of action of allopurinol and oxypurinol in myocardial salvage.

Xanthine oxidase (XO) has been hypothesized to be a potential source of oxygen-derived free radicals during reperfusion of ischemic myocardium based on the fact that allopurinol, a XO-inhibitor, can reduce reperfusion injury. In this communication we report that both allopurinol and oxypurinol, the principle metabolite of allopurinol, prevent the reperfusion injury in isolated pig heart. However, we found that neither pig heart nor pig blood contain any XO activity. Our study showed a direct free radical scavenging action of these XO-inhibitors during ischemia and reperfusion, as judged by the reduction of free radical signals when compared using an Electron Paramagnetic Resonance Spectrometer. Using a Luminometer, we also confirmed that both allopurinol and oxypurinol can scavenge ClO2, HOCl, and significantly inhibit free radical signals generated by activated neutrophils. These XO-inhibitors, however, failed to scavenge O2. and OH. radicals. Our results suggest that these XO-inhibitors salvaged the ischemic-reperfused myocardium by scavenging free radicals, and not by inhibiting XO in the pig heart.

Adenosine Triphosphate↗
PubMed1987

Simultaneous quantification of myocardial adenine nucleotides and creatine phosphate by ion-pair reversed-phase high-performance liquid chromatography.

A new ion-pair reversed-phase high-performance liquid chromatography method was applied to simultaneous measurements of porcine myocardial adenine nucleotides and creatine phosphate. The homogeneity of each desired peak was tested by the retention times of standards, chromatography of spiked samples, the absorbance ratios at various wavelengths, and the differing retention times for a number of other compounds found in porcine myocardial extracts.

Adenine Nucleotides↗
PubMed1987

Transatrial repair of postinfarction posterior ventricular septal defect.

Repair of a postinfarction posterior ventricular septal defect generally has been performed by ventriculotomy in the infarct zone. This approach carries a significant mortality and morbidity from hemorrhage, extending infarction, or further compromise of ventricular function secondary to suture placement. A successful transatrial repair of a postinfarction posterior ventricular septal defect is presented. The simplicity of this operation and the patient's rapid recovery contrasted remarkably with the transventricular approach used in previous patients.

Coronary Artery Bypass↗
PubMed1987

Age-related development profiles of the antioxidative defense system and the peroxidative status of the pig heart.

The developmental profiles of the antioxidative defense system and the peroxidative status of the heart during growth and development were studied in pigs of three different age groups. A unique age-specific myocardial lipid peroxidation expressed in terms of malonaldehyde formation occurred after incubation of neonatal and adult pig heart homogenates in the absence of any added factors. Very little malonaldehyde release was noticed in the 0- to 2-day age group, while considerably higher activity was found in the 8- to 10-day-old animals. The 2-month-old pig heart again formed very little malonaldehyde. Myocardial injury from lipid peroxidation was highest in the 0- to 2-day age group, as evidenced by the release of oxidized glutathione, lactate dehydrogenase (LDH) and creatine kinase (CK) activities. Release of glutathione, LDH and CK decreased with age and was minimal in the adult group. The antioxidative enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, increased during the first 10 days of neonatal growth and then levelled off. Glucose-6-phosphate dehydrogenase was present in appreciably lower amounts in adult hearts compared to neonatal hearts. Heart weight increased with aging, but myocardial water content decreased. Protein and DNA contents of hearts increased with age, such that the protein/DNA ratio almost doubled from the newborn to adult age. The results indicate that the newborn pig hearts are equipped with the antioxidative defense system, which undergoes significant development during the initial phase of neonatal growth and does not change appreciably thereafter. The results further suggest that the change in activity profile with aging is different for different enzymes, and the peroxidative status of the myocardium is not a function of these enzyme activities.

Aging↗
PubMed1987

Blood conservation for myocardial revascularization. Is it cost effective?

A total of 284 patients undergoing myocardial revascularization were prospectively studied to determine if the use of intraoperative autotransfusion or intraoperative autotransfusion plus postoperative reinfusion of shed mediastinal blood decreased transfusion requirements and the use of one or both techniques was cost effective. The Haemonetics Cell Saver System was used for intraoperative autotransfusion and the Sorenson Receptaseal autotransfusion system for postoperative reinfusion of shed mediastinal blood. During Phase 1, the Cell Saver System was used for 57 patients and 93 patients served as a control group. During Phase 2, the Cell Saver System plus the autotransfusion system were used in 43 patients and 91 patients were in the control group. Separate parallel analyses to compare the blood conservation groups to control groups were conducted for each phase of the study. The patient groups were comparable with regard to age, sex, preoperative red cell mass, preoperative hematocrit value, number of bypasses, and use of internal mammary grafts. Blood conservation techniques resulted in significant reductions in the use of bank blood. During Phase 1, Cell Saver System patients received an average of 2.8 units of packed cells versus 4.7 units for control patients. Transfusion was avoided entirely in 14% of Cell Saver System patients compared to 3% of control patients. During Phase 2, patients subjected to both the Cell Saver System and the autotransfusion system received an average of 1 unit of packed red cells versus 3 units for control patients. Transfusion was required in only 42% of patients subjected to both the Cell Saver System and the autotransfusion system compared to 85% of control patients. Multiple logistic regression analysis confirmed that the use of the Cell Saver System in Phase 1 and the Cell Saver System and autotransfusion system in Phase 2 were each independently predictive of decreased transfusion requirements. The total "blood-related costs" (including cost for all bank blood products plus Receptaseal and Cell Saver System equipment) was slightly lower for the blood conservation patients in both Phase 1 ($555.00 versus $615.00, no significant difference) and Phase 2 ($373.00 versus $426.00, no significant difference). Intraoperative use of the Cell Saver System is associated with substantial savings of bank blood, and the addition of postoperative reinfusion of shed mediastinal blood results in further bank blood savings. The use of blood conservation techniques is cost effective; that is, the costs incurred for the blood conservation equipment are more than offset by the resultant dollar savings for blood products.

Blood Transfusion, Autologous↗
PubMed1987

Catheter drainage of symptomatic postoperative mediastinal effusion guided by computed tomography. A nonoperative approach.

Postoperative mediastinal effusion after cardiac operations is a common phenomenon and has a potential for serious complications, such as tamponade necessitating urgent drainage. Computed tomography of the chest provides excellent postoperative visualization of the mediastinum. Catheter insertion or paracentesis guided by computed tomography has been used to accomplish nonoperative drainage of symptomatic postoperative mediastinal effusion in six cases. This technique offers simplicity, safety, and cost effectiveness.

Aged↗
PubMed1987

Aerobic vs anaerobic metabolism during ischemia in heart muscle.

Anaerobic metabolism in heart muscle plays a role in maintenance of myocardial preservation only during ischemia or hypoxia. In an ischemic state, such as during a heart attack or even during the induced ischemia of open heart surgery, there is impairment of blood flow to the myocardium. The major energy-yielding process in the heart is through the metabolism of glucose and lipids by oxidative reactions. Under anaerobic conditions, oxygen is not available to accept the electrons in the metabolic degradation of substrates and anaerobic glycolysis becomes important in the preservation of myocardial viability during the ischemic process. Unfortunately, the accumulated products of glycolysis, namely protons and lactate, work to inhibit glycolysis, ultimately resulting in a depression of anaerobic metabolism. Cardioplegia, as utilized during open heart surgery, has the effect of inducing instantaneous induction of myocardial mechanical and electrical arrest with a maximal inhibition of the energy utilizing metabolic processes. This effectively reduces substrate utilization and prevents the deleterious consequences of the ischemic process. Cardioplegia is most effective when combined with the additive properties of hypothermia, which plays a significant role in decreasing myocardial metabolism. However, during prolonged hypothermic cardioplegic arrest, sufficient ATP cannot be maintained for cellular integrity and anaerobic glycolysis becomes of increasing importance for maintenance of myocardial preservation. This presentation deals with the mechanics of aerobic versus anaerobic metabolism during the ischemic process of open heart surgery.

Adenosine Triphosphate↗
PubMed1987

The mechanism of myocardial reperfusion injury in neonates.

Oxygen free radicals and phospholipid degradation have been implicated in the pathogenesis of ischemia and reperfusion injury. The present study examines the involvement of such mechanisms in myocardial reperfusion injury in neonatal hearts. The isolated neonatal pig hearts from two different age groups, 0 to 2 days old (newborn) and 7 to 9 days old (week-old), were subjected to 60 min of normothermic global ischemia followed by 60 min of reperfusion. Although myocardial ischemia reduced superoxide dismutase, catalase, and glutathione peroxidase activities in both age groups, superoxide dismutase and catalase activities remained significantly lower in the newborn pig heart during ischemia and reperfusion. Oxidized glutathione release from the neonatal pig hearts was at minimum levels before ischemia, but it increased 10-fold at the onset of reperfusion and was significantly higher in the newborn heart. This indicates that generation of oxygen free radicals was enhanced in the newborn compared with that in the week-old heart. The increase in phospholipase A2 activity and decrease in acyl CoA synthetase and lysophosphatidylcholine acyl transferase activities during ischemia and reperfusion were associated with comparable loss of membrane phospholipids and accumulation of lysophosphatidylcholine and free fatty acids in both age groups, except that oleic acid content was significantly higher in the newborn heart during reperfusion. Myocardial damage appears to be potentiated in the newborn heart during reperfusion, as evidenced by higher release of creatine kinase and a lower content of high-energy phosphates. These results indicate that oxygen free radicals may play a crucial role in the occurrence of reperfusion injury in immature hearts.

Animals↗
PubMed1986

Enhanced prostaglandin synthesis due to phospholipid breakdown in ischemic-reperfused myocardium. Control of its production by a phospholipase inhibitor or free radical scavengers.

The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardioplegic arrest, followed by 60 mins of reperfusion. Myocardial biopsies were taken from the ischemic and non-ischemic regions of the myocardium for measurement of phospholipids, and samples of the perfusate were drawn for estimation of the end-products of arachidonic acid metabolism, 6-keto-prostaglandin-F1 alpha and thromboxane B2. A significant amount of 6-keto-prostaglandin F1 alpha and thromboxane B2 appeared during reperfusion, corresponding with the loss of membrane phospholipids in control animals. Mepacrine, a phospholipase inhibitor, protected the depletion of membrane phospholipids and inhibited the products of arachidonate metabolism. Superoxide dismutase (SOD) and catalase, on the other hand, enhanced the formation of 6-keto-prostaglandin F1 alpha and thromboxane B2. The effects of both mepacrine and the free radical scavengers were pronounced during the reperfusion phase when the most significant depletion in membrane phospholipids occurred. These results suggest that the arachidonate cascade is activated during reperfusion of ischemic myocardium as a consequence of phospholipid breakdown, and this activation can be attenuated by inhibiting phospholipases or enhanced by scavenging oxygen-free radicals generated during reperfusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion.

Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.

1-Acylglycerophosphocholine O-Acyltransferase↗