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Biomedical subjects

R M Engelman

Publications and source records attributed to R M Engelman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Does interruption of normothermic cardioplegia have adverse effects on myocardium? A retrospective and prospective clinical evaluation.

A total of 154 patients who underwent isolated coronary revascularization (coronary artery bypass grafting) using retrograde, near-continuous, warm cardioplegia for myocardial protection, were arbitrarily divided into three groups according to the cumulative cardioplegic interruption (i.e. the sum total of all the short cardioplegic interruption periods, expressed as a percentage of the cardiac arrest period). Group 1 (39 patients) had < 20% interruption (mean(s.e.m.) 12.5(0.01)%), group 2 (82 patients) had 20-39% interruption (mean(s.e.m.) 30.1(0.01)%) and group 3 (33 patients) had > 40% interruption (mean(s.e.m.) 45.4(0.01%). The three groups were comparable except for longer clamp time in group 3 and a lower cardiac index in group 1. The mean number and duration of cardioplegic interruptions and reperfusions and multiple clinical outcomes were recorded. Clinical outcomes (Q) wave perioperative infraction, use of an intra-aortic balloon pump, mortality, and length of stay in the intensive care unit and hospital) were the same in all groups despite significant differences in percent, number and duration of interruption and reperfusion as well as cardiac arrest. The only significant differences found were in the level of creatine kinase-MB (CK-MB) and use of inotropes after surgery, both being higher in group 1 than in groups 2 and 3 (which is the opposite of what would be expected). Intraoperative hemodynamic (cardiac index and left ventricular ejection fraction) and metabolic evaluations (CK-MB, lactate production and oxygen extraction) in 22 additional patients who underwent coronary artery bypass grafting showed no significant differences between two groups having < 30% versus > 30% cumulative cardioplegic interruption. It is concluded that warm cardioplegic interruption as used clinically has no adverse effects on the myocardium in patients undergoing coronary revascularization. Warm retrograde near-continuous blood cardioplegia is an effective method of myocardial protection.

Aged↗
PubMed1995

Constitutive nitric oxide release is impaired after ischemia and reperfusion.

Myocardial ischemia and reperfusion may result in endothelial dysfunction and reduced release of nitric oxide. With the use of an amperometric sensor, the first direct measurements of constitutive nitric oxide release from a beating heart were measured from the coronary effluent of isolated working rat hearts subjected to ischemia and reperfusion. Rats, six to eight per group, were randomly studied as follows: control (no pretreatment) and pretreatment with the nitric oxide donor L-arginine (3 mmol/L), its enantiomer D-arginine (3 mmol/L), nitric oxide inhibitor N omega-nitro-L-arginine methyl ester (100 mumol/L), and combined N omega-nitro-L-arginine methyl ester/L-arginine. Isolated hearts were pretreated for 10 minutes before 30 minutes of global ischemia and 30 minutes of reperfusion. A nonischemic control group (n = 4) was continuously perfused with oxygenated unsupplemented buffer. After ischemia/reperfusion, hearts supplemented with L-arginine recovered significantly (p < 0.05) increased developed pressure, first derivative of the aortic pressure (dP/dtmax), and aortic flow compared with all other hearts that underwent ischemia/reperfusion. In addition, nitric oxide release was significantly (p < 0.05) increased during reperfusion in the L-arginine group. During reperfusion, the recovery of aortic flow correlated with nitric oxide release (r = 0.81, p < 0.0001). We conclude that after ischemia/reperfusion, endothelial dysfunction results in decreased nitric oxide release, which can be ameliorated with L-arginine pretreatment. The direct cytoprotective properties of nitric oxide may contribute to improved functional recovery in hearts pretreated with L-arginine. Augmentation of the L-arginine/nitric oxide pathway may provide a new approach for improved recovery after cardiovascular operations.

Animals↗
PubMed1995

Does cardiopulmonary bypass temperature correlate with postoperative central nervous system dysfunction?

A National Institutes of Health-funded trial of perfusate temperature and neurological function was begun in the Baystate Medical Center in February 1994. It randomizes patients having coronary revascularization to three temperatures--warm (37 degrees C), tepid (32 degrees C), and cold (20 degrees C)--for systemic perfusate and blood cardioplegia temperature at 37 degrees C warm, 32 degrees C tepid, and 6 degrees C to 10 degrees C cold. The goal is to have a quantitated neurological examination performed prior to operation, prior to discharge at day 3 or 4, and at a 1-month follow-up interval. The initial 51 patients completing a 1-month follow-up broke down to 14 cold, 22 tepid, and 15 warm. The neurological examination quantitated their performance on the Mathew Scale, an ordinal measure from 1 to 100, with 100 being normal. There was a significant (p < 0.05) decrease across the entire study from preoperative to postoperative that was no longer present at late follow-up. Although the lowest mean scores (94.8) occurred in the warm group, they were not statistically different from the other groups', and there was no discernible influence of temperature on neurological function. Additional patients will be entered to validate a difference if such exists.

Aged↗
PubMed1995

Myocardial adaptation to ischemia by oxidative stress induced by endotoxin.

In this study, we examined the effects of oxidative stress adaptation on myocardial ischemic reperfusion injury. Oxidative stress was induced by injecting endotoxin (0.5 mg/kg) into the rat. After 24 h, rats were killed, hearts were isolated, and the effects of ischemia-reperfusion were studied using an isolated working heart preparation. The development of oxidative stress was examined by assessing malonaldehyde production in the heart. The antioxidant defense system was studied by estimating antioxidant enzyme activities and ascorbate- as well as thiol-dependent antioxidant reserve. The results of our study indicated that endotoxin induced oxidative stress within 1 h of treatment; the stress was reduced progressively and steadily up to 24 h. The antioxidant enzymes superoxide dismutase, catalase, glutathione (GSH) peroxidase, and GSH reductase were lowered up to 2 h and then increased. Both thiol- and ascorbate-dependent antioxidant reserve were enhanced, but the enhancement of the former was only transitory. After 24 h, endotoxin provided adequate protection to the heart from the ischemic-reperfusion injury, as evidenced by improved left ventricular function and aortic flow. Our results suggest that the induction of oxidative stress by endotoxin-induced adaptive modification of the antioxidant defense in the heart, thereby reducing ischemic-reperfusion injury.

Adaptation, Physiological↗
PubMed1995

Alpha-1 adrenergic receptor agonist-induced preconditioning in isolated working rat hearts.

The aim of this study was to determine whether pharmacologic preconditioning, without a short episode of myocardial hypoxia or ischemia, could improve myocardial function after a prolonged period of ischemia. Isolated rat hearts were perfused with .01, .1 or 1 mg/L of phenylephrine for 5 min followed by a 10-min washout period (preconditioning) before the induction of 30 min of normothermic global ischemia and 30 min of reperfusion. Hearts preconditioned with increasing concentrations of phenylephrine (an alpha-1 adrenergic receptor agonist) produced a reduction in the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). Preconditioning of the hearts with the highest dose of phenylephrine (1.0 mg/L), after 30 min of ischemia, reduced the incidence of reperfusion-induced VF and VT from their nonpreconditioned control values of 87% and 100% to 33% (P < .05) and 50% (P < .05), respectively. After 30 min of ischemia, the recovery of myocardial function was significantly improved in phenylephrine-preconditioned groups. Thus, .1 and 1.0 mg/L of phenylephrine increased aortic flow from its nonpreconditioned control value of 10.8 +/- .9 ml/min to 22.4 +/- 2.4 ml/min (P < .05) and 26.5 +/- 1.5 ml/min (P < .05), respectively. Phenylephrine (1.0 mg/L) preconditioning significantly reduced ischemia/reperfusion-induced tissue Na+ and Ca2+ gains and prevented K+ and Mg2+ loss measured by an atomic absorption spectro-photometer. Our results show that alpha-1 adrenergic stimulation (preconditioning) can prevent postischemic abnormalities in intracellular ions, reperfusion arrhythmias, and contractile function without the inhibition of O2 delivery.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1995

Hypoxic preconditioning preserves antioxidant reserve in the working rat heart.

OBJECTIVE: The aim was to examine whether intracellular antioxidants play a role in myocardial preservation following hypoxic preconditioning. METHODS: Isolated working rat hearts were subjected to 30 min ischaemia and 30 min reperfusion. Control hearts were compared to hearts preconditioned with 10 min hypoxia. Left ventricular function and lactate dehydrogenase (LDH) release were measured in each group. Ascorbate dependent (ADAR) and thiol dependent (TDAR) components of the endogenous myocardial antioxidant reserve were assessed using electron spin resonance spectroscopy. RESULTS: a Hypoxic preconditioning had no effect on left ventricular function after 10 min reoxygenation. During reperfusion, the hypoxically preconditioned hearts had a significantly increased survival rate, aortic flow, developed pressure, and dP/dtmax, and a reduced lactate dehydrogenase release, compared to non-preconditioned controls (P < 0.05). Preconditioned hearts also had significantly higher preservation of baseline ADAR (79%) and TDAR (96%) compared with control hearts, (70%) and (77%), respectively (P < 0.05). CONCLUSIONS: Hypoxic preconditioning enhances functional recovery and reduces cell necrosis following global ischaemia in the working rat heart. This phenomenon may, in part, be mediated through enhanced ascorbate and thiol components of the antioxidant reserve.

Animals↗
PubMed1995

Diabetes and ATP-sensitive potassium channel openers and blockers in isolated ischemic/reperfused hearts.

The incidence of reperfusion ventricular fibrillation (VF) and tachycardia (VT), heart function and the maldistribution of cardiac cations were studied in isolated ischemic/reperfused hearts obtained from streptozotocin-induced diabetic rats. Effects of an ATP-sensitive potassium (KATP) channel opener, cromakalim, and a KATP channel blocker, glibenclamide, also were studied. After 2 and 8 weeks of diabetes, hearts were isolated and subjected to 30 min of ischemia followed by reperfusion. After 2 weeks of diabetes, the incidence of VF and VT was reduced from their nondiabetic control values of 100 and 100 to 42% (P < .05) and 50% (P < .05), respectively. The reduction in VF and VT was not observed with progressive diabetes and after 8 weeks cardiac failure developed. In the 8-week diabetics, the development of cardiac failure was reflected in the aggravation of heart function (26, 16 and 17% reductions in aortic flow, left ventricular developed pressure and first derivative of developed pressure, respectively), and ion shifts (56 and 71% accumulation in cellular Na+ and Ca++, respectively, and 15% loss in cell K+) before the induction of ischemia. After ischemia/reperfusion, these changes were pronounced in diabetic groups. Cromakalim aggravated and glibenclamide attenuated the incidence of arrhythmias, contractile function and ion shifts induced by ischemia/reperfusion in diabetic hearts. The data show that the use of KATP channel openers as anti-ischemic agents may be of particular concern in the population of postinfarction diabetic patients who are known to be at high risk of sudden coronary death.

Adenosine Triphosphate↗
PubMed1995

Nitric oxide signaling in ischemic heart.

OBJECTIVE: Several recent studies have implicated a role of endogenous nitric oxide (NO) in the pathophysiology of myocardial ischemic/reperfusion injury. However, the mechanism by which NO exerts its beneficial/detrimental effects remains unknown. This study examined the intracellular signaling of NO by studying the role of the NO-cGMP signaling pathway on the phospho-diesteratic breakdown and turnover of phosphoinositides during myocardial ischemia and reperfusion. METHODS: Isolated working rat hearts were made ischemic for 30 min followed by 30 min of reperfusion. A separate group of hearts were pre-perfused with 3 mM L-arginine for 10 min prior to ischemia. The release of NO was monitored using an on-line amperometric sensor. The aortic flow and developed pressure were examined to determine the effects of L-arginine on ischemic/reperfusion injury. For signal transduction experiments, sarcolemmal membranes were radiolabeled by perfusing the isolated hearts with [3H]myoinositol and [14C]arachidonic acid. Hearts were then perfused for 10 min in the presence or absence of L-arginine via the Langendorff mode. Ischemia was induced for 30 min followed by 30 min of reperfusion. Experiments were terminated before L-arginine and after L-arginine treatment, after ischemia, and during reperfusion. Biopsies were processed to determine the isotopic incorporation into various phosphoinositols as well as phosphatidic acid and diacylglycerol. cGMP was assayed by radioimmunoassay and SOD content was determined by enzymatic analysis. RESULTS: The release of NO was diminished following ischemia and reperfusion and was augmented by L-arginine. L-Arginine reduced ischemic/reperfusion injury as evidenced by the enhanced myocardial functional recovery. cGMP, which remained unaffected by ischemia and reperfusion, was stimulated significantly after L-arginine treatment. The cGMP level persisted up to 10 min of reperfusion and then dropped slightly. Reperfusion of ischemic myocardium resulted in significant accumulation of radiolabeled inositol phosphate, inositol bisphosphate, and inositol triphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly during reperfusion. Reperfusion of the ischemic heart prelabeled with [14C]-arachidonic acid resulted in modest increases in [14C]diacylglycerol and [14C]phosphatidic acid. Pretreatment of the heart with L-arginine significantly reversed this enhanced phosphodiesteratic breakdown during ischemia and early reperfusion. However, at the end of the reperfusion the inhibitory effect of L-arginine on the phosphodiesterases seems to be reduced. In L-arginine-treated hearts, SOD activity was progressively decreased with the duration of reperfusion time. CONCLUSIONS: The results suggest for the first time that NO plays a significant role in transmembrane signaling in the ischemic myocardium. The signaling seems to be transmitted via cGMP and opposes the effects of phosphodiesterases by inhibiting the ischemia/reperfusion-induced phosphodiesteratic breakdown. This signaling effect appears to be reduced as reperfusion progresses. These results, when viewed in the light of free radical chemistry of NO, suggest that such on- and off-signaling of NO may be linked to its interaction with the superoxide radical generated during the reperfusion of ischemic myocardium.

Animals↗
PubMed1994

Improved postischemic ventricular functional recovery by amphetamine is linked with its ability to induce heat shock.

Heat shock has been shown to increase the cellular tolerances to ischemic injury. In this study, we examined the effects of heat shock induced by amphetamine on postischemic myocardial functional recovery in a setting of coronary revascularization for acute myocardial infarction. Intramuscular injection of amphetamine (3 mg/kg, i.m.) to pigs increased the body temperature to 42.5 degrees C within 1 h, and maintained this temperature for an additional 2 h. Fourty h after the amphetamine injection, the pigs were placed on by cardiopulmonary bypass and then isolated, in situ heart preparations were subjected to 1 h of global hypothermic cardioplegic arrest and 1 h of normothermic reperfusion. Postischemic myocardial performance was monitored by measuring left ventricular (LV) pressure, its dp/dt, myocardial segmental shortening (%SS), and coronary blood flow. Cellular injury was examined by measuring creatine kinase (CK) release. Biochemical measurements included quantification of plasma catecholamines and study of the induction of heat shock gene expression and antioxidative enzymes in the heart tissue. The results of this study indicated significantly greater recovery of LV contractile functions by amphetamine as demonstrated by improved recovery of LVDP (61% vs 52%), dp/dtmax (52% vs 44%), and segmental shortening (46.2% vs 10%). Myocardial CK release was significantly reduced in the amphetamine group. Furthermore, amphetamine pretreatment was associated with the induction of heat shock protein (HSP) 27 mRNA and stimulated Cu/Zn-superoxide dismutase and catalase levels, suggesting that amphetamine mediated improved postischemic ventricular recovery might be linked with its ability to induce heat shock and stimulate antioxidant enzymes.

Amphetamine↗
PubMed1994

Fast-track recovery of the coronary bypass patient.

A new approach termed "fast-track recovery" ws undertaken at both the Baystate Medical Center and Hartford Hospital. The fast-track protocol involves the following principles: (1) preoperative education; (2) early extubation; (3) methylprednisolone sodium succinate before bypass followed by dexamethasone for 24 hours postoperatively; (4) prophylactic digitalization, metoclopramide HCl, docusate sodium, and ranitidine HCl; (5) accelerated rehabilitation; (6) early discharge; (7) a dedicated fast-track coordinator to perform both daily telephone contact and a 1-week postoperative examination; and (8) a routine 1-month postoperative visit with a PA or MD. To evaluate the effects of this approach on patient care, a retrospective 1-year analysis was undertaken in both institutions with all coronary artery bypass grafting patients compared in a consecutive manner before the origin of the fast-track protocol and subsequent to its beginning. There were 280 patients in the fast-track and 282 in the non-fast-track group. The two groups were not significantly different except inexplicably there was a lower ejection fraction in the fast-track group and a longer cross-clamp time. Postoperatively, the mean time to extubation decreased from 22.1 to 15.4 hours, and peak weight gain decreased from 2.8 to 1.6 kg from the non-fast-track to the fast-track group (p < 0.01). This was accompanied by significant (p < 0.001) decreases in intensive care unit duration from 2.4 to 1.9 days and in postoperative length of stay from 8.3 to 6.8 days from the non-fast-track to the fast-track group. There was no increase in morbidity or mortality associated with the fast-track protocol either early or late. Thirty-day hospital readmission was not significantly different between the two groups. Fast-track methodology is effective, and we routinely employ this approach for all patients undergoing cardiopulmonary bypass.

Aged↗
PubMed1994

Myocardial salvage by 1-O-hexadecyl-Sn-glycerol: possible role of peroxisomal dysfunction in ischemia reperfusion injury.

A recent study demonstrated biochemical and structural alterations of peroxisomes in rat kidney after ischemia/reperfusion. We examined whether peroxisomes play any role in the pathophysiology of myocardial ischemia/reperfusion injury. Isolated perfused rat heart was made ischemic for 30 min by terminating coronary flow (CF), followed by 30-min reperfusion. Experiments were divided into two groups; the experimental group received 1-O-hexadecyl-Sn-glycerol (chimyl alcohol) (25, 50, and 100 microM) before ischemia, and the control group received an equivalent amount of saline. Two of the experimental groups (50 and 100 microM) demonstrated improved postischemic myocardial performance, as demonstrated by accelerated recovery in left ventricular developed pressure (LVDP) and CF, as well as reduction in the incidence of ventricular fibrillation (VF). However, because the heart rate (HR) was significantly reduced in the 100-microM chimyl alcohol group, subsequent studies were performed with 50 microM chimyl alcohol as the optimal dose. Chimyl alcohol (50 microM) also reduced cellular injury, as evidenced by reduced creatine kinase (CK) release, and decreased development of oxidative stress, as evidenced by reduced formation of malonaldehyde (MDA). Peroxisomal catalase activity was decreased in the control group after ischemia/reperfusion, and chimyl alcohol treatment restored the activity of the enzyme. Our results indicate that chimyl alcohol, a precursor of ether-linked phosphoglyceride biosynthesis, can reduce myocardial ischemia/reperfusion injury, possibly by restoring catalase activity and reducing oxidative stress through synthesis of ether lipids, suggesting a possible role of peroxisomal disorder in ischemia/reperfusion injury.

3,4-Methylenedioxyamphetamine↗
PubMed1994

Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts.

BACKGROUND: We studied the effect of preconditioning and Gikgo biloba extract (EGb 761) in relation to the recovery of contractile function after global ischemia in the isolated working rat heart. METHODS: Hearts (n = 12 in each group) were randomly divided into five groups: In group I, hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion; in group II, they were subjected to one cycle of preconditioning consisting of 5 min ischemia and 10 min reperfusion before the induction of 30 min of ischemia and 30 min of reperfusion; group III hearts underwent two cycles of preconditioning; group IV hearts underwent three cycles of preconditioning; and group hearts underwent four cycles of preconditioning before the onset of 30 min ischemia followed by 30 min of reperfusion. RESULTS: Ventricular fibrillation (total) and ventricular tachycardia (no preconditioning) both fell from 100% to 50% (P < 0.05) after four cycles of preconditioning. In relation to ventricular fibrillation, preconditioning significantly reduced the formation of oxygen free radicals, measured by electron spin resonance spectroscopy (ESR), but recovery of cardiac function was low in all preconditioned groups. Because of the relatively low incidence of arrhythmias (50% ventricular fibrillation and 50% ventricular tachycardia) and relatively low cardiac function in Group V, EGb 761, a free-radical scavenger, was chosen to improve myocardial contractile function in preconditioned hearts. Fifty and 100 mg/kg of EGb 761 (per os) significantly improved coronary flow, aortic flow, left ventricular developed pressure (LVDP), and the first derivative of LVDP (LVDdP/dtmax) in the four-cycle preconditioned group. Thus, after 30 min of reperfusion, aortic flow was improved from 11.6 +/- 0.9 ml/min to 19.7 +/- 1.2 ml/min (P < 0.05) with a dose of 50 mg/kg of EGb 761 and to 22.0 +/- 1.5 ml/min (P < 0.05) with a dose 100 mg/kg of EGb 761, in the four-cycle preconditioned group. During reperfusion, the formation of free radicals was reduced by approximately 50 and 60% using 50 mg/kg and 100 mg/kg of EGb 761, respectively, when compared with the four-cycle preconditioned drug-free control group. CONCLUSION: We have demonstrated that EGb 761 can improve contractile function after global ischemia in the isolated working rat heart by reducing the formation of oxygen free radicals, and we have shown that this protection is additive to that of ischemia-induced preconditioning.

Animals↗
PubMed1994

Myocardial stunning: a temperature dependent phenomenon.

Two recently completed studies in our laboratory have evaluated the relationship between myocardial temperature during cardioplegic preservation and calcium accumulation within the cell. In the large animal model, the pig, we investigated the influence of normothermic versus hypothermic blood cardioplegic preservation on sarcoplasmic reticulum calcium ATPase activity and calcium uptake following 2-hour cardioplegic arrest and 1 hour of normothermic reperfusion. The second investigation in the small animal model, the rat, measured intracellular calcium concentration in hearts subjected to cardioplegic arrest by continuous administration of cardioplegia at temperatures from 4 degrees to 37 degrees C. In the pig heart, global left ventricular function and coronary blood flow were improved, while creatine kinase release was reduced in the warm preserved heart. The rate of sarcoplasmic reticulum calcium uptake and calcium ATPase activity were impaired only in the presence of hypothermic preservation, and the higher calcium ATPase activity corresponded to the higher rate of sarcoplasmic reticulum calcium uptake observed in the warm preserved heart. Measurements of intracellular calcium concentration accomplished with a spectrofluorimeter documented a significant increase in free calcium in the 4 degrees C and 20 degrees C preserved rat heart during normothermic reperfusion. At both 28 degrees and 37 degrees C preservation, the free calcium level did not increase. It is concluded that intracellular calcium accumulation is associated with hypothermic preservation. Hypothermia appears to jeopardize the control of calcium homeostasis, which then is manifested as a more rapid increase of intracellular calcium during reperfusion. This would be associated with increased myocardial stunning in the hypothermic heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗