Papers by Richard Engelman
Chest, 1972
Two cases of aneurysm fonuation developing in an aberrant right subclavian artery are presented. ... more Two cases of aneurysm fonuation developing in an aberrant right subclavian artery are presented. The aberrant right subclavian artery repre8enCs an incomplete vascular ring which is generally asymptomatic and is nsuaUy noted as an accidental finding at necropsy. The development of an aneurysm in the aberrant vessel lying posterior to the esophagus and trachea can produce dysphagia and dyspnea from anterior displacement and narrowing. RadIographically, the aneurysm presents as a superior mediastinal tumor. Barium esopbagography, tomography, and fluoroscopy are indicated to demonstrate the vascular nature of the lesion. Thoracic aortography is necessary for diagnosis. Because of the anatomic location of the aneurysm, surgery should be entertained only if rupture appears imminent or symptoms develop.
The Journal of Thoracic and Cardiovascular Surgery, 1997
Ischemia-reperfusion damages endothelium and impairs basal production of nitric oxide. Basally re... more Ischemia-reperfusion damages endothelium and impairs basal production of nitric oxide. Basally released nitric oxide is cardioprotective by its inhibition of neutrophil activities. Loss of endogenous nitric oxide with endothelial injury may occur during two phases: cardioplegic ischemia and reperfusi0n (aortic declamping). This study tested the hypothesis that inhibition of endogenously released nitric oxide in hearts subjected to regional ischemia, cardioplegic arrest, and reperfusion (1) restricts endogenous cardioprotection and permits neutrophil-mediated damage and (2) expresses damage during the reperfusion phase. L-Nitro-arginine was used to block basal nitric oxide production. In 22 anesthetized dogs, the left anterior descending artery was ligated for 90 minutes followed by 1 hour of arrest with cold multidose (every 20 minutes) blood cardioplegia. Dogs were divided into three groups: the first group received standard unsupplemented blood cardioplegia (group 1, n = 8), in the second group L-nitroarginine was administered as an additive to blood cardioplegic solution (1 mmol) and as an infusion during reperfusion (34 mg/kg) (group 2, n = 7), and in the third group L-nitro-arginine was administered only at reperfusion (group 3, n = 7). The ligature was released during the second infusion of cardioplegic solution. Infarct size (triphenyltetrazolium chloride) was increased in group 3 (L-nitro-arginine only at reperfusion) compared with that in group 1 (standard blood cardioplegia) (49% + 6% vs 34% +_ 2%, respectively), but was not further extended in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion) (56%-3%, p > 0.05 vs group 3), which suggests primarily a reperfusion process. Polymorphonuclear neutrophil-specific myeloperoxidase activity in the area at risk was elevated comparably in groups 2 and 3 (group 2:2.9-0.5 units/gm tissue, p = 0.06 vs group 1; group 3:3.9 +-1.0 units/gm tissue, p < 0.05 vs group 1) compared with that in the standard blood cardioplegia group (1.7-0.3 units/gm tissue), suggesting polymorphonuclear neutrophil accumulation occurs primarily during reperfusion. Polymorphonuclear neutrophil adherence in ischemic-reperfused left anterior descending artery segments was comparably greater in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion: 195-+ 21 polymorphonuclear neutrophils/mm 2 of artery, p < 0.05 vs group 1) and group 3 (L-nitro-arginine only at reperfusion: 224-20 polymorphonuclear neutrophils/mm 2 of artery, p < 0.05 vs group 1) relative to that in group 1
Circulation, 2016
Introduction: The detriments of prolonged bedrest are well described, yet most hospitals fail to ... more Introduction: The detriments of prolonged bedrest are well described, yet most hospitals fail to provide enough ambulation to their patients to prevent significant deconditioning and patient harm. One potential strategy for overcoming this problem is the use of an ambulation orderly (AO), an employee whose primary responsibility is to walk patients up to 3-4 times per day. In May 2013, our hospital instituted an AO program among post-operative cardiac surgical patients. We hypothesized that the introduction of an AO program would be associated with improved patient outcomes. Methods: We evaluated all patients undergoing either coronary artery bypass and/or cardiac valve surgery between September 2012 and March 2014. We evaluated the impact of the AO program on post-operative length of stay (LOS), hospital complications, discharge disposition, and 30-day hospital readmission with both a pre-post study design and an interrupted time-series analysis. Results: We identified 925 patients...
The Journal of Thoracic and Cardiovascular Surgery, 2003
See related editorial on page 985. Objective: Diabetes mellitus is a risk factor for death after ... more See related editorial on page 985. Objective: Diabetes mellitus is a risk factor for death after coronary artery bypass grafting. Its relative risk may be related to the level of perioperative hyperglycemia. We hypothesized that strict glucose control with a continuous insulin infusion in the perioperative period would reduce hospital mortality. Methods: All patients with diabetes undergoing coronary artery bypass grafting (n ϭ 3554) were treated aggressively with either subcutaneous insulin (1987-1991) or with continuous insulin infusion (1992-2001) for hyperglycemia. Predicted and observed hospital mortalities were compared with both internal and external (Society of Thoracic Surgeons 1996) multivariable risk models. Results: Observed mortality with continuous insulin infusion (2.5%, n ϭ 65/2612) was significantly lower than with subcutaneous insulin (5.3%, n ϭ 50/942, P Ͻ .0001). Likewise, glucose control was significantly better with continuous insulin infusion (177 Ϯ 30 mg/dL vs 213 Ϯ 41 mg/dL, P Ͻ .0001). For internal comparison, multivariable analysis showed that continuous insulin infusion was independently protective against death (odds ratio 0.43, P ϭ .001). Conversely, cardiogenic shock, renal failure, reoperation, nonelective operative status, older age, concomitant peripheral or cerebral vascular disease, decreasing ejection fraction, unstable angina, and history of atrial fibrillation increased the risk of death. For external comparison, observed mortality with continuous insulin infusion was significantly less than that predicted by the model (observed/expected ratio 0.63, P Ͻ .001). Multivariable analysis revealed that continuous insulin infusion added an independently protective effect against death (odds ratio 0.50, P ϭ .005) to the constellation of risk factors in the Society of Thoracic Surgeons risk model. Conclusion: Continuous insulin infusion eliminates the incremental increase in inhospital mortality after coronary artery bypass grafting associated with diabetes. The protective effect of continuous insulin infusion may stem from the effective metabolic use of excess glucose to favorably alter pathways of myocardial adenosine triphosphate production. Continuous insulin infusion should become the standard of care for glycometabolic control in patients with diabetes undergoing coronary artery bypass grafting. D iabetes mellitus (DM) is a well-established risk factor for death after coronary artery bypass grafting (CABG). 1-3 DM has been recognized as an independent risk factor for CABG-related death since the inception of the Society of Thoracic Surgeons (STS) national risk model in 1991. 1 DM is present in 2.5% of the population in the United States, 4 but its national prevalence among patients undergoing CABG is as high as 28%, 1 making it an important component of the cardiac surgical milieu. DM is associated with higher incidences of preoperative comorbidities, including obesity, small vessel coronary artery disease, more severe and extensive atherosclerosis, peripheral vascular disease, renal insufficiency, hypertension, and increased rates of life-threatening postoperative infection. Conventional wisdom has held that
The Journal of Thoracic and Cardiovascular Surgery, 1998
We read with interest the article by Carias de Oliveira and coauthors from the Massachusetts Gene... more We read with interest the article by Carias de Oliveira and coauthors from the Massachusetts General Hospital, titled "Ischemic Intervals During Warm Blood Cardioplegia in the Canine Heart Evaluated by Phosphorus 31-Magnetic Resonance Spectroscopy" (J Thorac Cardiovasc Surg 1997;114:1070-80). We fully agree with the commentary by Borger and colleagues from Toronto and Winnipeg, Canada, that this is indeed an elegant evaluation of intermittent warm blood cardioplegia. The authors of this excellent article, as well as the commentators, should be congratulated for their attempts to define the limits of safe warm cardioplegia interruption. The authors' experimental findings seem to confirm what we observed in a clinical study presented at the Congress of the International Society for Cardiovascular Surgery in Portugal in 1993 and published in Cardiovascular Surgery in 1995. 1 In that study, we compared clinical and metabolic data in patients undergoing coronary revascularization who had shorter, intermediate, and longer cumulative interruptions of cardioplegia, expressed as a percent of the cardioplegic arrest. There were essentially no significant metabolic or clinical differences between these groups of patients studied retrospectively and some prospectively. We concluded that interruptions of up to 10 minutes were well tolerated, without any identifiable adverse effects. Furthermore, the mean duration of reperfusion after cardioplegic interruptions was about 5 minutes in the theoretically worse group, that is, those patients with the longest mean duration of individual interruption and the largest percent cumulative interruption of cardioplegia. From that clinical study and our long experience using warm cardioplegia in about 4000 adult cardiac operations, we are convinced that reperfusion periods of less than 15 minutes (as short as 3 to 5 minutes) compensate well for the oxygen debt produced during cardioplegic interruptions. The ischemic human heart may actually possess increased tolerance to more prolonged cardioplegic interruptions and shorter reperfusions than the canine heart because of preconditioning and species differences. This, however, has not yet been clearly demonstrated.
Molecular and Cellular Biochemistry, 1992
Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the... more Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (02-) to a highly reactive and cytotoxic hydroxyl radical (OH.). In the present study, we have examined the generation of OH. and free iron in reperfused hearts following either normothermic (37 ° C) or hypothermic ischemia (5 ° C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 rain at 37 ° C or 5 ° C and were then reperfused for 15 rain at 37 ° C. The results of the study suggest that both the OH. generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5 ° C as compared to 37 ° C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated 02-at 5 ° C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH. and free iron as compared to 37 ° C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH. and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals. (Moll Cell Biochem 111: 97-102, 1992)
Journal of the American College of Cardiology, 2002
312A ABSTRACTS-Myocardial Ischemia and Infarction necrosis leading to a cardiomyopathy with featu... more 312A ABSTRACTS-Myocardial Ischemia and Infarction necrosis leading to a cardiomyopathy with feature of hibernation. Early chemokine induction and interstitial fibrosis due to frequent sublethal ischemic episodes may have a role in mediating left ventricular dysfunction in ischemic cardiomyopathy. 4:15 p.m.
Journal of Cellular and Molecular Medicine, 2004
A large number of studies have demonstrated the role of angiotensin II in cardiac preconditioning... more A large number of studies have demonstrated the role of angiotensin II in cardiac preconditioning against ischemic reperfusion injury. Generally, angiotensin II is a detrimental factor for the heart, and its inhibition with an ACE inhibitor provides cardioprotection. This review provides an explanation for such paradoxical behavior of angiotensin II. Angiotensin II can potentiate the induction of the expression of a variety of redox-sensitive factors including p38 MAPK, JNK and Akt, IGF-IR, EGF-R, and HO-1 as well as redox-regulated genes and transcription factors such as NF B. It becomes increasingly apparent that during the earlier phase, the heart attempts to adapt itself against the detrimental effects of angiotensin II by upregulating several cardioprotective genes and proteins. These genes and proteins are redox-regulated and the antioxidants or ROS scavengers block their expressions. Interestingly, an identical pattern of cardioprotective proteins and genes are expressed in the preconditioned heart, which are also inhibited with ROS scavengers. It is tempting to speculate that the induction of the expression of the redox-sensitive cardioprotective proteins is the results of adaptation of the heart against the oxidative stress resulting from angiotensin II; and preconditioning is the net result of harnessing its own protection during ischemic and/or oxidative stress through its ability to trigger redox signaling.
Journal of Cardiovascular Pharmacology, 1996
Protein kinase C (PKC) has been implicated in the preconditioning-induced cardiac protection in i... more Protein kinase C (PKC) has been implicated in the preconditioning-induced cardiac protection in ischemic/reperfused myocardium. We studied the effect of PKC inhibition with calphostin C (25, 50, 100, 200, 400, and 800 nM), a potent and specific inhibitor of PKC, in isolated working nonpreconditioned and preconditioned ischemic/reperfused hearts. In the nonpreconditioned groups, all hearts underwent 30 min of nonmothermic global ischemia followed by 30 min of reperfusion. In the preconditioned groups, hearts were subjected to four cycles of ischemic preconditioning by using 5 min of ischemia followed by 10 min reperfusion, before the induction of 30 min ischemia and reperfusion. At low concentrations of calphostin C (25, 50, and 100 nM), the PKC inhibitor had no effect on the incidence of arrhythmias or postischemic cardiac function in the nonpreconditioned ischemic/reperfused groups. With 200 and 400 nM of calphostin C, a significant increase in postischemic function and a reduction in the incidence of arrhythmias were observed in the nonpreconditioned ischemic/reperfused groups. Increasing the concentration of calphostin C to 800 nM, the recovery of postischemic cardiac function was similar to that of the drug-free control group. In preconditioned hearts, lower concentrations (<100 nM) of calphostin C did not change the response of the myocardium to ischemia and reperfusion in comparison to the preconditioned drug-free myocardium. Two hundred and 400 nM of the PKC inhibitor further reduced the incidence of ventricular fibrillation (VF) from the preconditioned drug-free value of 50% to 0 (p < 0.05) and 0 (p < 0.05), respectively, indicating that the combination of the two, preconditioning and calphostin C, affords significant additional protection. Increasing the concentration of calphostin C to 800 nM blocked the cardioprotective effect of preconditioning (100% incidence of VF). The recovery of cardiac function was similarly improved at calphostin C doses of 200 and 400 nM and was reduced at 800 nM (p < 0.05). With 200 and 400 nM of calphostin C, both cytosolic and particulate PKC activity were reduced by [almost equal to]40 and 60%, respectively, in both preconditioned and
Gene Therapy, 2010
Recent studies suggest that glutaredoxin-1 (Glrx-1) may serve as therapeutic target for diabetic ... more Recent studies suggest that glutaredoxin-1 (Glrx-1) may serve as therapeutic target for diabetic hearts. As the level of reactive oxygen species (ROS) is increased in the pathologic hearts including ischemia/reperfusion (I/R) and diabetes, we assumed that upregulation of Glrx-1 could reduce the cardiac risk factors associated with I/R and/or diabetes. Diabetes was induced in mice by i.p. injection of streptozotocin (150 mg kg À1). Eight days after when the blood glucose was elevated to 400 mg per 100 ml, the animals were randomly assigned to one of the following three groups, which received either empty vector, or LacZ or Glrx-1 adenoviral construct. Four days later, isolated working hearts were subjected to 30 min ischemia followed by 2 h reperfusion. Glrx-1 gene therapy significantly enhanced the Glrx-1 level, which prevented I/R-mediated reduction of ventricular recovery, increased myocardial infarct size and cardiomyocyte apoptosis in diabetic myocardium. In concert, Glrx-1 prevented diabetes and ischemia-reperfusion induced reduction of cardioprotective proteins including Akt, FoxO-1, and hemeoxygenase-1, and abolished the death signal triggered by Jnk, p38 mitogen-activated protein kinase, and c-Src. Glrx-1 gene therapy seems to prevent cardiac complications in diabetic heart due to the I/R by switching the death signal into survival signal by activating Akt-FoxO-signaling network.
Circulation Research, 1988
In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an i... more 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]d...
Circulation Research, 1990
In this study, fatty acid binding protein was used to protect an ischemic heart from reperfusion ... more In this study, fatty acid binding protein was used to protect an ischemic heart from reperfusion injury. Isolated rat heart was preperfused in the presence of 1.4 microM liposome-bound fatty acid binding protein for 15 minutes, followed by 30 minutes of ischemia and 30 minutes of reperfusion. Our results indicated better preservation of myocardial high-energy phosphate compounds (including ATP and creatine phosphate), reduced creatine kinase and lactate dehydrogenase release from the heart, and improved coronary flow in hearts treated with fatty acid binding protein compared with untreated controls. Fatty acid binding protein enhanced reacylation of arachidonic acid into phospholipids, thereby preserving membrane phospholipids and reducing free fatty acid contents during ischemia and reperfusion. In addition, fatty acid binding protein-bound long-chain free fatty acids and their thioesters as well as carnitine esters were increased in the cytosolic compartment of the heart. These re...
Circulation Research, 2000
The role of Cu/Zn-superoxide dismutase (SOD) in myocardial ischemic reperfusion injury was studie... more The role of Cu/Zn-superoxide dismutase (SOD) in myocardial ischemic reperfusion injury was studied by using a mouse model with targeted disruption of the mouse Sod I gene. Inactivation of the functional mouse Sod I gene in hearts by gene targeting (Sod I ϩ/Ϫ) resulted in a 50% reduction of Cu/Zn-SOD mRNA and significant reduction of Cu/Zn-SOD enzyme activity compared with that of wild-type Sod I ϩ/ϩ mice. Cu/Zn-SOD mRNA could not be detected in Sod I Ϫ/Ϫ heart. The isolated buffer-perfused hearts from the knockout mice devoid of any functional copy of the Sod I (Sod I Ϫ/Ϫ) and matched nontransgenic control mice were subjected to 30 minutes of global ischemia followed by 2 hours of reperfusion. For both groups of mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the Sod I Ϫ/Ϫ was less compared with the wild-type mice. Thus, the postischemic recovery of the developed force and the maximum first derivative of the developed force were consistently lower for the Sod I Ϫ/Ϫ mouse hearts compared with wild-type control hearts. The coronary flow was lower compared with the baseline levels for both groups of hearts, but there was no significant difference between the groups. The myocardial infarction determined from the ratio of infarct size/area of risk was higher for the Sod I Ϫ/Ϫ mice compared with the control mice. The amount of creatine kinase release from the wild-type mouse hearts was less compared with the Sod I Ϫ/Ϫ mouse hearts. In concert, a reduced amount of oxidative stress was found in the hearts of wild-type mice compared with Sod I Ϫ/Ϫ mouse hearts. These results documented that Sod I Ϫ/Ϫ mouse hearts were more susceptible to ischemic reperfusion injury compared with corresponding wild-type mouse hearts, suggesting that the Sod I gene constitutes an important defense element for the hearts.
Circulation, 2004
Background— The signaling pathways that control ischemia/reperfusion-induced cardiomyocyte apopto... more Background— The signaling pathways that control ischemia/reperfusion-induced cardiomyocyte apoptosis in heart have not been fully defined. In this study, we investigated whether Akt signaling has a role in the antiapoptotic pathways of preconditioning against hypoxia/reoxygenation (H/R). Methods and Results— Primary cultures of adult rat ventricular myocytes (ARVMs) were subjected to preconditioning (PC) by exposing the cells to 10 minutes of hypoxia followed by 30 minutes of reoxygenation. Non-PC and PC myocytes were subjected to 90 minutes of hypoxia followed by 120 minutes of reoxygenation. Hypoxic-PC protected the myocytes from subsequent H/R injury, as evidenced by decreased apoptosis and LDH release and increased cell viability. H/R-induced cytochrome c release and activation of caspase-3 and -9 were blocked by PC. This protective effect was inhibited by treating the cells with LY294002 (50 μmol/L), a PI3 kinase inhibitor, for 10 minutes before and during PC. PC also induced p...
Circulation, 1999
Background-Reperfusion of ischemic myocardium causes cardiomyocyte apoptosis in concert with down... more Background-Reperfusion of ischemic myocardium causes cardiomyocyte apoptosis in concert with downregulation of Bcl-2 gene. Ischemic preconditioning (PC) mediated by cyclic episodes of short-term ischemia and reperfusion reduces apoptotic cell death. PC also triggers a signaling pathway by potentiating tyrosine kinase phosphorylation leading to the activation of p38 MAP kinase and MAPKAP kinase 2. The nuclear transcription factor, NFB, plays a crucial role in this signaling process. Because NFB is a target of oxygen free radicals and Bcl-2 is an antioxidant gene, we hypothesized that reactive oxygen species might play a role in the signaling process. Methods and Results-Isolated rat hearts were perfused in the absence or presence of either dimethyl thiourea (DMTU), a hydroxyl radical scavenger, or SN50 peptide, a NFB blocker. Hearts were then subjected to PC by 4 repeated episodes of 5-minute ischemia, each followed by 10 minutes reperfusion. All hearts were then made globally ischemic at normothermia for 30 minutes followed by 2 hours of normothermic reperfusion. Creatine kinase release and malonaldehyde formation were determined in the coronary effluent collected during reperfusion. At the end of each experiment, hearts were processed for infarct size determination and analyses of apoptosis, DNA fragmentation, NFB, and Bcl-2. Myocardial infarction was reduced by PC. DMTU and SN50 abolished this cardioprotective effect of PC. PC resulted upregulation of Bcl-2 gene which was partially prevented by DMTU and SN50. Both ischemia/reperfusion and PC caused nuclear translocation and activation of NFB, which was blocked by both DMTU and SN50. PC reduced cardiomyocyte apoptosis which was partially inhibited by DMTU and SN50. A substantial number of apoptotic cardiomyocytes were identified in the hearts subjected to 30 minutes ischemia and 2-hour reperfusion. PC significantly inhibited the extent of cardiomyocyte apoptosis and DMTU and SN50 reversed it only minimally. Conclusions-The results demonstrate that reactive oxygen species play a crucial role in signal transduction mediated by PC. This signaling process appears to involve NFB. NFB becomes translocated and activated by both ischemia/ reperfusion, which induces apoptosis and PC which reduces apoptosis. However, the amount of NFB binding activity is significantly higher in the PC hearts compared with ischemic reperfused hearts. The upregulation of the antioxidant gene, Bcl-2, is inversely correlated with the reduction of cardiomyocyte apoptosis associated with PC. (Circulation. 1999;100[suppl II]:II-369-II-375.
Cardiovascular Research, 1996
Objective: Studies have shown that the diabetic heart exhibits abnormalities in cellular ion tran... more Objective: Studies have shown that the diabetic heart exhibits abnormalities in cellular ion transport, which can affect susceptibility to reperfusion-induced ventricular fibrillation (VF), tachycardia (VT) and functional derangements. It has been shown that "preconditioning" renders the heart very resistant to a subsequent prolonged ischemic episode. This phenomenon has been extensively studied in healthy myocardium, but such a study has not been previously done in diseased (hypertrophic or myopathic) hearts. Methods: We studied the incidence of reperfusion-induced VF, VT, cardiac function, and ion shifts (Na+, K+, Ca2+, and Mg2+) induced by ischemia/reperfusion in isolated hearts from rats with streptozotocin-induced diabetes. Following 2, 4, 6, and 8 weeks of diabetes, hearts were isolated and subjected to 30 min global ischemia followed by reperfusion. Results: In the 2-week diabetic group the total incidence of VF and VT was reduced from their non-diabetic age-matched control value of 100 and 100% to 42 (P < 0.05) and 42% (P < 0.051, respectively. Such a reduction in the incidence of VF and VT was not observed with progressive diabetes (4, 6, and 8 weeks). In the 2-week diabetics, the reduction in the VF and VT was reflected in the improvement of postischemic function, the reduction of ischemia and reperfusion-induced Na+ and Ca2+ gains, and the prevention in K+ and Mg 2+ loss This diabetes-induced initial protection was not seen in the 4-and. 6-week diabetics, and a deterioration of postischemic function was observed in the 8-week diabetics. Four cycles of preconditioning, each consisting of 5 min ischemia followed by 10 min reperfusion, failed to reduce the incidence of VF and VT, improve cardiac function, and prevent ion shifts induced by 30 min ischemia followed by 30 min reperfusion in 4-and 8-week diabetics. Conclusions: In the early phase of diabetes the heart is pore resistant to ischemia/reperfusion than the non-diabetic heart. Preconditioning does not afford protection against a prolonged period of ischemia in diabetics, indicating that preconditioning may be a "healthy heart phenomenon".
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1995
The aim of this study was m establish whether or not al-adrenergic receptors are implicated in tr... more The aim of this study was m establish whether or not al-adrenergic receptors are implicated in triggering phosphoinositide hydrolysis and intracelhilar Ca 2+ accumulation during myocardial ischemia and reperfusion. In isolated perfused rat hearts, the selective avreceptor antagonist prazosin abolished the increase in radioactivity incorporation into cellular inositol phosphates induced by 30 min ischemia followed by 30 min reperfusion, and selectively blocked the degradation of phosphoinositides; only minor changes in the ischemia/reperfusion-induced loss of other classes of phospholipids were seen. In addition, a prazosin-induced decrease of ischemia/reperfusion Ca 2+ overloading was documented in real-time recordings of epicardial cytosolic free Ca 2+ in fura 2-10aded hearts. An inhibition of early ischemic Ca 2+ rise was observed, as well as a lower peak of cytosolic free Ca 2+ and a more rapid reversal to normal values during reperfusion. Moreover, a l-adrenergic blockade resulted in a significant improvement in the recovery of myocardial function during reperfusion: an increased left ventricular developed pressure and maximum rate of rise of systolic pressure paralleled the decrease in time-averaged cytosolic Ca 2+ and the increase in amplitude of Ca 2+ transients, respectively. It is concluded that myocardial Ca 2+ overloading during ischemia and reperfusion may be triggered by aradrenergic receptor-induced polyphosphoinositide hydrolysis.
Basic Research in Cardiology, 1987
The developmental profiles of the protectivc mechanisms of heart against peroxidative injury duri... more The developmental profiles of the protectivc mechanisms of heart against peroxidative injury during neonatal growth was examined in the pigs of three different age groups. Lipid peroxidation expressed in terms of malonaldehyde formation was considerably higher in the pig hearts of the 8-10 day age group compared to that either by newborn or adult age groups. The four principal antioxidative enzymes, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase (G6PD), were enhanced during early neonatal growth and, with the exception of G6PD, all other enzymes were further enhanced during further growth to adulthood. G6PD activity dropped significantly in adult heart. The phospholipid contents of myocardial membrane between newborn and week-old pigs did not vary significantly. Total phospholipids and phosphatidylcholine contents were significantly higher in adult heart compared to those in neonatal heart. The enzymes of phospholipid synthesis and degradation, fatty acyl CoA synthetase (FACS), phospholipase A2 (PLA~), lysophospholipase (LPL), and lysophosphatidyleholine acyltransferase (LPCAT) increased during early neonatal growth. During further growth to adulthood, FACS decreased, PLA2 did not change, whereas both LPL and LPCAT increased significantly. Analysis of free fatty acids showed that palmitic and stearic acids decreased during the first week of growth, but increased during further growth to adulthood. Oleic acid did not change with aging, but arachidonic acid dropped in adult heart compared to that in neonatal heart. Linoleic, palmitoleic and free fatty acids increased dramatically during the first week of neonatal growth, but dropped thereafter. These results suggest that the unusual peroxidative status of the week-old pig heart is related to the presence of high concentrations of polyunsaturated fatty acids in the membrane phospholipids and not with the antioxidative defense system.
The Annals of Thoracic Surgery, 2000
Background. Ischemic preconditioning has been proven to be a powerful tool for myocardial protect... more Background. Ischemic preconditioning has been proven to be a powerful tool for myocardial protection in the setting of ischemia and reperfusion. A new drug to provide pharmacologic preconditioning, monophosphoryl lipid A (MLA), was administered 24 hours before an acute coronary occlusion in pigs to determine the effect on pharmacologic preconditioning. Methods. Two studies were completed. In the first, swine were distributed into five groups: group I, control; group II,. aminoguanidine (AMG) (30 mg/kg), a selective inducible nitric oxide synthase (iNOS) blocker; group III, MLA (10 g/kg); group IV, MLA (35 g/kg); and group V, MLA and AMG (35 g/kg and 30 mg/kg, respectively). Twenty-four hours after administration of the MLA, AMG, or both, regional left anterior descending coronary artery ischemia was induced for 15 minutes followed by one hour of global normothermic cardioplegic arrest and three hour reperfusion. Left ventricular function, tissue injury, and percentage of myocardial infarction were measured. Left ventricular myocardium in the left anterior descending coronary artery region was sampled for iNOS messenger RNA (mRNA) during ischemia and reperfusion. In the second study, pigs were sacrificed 0, 4, 6, 8, and 24 hrs after MLA/AMG administration for iNOS mRNA determination in nonischemic myocardium. Results. Use of MLA significantly improved postischemic ventricular function, and reduced creatinine kinase release and percentage of infarction. Monophosphoryl lipid A induced expression of iNOS mRNA in nonischemic myocardium within four hours of administration which returned to base line by 24 hours. Normothermic regional ischemia then induced expression of iNOS mRNA, which returned to base line during reperfusion. Aminoguanidine completely abolished both MLAinduced and ischemia-induced iNOS mRNA and blocked the beneficial effects of MLA. Conclusions. Use of MLA can provide myocardial preservation through enhanced expression of iNOS mRNA.
To improve our understanding of the evidence-based literature supporting temperature management d... more To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.
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Papers by Richard Engelman