Biomedical subjects

H Schwalb

Publications and source records attributed to H Schwalb.

At least 19 recordsLinked to original sources

PubMed2001

Nicorandil decreases postischemic actin oxidation.

This study examined the hypothesis that preconditioning can decrease postischemic oxidative protein damage. Isolated rat hearts were subjected to 25 min of normothermic global ischemia followed by 45 min of reperfusion. These were compared with hearts pretreated with 20 microM nicorandil or preconditioned with two cycles of ischemia. Changes in the high energy phosphates, ATP and phosphocreatine, were followed using (31)P-NMR spectroscopy. Protein carbonyls were assessed using an immunoblot technique. Postischemic hemodynamic function and high energy phosphates recovered to significantly (p <.05) higher levels in nicorandil-treated and ischemic preconditioned hearts as compared to controls. Postischemic protein carbonyl formation was highest in control reperfused hearts but reduced to intermediate between control and preischemic hearts by ischemic preconditioning and virtually prevented by nicorandil pretreatment, with a prominent band at 43 kDa significantly affected (p <.05). Based on immunoshift and immunoprecipitation studies, this band was identified as a mixture of actin isoforms. These studies support the conclusion that nicorandil diminishes protein oxidative damage in general, and specifically actin oxidation, which in the presence of improved supply of high energy phosphates, leads to enhanced postischemic contractile function.

Actins↗

PubMed2001

Novel synthetic selectively degradable vascular prostheses: a preliminary implantation study.

BACKGROUND: Vascular grafts perform less well than autologous arterial or vein grafts. The purpose of this study was to evaluate the short-term performance of selectively biodegradable filament-wound vascular prostheses, comprising elastomeric poly(ether urethane) (Lycra) scaffolds and flexible, hydrophilic biodegradable coatings. MATERIALS AND METHODS: Two types of selectively biodegradable vascular grafts were manufactured, comprising a filament-wound Lycra scaffold, subsequently coated with a biodegradable poly(ethylene glycol)/poly(lactic acid) (PELA) block copolymer. The two types of grafts differed in both the overall porosity of the scaffold and the hydrophilicity of the biodegradable constituent. A 60-mm-long and 6-mm-diameter filament-wound and polytetrafluoroethylene (ePTFE) grafts were implanted as interposition prostheses, randomly, at the right- and left-side carotid arteries. RESULTS: Implantation studies proved the grafts to be patent and pulsatile for periods of up to 3 months. Increasing the scaffold porosity and enhancing the hydrophilicity of the biodegradable component improved both the transmural tissue ingrowth process and the vascularization of the prosthesis wall. Also, a well-adhered peripheral tissue and a thin, uniform intima and endothelial lining were obtained. All ePTFE graft controls, although patent, were rather stiff and nonpulsatile. A thick pseudointima, poorly attached to the prosthesis inner surface, was observed. The compliance of the wet grafts was significantly higher than in the dry state, stemming mainly from the water-plasticizing effect on the biodegradable component. The grafts explanted after a period of 6 weeks exhibited compliance only slightly lower than that of the wet grafts. After 12 weeks, however, the hoop compliance was 20% lower than that prior to implantation. At 100 mm Hg, for example, the original compliance of the wet graft was 2.5%/100 mm Hg decreasing to 2.0%/100 mm Hg after a 3-month implantation. The compliance reduction with implantation is attributed to the ingrowth of the perigraft tissue as revealed by the histological study. A compliance of 2.0%/100 mm Hg is slightly better than that of a standard PTFE graft with an original compliance of 1.6%/100 mm Hg. Yet it is still an order of magnitude smaller than that of a canine carotid artery. CONCLUSIONS: The improved mechanical properties and enhanced healing of the highly porous filament-wound Lycra scaffold graft coated with hydrophilic biodegradable PELA has the potential of being a highly effective small caliber prosthetic graft.

Absorbable Implants↗

PubMed2000

Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection.

BACKGROUND: Recent studies have postulated that mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel activation may modulate mitochondrial function with the resultant induction of a preconditioning phenotype in the heart. We hypothesized that the modulation of mitochondrial homeostasis might confer preconditioning-like cardioprotection. METHODS: We used a model of regional ischemia in Langendorff-perfused isolated rat hearts. Short-term administration of 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation and cyclosporin A (CSA), an inhibitor of mitochondrial respiration, was used in an attempt to elicit preconditioning-like cardioprotection. The anti-ischemic drug trimetazidine, known to attenuate CSA-induced disruption in mitochondrial function, and the mitoK(ATP) channel blocker 5-hydroxydecanoic acid (5-HD) were used to inhibit the effects of DNP and CSA. Finally, we studied the effect of trimetazidine on adenosine-induced and ischemic preconditioning. Risk zone and infarct size were measured and expressed as a percentage of the risk zone (I/R ratio). RESULTS: DNP, CSA and adenosine pretreatment reduced infarct size (I/R ratio: DNP 9.0+/-2.4%, CSA 12.5+/-1.4%, adenosine 11.9+/-3.6%, all P<0.001 vs. control, 30.2+/-1.3%) similarly to ischemic preconditioning (9.5+/-0.6%, P<0.001 vs. control). Trimetazidine limited the effect of ischemic preconditioning (22.2+/-2.0%, P<0.001 vs. ischemic preconditioning) and completely reversed the DNP, CSA, and the adenosine-mediated reduction in infarct size. 5-HD abolished the effect of ischemic preconditioning and CSA. CONCLUSION: DNP and CSA trigger preconditioning-like cardioprotection in the isolated rat heart. Trimetazidine, a known mitochondrial 'protector', attenuated both drug-induced and ischemic preconditioning. These data support the hypothesis that modulation of mitochondrial homeostasis may be a common downstream cellular event linking different triggers of preconditioning.

Animals↗

PubMed1998

Estrogen induces nitric oxide-mediated vasodilation of human mammary arteries in vitro.

Human internal mammary arteries (IMA) are relatively protected from atherosclerosis. Estrogen plays a protective role in cardiovascular disease. It causes in vitro and in vivo vasodilatation, but the mechanisms are contradictory. To investigate the in vitro vasomotor effect of estrogen on IMA and the role of endothelium, we studied 30 IMA segments harvested from 10 men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, and smoking were excluded. Twenty IMA rings had intact endothelium ((+)Endo) and 10 rings were denuded of endothelium ((-)Endo). Vasomotor response of each ring was expressed as the percentage of maximal response to norepinephrine (NE). Acetylcholine (10(-8)-10(-5) M) given to (+)Endo and (-)Endo rings induced vasorelaxation of 72 +/- 30.4% and vasoconstriction of 48.5 +/- 20.1%, respectively. 17-Beta-estradiol (10(-8)-10(-5) M) given after maximal precontraction with NE induced marked relaxation in (+)Endo (80.9 +/- 39.2%), but no significant vasomotor effect in (-)Endo rings (P < 0.0001). Vasorelaxation to 17-beta-estradiol (10(-6) M) in (+)Endo rings was 64.5 +/- 18.4 and 8.6 +/- 8.4%, before and after 15-min treatment with nitric oxide synthase inhibitor, L-nitroarginine methyl ester, respectively (n = 14, P < 0.0001). Tamoxifen (10(-6) M) decreased 17-beta-estradiol (10(-7) M)-induced relaxation by 71%. In conclusion, 17-beta-estradiol induces endothelium-dependent NO-mediated vasodilation of human mammary arteries in vitro. This response is mediated through estrogen receptors.

Aged↗

PubMed1998

Change in size, number and morphology of the nucleoli in human hearts as a result of hyperfunction.

In the present study we examined light-microscopically the nuclei of 16 hearts (7 normal hearts, 7 hearts with hypertrophy and 2 hearts with atrophy) for the size, number and morphology of their nucleoli. The size of the nucleoli, defined as the total area of all nucleoli per nucleus, was an early and sensitive indication of a beginning hypertrophy of the myocardium. It increased in parallel to the total heart weight and to the total area of the nucleus of the cell, but initially the size of the nucleoli changed earlier than the other parameters. We found an increase of the ratio in the total area of the nucleoli per nucleus to the total area of the nucleus at the beginning of clinical hyperfunction. This ratio normalised during chronic hyperfunction. The number of the nucleoli also increased during hyperfunction, but it did not exceed the number of nucleolus organiser regions (NOR) given by the number of chromosomes. Nevertheless, we found numbers of nucleoli higher than 10 because, the number of NORs increases during polyploidization. Regarding the morphology of the nucleoli in hearts with hypertrophy, we found a predomination of the nucleoli with a highly branched nucleolonemal structure as an indication of an increased RNA synthesis.

Atrophy↗

PubMed1998

New solution for prolonged myocardial preservation for transplantation.

BACKGROUND: A solution for prolonged cold storage of the heart has been developed. The Jerusalem-Cape Town Solution (JCT) is an "intracellular" type cardioplegic solution and is formulated to (1) minimize hypothermic-induced cell swelling, (2) diminish intracellular acidosis, (3) prevent the expansion of the interstitial space during the reperfusion, (4) protect against oxygen free radical injury during early reperfusion, and (5) provide substrates for regenerating high-energy phosphates. METHODS: With a Langendorff model, rat hearts were subjected to 15 minutes of perfusion with Krebs-Henseleit, 10 minutes of cardioplegic infusion and 20 hours of cold storage (5 degrees to 6 degrees C). Hearts were reperfused for 60 minutes and hemodynamic recovery was assessed. The hearts were assigned to three groups (eight hearts in each), according to the cardioplegic solution used: group 1, JCT; group 2, Bretschneider's HTK cardioplegic solution; and group 3 University of Wisconsin cold storage solution. RESULTS: After 60 minutes of reperfusion, the recovery of the coronary artery flow in group 1 (JCT) was significantly better than in group 2, and slightly better than in group 3 (64% +/- 8.9%, 47.2% +/- 11.6%, 52.5% +/- 19.9%, mean +/- SD, respectively; group 1 versus group 2, p < 0.01). The recovery of the left ventricular developed pressure (LVDP) was significantly better in group 1 compared with group 2 and group 3 (60.2% +/- 14.5%, 41.1% +/- 12.6% and 36.5% +/- 10.1%, respectively; p < 0.01). The recovery of the heart contractility expressed by the product of LVDP and the heart rate (LVDP x heart rate) was significantly higher in group 1 than in group 2 and group 3 (47.5% +/- 3.4%, 23.6% +/- 9.6%, and 28.7% +/- 8.3%, respectively, p < 0.001). In hearts stored for 12 hours in JCT or HTK, the recovery of the heart contractility did not differ significantly (73.4% +/- 12.7% or 70.8% +/- 30.8%, respectively). Modified reperfusion aimed to improve postischemic heart recovery did not bring significant changes in cardiac mechanical function but resulted in an increase in postischemic coronary artery flow recovery in hearts reperfused with amino acid-enriched buffer. CONCLUSIONS: The JCT solution is effective (as well as HTK) in preserving the ischemic hearts for up to 12 hours. It is superior to HTK or University of Wisconsin solution at 20 hours of isolated ischemic storage.

Adenosine Triphosphate↗

PubMed1998

Cardioprotective effect of L-arginine in myocardial ischemia and reperfusion in an isolated working rat heart model.

BACKGROUND: Studies in myocardial ischemia and reperfusion have demonstrated damage to endothelium, impaired production and release of vasoactive substances such as nitric oxide, and marked alteration in endothelium-dependent relaxatin of the coronary vasculature. This study was designed to examine the cardioprotective effect of exogenous administration of L-arginine, a precursor of nitric oxide, during ischemia and reperfusion, particularly using oxygenated crystalloid cardioplegia. METHODS: Seventy energy-depleted isolated working rat hearts were arrested by cardioplegia and subjected to 60 min normothermic global ischemia followed by 10 min nonworking and 30 min working reperfusion (Gr 1). L-arginine (3mM or 10mM) was added to the cardioplegic solution (Gr 2,3 respectively), reperfusion (Gr 6,7 respectively), throughout the experiment (Gr 4,5 respectively), and with Nw-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase (Gr 8). RESULTS: At 30 min of working heart reperfusion, compared to control all arginine containing groups (Gr 2-7) exhibited a significant improved recovery of cardiac output (64.7+/-21.2, 98.1+/-21.1, 90.9+/-11.7, 88.9+/-16.2, 83.1+/-7.4, and 90.8+/-10.6, mean +/- SD% Gr 2 to 7 respectively, vs Gr 1 36.3+/-20%, p<0.01). Significant recovery improvement was observed also in other hemodynamic parameters (coronary flow, aortic peak pressure), as well as biochemical recovery assessed by O2 consumption ratio, release of lactic dehydrogenase at reperfusion and regeneration of ATP. The L-NAME group had a significant poorer hemodynamic and biochemical recovery. L-arginine had no effect on the preischemic hemodynamic parameters. CONCLUSIONS: These results support the cumulative data considering L-arginine as a cardioprotective agent in postischemic reperfusion injury.

Animals↗

PubMed1997

Naturally produced extracellular matrix is an excellent substrate for canine endothelial cell proliferation and resistance to shear stress on PTFE vascular grafts.

PURPOSE: Successful development of a vascular prosthesis lined with endothelial cells (EC) may depend on the ability of the attached cells to resist shear forces after implantation. The present study was designed to investigate EC detachment from extracellular matrix (ECM) precoated vascular prostheses, caused by shear stress in vitro and to test the performance of these grafts in vivo. METHODS: Bovine aortic endothelial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE) vascular graft (10 x 0.6 cm), PTFE graft precoated with fibronectin (FN), or PTFE precoated with FN and a naturally produced ECM (10(6) cells/graft). Sixteen hours after seeding the medium was replaced and unattached cells counted. The strength of endothelial cell attachment was evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm2 for 1 h. The detached cells were collected and quantitated. PTFE or EC preseeded ECM coated grafts were implanted in the common carotid arteries of dogs. RESULTS: While little or no differences were found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated PTFE, or FN+ECM precoated PTFE, respectively), the number of cells retained after a shear stress was significantly increased on ECM coated PTFE (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, respectively, p <0.01). Implantation experiments in dogs revealed a significant increase in EC coverage and a reduced incidence of thrombus formation on ECM coated grafts that were seeded with autologous saphenous vein endothelial cells prior to implantation. CONCLUSION: ECM coating significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adhesive macromolecules and potent endothelial cell growth promoting factors may render the ECM a promising substrate for vascular prostheses.

Animals↗

PubMed1996

A 31P NMR study of preconditioned isolated perfused rat heart exposed to intermittent ischemia.

Exposure to a short ischemic period (ischemic preconditioning, IP) will protect the heart from damage following a subsequent longer ischemic episode. The aim of the study was to test whether IP is cardioprotective in the setting of repeated ischemia-reperfusion cycles. Thus, Langendorff-perfused hearts, exposed to IP, were subjected to three consecutive ischemia-reperfusion (10/15 min) cycles. Myocardial energetics, manifested by 31P NMR spectroscopy, was correlated with hemodynamics. ATP recovery was significantly higher for the IP group compared with control (P < 0.02) during reperfusions. However, there was no significant difference in ATP recovery during the three ischemic intervals. The supernormal recovery of phosphocreatine recorded during reperfusion was lower for the IP group (approximately 120%) compared with control (approximately 135%, P < 0.065). Better recovery of the left ventricular-developed pressure was noted during reperfusions for the IP group and became significant only during the last reperfusion (86% versus 68%, P < 0.025). In conclusion, the above results support prolonged IP cardioprotection.

Adenosine Triphosphate↗

PubMed1996

Variability of cardiomyocyte DNA content, ploidy level and nuclear number in mammalian hearts.

DNA content, ploidy level, cell size and nuclear number were investigated in 54 mammalian hearts from nine species. DNA content was determined biochemically and ploidy level of cells was studied by the means of Feulgen cytophotometry. Nuclear number was calculated by a new method, while cell size was determined by using ocular micrometry. In most mammals diploid cell nuclei predominate. Higher ploidy levels were found in the human and the pig hearts. The total amount of DNA correlated with the myocardial weight. Eight million heart muscle cell nuclei were found in mice (myocardial weight 160 mg), and 2600 million heart muscle cell nuclei in the human heart (myocardial weight 210 g), but in the hearts of horses up to 35000 million heart muscle cell nuclei (myocardial weight 3.4 kg) were found. The number of heart muscle and connective tissue cell nuclei was correlated with myocardial weight. The ratio of connective tissue cell nuclei to heart muscle cell nuclei was between 2:1 and 3:1. In cardiac growth this ratio shifted towards connective tissue cell nuclei. Increased heart weight corresponds to an increase in cell size. Diameter between 11 microns and 18 microns may be an optimum for heart muscle cells of mammals.

Animals↗

PubMed1996

Acute effect of thyroid hormone in the rat heart: role of calcium.

Several observations provide some clues as to the possible mode of the regulatory action of thyroid hormone (TH) in the heart, indicating delayed action at the level of the nucleus and acute effects on the plasma membrane. Here we present evidence for a direct and rapid stimulatory effect of TH in the intact normal heart. In the isolated perfused rat heart, 3,5,3'-tri-iodothyronine (T3) produced a positive inotropic effect increasing both the left ventricular peak systolic pressure (P) and +dP/dt values, but had no significant effect on heart rate. This effect of T3 was: (1) very rapid in onset (starting after 15 s) and transient, increasing gradually to reach a maximum (80% above control) at about 20 min, and declining progressively 20 to 30 min later; (2) dose-related and biphasic, occurring at physiological concentrations as low as 1 pM (+dP/dt) and 10 pM (P), reaching a maximum at 1 nM, and decreasing at higher concentrations; and (3) thyroid hormone specific, as shown by the effects of several TH analogs (L-T3 > L-thyroxine (T4) = D-T3 > D-T4; 3,3',5'-tri-iodothyronine (rT3), 3,5,-L-di-iodothyronine and DL-thyronine had no effect). The calcium blockers nifedipine and verapamil, at concentrations of 10(-8) - 10(-5) M given before or after the addition of T3 (10(-9) - 10(-6) M), inhibited the T3-induced increase in cardiac inotropic activity in a time- and dose-related fashion. We suggest that the acute effect of TH in the heart is plasma membrane-mediated and calcium-dependent.

Animals↗

PubMed1995

Interaction of thyroid hormone and heparin in postischemic myocardial recovery.

BACKGROUND: Triiodothyronine (T3) administration can improve postischemic myocardial recovery. Heparin can interfere with cellular binding of T3. Introduction of heparin into an isolated heart model may interfere with this effect. METHODS: Four groups of 8 rat hearts were placed on a modified Langendorff apparatus. All groups underwent 15 minutes of perfusion with modified Krebs-Henseleit solution (KH), followed by 20 minutes of normothermic global ischemia and 30 minutes of reperfusion. Group I underwent reperfusion with KH. Group II underwent reperfusion with KH and 1 x 10(-6) mol/L of T3. In group III, hearts underwent preischemic perfusion with heparinized KH (1,000 U/L) and reperfusion with KH containing 1 x 10(-6) mol/L of T3 and 1,000 U/L of heparin. In group IV, rats were given heparin at 2,000 IU/kg 30 minutes before sacrifice, and isolated hearts were reperfused with KH and 1 x 10(-6) mol/L of T3. A latex balloon in the left ventricle monitored hemodynamic variables. RESULTS: Left ventricular developed pressure throughout postischemic reperfusion was greater in all the groups receiving T3 when compared with group I. Group II showed significantly greater recovery than either group III (p < 0.05) or group IV (p < 0.05). CONCLUSIONS: Addition of T3 to the reperfusate enhances postischemic myocardial recovery in the isolated heart model, whereas addition of heparin reduces this effect.

Animals↗

PubMed1995

Myocardial protection by warm blood cardioplegia. A 31P nuclear magnetic resonance spectroscopy study of an isolated perfused rat heart.

OBJECTIVE: A study of the protective efficiency imparted by intermittent warm blood cardioplegia (WBCP) using perfused rat heart model. METHODS: Hemodynamic parameters were monitored simultaneously with metabolic changes in high-energy phosphates using 31P-NMR spectroscopy. Following 30 min perfusion with Krebs-Henseleit (KH) buffer, all hearts were arrested for one hour (G1 and G2) and than reperfused with KH for 30 minutes. A warm oxygenated crystalloid cardioplegia (WCCP, modified St Thomas' hospital solution) was used for the control group (G1). The second group of hearts (G2) were arrested with oxygenated WBCP (K+ = 15 mM; Hct = 15-20%) and the third group (G3), was subjected to a protocol consisting of 4 periods (10 min each) of WBCP interspersed by 10 min of global ischaemia. RESULTS: The post-arrest percentage recoveries of LVDP, +dP/dt and HR were respectively: 88, 93 and 90 for G1 (n = 8); 97, 100 and 98 for G2 (n = 10); 76, 79 and 91 for G3 (n = 12). The corresponding metabolic recoveries of ATP and PCr were respectively, 85 and 90 for G1; 91 and 98 for G2 and 73 and 85 for G3. The PCr level declined during the arrest period in G1 contrasting with elevated PCr level (> 140%) during the WBCP arrest in G2. After an initial rise to approximately 140%, PCr level gradually decreased during the intermittent WBCP interval (G3). CONCLUSIONS: At normothermia, with equal CF rates, continuous WBCP provides better myocardial protection, through an effective oxygen supply, compared with WCCP. During the intermittent periods of ischaemia, certain metabolic and hemodynamic dysfunction occurs.

Animals↗

PubMed1993

New experimental technique to study blood cardioplegia in the isolated, perfused rat heart.

Blood cardioplegia has been extensively studied clinically and in the large animal experimental model. We describe here a modification of the original Langendorff technique to study continuous warm blood cardioplegia in the isolated, perfused rat heart. The excised heart is mounted on the perfusion apparatus and perfused with Krebs-Henseleit buffer. Prearrest hemodynamics are recorded. The shed blood in the mediastinal cavity (8 to 12 mL) is collected, filtered, and reconstituted into cardioplegic solution (hematocrit, 0.20; K+, 15 mmol/L). Hearts are arrested and maintained at 37 degrees C by continuous recirculation of blood cardioplegia for 1 hour. The blood cardioplegia system consists of a Silastic tubing oxygenator, peristaltic pump, and two filters (40 microns pore size). The heart is reperfused with Krebs-Henseleit solution, and postarrest hemodynamics are recorded. Percentage recovery of peak left ventricular pressure, heart rate, and coronary flow were 98.5 +/- 3.1, 102 +/- 4.2, and 98.5 +/- 4.5 (mean +/- standard error of the mean; n = 6), respectively. Myocardial oxygen consumption during arrest was 57 microL.min-1.g-1 dry wt, which is 10% of the myocardial oxygen consumption of a beating heart in in-vivo and ex-vivo models. These results suggest the feasibility of studying blood cardioplegia in the isolated, perfused rat heart model under controlled conditions. Continuous warm blood cardioplegic arrest provided excellent myocardial protection for 1 hour in this model.

Animals↗

PubMed1993

An improved method of endothelial seeding on small caliber prosthetic vascular grafts coated with natural extracellular matrix.

The feature that clearly distinguishes natural blood vessels from their artificial counterparts is the presence of the endothelial cell lining that, besides being non-thrombogenic, is capable of repair and renewal. This study describes a method of coating vascular grafts with a uniform naturally produced subendothelial extracellular matrix (ECM) prior to implantation. Bovine aortic endothelial cells were seeded at a low density on untreated GORE-TEX, GORE-TEX that was precoated with ECM, or GORE-TEX that was first coated with fibronectin and then with ECM. The cells were maintained in the absence of fibroblast growth factor (FGF) and the cell number determined after 7 days in culture. Poor growth was observed on untreated GORE-TEX (6030 +/- 1030 cells/well), a 10-fold improved growth was observed on ECM coated GORE-TEX (59900 +/- 1560 cells/well) and best results were obtained on fibronectin-ECM precoated GORE-TEX (131000 +/- 21000 cells/well). The thrombogenicity of the ECM was reduced by a mild glutaraldehyde treatment, performed prior to seeding the cells, accompanied by a 40-50% reduced endothelial cell growth. These results indicate that ECM provides a suitable biolayer for endothelial cell adhesion, growth and differentiation. It contains both adhesion glycoproteins (fibronectin, laminin, collagen) and endothelial cell growth factors (basic fibroblast growth factor) that support adhesion and normal growth of suboptimal concentrations of endothelial cells. We suggest that the presence in ECM of both adhesive macromolecules and potent endothelial cell growth promoting factors will make the ECM a promising substrate for vascular grafts.

Animals↗

PubMed1993

Interaction between allopurinol and copper: possible role in myocardial protection.

Allopurinol, a potent inhibitor of xanthine oxidase, is known to effectively protect the heart against damage in patients undergoing cardiac bypass surgery. There is still an ambiguity concerning the presence of xanthine oxidase in the human heart. Thus, the mechanism underlying the protective effect of allopurinol is unclear. Transition metal ions, such as iron and copper, can participate in single-electron reactions and mediate the formation of oxygen-derived free radicals. In this study the interaction between allopurinol and Cu(II) was investigated. Spectrophotometric investigation shows that allopurinol (0-0.8 mM) form a 1:1 complex with Cu(II) ions (0-0.8 mM) with a specific absorbance peak at 364 nm. Also, the rate constant (k) for the copper-catalyzed aerobic oxidation of ascorbate was markedly decreased in the presence of allopurinol (from 0.068 min-1 to 0.014 min-1). Allopurinol substantially reduced the copper-mediated and ascorbate-driven DNA breakage. Spectrophotometric measurements did not indicate a specific interaction between iron ions and allopurinol. It is suggested that the beneficial effects of allopurinol during reperfusion of the heart could stem from its chelation of copper, yielding a complex with low redox activity.

Allopurinol↗

PubMed1992

Optimal level of hypothermia for prolonged myocardial protection assessed by 31P nuclear magnetic resonance.

The optimal level of hypothermia during myocardial preservation for cardiac transplantation is not known. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess the effect of different preservation temperatures (15 degrees C in group 1, 4 degrees C in group 2) on the myocardial high-energy phosphate profiles during prolonged global ischemia and subsequent reperfusion of isolated rat hearts. Adenosine triphosphate depletion during ischemia was more gradual in group 2, leading to significant differences in myocardial adenosine triphosphate concentrations between the two groups after 3 hours of ischemia. The fall in intracellular pH during ischemia was significantly less pronounced in hearts preserved at 4 degrees C as compared with those at 15 degrees C. The postischemic recovery of both the left ventricular peak systolic pressure and the maximum rate of increase of left ventricular pressure was enhanced in group 2, although the ischemic period was 3 hours longer than in group 1. Hypothermia at 4 degrees C as compared with 15 degrees C appears to prolong myocardial protection with respect to adenosine triphosphate preservation, prevention of the fall in intracellular pH, and the enhancement of postischemic hemodynamic recovery.

Adenosine Triphosphate↗

PubMed1992

Prolonged myocardial protection with St. Thomas' Hospital solution and University of Wisconsin solution. The importance of preservation techniques.

The effectiveness of University of Wisconsin solution (UWS) and oxygenated St. Thomas' Hospital solution (STS) for prolonged myocardial protection was evaluated in isolated working rat hearts preserved for 12 h at 4 degrees C using three different preservation techniques: induction of cardiac arrest and subsequent hypothermic storage with STS (group 1, n = 9) or UWS (group 4, n = 9), intermittent coronary flush (every 90 min) with STS (group 2, n = 9) or UWS (group 5, n = 9), or continuous coronary perfusion with STS (group 2, n = 7) or UWS (group 6, n = 7) before 60 min of reperfusion. In the UWS preserved hearts, recovery of aortic flow was greater when the simple storage technique was employed compared to intermittent or continuous coronary perfusion (groups 5 and 6). In the STS preserved hearts, aortic flow recovery was superior when the intermittent perfusion technique was applied. The same pattern was observed with regard to recovery of left ventricular pressure. Lactate dehydrogenase release during reperfusion was significantly less pronounced in group 4 (UWS, single flush, simple storage) as compared to group 1 (STS, single flush and simple storage), whereas best preservation of myocardial high energy phosphates was observed when hearts were preserved with multiple dose cardioplegia using STS. Simple hypothermic storage with UWS affords the best functional recovery after prolonged myocardial ischemia in all groups. Repetitive or continuous application of this solution is detrimental, possibly due to potassium overloading. In STS treated groups, multiple dose application of oxygenated STS enhances functional and metabolic recovery compared to its single dose application.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗