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Biomedical subjects

D Shum-Tim

Publications and source records attributed to D Shum-Tim.

36 records · Page 2Linked to original sources
PubMed1998

Effects of a monoclonal antibody to P-selectin on recovery of neonatal lamb hearts after cold cardioplegic ischemia.

BACKGROUND: The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia. METHODS AND RESULTS: Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic arrest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 micrograms/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70 +/- 4% in control versus 77 +/- 2% in group P-sel, P < 0.01), maximum positive first derivative of pressure (dP/dt) (64 +/- 7% in control versus 73 +/- 5% in group P-sel, P < 0.05), and maximum negative dP/dt (61 +/- 6% in control versus 70 +/- 6% in group P-sel, P < 0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135 +/- 40% in control versus 205 +/- 43% in group P-sel, P < 0.05). Myocardial myeloperoxidase activity was significantly lower (P < 0.05) in group P-sel (4.7 +/- 3.2) versus control (16.0 +/- 10.1). (Units are change in absorbance/min/g tissue.) CONCLUSIONS: The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion.

Animals↗
PubMed1998

Effects of oncotic pressure and hematocrit on outcome after hypothermic circulatory arrest.

BACKGROUND: A recent study found that a higher-perfusate hematocrit was associated with improved neurologic recovery after deep hypothermic circulatory arrest. The current study examined the relative contributions of oxygen delivery and colloid oncotic pressure to this result, as well as the efficacy of different colloidal agents and modified ultrafiltration. METHODS: Twenty-six piglets were randomized into five groups (n = 5 or 6 animals per group): control group 1--blood and crystalloid prime, hematocrit of 20%; group 2--blood and hetastarch prime, hematocrit of 20%; group 3--blood and pentafraction prime, hematocrit of 20%; group 4--blood and crystalloid prime with 10 minutes of modified ultrafiltration; group 5--whole blood prime, hematocrit of 30%. All groups underwent 60 minutes of deep hypothermic circulatory arrest at 15 degrees C. RESULTS: Groups 2 and 3 showed less body weight gain (analysis of variance, p = 0.001; group 2 versus group 1, p = 0.0009; group 3 versus group 1, p = 0.0009) and body water content after cardiopulmonary bypass (analysis of variance, p = 0.001; group 2 versus group 1, p = 0.003; group 3 versus group 1, p = 0.013). Group 5 showed more rapid recovery of phosphocreatine and intracellular acidosis, as measured by magnetic resonance spectroscopy, during rewarming than group 1 did (phosphocreatine, p = 0.0329; intracellular acidosis, p = 0.0462). Group 3 also showed accelerated recovery of intracellular acidosis (p = 0.0411). Cytochrome a,a3 recovery, determined by near-infrared spectroscopy, was significantly better in group 5 than in group 1 and worse in group 2 than in group 1 after rewarming. The neurologic deficit score and overall performance category score were best in group 5 (neurologic deficit score, p = 0.012; overall performance category score, p = 0.046) on the first postoperative day. Group 3 also had a better overall performance category score than group 1 did (p = 0.0068). Only group 1 and 2 animals showed histologic damage. CONCLUSIONS: Both higher hematocrit and higher colloid oncotic pressure with pentafraction improve cerebral recovery after deep hypothermic circulatory arrest. The higher hematocrit improves cerebral oxygen delivery but does not reduce total body edema. Modified ultrafiltration after cardiopulmonary bypass is less effective than having a higher initial prime hematocrit or colloid oncotic pressure.

Animals↗
PubMed1998

Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest.

BACKGROUND: Aggressive surface warming is a common practice in the pediatric intensive care unit. However, recent rodent data emphasize the protective effect of mild (2 degrees - 3 degrees C) hypothermia after cerebral ischemia. This study evaluates different temperature regulation strategies after deep hypothermic circulatory arrest with a survival piglet model. METHODS: Fifteen piglets were randomly assigned to 3 groups. All groups underwent 100 minutes of deep hypothermic circulatory arrest at 15 degrees C. Brain temperature was maintained at 34 degrees C for 24 hours after cardiopulmonary bypass in group I, 37 degrees C in group II, and 40 degrees C in group III. Neurobehavioral recovery was evaluated daily for 3 days after extubation by neurologic deficit score (0, normal; 500, brain death) and overall performance category (1, normal; 5, brain death). Histologic examination was assessed for hypoxic-ischemic injury (0, normal; 5, necrosis) in a blinded fashion. RESULTS: All results are expressed as mean +/- standard deviation. Recovery of neurologic deficit score (12.0 +/- 17.8, 47.0 +/- 49.95, 191.0 +/- 179.83; P = .05 for group I vs III), overall performance category (1.0 +/- 0.0, 1.4 +/- 0.6, 2.8 +/- 1.3; P < .05 for group I vs III), and histologic scores (0.0 +/- 0.0, 1.0 +/- 1.2, 2.8 +/- 1.8; P < .05 for group I vs III cortex) were significantly worse in hyperthermic group III. These findings were associated with a significantly lower cytochrome aa3 recovery determined by near-infrared spectroscopy in group III animals (P = .0041 for group I vs III). No animal recovered to baseline electroencephalographic value by 48 hours after deep hypothermic circulatory arrest. Recovery was significantly delayed in the hyperthermic group III animals, with a lower amplitude 14 hours after the operation, which gradually increased with time (P < .05 for group III vs groups I and II). CONCLUSIONS: Mild postischemic hyperthermia significantly exacerbates functional and structural neurologic injury after deep hypothermic circulatory arrest and should therefore be avoided.

Animals↗
PubMed1998

Myocardial tissue engineering with autologous myoblast implantation.

OBJECTIVE: Implanting myoblasts derived from autologous skeletal muscle, that is, satellite cells, for myocardial replacement has many advantages when compared with implanting either fetal cardiac myocytes (ethical and donor availability issues) or established cell lines (oncogenicity). Furthermore, autologous myoblasts do not require immunosuppression. The feasibility of satellite cell differentiation into muscle fibers, after implantation into the myocardium, was confirmed by means of a unique cell-labeling technique. METHODS: Myoblasts (satellite cells) isolated from the skeletal muscle of adult rats are labeled with 4',6-diamidino-2-phenylindone, which binds to DNA and to the protein tubulin to form a fluorescent complex, and implanted into the left ventricular wall of isogenic rats. The specimens are harvested 1 to 4 weeks after myoblast implantation. Histologic sections are examined under a fluorescent microscope. RESULTS: The labeling efficiency of satellite cells with 4',6-diamidino-2-phenylindole is nearly 100%. In 4 specimens, the progressive differentiation of implanted myoblasts into fully developed striated muscle fibers can be observed. CONCLUSION: Our earlier studies of autologous myoblast implantation into the cryoinjured myocardium of dogs suggested that these cells could differentiate into cardiac myocytes. However, it had been difficult to firmly establish these findings with the use of cell markers, thereby proving that the neomyocardium had indeed been derived from the implanted myoblasts. In this study, using 4',6-diamidino-2-phenylindole as a satellite cell marker, we were able to demonstrate that the implanted satellite cells did in fact differentiate into fully developed, labeled muscle fibers. Because of the obvious advantages of using autologous donor myoblasts, the clinical application of this approach may provide a novel strategy for the future management of heart failure.

Animals↗
PubMed1998

Creation of viable pulmonary artery autografts through tissue engineering.

BACKGROUND: "Repair" of many congenital cardiac defects requires the use of conduits to establish right ventricle to pulmonary artery continuity. At present, available homografts or prosthetic conduits lack growth potential and can become obstructed by tissue ingrowth or calcification leading to the need for multiple conduit replacements. Tissue engineering is an approach by which cells are grown in vitro onto biodegradable polymers to construct "tissues" for implantation. A tissue engineering approach has recently been used to construct living cardiac valve leaflets from autologous cells in our laboratory. This study assesses the feasibility of a tissue engineering approach to constructing tissue-engineered "living" pulmonary artery conduits. MATERIALS AND METHODS: Ovine artery (group A, n = 4) or vein (group V, n = 3) segments were harvested, separated into individual cells, expanded in tissue culture, and seeded onto synthetic biodegradable (polyglactin/polyglycolic acid) tubular scaffolds (20 mm long x 15 mm diameter). After 7 days of in vitro culture, the autologous cell/polymer vascular constructs were used to replace a 2 cm segment of pulmonary artery in lambs (age 68.4 +/- 15.5 days, weight 18.7 +/- 2.0 kg). One other control animal received an acellular polymer tube sealed with fibrin glue without autologous cells. Animals were sacrificed at intervals of 11 to 24 weeks (mean follow-up 130.3 +/- 30.8 days, mean weight 38.9 +/- 13.0 kg) after echocardiographic and angiographic studies. Explanted tissue-engineered conduits were assayed for collagen (4-hydroxyproline) and calcium content, and a tissue deoxyribonucleic acid assay (bis-benzimide dye) was used to estimate number of cell nuclei as an index of tissue maturity. RESULTS: The acellular control graft developed progressive obstruction and thrombosis. All seven tissue-engineered grafts were patent and demonstrated a nonaneurysmal increase in diameter (group A = 18.3 +/- 1.3 mm = 95.3% of native pulmonary artery; group V = 17.1 +/- 1.2 mm = 86.8% of native pulmonary artery). Histologically, none of the biodegradable polymer scaffold remained in any tissue-engineered graft by 11 weeks. Collagen content in tissue-engineered grafts was 73.9% +/- 8.0% of adjacent native pulmonary artery. Histologically, elastic fibers were present in the media layer of tissue-engineered vessel wall and endothelial specific factor VIII was identified on the luminal surface. Deoxyribonucleic acid assay showed a progressive decrease in numbers of cell nuclei over 11 and 24 weeks, suggesting an ongoing tissue remodeling. Calcium content of tissue-engineered grafts was elevated (group A = 7.95 +/- 5.09; group V = 13.2 +/- 5.48; native pulmonary artery = 1.2 +/- 0.8 mg/gm dry weight), but no macroscopic calcification was found. CONCLUSIONS: Living vascular grafts engineered from autologous cells and biodegradable polymers functioned well in the pulmonary circulation as a pulmonary artery replacement. They demonstrated an increase in diameter suggesting growth and development of endothelial lining and extracellular matrix, including collagen and elastic fibers. This tissue-engineering approach may ultimately allow the development of viable autologous vascular grafts for clinical use.

Animals↗
PubMed1997

Tissue-engineered heart valve leaflets: does cell origin affect outcome?

BACKGROUND: We previously reported the successful creation of tissue-engineered valve leaflet constructs and the implantation of these autologous tissue leaflets in the pulmonary valve position in a lamb model. The optimal cell origin for creating these valve leaflets remains unclear. This study was designed to compare dermal with arterial wall myofibroblasts as the cells of origin for the leaflet constructs. METHODS AND RESULTS: Mixed cell populations of endothelial cells and fibroblasts were isolated from ovine femoral arteries or subdermis and then expanded in vitro. A synthetic biodegradable polymer scaffold was then seeded with the cultured cells. The tissue scaffold was composed of a polyglactin woven mesh sandwiched between two nonwoven polyglycolic acid mesh sheets, which measured 3x3 cm in size and 3.2 mm in thickness. The cell-seeded polymer construct was implanted to replace one pulmonary valve leaflet in the same juvenile animal from which the cells had originally been obtained. Using cardiopulmonary bypass, the right posterior leaflet of the pulmonary valve was completely resected and replaced with an autologous engineered valve leaflet. In group D (n=5), the cells were obtained from subdermis, and in group A (n=4), they were obtained from the arterial wall. Eight to 10 weeks after leaflet implantation, the animals were killed, and the implanted valve leaflets were examined histologically, biochemically, and biomechanically. The dimensions of each tissue-engineered leaflet (TEL) were compared with those of the two remaining native valve leaflets to obtain a growth index. A 4-hydroxyproline assay was performed to evaluate collagen content. Leaflet tensile strength was evaluated in vitro by using a Vitrodyne V-1000 mechanical tester. Factor VIII and elastin stains were performed to histologically assess the presence of endothelial cells and elastin, respectively. In all animals, the TEL persisted in the pulmonary valve position after 8 to 10 weeks, and all polyglycolic acid polymer had been degraded. Group A leaflets had a higher growth index (0.86+/-0.11) than group D (0.41+/-0.08) (P<.05). Macroscopically, the group D leaflets appeared thicker and contracted. Histologically, elastic fibers were more abundant in group A than in group D. Total collagen content and biomechanical testing showed no differences between groups. Leaflets from both groups had positive staining for factor VIII on the surface, confirming growth of endothelial cells to cover the TEL. CONCLUSIONS: Autologous TEL derived from vascular fibroblasts seem to develop functionally and morphologically like the native valve leaflets in the pulmonary circulation. Use of arterial myofibroblasts for the creation of TEL seems preferable to dermal fibroblasts with current tissue culture conditions.

Animals↗
PubMed1997

Evaluation of a pulsatile pediatric ventricular assist device in an acute right heart failure model.

BACKGROUND: The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure. METHODS: Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. RESULTS: All results are expressed as mean +/- standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Base-line measurements were not significantly different between groups and included systemic arterial pressure, 80.6 +/- 12.7 mm Hg; right atrial pressure, 4.6 +/- 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 +/- 4.2 mm Hg; left atrial pressure, 4.8 +/- 0.8 mm Hg; and cardiac output, 1.4 +/- 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 +/- 10.4 mm Hg; right atrial pressure, 16.8 +/- 2.3 mm Hg; left atrial pressure, 1.4 +/- 0.5 mm Hg; and cardiac output, 0.6 +/- 0.1 L/min. All group 1 animals died at a mean of 71.4 +/- 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 +/- 13.0 mm Hg; right atrial pressure, 8.2 +/- 2.3 mm Hg; left atrial pressure, 6.4 +/- 2.1 mm Hg; and cardiac output, 1.0 +/- 0.2 L/min. CONCLUSIONS: The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.

Acute Disease↗
PubMed1997

Tissue engineering of cardiovascular structures.

Congenital and acquired diseases of the heart valves and great arteries are leading causes of morbidity and mortality. Current prosthetic or bioprosthetic replacement devices are imperfect and subject patients to one or more ongoing risks including thrombosis, limited durability, increased susceptibility to infection, and need for reoperations due to lack of growth. Tissue engineering (TE) is a new discipline that offers the potential to create replacement structures from autologous cells and biodegradable polymers. Because TE constructs contain living cells, they may have the potential for growth and self-repair and remodeling. Cardiac valve leaflets and large conduit arteries have been made with the TE approach. These TE structures have functioned in the pulmonary circulation of growing lambs for up to 4 months and have demonstrated 1) structural organization to resemble normal valve and artery, 2) satisfactory physiologic function, 3) lack of thrombus formation, and 4) growth.

Animals↗
PubMed1996

Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model.

BACKGROUND: We have previously reported the successful creation of tissue-engineered valve leaflets and the implantation of these autologous tissue leaflets in the pulmonary valve position. This study was designed to trace cultured cells that were seeded onto a biodegradable polymer with the use of a 1,1'-dioctadecyl-3,3,3' 3'-tetramethylindo-carbocyanine perchlorate (Di-1) cell-labeling method. We also examined the time-related biochemical, biomechanical, and histological characteristics and evolution of these tissue constructs. METHODS AND RESULTS: Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted ovine arteries. Endothelial cells were selectively labeled with an acetylated low density lipoprotein marker and separated from fibroblasts with the use of a fluorescence-activated cell sorter. A synthetic biodegradable scaffold consisting of polyglycolic acid fibers was seeded first with fibroblasts, then coated with endothelial cells. Using these methods, we implanted autologous cell/polymer constructs in six animals. In two additional control animals, a leaflet of polymer was implanted without prior cell seeding. In each animal, cardiopulmonary bypass was used to completely resect the right posterior leaflet of the pulmonary valve and replace it with an engineered valve leaflet with (n = 6) or without (n = 2) prior cultured cell seeding. The animals were killed either after 6 hours or after 1, 6, 7, 9, or 11 weeks, and the implanted valve leaflets were examined histologically, biochemically, and biomechanically. 4-Hydroxyproline assays were performed to determine collagen content. Leaflet strength was evaluated in vitro with a mechanical tester Factor VIII and elastin stains were done to verify histologically that endothelial cells and elastin, respectively, were present. Animals receiving leaflets made from polymers without cell seeding were killed and examined in a similar fashion after 8 weeks. In the control animals, the acellular polymer leaflets were completely degraded, with no residual leaflet tissue at 8 weeks. The tissue-engineered valve leaflet persisted in each animal in the experimental group. 4-Hydroxyproline analysis of the constructs showed a progressive increase in collagen content. Immunohistochemical staining demonstrated elastin fibers in the matrix and factor VIII on the surface of the leaflet. The cell-labeling experiments demonstrated that the cells on the leaflets had persisted from the in vitro seeding of the leaflets. CONCLUSIONS: In the tissue-engineered heart valve leaflet, transplanted autologous cells generated a proper matrix on the polymer scaffold in a physiological environment at a period of 8 weeks after implantation.

Animals↗
PubMed1996

Higher hematocrit improves cerebral outcome after deep hypothermic circulatory arrest.

BACKGROUND: Various degrees of hemodilution are currently in clinical use during deep hypothermic circulatory arrest to counteract deleterious rheologic effects linked with brain injury by previous reports. MATERIAL AND METHODS: Seventeen piglets were randomly assigned to three groups. Group I piglets (n = 7) received colloid and crystalloid prime (hematocrit < 10%), group II piglets (n = 5) received blood and crystalloid prime (hematocrit 20%), group III piglets (n = 5) received blood prime (hematocrit 30%). All groups underwent 60 minutes of deep hypothermic circulatory arrest at 15 degrees C with continuous magnetic resonance spectroscopy and near-infrared spectroscopy Neurologic recovery was evaluated for 4 days (neurologic deficit score 0, normal, to 500, brain death; overall performance category 1, normal, to 5, brain death). Neurohistologic score (0, normal, to 5+, necrosis) was assessed after the animals were euthanized on day 4. RESULTS: Group I had significant loss of phosphocreatine and intracellular acidosis during early cooling (phosphocreatine in group I, 86.3% +/- 26.8%; group II, 117.3% +/- 8.6%; group III, 110.9% +/- 2.68%; p = 0.0008; intracellular pH in group I, 6.95 +/- 0.18; group II, 7.28 +/- 0.04; group III, 7.49 +/- 0.04; p = 0.0048). Final recovery was the same for all groups. Cytochrome aa3 was more reduced in group I during deep hypothermic circulatory arrest than in either of the other groups (group I, -43.6 +/- 2.6; group II, -16.0 +/- 5.2; group III, 1.3 +/= 3.1; p < 0.0001). Neurologic deficit score was best preserved in group III (p < 0.05 group II vs group III) on the first postoperative day, although this difference diminished with time and all animals were neurologically normal after 4 days. Histologic assessment was worst among group I in neocortex area (group I, 1.33 +/- 0.3; group II, 0.22 +/- 0.1; group III, 0.40 +/- 0.2, p < 0.05, group I vs group II; p = 0.0287, group I vs group III). CONCLUSION: Extreme hemodilution during cardiopulmonary bypass may cause inadequate oxygen delivery during early cooling. The higher hematocrit with a blood prime is associated with improved cerebral recovery after deep hypothermic circulatory arrest.

Adenosine Triphosphate↗
PubMed1995

The management of chylothorax/chylopericardium following pediatric cardiac surgery: a 10-year experience.

We reviewed the management of 25 cases of chylothorax/chylopericardium (CT/CP) in 24 patients (9 females, 15 male; 3 days to 11-years-old) following 1605 cardiothoracic procedures (incidence of 1.5%) between January 1984 and December 1993 at our institution. The surgical procedures preceding the occurrence of lymph leak included ligation of patent ductus arteriosus (6 patients), coarctation/double aortic arch repairs (3), complex intracardiac repairs (11), and systemic to pulmonary shunts (5). There were 3 CPs and 22 CTs. All of the patients were initially treated nonsurgically with diet modification using either total parenteral nutrition (TPN) or enteral low fat solid food or enteral elemental diet supplemented with intravenous lipid emulsion. Twenty-one cases (84%) responded to conservative therapy. Of those, 15 had TPN as the initial treatment; the average duration of lymph leak was 13.7 (range 7 to 30) days and the average maximal lymph leak was 39.4 (range 15 to 130) mL/kg per day. The other six cases had low-fat enteral diet as the initial treatment, four resolved completely. Two with high-central venous pressure had to be switched to TPN prior to complete resolution. The average duration of lymph leak in this subgroup was 30 (range 12 to 56) days with the average maximal lymph leak was 30.1 (range 8.5 to 59) mL/kg per day. Excluding these two cases, the average lymph leak of the rest of the group was very compatible to the TPN group of 15 days. Lymphocytopenia and hyponatremia were frequently seen during CT/CP (47.6% and 43%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Surgical Procedures↗
PubMed1994

Newborn myocardial protection after prolonged prearrest cooling: a calcium overload phenomenon?

Prolonged cold perfusion of the nonarrested newborn heart has been shown to induce stunning and subsequent contracture when followed by ischemia. The underlying mechanism remains unknown. To test whether this phenomenon is due to cytosolic calcium (Ca2+) overload, a Ca(2+)-channel blocker (verapamil hydrochloride) was used to pretreat the newborn heart immediately before prolonged cold perfusion. Twenty-eight newborn piglets were studied in an isolated, Krebs-Henseleit-perfused Langendorff cardiac model. Group I control hearts (n = 8) were subjected to 90 minutes of cold perfusion at 15 degrees C, followed by 90 minutes of global ischemia and then 30 minutes of normothermic reperfusion. Group II hearts (n = 6) were pretreated with verapamil (0.2 x 10(-7) mol/L) for 3 minutes prior to similar experimentation. Groups III (control, n = 8) and IV (verapamil pretreatment, n = 6) underwent the same protocol without ischemia. Baseline functional measurements were obtained with left ventricular balloon inflated at baseline pressure of 10 to 15 mm Hg prior to cold perfusion and after 30 minutes of normothermic reperfusion. Perfusate creatine kinase level was analyzed, and electron microscopic examination was performed at the conclusion of each experiment. Fifty percent of group I control hearts had no postischemic recovery, and ultrastructural study revealed marked contraction bands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The enigma of myocardial preconditioning models.

Myocardial preconditioning has been reported in the hearts of many species of animals, including dogs, pigs, rabbits, rats, and anecdotally in humans. However, most studies were carried out in the regional ischemic model, although protection against global ischemic injury had been observed in rat models. Besides biochemical endpoints, the criterion of protection in regional ischemia was usually reduction in infarct size, while in global ischemia, recovery of contractile force and time-to-onset of ischemic contracture were used. We attempted to reproduce preconditioning of myocardium against global ischemic injury using an isolated perfused rabbit heart model with the rationale that global ischemia is more relevant to cardiac surgery, the rabbit model is logistically convenient, and it can be used for future comparison with the responses in immature hearts. The preconditioning was induced with 5 minutes of normothermic global ischemia followed by 10 minutes of reperfusion. The principal ischemic injury lasted 35 minutes, followed by 60 minutes of reperfusion. The control group underwent similar principal ischemic injury and reperfusion but no prior preconditioning ischemia. Results showed that there was no difference between the two groups in left ventricular resting tension, recovery in left ventricular developed pressure, contractility (dP/dt), and rate of relaxation (-dP/dt), nor were there any differences in heart rate and coronary flow rate. The reason for our negative findings is not clear, but if the results are confirmed, it will suggest that extrapolation of observations obtained from one experimental model to another should be made with caution.

Animals↗
PubMed1993

In vivo study of bleeding time and arterial hemorrhage in hypothermic versus normothermic animals.

This in vivo study confirmed impaired hemostasis during hypothermia in a swine model. Group I (normothermic, n = 8) and group II (hypothermic, n = 8) animals were anesthetized and instrumented for continuous peritoneal irrigation and monitoring of heart rate and blood pressure. The effects of hypothermia, hypotension, and inotrope on bleeding time and bleeding from two types of arterial injuries were evaluated. Our findings were that (1) bleeding time was significantly prolonged in hypothermic animals; (2) the differences in blood loss from partially torn artery (PTA) and completely cut artery (CCA) at both normothermic and hypothermic temperatures did not reach statistical significance; and (3) blood loss from PTA was greater than CCA when norepinephrine (Levophed) was infused to elevate blood pressure in hypotensive animals at normal core temperature.

Algorithms↗
PubMed1993

Contracture of the newborn myocardium after prolonged prearrest cooling.

Profound hypothermic circulatory arrest is frequently used to facilitate the surgical repair of congenital heart defects in neonates. Deep hypothermia is achieved by a period of core systemic cooling during cardiopulmonary bypass before cardioplegic arrest. There have been conflicting reports with respect to the consequence of perfusing a nonarrested newborn heart under hypothermic conditions. This in vitro study was designed to prolong the clinically simulated hypothermic perfusion sequence into an extreme condition and to test the hypothesis that prolonged cold perfusion of the nonarrested newborn myocardium could, in fact, be detrimental. Twenty-four newborn piglets (5 to 7 days old) were randomly assigned to four groups and studied in a crystalloid perfused Langendorff heart model. The first two groups of hearts (n = 6 per group) were subjected to either 30 minutes (group I) or 90 minutes (group II) of cold perfusion at 15 degrees C, followed by 90 minutes of ischemia and then 30 minutes of normothermic reperfusion. In a second experiment, group III hearts subjected to 30 minutes of cold perfusion were compared with group IV (90 minutes of cold perfusion) without ischemic insult in either case. Postischemic recovery of isovolumetric developed pressure was significantly impaired in group II (16.1% +/- 7.4% [II] versus 65.5% +/- 4.8% [I], p < 0.05), and 50% of the hearts had no spontaneous cardiac activity on reperfusion. End-diastolic pressure showed significant contracture with prolonged cold perfusion: group II 57.3 +/- 13.9 mm Hg versus group I 14.8 +/- 1.8 mm Hg, p < 0.05. In the absence of ischemia, a similar relationship was observed between groups IV and III (left ventricular developed pressure 68.5% +/- 3.6% versus 82.4% +/- 4.2%, p < 0.05, and left ventricular end-diastolic pressure 23.5 +/- 6.2 mm Hg versus 13.3 +/- 2.6 mm Hg, p = not significant. Ultrastructural examination revealed severe damage to the myocardial cells and contraction band necrosis in group II (prolonged cooling and ischemia). These results suggest that prolonged cold perfusion of the nonarrested newborn heart impairs functional recovery and is therefore detrimental. When followed by a period of ischemic arrest, it further potentiates the myocardial injury and induces severe contracture. This preceding adverse effect of prolonged myocardial cold perfusion before cardiac arrest may, in part, explain the suboptimal protective effect of cardioplegia in neonates.

Animals↗
PubMed1992

Oral vitamin E prophylaxis in the protection of newborn myocardium from global ischemia.

BACKGROUND: Oxygen-derived free radicals have been implicated in the pathophysiology of myocardial reperfusion injury after ischemic insult. Recent studies have demonstrated that free radical scavengers could afford protection to the mature myocardium from these injuries. The purpose of this study was to investigate whether oral vitamin E pretreatment could improve the tolerance of newborn hearts to ischemia. METHODS: Two groups of six newborn piglet hearts were randomly studied in an isolated, perfused Langendorff heart model. Group I control hearts were subjected to 30 minutes of cold perfusion at 15 degrees C, in which profound hypothermia was achieved over a period of 10 minutes. This was followed by 90 minutes of global ischemia arrest and 30 minutes of normothermic reperfusion. Group II piglets were pretreated with d-alpha-tocopherol (vitamin E) given by oral gavage for 4 days before similar experimentation. Baseline functional parameters were recorded before cold perfusion by a left intraventricular balloon inflated to a diastolic pressure of 11 to 14 mm Hg and repeated at the end of 30 minutes of normothermic reperfusion. Creatine phosphokinase leakage in the perfusate was analyzed immediately after reperfusion and the pressure/volume ratio was obtained at the conclusion of each experiment. RESULTS: Postischemic functional recovery of vitamin E-pretreated group II hearts was improved significantly compared with the control hearts (group I). Left ventricular diastolic pressure was 87.5% +/- 2.3% versus 66.1% +/- 2.3%, +dp/dt was 94.5% +/- 2.2% versus 68.0% +/- 5.6%, -dp/dt was 93.0% +/- 2.4% versus 69.6% +/- 6.0%, mean left ventricular end-diastolic pressure was 13.0 +/- 0.8 versus 22.0 +/- 3.5 mm Hg, and pressure/volume ratio was 29.2 +/- 2.3 versus 41.8 +/- 4.3 mm Hg/ml, respectively (p less than 0.05). Perfusate creatine phosphokinase leakage was also reduced significantly from 112.5 +/- 17.9 to 56.2 +/- 4.0 IU/L (p less than 0.05) in group II. CONCLUSIONS: Oral vitamin E pretreatment improved the ischemic tolerance of newborn myocardium and therefore might be considered a valuable, effective, and inexpensive method of myocardial protection.

Administration, Oral↗